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Background:Upadacitinib (UPA), an oral Janus kinase inhibitor, demonstrated significant improvements in signs, symptoms, and structural inhibition as monotherapy (mono) vs methotrexate (MTX) in MTX-naïve patients (pts) with rheumatoid arthritis (RA) through 48 weeks (wks).1Objectives:To report the efficacy and safety of UPA vs MTX mono up to 156 wks in pts with RA from the ongoing long-term extension (LTE) of the SELECT-EARLY trial.Methods:During the 48-wk double-blind study period, pts were randomized to UPA 15 or 30 mg once daily (QD) or MTX (titrated to 20 mg/wk by Wk 8). At Wk 26, pts who did not achieve Clinical Disease Activity Index (CDAI) remission (≤2.8) and had Results:Of 945 pts randomized and treated, 775 entered the LTE on study drug (including 57 rescued pts; MTX, 33; UPA 15 mg, 17; UPA 30 mg, 7). Overall, 161 (21%) pts discontinued during the LTE. At Wk 156, higher proportions of pts randomized to UPA achieved a 20/50/70% improvement in ACR response (ACR20/50/70), LDA, and remission vs MTX (Figure 1). Change from baseline in mTSS at Wk 96 favored UPA vs MTX (data not shown). Most AEs were numerically more frequent with UPA 30 mg. The overall rate of serious infection was numerically higher with UPA vs MTX (Table 1). Herpes zoster (HZ), neutropenia, non-melanoma skin cancer (NMSC), and creatine phosphokinase (CPK) elevation were more frequent with UPA vs MTX. Two active tuberculosis (TB) events were reported in each UPA arm; 3 adjudicated gastrointestinal (GI) perforation events were observed in the UPA 30 mg arm. Adjudicated major adverse cardiovascular events (MACEs) or venous thromboembolic events (VTEs) were comparable across treatment arms.Conclusion:UPA monotherapy showed sustained clinically meaningful responses including remission vs MTX through Wk 156 but higher rates of several AEs, including HZ, neutropenia, and CPK elevations; no new safety risks were observed compared with previous results.1,2References:[1]van Vollenhoven R, et al. Ann Rheum Dis 2019;78:376–7; 2. Cohen SB, et al. Ann Rheum Dis 2020;annrheumdis-2020-218510.Table 1.Safety overviewE/100 PY (95% CI)MTX mono(n=314; PY=601.9)UPA 15 mg QD mono(n=317; PY=703.4)UPA 30 mg QD mono(n=314; PY=687.6)Any AE240.2(228.0, 252.9)268.0(256.0, 280.4)292.5(279.8, 305.5)Any serious AE10.8 (8.3, 13.8)12.2 (9.8, 15.1)16.3 (13.4, 19.6)Any AE leading to discontinuation of study drug6.5 (4.6, 8.9)7.3 (5.4, 9.5)7.7 (5.8, 10.1)Any deatha0.7 (0.2, 1.7)0.9 (0.3, 1.9)1.0 (0.4, 2.1)Serious infection2.5 (1.4, 4.1)3.3 (2.1, 4.9)4.4 (2.9, 6.2)Opportunistic infection excluding TB and HZ0.2 (0.0, 0.9)0.1 (0.0, 0.8)0.3 (0.0, 1.1)HZ0.8 (0.3, 1.9)4.5 (3.1, 6.4)4.7 (3.2, 6.6)Active TB00.3 (0.0, 1.0)0.3 (0.0, 1.1)NMSC00.4 (0.1, 1.2)1.0 (0.4, 2.1)Malignancy other than NMSC1.0 (0.4, 2.2)0.6 (0.2, 1.5)1.2 (0.5, 2.3)Hepatic disorder14.1 (11.3, 17.5)12.5 (10.0, 15.4)15.0 (12.2, 18.2)GI perforationb000.4 (0.1, 1.3)Neutropenia2.2 (1.2, 3.7)4.5 (3.1, 6.4)5.7 (4.0, 7.8)CPK elevation1.8 (0.9, 3.3)7.7 (5.8, 10.0)15.4 (12.6, 18.6)MACEb0.3 (0.0, 1.2)0.4 (0.1, 1.2)0.6 (0.2, 1.5)VTEb0.3 (0.0, 1.2)0.4 (0.1, 1.2)0.6 (0.2, 1.5)Data were censored at the time of MTX or UPA addition for rescued ptsaIncludes treatment-emergent (≤30 days after the last dose of study drug) and non-treatment-emergent deaths. bAdjudicatedAcknowledgements:AbbVie funded this study; contributed to its design; participated in data collection, analysis, and interpretation of the data; and in the writing, review, and approval of the abstract. No honoraria or payments were made for authorship. Medical writing support was provided by Russell Craddock, PhD, of 2 the Nth (Cheshire, UK), and was funded by AbbVie.Disclosure of Interests:Ronald van Vollenhoven Speakers bureau: AbbVie, AstraZeneca, Biotest, Bristol-Myers Squibb, Galapagos, Gilead, GSK, Janssen, Pfizer, Sanofi, Servier, UCB, and Viela Bio, Consultant of: AbbVie, AstraZeneca, Biogen, Biotest, Bristol-Myers Squibb, Galapagos, Gilead, GSK, Janssen, Pfizer, Sanofi, Servier, UCB, and Viela Bio, Grant/research support from: Bristol-Myers Squibb, GSK, Eli Lilly, Pfizer, Roche, and UCB, Tsutomu Takeuchi Speakers bureau: AbbVie, AYUMI, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Dainippon Sumitomo, Eisai, Gilead, Mitsubishi Tanabe, Novartis, Pfizer, and Sanofi, Consultant of: Astellas, Chugai, and Eli Lilly, Grant/research support from: AbbVie, Asahi Kasei, Astellas, Chugai, Daiichi Sankyo, Eisai, Mitsubishi Tanabe, Nippon Kayaku, Shionogi, Takeda, and UCB, Jacob Aelion Grant/research support from: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos/Gilead, Genentech, GSK, Horizon, Janssen, Mallinckrodt, Nektar, Nichi-Iko, Novartis, Pfizer, Regeneron, Roche, Sanofi, Selecta, and UCB, Nilmo Chávez Speakers bureau: AbbVie, Janssen, and Pfizer, Consultant of: AbbVie, Janssen, and Pfizer, Grant/research support from: AbbVie, Galapagos, Gilead, Pfizer, and Sanofi, Pablo Mannucci Walter Consultant of: AbbVie, Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lilly, Genentech/Roche, GSK, Janssen, and UCB, Atul Singhal Consultant of: AbbVie, Aclaris, Amgen, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Gilead, Idorsia, Novartis, Oscotec, Pfizer, Regeneron, Roche/Genentech, Sanofi, Selecta, Takeda, UCB, and Viela Bio, Grant/research support from: AbbVie, Aclaris, Amgen, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Gilead, Idorsia, Novartis, Oscotec, Pfizer, Regeneron, Roche/Genentech, Sanofi, Selecta, Takeda, UCB, and Viela Bio, Jerzy Swierkot Speakers bureau: AbbVie, Accord, BMS, Janssen, MSD, Pfizer, Roche, Sandoz, and UCB, Consultant of: AbbVie, Accord, BMS, Janssen, MSD, Pfizer, Roche, Sandoz, and UCB, Grant/research support from: AbbVie, Accord, BMS, Janssen, MSD, Pfizer, Roche, Sandoz, and UCB, Alan Friedman Shareholder of: May own stock or options in AbbVie, Employee of: AbbVie, Nasser Khan Shareholder of: May own stocks or options in AbbVie, Employee of: AbbVie, Yihan Li Shareholder of: May own stocks or options in AbbVie, Employee of: AbbVie, Xianwei Bu Shareholder of: May own stocks or options in AbbVie, Employee of: AbbVie, Justin Klaff Shareholder of: May own stock or options in AbbVie, Employee of: AbbVie, Vibeke Strand Consultant of: AbbVie, Amgen, Arena, AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Celltrion, Eli Lilly, Genentech/Roche, Gilead, GSK, Ichnos, Inmedix, Janssen, Kiniksa, MSD, Myriad Genetics, Novartis, Pfizer, Regeneron, Sandoz, Sanofi, Setpoint, and UCB

Background:Risankizumab (RZB) is a humanized immunoglobin G1 monoclonal antibody that specifically inhibits interleukin 23 by binding its p19 subunit. RZB is being investigated as a treatment for adults with psoriatic arthritis (PsA).Objectives:To compare the efficacy and safety of RZB vs placebo (PBO) for the treatment of active PsA in patients who have had inadequate response or intolerance to 1 or 2 biologic therapies (Bio-IR) or to ≥ 1 conventional synthetic disease modifying antirheumatic drug (csDMARD-IR).Methods:KEEPsAKE 2 (NCT03671148) enrolled adults with active PsA (≥ 5 swollen joints [SJC] and ≥ 5 tender joints [TJC]) who were Bio-IR or csDMARD-IR. Patients were randomized to receive blinded subcutaneous RZB 150 mg or PBO at weeks 0, 4, and 16. The primary endpoint was the proportion of patients achieving ≥ 20% improvement in American College of Rheumatology score (ACR20) at week 24. Ranked secondary endpoints and other secondary endpoints are shown in the Table. Safety was assessed throughout the study. Results reported here are from the 24-week double-blind period; the open-label period with all patients receiving RZB is ongoing.Results:A total of 443 patients (RZB, N = 224; PBO, N = 219) were included in the analysis. Demographics and baseline disease characteristics were similar across treatment arms (mean SJC: 13.3; mean TJC: 22.6; mean duration of PsA: 8.2 years; mean body surface area involved with psoriasis [BSA] in patients with BSA ≥ 3%: 12.1%); 206 patients (46.5%) were Bio-IR. Significantly greater proportions of RZB-treated patients vs PBO-treated patients achieved the primary endpoint (51.3% vs 26.5%, respectively; P < .001) and all ranked secondary endpoints (P < .001 for all except for Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-Fatigue; P < .009]; Table). Other secondary outcomes also showed improvement for RZB- vs PBO-treated patients (Table). Serious adverse events were reported for 4.0% and 5.5% of RZB- and PBO-treated patients, respectively; serious infections were reported for 0.9% and 2.3%.Conclusion:RZB resulted in significantly greater improvements in signs and symptoms of PsA compared with PBO and was well tolerated in patients who were Bio-IR or csDMARD-IR.Disclosure of Interests:Andrew Ostor Speakers bureau: AÖ has received speaker or consulting fees and/or research grants from AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Sanofi, and UCB., Consultant of: AÖ has received speaker or consulting fees and/or research grants from AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Sanofi, and UCB., Grant/research support from: AÖ has received speaker or consulting fees and/or research grants from AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Sanofi, and UCB., Filip van den Bosch Speakers bureau: FVdB has received speaker and/or consulting fees from Abbvie, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB., Consultant of: FVdB has received speaker and/or consulting fees from Abbvie, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB., Kim Papp Speakers bureau: KP has received honoraria or fees for serving on advisory boards, as a speaker, and as a consultant, as well as grants as principal investigator from AbbVie, Amgen, Astellas, Bausch Health (Valeant), Baxalta, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Coherus, Dermira, EMD Serono, Forward Pharma, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa Kirin, LEO Pharma, Lilly, MedImmune, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Stiefel, Sun Pharma, Takeda, and UCB., Consultant of: KP has received honoraria or fees for serving on advisory boards, as a speaker, and as a consultant, as well as grants as principal investigator from AbbVie, Amgen, Astellas, Bausch Health (Valeant), Baxalta, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Coherus, Dermira, EMD Serono, Forward Pharma, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa Kirin, LEO Pharma, Lilly, MedImmune, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Stiefel, Sun Pharma, Takeda, and UCB., Grant/research support from: KP has received honoraria or fees for serving on advisory boards, as a speaker, and as a consultant, as well as grants as principal investigator from AbbVie, Amgen, Astellas, Bausch Health (Valeant), Baxalta, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Coherus, Dermira, EMD Serono, Forward Pharma, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa Kirin, LEO Pharma, Lilly, MedImmune, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Stiefel, Sun Pharma, Takeda, and UCB., CECILIA ASNAL Speakers bureau: CA has received honoraria or fees for serving on advisory boards or as a speaker, as well as research support from AbbVie, Genentech, Janssen, Lilly, Pfizer, and Roche., Grant/research support from: CA has received honoraria or fees for serving on advisory boards or as a speaker, as well as research support from AbbVie, Genentech, Janssen, Lilly, Pfizer, and Roche., Ricardo Blanco Speakers bureau: RB has received grants or research support from AbbVie, Merck, and Roche; and has received consultation fees or honoraria for serving as a speaker for AbbVie, Bristol-Myers Squibb, Janssen, Lilly, Merck, Pfizer, and Roche., Consultant of: RB has received grants or research support from AbbVie, Merck, and Roche; and has received consultation fees or honoraria for serving as a speaker for AbbVie, Bristol-Myers Squibb, Janssen, Lilly, Merck, Pfizer, and Roche., Grant/research support from: RB has received grants or research support from AbbVie, Merck, and Roche; and has received consultation fees or honoraria for serving as a speaker for AbbVie, Bristol-Myers Squibb, Janssen, Lilly, Merck, Pfizer, and Roche., Jacob Aelion Grant/research support from: JA has received grants or research support from AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Galapagos/Gilead, Genentech, GlaxoSmithKline, Lilly, Mallinckrodt, Nektar Therapeutics, Nichi-Iko, Novartis, Pfizer, Regeneron, Roche, Sanofi, Selecta Biosciences, and UCB., Gabriela Alperovich Shareholder of: GA is a full-time employee of AbbVie, and may hold AbbVie stock or stock options., Employee of: GA is a full-time employee of AbbVie, and may hold AbbVie stock or stock options., Ying Zhang Shareholder of: YZ is a former AbbVie employee, and may hold AbbVie stock or stock options., Employee of: YZ is a former AbbVie employee, and may hold AbbVie stock or stock options., Zailong Wang Shareholder of: ZW is a full-time employee of AbbVie, and may hold AbbVie stock or stock options., Employee of: ZW is a full-time employee of AbbVie, and may hold AbbVie stock or stock options., Ahmed M. Soliman Shareholder of: AS is a full-time employee of AbbVie, and may hold AbbVie stock or stock options., Employee of: AS is a full-time employee of AbbVie, and may hold AbbVie stock or stock options., Ann Eldred Shareholder of: AE is a full-time employee of AbbVie, and may hold AbbVie stock or stock options., Employee of: AE is a full-time employee of AbbVie, and may hold AbbVie stock or stock options., Alan Kivitz Shareholder of: AK is a shareholder of or has received honoraria or fees as a consultant, speaker, or expert witness for AbbVie, Boehringer Ingelheim, Celgene, Flexion, Gilead, GlaxoSmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharma, and UCB., Speakers bureau: AK is a shareholder of or has received honoraria or fees as a consultant, speaker, or expert witness for AbbVie, Boehringer Ingelheim, Celgene, Flexion, Gilead, GlaxoSmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharma, and UCB., Consultant of: AK is a shareholder of or has received honoraria or fees as a consultant, speaker, or expert witness for AbbVie, Boehringer Ingelheim, Celgene, Flexion, Gilead, GlaxoSmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharma, and UCB.

