Search

OBJECTIVE Assess long-term efficacy and safety of guselkumab, an IL-23p19-subunit inhibitor, in patients with active psoriatic arthritis (PsA) from the Phase-3 DISCOVER-2 trial. METHODS In DISCOVER-2, patients with active PsA (≥5 swollen and ≥5 tender joints; CRP ≥0.6 mg/dL) despite prior nonbiologic therapy were randomized to: guselkumab 100mg every-4-weeks (Q4W); at Week0, Week4, and Q8W; or placebo➔guselkumab Q4W at Week24. Efficacy assessments included ≥20%/50%/70% improvement in ACR components (ACR20/50/70), Investigator's Global Assessment of psoriasis score=0 (IGA=0; indicating complete skin clearance), enthesitis (Leeds Enthesitis Index) and dactylitis (Dactylitis Severity Score) resolution, and changes in PsA-modified van der Heijde-Sharp (vdH-S) radiographic scores. Clinical data (imputed as no response/no change from baseline if missing) and observed radiographic data were summarized through Week100; safety assessments continued through Week112. RESULTS Of 739 randomized and treated patients, 652 (88%) completed treatment through Week100. Across groups of guselkumab-treated patients (including placebo➔Q4W) ACR20 (68%-76%), ACR50 (48%-56%), ACR70 (30%-36%), and IGA=0 (55%-67%) responses and enthesitis (62%-70%) and dactylitis (72%-83%) resolution rates at Week100 indicated amelioration of arthritis signs/symptoms and extra-articular manifestations was durable through 2years. Mean changes in PsA-modified vdH-S scores from Week52-100 (0.13-0.75) indicated the low rates of radiographic progression observed among guselkumab-treated patients at earlier timepoints extended through Week100. Through Week112, 8% (5.8/100 patient-years) and 3% (1.9/100 patient-years) of 731 guselkumab-treated patients had a serious adverse event or serious infection, respectively; one death occurred (road traffic accident). CONCLUSION In biologic-naive PsA patients, guselkumab provided durable improvements in multiple disease domains with no unexpected safety findings through 2years.

BackgroundGuselkumab (GUS), an anti-IL23p19-subunit mAb, demonstrated significant efficacy vs placebo (PBO) in achieving ACR20 response at week (W) 24 in patients (pts) with active PsA in phase 3 trials, DISCOVER-1&2 (D1&2).1,2 Pts with PsA report pain relief as a treatment priority.3ObjectivesTo assess GUS treatment effect through 2 years on pt-reported pain across outcome measures.MethodsPts with active PsA in D1 (n=381; 31% received 1-2 prior TNFi) and D2 (n=739; biologic-naïve) were randomized (1:1:1) to GUS 100 mg every 4 weeks (Q4W); GUS 100 mg at W0, W4, then Q8W; or PBO with crossover to GUS 100 mg Q4W at W24 (PBO→Q4W). Pts rated pain using visual analog scale (VAS; 0-10; Pt Pain) and reported Bodily Pain intensity over past 4 W via 36-Item Short-Form Health Survey question 21 (0-5). Pts with spondylitis and peripheral arthritis at baseline (BL) rated Spinal and Joint Pain (0-10). Observed mean change, % improvement from BL in tender (TJC; 0-68) and swollen joint counts (SJC; 0-66), and proportion of pts achieving ≥20/≥50% improvement in Pt Pain (nonresponder imputation [NRI]) were evaluated.ResultsIn D2, mean BL for Bodily Pain (range: 4.4-4.5), Pt Pain (6.2-6.3), Spinal Pain (6.5-6.7), Joint Pain (6.3-6.8), SJC (11.7-12.9) and TJC (19.8-22.4) indicated moderate pain and disease activity at study outset. GUS-treated pts reported ~2x improvement in Pt Pain, Spinal Pain, Joint Pain, and Bodily Pain intensity at W24 vs PBO, which were maintained or increased at W52 and W100. PBO→Q4W pts had similar improvements. Pt-reported pain appeared more sensitive to treatment effect, with larger differences in % improvement vs PBO than physician-reported TJC/SJC at W24. D1 showed consistent results through 1 year. In 748 GUS-treated pts across D1&2, substantial proportions achieved meaningful improvement in Pt Pain at early time points: 32% (W4) and 48% (W8) achieved ≥20% improvement; 28% (W12) and 33% (W16) achieved ≥50% improvement. At W24, 63%/39% reported ≥20%/≥50% improvement in pain.ConclusionGUS provided consistent and durable improvements in pt-reported pain across several outcome measures. Pt-reported pain as an early and sensitive indicator of treatment effect in pts with active PsA and additional factors merits further evaluation.References[1]Deodhar A et al. Lancet. 2020;395:1115-25[2]Mease P et al. Lancet. 2020;395:1126-36[3]Gudu T et al. Expert Rev Clin Immunol. 2018;14:405-17Table 1.Observed Mean (SD) Change from Baseline in Pain Scores, TJC, and SJC at W24, W52, and W100 in DISCOVER-2W24W52W100GUS Q4WGUS Q8WPBOGUS Q4WGUS Q8WPBO→Q4WGUS Q4WGUS Q8WPBO→Q4WPt Pain (0-10),* N240243243229234231220224215-2.39 (2.35)-2.53 (2.47)-1.08 (2.42)-2.89 (2.68)-3.20 (2.56)-2.75 (2.66)-3.52 (2.62)-3.69 (2.63)-3.41 (2.58)Spinal Pain (0-10), +N806592796488766182-2.26 (2.57)-2.54 (2.70)-1.13 (2.48)-2.74 (2.63)-2.67 (2.71)-2.65 (2.69)-3.11 (2.67)-3.44 (2.71)-3.37 (2.66)Joint Pain (0-10),+N806592796488766182-2.88 (2.17)-2.90 (2.68)-1.40 (2.91)-3.32 (2.27)-3.21 (2.76)-3.42 (2.92)-3.54 (2.35)-3.61 (2.77)-3.80 (2.95)SF-36 (Q21; 0-5), N240243242229234230220224214-0.99 (1.03)-1.03 (1.12)-0.50 (1.11)-1.18 (1.33)-1.29 (1.17)-1.10 (1.16)-1.39 (1.25)-1.47 (1.38)-1.36 (1.27)TJC (0-68), N240243243228234231220224213-11.85(9.88)-10.37(9.49)-7.26(11.15)-15.04(10.51)-13.44(10.03)-14.15(11.39)-16.37(10.70)-15.27(11.10)-16.29(11.27)SJC (0-66), N240243243228234231220224213-8.77(5.46)-8.14(6.07)-6.44(7.20)-10.38(6.17)-9.56(6.28)-10.17(6.79)-10.83(6.66)-10.20(6.88)-10.58(6.15)*ACR, DAPSA, MDA: VAS 0-10; +BASDAI: VAS 0-10ACR=American College of Rheumatology; BASDAI=Bath Ankylosing Spondylitis Disease Activity Index; DAPSA=Disease Activity in Psoriatic Arthritis; GUS=guselkumab; MDA=minimal disease activity; PBO=placebo; pt=patient; Q=question; QxW=every x week; SD=standard deviation; SF-36=36-Item Short-Form Survey; SJC=swollen joint count; TJC=tender joint count; VAS=visual analog scale; W=weekDisclosure of InterestsPeter Nash Consultant of: AbbVie, Bristol Myers Squibb, Boehringer, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Roche, Sandoz, and Sun Pharma, Grant/research support from: AbbVie, Bristol Myers Squibb, Boehringer, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Roche, Sandoz, and Sun Pharma, Lai-Shan Tam Consultant of: AbbVie, Boehringer Ingelheim, Eli Lilly, Janssen, Pfizer, and Sanofi, Grant/research support from: Amgen, Boehringer Ingelheim, GSK, Janssen, Novartis, and Pfizer, Wen-Chan Tsai Consultant of: AbbVie, Eli Lilly, Novartis, Pfizer, and Janssen, Ying Ying Leung Consultant of: AbbVie, Eli Lilly, Janssen, and Novartis and on advisory board for Janssen, Daniel Furtner Shareholder of: Johnson & Johnson, Employee of: Janssen, a division of Johnson & Johnson Pte. Ltd, Shihong Sheng Shareholder of: Johnson & Johnson, Employee of: Janssen Research and Development, LLC, Yanli Wang Consultant of: Janssen, Employee of: Cytel, Inc., May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research and Development, LLC, Jonathan Sherlock Shareholder of: Johnson & Johnson, Employee of: Janssen Research and Development, LLC, Daniel Cua Shareholder of: Johnson & Johnson, Employee of: Janssen Research and Development, LLC

BackgroundPsoriatic arthritis (PsA) impacts patients’ (pts) work productivity (WP) and daily activity.1 DISCOVER-2 (D2), a Phase 3 trial of the selective interleukin-23 p19-subunit inhibitor guselkumab (GUS) in biologic-naïve pts with PsA,2 demonstrated significant improvements in pt-reported WP and daily activity following 1 year (Y) of GUS treatment.3ObjectivesAssess WP and daily activity impairment in D2 pts through 2Y. Estimate indirect savings associated with GUS treatment and assess changes in employment status.MethodsPts with active PsA received GUS 100 mg every 4 weeks (Q4W); GUS 100 mg at W0, W4, then Q8W; or placebo (PBO). At W24, PBO pts crossed over to GUS 100 mg Q4W. WPAI-PsA assesses PsA-related work time missed (absenteeism), impairment while working (presenteeism), and impaired overall WP (absenteeism + presenteeism) for pts employed at baseline (EBL) and daily activity for all pts, including those unemployed at baseline (UBL) during the previous week. Mean changes in WPAI-PsA domains were calculated for each multiple imputation (MI) dataset using an analysis of covariance (ANCOVA); the reported LS mean is the average of all MI datasets. Significance was defined as p4 A shift analysis evaluated proportions of pts employed vs unemployed by treatment group using observed data over time.ResultsPts EBL comprised 64% of the analysis cohort. Significant improvements in WP in pts EBL and in daily activity among all pts were observed with GUS Q4W/Q8W vs PBO at W24;3 mean improvements in WP and daily activity increased with continued GUS through 2Y (Table 1). Potential annual indirect savings from improved overall WP in pts EBL were €10,826 GUS Q4W, €12,712 GUS Q8W, and €10,948 PBO→ GUS Q4W at 2Y. Shift analysis showed relatively stable employment in pts EBL with GUS up to 2Y (>83% continued to work). Among pts UBL (36% of cohort), the proportion of pts employed increased by >20% through 2Y of GUS (Figure 1).Table 1.Model-Based Estimates of Change From BL in WPAI-PsA Domains1GUS 100mg Q4WGUS 100mg Q8WPBO (W0-24) → GUS 100 mg Q4W (W24-100)VisitW24W100W24W100W24W100Absenteeism, N145147147149162166 LS Mean (95% CI)-3.4 (-6.5, -0.3)-1.8 (-4.5, 0.9)-3.0 (-6.0, 0.1)-4.2 (-6.8,-1.5)-3.0 (-6.0, 0.04)-4.2 (-6.8,-1.6) Diff vs. PBO-0.4 (-4.6, 3.8)--0.01 (-4.2, 4.2)---Presenteeism, N145147147149162166 LS Mean (95% CI)-20.1 (-23.7, -16.6)-26.3 (-30.1,-22.5)-19.6 (-23.2, -16.1)-28.0 (-31.8, -24.2)-10.5 (-13.9, -7.0)-24.2 (-27.9, -20.5) Diff vs PBO-9.7* (-14.4, -5.0)--9.2* (-13.9, -4.5)---Work productivity, N145147147149162166 LS Mean (95% CI)-20.1 (-24.1, -16.1)-23.8 (-28.0, -19.6)-19.2 (-23.1, -15.2)-28.0 (-32.1, -23.8)-10.6 (-14.4, -6.8)-24.1 (-28.1, -20.1) Diff vs PBO-9.5* (-14.8, -4.2)--8.6* (-13.9, -3.3)---Daily Activity, N242242246246245245 LS Mean (95% CI)-20.5 (-23.3, -17.7)-29.2 (-32.2, -26.1)-21.2 (-23.9, -18.4)-28.0 (-31.0, -24.9)-9.9 (-12.6, -7.1)-26.6 (-29.6, -23.6) Diff vs PBO-10.6* (-14.4, -6.8)--11.3* (-15.1, -7.5)-1Mean changes in WPAI-PsA domains were calculated for each MI dataset using an ANCOVA; reported LS mean (95% confidence interval [CI]) = average of all MI datasets.*pConclusionIn GUS-treated bio-naïve PsA pts, robust improvements in WP and daily activity seen at W24 were maintained and increased through 2Y of GUS. Long-term improvements in WP achieved may result in substantial indirect cost savings for GUS-treated pts. Rates of employment remained stable in pts employed and increased in those unemployed at BL.References[1]Tillett W et al. Rheumatol (Oxford). 2012;51:275–83.[2]Mease PJ, et al. Lancet. 2020;395:1126–36.[3]Curtis JR et al. EULAR, June 2–5, 2021. POS1026.[4]OECD (2020). Average wages (indicator). https://data.oecd.org/earnwage/average-wages.htmDisclosure of InterestsJeffrey Curtis Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, CorEvitas, Eli Lilly and Company, Janssen, Myriad, Novartis, Pfizer, Sanofi, and UCB, Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, CorEvitas, Eli Lilly and Company, Janssen, Myriad, Novartis, Pfizer, Sanofi, and UCB, Iain McInnes Shareholder of: Causeway Therapeutics, and Evelo Compugen, Consultant of: Astra Zeneca, AbbVie, Bristol-Myers Squibb, Amgen, Eli Lilly and Company, Cabaletta, Compugen, GSK, Gilead, Janssen, Novartis, Pfizer, Sanofi, Roche, and UCB, Grant/research support from: Astra Zeneca, Bristol-Myers Squibb, Amgen, Eli Lilly and Company, GSK, Janssen, Novartis, Roche, and UCB, Proton Rahman Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, and UCB, Grant/research support from: Janssen and Novartis, Dafna D Gladman Consultant of: Abbvie, Amgen, BMS, Eli Lilly, Galapagos, Gilead, janssen, Novartis, Pfizer and UCB., Grant/research support from: Abbvie, Amgen, Eli Lilly, Janssen, Pfizer, UCB, Feifei Yang Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, Steve Peterson Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Natalie Shiff Shareholder of: Johnson & Johnson, Abbvie, Gilead, Employee of: Janssen Scientific Affairs, LLC, Chenglong Han Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, May Shawi Shareholder of: Johnson & Johnson, Employee of: Immunology Global Medical Affairs, Janssen Pharmaceutical Companies, William Tillett Speakers bureau: Abbvie, Amgen, Eli-Lilly, Janssen, MSD, Novartis, Pfizer, and UCB, Consultant of: Abbvie, Amgen, Eli-Lilly, Janssen, MSD, Novartis, Pfizer, and UCB, Grant/research support from: Abbvie, Amgen, Eli-Lilly, Janssen, and UCB, Philip J Mease Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Consultant of: AbbVie, Aclaris, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sun Pharma, and UCB

BackgroundGuselkumab (GUS) demonstrated efficacy and a favorable safety profile in active PsA in the Phase (Ph) 21 and Ph3 DISCOVER-1&2 trials2,3 and in moderate-to-severe plaque psoriasis (PsO) in the Ph3 VOYAGE-1&2 trials.4,5ObjectivesTo assess long-term safety of GUS across PsA/PsO trials.MethodsUsing pooled safety data through 2 years (yrs) from PsA trials (N=1229; GUS 100 mg every 4/8 weeks [Q4W/Q8W])1-3 and through 5 yrs from PsO trials (N=1721; GUS 100 mg Q8W),4,5 incidences of serious adverse events (SAEs); gastrointestinal (GI)-related SAEs and other targeted AEs; including candidiasis, uveitis, and opportunistic infections (OIs) were evaluated. Incidence rates (IRs) were calculated as the number of events per 100 pt-yrs (PY) of follow-up with 95% CI. Patients (pts) with an IBD history were not excluded in PsA/PsO trials. Max exposure duration was W100 for PsA trials and W252 for PsO trials.ResultsThe PsA and PsO populations had comparable mean age and BMI. IRs of SAEs and GI-related SAEs were generally similar between GUS- and PBO-treated pts during PBO-controlled periods, and between PsA pts receiving GUS Q4W/Q8W for up to 2 yrs and PsO pts receiving GUS Q8W for up to 5 yrs (Table 1). IRs of other targeted AEs of interest were low. OIs did not occur in PsO pts and were infrequent in PsA pts (Table 1). Candidal infections were infrequent and non-serious. Iridocyclitis was reported in 1 PBO- and 1 GUS Q8W-treated PsA pt. No exacerbations or new onset of IBD or active tuberculosis was reported in GUS-treated PsA/PsO pts.Table 1.Targeted AEs of InterestPooled PsA*Pooled PsOThrough 2 YrsThrough 5 YrsGUS 100 mg Q4W (N=373)GUS 100 mg Q8W (N=475)PBO→GUS 100 mg Q4W (N=352)aPBO→GUS 100 mg Q8W (N=29)aGUS Combined (N=1229)GUS 100 mg Q8W (N=1221)bADA→GUS 100 mg Q8W (N=500)cGUS Combined (N=1721)Total PY645748461171871525419127166Mean PY1.71.61.30.61.54.33.84.2Events/100 PY (95% CI)Overall SAEs4.65(3.14, 6.64)6.42(4.73, 8.51)5.86(3.86, 8.52)0.00(0.00, 17.24)5.61(4.59, 6.79)5.18(4.58, 5.83)4.55(3.64, 5.61)5.01(4.50, 5.56)GI-related SAEs0.46(0.10, 1.36)0.27(0.03, 0.97)0.00 (0.00, 0.65)0.00(0.00, 17.24)0.27(0.09, 0.62)0.44(0.28, 0.66)0.42(0.18, 0.82)0.43(0.29, 0.61)OIsd0.00(0.00, 0.46)0.27(0.03, 0.97)0.22(0.01, 1.21)0.00(0.00, 17.24)0.16(0.03, 0.47)0.00(0.00, 0.06)0.00(0.00, 0.16)0.00(0.00, 0.04)Candida infections0.31(0.04, 1.12)0.00(0.00, 0.40)0.00(0.00, 0.65)0.00(0.00, 17.24)0.11(0.01, 0.39)0.49(0.32, 0.73)0.52(0.25, 0.96)0.50(0.35, 0.70)Non-pathogen specific fungal infections, suspicious for candida0.00(0.00, 0.46)0.27(0.03, 0.97)0.00(0.00, 0.65)0.00(0.00, 17.24)0.11(0.01, 0.39)0.11(0.04, 0.25)0.16(0.03, 0.46)0.13(0.06, 0.24)Uveitis/ Iridocyclitis0.00(0.00, 0.46)0.13(0.00, 0.75)0.00(0.00, 0.65)0.00(0.00, 17.24)0.05(0.00, 0.30)0.00(0.00, 0.06)0.00(0.00, 0.16)0.00(0.00, 0.04)*In PsA Ph2, data after early escape at W16 were excluded. AEs are coded using MedDRA Version 23.1aFor PBO→GUS, data on/after 1st GUS administration were includedbPBO crossover pts were included in GUS column after crossover to GUScEvents prior to GUS (ADA events) were excluded. Only includes pts randomized to ADA at W0 and crossed over to GUS at/after W52 for VOYAGE-1 & W28 for VOYAGE-2dHerpes zoster disseminated, fungal oesophagitis, and meningitis listeria (1 each)ADA=AdalimumabConclusionIRs of SAEs; GI-related SAEs; and AEs of interest including candidiasis, uveitis, and OIs were low, or no cases were reported. No new safety concerns were identified with GUS treatment through 2 yrs and 5 yrs of follow-up in the pooled PsA and PsO trials, respectively, supporting a durable and favorable GUS safety profile consistent between pts with active PsA and moderate-to-severe PsO.References[1]Deodhar A, et al. Lancet. 2018;391:2213-2224.[2]Deodhar A, et al. Lancet. 2020;395:1115-1125.[3]Mease PJ, et al. Lancet. 2020;395:1126-1136.[4]Blauvelt A, et al. J Am Acad Dermatol. 2017;76:405-417.[5]Reich K, et al. J Am Acad Dermatol. 2017;76:418-431.Disclosure of InterestsPhilip J Mease Speakers bureau: AbbVie, Aclaris, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Celgene, Crescendo Bioscience, Genentech, Inmagene, Janssen, Lilly, Merck, Novartis, Pfizer, SUN Pharma, and UCB, Consultant of: AbbVie, Aclaris, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Celgene, Crescendo Bioscience, Genentech, Inmagene, Janssen, Lilly, Merck, Novartis, Pfizer, SUN Pharma, and UCB, Grant/research support from: AbbVie, Aclaris, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Celgene, Crescendo Bioscience, Genentech, Inmagene, Janssen, Lilly, Merck, Novartis, Pfizer, SUN Pharma, and UCB, Peter Foley Speakers bureau: AbbVie, Celgene, Janssen, Eli Lilly, Merck, Novartis, Pfizer, Valeant, Galderma, GlaxoSmithKline, Leo Pharma, and Roche, Paid instructor for: (Advisory boards) AbbVie, Amgen, Aslan, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Janssen, Eli Lilly, Merck, Novartis, Pfizer, Sun Pharma, UCB Pharma, Valeant, Galderma, GlaxoSmithKline, Leo Pharma, and Sanofi, Consultant of: Janssen, Eli Lilly, Novartis, Pfizer, UCB Pharma, Bristol-Myers Squibb, Galderma, Leo Pharma, and Roche; investigator for AbbVie, Amgen, AstraZeneca, Arcutis, Aslan, Boehringer Ingelheim, Celgene, Hexima, Janssen, Eli Lilly, Merck, Novartis, Pfizer, Sun Pharma, UCB Pharma, Valeant, Bristol-Myers Squibb, Celtaxsys, CSL, Cutanea, Dermira, Galderma, Genentech, GlaxoSmithKline, Leo Pharma, Regeneron Pharmaceuticals Inc, Reistone, Roche, and Sanofi, Grant/research support from: AbbVie, Amgen, Celgene, Janssen, Leo Pharma, Eli Lilly, Merck, Novartis, Pfizer, Sanofi, and Sun Pharma; travel grants from AbbVie, Janssen, Eli Lilly, Merck, Novartis, Pfizer, Galderma, Leo Pharma, Roche, Sun Pharma, and Sanofi; served as speaker for or received honoraria from AbbVie, Celgene, Janssen, Eli Lilly, Merck, Novartis, Pfizer, Valeant, Galderma, GlaxoSmithKline, Leo Pharma, and Roche, Kristian Reich Speakers bureau: Abbvie, Affibody, Amgen, Biogen, Boehringer Ingelheim Pharma, Bristol Myers Squibb, Celgene, Centocor, Covagen, Eli Lilly, Forward Pharma, Galderma, GlaxoSmithKline, Janssen-Cilag, Leo, Medac, Merck Sharp & Dohme Corp., Novartis, Ocean Pharma, Pfizer, Regeneron, Sanofi, Takeda, UCB Pharma, and Xenoport, Paid instructor for: Abbvie, Affibody, Amgen, Biogen, Boehringer Ingelheim Pharma, Bristol Myers Squibb, Celgene, Centocor, Covagen, Eli Lilly, Forward Pharma, Galderma, GlaxoSmithKline, Janssen-Cilag, Leo, Medac, Merck Sharp & Dohme Corp., Novartis, Ocean Pharma, Pfizer, Regeneron, Sanofi, Takeda, UCB Pharma, and Xenoport, Consultant of: Participated in clinical trials sponsored by Abbvie, Affibody, Amgen, Biogen, Boehringer Ingelheim Pharma, Bristol Myers Squibb, Celgene, Centocor, Covagen, Eli Lilly, Forward Pharma, Galderma, GlaxoSmithKline, Janssen-Cilag, Leo, Medac, Merck Sharp & Dohme Corp., Novartis, Ocean Pharma, Pfizer, Regeneron, Sanofi, Takeda, UCB Pharma, and Xenoport, Soumya D Chakravarty Employee of: Janssen Scientific Affairs, LLC and may own stock or stock options in Johnson & Johnson, May Shawi Employee of: Janssen Global Services, LLC and may own stock or stock options in Johnson & Johnson, Ya-Wen Yang Employee of: Janssen Global Services, LLC and may own stock or stock options in Johnson & Johnson, Megan Miller Employee of: Janssen Research & Development, LLC and may own stock or stock options in Johnson & Johnson, Alexa Kollmeier Employee of: Janssen Research & Development, LLC and may own stock or stock options in Johnson & Johnson, Xie L Xu Employee of: Janssen Research & Development, LLC and may own stock or stock options in Johnson & Johnson, Jenny Yu Employee of: Janssen Research & Development, LLC and may own stock or stock options in Johnson & Johnson, Yanli Wang Employee of: Janssen Research & Development, LLC and may own stock or stock options in Johnson & Johnson, Shihong Sheng Employee of: Janssen Research & Development, LLC and may own stock or stock options in Johnson & Johnson, Yin You Employee of: Janssen Research & Development, LLC and may own stock or stock options in Johnson & Johnson, Iain McInnes Consultant of: AbbVie, Bristol-Myers Squibb, Boehringer-Ingelheim, Celgene, Eli Lilly, Gilead, Janssen, Novartis and UCB., Grant/research support from: Astra Zeneca, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, and UCB