Background:Remission, LDA and LDAS have been proposed as treatment goals for SLE. However, the independent impact of these states on damage accrual has not been fully evaluated.Objectives:To determine the independent impact of remission (both off & on treatment), LDA, and LLDAS on damage accrual.Methods:We studied a long-term longitudinal multinational SLE cohort, including patients completing at least two annual assessments. Remission off-treatment was defined as a SLEDAI (excluding serology) =0, without prednisone and immunosuppressive (IS) drugs. Remission on-treatment was defined as a SLEDAI (excluding serology) =0, prednisone daily doseResults:There were 1,652 patients, 1464 (88.6%) were female, mean age at diagnosis was 34.6 (SD 13.4) years and mean baseline disease duration was 5.5 (SD 4.1) months. Patients had a mean follow-up of 6.5 (SD 4.3) years, 11686 visits were included. 763 patients (46.2%) had an increase in SDI score ≥1 during follow-up. 2483 (21.2%) of the visits were classified as remission off-treatment, 2276 (19.5%) as remission on-treatment, 544 (4.7%) as LDA, 657 (5.6%) as LLDAS and 5726 (49.0%) as not-optimally controlled. Being in remission off-treatment, remission on-treatment, LDA and LLDAS were predictive of a lower probability of damage accrual [remission off-treatment IRR=0.403, 95% CI 0.301-0.541); remission on-treatment IRR=0.313 (95% CI 0.218-0.451) LDA: IRR=0.469 (CI 95% CI 0.272-0.809); LLDAS IRR=0.440 (95% CI 0.241-0.803)]. The multivariable model is summarized in Table 1.Table 1.Multivariable GEE model of the impact of disease activity states on damage accrual.Incidence Rate Ratio95% CIDisease activity stateRemission off treatment0.4030.301-0.541Remission on treatment0.3130.218-0.451LDA0.4690.272-0.809LLDAS0.4400.241-0.803Gender, male1.2741.086-1.495Age at diagnosis1.0241.020-1.029EthnicityCaucasian USRef.Caucasian other1.0170.849-1.217African1.4671.211-1.776Asian0.8630.693-1.075Hispanic1.2661.034-1.550Other1.1210.759-1.656Educational level, years0.9770.957-0.996Disease duration at baseline0.9600.801-1.150Follow-up time0.9420.923-0.960Antimalarial use0.7860.681-0.908Highest prednisone dose before baseline1.0021.001-1.007SDI before1.1001.050-1.1152LLDAS: Low lupus disease activity state LDA: Low disease activity SDI: SLICC/ACR Damage IndexConclusion:Remission on- and off-treatment, LDA and LLDAS were associated with less damage accrual, even adjusting for possible confounders and effect modifiers. This highlights the importance of treating to target in SLE.Disclosure of Interests:Manuel F. Ugarte-Gil Grant/research support from: Pfizer, Janssen, John Hanly: None declared, Murray B Urowitz: None declared, Caroline Gordon Speakers bureau: UCB, Consultant of: Center for Disease Control, Astra-Zeneca, MFP, Sanofi, UCB, Sang-Cheol Bae: None declared, Juanita Romero-Diaz: None declared, Jorge Sanchez-Guerrero: None declared, Sasha Bernatsky: None declared, Ann E Clarke Consultant of: AstraZeneca, BristolMyersSquibb, GlaxoSmithKline, and Exagen Diagnostics, Daniel J Wallace Grant/research support from: Exagen, David Isenberg: None declared, Anisur Rahman: None declared, Joan T Merrill: None declared, Paul Fortin: None declared, Dafna D Gladman Consultant of: Abbvie, Janssen, Pfizer, Novartis, Amgen, Grant/research support from: Abbvie, Janssen, Pfizer, Novartis, Amgen, Ian N. Bruce: None declared, Michelle A Petri: None declared, Ellen M Ginzler Grant/research support from: Aurinia pharmaceutical, M.A. Dooley: None declared, Rosalind Ramsey-Goldman: None declared, Susan Manzi: None declared, Andreas Jonsen: None declared, Ronald van Vollenhoven Speakers bureau: AbbVie, Galapagos, GSK, Janssen, Pfizer, UCB, Consultant of: Abbvie, AstraZeneca, Biogen, Biotest, Celgen, Galapagos, Gilead, Janssen, Pfizer, Sanofie, Servier, UCB, Vielabo, Grant/research support from: BMS, GSK, Lilly, UCB, Cynthia Aranow: None declared, Meggan Mackay: None declared, Guillermo Ruiz-Irastorza: None declared, S. Sam Lim: None declared, Murat Inanc: None declared, Kenneth C Kalunian Consultant of: Roche, Biogen, Janssen, AstraZeneca, Eli Lilly, Genetech, Gilead, ILTOO, Nektar, Viela, Equillium, Bristol-Meyers Squibb, Soren Jacobsen Grant/research support from: BMS, Christine Peschken: None declared, Diane L Kamen: None declared, Anca Askanase Consultant of: Abbvie, Grant/research support from: Glaxo Smith Kline, Astra Zeneca, Janssen, Eli Lilly and Company, Mallinckrodt, Pfizer, Bernardo Pons-Estel Consultant of: GSK, Janssen, Graciela S Alarcon: None declared.

Background:Structural damage was identified as an important outcome domain in the Psoriatic Arthritis (PsA) Core Domain Set and should be assessed at least once in the development of a new therapeutic.Objectives:To conduct a systematic literature review (SLR) to identify studies addressing the measurement properties (MPs) for ROIs and appraise the evidence through the OMERACT Filter 2.1 Framework Instrument Selection Algorithm (OFISA). [1]Methods:An SLR was conducted in EMBASE and MEDLINE to identify full-text English studies developing or assessing MPs of ROIs in PsA. Determination of eligibility, data extraction and methodology asssessment were performed by 2 reviewers. MPs were rated according to the ‘Provisional Standards’ and assigned a Red/Amber/White/Green (RAWG) rating (Figure 1). [1, 2]Results:3621 references were screened, 531 full-text articles reviewed, and 12 were included (Figure 2). Nine instruments assessing peripheral radiographs and six assessing axial radiographs were identified (Table 1). Three of the nine peripheral radiographic instruments had adequate evidence for reliability and some evidence for construct validity: the modified Steinbrocker, Ratingen, and modified Sharp van der Heijde scores. There was scant evidence for reliability, construct validity and responsiveness for the axial ROIs, compounded by the lack of a standardized definition of axial PsA.Conclusion:This SLR summarizes the MPs of ROIs and identifies relevant knowledge gaps that need to be addressed prior to endorsement of an instrument for the PsA Core Domain Set.References:[1]Richards P and De Wit M, editors. The OMERACT Handbook (March 2019)[2]Mokkink LB and D’Agostino MA. Protocol for performing a systematic review on imaging techniques (unpublished)Figure 1.Criteria for the RAWG RatingFigure 2.PRISMA DiagramTable 1.Summary of Measurement PropertiesROIDomain MatchFeasibilityConstruct ValidityDiscriminationReliabilityResponsivenessInter-raterIntra-raterMeasurement ErrorLongitudinal Construct ValidityClinical Trial DiscriminationThresholds of MeaningOriginal Steinbrocker ScoreA[1]A[1]R[1]Modified Steinbrocker Score#G[2]G[2]A[1]A[2]Modified Larsen ScoreA[1]A[1]A[1]*Ratingen Score#A[1]G[3]G[3]A[3]A[1]mTSS-AA[1]A[1]A[1]mTSS-B#A[1]A[1]A[1]A[1]*mSvdHs#A[2]G[2]G[2]A[1]A[1]*ReXPsAR[0]SPARS#A[1]A[1]A[1]Axial PsA Definition 1MSASSS#A[2]R[0]BASRI - Total#A[2]R[0]PASRI#A[2]R[0]Axial PsA Definition 2MSASSS#A[1]R[1]A[1]A[1]BASRI - Spine#R[1]A[1]A[1]PASRI#A[1]A[1]A[1]Modified NYC#R[1]A[1]RASSS#R[1]A[1]A[1]A = Amber, R = Red, G = Green[Total available studies for synthesis following excluding studies with poor methodology]* RCT data available but no published effect sizes# Feasibility data availableDisclosure of Interests:Anna Antony: None declared, Richard Holland: None declared, Wieneke Mokkink: None declared, Maria-Antonietta d’Agostino: None declared, Walter P Maksymowych Grant/research support from: Received research and/or educational grants from Abbvie, Novartis, Pfizer, UCB, Consultant of: WPM is Chief Medical Officer of CARE Arthritis Limited, has received consultant/participated in advisory boards for Abbvie, Boehringer, Celgene, Eli-Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, UCB, Speakers bureau: Received speaker fees from Abbvie, Janssen, Novartis, Pfizer, UCB., Heidi Bertheussen: None declared, Lori Schick: None declared, Niti Goel Shareholder of: UCB and Galapagos, Consultant of: VielaBio, Mallinckrodt, and IMMVention, Alexis Ogdie Grant/research support from: Pfizer, Novartis, Consultant of: Abbvie, Amgen, BMS, Celgene, Corrona, Janssen, Lilly, Pfizer, Novartis, Ana-Maria Orbai Grant/research support from: Abbvie, Eli Lilly and Company, Celgene, Novartis, Janssen, Horizon, Consultant of: Eli Lilly; Janssen; Novartis; Pfizer; UCB. Ana-Maria Orbai was a private consultant or advisor for Sun Pharmaceutical Industries, Inc, not in her capacity as a Johns Hopkins faculty member and was not compensated for this service., Pil Hoejgaard: None declared, Laura C Coates: None declared, Vibeke Strand Consultant of: AbbVie, Amgen, Biogen, Celltrion, Consortium of Rheumatology Researchers of North America, Crescendo Bioscience, Eli Lilly, Genentech/Roche, GlaxoSmithKline, Hospira, Janssen, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi, UCB, Dafna D Gladman Grant/research support from: AbbVie, Amgen Inc., BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB – grant/research support, Consultant of: AbbVie, Amgen Inc., BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB – consultant, Robin Christensen: None declared, Ying Ying Leung Speakers bureau: Novartis, Janssen, Eli Lilly, Philip J Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/research support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau, William Tillett Grant/research support from: AbbVie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, UCB, Consultant of: AbbVie, Amgen, Celgene, Lilly, Janssen, Novartis, MSD, Pfizer Inc, UCB, Speakers bureau: AbbVie, Amgen, Celgene, Lilly, Janssen, Novartis, Pfizer Inc, UCB

Background:Infections are the most common cause of morbidity and mortality in idiopathic inflammatory myositis (IIM). India is endemic for Tuberculosis (TB) with a prevalence of 2.3 cases per thousand population.Objectives:Thus, we studied the prevalence of TB in our cohort of IIM patients and compared with that in systemic lupus erythematosus (SLE).Methods:Medical records from paper charts and electronic medical records were reviewed for adults and juvenile patients with SLE (ACR criteria 1997) and IIM (Bohan and Peter criteria 1975) first presented at a tertiary care hospital in India from 1989 to 2016. Clinical variables including disease characteristics variables, the frequency, site, duration and complication of active TB as well as dose of corticosteroids and other immunosuppressive drugs were extracted retrospectively from the medical records. Descriptive statistics were used to describe the cohort and TB characteristics. Chi-square and t-test were used to evaluate association of TB with clinical diagnosis as well as medication data.Results:There were 167 (132 adults and 35 juvenile) IIM and 280 (131 adults and 149 juvenile) SLE in our cohort. Active TB occurred in 24 (14.4%) of all IIM cases (18, 13.6% adults; 6, 17.1% juvenile) as compared to 18 (6.4%) of all SLE cases (8, 6.1% adults; 10, 6.7% juvenile, p value < 0.01). Of all the TB in myositis, most often it was seen in Dermatomyositis (n=11, 45.8%) followed by Polymyositis (5, 20.8%), and occasionally in Overlap myositis (3, 12.5) and juvenile dermatomyositis (1,4.1%).Considering an annual TB rate of 211 per 100,000 of the general population, the risk of developing active TB was 62-fold higher in patients with IIM and 27-fold higher in those with lupus. Patients with IIM had higher odds of developing TB as compared with Lupus [odds ratio 2.86 (CI 1.5-5.47), p=0.007).Amongst 24 IIM patients with TB, 10 had pulmonary TB and 14 had extra-pulmonary TB. The median glucocorticoid dose at the diagnosis of TB was 0.25 (0-1.5) mg/kg/day. Half the cases of active TB occurred during inactive myositis. Seventeen patients with active TB were followed up over 27 months (8-184), with remission of TB in all cases but required prolonged courses of Anti-Tuberculous Therapy (ATT) in 25% cases with 10 ATT related adverse events in 8 patients and 5 patients with relapse of myositis due to lowering of immunosuppression.Conclusion:Patients with IIM have higher prevalence of active TB as compared with SLE patients. The risk is highest in patients with Dermatomyositis possibly related to high doses of steroids. Extra-pulmonary forms of TB are more common, and patients commonly require prolonged course of ATT and may suffer relapses of myositis during ATT. Screening for latent TB may be useful in IIM patients before prescribing steroids and other immunosuppressive drugs.References:[1]TB Statistics India | National, treatment outcome & state statistics [Internet]. TB Facts | TB, tests, drugs, statistics. [cited 2019 Jun 13]. Available from:https://www.tbfacts.org/tb-statistics-india/[2]Muhammed H, Gupta L, Zanwar A, Misra DP, Lawrence A, Agarwal V, Aggarwal A, Misra R;OPC0243: Infections are leading cause of in-hospital mortality in patients with inflammatory myositis; Indian J Rheumatol 2018;13, Suppl S2:93-241[3]Gaitonde S, Pathan E, Sule A, Mittal G, Joshi VR. Efficacy of isoniazid prophylaxis in patients with systemic lupus erythematosus receiving long term steroid treatment. Ann Rheum Dis. 2002 Mar;61(3):251–3.[18]He D, Bai F, Zhang S, Jiang T, Shen J, Zhu Q, et al. High incidence of tuberculosis infection in rheumatic diseases and impact for chemoprophylactic prevention of tuberculosis activation during biologics therapy. Clin Vaccine Immunol CVI. 2013 Jun;20(6):842–7.Figure 1.(A) Prevalence and (B) sites of tuberculosisTable 1.Table 2.Clinical profile of patients with TuberculosisDisclosure of Interests:Latika Gupta: None declared, Abhishek Zanwar: None declared, Rohit Aggarwal Grant/research support from: Pfizer, Genentech, BMS, Mallinckrodt, Consultant of: Pfizer, Genentech, BMS, Mallinckrodt, Bristol Myers-Squibb, octapharma, CSL Behring, AstraZeneca, Corbus, Kezar, Abbvie, Able Lawrence: None declared, Durga Misra: None declared, Vikas Agarwal: None declared, Ramnath Misra: None declared, Amita Aggarwal: None declared

Background:Osteoarthritis (OA) commonly affects joints in the hand. The natural history of hand OA is not well understood, and the local determinants of symptoms and structural changes over time remain unclear.Objectives:To investigate, in both cross-sectional and prospective studies, the association between imaging (ultrasound [US] and magnetic resonance imaging [MRI]) features and symptoms of hand OA, and to examine in prospective studies whether imaging-detected features at baseline predict subsequent clinical and radiographic outcomes.Methods:A systematic literature search was conducted in five databases including Medline, Web of Science, EMBASE, CINAHL and AMED in April 2018. The search was designed to capture published observational studies on the use of US and MRI in hand OA with no language restrictions. Odds ratios (OR), risk ratios (RR), and 95% confidence interval (CI) between [1] imaging features and hand OA symptoms at baseline, and [2] baseline-imaging features and follow-up outcomes were extracted and pooled using random effects model. Outcomes were defined as either incidence or progression of pre-existing features. Risk of bias assessment was performed using the Newcastle-Ottawa Scales. Heterogeneity and publication bias were assessed.Results:The search identified 2818 citations, which reduced to 2216 after duplicate removal. Screening of titles and abstracts found 140 articles which met the inclusion criteria. After full text screening, 25 were included for analysis, including 452 participants (87% women) for US and 298 participants (86% women) for MRI with mean ages 60.3 and 62.5, respectively. Imaging-detected structural OA features were preferentially found in distal interphalangeal joints (DIPJs) followed by carpometacarpal (CMCJ) and proximal interphalangeal (PIPJ) joints. Metacarpophalangeal joints were least affected. However, the distribution pattern was different for inflammatory features for which the CMCJ was the most affected, and with no clear difference between DIPJs and PIPJs (Figure 1).Figure 1.Hand map of grey-scale synovitis derived from pooled estimates of prevalence across studies (%[95% CI])Of 10 US and 5 MRI studies examining association at baseline, joint tenderness was associated with US osteophytes (pooled ORs 2.30, 95% CI 1.90-2.79), grey-scale synovitis (3.00, 2.33-3.84), synovial effusion (2.92, 2.29-3.72), and power Doppler (PD) (2.30, 1.68-3.15). Similar relationships were observed with MRI features (Figure 2). Six studies did not find any association between imaging features and self-reported outcomes. However, association was observed with US- and MRI-detected synovitis in one study each, and MRI-detected structural features in two. Statistical pooling was not possible for these outcomes due to heterogeneous data.Figure 2.Forest plot showing pooled odds ratio between baseline magnetic resonance imaging features of hand osteoarthritis and joint tenderness.Of the 9 US and 5 MRI studies for prediction, a dose-dependent relationship was observed between baseline PD and radiographic change at follow-up (Figure 3). Similar results were observed for MRI features and Kellgren-Lawrence change. The pooled ORs (95% CI) was 2.66 (1.88, 3.78) for bone marrow lesions, and 2.18 (1.53, 3.10) and 4.7 (3.08, 7.18) for grades 1 and 2 synovitis, respectively. Data to predict change in clinical outcomes however, were lacking.Figure 3.Forest plot showing pooled odds ratio between baseline power Doppler and radiographic change over timeConclusion:Imaging-detected inflammatory features and osteophytes associate with joint tenderness. In addition, imaging-detected inflammatory changes at baseline predict future development and progression of structural OA changes, indicating that inflammation may precede radiographically-detectable structural changes.Disclosure of Interests:Abasiama Obotiba: None declared, Subhashisa Swain: None declared, Jaspreet Kaur: None declared, Khalid Yaseen: None declared, Michael Doherty Grant/research support from: AstraZeneca funded the Nottingham Sons of Gout study, Consultant of: Advisory borads on gout for Grunenthal and Mallinckrodt, Weiya Zhang Consultant of: Grunenthal for advice on gout management, Speakers bureau: Bioiberica as an invited speaker for EULAR 2016 satellite symposium, Abhishek Abhishek Grant/research support from: AstraZeneca and OxfordImmunotech, Speakers bureau: Menarini pharmaceuticals

Background:Secukinumab was the first anti-interleukin 17A monoclonal antibody treatment approved by the FDA for ankylosing spondylitis (AS). There is scarce information on the characteristics of secukinumab vs other biologic initiators with AS.Objectives:To describe real-world physician and patient characteristics, and treatment patterns of secukinumab and tumor necrosis factor inhibitor (TNFi) initiators.Methods:Electronic health records (EHR) data from adult patients with AS who initiated a biologic therapy between January 2018 and March 2019 (index date) were included from the Columbus Repository, a network capturing EHR data from 120 US rheumatology providers. Physician and patient characteristics, and treatment patterns were reported for patients who were prescribed secukinumab and TNFis (adalimumab, etanercept, certolizumab pegol, infliximab, infliximab-abda, and golimumab). Categorical variables were summarized using frequency counts and percentages and continuous variables were presented using means and standard deviations. Standardized mean differences andPvalues were used to compare treatment groups.Results:As of March 2019, AS treatment data were available for 82 secukinumab initiators and 160 TNFi initiators. Regarding overall practice size, 33% of practices had a single physician, and 65% of physicians were located in the South US region. Secukinumab initiators were younger than TNFi initiators (47.4 vs 49.8 years) and had a similar prevalence of HLA-B27 positivity (≈ 55%; Table 1). Comorbid psoriatic arthritis (PsA) was more commonly reported among secukinumab initiators vs TNFi initiators (17% vs 9%), while hypertension (5% vs 11%), obesity (2% vs 11%), and uveitis (2% vs 9%) were less common (Figure 1). Secukinumab initiators were more likely to have prior opioid use vs TNFi initiators but were less likely to have prior methotrexate use (Figure 2A); 67% of secukinumab initiators and 49% of TNFi initiators were biologic experienced, of whom 73% and 76%, respectively, used 1 prior biologic, 25% and 20% used 2 prior biologics, and 2% and 4% used ≥ 3 prior biologics (Figure 2B). The most common reasons for discontinuation of prior biologics among secukinumab and TNFi initiators were because the biologic was no longer required (47% vs 41%) and lack of efficacy (20% vs 24%) (Figure 2C).Table 1.Baseline Demographics and Disease Characteristics Among Patients With AS at the Index Date..CharacteristicSecukinumab(N = 82)TNFi(N = 160)SMD*PValueAge, mean (SD), years47.4 (12.8)49.8 (14.6)0.170.21Female, n (%)43 (52)90 (56)0.080.57Race/ethnicity, n (%)N = 65N = 1290.200.66White52 (80)106 (82)Hispanic8 (12)13 (10)Black3 (5)8 (6)Asian1 (2)2 (2)Other1 (2)0Geographic distribution, n (%)0.370.05South49 (60)113 (71)Midwest27 (33)28 (18)West5 (6)16 (10)Northeast1 (1)3 (2)Health insurance, n (%)N = 79N = 1560.410.39Commercial57 (72)94 (60)Medicare8 (10)33 (21)Medicaid2 (3)4 (3)Other12 (15)25 (16)HLA-B27 positivity, n (%) [N]14 (54) [N = 26]31 (56) [N = 55]0.051.00Body mass index, mean (SD), kg/m230.6 (6.1)30.9 (7.7)0.030.82SMD, standardized mean difference.* Comparisons with SMD > 0.1 were suggestive of clinically relevant differences.Conclusion:Secukinumab initiators with AS were younger and more opioid and biologic experienced, were more likely to have a PsA diagnosis, and were more likely to discontinue their previous biologic because the biologic was no longer required compared to patients who initiated TNFis.Acknowledgments:This study was funded by Novartis Pharmaceuticals Corporation, East Hanover, NJ. Support for third-party writing assistance for this abstract, furnished by Kheng Bekdache, PhD, of Health Interactions, Inc, was provided by Novartis Pharmaceuticals Corporation, East Hanover, NJ.Disclosure of Interests:Howard Busch Speakers bureau: AbbVie, Amgen, Crescendo, Exagen, Genentech, Mallinckrodt, Novartis, Primus, Sanofi/Regeneron, and UCB, Jeffrey Curtis Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Lilly, Myriad, Pfizer, Regeneron, Roche, UCB, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Lilly, Myriad, Pfizer, Regeneron, Roche, UCB, Peter Hur Employee of: Novartis Pharmaceuticals Corporation, Esther Yi Employee of: Novartis Pharmaceuticals Corporation

Background:Intra-articular therapy (IAT) is routinely used in rheumatic and musculoskeletal diseases (RMDs). In order to improve the effectiveness and safety of IAT, it is essential to understand patients’ perceptions and needs.Objectives:To assess the perspective of persons who have experienced IAT, including perceptions on benefits and safety.Methods:A steering committee (including a patient research partner) prepared a 44-item questionnaire based on the information needs of a Taskforce on IAT in adult patients with RMDs. The questionnaire was translated into 11 languages and disseminated via EULAR PARE associations and social media. Persons who had experienced at least two IAT procedures were eligible for the survey. Descriptive statistics were used to summarise results as well as inductive codification of open-ended questions.Results:The survey was answered by 200 individuals diagnosed with rheumatoid arthritis (66%), osteoarthritis (21%), spondyloarthritis (10%), psoriatic arthritis (9%), and others (16%). The mean number of IATs received was 7 (SD 8), mainly in the knee (66%), shoulder (42%), and wrist (28%), and primarily with corticosteroids (83%) or hyaluronic acid (16%). Twenty-seven percent had not been informed about benefits or potential complications of IAT, and 73% had not been asked whether they wanted local anaesthetic. Consent was deemed necessary by 82 (41%). Most (65%) had never received an ultrasound (US)-guided injection, and of those who had experienced blinded and guided injections, 42 (63%) preferred US-guided because of increased perceived accuracy and confidence in the procedure. Only 50% reported a clear benefit of IAT, mainly in terms of reduced pain and increased joint mobility, but also perceived reduced inflammation, with effect from immediate to 36 hours or even 3 weeks post-injection, and that lasted from as little as less than one week to years. Regarding safety, 40 (20%) had experienced some complications from IAT, including but not limited to increased pain, impaired mobility, rashes, or swelling.Finally, the respondents suggested improvements in the procedure, including: (1) wider availability; (2) less painful procedures; (3) greater efficacy, faster and longer-lasting; (4) fewer side effects; (5) a clear diagnosis beforehand; (6) better shared decision-making, including better information; (7) follow-up, (8) better accuracy; and (9) more expertise.Conclusion:The survey has identified gaps in the IAT procedures, such as a need for clearer information. Patients perceive IAT as relatively safe, though painful, and with varying effect. Suggestions for improving the procedure, including more expertise, should be relayed to professionals and relevant organisations.Acknowledgments:Eular Taskforce grant CL109Disclosure of Interests:IRENE Pitsillidou: None declared, Jenny de la Torre-Aboki: None declared, Jacqueline Uson Jaeger: None declared, Esperanza Naredo: None declared, Lene Terslev: None declared, Mikael Boesen Consultant of: AbbVie, AstraZeneca, Eli Lilly, Esaote, Glenmark, Novartis, Pfizer, UCB, Paid instructor for: IAG, Image Analysis Group, AbbVie, Eli Lilly, AstraZeneca, esaote, Glenmark, Novartis, Pfizer, UCB (scientific advisor)., Speakers bureau: Eli Lilly, Esaote, Novartis, Pfizer, UCB, Hemant Pandit Grant/research support from: Glaxo Smith Kline (GSK) for work on Diclofenac Gel, Speakers bureau: Bristol Myers Squibb for teaching their employees about hip and knee replacement, Ingrid Möller: None declared, Maria Antonietta D’Agostino Consultant of: AbbVie, BMS, Novartis, and Roche, Speakers bureau: AbbVie, BMS, Novartis, and Roche, Willm Uwe Kampen: None declared, Terence O’Neill: None declared, Michael Doherty Grant/research support from: AstraZeneca funded the Nottingham Sons of Gout study, Consultant of: Advisory borads on gout for Grunenthal and Mallinckrodt, Francis Berenbaum Grant/research support from: TRB Chemedica (through institution), MSD (through institution), Pfizer (through institution), Consultant of: Novartis, MSD, Pfizer, Lilly, UCB, Abbvie, Roche, Servier, Sanofi-Aventis, Flexion Therapeutics, Expanscience, GSK, Biogen, Nordic, Sandoz, Regeneron, Gilead, Bone Therapeutics, Regulaxis, Peptinov, 4P Pharma, Paid instructor for: Sandoz, Speakers bureau: Novartis, MSD, Pfizer, Lilly, UCB, Abbvie, Roche, Servier, Sanofi-Aventis, Flexion Therapeutics, Expanscience, GSK, Biogen, Nordic, Sandoz, Regeneron, Gilead, Sandoz, Valentina Vardanyan: None declared, Elena Nikiphorou: None declared, Sebastian C Rodriguez-García Speakers bureau: Novartis Farmaceutica, S.A., Merck Sharp & Dohme España, S.A., Sanofi Aventis, UCB Pharma, Raul Castellanos-Moreira: None declared, Loreto Carmona Grant/research support from: Novartis Farmaceutica, SA, Pfizer, S.L.U., Merck Sharp & Dohme España, S.A., Roche Farma, S.A, Sanofi Aventis, AbbVie Spain, S.L.U., and Laboratorios Gebro Pharma, SA (All trhough institution)