BackgroundGuselkumab (GUS), a selective IL-23p19 subunit inhibitor, demonstrated efficacy and a favorable safety profile in active psoriatic arthritis (PsA) in the Phase (Ph)21, Ph3 (DISCOVER [D]-1&2)2,3, and Ph3b COSMOS4 randomized controlled trials (RCTs).ObjectivesAssess GUS safety through 2 years (Y) in biologic (bio)-naïve and tumor necrosis factor inhibitor (TNFi)-experienced (exp) active PsA patients (pts) pooled across 4 RCTs (Week [W] 56: Ph2 and COSMOS; W60: D1; W112: D2).MethodsEligible pts in COSMOS had inadequate response to 1 or 2 prior TNFi; 9% of Ph2 pts and 30% of D1 pts had 1 or 2 prior TNFi; D2 pts were bio-naïve. Incidence rates of adverse events (AEs) are summarized among all treated pts for the placebo (PBO)-controlled (W0-24) and active treatment periods through 2Y (max duration of exposure 100 W) according to actual treatment received, calculated as the number of events per 100 pt-Y of follow-up (PY), along with 95% confidence intervals (CI). Gastrointestinal (GI)-related serious AEs (SAEs) were identified using the Medical Dictionary for Regulatory Activities (MedDRA) system-organ class; major adverse cardiovascular events (MACE; predefined as MI, Stroke, or CV death) and opportunistic infections (OIs) were identified through medical review.ResultsAcross the 4 RCTs, 1508 pts with active PsA received GUS 100 mg every 4 weeks (Q4W) or Q8W and were followed for a median of 1.2 Y, representing 2125 PY. In the overall population (N=1554), which includes PBO-treated pts that discontinued study agent prior to W24, 1138 pts were bio-naïve and 416 pts were TNFi-exp. Among all treated pts, the overall GUS safety profile was generally consistent with that of PBO through W24; rates remained low through 2Y of GUS (Table 1). The GUS safety profile was similar to that observed with PBO within the bio-naïve and TNFi-exp cohorts through W24. Incidence rates of AEs were generally consistent between cohorts in GUS-treated pts; whereas, TNFi-exp PBO-treated pts had more SAEs, study agent d/c due to AEs, and serious infections than bio-naïve PBO pts (Figure).Table 1.Overall Treatment-emergent AEsPBO-controlled (W0-24)aThrough up to 2YPBOb(N=517)GUS Q8W (N=664)GUS Q4W (N=373)Combined GUS (N=1037)GUS Q8W (N=664)GUS Q4W (N=373)Combined GUSc(N=1508)Total (median) PY230 (0.5)305 (0.5)172 (0.5)478 (0.5)941 (1.1)645 (2.1)2125 (1.2)Events/100 PY (95% CI)AEs223 (204, 243)233 (216, 250)223 (201, 246)229 (216, 243)164 (156, 172)139 (130, 148)146 (141, 151)SAEs8.7 (5.3, 13)4.9 (2.8, 8.1)5.2 (2.4, 9.9)5.0 (3.2, 7.5)6.4 (4.9, 8.2)4.7 (3.1, 6.6)5.7 (4.7, 6.8)AEs leading to study agent d/c4.4 (2.1, 8.0)3.6 (1.8, 6.5)7.0 (3.6, 12.2)4.8 (3.1, 7.2)2.6 (1.6, 3.8)2.9 (1.8, 4.6)2.7 (2.1, 3.5)Infections59 (50, 70)56 (48, 65)57 (47, 70)57 (50, 64)43 (38, 47)37 (33, 42)39 (36, 42)Serious Infections2.2 (0.71, 5.1)0.33 (0.01, 1.8)1.7 (0.36, 5.1)0.84 (0.23, 2.1)1.7 (0.97, 2.8)0.77 (0.25, 1.8)1.5 (1.0, 2.1)Malignancy0.44 (0.01, 2.4)0.98 (0.20, 2.9)0.00 (0.00, 1.7)0.63 (0.13, 1.8)0.42 (0.12, 1.1)0.00 (0.00, 0.46)0.28 (0.10, 0.61)MACE0.44 (0.01, 2.4)0.33 (0.01, 1.8)0.58 (0.01, 3.2)0.42 (0.05, 1.5)0.21 (0.03, 0.77)0.46 (0.10, 1.4)0.24 (0.08, 0.55)GI-related SAEs1.3 (0.27, 3.8)0.33 (0.01, 1.8)0.00 (0.00, 1.7)0.21 (0.01, 1.2)0.32 (0.07, 0.93)0.46 (0.10, 1.4)0.28 (0.10, 0.61)OIs0.00 (0.00, 1.3)0.00 (0.00, 0.98)0.00 (0.00, 1.7)0.00 (0.00, 0.63)0.21 (0.03, 0.77)0.00 (0.00, 0.46)0.14 (0.03, 0.41)MedDRA Version 23.1.a Includes safety follow-up data through 2Y for pts who d/c study agent prior to W24 and did not receive any study agent at or after W24.b Includes data prior to GUS in PBO pts who switched from PBO to GUS.c Includes PBO to GUS cross-over at W24.ConclusionThe favorable GUS safety profile demonstrated through W24 persisted through 2Y across bio-naïve and TNFi-exp pts.References[1]Deodhar A, et al. Lancet. 2018;391:2213-2224.[2]Deodhar A, et al. Lancet. 2020;395:1115-1125.[3]Mease PJ, et al. Lancet. 2020;395:1126-1136.[4]Coates LC, et al. ARD. 2021;80:140-141. OP0230.Disclosure of InterestsProton Rahman Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, and UCB, Grant/research support from: Janssen and Novartis, Wolf-Henning Boehncke Speakers bureau: AbbVie, Almirall, Janssen, Leo, Lilly, Novartis, and UCB, Consultant of: AbbVie, Almirall, Janssen, Leo, Lilly, Novartis, and UCB, Philip J Mease Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Consultant of: AbbVie, Aclaris, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Alice B Gottlieb Consultant of: AnaptsysBio, Avotres Therapeutics, Beiersdorf, Boehringer Ingelheim, Bristol-Myers Squibb, Incyte, GSK, Janssen, LEO Pharma, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical Industries, Inc., UCB, and Dermavant, Grant/research support from: Boehringer Ingelheim, Incyte, Janssen, Novartis, UCB, Xbiotech, and Sun Pharma, Iain McInnes Shareholder of: Causeway Therapeutics and Evelo Compugen, Consultant of: Astra Zeneca, AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Cabaletta, Compugen, GSK, Gilead, Janssen, Novartis, Pfizer, Sanofi, Roche, and UCB, Grant/research support from: Astra Zeneca, Bristol-Myers Squibb, Amgen, Eli Lilly, GSK, Janssen, Novartis, Roche, and UCB, Marlies Neuhold Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Pharmaceutical Companies of Johnson & Johnson, Yanli Wang Consultant of: Janssen, Employee of: IQVIA, Shihong Sheng Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Paul Bergmans Shareholder of: Johnson & Johnson, Employee of: Janssen Biostatistics, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Elke Theander Employee of: Janssen Scientific Affairs, LLC, Jenny Yu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Evan Leibowitz Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC, Marilise Marrache Shareholder of: Johnson & Johnson, Employee of: Medical Affairs, Janssen Inc., Laura Coates Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Medac, Novartis, Pfizer and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, and UCB

BackgroundPsoriatic arthritis (PsA) is characterized by a range of musculoskeletal and extra-articular disease manifestations. Composite indices are valuable tools to assess the multidimensional nature of PsA. The Psoriatic Arthritis Disease Activity Score (PASDAS)1 provides robust assessment of both joint and skin domains but is cumbersome to use in clinical practice. The Disease Activity Index for Psoriatic Arthritis (DAPSA)2 is relatively easy to use but does not assess skin disease.ObjectivesUsing pooled data from the phase 3 DISCOVER-1 and DISCOVER-2 studies of guselkumab (GUS) for the treatment of active PsA:3,4 (1) Describe the rate of achievement of a new composite endpoint combining DAPSA low disease activity (LDA; score ≤14, including remission) and Investigator Global Assessment (IGA) of psoriasis score ≤1 (range=0 [clear] to 4 [severe]); (2) Determine whether earlier (Week [W] 16) DAPSA LDA + IGA ≤1 is predictive of future achievement of minimal disease activity (MDA) or American College of Rheumatology (ACR) 50 response criteria; and (3) Contrast the performance of DAPSA LDA + IGA ≤1 with that of PASDAS LDA (score ≤3.2).MethodsPatients (pts) with active PsA despite standard therapies (DISCOVER-1: ≥3 swollen + ≥3 tender joints; CRP ≥0.3 mg/dL; ~30% had prior use of up to 2 TNF inhibitors; DISCOVER-2: ≥5 swollen + ≥5 tender joints; CRP ≥0.6 mg/dL; all pts were biologic-naïve) were randomized 1:1:1 to GUS 100 mg at W0, W4, then Q4W or Q8W; or placebo (PBO) with crossover to GUS Q4W at W24. In both studies, efficacy of GUS vs PBO was compared at W24 (primary endpoint). The number (%) of pts with DAPSA LDA + IGA ≤1 was determined at W24 for pts randomized to GUS or PBO. For all GUS-randomized pts, baseline variables associated with DAPSA LDA + IGA ≤1 and PASDAS LDA at W16 and the predictive value of W16 DAPSA LDA + IGA ≤1 or PASDAS LDA for achieving ACR50, MDA, and DAPSA LDA at W52 were assessed using logistic regression models.ResultsAt W24, DAPSA LDA + IGA ≤1 was met by 37% (277/748) of GUS-treated pts vs 13% (48/372) in the PBO group. At W16, 27% (203/748) of GUS-randomized pts had DAPSA LDA + IGA ≤1, and 22% (164/748) had PASDAS LDA. Among the 73% (545/748) of pts who did not have DAPSA LDA + IGA ≤1 at W16, most (77% [418/545]) had IGA ≤1 but not DAPSA LDA; 4% (23/545) had DAPSA LDA but not IGA ≤1, and 19% (104/545) had neither component. Baseline predictors of DAPSA LDA + IGA ≤1 at W16 were male gender, lower dactylitis score, lower Health Assessment Questionnaire-Disability Index (HAQ-DI) score, lower tender joint count (TJC), and higher Psoriasis Area and Severity Index (PASI) score. Baseline predictors of PASDAS LDA at W16 were younger age, lower dactylitis score, lower HAQ-DI score, lower TJC, and higher PASI score. As shown (Figure 1), pts who had DAPSA LDA + IGA ≤1 and PASDAS LDA at W16 were significantly more likely to achieve ACR50, MDA, and DAPSA LDA at W52 than pts without W16 responses; odds ratios (ORs) for achievement of ACR50, MDA, and DAPSA LDA responses at W52 were similar for pts who had DAPSA LDA + IGA ≤1 and for pts who had PASDAS LDA at W16. ORs for achievement of ACR50 and MDA at W52 were higher for pts who had both DAPSA LDA and IGA ≤1 at W16 (9.5 and 10.7) than for pts who had DAPSA LDA but not IGA ≤1 (6.5 and 3.5) or IGA ≤1 but not DAPSA LDA (1.6 and 1.5).ConclusionDAPSA LDA at W16 predicted future (W52) achievement of the stringent treatment targets of ACR50 and MDA; associations with W52 response were greater when W16 IGA ≤1 was added to DAPSA LDA. DAPSA LDA + IGA ≤1 at W16 as a predictor of W52 ACR50 and MDA response performed similarly to PASDAS LDA. The novel composite of DAPSA LDA + IGA ≤1 may be a reliable predictor of long-term PsA skin and joint response that is more practical to implement than the PASDAS.References[1]Helliwell PS et al. Ann Rheum Dis. 2013;72:986-91.[2]Schoels M et al. Ann Rheum Dis 2010;69:1441-47.[3]Deodhar A et al. Lancet 2020;395:1115-25.[4]Mease PJ et al. Lancet 2020;395:1126-36.Disclosure of InterestsWolf-Henning Boehncke Speakers bureau: AbbVie, Almirall, Janssen, Leo, Lilly, Novartis, and UCB, Consultant of: AbbVie, Almirall, Janssen, Leo, Lilly, Novartis, and UCB, Alice B Gottlieb Consultant of: AnaptsysBio, Avotres Therapeutics, Beiersdorf, Boehringer Ingelheim, Bristol-Myers Squibb Co., Incyte, GSK, Janssen, LEO Pharma, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical Industries, Inc., UCB, and Dermavant, Grant/research support from: Boehringer Ingelheim, Incyte, Janssen, Novartis, UCB, Xbiotech, and Sun Pharma, Enrique Soriano Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Consultant of: AbbVie, Janssen, Novartis, and Roche, Grant/research support from: AbbVie, Janssen, Novartis, Pfizer, Roche, and UCB, Alexis Ogdie Consultant of: Abbvie, Amgen, BMS, Celgene, CorEvitas, Gilead, Happify Health, Janssen, Lilly, Novartis, Pfizer, and UCB, Grant/research support from: Abbvie, Pfizer and Novartis and to Forward from Amgen, Olga Ziouzina Consultant of: AbbVie, Amgen, Janssen, Novartis, Eli Lilly, Pfizer, UCB, Celltrion, and Fresenius-Kabi, Emmanouil Rampakakis Consultant of: Janssen, Employee of: JSS Medical Research, Xie L Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Soumya D Chakravarty Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Pharmaceutical Companies of Johnson & Johnson, Marilise Marrache Shareholder of: Johnson & Johnson, Employee of: Janssen Inc, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Atul Deodhar Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Aurinia, Bristol Myers Squibb, Celgene, Eli Lilly, GlaxoSmithKline, Janssen, MoonLake, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer, and UCB

BackgroundGuselkumab (GUS), a selective inhibitor of IL-23, significantly improved the diverse manifestations of active psoriatic arthritis (PsA), including dactylitis and enthesitis, in DISCOVER (D)-1 & 2 trials of patients (pts) with active PsA1,2, with maintenance of response rates through 1 year (yr).3,4 Dactylitis and enthesitis, extra-articular manifestations of PsA, can be difficult to treat and cause significant disease burden.5,6ObjectivesTo evaluate the ability of GUS to provide long-term resolution of dactylitis and enthesitis in pts with PsA through 2 yrs of D-2.MethodsD-2 biologic naïve pts with active PsA were randomized 1:1:1 to GUS 100 mg every 4 weeks (Q4W); GUS 100 mg at W0, W4, Q8W; or placebo (PBO). At W24, PBO pts crossed over to GUS Q4W. Independent assessors evaluated dactylitis (total score: 0-60) and enthesitis (Leeds Enthesitis Index [LEI]; total score 0-6). These post hoc analyses assessed baseline (BL) frequency and severity of enthesitis in pts with dactylitis and dactylitis frequency in pts with enthesitis. Post BL, changes in dactylitis and LEI scores over time (least squares [LS] mean changes; analysis of covariance [ANCOVA]) and rates of resolution of dactylitis and enthesitis (Chi square correlation test) were determined in pts with these manifestations at BL (missing data imputed as no change/response).ResultsAt BL, more D-2 pts had enthesitis (68%) than dactylitis (45%). At BL, 78% of pts with dactylitis vs 61% without (w/o) dactylitis had enthesitis and 51% of pts with enthesitis vs 32% w/o enthesitis had dactylitis. Among pts with enthesitis at BL, a higher percentage of pts with dactylitis (52%) had severe enthesitis (LEI score ≥3) vs pts w/o dactylitis (44%). Among those with the condition at BL, resolution rates of dactylitis (57%, Q4W; 64%, Q8W) and enthesitis (44%, Q4W; 54%, Q8W) at W24 increased through W52 (dactylitis: 74%, Q4W; 78%, Q8W; enthesitis: 57%, Q4W; 61%, Q8W) and were maintained at W100 (dactylitis: 72%, Q4W; 83%, Q8W; enthesitis: 62%, Q4W; 70%, Q8W). Consistent results were observed when evaluating mean changes in dactylitis and LEI scores and in pts who crossed over from PBO to GUS Q4W at W24 (Table 1). In pts with dactylitis and enthesitis at BL, GUS-treated pts showed significant correlations between resolution of enthesitis and dactylitis at W24 (p=0.004), W52 (pTable 1.LS mean change from baseline over time in dactylitis and LEI scores in pts with manifestation at baselineGUS 100 mg Q4WGUS 100 mg Q8WPBO → GUS 100 mg Q4WDactylitis score (0-60)Pts, N12111199W24a-5.9 (-6.7, -5.0)-6.0 (-6.8, -5.1)-4.0 (-5.0, -3.1)W52a-6.5 (-7.2, -5.8)-7.2 (-7.9, -6.5)-6.9 (-7.6, -6.2)W100a-6.5 (-7.1, -5.8)-7.5 (-8.1, -6.8)-6.9 (-7.6, -6.2)LEI score (1-6)Pts, N170158178W24a-1.5 (-1.8, -1.3)-1.6 (-1.8, -1.4)-1.0 (-1.3, -0.8)W52a-1.8 (-2.0, -1.6)-1.9 (-2.1, -1.7)-2.0 (-2.2, -1.8)W100a-1.9 (-2.1, -1.7)-2.1 (-2.3, -1.8)-2.1 (-2.3, -1.9)aResults are LS mean change (95% confidence interval [CI]); LS mean change determined by ANCOVA; missing data was imputed as no change for pts who discontinued treatment and using multiple imputation for remaining missing dataGUS, guselkumab; LEI, Leeds Enthesitis Index; LS, least squares; PBO, placebo; pts, patients; Q4W, every 4 weeks; Q8W, every 8 weeks; W, weekConclusionPts with PsA often present with concurrent enthesitis and dactylitis, both of which can be recalcitrant to treatment. GUS resolved enthesitis and dactylitis in substantial proportions of pts through W100. GUS-treated pts who achieved enthesitis resolution were more likely to achieve dactylitis resolution and vice versa.References[1]Deodhar A et al. Lancet. 2020;395:1115[2]Mease PJ et al. Lancet. 2020;395:1126[3]Ritchlin C et al. RMD Open. 2021;7(1):e001457[4]McInnes IB et al. Arthritis Rheumatol. 2021;73:604[5]Kaeley GS et al. Semin Arthritis Rheum. 2018;48:35[6]McGonagle D et al. Nat Rev Rheumatol. 2019;15:113Disclosure of InterestsProton Rahman Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Grant/research support from: Janssen and Novartis, Iain McInnes Consultant of: AbbVie, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Gilead, Janssen, Novartis, and UCB, Grant/research support from: AstraZeneca, Bristol Myers Squibb, Celgene, Janssen, Eli Lilly, Novartis, and UCB, Atul Deodhar Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, GlaxoSmithKline, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer, and UCB, Georg Schett Speakers bureau: Abbvie, Janssen, and Novartis, Philip J Mease Speakers bureau: AbbVie, Aclaris, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Consultant of: AbbVie, Aclaris, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Grant/research support from: AbbVie, Aclaris, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, May Shawi Shareholder of: Janssen Global Services, LLC, Employee of: Janssen Global Services, LLC, Daniel Cua Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, Jonathan Sherlock Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, Alexa Kollmeier Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, Xie L Xu Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, Yusang Jiang Consultant of: Janssen, Employee of: Cytel Inc, Shihong Sheng Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, Christopher T. Ritchlin Consultant of: AbbVie, Amgen, Gilead, Janssen, Eli Lilly, Novartis, Pfizer, and UCB Pharma, Grant/research support from: AbbVie, Amgen, and UCB Pharma, Dennis McGonagle Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB

BackgroundEstablished criteria for classifying axial psoriatic arthritis (PsA) are lacking, and assessments of disease activity often rely on measures developed for ankylosing spondylitis (AS). There is an unmet need to systematically identify and measure efficacy of treatments for axial PsA patients (pts). Guselkumab (GUS), a selective interleukin (IL)-23p19 inhibitor, was efficacious in improving signs and symptoms of active PsA in 2 phase 3, randomized, placebo (PBO)-controlled studies: DISCOVER-1 and DISCOVER-2. In a post-hoc pooled analysis of DISCOVER-1&2 pts with investigator-confirmed sacroiliitis, GUS-treated pts had greater improvements in axial symptoms compared with PBO.1 Imaging in DISCOVER-1&2 was restricted to the sacroiliac (SI) joints, occurring prior to/at screening as confirmed by the investigator, and locally read.ObjectivesTo design a new, dedicated study to evaluate the effects of GUS on axial PsA prospectively.MethodsCumulative evidence from DISCOVER-1&2, including exposure–response relationship, covariate adjustment for modest baseline imbalances across treatment groups, subgroup analyses, and comparisons within and across these studies, was considered in designing a new trial. Data from the pivotal registrational studies suggest similar efficacy with GUS every-4-weeks (Q4W) and Q8W regimens in treating PsA signs and symptoms, including symptoms of axial involvement. Power calculations were based on mean changes in Bath AS Disease Activity Index (BASDAI) scores in DISCOVER-1&2.ResultsThe phase 4, randomized, PBO-controlled STAR study is specifically designed to prospectively assess efficacy outcomes in PsA pts with magnetic resonance imaging (MRI)-confirmed axial inflammation. Based on observed mean (SD) changes from baseline in BASDAI score from DISCOVER-1&2 (Table 1), 405 pts, randomized (1:1:1) to GUS Q4W, GUS at W0, W4, then Q8W, or PBO →GUS Q8W at W24, are planned for enrollment (Figure 1). STAR eligibility criteria include PsA ≥6 months and active disease (≥3 swollen & ≥3 tender joints, C-reactive protein [CRP] ≥0.3 mg/dL) despite prior non-biologic disease-modifying antirheumatic drugs, apremilast, and/or non-steroidal anti-inflammatory drugs. Pts will be naïve to biologics and Janus kinase inhibitors and have BASDAI ≥4, spinal pain score (visual analog scale [VAS]) ≥4, and screening MRI-confirmed axial disease (positive spine and/or SI joints defined as centrally read Spondyloarthritis Research Consortium of Canada [SPARCC] score ≥3). Follow-up MRIs of spine and SI joints will be obtained at W0, W24, and W52 and also centrally read, with readers blinded to treatment group and timepoint. Spinal/SI joint inflammation will be scored using the SPARCC method, with the former also assessed using the CAN-DEN method. The primary endpoint is mean change in BASDAI at W24; controlled (hierarchical) secondary endpoints, all at W24, include AS Disease Activity Score (ASDAS-CRP), Disease Activity Index for PsA (DAPSA), ≥40% improvement in Assessment in AS criteria (ASAS40), and mean changes in spine/SI joint SPARCC scores.Table 1.Power calculations for the primary endpoint in the Phase 4 STAR study.Historical trial data*Observed mean (SD) change in BASDAI from W0-24Effect sizePower(N=135; α=0.05)**PBO-1.28 (2.24)GUS 100 mg Q4W-2.51 (2.00)1.23>99%GUS 100 mg Q8W-2.61 (2.47)1.33>99%* From the pooled DISCOVER-1&2 trials**Power calculations based on N=135 per study group (1:1:1 randomization) and 2-sided significance of 0.05 using a 2-sample T-test assuming equal variancesBASDAI, Bath Ankylosing Spondylitis Disease Activity Index; GUS, guselkumab; PBO, placebo; Q4W, every 4 weeks; Q8W, every 8 weeks; SD, standard deviation; W, weekConclusionThe phase 4 STAR study will allow for an in-depth, prospective evaluation of the effects of selectively inhibiting the IL-23p19 subunit with GUS in pts with MRI-confirmed axial PsA.References[1]Mease, et al. Lancet Rheum. 2021;3(10):e715-e723.Disclosure of InterestsDafna D Gladman Consultant of: AbbVie, Amgen, BMS, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: Abbvie, Amgen, BMS, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB, Philip J Mease Speakers bureau: AbbVie, Aclaris, Amgen, BMS, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Consultant of: AbbVie, Aclaris, Amgen, BMS, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Grant/research support from: AbbVie, Aclaris, Amgen, BMS, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Paul Bird Speakers bureau: AbbVie, Eli Lilly, Gilead, Janssen, MSD, Pfizer, and UCB, Consultant of: Eli Lilly, Gilead, Janssen, Novartis, and Pfizer, Enrique Soriano Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Consultant of: AbbVie, Janssen, Novartis, and Roche, Grant/research support from: AbbVie, Janssen, Novartis, Pfizer, Roche, and UCB, Soumya D Chakravarty Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, Stephen Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Sean Quinn Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC, Cinty Gong Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC, Evan Leibowitz Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC, Lai-Shan Tam Consultant of: Janssen, Pfizer, Sanofi, AbbVie, Boehringer Ingelheim, and Lilly, Grant/research support from: Amgen, Boehringer Ingelheim, Janssen, GSK, Novartis, and Pfizer, Philip Helliwell Speakers bureau: AbbVie, Janssen, and Novartis, Consultant of: Galapagos and Janssen, Grant/research support from: AbbVie, Janssen, and Pfizer, Arthur Kavanaugh Consultant of: Abbvie, Amgen, Bristol Myers Squibb, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB, Atul Deodhar Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Glaxo Smith & Kline, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Eli Lilly, Glaxo Smith & Kline, Novartis, Pfizer, and UCB, Mikkel Østergaard Speakers bureau: AbbVie, Boehringer-Ingelheim, Bristol Myers Squibb, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Consultant of: AbbVie, Boehringer-Ingelheim, Bristol Myers Squibb, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Grant/research support from: AbbVie, Bristol Myers Squibb, Celgene, and Novartis, Xenofon Baraliakos Speakers bureau: AbbVie, Biocad, Chugai, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, Consultant of: AbbVie, Biocad, Chugai, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, Grant/research support from: AbbVie, Biocad, Chugai, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche, and UCB

BackgroundPsoriasis (PsO) and psoriatic arthritis (PsA) and are chronic immune-mediated diseases characterised by joint inflammation and skin lesions which negatively impact patients’ health-related quality of life (HRQoL). Several previous comparative studies have focused on PsA patients with or without skin involvement. Better understanding of the impact of both PsO and PsA on HRQoL and work / activity impairment will improve understanding of the incremental burden of PsA compared to PsO, and may lead to more personalised treatment options.ObjectivesTo compare HRQoL, work impairment, and daily activity impairment of patients with a PsO diagnosis (dx) only, PsO dx with musculoskeletal (MSK) symptoms (sx), PsA dx with active skin sx, and PsA dx without active skin sx.MethodsData were drawn from the Adelphi PsO & PsA Disease Specific Programmes™ (DSP), real-world point-in-time surveys of rheumatologists, dermatologists and their consulting patients in the United States and Europe (France, Germany, Italy, Spain and UK); conducted in 2018/19. Patients were grouped according to their symptoms and confirmed diagnoses, comprising four groups:1. Patients with PsO dx only,2. Patients with PsO dx and with MSK sx,3. Patients with PsA dx and with active skin sx,4. Patients with PsA dx with no active skin sx,Multivariate linear regression analyses with marginal mean predictions examined differences in patient-reported outcome measures (PROMs) between the four groups. Measures included HRQoL (EuroQol 5-Dimension 5-Level [EQ-5D Utility] and EuroQoL Visual Analogue Scale [EQ-VAS]), work impairment, and daily activity impairment (Work Productivity and Activity Impairment Questionnaire [WPAI]). Analyses controlled for demographics (age, sex, BMI), comorbidities present in >10% of patients and current treatment class (biologics, csDMARDs, steroids & other).Results4491 patients were included: Group 1 (n=1833), Group 2 (n=91), Group 3 (n=2451), and Group 4 (n=116). 54% of patients were male, 89% of patients were white, with a mean age of 46.6 years. Demographics were consistent across all patient groups.The model-predicted EQ-5D-Utility was lower in Groups 2, 3 and 4, compared with Group 1 (p=0.003, pTable 1.Predictions of PROMs for PsO-PsA patient groupsPRO toolGroup [n]*Predicted PRO valuePopulation norm (MCID)Regression model p-value (vs. reference group)EQ-5D Utility score (n=1839)1 (ref) [743]0.9220.88 (0.07)2 [32]0.8160.0033 [1023]0.8104 [41]0.8500.004EQ-VAS (n=1882)1 (ref) [763]78.7878.2 (n/a)2 [36]70.560.0573 [1040]73.890.0064 [43]75.230.248WPAI % overall work impairment (n=1015)1 (ref) [422]15.36n/a (15.0)2 [14]17.860.5603 [558]22.164 [21]26.090.014WPAI % work time missed (n=1028)1 (ref) [424]0.91n/a (n/a)2 [14]3.570.4863 [569]4.460.0024 [21]10.430.003WPAI % impairment while working (n=1153)1 (ref) [486]14.90n/a (20.0)2 [18]13.890.8463 [626]19.634 [23]17.390.435WPAI % activity impairment (n=1818)1 (ref) [732]18.02n/a (20.0)2 [32]26.250.1223 [1012]26.144 [42]25.240.044*n values provided for reference, but margins are predictions as a result of the model and not for the specific number of patients in each subgroup.(1) patients with PsO dx only(2) Patients with PsO dx and MSK sx(3) Patients with PsA dx and with active skin sx(4) Patients with PsA dx with no active skin sxOverall work impairment increased in Groups 3 and 4, compared with Group 1 (pConclusionPatients experiencing PsA dx or MSK sx experienced an additional disease burden compared to patients with PsO sx alone, as measured by worse HRQoL and work impairment.Disclosure of InterestsJoseph F. Merola Consultant of: Merck Research Laboratories, Abbvie, Dermavant, Eli Lilly and Company, Novartis, Janssen, UCB, Samumed, Celgene, Sanofi Regeneron, GSK, Almirall, Sun Pharma, Biogen, Pfizer, Incyte, Aclaris, and Leo Pharma, Lars Erik Kristensen Speakers bureau: Pfizer, AbbVie, Amgen, UCB, Gilead, Biogen, BMS, MSD, Novartis, Eli Lilly, and Janssen Pharmaceuticals, Consultant of: Pfizer, AbbVie, Amgen, UCB, Gilead, Biogen, BMS, MSD, Novartis, Eli Lilly, and Janssen Pharmaceuticals, Grant/research support from: Novo, UCB, Eli Lilly; Novartis and Abbvie, Feifei Yang Employee of: Employee of Janssen Pharmaceuticals, Steve Peterson Employee of: Employee of Janssen Pharmaceuticals, Rachel Teneralli Employee of: Employee of Janssen Pharmaceuticals, Nicola Massey Employee of: Adelphi Real World, Soumya D. Chakravarty Employee of: Employee of Janssen Pharmaceuticals, Megan Hughes Employee of: Adelphi Real World, May Shawi Employee of: Employee of Janssen Pharmaceuticals, Sarah Weatherby Employee of: Adelphi Real World, Christine Contre Employee of: Employee of Janssen Pharmaceuticals, Iris Lin Employee of: Employee of Janssen Pharmaceuticals, Fareen Hassan Employee of: Employee of Janssen Pharmaceuticals, M Elaine Husni Consultant of: Abbvie, Amgen, Eli Lilly, Novartis, Janssen, UCB, Pfizer, Regeneron, and BMS

BackgroundPatients with chronic inflammatory diseases can experience significant fatigue, negatively impacting health-related quality-of-life.1,2ObjectivesThis post-hoc analysis evaluated baseline fatigue severity among patients with psoriasis and/or psoriatic arthritis (PsA) and the effect of guselkumab treatment on patient-reported fatigue.MethodsVOYAGE-2 evaluated guselkumab every 8 weeks (Q8W) versus placebo (W16→guselkumab) and adalimumab in treating moderate-to-severe psoriasis.3 DISCOVER-14 and DISCOVER-25 evaluated guselkumab Q4W and Q8W versus placebo in treating active PsA. Fatigue was assessed using 36-item Short Form (SF-36) vitality scale score (includes 4 questions on fatigue/energy level); the US population norm=50±10; 5-10-point decrements are typically observed in conditions known to cause fatigue2; scores ≤35 indicate clinically important fatigue1; increases ≥5 indicate clinically meaningful improvement.2ResultsAcross randomized groups at baseline, mean SF-36 vitality scores were 47.7-48.5 in psoriasis and 42.2-44.0 in PsA patients; 11%-15% of psoriasis and 20%-28% of PsA patients had scores ConclusionAt baseline, patients with psoriatic disease experienced clinically important fatigue, more so with PsA (20%-28%) than psoriasis (11%-15%). In guselkumab-treated psoriasis and PsA patients, clinically meaningful improvements in fatigue were achieved at W16 and W24, respectively.References[1]Skoie IM et al. Br J Dermatol. 2017;177:505-12[2]Bjorner JB et al. Curr Med Res Opin. 2007;23:731-9[3]Reich K et al. J Am Acad Dermatol. 2017;76:418-31[4]Deodhar A et al. Lancet. 2020;395:1115-25[5]Mease PJ et al. Lancet. 2020;395:1126-36Disclosure of InterestsJoseph F. Merola Consultant of: AbbVie, Arena, Biogen, Bristol-Myers Squibb, Dermavant, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, and UCB Pharma, Yi-Hsuan Liu Employee of: Janssen Global Services, LLC and may own stock or stock options in Johnson & Johnson, Ya-Wen Yang Employee of: Immunology Global Medical Affairs, Janssen Pharmaceutical Companies of Johnson & Johnson, and may own stock or stock options in Johnson & Johnson, Megan Miller Employee of: Janssen Research & Development, LLC and may own stock or stock options in Johnson & Johnson, May Shawi Employee of: Immunology Global Medical Affairs, Janssen Pharmaceutical Companies of Johnson & Johnson, and may own stock or stock options in Johnson & Johnson, Daphne Chan Employee of: Janssen Scientific Affairs, LLC and may own stock or stock options in Johnson & Johnson, Saakshi Khattri Speakers bureau: Abbvie, Eli Lilly, UCB, Janssen, Paid instructor for: Abbvie, Eli Lilly, UCB, Janssen, Consultant of: Abbvie, Eli Lilly, UCB, Janssen, Grant/research support from: Pfizer, Abbvie, Leo, BMS, Eli Lilly, Laura Savage Speakers bureau: AbbVie, Almirall, Amgen, Celgene, Celltrion, Eli Lilly, Galderma, Janssen, LEO Pharma, MSD, Novartis, Sanofi and UCB Pharma, Consultant of: AbbVie, Almirall, Amgen, Celgene, Celltrion, Eli Lilly, Galderma, Janssen, LEO Pharma, MSD, Novartis, Sanofi and UCB Pharma, Grant/research support from: Janssen and Pfizer, Wolf-Henning Boehncke Speakers bureau: AbbVie, Almirall, Celgene, Eli Lilly, Janssen, LEO Pharma, Novartis, and UCB Pharma; and has received a research grant from Pfizer, Consultant of: AbbVie, Almirall, Celgene, Eli Lilly, Janssen, LEO Pharma, Novartis, and UCB Pharma; and has received a research grant from Pfizer, Chenglong Han Employee of: Janssen Global Services, LLC and may own stock or stock options in Johnson & Johnson

BackgroundFatigue, one of the top 3 patient (pt)-reported symptoms of psoriatic arthritis (PsA) and a recent PsA outcome domain,1 causes impaired health-related quality-of-life, diminished productivity, and disability.1-3 Although the origins of fatigue are multifactorial, inflammation is hypothesized to play an important role.4 In pts with active PsA, treatment with guselkumab (GUS) led to clinically meaningful and sustained improvements in fatigue through 1 year in DISCOVER-1 (D1) and DISCOVER-2 (D2).5ObjectivesTo identify 1) factors associated with fatigue and 2) factors associated with change in fatigue among pts with PsA treated with GUS.MethodsIn the Phase 3 D1 (N=381, biologic-naïve and tumor necrosis factor inhibitor-experienced) and D2 (N=739, biologic-naïve) studies, pts with active PsA despite standard therapies and/or biologic disease-modifying antirheumatic drugs were randomized 1:1:1 to GUS 100 mg every 4 weeks (Q4W); GUS 100 mg at W0, W4, then Q8W; or placebo (PBO) with crossover to GUS 100 mg Q4W at W24. The pt-reported Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale measured fatigue (scored 0-52). In these post-hoc analyses of D1 and D2 pts, a principal component analysis (PCA) was performed using W0 data to identify the underlying baseline factors associated with fatigue. Additionally, linear regression analyses were performed to identify covariates associated with change in fatigue from W0 to W24.ResultsIn 1120 pts (mean age 47 yrs, mean disease duration 5.9 yrs, 48% female), mean FACIT-Fatigue scores at baseline ranged from 29.1 to 31.4 (vs 43.6 for the general US population).5 PCA showed that 62% of the variability in fatigue could be explained by 3 components (Figure 1). The first component, explaining 34% of variability in fatigue, largely comprised systemic disease activity and function measures such as pain, pt global assessment of disease activity (PtGDA), physician’s global assessment of disease activity, and Health Assessment Questionnaire-Disability Index (HAQ-DI). The second component, explaining 16% of variability, comprised joint manifestations including swollen joint count (SJC) and tender joint count (TJC). Skin involvement as assessed by Psoriasis Area and Severity Index (PASI) and systemic inflammation (C-reactive protein [CRP]) could explain 12% of the variability in fatigue (Figure 1 and Table 1). In a multivariate linear regression analysis, after adjusting for effects from other variables, improvement in CRP, physical function (HAQ-DI), PtGDA, and PASI score were significantly associated with fatigue improvement in GUS-treated pts at W24 (all pTable 1.PCA of Pts With Active PsA in D1+D2 (N=1120; Pooled W0 data): Factor Loading Estimates by CovariatesComponent1 Systemic Disease Activity and FunctionComponent 2 Joint ManifestationsComponent 3 Skin Involvement and InflammationPsA disease duration, yr0.100.140.25PASI total score (0-72)0.220.230.74CRP, mg/dL0.36-0.130.55HAQ-DI score (0-3)0.73-0.09-0.19Pain (0-10 VAS)0.83-0.35-0.13PtGDA (0-10 VAS)0.82-0.36-0.16Physician global assessment of disease activity (0-10 VAS)0.65-0.180.23SJC (0-66)0.500.74-0.12TJC (0-68)0.540.70-0.18VAS=Visual Analog Scale.ConclusionAmong pts with PsA, measures of systemic disease activity and function, followed by joint manifestations, and skin involvement/inflammation accounted for 62% of the variability in fatigue. The large residual effect (38%) that was unexplained by the current model suggests the need for further research to identify additional factors (eg, distinct molecular pathways) contributing to the fatigue reported by PsA pts.References[1]Leung YY, et al. J Rheumatol (Suppl). 2020;96:46-9.[2]Gudu T, et al. Joint Bone Spine. 2016;83:439-43.[3]Husted JA, et al. Ann Rheum Dis. 2009;68:1553-8.[4]Krajewska-Włodarczyk M, et al. Reumatologia. 2017;55:125-30.[5]Rahman P, et al. Arthritis Res Ther. 2021;23:190.Disclosure of InterestsProton Rahman Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, and UCB, Grant/research support from: Janssen and Novartis, Philip J Mease Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Consultant of: AbbVie, Aclaris, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GSK, Inmagene, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Atul Deodhar Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Aurinia, Bristol Myers Squibb, Celgene, Eli Lilly, GlaxoSmithKline, Janssen, MoonLake, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer, and UCB, Arthur Kavanaugh Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Genentech, Janssen, Merck, Novartis, Pfizer and UCB, Soumya D Chakravarty Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Yan Liu Shareholder of: 3 Johnson & Johnson, Employee of: Janssen Research & Development, LLC, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Pharmaceutical Companies of Johnson & Johnson, Chenglong Han Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC.

BackgroundDactylitis is a biomarker of disease severity in psoriatic arthritis (PsA) associated with functional disability, impaired quality of life and radiographic progression. The COSMOS study demonstrated the efficacy and safety of guselkumab (GUS), an IL-23 p19 subunit inhibitor (i), in patients (pts) with PsA who had inadequate response (IR; insufficient efficacy or intolerance) to 1–2 TNFi.1ObjectivesEvaluate the effect of GUS 100 mg Q8W on dactylitis, and assess the relationship between dactylitis resolution and improvement in other clinical outcomes, through 1 year in TNFi-IR PsA pts.MethodsPts received GUS or placebo (PBO); PBO pts crossed over to GUS at either Week (W) 16 (early escape [EE], n=45/96) or W24 (planned, n=51/96). Each of 20 digits was determined by the investigator to have no (0) to severe (3) dactylitis (Dactylitis Severity Scale [DSS]; total score: 0–60). Presence of dactylitis was defined by DSS score ≥1; complete or partial resolution was defined as a DSS score=0, or lower than baseline (BL), respectively. Change in DSS from BL at W24 was a secondary endpoint. Other clinical response outcomes including DAPSA LDA/remission, MDA and enthesitis resolution (Leeds Enthesitis Index score=0) were assessed by dactylitis resolution status. Both as observed and non-responder imputation (NRI; for missing data or EE) data are presented.ResultsOf 285 pts, 103 (36%; 67 GUS, 36 PBO) had dactylitis and 190 (67%) had enthesitis at BL. The majority of pts with dactylitis (76%) also had enthesitis. Pts with dactylitis had more severe joint and skin disease than those without (Table 1).Table 1.BL characteristics for TNFi-IR PsA pts with/without dactylitisWith dactylitisWithout dactylitisN103182Age, mean years (SD)48.3 (11.8)49.6 (12.5)Sex: male, %5048Years since PsA diagnosis; mean (SD)8.1 (7.2)8.6 (7.8)BMI, mean kg/m2 (SD)28.5 (5.8)30.1 (6.6)PsA characteristicsSwollen joint count, 0–66; mean (SD)12.3 (8.1)8.5 (4.8)Tender Joint count, 0–68; mean (SD)22.0 (12.9)19.1 (12.2)DAPSA score; mean (SD)48.6 (20.9)41.2 (16.8)Spondylitis with peripheral arthritis, %2824Enthesitis, %7662Psoriasis characteristics, mean (SD) PASI score, 0–7214.5 (12.7)8.8 (9.6) BSA, %23.4 (23.6)12.4 (17.1) DLQI score, 0–3014.1 (7.0)12.6 (6.9)In an as-observed analysis of pts with BL dactylitis, numerically more GUS- (55%) than PBO- (33%) treated pts achieved complete dactylitis resolution at W16. By W48, 80% of GUS-randomized pts achieved complete resolution (NRI: 57% at W24, 67% at W48; Figure 1).Among 12 GUS pts with persistent dactylitis at W48, 9 (75%) had partial resolution. The 36 PBO pts with dactylitis crossed over to GUS at W16 (n=23; EE) or W24 (n=13; planned). As observed, 88% of these PBO→GUS pts had complete resolution of dactylitis at W48 (Figure 1).Of 105 dactylitis-free pts at BL in the GUS arm, 8 (8%) developed dactylitis before W48: 4 at W4, 2 at W8 and 1 each at W16 and 36. Complete resolution was seen in 6 (75%) of the 8 pts by W48, when 1 further new-onset case occurred.Utilizing observed data among GUS-randomized pts with and without BL dactylitis, 32% and 34%, respectively, achieved MDA at W48. Respective response rates were 59% and 55% for DAPSA LDA, and 28% and 15% for DAPSA remission. In those who did and did not achieve complete dactylitis resolution at W48, respective response rates were 38% and 0% for MDA, 68% and 13% for DAPSA LDA, and 31% and 0% for DAPSA remission. Of 69 pts with both enthesitis and dactylitis at BL who continued to receive GUS through W48, GUS resolved both manifestations in 72%, neither in 16%, only enthesitis in 4%, and only dactylitis in 7% of pts.ConclusionComplete dactylitis resolution was achieved in ≥80% of pts who continued to receive GUS at W48, with partial resolution seen in most remaining pts in an as-observed analysis. Response rates increased through W48. Dactylitis resolution in this difficult-to-treat TNFi-IR PsA population was frequently associated with enthesitis resolution and achievement of clinical outcomes representing low levels of disease activity.References[1]Coates LC et al. Ann Rheum Dis 2021Disclosure of InterestsHelena Marzo-Ortega Speakers bureau: Abbvie, Biogen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Takeda, UCB, Consultant of: Abbvie, Eli Lilly, Janssen, Moonlake, Novartis, Pfizer, Takeda, UCB, Grant/research support from: Janssen, Novartis, UCB, Elke Theander Employee of: Employed by Janssen Scientific Affairs, LLC (a subsidiary of Johnson & Johnson), Marlies Neuhold Shareholder of: Own Johnson & Johnson stock and/or stock options, Employee of: Employed by Janssen Scientific Affairs, LLC (a subsidiary of Johnson & Johnson), Paul Bergmans Shareholder of: Own Johnson & Johnson stock and/or stock options, Employee of: Employed by Janssen Scientific Affairs, LLC (a subsidiary of Johnson & Johnson), May Shawi Shareholder of: Own stock in Johnson & Johnson, Employee of: Employed by Immunology Global Medical Affairs, Janssen Pharmaceutical Companies of Johnson & Johnson, Michelle Perate Shareholder of: Own stock in Johnson & Johnson, Employee of: Employed by Immunology Global Medical Affairs, Janssen Pharmaceutical Companies of Johnson & Johnson, Christine CONTRE Shareholder of: Own Johnson & Johnson stock and/or stock options, Employee of: Employed by Janssen Scientific Affairs, LLC (a subsidiary of Johnson & Johnson), Iain McInnes Consultant of: Abbvie, Amgen, Astra Zeneca, BMS, Cabaletta, Causeway Therapeutics, Compugen, Evelo, Gilead, GSK, Janssen, Lilly, Moonlake, Novartis, Pfizer, Sanofi, UCB, Grant/research support from: Amgen, AstraZeneca, BMS, GSK, Janssen, Lilly, Novartis, Pfizer, UCB, Georg Schett: None declared