Background:Upadacitinib (UPA), an oral selective JAK1 inhibitor, has demonstrated favorable efficacy and acceptable safety in five Phase 3 global studies in patients with moderately to severely active rheumatoid arthritis (RA).1–5Objectives:This analysis reports the efficacy and safety of UPA in predefined RA patient subgroups based on differences in baseline demographics and disease activity.Methods:Data were pooled from three pivotal, double-blind, PBO-controlled, multicenter, Phase 3 studies in patients with RA who had an inadequate response(IR) to conventional synthetic DMARDs (csDMARD-IR: SELECT-NEXT [N=661]), MTX(MTX-IR; SELECT-COMPARE[N=1629]), or biologic DMARDs(bDMARD-IR: SELECT-BEYOND[N=498]). Two integrated analysis sets were evaluated: one comparing UPA 15 mg QD vs PBO(SELECT-NEXT, SELECT-COMPARE, SELECT-BEYOND) and the other comparing UPA 15 mg QD and UPA 30 mg QD vs PBO(SELECT-NEXT, SELECT-BEYOND). All patients received background treatment with csDMARDs. The proportion of patients achieving ACR20 and DAS28(CRP) ≤3.2 at Week 12 was evaluated by predefined baseline demographics and disease activity measure groups, including age, sex, weight, BMI, race, geographic region, duration of RA, RF, and ACPA status, and level of high sensitivity CRP. Non-responder imputation was used for missing data. Subgroup analyses for safety were performed for age, race, sex, weight, BMI, and Asian region.Results:Across the three Phase 3 studies, 1036, 384, and 1041 patients received UPA 15 mg QD, UPA 30 mg QD or PBO, respectively. The demographic and baseline disease characteristics in the two integrated analysis sets were balanced across treatment groups. ACR20 and DAS28 ≤3.2 response rates at Week 12 were consistently higher with UPA 15 mg and UPA 30 mg vs PBO across the evaluated demographic and baseline disease characteristics(Figure 1a,Figure 1b). The efficacy of UPA 15 mg QD was generally similar to that observed with UPA 30 mg QD. At 12 weeks, the proportion of patients with treatment-emergent AEs, serious AEs, severe AEs, and AEs leading to discontinuation were generally comparable across different age, sex, race, weight, and BMI groups. Compared with the global population, patients receiving UPA in the Asian region had a higher rate of CPK elevations(UPA 30 mg only) and herpes zoster; herpes zoster also has been observed to be higher in the Asian region with other JAK inhibitors.6,7Conclusion:In this analysis of pooled integrated efficacy data in csDMARD-IR or bDMARD-IR patients with RA, UPA 15 mg or 30 mg QD in combination with csDMARDs improved efficacy outcomes at Week 12 when compared with PBO across all predefined subgroups evaluated.References:[1]Burmester GR, et al. Lancet 2018 23;391:2503–2512;[2]Genovese MC, et al. Lancet 2018; 391:2513–24;[3]Smolen JS, et al. Lancet 2019 May 23[Epub ahead of print];[4]van Vollenhoven R, et al. Arthritis Rheumatol 2018;70(Suppl. 10): Abstract 891;[5]Fleischmann R, et al. Arthritis Rheumatol 2018;70(Suppl. 10): Abstract 890;[6]Winthrop KL, et al. Arthritis Rheum 2014;66:2675-84;[7] Winthrop KL, et al. ACR 2016 [Abstract 3027]Disclosure of Interests:Michael Weinblatt Grant/research support from: Amgen, Bristol-Myers Squibb, Crescendo, Lily, Sanofi/Regeneron, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Crescendo, Gilead, Horizon, Lily, Pfizer, Roche, Eduardo Mysler Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Roche, Eli Lilly, Novartis, Janssen, Sanofi, and Pfizer., Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Roche, Eli Lilly, Novartis, Janssen, Sanofi, and Pfizer, Andrew Ostor Consultant of: MSD, Pfizer, Lilly, Abbvie, Novartis, Roche, Gilead and BMS, Speakers bureau: MSD, Pfizer, Lilly, Abbvie, Novartis, Roche, Gilead and BMS, Aaron Broadwell Grant/research support from: Janssen Research & Development, LLC, Janssen, Eli Lilly, Consultant of: AbbVie, Amgen, AstraZeneca, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Sandoz, Speakers bureau: AbbVie, Amgen, Celgene, GSK, Horizon, Janssen, Mallinckrodt, Novartis, Pfizer, Radius, Sanofi-Regeneron, UCB, Sławomir Jeka Grant/research support from: AbbVie, Pfizer, Roche, Novartis, MSD, Sandoz, Eli Lilly, Egis, UCB, Celgene, Speakers bureau: AbbVie, Pfizer, Roche, Novartis, MSD, Sandoz, Eli Lilly, Egis, UCB, Celgene, Kendall Dunlap Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Jessica Suboticki Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Jeffrey Enejosa Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Barbara Hendrickson Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Sheng Zhong Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Katya Cherny Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Grace Wright Consultant of: AbbVie, Amgen, BMS, Exagen, Janssen, Lilly, Medac, Myriad Autoimmune, Novartis, Pfizer, Sanofi Genzyme Regeneron, and UCB, Speakers bureau: AbbVie, Amgen, BMS, Exagen, Lilly, Medical Education Resource, Myriad Autoimmune, Novartis, Sanofi Genzyme Regeneron, UCB, and Vindico

Background:Some patients with SSc-ILD develop dyspnoea secondary to parenchymal lung disease, while others do not report dyspnoea even when their lung function is impaired. It is unclear whether the presence of dyspnoea is associated with a worse course of SSc-ILD or with response to therapy.Objectives:To investigate the rate of decline in FVC in patients with SSc-ILD in the SENSCIS trial in subgroups by patient-reported dyspnoea at baseline.Methods:The SENSCIS trial enrolled patients with SSc-ILD with first non-Raynaud symptom within ≤7 years before screening, extent of fibrotic ILD ≥10% on HRCT and FVC ≥40% predicted. Patients were randomised to receive nintedanib or placebo until the last patient reached week 52. In post-hoc analyses, we analysed the rate of decline in FVC (mL/year) over 52 weeks in patients with and without dyspnoea at baseline based on the question about dyspnoea in the St. George’s Respiratory Questionnaire (SGRQ). Patients who reported having shortness of breath “most days a week”, “several days a week” or “a few days a month” (rather than “only with chest infection” or “not at all”) over the last month were considered to have dyspnoea at baseline. A random slope and intercept model was used to assess the rate of decline in FVC (mL/year) and an interaction test was applied to assess potential heterogeneity in the treatment effect of nintedanib between the subgroups.Results:Of 576 patients, 69.8% had dyspnoea at baseline. At baseline, in patients with and without dyspnoea, respectively, mean (SD) extent of fibrotic ILD on HRCT was 37.7 (21.7)% and 31.6 (19.4)%; mean (SD) FVC was 71.0 (16.3) and 76.5 (16.8) % predicted; 50.7% and 44.8% were taking mycophenolate; 53.5% and 41.9% were taking corticosteroids. In the placebo group, the rate of decline in FVC (mL/year) was similar in patients with and without dyspnoea at baseline (Figure). The effect of nintedanib versus placebo on reducing the rate of decline in FVC (mL/year) was numerically more pronounced in patients without dyspnoea (difference: 79.8 [95% CI: 9.8, 149.7]) than with dyspnoea (difference: 25.7 [-19.9, 71.3]), but the exploratory interaction p-value did not indicate heterogeneity in the treatment effect between subgroups (p=0.20).Conclusion:In the SENSCIS trial, patients with SSc-ILD who had dyspnoea at baseline had a numerically greater extent of fibrotic ILD on HRCT and numerically lower FVC % predicted at baseline. The rate of decline in FVC in the placebo group was similar in patients with and without dyspnoea. Nintedanib had a numerically greater treatment effect in patients without dyspnoea. These data suggest that the presence of dyspnoea should not be used as a criterion for starting nintedanib in patients with SSc-ILD.Acknowledgements:The SENSCIS trial was funded by Boehringer Ingelheim. Medical writing support was provided by Fleishman Hillard Fishburn, London, UK. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE).Disclosure of Interests:Elizabeth Volkmann Consultant of: Boehringer Ingelheim, Grant/research support from: Corbus and Forbius, Michael Kreuter Speakers bureau: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Grant/research support from: Boehringer Ingelheim and Roche, Anna-Maria Hoffmann-Vold Speakers bureau: Actelion, Boehringer Ingelheim, Lilly, Merck Sharp & Dohme and Roche, Consultant of: Actelion, Arxx Therapeutics, Bayer, Boehringer Ingelheim, Lilly, Medscape, Merck Sharp & Dohme and Roche, Grant/research support from: Boehringer Ingelheim, Marlies Wijsenbeek Speakers bureau: Boehringer Ingelheim (fees paid to institution) and Hoffmann-La Roche (fees paid to institution), Consultant of: Boehringer Ingelheim (fees paid to institution), Bristol-Myers Squibb (fees paid to institution), Galapagos NV (fees paid to institution), Hoffmann-La Roche (fees paid to institution), NeRRe Therapeutics (fees paid to institution), OncoArendi Therapeutics (fees paid to institution), Respivant Sciences (fees paid to institution) and Savara (fees paid to institution), Grant/research support from: Boehringer Ingelheim (fees paid to institution) and Hoffmann-La Roche (fees paid to institution), Vanessa Smith Speakers bureau: Boehringer Ingelheim and Janssen-Cilag NV, Consultant of: Boehringer Ingelheim, Grant/research support from: Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim, Janssen-Cilag NV and Research Foundation - Flanders (FWO), Dinesh Khanna Shareholder of: Eicos Sciences, Inc. (less than 5%), Consultant of: Acceleron Pharma, Actelion, AbbVie, Amgen, Bayer, Boehringer Ingelheim, CSL Behring, Corbus, Gilead Sciences, Galapagos NV, Genentech/Roche, GlaxoSmithKline, Horizon Therapeutics, Merck Sharp & Dohme, Mitsubishi Tanabe Pharma, Sanofi-Aventis and United Therapeutics, Grant/research support from: Bayer, Bristol-Myers Squibb, Horizon Therapeutics, Immune Tolerance Network, National Institutes of Health and Pfizer, Employee of: Chief Medical Officer- CiviBioPharma/Eicos Sciences, Inc., Christopher Denton Speakers bureau: Boehringer Ingelheim, Corbus, Janssen, and Mallinckrodt Pharmaceuticals, Consultant of: Acceleron Pharma, Arxx Therapeutics, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galapagos NV, GlaxoSmithKline, Horizon Therapeutics, Janssen, Mallinckrodt Pharmaceuticals, Roche, Sanofi and UCB, Grant/research support from: Arxx Therapeutics, GlaxoSmithKline and Servier, Wim Wuyts: None declared, Corinna Miede Employee of: Currently an employee of mainanalytics GmbH, contracted by Boehringer Ingelheim, Margarida Alves Employee of: Currently an employee of Boehringer Ingelheim, Steven Sambevski Employee of: Currently an employee of Boehringer Ingelheim, Yannick Allanore Consultant of: Boehringer Ingelheim, Medsenic, Menarini and Sanofi, Grant/research support from: Alpine Pharmaceuticals