BackgroundDespite effective treatments, a minority of psoriatic arthritis (PsA) patients (pts) realize sustained minimal disease activity (MDA).1 Pt-driven domains of MDA are less frequently achieved, potentially arising from comorbid conditions.1ObjectivesIdentify domains contributing to and factors influencing MDA achievement in the 2-year Phase 3 DISCOVER-2 trial.MethodsRandomized and treated adults (N=739) had active PsA, were biologic/JAK inhibitor-naive, and had swollen and tender joint counts (SJC/TJC) each ≥5 and C-reactive protein ≥0.6 mg/dL. Pts with medical history of fibromyalgia (FM) were not excluded. Pts were randomized 1:1:1 to GUS 100 mg every 4 weeks (Q4W); GUS 100 mg at W0, W4, then every 8 weeks (Q8W); or placebo (PBO); PBO pts crossed over to GUS 100 mg Q4W at W24. MDA requires fulfillment of ≥5/7 criteria: TJC ≤1, SJC ≤1, Psoriasis Area and Severity Index (PASI) score ≤1, Pt Pain score ≤15, Pt global disease activity (PtGA) score ≤20, Health Assessment Questionnaire – Disability Index (HAQ-DI) score ≤0.5, and ≤1 tender entheses. A longitudinal trajectory of achieving each MDA criterion through W100 was derived (nonresponder imputation [NRI]). Time to achieve was estimated via Kaplan-Meier survival curve for scores deriving from native scales and those normalized to a 0-66 scale (corresponding to SJC). Multivariate regression models for time to achievement (cox proportional hazard) and achievement (logistic regression) of MDA at W100 identified predictors of response.ResultsAmong 492 GUS pts, continuous improvement across all MDA domains was shown through proportions of pts achieving criteria at W24 & W100 (NRI): SJC (45% & 65%), TJC (16% & 34%), PASI (71% & 72%), Pt Pain (23% & 37%), PtGA (29% & 45%), HAQ-DI (34% & 44%), entheseal points (75% & 80%). Times to achieve minimal SJC, PASI, and enthesitis with GUS were significantly faster than for PtGA, Pt Pain, TJC, and HAQ-DI for native-scale scores; when normalized, PtGA, Pt Pain, and HAQ-DI were achieved less often (Figure 1). Higher baseline (BL) Pt Pain score and lower BL Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score (worse fatigue) were significant predictors of longer time; lower BMI was associated with shorter time to achieve Pt Pain ≤15. Results for achieving Pt Pain ≤15 at W100 were similar. Worse baseline fatigue and PtGA were significant predictors of longer time to PtGA ≤20; worse fatigue also predicted non-achievement of PtGA ≤20 at W100. For time to achieve HAQ-DI ≤0.5, significant BL negative predictors were higher age and BL HAQ-DI score, which were also significant predictors of HAQ-DI ≤0.5 non-achievement at W100. Although seen in only a small number of pts, a significant impact of FM history and suicidal ideation/behavior on Pt Pain ≤15 and HAQ-DI ≤0.5, respectively, was observed (Table 1).Table 1.Predictors of Time to Achievement and Achievement of Recalcitrant MDA Domains at Week 100 in GUS-randomized Pts (N=492)Time to achievementIndependent BL VariablesPt Pain ≤15PtGA ≤20HAQ-DI ≤0.5HR (95% CI)HR (95% CI)HR (95% CI)Age-0.98 (0.97-0.99)†HAQ-DI-0.26 (0.19-0.36)‡PtGA VAS-0.99 (0.98-1.00)*-Pain VAS0.99 (0.98-1.00)†-FACIT-Fatigue§1.02 (1.00-1.03)*1.02 (1.01-1.04)‡-BMI0.98 (0.96-1.00)*FM (N=8)0.70 (0.55-0.90)†--Achievement at W100OR (95% CL)∥OR (95% CL)∥OR (95% CL)∥Age--0.98 (0.96: 1.00)*HAQ-DI--0.13 (0.08: 0.20)‡Pain VAS0.98 (0.97: 1.00)†--FACIT-Fatigue§1.02 (1.00: 1.05)*1.05 (1.03: 1.07)‡-BMI0.97 (0.94: 1.00)*--Suicidal Ideation/Behaviour (N=9)--0.16 (0.03: 0.86)*FM (N=8)0.59 (0.40: 0.86)†--HR Hazard Ratio CI Confidence Interval OR Odds Ratio CL Confidence Limits*p †p ‡p ≤0.0001§Higher score indicates less fatigue∥Wald CLConclusionGUS provided continuous improvement in each MDA domain through W100. BL domain score, as well as age, fatigue, and BMI, were significant determinants of MDA achievement in recalcitrant pt-driven domains (Pt Pain, PtGA, HAQ-DI). The impact of FM and mental health status merits further evaluation.References[1]Rahman et al. BMJ Open 2017;7(8): e016619Disclosure of InterestsLaura Coates Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Medac, Novartis, Pfizer and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Proton Rahman Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, and UCB, Grant/research support from: Janssen and Novartis, Philip J Mease Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Consultant of: AbbVie, Aclaris, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GSK, Inmagene, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Pharmaceutical Companies of Johnson & Johnson, Emmanouil Rampakakis Consultant of: Janssen, Employee of: JSS Medical Research, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Xie L Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC,, Soumya D Chakravarty Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC, Iain McInnes Shareholder of: Causeway Therapeutics, and Evelo Compugen, Consultant of: Astra Zeneca, AbbVie, Bristol-Myers Squibb, Amgen, Eli Lilly and Company, Cabaletta, Compugen, GSK, Gilead, Janssen, Novartis, Pfizer, Sanofi, Roche, and UCB, Grant/research support from: Astra Zeneca, Bristol-Myers Squibb, Amgen, Eli Lilly and Company, GSK, Janssen, Novartis, Roche, and UCB, Lai-Shan Tam Consultant of: Janssen, Pfizer, Sanofi, AbbVie, Boehringer Ingelheim, and Lilly, Grant/research support from: Amgen, Boehringer Ingelheim, Janssen, GSK, Novartis and Pfizer

BackgroundAccurate assessment of psoriatic arthritis (PsA) disease activity in clinical practice requires a feasible, continuous, multidimensional composite instrument to assess key domains of this heterogeneous disease. While currently available composite tools used in PsA, including the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis Composite Exercise (GRACE) and the PsA Disease Activity Score (PASDAS), are useful in clinical trials, their complexity and time required to complete limit their use in clinical practice.1 Abbreviated instruments, known as 3 visual analogue scale (VAS) and 4VAS, have demonstrated good performance in an observational study, but further testing was recommended.2ObjectivesExplore the correlation between 3VAS or 4VAS and GRACE, PASDAS and measures of quality of life using data from COSMOS.MethodsThe Phase 3b COSMOS study assessed guselkumab (GUS) 100mg Q8W versus placebo (PBO) in tumour necrosis factor inhibitor (TNFi) inadequate response (IR, inadequate efficacy or intolerance) pts with active PsA.3 Pts who received PBO crossed over to GUS at either Week (W) 16 (early escape [EE], n=45/96) or W24 (planned, n=51/96). Each domain of the 3VAS (physician global, pt global, pt skin) and 4VAS (physician global, pt pain, pt joint, pt skin) was evaluated using a 0–10 VAS (higher score=more active disease), and calculated mean scores were plotted over time in apt-continuer population (those with W0 and W48 data). Pearson correlation assessed relationships between observed values over time for 3VAS/4VAS versus GRACE, PASDAS, the Health Assessment Questionnaire-Disability Index (HAQ-DI), and the 36-item Short Form Health Survey Physical Component Summary (SF-36 PCS) score.ResultsData from 285 pts were examined (GUS, n=189; PBO, n=96). Substantial improvements (>45%) were seen in GRACE, PASDAS, 3VAS and 4VAS scores through W48 in GUS-treated pts (Table 1), with separation from PBO as early as W8 (Figure 1). Strong correlations between 3VAS/4VAS and GRACE (r=0.83–0.92)/PASDAS (r=0.72–0.85) were observed in GUS-randomized pts at each visit (Table 1). 3VAS/4VAS showed moderate correlation with HAQ-DI (r=0.45–0.63) and SF-36 PCS (r=–0.40 toTable 1.Observed composite index scores and Pearson correlation coefficients by visitMean (SD)Correlation of 3VAS withCorrelation of 4VAS withVisitGRACEPASDAS3VAS4VASGRACEPASDASGRACEPASDASGUSBLN6.0 (1.1) 1886.4 (1.0) 1876.6 (1.5) 1886.6 (1.5) 1880.850.720.830.72W8N–5.2 (1.3) 1874.5 (1.8) 1884.7 (1.8) 188–0.80–0.81W16 N4.0 (1.7) 1854.7 (1.6) 1844.1 (2.0) 1854.2 (2.1) 1850.910.850.920.85W24 N3.7 (1.6) 1834.3 (1.5) 1823.7 (1.9) 1833.9 (2.0)1830.880.840.890.84W48 N2.8 (1.7) 1653.5 (1.5) 1612.7 (1.9) 1682.8 (2.0) 1680.900.830.900.83PBO→GUS (at W16 [n=45] or W24 [n=51)BL N5.7 (1.0) 966.2 (0.9) 966.1 (1.5) 966.1 (1.5) 960.810.630.830.66W8 N–5.5 (1.3) 935.3 (1.9) 945.3 (1.9) 94–0.78–0.80W16 N5.1 (1.6) 935.5 (1.5) 935.3 (2.1) 945.4 (2.1) 940.910.870.920.88W24 N4.4 (1.4) 934.8 (1.3) 924.4 (1.9) 934.5 (1.9) 930.910.820.900.81W48 N2.9 (1.6) 843.6 (1.4) 842.8 (2.0) 853.0 (2.1) 850.910.860.920.85BL, baseline; SD, standard deviation–0.65). Consistent results were observed in PBO→GUS pts.Figure 1.ConclusionIn these TNFi-IR pts, GUS treatment led to substantial improvements in PsA disease activity through 1 year using several composite indices. All indices, including the 3VAS/4VAS, allowed early discrimination between the GUS and PBO cohorts. The strong correlation between 3VAS/4VAS and GRACE/PASDAS in this pt population is promising and highlights that abbreviated composite indices can provide an accurate assessment of disease activity that may, because of better feasibility, lead to a wider use of such instruments and thus improve pt care. As a next step, thresholds for disease states should be further evaluated.References[1]Tillett W et al. J Rheumatol Suppl 2020;96:11–8[2]Tillett W et al. J Rheumatol Suppl 2021;97:45–9[3]Coates LC et al. Ann Rheum Dis 2021 (epub)Disclosure of InterestsWilliam Tillett Speakers bureau: Abbvie, Amgen, Celgene, Eli Lilly, Janssen, MSD, Novartis, Pfizer, UCB, Consultant of: Abbvie, Amgen, Celgene, Eli Lilly, Janssen, MSD, Novartis, Pfizer, UCB, Grant/research support from: Abbvie, Celgene, Eli Lilly, Janssen, Pfizer, UCB, Laura Coates Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Medac, Novartis, Pfizer and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Moonlake, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB, Marlies Neuhold Shareholder of: Own Johnson & Johnson stock and/or stock options, Employee of: Employed by Janssen Scientific Affairs, LLC (a subsidiary of Johnson & Johnson), Elke Theander Employee of: Employed by Janssen Scientific Affairs, LLC (a subsidiary of Johnson & Johnson), Paul Bergmans Shareholder of: Own Johnson & Johnson stock and/or stock options, Employee of: Employed by Janssen Scientific Affairs, LLC (a subsidiary of Johnson & Johnson), May Shawi Shareholder of: Own stock in Johnson & Johnson, Employee of: Employed by Immunology Global Medical Affairs, Janssen Pharmaceutical Companies of Johnson & Johnson, Michelle Perate Shareholder of: Own stock in Johnson & Johnson, Employee of: Employed by Immunology Global Medical Affairs, Janssen Pharmaceutical Companies of Johnson & Johnson, Christine CONTRE Shareholder of: Own Johnson & Johnson stock and/or stock options, Employee of: Employed by Janssen Scientific Affairs, LLC (a subsidiary of Johnson & Johnson), Philip Helliwell Speakers bureau: Abbvie, Amgen, Novartis, Janssen, Consultant of: Eli Lilly

BackgroundPsoriatic arthritis (PsA) patients (pts) with differing baseline (BL) characteristics may vary in their response to treatment. In the phase 3 DISCOVER-1 and DISCOVER-2 studies, guselkumab (GUS) significantly improved joint symptoms, skin disease, enthesitis, dactylitis, physical function, and quality of life at Week (W) 24 in pts with PsA.1,2 Clinical responses across these disease domains were maintained or increased with GUS at W52,3.4 regardless of BL pt demographics, disease characteristics, or conventional synthetic disease-modifying antirheumatic drug (csDMARD) use.5 Durable efficacy with GUS through W100 across multiple disease domains was observed.6ObjectivesAssess both BL predictors of, and by BL pt subgroups, GUS efficacy across PsA disease domains through W100 of DISCOVER-2.MethodsBiologic-naïve adults with active PsA despite standard therapies were enrolled in DISCOVER-2 (swollen joint count [SJC] ≥5 & tender joint count [TJC] ≥5, C-reactive protein [CRP] ≥0.6 mg/dL). Pts were randomized 1:1:1 to GUS 100 mg every 4 weeks (Q4W); GUS 100 mg at W0, W4, then Q8W; or placebo (PBO).2 GUS effects on joint, skin, enthesitis, dactylitis, spinal pain, and disease severity endpoints (change in Disease Activity in PsA [DAPSA], SJC, and TJC scores; Psoriasis [PsO] Area Severity Index [PASI] score [among pts with BL IGA ≥2 and body surface area [BSA] with PsO ≥3%]; Leeds enthesitis index [LEI] score [among pts with enthesitis at BL]; dactylitis score [among pts with dactylitis at BL]; spinal pain score; and PsA Disease Activity Score [PASDAS], respectively) at W100 were evaluated for GUS-randomized pts, both by treatment group and by pooling pts across Q4W and Q8W treatment arms. A multivariate linear model adjusting for BL pt characteristics assessed associations between BL predictors of interest and changes in DAPSA, PASI, and LEI scores from BL to W100, and to assess least squares mean (LSM) changes and 95% confidence intervals (CIs) in all continuous endpoints from BL to W100 within subgroups of pts defined by BL sex, body mass index (BMI), PsA duration, SJC, TJC, CRP level, %BSA, PASI score, and csDMARD use.Results442 (90%) GUS-randomized pts completed study treatment through W100.6 Among the BL predictors of long-term GUS efficacy assessed (see above), only PsA duration (p=0.032), SJC (pConclusionGUS significantly improved PsA signs and symptoms through W100 across all BL pt subgroups evaluated, including pts with highly active disease, and regardless of dosing regimen.References[1]Deodhar A et al. Lancet 2020;395:1115-25.[2]Mease PJ et al. Lancet 2020;395;1126-36.[3]Ritchlin CT et al. RMD Open 2021;7(1):e001457.[4]McInnes IB et al. Arthritis Rheumatol 2021;73:604-16.[5]Ritchlin CT et al. Ann Rheum Dis 2021;80:1291-2.[6]McInnes IB et al. Arthritis Rheumatol 2021;doi: 10.1002/art.42010.Disclosure of InterestsIain McInnes Shareholder of: Causeway Therapeutics, and Evelo Compugen, Consultant of: AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Eli Lilly, Cabaletta, Compugen, GSK, Gilead, Janssen, Novartis, Pfizer, Sanofi, Roche, and UCB, Grant/research support from: Amgen, AstraZeneca, Bristol Myers Squibb, Eli Lilly, GSK, Janssen, Novartis, Roche, and UCB, John Tesser Speakers bureau: AbbVie, Amgen, BMS, Eli Lilly, Janssen and Pfizer, Consultant of: AbbVie, Eli Lilly, Gilead, Janssen, Novartis, and Pfizer, Grant/research support from: AbbVie, Amgen, BMS, Celgene, CoreVitas, Eli Lilly, Gilead, Janssen, Pfizer, and Sun Pharma, Elena Schiopu Consultant of: Janssen, Grant/research support from: Janssen, Joseph F. Merola Consultant of: AbbVie, Arena, Biogen, Bristol Myers Squibb, Dermavant, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Grant/research support from: AbbVie, Arena, Biogen, Bristol Myers Squibb, Dermavant, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Soumya D Chakravarty Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC (a wholly owned subsidiary of Johnson & Johnson), Emmanouil Rampakakis Consultant of: Janssen, Employee of: JSS Medical Research, Natalie Shiff Shareholder of: AbbVie, Gilead, Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC (a wholly owned subsidiary of Johnson & Johnson), Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC (a wholly owned subsidiary of Johnson & Johnson), Xie L Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC (a wholly owned subsidiary of Johnson & Johnson), May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Pharmaceutical Companies of Johnson & Johnson, Frederic Lavie Shareholder of: Johnson & Johnson, Employee of: Janssen Pharmaceutical Companies of Johnson & Johnson, Paul Bird Speakers bureau: AbbVie, Eli Lilly, Gilead, Janssen, MSD, Pfizer, and UCB, Consultant of: Eli Lilly, Gilead, Janssen, Novartis, and Pfizer, Philip J Mease Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Consultant of: AbbVie, Aclaris, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GSK, Inmagene, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sun Pharma, and UCB

BackgroundGuselkumab (GUS) is a human monoclonal antibody targeting the interleukin-23p19-subunit. It has demonstrated efficacy at Week 24 in the Phase IIIb COSMOS clinical trial of patients with active psoriatic arthritis (PsA) and inadequate response or intolerance to one or two tumour necrosis factor inhibitors (TNFis).1ObjectivesThe aim of this post hoc analysis was to identify predictors of minimal disease activity (MDA) with GUS at Week 24 in patients with active PsA and inadequate response or intolerance to one or two TNFis.MethodsA multiple logistic regression analysis was performed to identify potential predictors of MDA with GUS at Week 24 in TNFi-refractory patients with PsA. Odds ratios, 95% confidence intervals and p-values were calculated. Baseline characteristics assessed as predictors included age, sex, body mass index (BMI), C-reactive protein (CRP), other medication use and disease duration. Clinical features included tender and swollen joint counts (TJC/SJC), affected joint location, dactylitis, enthesitis, spondylitis, Psoriasis Area and Severity Index (PASI) score and psoriasis (PsO) localisation (Figure 1). Missing data for MDA at Week 24 were imputed as non-response; missing baseline values were imputed for two patients.Figure 1.Odds ratios and 95% CIs for potential predictors of minimal disease activity response to guselkumab 100 mg every 8 weeks at Week 24 in patients with PsA and an inadequate response or intolerance to one or two prior TNF inhibitors.BMI, body mass index; CI, confidence interval; CRP, C-reactive protein; csDMARD, conventional systemic disease-modifying anti-rheumatic drug; HAQ-DI, Health Assessment Questionnaire - Disability Index; MDA, minimal disease activity; PASI, Psoriasis Area and Severity Index; PsA, psoriatic arthritis; PsO, psoriasis; TNF, tumour necrosis factor.N=187 for all clinical features and baseline characteristics. Negative predictors are indicated by bold text and positive predictors by italicisation (pResultsOf the 187 patients in this study, 54.6% were women and the mean disease duration was 8.3 years. The patients had a mean TJC 0–68 of 21.0, a mean SJC 0–66 of 10.3, a mean PASI score of 11.6 and a mean BMI of 28.9. Furthermore, 67.9% had enthesitis and 35.8% had dactylitis at baseline. One prior TNFi had been received by 88.2% of patients, and two received by 11.8%. At Week 24, 17.1% of patients (32/187) achieved MDA. Wrist involvement (p=0.031) and scalp PsO (p=0.049) were positive predictors of MDA. Women were significantly less likely to achieve MDA (p=0.036) than men; other negative predictors included involvement of shoulder or small joints of the hand, and hand/foot PsO (all pConclusionBaseline characteristics and clinical features may be positively (wrist involvement, scalp PsO) or negatively (female sex, involvement of shoulder or small joints of the hand, hand/foot PsO) associated with achieving MDA with GUS at Week 24 in a TNFi-refractory population. Though the low patient number limits the generalisability of this analysis, assessment of Week 48 data may further elucidate potential predictors of MDA after longer-term treatment.References[1]Coates C et al. Ann Rheum Dis 2021; 0: 1–11.Disclosure of InterestsWilliam Tillett Speakers bureau:, Consultant of:, Grant/research support from: William Tillett has received research grants and consulting or speaker fees from AbbVie, Amgen, Celgene, Eli Lilly, Janssen, MSD, Novartis, Pfizer and UCB., Sarah Ohrndorf Speakers bureau: Sarah Ohrndorf has received speaker fees or travel expense reimbursements from AbbVie, BMS, Janssen, Novartis and Pfizer., Julio Ramírez Speakers bureau:, Consultant of: Julio Ramírez has received consulting or speaker fees from AbbVie, Amgen, Eli Lilly, Janssen, Novartis and UCB., Marlies Neuhold Shareholder of: Johnson & Johnson., Employee of: Janssen, Robert Wapenaar Shareholder of: Johnson & Johnson., Employee of: Janssen, Elke Theander Shareholder of: Johnson & Johnson., Employee of: Janssen, Christine CONTRE Shareholder of: Johnson & Johnson., Employee of: Janssen, Mohamed Sharaf Shareholder of: Johnson & Johnson., Employee of: Janssen, May Shawi Shareholder of: Johnson & Johnson., Employee of: Janssen, Marijn Vis Speakers bureau:, Consultant of:, Grant/research support from: Marijn Vis has received research grants and consulting or speaker fees from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, UCB and the Dutch Arthritis Foundation.