Background:ABBV-3373 is a novel antibody drug conjugate composed of adalimumab (ADA) linked to a proprietary and highly potent glucocorticoid receptor modulator (the anti-inflammatory payload) currently evaluated for the treatment of rheumatoid arthritis (RA).Objectives:To assess the efficacy and safety of ABBV-3373 vs ADA in RA patients (pts).Methods:This was a 24-week (wk) randomized, double-blind, double-dummy, active-controlled Phase 2a study of intravenously (IV)-administered ABBV-3373 100 mg (for 12 wks followed by placebo [PBO] for 12 wks) vs subcutaneous injections of ADA 80 mg every other wk (for 24 wks) in pts on background methotrexate. The primary endpoint was the change from baseline (BL) in DAS28(CRP) at Wk 12. Pre-planned statistical methods incorporating pre-specified historical ADA data both alone (pre-specified success criterion, 2-sided P ≤0.1) and supplemented with in-trial ADA data (pre-specified success criterion, probability >95%) were used to achieve adequate statistical power with a reduced trial size. Assay sensitivity was evaluated through construction of a synthetic PBO arm by propensity score matching, using individual pt-level PBO data from 3 recent sponsor-run trials of similar populations and trial settings. Secondary endpoints at Wk 12 included 1) mean change from BL in CDAI, SDAI, DAS28(ESR), HAQ-DI; 2) proportion of pts achieving DAS28(CRP)≤3.2, ACR20/50/70 responses, HAQ-DI≤-0.22. Continuous and categorical efficacy variables were analyzed using mixed effect model repeated measurements and Cochran-Mantel-Haenszel test, respectively; non-responder imputation was applied to missing categorical data. Treatment-emergent adverse events were summarized through Wk 12.Results:A total of 48 pts were randomized and treated (ABBV-3373: 31; ADA: 17); 46 pts (96%) completed 12 wks of study treatment. BL demographics and disease characteristics were indicative of established RA and similar among the 2 treatment arms and the synthetic PBO arm. ABBV-3373 demonstrated significant improvement in mean DAS28(CRP) at Wk 12 vs the pre-specified historical ADA (-2.65 vs -2.13; P=0.022) and numerically greater improvement vs the combined in-trial and historical ADA arm (-2.65 vs -2.29; probability 90%; Figure). Comparable improvements in disease activity and targets were observed for ABBV-3373 and in-trial ADA. Assay sensitivity was supported by the fact that both ABBV-3373 and ADA arms were superior to synthetic PBO (PTable 1.Treatment Emergent Adverse Events up to Week 12Event, n (%)ADA(N = 17)ABBV-3373(N = 31)Adverse event (AE)12 (70.6)11 (35.5)AE with reasonable possibility of being drug related$3 (17.6)2 (6.5)Severe AE01 (3.2)Serious AE04 (12.9) #AE leading to Discontinuation of Study Drug1 (5.9)1 (3.2)Serious infections02 (6.5)Opportunistic infection excluding Tuberculosis00Allergic Reactions Including Hypersensitivity, Angioedema, and Anaphylaxis2 (11.8) &1 (3.2) ^Systemic glucocorticoid events00All deaths00$As assessed by investigator. #Serious AEs: 1 non-cardiac chest pain, 1 pneumonia, 1 upper respiratory tract disease and 1 anaphylactic shock. &1 Type I hypersensitivity, 1 Pruritus ^1 Anaphylactic shockConclusion:These data demonstrate the clinical efficacy of ABBV-3373 and its potential to provide improved outcomes for RA pts compared to ADA. The safety profile of ABBV-3373 was generally similar to ADA.Acknowledgements:AbbVie and the authors we thank the patients, trial sites, and investigators who participated in this clinical trial. AbbVie, Inc was the trial sponsor, contributed to trial design, data collection, analysis & interpretation, and to writing, reviewing, and approval of final version. No honoraria or payments were made for authorship. The authors thank Yang Yang of AbbVie Inc for supporting the statistical analysis and data reporting. Medical writing support was provided by Ramona Vladea, PhD of AbbVie, Inc.Disclosure of Interests:Frank Buttgereit Consultant of: AstraZeneca, AbbVie, Grünenthal, Horizon Pharma, Pfizer, and Roche, Grant/research support from: AbbVie, Horizon Pharma, Pfizer, and Roche, Jacob Aelion Grant/research support from: AbbVie, Amgen, AstraZeneca, BMS, Celgene, Eli Lilly, Galapagos/Gilead, Genentech, GlaxoSmithKline, Horizon, Janssen, Mallinckrodt, Nektar, Nichi-Iko, Novartis, Pfizer, Regeneron, Roche, Sanofi-Aventis, Selecta, UCB, Bernadette Rojkovich: None declared, Anna Zubrzycka-Sienkiewicz Consultant of: Astellas and Roche, Grant/research support from: AbbVie, Astellas, Galapagos NV, Gilead Sciences, Janssen, Lilly, Mabion, Pfizer, Roche, and UCB SA, Timothy Radstake Shareholder of: AbbVie, Employee of: AbbVie, Su Chen Shareholder of: AbbVie, Employee of: AbbVie, Dilek Arikan Shareholder of: AbbVie, Employee of: AbbVie, Hartmut Kupper Shareholder of: AbbVie, Employee of: AbbVie, Howard Amital Consultant of: Abbvie, Janssen, Novartis, Roche, Perrigo, Pfizer, Neopharm, Elly Lilly, Gilead, Sanofi, Teva and Rafa, Grant/research support from: Yansen, Pfizer

Background:Dermatomyositis (DM) is a rare chronic systemic autoimmune disease with characteristic skin rash and progressive proximal muscle weakness. Current therapies encompass corticosteroids and other immunosuppressants and intravenous immunoglobulins (IVIg), however, none of these therapies are proven by randomized controlled phase 3 studies. There have been no large randomized clinical trials supporting the efficacy and safety of IVIg in DM.Objectives:The ProDERM study aimed to evaluate the efficacy and safety/tolerability of IVIg in DM patients in a double-blind, randomized, placebo-controlled, international multi-center, phase III clinical trial.Methods:The trial consisted of a double-blind, placebo-controlled First Period (16 weeks), in which adult patients with definite or probable DM (according to Bohan and Peter criteria) were randomized 1:1 to either high dose IVIg (2g/kg every 4 weeks) or placebo. Patients on placebo and patients without clinical worsening while on IVIg treatment entered the open label Extension Period (24 weeks) and received 2g/kg IVIg infusions every 4 weeks. To be included, subjects must have active disease with a manual muscle testing-8 (MMT-8) score < 142/150. Patients who showed clinical worsening (defined according to Oddis et al, 2013 - with slight adaptation) at 2 consecutive visits between week 8 and week 16 were switched to the alternate treatment arm.Primary endpoint was the proportion of responders in the IVIg vs. placebo arm at week 16, where response was defined per 2016 ACR/EULAR Myositis response criteria of at least minimal improvement [Total Improvement Score (TIS) ≥ 20 points)] and without clinical worsening at 2 consecutive visits up to week 16.Results:A total of 95 adult DM patients (mean age: 53 years; 75% females; 92% Caucasian) were enrolled, with 47 and 48 randomized to IVIg and placebo, respectively. Baseline clinical characteristics (including medical history and prior DM medication) were balanced between the 2 arms.The study met the primary endpoint at week 16, with the proportion of responders being significantly higher in the IVIg group (37/47; 78.7%) as compared to the placebo group (21/48; 43.8%; p-value 0.0008; Table 1).Table 1.Total Improvement Score – Analysis of Proportion of Responders at Week 16 (Full Analysis Set, N=95)TIS Responseoctagam 10%N=47PlaceboN=48Difference octagam 10% – placeboNumber (%) of responders37 (78.72%)21 (43.75%)Difference in response rates34.97[95% CI] p-valuea[16.70, 53.24] 0.0008aCochran-Mantel-Haenszel TestCI=confidence interval; N=number of patients; TIS=total improvement scoreIn the analysis of responders per improvement category at Week 16, a 45.2% higher response rate for at least moderate improvement (TIS ≥n40 points; p < 0.0001) and a 23.6% higher response rate for at least major improvement (TIS ≥060 points; p < 0.0062) was observed in the IVIG group as compared to the placebo group.The mean (SD) TIS was significantly higher in IVIg group [48.4 (24.4)] than in placebo arm [21.6 (20.2)] at week 16 (Fig 1).Figure 1.After switching to IVIG in the Extension Period the placebo group attained a similar response rate at Week 40 as did the IVIg treated patients at Week 16, i.e approx. 70% for minimal improvement.In line with the overall primary endpoint, secondary end points including all of the sub-components of TIS except muscle enzyme (MMT-8, MD global, Extramuscular global, patient global, HAQ,) as well as CDASI (Cutaneous Dermatomyositis Disease Area and Severity Index), also showed statistically significant improvement under IVIg treatment compared to placebo treatment.The safety and tolerability profile of IVIg was consistent with previously reported safety outcomes for IVIg administration.Conclusion:This is the first large international phase III randomized, placebo-controlled trial demonstrating the efficacy and safety of IVIg as a treatment for patients with DM.References:[1]Oddis, C. V. et al. Arthritis Rheum (2013), 65, 314–324Acknowledgements:Acknowledgments to all participating investigators, centers and patients and their familiesDisclosure of Interests:Rohit Aggarwal Consultant of: Q32, Alexion, Argenx, AstraZeneca, BMS, Boehringer Ingelheim, Corbus, Csl Behring, EMD Serono, Janssen, Kezar, Mallinckrodt, Kyverna, Octapharma, Orphazyme, Pfizer., Grant/research support from: BMS, Mallinckrodt, Pfizer, EMD Serono, Christina Charles-Schoeman Consultant of: Pfizer, Abbvie, Octapharma, Gilead, Regeneron-Sanofi, Grant/research support from: Bristol Myers Squibb, Pfizer, Abbvie, Octapharma, Joachim Schessl Speakers bureau: Octapharma, Grifols, CSL Behring, Consultant of: Octapharma, Zsuzsanna Bata-Csorgo Speakers bureau: Novartis, Sanofi-Genzyme, Ewopharma, Consultant of: Sanofi-Genzyme, Novartis, Ewopharma, Mazen Dimachkie Consultant of: ArgenX, Catalyst, Cello, CSL-Behring, EcoR1, Kezar, Momenta, NuFactor, Octapharma, RaPharma/UCB, RMS Medical, Sanofi Genzyme, Shire Takeda, Spark Therapeutics and UCB Biopharma., Grant/research support from: Alexion, Alnylam Pharmaceuticals, Amicus, Biomarin, Bristol-Myers Squibb, Catalyst, Corbus, CSL-Behring, GlaxoSmithKline, Genentech, Grifols, Kezar, Mitsubishi Tanabe Pharma, Novartis, Octapharma, Orphazyme, Ra Pharma/UCB, Sanofi Genzyme, Sarepta Therapeutics, Shire Takeda, Spark Therapeutics, UCB Biopharma, Viromed/Healixmith., Zoltán Griger Speakers bureau: Abbvie, CSL-Behring, Eli-Lilly, Roche, Boehringer Ingelheim, Consultant of: Octapharma, Sergey Moiseev: None declared, Chester V Oddis Consultant of: EMD Serono; Alexion Pharmaceuticals, Inc, Grant/research support from: Genentech (Clinical trial support); Bristol Myers Squibb (Clinical trial support), Elena Schiopu Consultant of: Octapharma, Grant/research support from: Octapharma, Janssen (Johnson & Johnson), BMS, Pfizer, Abbvie, Jirˇí Vencovský Speakers bureau: Abbvie, Biogen, MSD, Pfizer, Roche, Sanofi, UCB, Consultant of: Abbvie, Boehringer, Eli Lilly, Octapharma, Gilead, Irene Beckmann Employee of: Octapharma, Todd Levine Shareholder of: Corinthian Reference Labs, CND Life Sciences, Consultant of: Grifols, Octapharma, Alexion, Elisabeth Clodi Employee of: Octapharma PPG, Vienna Austria, and the ProDERM Investigators: None declared

Background:AWARE is a real-world evidence-based (RWE) study evaluating the safety and efficacy of IV golimumab (GLM) and infliximab (IFX) in adults with RA.Objectives:Evaluate safety and efficacy of IV GLM and IFX in elderly AWARE participants.Methods:AWARE, a prospective non-interventional study (88 US sites), enrolled patients (pts) initiating either IV GLM or IFX. Pt management was at the discretion of treating rheumatologists. In a post hoc analysis, pts were grouped by age (Results:1270 pts were enrolled (685 IV GLM; 585 IFX). 1047 (82%) pts were female; mean age was 60 yrs (57% 1 rates of serious AEs (SAEs) and serious infections increased with age for both IV GLM and IFX; however, increases were more notable in IFX- than IV GLM-treated pts ≥65 yrs. The incidence of serious infections was highest in pts ≥75 yrs for both treatments, although small sample size may limit data interpretation. No increase in opportunistic infections, including Varicella, was observed in pts ≥65 vs Table 1.% of pts with ≥1 AE through W52 DBLIV GLMIFX≥65 yrs≥75 yrs≥65 yrs≥75 yrsPatients, n3513349137021546Discontinued due to AE8.5%12.6%16.5%15.1%17.7%21.7%AE52.4%58.4%57.1%63.5%66.5%71.7%Most common AEs (≥5% of pts in either treatment group)Nausea3.7%3.3%3.3%8.4%6.0%2.2%Worsening of RA5.4%4.5%3.3%7.3%7.0%4.3%Upper respiratory tract infection5.7%5.1%4.4%6.2%5.6%2.2%Pruritis1.4%2.4%3.3%6.8%2.8%2.2%Sinusitis7.1%3.3%0%3.8%3.7%2.2%Urinary tract infection4.8%5.1%5.5%4.3%5.1%6.5%SAE7.7%16.8%20.9%9.7%18.6%26.1%Infection30.5%27.2%27.5%32.2%28.8%32.6%Serious infection3.7%6.3%7.7%3.5%7.9%15.2%Neoplasms benign, malignant and unspecified0.6%2.7%1.1%0.8%2.3%6.5%Latent tuberculosis0.3%0%00.3%0%0%Opportunistic infection1.4%1.8%4.4%1.9%1.4%4.3%Infusion reaction5.1%2.7%1.1%17.3%8.8%8.7%Death0.3%2.4%2.2%0%2.3%6.5%Conclusion:Elderly RA pts receiving IV GLM or IFX in this RWE study demonstrated similar safety and efficacy as reported in Phase 3 trials.2,3 The higher rates of AEs, discontinuations due to AE, and SAEs (mainly serious infections) observed in pts ≥65 yrs are in line with increased safety events seen in elderly vs younger individuals in the general population. Rates of AEs, SAEs, and infusion reactions were higher for IFX vs IV GLM. Infusion reactions were more common in pts References:[1]Castle SC. Clin Infect Dis 2000;31:578–85.[2]Lipsky PE, et al. N Engl J Med 2000;343:1594-602.[3]Weinblatt ME, et al. Ann Rheum Dis 2013;72:381-9.Disclosure of Interests:Joy Schechtman: None declared, Aaron Broadwell Speakers bureau: Amgen, AbbVie, Eli Lilly, Horizon, Janssen, Mallinckrodt, Novartis, Pfizer, Radius, Sanofi/Regeneron, and UCB, Consultant of: AbbVie, Amgen, Aurinia, Celegene, Eli Lilly, Janssen, Novartis, Pfizer, and Sandoz, Shelly Kafka Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Shawn Black Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Stephen Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Wayne Langholff Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Sergio Schwartzman Shareholder of: Amgen, Boston Scientific, Gilead, Medtronic, and Pfizer, Speakers bureau: AbbVie, Janssen, Eli Lily, Novartis, Pfizer, Regeneron, Sanofi, and UCB, Consultant of: AbbVie, Gilead, Eli Lilly, Janssen, Myriad, Novartis, Regeneron, Samsung, Sanofi, and UCB

Background:Current treatments for systemic sclerosis-associated interstitial lung disease (SSc-ILD) are characterised by different attributes such as mode of administration, adverse events (AE) and efficacy. Physicians and patients often have different perspectives on treatments, thus shared decision-making between patients and physicians is essential. An understanding of patients’ decision processes when weighing treatment attributes and the trade-offs they are willing to make is important for shared decision-making.Objectives:The study aimed to 1) identify relevant treatment attributes, 2) elicit patient preferences for these attributes and 3) quantify preference as relative attribute importance (RAI; a higher RAI indicates that more of the variability in patients’ responses may be explained by changes in the attribute); and maximum acceptable risk (MAR) of diarrhoea, nausea and/or vomiting (MAR is a trade-off measure that evaluates attributes in risk-equivalences as a unit of measurement).Methods:A discrete choice experiment (DCE) was created, based on a literature review, a patient advisory board, qualitative patient interviews, and a workshop involving SSc-ILD expert physicians. Seven SSc-ILD treatment attributes were identified: 1) mode of administration; 2) shortness of breath; 3) skin tightness; 4) cough; 5) tiredness; 6) risk of gastrointestinal tract (GIT) AEs; and 7) risk of serious and non-serious infections. The levels of AE risk were informed by frequencies observed in clinical trials and patient input during the interviews. The DCE was integrated into an online survey, which asked patients to make repeated choices between two alternatives described by varying levels of included attributes. Patients with SSc-ILD were recruited by physician referral from Switzerland, Norway, France, Germany and the USA. DCE data were analysed using a logit model, and RAI and MAR measures were calculated.Results:A total of 231 patients with physician-confirmed SSc-ILD (mean age 52.6±13.2 years; 54% diagnosed for >5 years) completed the survey. Patients with SSc-ILD mostly preferred twice-daily oral treatments (pPatients accepted an additional 21% risk (95% CI 13–29%) of GIT AEs if they could reduce the frequency of infusions from monthly to 6–12 monthly, or accepted an extra 15% (95% CI 7–23%) increase in risk if changing to an oral treatment twice daily. Among symptoms, an additional 28% (95% CI 20–36%) risk of GIT AEs was considered acceptable if the severity of patients’ persistent cough was reduced to a level that was easier to tolerate, even if it remained persistent. Similarly, a 37% (95% CI 28–46%) increase in the risk of GIT AEs was acceptable if it resulted in breathlessness during routine activities rather than breathlessness at rest. Finally, patients were willing to accept an additional 36% risk (95% CI 27–45%) of GIT AEs if it reduced their risk of non-serious infections from 30% to 15% and of serious infections from 10% to 5%.Conclusion:This is the first study to quantitatively elicit patients’ preferences for attributes of SSc-ILD treatments. Preferences were driven by safety, efficacy and technical considerations. Patients showed willingness to make trade-offs, providing a firm basis for shared decision-making in routine clinical practice.Disclosure of Interests:Cosimo Bruni Speakers bureau: Actelion, Consultant of: Eli Lilly, Grant/research support from: Gruppo Italiano Lotta alla Scleroderma (GILS), Fondazione Italiana per la Ricerca sull’Artrite (FIRA), New Horizon Fellowship, European Scleroderma Trial and Research (EUSTAR), Foundation for Research in Rheumatology (FOREUM)., Sebastian Heidenreich Consultant of: Sebastian Heidenreich, PhD is employed by Evidera Inc, a business unit of PPD. Evidera is a CRO that offers paid research services to pharmaceutical companies., Ashley Duenas Consultant of: Yes. I am an employee of Evidera which received funding from Boehringer Ingelheim for work related to this study., Anna-Maria Hoffmann-Vold Speakers bureau: Boehringer Ingelheim, Actelion, Roche, Merck Sharp & Dohme, Lilly, Consultant of: Actelion, Boehringer Ingelheim, Roche, Bayer, Merck Sharp & Dohme, ARXX, Lilly and Medscape, Grant/research support from: Boehringer Ingelheim, Armando Gabrielli Grant/research support from: Pfizer Bhering, Yannick Allanore Consultant of: Honorarium received from Boehringer, Medsenic,Sanofi, Menarini, Grant/research support from: Grants received from Alpine, Ose Immunogenetics, Emmanuel Chatelus: None declared, Jörg H.W. Distler Shareholder of: JHWD is stock owner of 4D Science, Consultant of: JHWD has consultancy relationships with Actelion, Active Biotech, Anamar, ARXX, Bayer Pharma, Boehringer Ingelheim, Celgene, Galapagos, GSK, Inventiva, JB Therapeutics, Medac, Pfizer, RuiYi and UCB, Grant/research support from: JHWD has received research funding from Anamar, Active Biotech, Array Biopharma, ARXX, aTyr, BMS, Bayer Pharma, Boehringer Ingelheim, Celgene, Galapagos, GSK, Inventiva, Novartis, Sanofi-Aventis, RedX, UCB, Eric Hachulla: None declared, Vivian Hsu Speakers bureau: I am a speaker for Boehringer Ingelheim Pharmaceuticals, Consultant of: with Boehringer Ingelheim Pharmaceuticals, Grant/research support from: Principal Investigator for several clinical trials, currently with Genentech, Corbus Pharmaceutical, and EICOS, Nicolas Hunzelmann Speakers bureau: Boehringer, Roche, Sanofi, Dinesh Khanna Shareholder of: Eicos Sciences, Inc (less than 5%), Consultant of: Paid Consultant for: Acceleron, Actelion, Abbvie, Amgen, Bayer, Boehringer Ingelheim, CSL Behring, Corbus, Gilead, Galapagos, Genentech/Roche, GSK, Horizon, Merck, Mitsubishi Tanabe Pharma, Sanofi-Aventis, and United Therapeutics, Grant/research support from: Research Grant support from: Immune Tolerance Network, Bayer, BMS, Horizon, Pfizer, Employee of: Leadership/Equity position – Chief Medical Officer, CiviBioPharma/Eicos Sciences, Inc – recieves a stipend for role as Chief Medical Officer, which would technically qualify as emplyoment., Marie-Elise Truchetet Speakers bureau: Abbvie, Lilly, Sobi, Boehringer, Paid instructor for: Lilly, Consultant of: UCB, Sobi, Abbvie, Grant/research support from: UCB, Gilead, Ulrich Walker Shareholder of: Bayer, NASDAQ, MSCI-World ETF’s, Speakers bureau: All companies producing pharmaceuticals used in AIDS, Paid instructor for: Roche, Abbvie, Novartis, Consultant of: All companies producing pharmaceuticals used in AIDS, Grant/research support from: Gilead, Abbvie, (in the last two years). Other companies in previous years., Margarida Alves Employee of: Boehringer Ingelheim, Nils Schoof Employee of: Employee of Boehringer Ingelheim International GmbH, Lesley Ann Saketkoo Speakers bureau: Boehringer Ingelheim, Actelion, Janssen, Mallinckrodt, United Therapeutics, Consultant of: Actelion, Boehringer Ingelheim, Bayer, Bristol Meyer Squibb, Corbus, EICOS, Janssen, Horizon, United Therapeutics, Inc, Grant/research support from: Mallinckrodt, United Therapeutics, Oliver Distler Speakers bureau: Boehringer Ingelheim, Medscape, IQone, Roche, Consultant of: OD has/had consultancy relationship and/or has received research funding in the area of potential treatments for systemic sclerosis and its complications from (last three years):Abbvie, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Baecon Discovery, Blade Therapeutics, Bayer, Boehringer Ingelheim, ChemomAb, Corbus Pharmaceuticals, CSL Behring, Galapagos NV, Glenmark Pharmaceuticals, GSK, Horizon (Curzion) Pharmaceuticals, Inventiva, iQvia, Italfarmaco, iQone, Kymera Therapeutics, Lilly, Medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, Serodapharm, Topadur, Target Bioscience and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Grant/research support from: Kymera Therapeutics, Mitsubishi Tanabe

Background:The ACR Composite Response Index in diffuse cutaneous Systemic Sclerosis (CRISS) was developed to measure the probability of improvement in response to treatment in patients with early diffuse cutaneous SSc (dcSSc), accounting for new/worsening cardiopulmonary involvement and/or renal crisis, and changes in modified Rodnan skin score, forced vital capacity, health assessment questionnaire disability index, and patient’s and physician’s global impressions. In patients with SSc-ILD, treatment response may be reflected as slower progression, stabilisation or improvement.Objectives:Using data from patients with dcSSc and ILD in the placebo group of the SENSCIS trial, we analysed the probability of improvement using the ACR CRISS score at week 52. We also evaluated whether the CRISS numerator could provide information on the spectrum of responses in this patient population.Methods:The SENSCIS trial enrolled subjects with SSc-ILD with onset of first non-Raynaud symptom ≤7 years before screening, FVC ≥40% predicted, and fibrotic ILD ≥10% extent on an HRCT scan. Subjects on prednisone ≤10 mg/day (or equivalent) and/or stable therapy with mycophenolate or methotrexate were allowed to participate. Subjects were randomised to receive nintedanib or placebo. Subjects were not randomised by use of mycophenolate. In patients randomised to receive placebo who had dcSSc and/or mRSS >15 at baseline, we analysed the ACR CRISS and its numerator at week 52 in subgroups by use of mycophenolate at baseline. Analyses were exploratory and descriptive.Results:Of 117 analysed subjects in the placebo group who had dcSSc and/or mRSS >15 at baseline, 60 (51.3%) were taking mycophenolate at baseline. Compared with patients not taking mycophenolate at baseline, those taking mycophenolate had a lower mean age (48.4 [SD 11.8] vs 53.1 [13.4] years), lower mean FVC % predicted (68.8 [17.0] vs 73.0 [14.6]), and a greater proportion were female (76.7% vs 71.9%); median time since first onset of non-Raynaud symptom was similar (3.9 vs 4.5 years, respectively) as was mean (SD) mRSS (16.5 [7.7] vs 15.9 [8.0], respectively). One patient (taking mycophenolate at baseline) had limited cutaneous SSc. At week 52, median (Q1, Q3) ACR CRISS score was 0.036 (0.001, 0.601) in subjects taking mycophenolate and 0.002 (0.000, 0.112) in subjects not taking mycophenolate at baseline, and mean (SD) ACR CRISS score was 0.28 (0.37) in subjects taking mycophenolate and 0.16 (0.31) in subjects not taking mycophenolate at baseline (Figure 1). In these groups, respectively, 25.0% and 14.0% of subjects had CRISS score >0.6 (considered improved) at week 52. The CRISS numerator provided a broader distribution of response values, but was not informative in this patient population.Conclusion:In exploratory analyses, among subjects with dcSSc and ILD who received placebo in the SENSCIS trial, the proportion considered improved at week 52 based on ACR CRISS score was numerically greater in patients taking than not taking mycophenolate at baseline. There remains a need for composite scores that provide better interpretation of the magnitude of response in patients with SSc.Acknowledgements:The SENSCIS trial was funded by Boehringer Ingelheim. Medical writing support was provided by FleishmanHillard Fishburn, London, UK. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE).Disclosure of Interests:Francesco Del Galdo Speakers bureau: Actelion and AstraZeneca, Consultant of: Actelion, AstraZeneca, Boehringer Ingelheim, Capella BioScience, ChemomAb and Mitsubishi Tanabe Pharma, Grant/research support from: Capella BioScience, Kymab and Mitsubishi Tanabe Pharma, Oliver Distler Consultant of: AbbVie, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Baecon Discovery, Bayer, Blade Therapeutics, Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos NV, GlaxoSmithKline, Glenmark Pharmaceuticals, Horizon (Curzion) Pharmaceuticals, Inventiva, IQVIA, Italfarmaco, iQone, Kymera Therapeutics, Lilly, Medac, Medscape, Merck Sharp & Dohme, Mitsubishi Tanabe Pharma, Novartis, Pfizer, Roche, Sanofi, Serodapharm, Target Bioscience, Topadur Pharma and UCB, Grant/research support from: Kymera Therapeutics and Mitsubishi Tanabe Pharma, Christopher Denton Speakers bureau: Boehringer Ingelheim, Corbus, Janssen, and Mallinckrodt Pharmaceuticals, Consultant of: Acceleron Pharma, Arxx Therapeutics, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galapagos NV, GlaxoSmithKline, Horizon Therapeutics, Janssen, Mallinckrodt Pharmaceuticals, Roche, Sanofi and UCB, Grant/research support from: Arxx Therapeutics, GlaxoSmithKline and Servier, Yannick Allanore Consultant of: Boehringer Ingelheim, Medsenic, Menarini and Sanofi, Grant/research support from: Alpine Pharmaceuticals, Daniel Wachtlin Employee of: Currently an employee of Boehringer Ingelheim, Margarida Alves Employee of: Currently an employee of Boehringer Ingelheim, Dinesh Khanna Shareholder of: Eicos Sciences, Inc. (less than 5%), Consultant of: Acceleron Pharma, Actelion, AbbVie, Amgen, Bayer, Boehringer Ingelheim, CSL Behring, Corbus, Gilead Sciences, Galapagos NV, Genentech/Roche, GlaxoSmithKline, Horizon Therapeutics, Merck, Mitsubishi Tanabe Pharma, Sanofi-Aventis and United Therapeutics, Grant/research support from: Bayer, Bristol-Myers Squibb, Horizon Therapeutics, Immune Tolerance Network, National Institutes of Health and Pfizer, Employee of: Chief Medical Officer- CiviBioPharma/Eicos Sciences, Inc.