To compare healthcare resource utilization and costs among patients with psoriasis, psoriatic arthritis (PsA), and a control group of patients without psoriasis and PsA in the USA.The IBM® MarketScan® Commercial Database was used to identify three adult patient groups from 1/1/2009 through 4/30/2020: (1) Psoriasis: ≥ 2 diagnoses ≥ 30 days apart for psoriasis (no PsA diagnoses); (2) PsA: ≥ 2 diagnoses for PsA; (3) Control: no psoriasis or PsA diagnoses in their entire claims records. Patients with comorbid rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, or ulcerative colitis were excluded from the analyses. Controls were matched 1:1 to psoriasis and PsA patients based on age, gender, index year, and number of non-rheumatological comorbidities. Healthcare resource utilization and costs (in 2019 USD) were evaluated descriptively and through mixed models for five years of follow-up.A total of 142,531 psoriasis and 21,428 PsA patients were matched to the control group (N = 163,959). Annual all-cause healthcare costs per patient were $7,470, $11,062, and $29,742 for the control, psoriasis, and PsA groups, respectively. All-cause healthcare costs increased over time and were significantly greater among PsA vs. psoriasis (p0.0001) and the control groups (p0.0001). Across all categories of healthcare resources, utilization was greatest among patients with PsA and lowest in the control group.Annual healthcare costs and resource utilization were significantly higher with PsA compared with psoriasis and the control group, confirming the substantial economic burden of PsA. The cost disparity between these patient groups highlights a continued unmet medical need. Key Points • Patients with PsA incurred significantly greater healthcare resource utilization and costs than patients with psoriasis and patients without psoriasis and PsA. • Significantly greater costs and healthcare resource utilization were also observed among patients with psoriasis compared with patients without psoriasis and PsA.

BackgroundPsoriatic arthritis (PsA) and ankylosing spondylitis (AS) represent the prototypical spondyloarthritides. PsA patients may also suffer from axial disease (axPsA). Despite overlapping symptoms, axPsA and AS may be distinct disorders with differing clinical manifestations, genetic associations, and radiographic findings.1 These disorders also respond differently to immunomodulatory therapies such as anti-interleukin (IL)-23 inhibitors. While guselkumab, a human monoclonal antibody targeting the IL-23p19 subunit, improved symptoms of axPsA,2 risankizumab, a humanized monoclonal antibody targeting the IL-23p19 subunit, did not show improvement in the primary endpoint of proportion of AS patients achieving an Assessment of SpondyloArthritis International Society 40% (ASAS40) response at week (W) 12.3ObjectivesTo understand molecular distinctions between axPsA and AS to differentiate these diseases and guide treatment choice.MethodsWhole blood and serum samples were collected from consenting patients in the NCT03162796/NCT0315828 studies of guselkumab in PsA and the NCT02437162/NCT02438787 studies of ustekinumab in AS. axPsA patients were investigator-verified as having magnetic resonance imaging- or pelvic x-ray-confirmed sacroiliitis at screening (locally read). Human leukocyte antigen (HLA) genotypes were determined by RNA sequencing, limited to Caucasian patients to reduce genetic variability,4 and select serum cytokine levels were analyzed alongside samples from healthy individuals. Differential prevalence of HLA alleles in axPsA versus AS was determined using a Fisher’s Exact test. Statistical significance of differential baseline serum cytokine expression among axPsA versus non-axPsA versus AS patients, and of guselkumab effect on serum cytokine reduction versus placebo among axPsA and non-axPsA patients, were determined with a generalized linear model performed on log2-transformed data. Biomarker data from guselkumab every-4-weeks and every-8-weeks treatment arms were pooled.ResultsAmong the 186/234 Caucasian axPsA/AS patients with available data, 34%/15% were female, 70%/14% used methotrexate at baseline, mean serum C-reactive protein (CRP) levels were 2.8/2.4 mg/dL and mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores were 6.4/7.5, respectively. Aside from race, baseline demographics and disease characteristics were representative of the overall population. The prevalence of class I HLA allele -B27, -C01, and -C02 carriers was significantly lower in axPsA than AS patients (30.7% versus 92.3%, pConclusionAdults with axPsA and AS exhibit different genetic risk factors and serum IL-17 levels, supporting the concept of distinct disorders. Guselkumab demonstrated significant pharmacodynamic effects in axPsA patients that aligned with such effects in non-axPsA patients, consistent with observed clinical improvement.2References[1]Feld et al. Nat Rev Rheumatol. 2018;14(6):363-371.[2]Mease et al. Lancet Rheumatol. 2021;3(10)E715-E723.[3]Baeten et al. Ann Rheum Dis. 2018;77(9):1295-1302.[4]Buchkovich et al. Genome Med. 2017;9(86).Disclosure of InterestsArthur Kavanaugh Consultant of: AbbVie, Amgen, BMS, Genentech, Janssen, Eli Lilly, Merck, Novartis, Pfizer and UCB, Xenofon Baraliakos Consultant of: AbbVie, Chugai, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, Grant/research support from: AbbVie, MSD, and Novartis, Sheng Gao Employee of: Janssen Research & Development, LLC, and may own stock or stock options in Johnson & Johnson, Warner Chen Employee of: Janssen Research & Development, LLC, and may own stock or stock options in Johnson & Johnson, Kristen Sweet Employee of: Janssen Research & Development, LLC, and may own stock or stock options in Johnson & Johnson, Soumya D Chakravarty Employee of: Janssen Scientific Affairs, LLC, and may own stock or stock options in Johnson & Johnson, Qingxuan Song Employee of: Janssen Research & Development, LLC, and may own stock or stock options in Johnson & Johnson, May Shawi Employee of: Janssen Pharmaceutical Companies of Johnson & Johnson, and may own stock or stock options in Johnson & Johnson, Frank Behrens Speakers bureau: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Chugai, Eli Lilly, Galapagos, Genzyme, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB, Consultant of: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Chugai, Eli Lilly, Galapagos, Genzyme, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB, Grant/research support from: Celgene, Chugai, Janssen, Pfizer, and Roche, Proton Rahman Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, and UCB, Grant/research support from: Janssen, research grants from Janssen and Novartis

BackgroundIn the phase 3 DISCOVER-2 (D2) study, guselkumab (GUS) 100 mg every 4/8 weeks (Q4W/Q8W) significantly improved joint and skin symptoms in patients (pts) with active psoriatic arthritis (PsA); GUS-treated pts had smaller mean changes in radiographic progression vs placebo (PBO) at W24.1 Clinical response rates and favorable safety profile were durable through W100.2, 3ObjectivesTo report details of radiographic assessments comprising Reading Session 3 through W100 of D2, including relationships between radiographic changes and measures of clinical outcomes.MethodsBiologic-naïve adults with active PsA (≥5 swollen + ≥5 tender joint count; CRP ≥0.6 mg/dL) were randomized (1:1:1) to GUS 100 mg Q4W; GUS 100 mg at W0, W4, then Q8W; or PBO with crossover to GUS 100 mg Q4W (PBO→Q4W) at W24, all through W100. Radiographic Reading Session 3 included assessments at W0/24/52/100 (or at discontinuation after W52) from pts ontinuing study treatment at W52; readers were blinded to treatment group and timepoint. Observed mean changes in total PsA-modified van der Heijde-Sharp (vdH-S), joint space narrowing (JSN), and erosion scores were reported. Changes in total vdH-S scores from W0-100 were determined in pts who did and did not achieve clinical response at W100, assessed by ACR20/50/70, low disease activity (LDA) based on Disease Activity in Psoriatic Arthritis score (DAPSA; ≤14) or Psoriatic Arthritis Disease Activity Score (PASDAS; ≤3.2), minimal disease activity (MDA), and normalized Health-Assessment Questionnaire-Disability Index (HAQ-DI) score (ResultsOf 739 randomized pts, 664 had evaluable data from Reading Session 3; 629 had evaluable data from W52-100. Mean total baseline vdH-S scores were: Q4W, 28.0; Q8W, 23.9; PBO→Q4W, 25.6. Mean progression of joint damage from W0-24 was numerically lower in GUS- than PBO-treated pts for erosion, JSN, and total vdH-S scores (Table 1), consistent with the results from Reading Session 1.1 Mean changes in radiographic scores from W52-100 indicated low rates of radiographic progression across GUS groups. Among GUS-randomized pts, mean changes in vdH-S score from W0-100 were numerically lower for pts achieving clinical response assessed using ACR20/50/70, DAPSA LDA, PASDAS LDA, MDA, and HAQ-DI vs pts not achieving response at W100 (Figure 1).Table 1.Observed erosion, joint space narrowing, and total PsA-modified vdH-S scores through W100 of DISCOVER-2GUS Q4WGUS Q8WPBO→GUS Q4WBaseline PsA-modified vdH-S score, n221228215Erosion14.2 (23.3)12.0 (21.9)12.1 (21.9)Joint space narrowing13.8 (21.8)11.9 (19.5)13.5 (21.6)Total28.0 (43.6)23.9 (40.4)25.6 (42.4)Mean (SD) change in PsA-modified vdH-S scoreW0-24 N=221W24-52 N=221W52-100 N=211W0-24 N=228W24-52 N=228W52-100 N=216W0-24 N=215W24-52 N=213W52-100 N=202Erosion0.27 (1.91)0.36 (1.77)0.45 (2.90)0.51 (1.96)0.20 (1.24)0.26 (1.75)0.73 (2.20)0.25 (1.85)0.09 (1.98)Joint space narrowing0.21 (1.17)0.21 (1.11)0.30 (1.32)0.17 (0.69)0.12 (0.66)0.20 (0.92)0.39 (1.72)0.09 (1.11)0.04 (1.90)Total0.48 (2.70)0.57 (2.66)0.75 (4.02)0.68 (2.36)0.31 (1.57)0.46 (2.42)1.12 (3.80)0.34 (2.79)0.13 (3.74)Data presented as mean (SD).GUS, guselkumab; PBO, placebo; PsA, Psoriatic Arthritis; Q4W, every 4 weeks; Q8W, every 8 weeks; SD, standard deviation; vdH-S, van der Heijde-Sharp; W, weekConclusionIn biologic-naïve pts with active PsA enriched for greater risk of radiographic progression, GUS 100 mg (Q4W or Q8W) was associated with low rates of radiographic progression through 2 years. Pts achieving clinical response across several global measures of disease activity or normalized physical function at W100 had lower mean changes in total PsA-modified vdH-S scores compared with nonresponders.References[1]Mease PJ. Lancet. 2020;395:1126-1136[2]McInnes IB. Arthritis Rheumatol. 2021;73:604-616[3]McInnes IB. Innovations in Dermatology. Presentation: March 16-20, 2021Disclosure of InterestsPhilip J Mease Consultant of: AbbVie, Aclaris, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Grant/research support from: AbbVie, Aclaris, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Alice B Gottlieb Shareholder of: Xbiotech (stock options only), Consultant of: Anaptyps Bio, Avotres Therapeutics, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly, Incyte, Janssen, LEO Pharma, Novartis, Pfizer, Sun Pharmaceuticals, UCB, Grant/research support from: Boehringer Ingelheim, Janssen, Novartis, Sun Pharmaceuticals, UCB, and Xbiotech, Iain McInnes Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, Proton Rahman Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Grant/research support from: Janssen and Novartis, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research and Development, LLC, Xie L Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research and Development, LLC, Yusang Jiang Employee of: Cytel, Inc., Shihong Sheng Shareholder of: Johnson & Johnson, Employee of: Janssen Research and Development, LLC, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, Soumya D Chakravarty Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC, Frederic Lavie Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, and UCB Pharma, Employee of: Director of Imaging and Rheumatology BV

BackgroundPatients (pts) with psoriatic arthritis (PsA) experience pain, fatigue, anxiety, depression, sleep disturbance, and impaired physical function that can negatively affect health-related quality of life (HRQoL).1 As the Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29) Profile is a generic instrument assessing 7 health outcome domains, composite scores to summarize these domains into generalized concepts of mental and physical health using physical component summary (PCS) and mental component summary (MCS) scores2,3 will be useful to evaluate overall HRQoL in pts with PsA.ObjectivesCalculate and validate PCS and MCS scores, using PROMIS-29 data from the DISCOVER-1 Phase 3 study, and compare the scores for guselkumab (GUS) vs placebo (PBO).MethodsThe DISCOVER-1 study evaluated 381 pts with active PsA (≥3 swollen & ≥3 tender joints; C-reactive protein ≥0.3 mg/dL; 31% with prior tumor necrosis factor inhibitor exposure) and inadequate response to standard therapies.4 The PROMIS-29 Profile contains 4 items for each of 7 domains (physical function, anxiety, depression, fatigue, sleep disturbance, social participation, pain interference; 28 items scored on 5-point Likert scale) and 1 pain intensity item (0-10 visual analog scale). Using standardized scoring coefficients,3 PROMIS-29 PCS/MCS at baseline and Week 24 were calculated based on the 7 domains and pain intensity item. The validity of scores was assessed by Spearman correlation between PROMIS-29 PCS/MCS and 36-item Short-Form (SF-36) PCS/MCS, Health Assessment Questionnaire-Disability Index (HAQ-DI), and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scores. To evaluate the ability of derived PROMIS-29 PCS/MCS scores to distinguish between treatments, responder analyses (employing an improvement of ≥1/2 standard deviation [SD] of baseline scores) by treatment group (GUS 100 mg Q4W, GUS 100 mg Q8W, PBO) were conducted and compared with SF-36 PCS/MCS scores.ResultsAs construct validity analysis, PROMIS-29 PCS/MCS strongly/very strongly correlated with SF-36 PCS/MCS scores at baseline and Week 24 (coefficients 0.66-0.86; Table 1). PROMIS-29 and SF-36 PCS scores showed strong/very strong correlations with HAQ-DI scores, a key component of physical health (coefficients 0.66-0.83), while PROMIS-29 MCS and SF-36 MCS scores showed strong/very strong correlations with FACIT-F scores, a key component of mental health (coefficients 0.63-0.91). The proportions of pts achieving improved PROMIS-29 PCS/MCS scores (≥1/2 SD at baseline) were similar to a comparable degree of improvement in SF-36 PCS/MCS scores (≥1/2 SD at baseline). For both PROMIS-29 PCS/MCS and SF-36 PCS/MCS scores, significantly higher proportions of GUS Q4W/Q8W- vs PBO-treated pts achieved these response thresholds (all pTable 1.Mean (SD) PCS and MCS Scores: Construct ValidityInstruments Assessing Physical Aspects of HRQoLInstruments Assessing Mental Aspects of HRQoLSF-36 PCSPROMIS-29 PCSSF-36 MCSPROMIS-29 MCSBaseline, N381381381381Mean (SD)34.6 (8.2)39.4 (7.2)47.4 (10.2)45.3 (7.7)Median34.438.247.845.1Spearman’s correlationPROMIS-29 vs SF-360.760.66Week 24, N380381380381Mean (SD)39.6 (9.3)43.3 (8.3)50.3 (9.7)49.3 (8.5)Median39.342.252.350.0Spearman’s correlationPROMIS-29 vs SF-360.860.71ConclusionPROMIS-29 PCS/MCS scores calculated in DISCOVER-1 showed evidence of validity as summary scores with the ability to efficiently evaluate pt-reported HRQoL outcome in PsA. PROMIS-29 PCS/MCS scores, similar to the commonly employed and validated SF-36 PCS/MCS scores, may reliably be used to assess physical and mental health in pts with PsA.References[1]Orbai A et al. Ann Rheum Dis. 2017;76:673-80.[2]Orbai A et al. Poster presented at ACR October, 2021.[3]Hays RD, et al. Qual Life Res. 2018;27:1885–91.[4]Deodhar A et al. Lancet. 2020; 395: 1115–25.Disclosure of InterestsLaura Coates Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Medac, Novartis, Pfizer and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Ana-Maria Orbai Consultant of: Bristol Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Eli Lilly and Company, Celgene, Novartis, Janssen, and Horizon, Atul Deodhar Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Aurinia, Bristol Myers Squibb, Celgene, Eli Lilly, GlaxoSmithKline, Janssen, MoonLake, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer, and UCB, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Pharmaceutical Companies of Johnson & Johnson, Yi-Hsuan Liu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Yan Liu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Chenglong Han Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC

BackgroundGuselkumab (GUS), a selective IL-23p19 inhibitor, showed greater mean improvements in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores vs placebo (PBO) at Week (W) 24 in patients (pts) with active PsA and investigator-confirmed sacroiliitis in pooled post hoc analyses of data from phase 3 DISCOVER (D)-1&2 trials. Improvements in symptoms of axial involvement were maintained through 1 year.1ObjectivesTo assess maintenance of GUS effect on symptoms of axial involvement in biologic-naïve PsA pts with investigator-confirmed sacroiliitis through 2 years of D-2.MethodsIn D-2, 739 bio-naïve pts with active PsA (≥5 swollen + ≥5 tender joints, CRP ≥0.6 mg/dL despite standard therapies) were randomized 1:1:1 to GUS 100 mg every 4W (Q4W; n=245), GUS 100 mg at W0, W4, then Q8W (n=248), or PBO (n=246) with PBO→GUS 100 mg Q4W at W24. Pts with investigator-identified axial symptoms and sacroiliitis (prior X-ray or MRI, or pelvic X-ray at screening) were evaluated. Efficacy was assessed by changes in BASDAI, modified BASDAI (mBASDAI, excluding Q3 [peripheral joint pain]), and BASDAI Q2 (Spinal Pain) scores, and proportions of pts achieving BASDAI 50, Spinal Pain score ≤2, and AS Disease Activity Score (ASDAS) responses through W100. Through W24, pts who met treatment failure criteria or had missing data were considered nonresponders. After W24, missing data were imputed as nonresponse for binary endpoints or no change from baseline for continuous endpoints (nonresponder imputation [NRI]). Axial-related outcomes were also summarized by HLA-B27 status (+/-).Results246 pts had investigator-confirmed sacroiliitis. Baseline characteristics were similar across treatment groups (62% male; mean age 44.4 years; mean BASDAI scores 6.5-6.6). At W24, LS mean/mean changes in BASDAI (-2.4/-2.6) and ASDAS (-1.3/-1.5) scores were greater in GUS- vs PBO-treated pts. Improvements were maintained through W100 in GUS-treated pts: BASDAI, -3.1; Spinal Pain, -3.1; mBASDAI, -3.1; ASDAS, -1.7. Response patterns were similar for BASDAI 50 response rates in GUS-treated pts (W24 38-40%; W100 49-54%). At W24, GUS-treated pts had higher response rates for achievement of ASDAS inactive disease, major improvement, and clinically important improvement vs PBO; response rates (NRI) were maintained, or in some cases further increased, at 2 years. Results were consistent for achievement of ASDAS LDA and Spinal Pain score ≤2 (data not shown). GUS-related improvements in axial symptoms through W100 were generally consistent in HLA-B27+/- pts (data not shown).ConclusionIn bio-naïve pts with active PsA and investigator-confirmed sacroiliitis, GUS provided durable improvements in axial symptoms through W100, with substantial proportions of pts achieving and maintaining clinically meaningful improvements.References[1]Mease PJ et al. Lancet Rheumatol 2021;3:e715-723Table 1.Axial symptom assessments through W100 in PsA pts with investigator-confirmed sacroiliitis in DISCOVER-2 (NRI)GUS Q4W N=82GUS Q8W N=68PBO→GUS Q4W N=96Change in BASDAI scoreW24, LS mean (95% CI)-2.5 (-2.9, -2.0)-2.4 (-3.0, -1.8)-1.2 (-1.7, -0.7)Mean (SD)-2.5 (2.0)-2.6 (2.4)-1.4 (2.4)W52, mean (SD)-2.9 (2.3)-2.7 (2.5)-2.9 (2.6)W100, mean (SD)-3.0 (2.3)-3.1 (2.6)-3.3 (2.6)Change in mBASDAI (excludes Q3) scoreW24, LS mean (95% CI)-2.4 (-2.9, -1.9)-2.4 (-2.9, -1.8)-1.2 (-1.7, -0.7)Mean (SD)-2.5 (2.1)-2.6 (2.5)-1.3 (2.3)W52, mean (SD)-2.7 (2.6)-2.6 (2.5)-2.9 (2.4)W100, mean (SD)-3.3 (2.6)-3.1 (2.6)-3.0 (2.4)Change in Spinal Pain (BASDAI Q2) scoreW24, LS mean (95% CI)-2.2 (-2.7, -1.7)-2.3 (-2.9, -1.7)-0.9 (-1.5, -0.4)Mean (SD)-2.3 (2.6)-2.5 (2.8)-1.1 (2.5)W52, mean (SD)-2.6 (2.7)-2.5 (2.7)-2.5 (2.7)W100, mean (SD)-2.8 (2.7)-3.1 (2.8)-3.0 (2.8)Change in ASDAS scoreW24, LS mean (95% CI)-1.3 (-1.6, -1.1)-1.3 (-1.6, -1.1)-0.6 (-0.8, -0.4)Mean (SD)-1.4 (1.0)-1.5 (1.2)-0.7 (1.1)W52, mean (SD)-1.5 (1.1)-1.5 (1.3)-1.5 (1.3)W100, mean (SD)-1.6 (1.2)-1.7 (1.2)-1.6 (1.2)Disclosure of InterestsPhilip J Mease Speakers bureau: AbbVie, Aclaris, Amgen, BMS, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Consultant of: AbbVie, Aclaris, Amgen, BMS, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Grant/research support from: AbbVie, Aclaris, Amgen, BMS, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Philip Helliwell Speakers bureau: AbbVie, Janssen, and Novartis, Consultant of: Eli Lilly, Janssen, and Pfizer, Dafna D Gladman Consultant of: AbbVie, Amgen, BMS, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: Abbvie, Amgen, BMS, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB, Denis Poddubnyy Consultant of: AbbVie, Eli Lilly, GlaxoSmithKline, MSD, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Eli Lilly, MDS, Novartis, and Pfizer, Xenofon Baraliakos Speakers bureau: AbbVie, Biocad, Chugai, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, Consultant of: AbbVie, Biocad, Chugai, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, Grant/research support from: AbbVie, Biocad, Chugai, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, Soumya D Chakravarty Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Xie L Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Shihong Sheng Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Stephen Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, and UCB Pharma, Employee of: Imaging Rheumatology BV, Atul Deodhar Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Glaxo Smith & Kline, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Eli Lilly, Glaxo Smith & Kline, Novartis, Pfizer, and UCB

BackgroundPain in patients (pts) with psoriatic arthritis (PsA) has multifaceted origins; sustained improvement is difficult to achieve.1 Guselkumab (GUS), a fully human monoclonal antibody that selectively inhibits IL-23, is effective in treating multiple domains of PsA including joint, skin, and entheseal symptoms, and also elicits long-lasting improvements in pt-reported pain in the DISCOVER-1&2 trials of pts with active PsA.2ObjectivesThese post hoc analyses were conducted to identify determinants of changes in pt-reported pain in PsA pts using pooled data through 1 year of DISCOVER-1&2.MethodsEnrolled adult pts had active PsA despite standard therapies. DISCOVER-1 pts had ≥3 swollen and ≥3 tender joints and C-reactive protein (CRP) ≥0.3 mg/dL; DISCOVER-2 pts had ≥5 swollen and ≥5 tender joints and CRP ≥0.6 mg/dL. 31% of DISCOVER-1 pts received 1-2 prior tumor necrosis factor inhibitors; DISCOVER-2 pts were biologic-naïve. Pts were randomized 1:1:1 to GUS 100 mg every 4 weeks (wks) (Q4W); GUS 100 mg at W0, W4, then every 8 wks (Q8W); or placebo (PBO); PBO pts crossed over to GUS 100 mg Q4W at W24. Determinants with a statistically important effect (pout=0.1) to identify independent determinants of pain improvement over 24 wks; the model was then tested separately in pts treated with PBO (through W24) and with GUS (through W24 and through W52).ResultsGUS was associated with significantly greater improvement in pain compared to PBO as early as 2 wks post-treatment; there was a significant interaction between treatment group and time, with effect of GUS on pain continuously enhanced through W24. Higher baseline (BL) pain score, worse mental health (assessed with the Short-Form-36 Mental Component Summary [SF-36 MCS] score), and lower fatigue level and lower tender joint count [TJC] were also associated with significantly greater pain improvements at W24, while background use of NSAIDs was a negative predictor of pain improvement (Table 1). Treatment effect on pain was independent of PsA duration, gender, PsA subtype, prior TNFi exposure, BL skin disease, and BL swollen joint count (SJC). Continuous significant improvement from BL in pain with GUS extended through W52 even after adjustment for the identified determinants of pain improvement through W24 (Figure 1). At W52, predictors of change in pain remained significant with the exception of SF-36 MCS score (Table 1). Results did not exclude a small number of enrolled pts with fibromyalgia (FM: nGUS=8; nPBO=4). According to these exploratory findings, medical history of FM was associated with lower pain improvement through W24 (p=0.066); in the models run separately in pts with GUS and PBO, pts with FM treated with GUS had a mean (95% CI) pain improvement (-9.1 [-19.5, 1.2]) while pts treated with PBO had a mean worsening (0.7 [-12.5, 13.9]). Pain improvement through 52 wks was significant regardless of FM: pts with FM had a mean (95% CI) improvement of -14.7Table 1.Significant Predictors of Change in Pain (W24 and W52)BL DeterminantW24W52Estimate (95% CL)Estimate (95% CL)Pain score-0.62 (-0.69:-0.55) ‡-0.75 (-0.83:-0.67) ‡Fatigue-0.38 (-0.50:-0.27) ‡-0.37 (-0.53:-0.22) ‡SF-36 MCS0.20 (0.11:0.30)‡0.11 (-0.02:0.24)TJC0.13 (0.06:0.19) †0.12 (0.04:0.21) †NSAID use (Y vs N)2.29 (0.62:3.96) †2.76 (0.55:4.98) ** p †p ‡p ≤0.0001(-25.9, -3.6) comparable to non-FM pts at W24, while pain improvement in pts with no FM was -22.2 (-24.0, -20.4).ConclusionEarly significant effects of GUS on pain were enhanced through 1 year. Significant predictors of change in pain were consistent at W24 and W52, with the exception of mental health measures. The impact of mental status on pt-reported pain and the potential for GUS to improve pain in pts with FM warrant further consideration.References[1]Gudu T et al. Expert Rev Clin Immunol 2018;14(5):405-17.[2]Nash P et al. ACR Convergence 2021;Nov 5-9 (Poster 21-1368).Disclosure of InterestsPeter Nash Grant/research support from: Janssen, Abbvie, Pfizer, Novartis, Lilly, Gilead, Roche, Sandoz, Celgene, Sun, Boehringer, and Bristol Myers Squibb, Christopher T. Ritchlin Consultant of: UCB Pharma, Amgen, AbbVie, Lilly, Pfizer, Novartis, Gilead, Janssen, Grant/research support from: UCB Pharma, AbbVie, Amgen, Proton Rahman Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, and UCB, Grant/research support from: Janssen and Novartis, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Pharmaceutical Companies of Johnson & Johnson, Emmanouil Rampakakis Consultant of: Janssen, Employee of: JSS Medical Research, YoungJa Lee Shareholder of: Johnson & Johnson, Employee of: Janssen Asia Pacific, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Xie L Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Jonathan Sherlock Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Daniel Cua Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Saakshi Khattri Speakers bureau: AbbVie, Eli Lilly, Glenmark, Ichnos Sciences, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Eli Lilly, Glenmark, Ichnos Sciences, Janssen, Novartis, Pfizer, and UCB, Enrique Soriano Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Consultant of: AbbVie, Janssen, Novartis, and Roche, Grant/research support from: AbbVie, Janssen, Novartis, Pfizer, Roche, and UCB, Dennis McGonagle Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB

BackgroundGuselkumab (GUS), a human monoclonal antibody targeting the interleukin-23p19 subunit, demonstrated joint and skin efficacy in patients with active psoriatic arthritis (PsA) in the Phase III DISCOVER-1/-2 trials.1,2 Minimal disease activity (MDA), a multi-domain composite outcome, is a clinically relevant measure of therapeutic response in PsA.3 However, response dynamics and the effect of individual domains on achieving MDA are not well understood.ObjectivesCharacterise response patterns in MDA domains over time and identify potential baseline (BL) response predictors using machine learning.MethodsData from bio-naïve patients with active PsA receiving GUS 100 mg every 4 or 8 weeks were pooled across DISCOVER-1/-2. Eligibility criteria are described elsewhere.1,2 Unsupervised machine learning using the time-series K-means clustering algorithm was performed to identify clusters according to MDA domain responses over 52 weeks. MDA domain thresholds were tender joint count (TJC), swollen joint count (SJC), Psoriasis Area and Severity Index (PASI) and Leeds Enthesitis Index (LEI) each ≤1; patient global assessment (PtGA) visual analogue scale (VAS) ≤20; patient pain VAS ≤15 and Health Assessment Questionnaire-Disability Index (HAQ-DI) ≤0.5. BL characteristics were described for each cluster (Table 1). Missing data were not imputed.Table 1.BL characteristics of four MDA response clusters (C1–4) in bio-naïve patients with active PsA treated with GUS 100 mg every 4 or 8 weeksClusterC1C2C3C4Patients, N2019720964Age, years46.1 ± 12.245.5 ± 11.546.1 ± 11.347.0 ± 11.1Female, %47.855.736.443.8BMI, kg/m229.4 ± 6.329.2 ± 6.528.9 ± 5.428.7 ± 5.7CRP, mg/dl1.8 ± 2.41.8 ± 1.61.4 ± 2.01.9 ± 2.1PsA disease duration, years5.5 ± 5.85.3 ± 5.75.2 ± 5.95.8 ± 5.9SJC (0–66)10.7 ± 5.410.6 ± 5.010.1 ± 6.221.1 ± 12.2TJC (0–68)18.1 ± 9.618.8 ± 8.816.3 ± 10.741.2 ± 13.3Spondylitis, %28.926.829.742.2PASI score (0–72)8.6 ± 8.97.8 ± 8.010.6 ± 12.013.1 ± 14.6Dactylitis, %42.842.335.471.9Dactylitis score (0–60)3.7 ± 6.91.6 ± 2.92.0 ± 4.411.7 ± 15.2Dactylitis count (0–20)2.1 ± 4.00.9 ± 1.71.3 ± 2.86.0 ± 6.8Enthesitis, %62.262.956.989.1LEI (0–6)1.5 ± 1.61.7 ± 1.81.5 ± 1.73.6 ± 2.0HAQ-DI (0–3)1.3 ± 0.61.5 ± 0.50.9 ± 0.61.5 ± 0.5PtGA (0–100 VAS)68.3 ± 17.878.2 ± 14.157.6 ± 21.673.7 ± 15.8Pain (0–100 VAS)62.1 ± 17.074.3 ± 13.750.8 ± 21.367.2 ± 15.2Data are mean ± standard deviation or %.CRP, C-reactive protein.ResultsThis analysis included 571 of 669 patients receiving GUS and identified four distinct response clusters (C1–4; Table 1). Mean age and body mass index (BMI) were similar across clusters; C3 had a lower proportion of female patients. Relative to C3, a high burden of BL disease was observed in C4 across clinical measures and patient-reported outcomes (PROs), and across PROs only in C2. Through Week 52, MDA response rates were highest in C3 and lowest in C4, yet all clusters showed continuous improvement in mean values across all MDA domains (Figure 1). In C3, all individual domain thresholds were rapidly reached. C1, 2 and 4, met PASI threshold and showed a substantial reduction in SJC while other domains varied. In C1 and 2, improvement in clinical measures paralleled that of C3; however, PROs appeared to take longer to resolve. Responses were slowest in C4, though improvements were substantial given the high BL disease burden. Improvement in pain, PtGA and HAQ-DI occurred earlier in C1 than C2.ConclusionMachine learning identified four clusters of GUS-treated PsA patients based on differing response patterns in individual MDA domains. Response types may differ due to BL disease burden, especially in patients with higher pain, PtGA and functional disability scores. These results offer an innovative, complementary approach to identifying treatment response patterns across diverse clusters of bio-naïve patients with PsA, which may facilitate clinical decision-making.References[1]Deodhar et al. Lancet 2020; 395: 1115–25.[2]Mease et al. Lancet 2020; 395: 1126–36.[3]Coates et al. Ann Rheum Dis 2010; 69: 48–53.Disclosure of InterestsAlen Zabotti Speakers bureau: AbbVie, Amgen, Janssen, Lilly, Novartis and UCB, Grant/research support from: Novartis, Sarah Ohrndorf Speakers bureau: Sarah Ohrndorf has received speaker fees or travel expense reimbursements from AbbVie, BMS, Janssen, Novartis and Pfizer., William Tillett Speakers bureau:, Consultant of:, Grant/research support from: William Tillett has received research funding, consulting and/or speaker fees from AbbVie, Amgen, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer and UCB., Marlies Neuhold Shareholder of: Johnson & Johnson, Employee of: Janssen, Michel van Speybroeck Shareholder of: Johnson & Johnson, Employee of: Janssen, Elke Theander Shareholder of: Johnson & Johnson, Employee of: Janssen, Christine CONTRE Shareholder of: Johnson & Johnson, Employee of: Janssen, Mohamed Sharaf Shareholder of: Johnson & Johnson, Employee of: Janssen, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen, Michelle Perate Shareholder of: Johnson & Johnson, Employee of: Janssen, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen, Pascal Richette Speakers bureau:, Consultant of: Pascal Richette has received fees from AbbVie, Amgen, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer and UCB.

BackgroundGuselkumab (GUS), an IL-23p19-subunit inhibitor, demonstrated efficacy and a favorable safety profile in patients (pts) with psoriasis (PsO) and psoriatic arthritis (PsA). In the Phase 3, double-blind, placebo (PBO)-controlled DISCOVER-2 study, GUS 100 mg every 4 or 8 weeks (Q4W or Q8W) significantly improved joint and skin symptoms; GUS-treated pts had smaller mean changes in radiographic progression vs. PBO at W24.1 Low rates of radiographic progression were observed through 2 years among GUS-treated pts, regardless of dosing regimen.2,3ObjectivesDetermine whether earlier clinical improvement predicts long-term radiographic progression through 2 years in DISCOVER-2.MethodsDISCOVER-2 included biologic-naïve pts with active PsA (≥5 swollen and ≥5 tender joint counts [SJC/TJC]; CRP ≥0.6 mg/dL) randomized (1:1:1) to GUS 100 mg Q4W; GUS 100 mg at W0, W4, then Q8W; or PBO with crossover to GUS 100 mg Q4W (PBO→Q4W) at W24. For pts randomized to GUS Q4W or Q8W, predictive models (mixed linear) were developed post-hoc to assess the associations of earlier (at W16) improvement in disease activity (DAPSA remission, DAPSA Improvement, DAPSA Improvement more than the median of 20.7 [>20.7]) or skin improvement (PASI90, PASI≤1) with changes in total PsA modified van der Heijde-Sharp [vdH-S] score through W100, after adjusting for known baseline (BL) determinants of radiographic progression (vdH-S score, age, gender, and CRP).ResultsPsA duration, CRP, and SJC at BL weakly correlated with BL vdH-S score. No correlation was seen between BL PASI and BL vdH-S score (Table 1). Greater improvement in DAPSA score (β [95%CI]: -0.03 [-0.04, -0.01]) and improvement >20.7 in DAPSA from BL to W16 was associated with significantly less radiographic progression through W100 after adjusting for BL DAPSA score, vdH-S score, age, gender, and CRP level. Achievement of PASI90, PASI≤1, and DAPSA remission at W16 was associated with numerically less radiographic progression through W100 after adjusting for BL PASI, vdH-S score, age, gender, and CRP (Figure).Table 1.Correlation of Select BL Disease Characteristics with BL vdH-S Score Among GUS Randomized PtsBL DeterminantsSpearman’s correlation coefficientp-valueAge0.27335CRP0.28181PASI Score0.030780.5153PsA Duration0.37070PsO Duration0.20509SJC (66)0.26321ConclusionIn GUS-treated biologic-naïve pts with active PsA, following adjustment for known BL determinants of radiographic progression, earlier (W16) DAPSA improvement was a significant predictor of less radiographic progression through W100; DAPSA remission and skin improvement at W16 each showed a numerical trend toward less radiographic progression through W100.References[1]Mease PJ, et al. Lancet. 2020;395:1126–36.[2]McInnes IB, et al. Arthritis Rheumatol. 2021;73:604-16.[3]McInnes IB, et al. Arthritis Rheumatol. 2021 Nov 1. doi: 10.1002/art.42010. Online ahead of print.Disclosure of InterestsPhilip J Mease Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Consultant of: AbbVie, Aclaris, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Alice B Gottlieb Speakers bureau: AnaptsysBio, Avotres Therapeutics, Beiersdorf, Boehringer Ingelheim, Bristol-Myers Squibb, Incyte, GSK, Janssen, LEO Pharma, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical Industries, Inc., UCB, and Dermavant, Consultant of: AnaptsysBio, Avotres Therapeutics, Beiersdorf, Boehringer Ingelheim, Bristol-Myers Squibb, Incyte, GSK, Janssen, LEO Pharma, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical Industries, Inc., UCB, and Dermavant, Grant/research support from: Boehringer Ingelheim, Incyte, Janssen, Novartis, UCB, Xbiotech, and Sun Pharma, Alexis Ogdie Consultant of: Abbvie, Amgen, BMS, Celgene, CorEvitas, Gilead, Happify Health, Janssen, Lilly, Novartis, Pfizer, and UCB, Grant/research support from: University of Pennsylvania from Abbvie, Pfizer and Novartis and to Forward from Amgen, Iain McInnes Shareholder of: Causeway Therapeutics, and Evelo Compugen, Consultant of: Astra Zeneca, AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Cabaletta, Compugen, GSK, Gilead, Janssen, Novartis, Pfizer, Sanofi, Roche, and UCB, Grant/research support from: Astra Zeneca, Bristol-Myers Squibb, Amgen, Eli Lilly, GSK, Janssen, Novartis, Roche, and UCB, Soumya D Chakravarty Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC and Drexel University College of Medicine, Emmanouil Rampakakis Consultant of: Janssen, Employee of: JSS Medical Research, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Xie L Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Pharmaceutical Companies of Johnson & Johnson, Frederic Lavie Shareholder of: Johnson & Johnson, Employee of: Janssen Cilag Global Medial Affairs, Mitsumasa Kishimoto Speakers bureau: AbbVie, Amgen-Astellas BioPharma, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Kyowa Kirin, Novartis, Pfizer, Tanabe-Mitsubishi, Teijin Pharma, and UCB, Consultant of: AbbVie, Amgen-Astellas BioPharma, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Kyowa Kirin, Novartis, Pfizer, Tanabe-Mitsubishi, Teijin Pharma, and UCB, Proton Rahman Speakers bureau: Janssen, Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, and UCB, Grant/research support from: Janssen and Novartis

BackgroundPsoriatic arthritis (PsA), a chronic inflammatory disease characterized by peripheral arthritis, axial inflammation, dactylitis, enthesitis, and skin/nail psoriasis, is associated with reduced health-related quality of life (HRQoL).ObjectivesTo assess long-term effect of guselkumab (GUS), a human monoclonal antibody that selectively targets the interleukin (IL)-23p19 subunit, on HRQoL of bio-naïve PsA patients (pts) who participated in the Phase 3 2-year DISCOVER-2 trial.1MethodsPts with active PsA despite nonbiologic disease-modifying antirheumatic drugs (DMARDs) and/or nonsteroidal anti-inflammatory drugs (NSAIDs) received GUS 100 mg every 4 weeks (Q4W); GUS 100 mg at W0, W4, then Q8W; or placebo (PBO). At W24, PBO pts crossed over to GUS 100 mg Q4W. HRQoL was assessed using the pt-reported EuroQoL-5 Dimension-5 Level (EQ-5D-5L) questionnaire index and EuroQol Visual Analog Scale (EQ-VAS), widely used and complimentary tools that allow pts to provide a global assessment of their HRQoL. The EQ-5D-5L index assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression; an index score is derived ranging from 0 (death) to 1 (perfect health).2 EQ-VAS assesses pt health state on a scale of 0-100, with higher scores indicating better health. Using mixed effects models for repeated measures (MMRM), least squares (LS) mean changes from baseline in the EQ-5D-5L index and EQ-VAS through W100 were assessed. Observed changes from baseline were evaluated; in pts who met treatment failure rules before W24 and in pts who discontinued with missing data after W24, changes from baseline were imputed as 0.ResultsGUS-treated pts achieved greater improvements in pt-reported health status than PBO at both W16 and W24 when evaluated using both the EQ-5D-5L index score and the EQ-VAS. The improvements by GUS in EQ-5D-5L index scores through W24 (0.12 for GUS Q4W/Q8W vs 0.05 for PBO; each nominal pTable 1.LS mean change from baseline through W100 in EQ-5D-5L indexGUS 100mg Q4W(W0-100)GUS 100mg Q8W(W0-100)PBO → GUS 100 mg Q4WPBO(W0-24)GUS(W24-100)Week162410016241001624100N243244243247246248244244244LS mean change (95% CI)0.10 (0.09,0.12)0.12 (0.1,0.13)0.15 (0.13,0.16)0.11 (0.1,0.13)0.12 (0.1,0.13)0.15 (0.13,0.17)0.06 (0.04,0.07)0.05 (0.04,0.07)0.14 (0.12,0.16) Diff vs. PBO0.04 (0.02,0.06)0.06 (0.04,0.09)--0.05 (0.03,0.07)0.06 (0.04,0.08)-------- Nominal p-value----------CI=Confidence interval; Diff=DifferenceConclusionIn bio-naïve pts with active PsA receiving GUS, earlier improvements (at the first timepoint assessed) in self-reported HRQoL measures were sustained through 2 years.References[1]Mease PJ, et al. Lancet. 2020;395:1126–36.[2]EuroQol Group. 1990;16:199-208.Disclosure of InterestsJeffrey Curtis Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, CorEvitas, Eli Lilly, Janssen, Myriad, Novartis, Pfizer, Sanofi, and UCB, Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, CorEvitas, Eli Lilly, Janssen, Myriad, Novartis, Pfizer, Sanofi, and UCB, Iain McInnes Shareholder of: Causeway Therapeutics, and Evelo Compugen, Consultant of: Astra Zeneca, AbbVie, Amgen, Bristol-Myers Squibb, Cabaletta, Compugen, Eli Lilly, Gilead, GSK, Janssen, Novartis, Pfizer, Roche, Sanofi, and UCB, Grant/research support from: Astra Zeneca, Amgen, Bristol-Myers Squibb, Eli Lilly, GSK, Janssen, Novartis, Roche, and UCB, Proton Rahman Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, and UCB, Grant/research support from: Janssen and Novartis, Dafna D Gladman Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Eli Lilly, Janssen, Pfizer, and UCB, Feifei Yang Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC (a wholly owned subsidiary of Johnson & Johnson), Steve Peterson Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC (a wholly owned subsidiary of Johnson & Johnson), Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC (a wholly owned subsidiary of Johnson & Johnson), Natalie Shiff Shareholder of: AbbVie, Gilead, and Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC (a wholly owned subsidiary of Johnson & Johnson), Chenglong Han Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC (a wholly owned subsidiary of Johnson & Johnson), May Shawi Shareholder of: Johnson & Johnson, Employee of: Immunology Global Medical Affairs, Janssen Pharmaceutical Companies (a wholly owned subsidiary of Johnson & Johnson), William Tillett Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, MSD, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Eli Lilly, Janssen, MSD, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Eli Lilly, Janssen, and UCB, Philip J Mease Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Consultant of: AbbVie, Aclaris, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead, GSK, Inmagene, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, SUN Pharma, and UCB

BackgroundPsoriatic arthritis (PsA) is typically described by its individual domains or clinical components.1,2ObjectivesThis post hoc analysis aimed to identify hypothesis-free phenotype clusters according to patients’ clinical features and baseline (BL) characteristics with data from the Phase 3 DISCOVER-1 and -2 guselkumab (GUS) clinical trials.MethodsData from bio-naïve patients with PsA treated with GUS 100 mg every 4 or 8 weeks in DISCOVER-1 and -2 were retrospectively analysed. Non-negative matrix factorisation was used as an unsupervised machine learning technique to identify clusters of PsA phenotypes, with BL characteristics and clinical observations as input features, according to which clusters were described.ResultsData from 661 patients were pooled and 8 distinct clusters of PsA phenotypes identified (Table 1). Cluster 1 was characterised by lower limb involvement and the lowest rates of severe skin involvement (Figure 1); Cluster 2 by high skin involvement, the lowest proportion of women and highest proportion of overweight patients (body mass index [BMI] 25–30, 67%). Minimal disease activity (MDA) response rates at Week (W)24 and W52 were highest in Cluster 2 and lowest in Cluster 5. Clusters 3 and 4 had low MDA response rates at W24, increasing at W52.Table 1.Baseline characteristics of PsA phenotype clusters.Cluster 1Cluster 2Cluster 3Cluster 4Cluster 5Cluster 6Cluster 7Cluster 8Feet dominantMale, overweight, psoriasis burdenHand dominantDactylitis dominantEnthesitis and large jointsEnthesitis and small jointsAxial dominantFemale, obese, large jointsRandomised and treated patients, n791259538576083124Age, years45.8 (10.4)45.8 (13.2)48.9 (11.8)44.8 (12.3)43.6 (13.3)45.8 (11.6)43.8 (10.4)47.5 (11.1)Female %54.420.060.026.364.941.736.161.3BMI, kg/m229.3 (5.4)27.4 (3.6)29.3 (6.1)26.9 (4.6)28.6 (7.5)29.0 (6.2)28.4 (6.9)32.1 (6.5)CRP, mg/dL1.7 (1.8)1.7 (2.0)1.4 (2.3)2.5 (2.8)1.7 (1.9)1.7 (1.8)2.2 (3.1)1.5 (1.8)Disease duration, years5.0 (5.3)5.1 (4.8)5.8 (6.5)6.1 (5.5)6.8 (7.6)6.1 (5.6)4.7 (4.6)5.2 (6.7)SJC, 0–6613.2 (7.1)8.2 (3.8)15.0 (8.0)18.0 (10.1)10.1 (5.1)17.5 (11.8)9.0 (4.2)8.8 (3.9)TJC, 0–6823.4 (10.1)12.8 (5.9)26.0 (12.0)30.6 (15.3)23.2 (12.6)37.5 (18.6)14.6 (6.5)12.7 (5.2)BSA, %12.6 (19.4)20.7 (19.8)14.8 (19.5)29.7 (26.4)14.6 (21.6)14.5 (18.4)15.2 (19.4)14.4 (15.7)Dactylitis %48.130.442.1100.036.853.349.431.5Dactylitis score3.0 (4.8)1.4 (3.2)2.7 (4.8)27.5 (12.3)2.3 (5.2)3.9 (6.8)2.2 (2.9)1.3 (2.5)Enthesitis %70.949.658.981.696.573.369.945.2LEI score2.0 (1.7)1.0 (1.3)1.7 (1.8)2.9 (1.9)4.2 (1.6)2.7 (2.3)1.3 (1.2)1.0 (1.3)Data shown are mean (standard deviation) or %. Bold font indicates differentiating features of individual clusters. BMI, body mass index; BSA, body surface area; CRP, C-reactive protein; LEI, Leeds Enthesitis Index; PsA, psoriatic arthritis; SJC, swollen joint count; TJC, tender joint count.ConclusionUnsupervised machine learning identified 8 clusters of PsA phenotypes with significant differences in demographic and clinical features, including patterns of domain involvement and MDA responses. These clusters differ in their initial vs. later responses to GUS.References[1]Coates C et al. Arthritis Rheumatol 2016; 68: 1060–1071.[2]Gossec L et al. Ann Rheum Dis 2012; 71: 4–12.Disclosure of InterestsPascal Richette Speakers bureau:, Consultant of: Pascal Richette has received fees from AbbVie, Amgen, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer and UCB., Marijn Vis Speakers bureau:, Consultant of:, Grant/research support from: Marijn Vis has received research grants, consulting or speaker fees from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, UCB and the Dutch Arthritis Foundation., Sarah Ohrndorf Speakers bureau: Sarah Ohrndorf has received speaker fees or travel expense reimbursements from AbbVie, BMS, Janssen, Novartis and Pfizer., William Tillett Speakers bureau:, Consultant of:, Grant/research support from: William Tillett has received research grants, consulting or speaker fees from AbbVie, Amgen, Celgene, Eli Lilly, Janssen, MSD, Novartis, Pfizer and UCB., Marlies Neuhold Shareholder of: Johnson & Johnson, Employee of: Janssen, Michel van Speybroeck Shareholder of: Johnson & Johnson, Employee of: Janssen, Elke Theander Shareholder of: Johnson & Johnson, Employee of: Janssen, Wim Noel Shareholder of: Johnson & Johnson, Employee of: Janssen, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen, Alen Zabotti Speakers bureau: AbbVie, Amgen, Eli Lilly, Novartis and UCB, Grant/research support from: Novartis