Background:The treatment goal in rheumatoid arthritis (RA) is sustained remission and prevention of RA flares [1]. While targeted biologics have improved disease outcomes, almost one-third of patients (pts) discontinue treatment by 1 year and 50% by 2 years, with lack of efficacy as the most common reason [2]. Repository corticotropin injection (RCI) is a naturally sourced complex mixture of adrenocorticotropic hormone analogues and other pituitary peptides and is an agonist for all 5 melanocortin receptors (MCRs). Activation of MCRs by RCI has been shown to have direct and indirect anti-inflammatory and immunomodulatory effects. RCI is indicated for adjunctive therapy for short-term administration in RA flares or uncontrolled disease [3].Objectives:To characterize RA pts that initiate RCI therapy and identify predictors of RCI initiation, compared to biologic disease-modifying antirheumatic drugs (DMARDs).Methods:This retrospective cohort study identified pts with ICD-9/10 diagnosis for RA over an 11-year period (2008-2018) in a large claims database (Truven MarketScan®). Adults with ≥1 claim for RCI (RCI cohort) or ≥1 RA-related biologic claim but no RCI (non-RCI cohort) were selected and characterized by demographics, disease severity (Claims-based Index for RA Severity, CIRAS), comorbidities (Charlson Comorbidity Index, CCI), treatment patterns, and healthcare resource utilization in the 12-month baseline (BL) period prior to their index date (i.e., the 1stRCI claim or last claim for biologic for non-RCI cohort). Predictors of RCI initiation were identified by multivariable logistic regression, controlling for demographics and BL characteristics.Results:A total of 393 pts initiated RCI therapy while 188,062 initiated biologic treatment with no RCI claims. At BL, cohorts were similar with respect to mean age (~56 years), gender (76-79% female), and insurance type (79-80% commercial). Cohorts differed by region, plan type, and index year. Compared to non-RCI patients, the RCI cohort had significantly higher CCI and CIRAS scores; higher use of traditional DMARDs (65.6% vs. 61.9%), corticosteroids (CS, 91.3% vs 68.8%), prescription nonsteroidal anti-inflammatory drugs (NSAIDs, 66.9% vs 58.5%), and opioids (67.7% vs 47.5%), but lower biologic use (45.8% vs. 87.7%) (all pRCI therapy initiation was most significantly impacted by treatment patterns, including number of DMARDs, CS, and opioids tried in the previous year (Figure 1). Corticosteroid use was the strongest predictor of RCI initiation, especially extended use at any dose (OR≥2.6) and extended use of the highest doses (>15 mg/day, OR=8.5), present in 21% of the RCI cohort (Figure 1). Drug benefit generosity (proportion of out-of-pocket costs) was also associated with RCI initiation in any plan qualified as better than “below average” (OR=2.1-2.9). Anemia, renal disease, and Sjogren’s syndrome were also associated with higher odds of RCI initiation (OR=1.4-2.1).Conclusion:RA pts initiating RCI therapy were prescribed a greater number of traditional DMARDs, CS, and opioids in the previous 12 months compared to non-RCI pts, and have evidence of more severe disease and comorbidities. Extended and high dose CS use were the factors most associated with RCI initiation.References:[1]Smolen JS, et al. Ann Rheum Dis. 2017;76:960–977[2]Strand V, et al.. Rheumatol Ther. 2017;4(2):489-502.[3]Acthar Gel (repository corticotropin injection; perscribing information). Mallinckrodt ARD LLC, Bedminster, NJ 07921 USA. 2019.Disclosure of Interests:Kyle Hayes Employee of: Mallinckrodt ARD, LLC, Mary Panaccio Employee of: Mallinckrodt Pharmaceuticals, Huanxue Zhou Consultant of: I am full time employee in KMK Consulting Inc. and providing consulting service to Mallinckrodt, Mohammed Fahim Consultant of: I am full time employee in KMK Consulting Inc. and providing consulting service to Mallinckrodt

Background:Hyperuricemia is associated with non-alcoholic fatty liver disease (NAFLD)1,2, but the relationship to fibrosis remains uncertain3. Moreover, it is not known whether lowering serum urate will affect the course of NAFLD. The availability of data from two randomized trials of pegloticase, a pegylated recombinant mammalian uricase, that profoundly decreases serum urate afforded the opportunity to test the hypothesis that lowering urate might improve NAFLD.Objectives:To determine whether treatment of chronic refractory gout patients with pegloticase was associated with improvement in NAFLD determined by Fibrosis 4 index (Fib4).Methods:Databases from patients with chronic refractory gout who participated in two randomized 6 month clinical trials (RCTs) of pegloticase were analyzed4. Sub-sets who had persistent urate lowering to levels 5,6calculated from measurements of AST, ALT, platelet count and age (Age x AST/platelets x √ALT). A Fib4 value of 1.3 is an indication that further evaluation of liver disease is warranted.Results:At baseline, the mean Fib4 values were 1.40 ± 0.86 in pegloticase responders and 1.04 ± 0.53 in subjects receiving placebo. As shown in figure 1, subjects receiving placebo exhibited a change of 0.26 ± 0.41 in the Fib4 score over the six months of the RCTs compared with 0.13 ± 0.62 in the pegloticase responders (p=0.048; by linear regression). When only the subjects with a Fib4 value > 1.3 were considered, a significant difference in the change in the Fib4 values over the 6 months of the trial between pegloticase responders and those receiving placebo was also observed (-0.15 ± 0.67 vs 0.37 ± 0.42, p=0.004, by linear regression). The correlations between serum urate area under the curve (AUC) over the 6 months of the trial and the change in Fib4 value was rs=0.33, p=0.0.0004 (Spearman rank-order correlation coefficient). Finally, multiple linear regression analysis indicated serum urate AUC (as a surrogate measure for group) is the main contributor to the change in Fib4 (p=0.018 by linear regression).Conclusion:The data are consistent with the conclusion that persistent lowering of serum urate had a significant impact on Fib4 levels, implying a possible effect on the course of NAFLD. The results support a more complete analysis involving biopsy examination of the impact of urate on liver inflammation and fibrosis.References:[1]Yang C et al. PlosOne2017; 12:e0177249[2]Jaruvongvanich V et al. Eur J Gastroenterol Hepatol 2017; 29:1031[3]Jaruvongvanich V et al. Eur J Gastroenterol Hepatol 2017; 29:694[4]Sundy JS, et al. JAMA. 2011; 306 (7):711-20[5]Sterling RK et al. Hepatol 2006; 43:1317[6]Shah AG et al. Clin Gastroenterol Hepatol 2009;7:1104Disclosure of Interests: :Naomi Schlesinger Grant/research support from: Pfizer, Amgen, Consultant of: Novartis, Horizon Therapeutics, Selecta Biosciences, Olatec, IFM Therapeutics, Mallinckrodt Pharmaceuticals, Anthony Yeo Employee of: Horizon Therapeutics, Peter Lipsky Consultant of: Horizon Therapeutics

Background:Repository corticotropin injection (RCI) is a naturally sourced complex mixture of adrenocorticotropic hormone analogs and other pituitary peptides approved for short-term adjunctive treatment of rheumatoid arthritis (RA).Objectives:This two-part, international, multicenter, placebo (PBO)-controlled study assessed the efficacy of RCI in persistently active RA patients (pts) using clinical and patient-reported outcome measures (PROMs) (ClinicalTrials.govNCT02919761).Methods:Adults ≥18 years with persistently active RA (DAS28-ESR >3.2) despite disease-modifying anti-rheumatic drug and glucocorticoid use received open-label RCI (80 U) subcutaneously 2x/week (BIW) for 12 weeks (Part 1). Pts with DAS28-ESR Results:In the mITT-P (N=259), 62.9% (pp=0.035) vs. PBO (43.4%). Clinically significant improvements in PROMs from BL were observed through W12 and sustained to W24 (Table 1), with mean changes exceeding the reported minimal clinically important difference thresholds (MCIDs) for each.Conclusion:RCI for persistently active RA resulted in clinically significant improvements in efficacy endpoints and PROMs for up to 6 months in pts who continued and discontinued RCI after 3 months of initial therapy.References:Acknowledgments:Editorial support was provided by MedLogix Communications, LLC, Itasca, Illinois, under the direction of authors and funded by Mallinckrodt Pharmaceuticals.Disclosure of Interests:Roy Fleischmann Grant/research support from: AbbVie, Akros, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer, IngelhCentrexion, Eli Lilly, EMD Serono, Genentech, Gilead, Janssen, Merck, Nektar, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Roche, Samsung, Sandoz, Sanofi Genzyme, Selecta, Taiho, UCB, Consultant of: AbbVie, ACEA, Amgen, Bristol-Myers Squibb, Eli Lilly, Gilead, GlaxoSmithKline, Novartis, Pfizer, Sanofi Genzyme, UCB, Daniel Furst Grant/research support from: AbbVie, Actelion, Amgen, BMS, Corbus Pharmaceuticals, the National Institutes of Health, Novartis, Pfizer, and Roche/Genentech, Consultant of: AbbVie, Actelion, Amgen, BMS, Cytori Therapeutics, Corbus Pharmaceuticals, the National Institutes of Health, Novartis, Pfizer, and Roche/Genentech, Speakers bureau: CMC Connect (McCann Health Company), George Wan Employee of: Mallinckrodt Pharmaceuticals, Mary Panaccio Employee of: Mallinckrodt Pharmaceuticals, Jingyu Liu Employee of: Mallinckrodt Pharmaceuticals, Julie Zhu Employee of: Mallinckrodt Pharmaceuticals, Richard Brasington Speakers bureau: Amgen, Mallinckrodt Pharmaceuticals, Novartis, and Pfizer

Background:Gout is the most common form of inflammatory arthritis and its economic burden is substantial, with estimates for the overall cost exceeding $20 billion (US) annually. Contributing to the economic burden are hospital admissions and iatrogenic events associated with pharmacotherapy. Identification of modifiable risk factors would be an important contribution to clinical practice.Objectives:The aim of this study was to identify opportunities for enhancing gout care in patients presenting to the Emergency Department (ED) with gout flares.Methods:This retrospective cohort study used data from electronic medical records (EMR) at a large community hospital. All consecutive patients visiting the medical center ED with a primary diagnosis of gout from 1/1/2016 to 7/1/2019 were included. Patients were then followed for 90 days to determine whether they were readmitted to the ED for any reason. A chart review identified whether they were on appropriate medications in terms of gout flare management. All data were summarized using descriptive statistics. A multiple logistic regression was constructed to identify risk factors for ED utilization within 90 days of the index visit.Results:A total of 214 patients were included in the analysis. Most patients were male (79%), mean age was 59.4 ± 15.6 years, and mean Charlson comorbidity index was 0.5 ± 1.14. The most common medications prescribed during the ED visit included NSAIDs (41.6%), opioids (28%), corticosteroids (26.6%), and colchicine (21%). Allopurinol and febuxostat were initiated in the ED in 4.7% and 0.9%, respectively. Discharge medications for the management of gout included NSAIDs (37%), corticosteroids (34.6%), opioids (23.8%), colchicine (14%), febuxostat (7%), and allopurinol (6.5%). Of the patients sent home with an opioid, 40% were newly prescribed. An anti-inflammatory medication was not prescribed in 29.6% of patients discharged from the ED. Readmission within 90 days was recorded in 16.8% of patients. Of these readmissions, 33.3% were gout-related and 11.1% were cardiac related.After adjusting for age and comorbidity index, patients receiving colchicine were 2.8 times more likely (OR, 2.81; 95% CI, 1.12 to 7.02; p=0.027) to return to the ED within 90 days. The most common cause of readmission in this subset was gout-related (54.5%).Conclusion:Nearly 30% of patients were discharged from the ED without an anti-inflammatory medication, whereas initiation of urate lowering therapy was rare. Opiates were used frequently, but the indication was uncertain. Only 5.6% of subjects revisited the ED for gout-related diagnoses in the subsequent 3 months. Colchicine prescription was associated with an increased risk of gout-related ED utilization within 90 days. Treatment of gout in the ED is sub-optimal and often does not follow established guidelines.Disclosure of Interests: :Luigi Brunetti Grant/research support from: Astellas Pharma, CSL Behring, Consultant of: Horizon Foundation of New Jersey, Janaki Vekaria: None declared, Peter Lipsky Consultant of: Horizon Therapeutics, Naomi Schlesinger Grant/research support from: Pfizer, AMGEN, Consultant of: Novartis, Horizon Pharma, Selecta Biosciences, Olatec, IFM Therapeutics, Mallinckrodt Pharmaceuticals, Speakers bureau: Takeda, Horizon