BackgroundGuselkumab (GUS), a selective IL-23 inhibitor, is efficacious in treating bio-naïve and TNFi-experienced active PsA patients (pts).1.2 In the COSMOS study of active PsA pts with lack of efficacy/intolerance, i.e., inadequate response (IR), to 1-2 TNFi, GUS demonstrated significantly greater response rates and mean improvements in PsA signs and symptoms vs. placebo (PBO) at Week (W) 24.3ObjectivesEvaluate baseline (BL) serum levels of pro-inflammatory biomarkers (CRP, serum amyloid A [SAA], TNFα, IFNɣ, IL-6, IL-10, IL-17F, IL-17A, IL-22) and their relationship to BL disease activity, GUS treatment (tx), and clinical response in COSMOS TNFi-IR pts.MethodsTNFi-IR pts ≥18 yrs with active PsA (≥3 swollen & ≥3 tender joint counts [SJC/TJC]) were randomized 2:1 to GUS 100 mg every 8 W (Q8W) through W44 or PBO with early escape (W16) or crossover (W24) to GUS Q8W. Samples for serum biomarker analyses, collected at W0, 4, 16, 24, and 48 from consenting pts, were compared with healthy controls (HC; independent of COSMOS). Associations between early biomarker changes and BL disease activity, GUS tx, and clinical response at W24 were assessed.ResultsAmong 285 COSMOS pts, 50/95 PBO and 100/190 GUS pts had available biomarker data. BL characteristics of the biomarker cohort were similar to the overall COSMOS population and well balanced across tx arms. At BL, levels of TNFα, IFNɣ, IL-6, IL-10, IL-17A, IL-17F, and IL-22 were significantly upregulated in TNFi-IR pts vs. HC (Table 1). IL-6, CRP, and SAA levels were associated with BL joint disease severity per Disease Activity Score (DAS) 28-CRP (but not with SJC [0-66]/TJC [0-68]). IL-17A and IL-17F levels were associated with BL PASI score. Through W24, significant decreases from BL in levels of CRP, SAA, IL-6, IL-17A, IL-17F, and IL-22 were seen in GUS-, but not PBO-tx pts. Reductions in IL-17A, IL-17F and IL-22 with GUS were significant by W4, decreased further by W16, and were sustained through W24 and W48. In GUS-tx pts, serum levels of IL-17F (from W16) and IL-22 (from W4) were not significantly different vs. HC. At W48, reductions in these same markers were seen in PBO-tx pts who crossed over to GUS at W16/24 (Figure 1; IL-17A, IL-17F, & IL-22 data shown). In these TNFi-IR pts, GUS-tx pts achieving ACR20 at W24 exhibited higher IL-22 and IFNɣ levels at BL than nonresponders (NR). All other biomarkers evaluated were not significantly associated with ACR20 response to GUS. In the subset of pts with IGA of psoriasis assessed, BL IL-6 and SAA levels were upregulated in W24 IGA 0/1 responders (R) vs. NR in the GUS arm. ACR20 and IGA 0/1 R at W24 exhibited an early greater reduction in IL-6 expression (at W4) than did respective NR in the GUS arm. No BL biomarkers were associated with ACR50 or PASI75 responses to GUS at W24.Table 1.Select Serum Biomarkers at BL in TNFi-IR pts vs. HC▫Biomarker, pg/mLHC N=24TNFi-IR N=150Fold differencep-valueCRP22.1 (1.5)22.8 (2.2)1.60.2895SAA21.7 (1.2)22.8 (2.4)2.10.0794IL-60.07 (1.1)0.98 (1.7)1.90.0314*IL-10-2.3 (1.1)-1.7 (1.0)1.50.0272*IL-17A-2.1 (1.3)-0.3 (1.5)3.3*IL-17F0.05 (1.1)1.3 (1.5)2.40.0007*IL-221.9 (1.1)3.1 (1.3)2.40.0002*TNFα0.5 (0.75)1.4 (1.1)1.80.0002*IFNɣ2.4 (0.84)2.9 (1.3)1.50.0259*Data are mean (SD); *p1.4; ▫adjusted for confounding factors age & sex.ConclusionGUS-tx TNFi-IR pts showed response-specific associations with BL biomarkers (IL-22, IFNɣ, IL-6, and SAA). GUS resulted in decreased levels of elevated CRP, SAA, IL-6, IL-17A, IL-17F, and IL-22, while no significant change was observed with PBO tx. Reductions in these biomarkers were evident as early as W4 and approximated levels seen in HC from W16 onward (W4 for IL-22), suggesting apparent normalization of effector cytokines associated with the IL-23/Th17 axis following GUS tx.References[1]Deodhar A et al. Lancet 2020;395:1115-25.[2]Mease PJ et al. Lancet 2020;395:1126-36.[3]Coates LC et al. doi:10.1136/annrheumdis-2021-220991.Disclosure of InterestsGeorg Schett Speakers bureau: Amgen, AbbVie, Bristol Myers Squibb, Eli Lilly, Gilead, Janssen, Novartis and UCB, Warner Chen Shareholder of: Janssen, Employee of: Janssen, Sheng Gao Shareholder of: Janssen, Employee of: Janssen, Soumya D Chakravarty Shareholder of: Janssen, Employee of: Janssen, May Shawi Shareholder of: Janssen, Employee of: Janssen, Frederic Lavie Shareholder of: Janssen, Employee of: Janssen, Elke Theander Shareholder of: Janssen, Employee of: Janssen, Marlies Neuhold Shareholder of: Janssen, Employee of: Janssen, Laura Coates Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Medac, Novartis, Pfizer and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Stefan Siebert Speakers bureau: AbbVie, Biogen, GSK, Janssen, Novartis, UCB, Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, GSK, Janssen, Novartis, UCB

BackgroundA better understanding of the immunological differences between psoriatic arthritis (PsA) patients (pts) who are tumor necrosis factor inhibitor (TNFi)-naïve & who have inadequate response to TNFi (TNFi-IR) may guide treatment choices. In DISCOVER-1, benefit of the IL-23p19 subunit inhibitor guselkumab (GUS) every-four-weeks (Q4W) & Q8W vs placebo (PBO) in improving PsA signs & symptoms was seen in adults with active PsA.1 The Ph3b COSMOS study of GUS Q8W vs PBO in TNFi-IR PsA pts corroborated these findings.2ObjectivesAssess baseline (BL) molecular differences between TNFi-naïve & -IR PsA pts & investigate GUS pharmacodynamic (PD) effect on cytokine expression over time in these cohorts.MethodsSerum samples collected from consenting biomarker substudy pts in DISCOVER-11 (TNFi-naïve [n=101] & -IR [n=17]), DISCOVER-23 (TNFi-naïve [n=150]), & COSMOS2 (TNFi-IR [n=76]) were analyzed for selected serum cytokine levels. TNFi-IR pts in this post-hoc analysis had active PsA & discontinued 1-2 TNFi due to inadequate efficacy; these pts required a TNFi-specific washout period prior to starting GUS. PD effect of GUS Q8W on cytokine levels was assessed. Differential BL cytokine expression, associations between BL cytokine levels & clinical response (Psoriasis [PsO] Area & Severity Index 75% improvement from BL [PASI75] & American College of Rheumatology 20% improvement [ACR20]), & GUS effect on cytokine levels were analyzed with a General linear model & Spearman linear regression.ResultsBL pt demographics, disease characteristics, & conventional synthetic disease-modifying antirheumatic drug (csDMARD) use were comparable between TNFi-naïve (DISCOVER-1 & -2, N=251) & -IR (DISCOVER-1 & COSMOS, N=93) pts, with differences in mean PASI score (8.9 v 12.5), swollen joint count (SJC) (11.7 v 10.3), PsA duration (5.8 v 9.8 yrs), & PsO duration (16.7 v 20.4 yrs; Table 1). BL serum IL-22 & TNFα levels for pooled treatment groups were higher in TNFi-IR than -naïve pts (pTable 1.BL demographics, disease characteristics, & drug use in TNFi-naïve & -IR cohorts with available cytokine data in DISCOVER-1&2 & COSMOS.*TNFi-naïve (N=251)TNFi-IR (N=93)Age [yrs]47.2 (11.3)48.5 (11.1)Female, n (%)132 (52.6)46 (49.5)Body mass index [kg/m2]29.6 (6.1)30.3 (6.4)Median (range) CRP [mg/dL]0.9 (0.0-12.9)1.0 (0.0-13.2)Log2 IL-22 / TNFα [pg/mL]2.0 (1.4) / 1.1 (0.6)2.5 (1.5) / 1.9 (1.2)Log2 IL-17A / F [pg/mL]-0.4 (1.5) / 1.7 (1.5)-0.1 (1.7) / 2.0 (1.6)SJC [0-66]11.7 (7.1)10.3 (8.3)TJC [0-68]20.3 (13.1)20.6 (14.2)PsA duration [yrs]5.8 (5.9)9.8 (8.2)PsO duration [yrs]16.7 (12.8)20.4 (12.0)PsO Body surface area (%)14.8 (18.6)19.1 (21.3)Investigator’s Global Assessment score [0-4]2.3 (0.9)2.3 (1.0)PASI score [0-72]8.9 (10.6)12.5 (12.0)Enthesitis [Y], n (%)160 (63.7)58 (62.4)csDMARD use [Y], n (%)164 (65.3)62 (66.7)Corticosteroid use (Y), n (%)45 (17.9)19 (20.4)Methotrexate use [Y], n (%)136 (54.2)54 (58.1)Data are mean (SD) unless otherwise noted. *Pts with serum CRP level ≥0.3 mg/dL, SJC ≥3, & TJC ≥3 (to mimic D1 inclusion criteria1). TJC= tender joint countConclusionElevated BL IL-22 expression & association between BL IL-22 levels & W24 PASI75 response, & a W24 trend for an association between upregulated BL IL-22 & ACR20 response, in TNFi-IR pts seen in this exploratory analysis may suggest increased involvement of the IL-23 pathway in TNFi-IR pts. GUS showed comparable & significant PD effects for TNFi-naïve & -IR pts, consistent with observed clinical responses.References[1]Deodhar A, et al. Lancet. 2020;395:1115-25.[2]Coates LC, et al. Ann Rheum Dis. 2021;80:140-1.[3]Mease P, et al. Lancet. 2020;395:1126-36.Disclosure of InterestsStefan Siebert Speakers bureau: AbbVie, Biogen, GSK, Janssen, Novartis, UCB, Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, GSK, Janssen, Novartis, and UCB, Laura Coates Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Medac, Novartis, Pfizer and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Georg Schett Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Gilead, Janssen, Novartis, and UCB, Siba P Raychaudhuri Speakers bureau: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Consultant of: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Warner Chen Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC (a wholly owned subsidiary of Johnson & Johnson), Sheng Gao Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC (a wholly owned subsidiary of Johnson & Johnson), Soumya D Chakravarty Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC (a wholly owned subsidiary of Johnson & Johnson), May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Pharmaceutical Companies of Johnson & Johnson, Frederic Lavie Shareholder of: Johnson & Johnson, Employee of: Janssen Pharmaceutical Companies of Johnson & Johnson, Elke Theander Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC (a wholly owned subsidiary of Johnson & Johnson), Marlies Neuhold Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC (a wholly owned subsidiary of Johnson & Johnson), Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC (a wholly owned subsidiary of Johnson & Johnson), Xie L Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC (a wholly owned subsidiary of Johnson & Johnson), Proton Rahman Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, and UCB, Grant/research support from: Janssen and Novartis, Philip J Mease Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Consultant of: AbbVie, Aclaris, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GSK, Inmagene, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Atul Deodhar Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Aurinia, Bristol Myers Squibb, Celgene, Eli Lilly, GSK, Janssen, MoonLake, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, and UCB

ObjectiveEvaluate the safety of guselkumab (monoclonal antibody targeting interleukin [IL]-23p19) in patients with psoriatic arthritis (PsA) through 1 year (1Y) of the phase III DISCOVER-1 and DISCOVER-2 trials.MethodsPatients with active PsA (n = 1120; biologic-naïve except 118 patients treated with tumor necrosis factor inhibitors in DISCOVER-1) were randomized to subcutaneous guselkumab 100 mg every 4 weeks (Q4W) or at Week 0, Week 4, then every 8 weeks (Q8W); or placebo. At Week 24, patients in the placebo group switched to guselkumab 100 mg Q4W. Treatment continued through 1Y and 2 years for DISCOVER-1 and DISCOVER-2, respectively. In this pooled analysis, patients with ≥ 1 adverse event (AE) through 1Y were standardized for 100 patient-years [100 PYs] of follow-up.ResultsThrough Week 24, adverse events (AEs) were consistent between patients treated with placebo and guselkumab (Q4W + Q8W). AEs were 142.8/100 PYs and 150.6/100 PYs, serious AEs were 7.1/100 PYs and 4.4/100 PYs, and AEs leading to study agent discontinuation were 4.1/100 PYs and 3.8/100 PYs, respectively. Through 1Y in patients treated with guselkumab, no uveitis, active tuberculosis, opportunistic infections, or inflammatory bowel disease were observed, and low rates of malignancy and major adverse cardiovascular (CV) events were observed. Injection-site reactions occurred in 1.7%, and antibodies to guselkumab in 4.5% of patients treated with guselkumab through 1Y; the vast majority of antibodies to guselkumab were nonneutralizing. Serum hepatic transaminase elevations (more common with Q4W than Q8W dosing) and decreased neutrophil counts were generally mild, transient, and did not require treatment discontinuation, with minimal change from Week 24 to 1Y.ConclusionGuselkumab 100 mg Q4W and Q8W were well tolerated in patients with PsA, with no new safety concerns through 1Y of the phase III DISCOVER trials. Guselkumab safety through 1Y in patients with PsA is consistent with that established in patients with psoriasis who were treated with guselkumab. [ClinicalTrials.gov:NCT03162796andNCT03158285]

ObjectiveTo evaluate efficacy and safety of guselkumab, an anti-interleukin-23p19-subunit antibody, in patients with psoriatic arthritis (PsA) with prior inadequate response (IR) to tumour necrosis factor inhibitors (TNFi).MethodsAdults with active PsA (≥3 swollen and ≥3 tender joints) who discontinued ≤2 TNFi due to IR (lack of efficacy or intolerance) were randomised (2:1) to subcutaneous guselkumab 100 mg or placebo at week 0, week 4, then every 8 weeks (Q8W) through week 44. Patients receiving placebo crossed over to guselkumab at week 24. The primary (ACR20) and key secondary (change in HAQ-DI, ACR50, change in SF-36 PCS and PASI100) endpoints, at week 24, underwent fixed-sequence testing (two-sided α=0.05). Adverse events (AEs) were assessed through week 56.ResultsAmong 285 participants (female (52%), one (88%) or two (12%) prior TNFi), 88% of 189 guselkumab and 86% of 96 placebo→guselkumab patients completed study agent through week 44. A statistically significantly higher proportion of patients receiving guselkumab (44.4%) than placebo (19.8%) achieved ACR20 (%difference (95% CI): 24.6 (14.1 to 35.2); multiplicity-adjusted p80% of week 24 responders maintained response at week 48. Through week 24, serious AEs/serious infections occurred in 3.7%/0.5% of 189 guselkumab-randomised and 3.1%/0% of 96 placebo-randomised patients; the guselkumab safety profile was similar through week 56, with no deaths or opportunistic infections.ConclusionGuselkumab significantly improved joint and skin manifestations and physical function in patients with TNFi-IR PsA. A favourable benefit–risk profile was demonstrated through 1 year.Trial registration numberNCT03796858.

Background:DISCOVER 1 & 2, two double-blind, phase-3, psoriatic arthritis (PsA) trials of guselkumab (GUS, an IL-23 inhibitor), demonstrated significant improvement with GUS vs placebo (PBO) in signs and symptoms of PsA, with good tolerability, at week (w) 24 during the PBO-controlled period.1,2 Beyond w24, all patients (pts) switched to GUS. Continued treatment maintained efficacy through w52.3,4Objectives:To describe pooled safety results from the DISCOVER 1 & 2 trials through 1-year of GUS treatment.Methods:Adults with active PsA (DISCOVER 1: ≥3 tender/swollen joints and C-Reactive protein [CRP] ≥0.3 mg/dL; DISCOVER 2: ≥5 tender/swollen joints and CRP ≥0.6 mg/dL) were randomized to subcutaneous GUS 100 mg at w0, w4, then every 8 w (q8w); GUS 100 mg q4w; or PBO. At w24, PBO pts switched to GUS 100 mg q4w. Pts were biologic naive except ~30% pts in DISCOVER 1. Safety was reported through w60 in DISCOVER 1 and through w52 in DISCOVER 2.Results:Baseline characteristics were similar between treatment groups in the pooled studies. Through w24 and 1 year, numbers of pts per 100 patient years with ≥1 event were similar among treatment groups for adverse events (AEs), serious AEs, infections, serious infections, and discontinuations due to AE (Table 1). At 1 year, there were no cases of active tuberculosis, opportunistic infections (including candida), or inflammatory bowel disease in GUS-treated pts; 2 deaths in PBO pts; and low incidences that were similar across treatment groups for malignancy, major adverse cardiac events, and injection-site reactions. Incidence of anti-GUS antibodies was 4.5%, and most were not neutralizing. Mild elevations in serum hepatic transaminases and decreases in neutrophil counts were consistent at 1 year with the results at w24 (Table 1).Conclusion:GUS regimens of q8w and q4w were well tolerated in PsA pts through 1 year of treatment in the phase-3 DISCOVER trials, consistent with the w24 results. No meaningful differences between incidences of AEs were reported in the q8w and q4w groups. The safety profile of GUS in PsA pts is generally comparable with the previously established safety profile of GUS.References:[1]Deodhar A et al. Lancet. 2020;395:1115[2]Mease P et al. Lancet. 2020;395:1126[3]Ritchlin C et al. EULAR 2020 # SAT0397[4]McInnes I et al. EULAR 2020 # SAT0402Table 1.Number of Patients with AEs per 100 PY and Incidence of AEs of InterestTime Period24 Weeks1 Year*Treatment GroupPBOGUS SC 100 mgPBO to GUS‡GUS SC 100 mgDosing ScheduleMatchingq8wq4wGUSCombined†q4wq8wq4wGUSCombined‡ N3723753737483523753731100Total PY Follow-Up173173172346204384385589Patients with AEs per 100 PY, n (95% CI)≥1 AE143 (123, 166)148 (127, 171)154 (132, 178)151 (136, 167)92 (77, 108)114 (100, 130)115 (101, 131)109 (100, 117)≥1 Serious AE7.1 (3.7, 12)4.1 (1.6, 8.4)4.7 (2.0, 9.3)4.4 (2.5, 7.3)7.0 (3.8, 11.8)4.8 (2.9, 7.6)4.0 (2.2, 6.6)4.9 (3.6, 6.6)≥1 Infection50 (39, 62)47 (37, 59)52 (42, 65)49 (42, 58)39 (31, 49)41 (34, 48)38 (31, 45)39 (35, 44)≥1 Serious Infection1.7 (0.4, 5.1)0.6 (0.0, 3.2)1.8 (0.4, 5.1)1.2 (0.3, 3.0)2.5 (0.8, 5.8)1.3 (0.4, 3.1)0.8 (0.2, 2.3)1.3 (0.7, 2.3)Discontinued due to AE4.1 (1.6, 8.4)2.9 (1.0, 6.8)4.7 (2.0, 9.3)3.8 (2.0, 6.5)3.5 (1.4, 7.1)2.1 (0.9, 4.1)2.6 (1.3, 4.8)2.6 (1.7, 3.8)AEs of Interest§, n (%)Death2 (0.5)0000000Malignancy1 (0.3)2 (0.5)02 (0.3)1 (0.3)2 (0.5)03 (0.3)Major Adverse Cardiac Events1 (0.3)01 (0.3)1 (0.1)001 (0.3)1 (0.1)Opportunistic Infections00000000Tuberculosis00000000Inflammatory Bowel Disease1 (0.3)0000000Injection-Site Reaction1 (0.3)5 (1.3)4 (1.1)9 (1.2)4 (1.1)6 (1.6)9 (2.4)19 (1.7)Anti-GUS Antibody+-6/373 (1.6)9/371 (2.4)15/744 (2.0)14/350 (4.0)18/373 (4.8)17/371 (4.6)49/1094 (4.5)*Through w60 for DISCOVER 1 and w52 for DISCOVER 2; †Combined GUS q8w and q4w; ‡For patients who switched from PBO to GUS, only data on and after first GUS administration were included in this group; §PBO N=370.AE, adverse event; CI, confidence interval; GUS, guselkumab; PBO, placebo; PY, patient year; q4w, every 4 weeks; q8w, every 8 weeks; SC, subcutaneous; w, weekDisclosure of Interests:Christopher T. Ritchlin Grant/research support from: Received grant/research support from UCB Pharma, AbbVie, Amgen, consultation fees from UCB Pharma, Amgen, AbbVie, Lilly, Pfizer, Novartis, Gilead, Janssen, Proton Rahman Speakers bureau: Received speakers fees from Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, Pfizer, Grant/research support from: Received grant/research support from Janssen and Novartis, consultation fees from Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, and Pfizer., Philip Helliwell Consultant of: Consultation fees paid to charity (AbbVie, Amgen, Pfizer, UCB) or himself (Celgene, Galapagos), Grant/research support from: Received grants/research support paid to charity (AbbVie, Janssen, Novartis), Wolf-Henning Boehncke Consultant of: Received consultation fees from Janssen, Grant/research support from: Received grant/research support from Janssen Research & Development, LLC, Iain McInnes Consultant of: Received consultation fees from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: Received grant/research support from Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, Alice B Gottlieb Speakers bureau: Received speakers fees from Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB, Consultant of: Received consultation fees from Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB, Grant/research support from: Received grant/research support from Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB, Shelly Kafka Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Alexa Kollmeier Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Elizabeth C Hsia Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Xie L Xu Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, May Shawi Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Shihong Sheng Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Prasheen Agarwal Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Bei Zhou Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Paraneedharan Ramachandran Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Philip J Mease Speakers bureau: Received speakers fees from Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau, Consultant of: Received consultation fees from Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB, Grant/research support from: Received grant/research support from Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB.

Background:Guselkumab (GUS), a selective IL-23 inhibitor dosed every 4 or 8 weeks (Q4W or Q8W), demonstrated efficacy for joint and skin symptoms, inhibition of structural damage progression (Q4W), and safety vs. placebo (PBO) through Week 24 (W24) of the Ph3, double-blind, PBO-controlled trial in biologic-naïve pts with PsA (DISCOVER-2).1 Favorable benefit-risk was also seen through 1 year.2Objectives:To assess GUS efficacy and safety through 2 years.Methods:Biologic-naïve adults with active PsA (≥5 swollen joint count [SJC] + ≥5 tender joint count [TJC]; CRP ≥0.6 mg/dL) were randomized (1:1:1) to GUS 100 mg Q4W; GUS 100 mg at W0, W4, Q8W; or PBO with crossover to GUS 100 mg Q4W (PBO→Q4W) at W24. Clinical efficacy (ACR/PASI/IGA/HAQ-DI) was assessed in the modified intention to treat (mITT) population through W100 with missing data imputation (nonresponse for categorical endpoints; no change/multiple imputation for continuous endpoints). Observed PsA-modified van der Heijde Sharp (vdH-S) scores derived from blinded radiographic images collected at W0, W24, W52, W100 (or at discontinuation [d/c]) and adverse events (AEs) through W112 were collected.Results:712/739 (96%) randomized pts continued study agent at W24; 687/739 (93%) continued at W52; 652/739 (88%) completed W100. ACR20 response rates in the mITT population continued to increase after W24, and at W100 were 76% for Q4W and 74% for Q8W (Figure 1). Similar response patterns were seen for ACR50/70, HAQ-DI and PASI90/100 (Table 1), and IGA0/1 and PASI75 response rates were consistent through W100 in pts randomized to Q4W and Q8W; W100 data for PBO→Q4W pts were consistent with pts treated with Q4W and Q8W (Table 1). GUS improvements in SF-36 PCS/MCS at W52 also persisted through W100 (data not shown). Low rates of radiographic progression (as measured by PsA-modified vdH-S scores) were observed during W52-100 for Q4W (n=227; 0.75) and Q8W (n=232; 0.46). In the PBO→Q4W group (n=228), radiographic progression was 1.12 during W0-24 (while on PBO), 0.51 during W24-100 (while on Q4W), and 0.13 during W52-100. Through W112, the incidences of AEs, serious AEs (SAEs), AEs leading to d/c, infections, serious infections, and injection site reactions were generally consistent with the PBO-controlled period and through 1 year. Of the pts in the Q4W (n=245), Q8W (n=248), and PBO→Q4W (n=238) groups, 9%, 9% and 7% had ≥1 SAE; 2%, 3% and 3% had ≥1 serious infection; 2 Q8W pts (fungal esophagitis, disseminated herpes zoster) and 1 PBO→Q4W pt (listeria meningitis) had opportunistic infections; 1 PBO→Q4W pt died (road traffic accident); 1 PBO-randomized pt had IBD; no pt had anaphylactic or serum sickness reaction, or active TB.Conclusion:In biologic-naïve PsA pts, GUS improvements in joint and skin symptoms, physical function, and low rates of radiographic progression persisted through 2 years. GUS safety in PsA through 2 years was comparable with safety at 6 months and 1 year, similar between Q4W and Q8W, and consistent with GUS safety in psoriasis.References:[1]Mease PJ. Lancet. 2020 Apr 4;395(10230):1126-1136. [2] McInnes IB. Arthritis Rheumatol. 2020 Oct 11. doi: 10.1002/art.41553.Table 1.Efficacy Through W100 (NRI)Data are %GUS Q4WGUS Q8WPBO→GUS Q4WW24W52W100W24W52W100W24W52W100Analysis set, n245248246 ACR 50334656324855144148 ACR 7013263519283641830BL HAQ-DI ≥0.35, n228228236Improvement ≥0.35a565963505864314856BL ≥3% BSA psoriasis + IGA ≥2, n184176183 IGA0/1696362715855196367 PASI75788783798682238380PASI90617774697470107277PASI10045585945535335261BL, Baseline; BSA, Body surface area; HAQ-DI, Health assessment questionnaire disability index; IGA, Investigator global assessment; NRI, nonresponder imputation; PASI, Psoriasis area and severity index. a≥0.35 improvement among pts with HAQ-DI ≥0.35 at BL.Disclosure of Interests:Iain McInnes Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, Proton Rahman Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Grant/research support from: Janssen and Novartis, Alice B Gottlieb Consultant of: Avotres Therapeutics, Beiersdorf, Boehringer Ingelheim, Bristol-Myers Squibb Co, Incyte, Janssen, LEO Pharma, Eli Lilly, Novartis, Sun Pharmaceutical Industries Inc, UCB, and Xbiotech, Grant/research support from: Boehringer Ingelheim, Incyte, Janssen, Novartis, Sun Pharmaceuticals Industries Inc, UCB, and Xbiotech, Elizabeth C Hsia Shareholder of: Johnson & Johnson, Employee of: Janssen Research and Development, LLC, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Xie L Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Shihong Sheng Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Yusang Jiang Employee of: Cytel, Inc. providing statistical support (funded by Janssen), May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC, Soumya D Chakravarty Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC, Désirée van der Heijde Paid instructor for: Director of Imaging and Rheumatology BV, Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, and UCB, Philip J Mease Speakers bureau: Boehringer Ingelheim and GlaxoSmithKline, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, SUN, and UCB.

Background:The monoclonal antibody guselkumab (GUS; anti- IL-23p19-subunit) is approved to treat psoriatic arthritis (PsA). Post hoc analyses of DISCOVER-1&2 suggested that GUS may be effective in improving symptoms of axial manifestation of PsA.Objectives:Evaluate the efficacy of GUS across components of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in improving symptoms of axial manifestations of active PsA patients (pts) using data from Phase 3, randomized, placebo (PBO)-controlled studies.Methods:DISCOVER-1&2 enrolled pts with active PsA; pts were randomized to subcutaneous injections of guselkumab 100 mg every 4 weeks (Q4W) or at Wk0, 4, and Q8W, or PBO. These post hoc analyses included pts who were identified by the investigator as having axial symptoms and sacroiliitis (prior X-ray or MRI or screening X-ray). BASDAI scores were assessed at Wks 0, 8, 16, 24, and 52. Mean BASDAI component scores through Wk52 are reported by treatment group. Pooled data from the two studies are reported. Mean BASDAI component scores are reported using observed data; total BASDAI scores with missing components were set to missing. The proportion of pts achieving ≥50% improvement in BASDAI (BASDAI 50) was also determined; pts with missing data or who met the treatment failure criteria (discontinued study agent or used prohibited medications) were considered nonresponders at all subsequent timepoints.Results:These analyses included 312 pts from DISCOVER-1&2 (103 GUS Q4W, 91 GUS Q8W, 118 PBO); mean total BASDAI scores at Wk0 were 6.4, 6.5, and 6.6, respectively. Demographics and mean baseline BASDAI component scores (ie, fatigue, spinal pain, joint pain, enthesitis, qualitative morning stiffness, and quantitative morning stiffness) were similar across treatment groups (Table 1). In comparison with the total study population, this subgroup of pts had a higher mean C-reactive protein level at baseline and a higher proportion of pts with enthesitis and included a slightly higher proportion of males. Mean scores for all six BASDAI components, including spinal pain, decreased through Wk24 in GUS-treated pts, with separation from PBO observed as early as Wk8; improvements were maintained at Wk52. At Wk24, BASDAI 50 response rates were higher in the Q4W and Q8W groups vs PBO (38% and 40% vs 19%).1 At WK52, mean BASDAI component scores for PBO pts who crossed over to GUS Q4W at Wk24 were similar to those for pts who were randomized to GUS.2 A similar trend was observed for BASDAI50 response.Conclusion:Among PsA pts with axial symptoms and sacroiliitis (via investigator-confirmed imaging) in the DISCOVER-1&2 trials, GUS treatment resulted in lower mean scores for all six BASDAI components compared with PBO as early as Wk 8 and through Wk24, with mean scores maintained at Wk52.References:[1]Helliwell P, et al. Ann Rheum Dis. 2020; 79; Suppl 1.[2]Mease PJ, et al. Arthritis Rheumatol. 2020; 72 (suppl 10).Table 1.Baseline demographic and disease characteristics for patients who were identified by physicians as having symptoms consistent with spondylitis and had sacroiliitis confirmed via prior radiograph/MRI or screening radiographGUS Q4WGUS Q8WPlaceboPatients, n10391118Male, n (%)68 (66)54 (59)69 (59)Age, years44.9 ± 11.845.0 ± 10.745.3 ± 11.0BASDAIPatients, n9584110Score6.4 ± 1.76.5 ± 1.86.6 ± 1.5BASDAI ComponentsFatigue6.4 ± 2.06.7 ± 1.96.5 ± 1.9Spinal pain6.6 ± 2.16.5 ± 2.36.7 ± 2.0Joint pain6.3 ± 1.96.5 ± 2.26.8 ± 1.7Enthesitis6.3 ± 2.16.4 ± 2.26.3 ± 2.2Qualitative morning stiffness6.8 ± 2.16.7 ± 2.57.0 ± 2.0Quantitative morning stiffness6.2 ± 2.95.7 ± 2.96.1 ± 2.8Data are mean ± standard deviation unless otherwise noted.BASDAI, Bath ankylosing spondylitis disease activity indexDisclosure of Interests:Frank Behrens Speakers bureau: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Chugai, Eli Lilly, Galapagos, Genzyme, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB, Consultant of: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Chugai, Eli Lilly, Galapagos, Genzyme, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB, Grant/research support from: Celgene, Chugai, Janssen, Pfizer, and Roche, Philip J Mease Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, SUN, and UCB, Philip Helliwell Consultant of: Galapagos, Janssen, Novartis, Grant/research support from: AbbVie, Janssen, Pfizer, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, Wim Noel Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, Soumya D Chakravarty Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, Xie L Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, Stephen Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, Yanli Wang Employee of: IQVIA providing statistical support (funded by Janssen), Xenofon Baraliakos Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB.

Background:Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by peripheral arthritis, axial inflammation, dactylitis, enthesitis, & skin/nail psoriasis. Patients (pts) with PsA often experience reduced health-related quality of life (HRQoL) due to these features.Objectives:Using EuroQoL-5 dimension-5 level (EQ-5D-5L) questionnaire index & visual analog scale (EQ-VAS) scores, we assessed HRQoL in pts with PsA & its association with pt characteristics & clinical features of PsA, including fatigue.Methods:The Phase 3 DISCOVER-2 trial evaluated guselkumab (GUS), a human monoclonal antibody targeting the IL-23p19-subunit, in bio-naïve adults with active PsA (swollen joint count [SJC] ≥5, tender joint count [TJC] ≥5, C-reactive protein [CRP] ≥0.6 mg/dL) despite standard therapies.1 Pts were randomized 1:1:1 to GUS 100 mg every 4 weeks (Q4W); GUS 100 mg at Week 0 (W0), W4, then Q8W; or placebo (PBO). EQ-5D-5L index assesses mobility, self-care, usual activities, pain/discomfort, & anxiety/depression. EQ-VAS assesses pt health state. Spearman correlation testing was used to evaluate relationships between baseline (BL) pt characteristics & PsA clinical features & BL EQ-5D-5L index & EQ-VAS scores (Figure 1). Employing absolute observed scores at both W0 & W24, univariate linear regression was used to assess the association between EQ-5D-5L index & EQ-VAS scores & pt characteristics/PsA clinical features. Variables with pResults:Among 738 pts, BL EQ-5D-5L index & EQ-VAS scores were moderately to strongly correlated (ie, ≥0.4) with BL pt-reported pain (0-10 VAS), physical function (Health Assessment Questionnaire-Disability Index [HAQ-DI]), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F] scale), & 36-item Short Form Health Survey (SF-36) physical & mental component summary (PCS & MCS) scores & weakly correlated with other variables (Figure 1). Based on univariate analyses (pConclusion:Joint & skin symptoms, dactylitis, fatigue, pain, & elevated levels of CRP were significantly associated with reduced HRQoL (measured by EQ-5D-5L index & EQ-VAS) in bio-naïve pts with active PsA. Treatment of multiple PsA domains may help optimize HRQoL. Improvement across clinical domains1 & in HRQoL has been observed in GUS-treated pts with PsA.References:[1]Mease P, et al. Lancet 2020;395:1126-36.Table 1.Multivariate analysis of pt characteristics/clinical features & EQ-5D-5L index & EQ-VAS scores at W0 & W24ParameterEQ-5D-5L IndexEQ-VASEstimatep valueEstimatep valueAge (y)-0.00010.690.060.12Female-0.0030.531.110.20CRP (mg/dL)-0.005-0.510.007FACIT-F (0-52)0.0070.57Pain (0-10)-0.02-3.47PASI (0-72)-0.0010.03-0.17SJC (0-66)-0.0010.21-0.170.02TJC (0-68)-0.0010.04-0.040.41Dactylitis (Y/N)0.010.021.740.49Enthesitis (Y/N)-0.0040.33-0.980.22Disclosure of Interests:Jeffrey Curtis Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Eli Lilly, Janssen, Myriad, Pfizer, Regeneron, Roche, and UCB, Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Eli Lilly, Janssen, Myriad, Pfizer, Regeneron, Roche, and UCB, Iain McInnes Consultant of: AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, and UCB, Dafna D Gladman Consultant of: Abbvie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer and UCB, Grant/research support from: Abbvie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer and UCB, Feifei Yang Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, Steve Peterson Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, Prasheen Agarwal Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Elizabeth C Hsia Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Chenglong Han Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, William Tillett Speakers bureau: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, MSD, Pfizer, and UCB, Grant/research support from: AbbVie, Celgene, Eli Lilly, Janssen, Novartis, Philip J Mease Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, SUN, and UCB, Proton Rahman Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Grant/research support from: Janssen and Novartis.

Background:Guselkumab (GUS) is a human monoclonal antibody specific to the p19-subunit of interleukin-23. GUS significantly improved signs and symptoms of PsA through Week24 (Wk24), and improvements were maintained through Wk52 in the Phase 3 DISCOVER-11 and DISCOVER-22 studies.Objectives:Assess GUS efficacy through Wk52 in both studies utilizing composite indices.Methods:Adult patients (pts) enrolled had active PsA despite standard therapies. Pts in DISCOVER-1 had ≥3 swollen and ≥3 tender joints and C-reactive protein (CRP) ≥0.3 mg/dL; in DISCOVER-2, pts had ≥5 swollen and ≥5 tender joints and CRP ≥0.6 mg/dL. 31% of DISCOVER-1 pts received 1-2 prior tumor necrosis factor inhibitors; DISCOVER-2 pts were biologic-naïve. Pts were randomized 1:1:1 to GUS 100 mg every 4 weeks (Q4W); GUS 100 mg at Wk0, Wk4, then every 8 weeks (Q8W); or placebo (PBO); PBO pts crossed over to GUS 100 mg Q4W at Wk24. Composite endpoints pooled across the two studies were: Disease Activity Index for Psoriatic Arthritis (DAPSA), Psoriatic Arthritis Disease Activity Score (PASDAS), Minimal Disease Activity (MDA), and Very Low Disease Activity (VLDA). GUS vs PBO comparisons through Wk24 employed a Cochran-Mantel-Haenszel test with baseline stratification factors or Fisher’s exact test; no treatment group comparisons were performed beyond Wk24. P-values were not adjusted for multiplicity. From Wk24 -Wk52, pts with missing data were considered nonresponders (>90% of pts completed study treatment through Wk52).Results:In randomized and treated pts from DISCOVER-1 (N=381) and DISCOVER-2 (N=739), pooled baseline characteristics were generally well-balanced across treatment groups and reflected active disease. Differences in response rates between GUS Q4W or Q8W and PBO were seen as early as Wk8 and increased over time through Wk24. In pts continuing GUS Q4W or Q8W, respectively, post-Wk24 response rates associated with these composite indices continued to increase through Wk52, at which time they were 54.2% and 52.5% for DAPSA LDA, 45.3% and 41.9% for PASDAS LDA, 35.9% and 30.7% for MDA, 18.2% and 17.6% for DAPSA remission, and 13.1% and 14.4% for VLDA, with no discernable difference between the GUS Q4W and Q8W dosing regimens (Table 1 and Figure 1). After PBO pts crossed over to GUS Q4W at Wk24, response rates increased through Wk52.Conclusion:GUS 100 mg Q4W and Q8W provided robust and sustained benefits to pts with active PsA across multiple domains, indicating that GUS may provide an alternative treatment option for the diverse manifestations of PsA.References:[1]Ritchlin CR et al. RMD Open 2021; 1–11. doi: rmdopen-2020-001457[2]McInnes IB, et al. Arthritis Rheumatol 2020 Oct 11. doi: 10.1002/art.41553.Table 1.Pooled response rates for DISCOVER-1 and DISCOVER-2 randomized and treated patients.DISCOVER-1&2GUS Q4WGUS Q8WPBO -->GUS Q4W1Randomized and treated patients, n373375372PASDAS2LDAWk 2427.9%**30.1%**8.9%Wk 5245.3%41.9%36.8%MDA3Wk 2422.8%**24.3%**7.8%Wk 5235.9%30.7%28.2%DAPSA4RemissionWk 2410.2%**8.3%**2.2%Wk 5218.2%17.6%11.0%VLDA3Wk 246.4%**4.3%*1.3%Wk 5213.1%14.4%8.3%Data reported as proportions of patients, %. Unadjusted p values at Wk24 vs PBO: *p1 Pts randomized to PBO crossed over to GUS Q4W at Wk24.2 PASDAS is derived from Pt global assessment of arthritis and psoriasis (0-100), Physician global assessment (0-100), swollen joint count (0-66), tender joint count (0-68), CRP (mg/L), Leeds enthesitis index score, tender dactylitis count, and the 36-item Short-Form Health Survey Physical Component Summary score. PASDAS LDA ≤3.2.3 MDA is 5/7 criteria met; VLDA is 7/7 criteria met: tender joint count ≤1, swollen joint count ≤1, Psoriasis Activity and Severity Index ≤1, Pt assessment of pain ≤15 (0-100), Pt global assessment of disease activity ≤20 (0-100), Health Assessment Questionnaire-Disability Index score ≤0.5, Tender entheseal points ≤1.4 DAPSA Remission: score ≤4 (definition in Figure 1 legend).Disclosure of Interests:Laura C Coates Consultant of: AbbVie, Amgen, Biogen, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Domain, Eli Lilly, Gilead, Janssen, Medac, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Gilead, Novartis, Pfizer, Christopher T. Ritchlin Consultant of: Amgen, AbbVie, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, and UCB, Laure Gossec Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Biogen, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis, and UCB., Grant/research support from: Amgen, Eli Lilly, Galapagos, Janssen, Pfizer, Sandoz, and Sanofi, Philip Helliwell Consultant of: Galapagos, Janssen, and Novartis, Grant/research support from: AbbVie, Janssen, Pfizer, Proton Rahman Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Grant/research support from: Janssen and Novartis, Elizabeth C Hsia Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Xie L Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Chetan Karyekar Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, Wim Noel Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC, Yusang Jiang Employee of: Cytel, Inc. providing statistical support (funded by Janssen), Shihong Sheng Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Yanli Wang Employee of: IQVIA providing statistical support (funded by Janssen), Philip J Mease Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, SUN, and UCB.

Objectives The aim of this analysis was to evaluate the prevalence of unemployment due to work disability in RA patients initiating treatment with infliximab (IFX) or golimumab (GLM) and to identify determinants of disability. Methods BioTRAC is an ongoing, prospective registry of patients initiating treatment for RA, AS, or PsA with IFX or GLM as first biologics. Data were obtained from RA patients treated with IFX (2002-2014) or GLM (2010-2014). Between employment group differences were assessed for statistical significance with the independent samples t-test or the chi-square. Time to employment and time to unemployment were assessed with the Kaplan-Meier (KM) estimator of the survival function. Cox regression was used to identify predictors of time to unemployment. Results A total of 581 RA patients were included; 374 (64.4%) employed and 207 (35.6%) unemployed due to disability. The following baseline parameters were associated with significantly increased likelihood of being unemployed due to disability: female vs. male gender (40.1% vs. 27.6%; P=0.006), earlier enrolment period (2002-05 vs. 2006-09 vs. 2010-14: 49.3% vs. 30.5% vs. 22.4%; P Among disabled patients, 10.1% were able to return to work upon treatment with TNF a mean KM-based duration of 119.5 months from baseline; whereas 6.4% of employed patients became disabled (2002-05 vs. 2006-09 vs. 2010-14: 7.0% vs. 10.1% vs. 1.7%; P=0.021) with a mean time to unemployment of 113.4 months. Multivariate survival analysis showed that, upon adjusting for enrolment period, higher baseline HAQ [HR (95%CI): 3.59 (1.64, 7.87), P=0.001], and higher baseline SJC [HR (95%CI): 1.09 (1.02, 1.16), P=0.011] were significant predictors of unemployment due to disability. Conclusions A significant proportion of RA patients are unemployed due to disability. At anti-TNF initiation, work disability was associated with higher disease activity, female gender, earlier enrolment period, and provincial insurance. Increased HAQ and higher SJC were significant predictors of progression to unemployment. Anti-TNF treatment was effective in enabling a considerable portion of disabled patients to return to employment. Disclosure of Interest A. Chow: None declared, W. Bensen Consultant for: Janssen, R. Arendse Consultant for: Janssen, E. Keystone Consultant for: AbbVie, Amgen, BMS, Janssen, Pfizer, Roche, Speakers bureau: AbbVie, Amgen, BMS, Janssen, Pfizer, Roche, P. Baer Consultant for: AbbVie, Amgen, BMS, Janssen, Pfizer, Roche, Speakers bureau: AbbVie, Amgen, BMS, Janssen, Pfizer, Roche, J. Kelsall Consultant for: Janssen, W. Olszynski: None declared, J. Rodrigues: None declared, A. Avina-Zubieta: None declared, M. Baker: None declared, W. Olszynski: None declared, W. Bensen Consultant for: Janssen, P. Baer Consultant for: Janssen, D. Choquette Consultant for: AbbVie, Amgen, Celgene, BMS Canada, Janssen, Pfizer, S. Kapur: None declared, A. Jaroszynska: None declared, J. Sampalis Shareholder of: JSS Medical Research, Employee of: JSS Medical Research, D. Choquette Consultant for: AbbVie, Amgen, Celgene, BMS Canada, Janssen, Pfizer, E. Rampakakis Employee of: JSS Medical Research, S. Kapur: None declared, J. Stewart: None declared, C. Tkaczyk Employee of: Janssen, J. Sampalis Shareholder of: JSS Medical Research, Employee of: JSS Medical Research, M. Shawi Employee of: Janssen, E. Rampakakis Employee of: JSS Medical Research, A. Lehman Employee of: Janssen, F. Nantel Employee of: Janssen, S. Otawa Employee of: Janssen, C. Tkaczyk Employee of: Janssen, A. Lehman Employee of: Janssen

This paper presents a parsing technique with certain advantages for a compiler system. A review and a comparison with other techniques are given.