Background:Dermatomyositis (DM) is a systemic, autoimmune disease affecting the skin and proximal skeletal muscles. A subset of DM patients present with subclinical or resolved muscle involvement but continue to have skin disease. In these cases, first and second line treatments including glucocorticoids are sometimes insufficient for controlling the disease, necessitating escalation of treatment. Several recent studies have investigated the response of Tofacitinib, an oral Janus Kinase inhibitor approved for the treatment of rheumatoid arthritis, in DM patients and patients with inflammatory skin diseases.Objectives:Due to the reported ability of JAK inhibitors to suppress type 1 interferon (IFN) signaling, which is suspected to be upregulated in DM, we evaluated the efficacy of treatment with Tofacitinib in four refractory DM patients.Methods:Four patients with dermatomyositis without evidence of current muscle involvement began treatment with Tofacitinib 11 mg daily after they had failed or had adverse effects to first and second line immunosuppressive agents. Their medical records were reviewed at 0, 3, and 6 months, with improvement measured using the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) activity score. Throughout their treatment they were additionally monitored for improvement in markers of inflammation and the necessity for concomitant treatments. Patients were monitored for adverse effects to Tofacitinib treatment.Results:All four patients within the case series showed significant improvement of their cutaneous disease activity (CDASI scores improved by 8-15 points) over the first 6 months, with three of the four having achieved minimal clinically improved difference of >= 5 point by three months. Based on the CDASI, three of the cases’ disease classification changed from moderate-to-severe disease to mild disease. The last patient initially presented with mild disease. Other outcomes noted included improved pruritus in 3 patients and improvement of calcinosis in 1 patient. One patient was additionally able to stop concomitant treatment with prednisone and IVIG at 3 and 6 months, respectively. This patient had been on daily prednisone for 4 years. Only other patient on prednisone was on low dose of 3mg daily. The patients all had normal muscle exams prior to treatment with Tofacitinib. No worsening muscle involvement or adverse effects were noted with Tofacitinib use.Conclusion:Tofacitinib is believed to play a role in the inhibition of IFN signaling pathways that are overactive in dermatomyositis. All four patients within this retrospective study showed significant improvement of cutaneous disease with Tofacitinib use.References:[1]Moghadam-Kia S.Rheumatology. 2019;58(6):1011-1015.[2]Kurtzman D.JAMA Dermatol. 2016;152(8):944.[3]Paik J.Semin Arthritis Rheum. 2017;46(4):e19.[4]Kurasawa K.Rheumatology. 2018;57(12):2114-2119.[5]Anyanwu CO.Br J Dermatol. 2015; 173(4):969-974.Gender/ Age/ EthnicityDM Subtype /disease durationPrevious TreatmentConcomitant Treatment with TOFCDASI ActivityCDASI Activity 3 monthCDASI Activity 6 monthOther OutcomeM/ 55/ CaucasianAmyopathic DM; 5 yearsAZA, HCQ, IVIG, MTX, MMF, Prednisone, RCI, RTX, TACHCQ1254NoneF/ 37/ CaucasianAmyopathic DM; 7 yearsAZA, HCQ, IVIG, MTX, MMF, Prednisone, RCI, TACPrednisone, IVIG, MTX1585Pruritus and CRP improvedF/ 60/ CaucasianAmyopathic DM; 4 yearsAZA, MTX, PrednisonePrednisone, MTX17155Pruritus improvedF/ 47 African AmericanClassic DM; 5 yearsAZA, colchicine, HCQ, IVIG, MTX, MMF, pamidronate Prednisone, RCI, RTX, TACIVIG, Colchicine2287Pruritus and calcinosis improvedAbbreviations: CDASI, Cutaneous Dermatomyositis Disease Area and Severity Index; AZA, azathioprine; CRP, C-reactive protein; DM, Dermatomyositis, HCQ, hydroxychloroquine; IVIG, intravenous immunoglobulin; MTX, methotrexate; MMF, mycophenolate mofetil; RCI, repository-corticotropin injection; RTX, rituximab; TAC, tacrolimus; TOF, tofacitinib;Disclosure of Interests:Kirsten Riggle: None declared, Aarat Patel Speakers bureau: Abbvie, Mallinckrodt, Celgene, Lilly, Rohit Aggarwal Grant/research support from: Pfizer, Genentech, BMS, Mallinckrodt, Consultant of: Pfizer, Genentech, BMS, Mallinckrodt, Bristol Myers-Squibb, octapharma, CSL Behring, AstraZeneca, Corbus, Kezar, Abbvie

Background:Dual-Energy CT (DECT) has high sensitivity and specificity for detecting monosodium urate (MSU) crystal deposition. Although widely used in research, few studies have evaluated the usefulness of DECT in clinical practice.Objectives:To evaluate the use of DECT in a clinical setting and determine its utilityMethods:We retrospectively evaluated the records of all patients referred for DECT scans over a 6.5-year period. Patient charts were reviewed for clinical features.Results:113 patients (17.5/yr) received DECT evaluation at a university hospital over the study period (234 scans). All were referred by rheumatologists. Medical records were available for 69 patients (134 scans), including 44 males and 25 females (mean age 62 (SD, 12.9, range: 34-85 yrs). Mean duration of gout was 6.7 (SD, 8.1) yrs. DECT was ordered to evaluate known gout (36/69, 52.1%), suspected gout (32/69, 46.4%), and suspected calcium pyrophosphate (CPP) disease (1/69, 1.4%). 32/69 (46.4%) of patients were on urate-lowering therapy.61% (42/69) had MSU crystal and none had CPP deposition. Mean MSU volume was 1.6cc (SD, 5.2cc; range: 0.01-35 cc.) The joints imaged were feet/ankles (80/134, 60%) and hands/wrists (53/134, 40%). 23/33 (69.7%) patients with DECT positivity had elevated serum urate (SU) levels >6mg/dL; however, elevated SU was not significantly associated with DECT positivity (odds ratio (OR) 1.9, 95% CI:0.59-5.95, p=0.28).For patients with positive scans, mean gout duration from first known flare was 9.5 (SD, 8.8) yrs.Among patients who had scans completed within 1 yr of the first known gout flare, 1/10 were positive (10%); 4/16 within 2 yrs (25%); and 8/21 within 3 yrs (29.6%).Of patients with positive DECT scans, 24/42 (57%) had symmetric distribution of MSU crystal deposition: 10/24 (42%) hands and 14/24 (58%) feet; with gout duration of 7.9 (SD, 8.0) yrs.Conclusion:DECT was infrequently utilized and only by rheumatologists. Only 60 % of patients referred for DECT scanning because of known or suspected gout had MSU deposition. DECT was uncommonly positive in patients with a 1-3 yr history of gout. When positive, the MSU crystal deposition was symmetrical in most gout patients. DECT scans, while important in furthering our understanding of gout biology, are not routinely used in general practice and often do not provide important decision support information. Establishment of practice guidelines might be important in developing more appropriate utilization of DECT.Disclosure of Interests:Yekaterina Sherman: None declared, Peter Lipsky Consultant of: Horizon Therapeutics, Mark Bramwit: None declared, Naomi Schlesinger Grant/research support from: Pfizer, AMGEN, Consultant of: Novartis, Horizon Pharma, Selecta Biosciences, Olatec, IFM Therapeutics, Mallinckrodt Pharmaceuticals, Speakers bureau: Takeda, Horizon

Background:Idiopathic Inflammatory Myositis (IIM) are heterogenous, with distinct autoantibodies reflecting upon possible clinical evolution and outcomes. Ethnicity has major influence on both antibody prevalence patterns as well as phenotypic behaviours linked to them.Objectives:Thus we sought prevalence and co-existence of myositis specific autoantibodies (MSAs) and myositis associated autoantibodies (MAAs) and associated clinical characteristics in a large cohort of patients with IIM.Methods:Adult patients with a physician diagnosis of IIM as per ACR/EULAR classification criteria were investigated for the presence of MSAs/MAAs by Line immunoassay (G4, Euro-Immune, Lubeck, Germany). Anti-Nuclear Antibody (ANA) was tested by Immunofluorescence assay (IFA), and patterns in various antibody subsets explored. Prevalence and associations of different antibodies were assessed in disease subsets and clinical phenotypes.Results:MSA and MAAs were tested in 250 IIM patients (F:M 3.8:1) of median age 37 (25-47) and disease duration 6 (3-17) years. Dermatomyositis (DM) was seen in most patients 83 (33.2%) followed by overlap myositis (OM), juvenile DM, Anti-synthetase syndrome (ASS), polymyositis (PM), and cancer associated myositis (CAM). MSAs/MAAs were found in 148 (59.2%) of patients, of which 95 (64.2%) had an MSA and 53 (35.8%) had MAAs (Fig, 1A). 93 (62.8%) of autoantibody positive patients were positive for a single antibody, and only 2 (0.8%) of total had more than one MSA (Table 1).Table 1.Multiple antibodies positive upon testing for MSA and MAA by the LIANote: ** PL-7 co-exists with Ku + Pm/Scl, **PL-12 co-exists with Pm/Scl + Ro52, **SRP co-exists with Pm/Scl + Ro52The most frequently detected MSA was anti-Jo-1 (8%), with a further 9 specificities each found in 0.5–7.0% of patients. Amongst the autoantibody positive patients, 21% (n=53) had isolated MAA positivity, anti-Ro52 (33, 62.3%) being the most common, followed by anti-Pm/Scl (11, 20.8%) and anti-Ku (9, 17.0%) (Fig. 1B).Figure 1.A. MSA and MAA in Indian cohort of myositis B. ANA patterns in myositis C. MSA in ANA negative IIMOn ANA, 76.0% (172 of 226) were positive, with speckled being the most common pattern (37%,Fig. 1C). Of those ANA negative (n=54), 61% had either MSA or MAA (Fig 1D). 18 (54.6%) had autoantibodies associated with cytoplasmic patterns suggesting that cytoplasmic ANA may be underreported.Clinical presentation akin to DM was seen with all MSA except anti-SRP. PM group was heterogenous, and included ASS, OM and necrotizing phenotype (Fig. 2A). On occasion, anti-SRP, anti-Mi-2 and anti-MDA5 presented with clinical phenotype of ASS. (Fig 2A,C). Patients with ARS or anti-SAE were often clinically amyopathic (Figure 2B,C)Figure 2.A. Phenotypic associated with various antibody subsets B,C,and D. MSA/MAA in muscle weakness, rash and ILD phenotype. E. Unique feature of eye-lid edema in some patients with MDA-5 positive myositisARS were associated with mechanic’s hand (pE) and arthritis in children (p=0.01, OR 11.5). Anti-TIF-1ɣ associated with alopecia (p=0.007,OR 5.9) and malignancy (p= Conclusion:Myositis autoantibodies are seen in two-thirds IIM and identify distinct clinical subsets as well as unique phenotypes. MSA/MAA are positive in two-thirds of those negative on ANA, adding diagnostic value. MSAs are nearly always mutually exclusive and thus useful as biomarkers for diagnosis.Acknowledgments:MSA testing supported by grants from APLAR and Association of Physicians of India.Disclosure of Interests:Latika Gupta: None declared, Priyanka Gaur: None declared, Vikas Agarwal: None declared, Rohit Aggarwal Grant/research support from: Pfizer, Genentech, BMS, Mallinckrodt, Consultant of: Pfizer, Genentech, BMS, Mallinckrodt, Bristol Myers-Squibb, octapharma, CSL Behring, AstraZeneca, Corbus, Kezar, Abbvie, Ramnath Misra: None declared

Background:AWARE (Comparative and Pragmatic Study of Golimumab IV Versus Infliximab in Rheumatoid Arthritis) is an ongoing Phase 4 comparator study designed to provide a real-world assessment of intravenous golimumab (GLM) and intravenous infliximab (IFX) in patients (pts) with rheumatoid arthritis (RA). The study recently reached its primary endpoint (comparison of overall incidence of infusion reactions in GLM- vs IFX-treated pts after 52 weeks) with the last patient reaching 52 weeks of treatment or discontinuation from the study. AWARE also records prior use of biologic medications and concomitant use of methotrexate (MTX).Objectives:To assess the incidence of infusion reactions among GLM and IFX pts reported at baseline by examining the influence of prior biologic exposure or concurrent use of MTX.Methods:AWARE is a prospective, noninterventional, observational, multicenter, 3-year study conducted in the US. RA patients (1,270 adults) were enrolled at the time of initiating treatment with GLM or IFX. All treatment decisions were made at the discretion of the treating rheumatologist. An infusion reaction was any adverse event that occurred during an infusion or within 1 hour after the infusion of either GLM or IFX. Imputations were not performed on these AWARE data. Data shown are mean ± standard deviation.Results:Demographics are shown in Table 1 and the incidence of infusion reactions in different AWARE cohorts is shown in Table 2. GLM and IFX pts were comparable in sex and utilization of MTX at baseline. Both age and disease duration of GLM pts was greater than IFX pts by ~2 years. There was a higher proportion of bionaïve pts in IFX-treated group compared to GLM-treated group. Overall, infusion reactions occurred more frequently among IFX-treated pts compared to GLM-treated pts. The difference in infusion reaction rates between IFX- and GLM-treated pts was also evident among subgroups of bionaïve vs non-bionaïve pts, and among MTX non-users vs MTX users (characteristics reported at baseline). GLM pts did not report any serious or severe infusion reactions. These were reported rarely (3/585 pts) in IFX-treated pts. Among GLM and IFX pts with an infusion reaction, 55.6% of GLM and 77.1% of IFX pts had at least one medication for infusion reaction. Infusion reactions accounted for 9.7% and 35.1% of discontinuations due to adverse events in GLM and IFX pts, respectively.Table 1.Baseline Characteristics in the AWARE StudyGLM (n=685)IFX (n=585)Age (years)60.9 ± 13.4358.0 ± 12.85Sex (% female)85.0 %79.5 %Disease Duration (years)9.16 ± 9.9757.20 ± 9.716Bionaïve (%)33.0%48.6%MTX plus (%)75.4%75.1%MTX=methotrexateTable 2.Infusion Reactions in AWARE in Subsets of Patients ± Prior Biologic Use or ± Concurrent MTXGLM (n=685)IFX (n=585)GLM (n=685)IFX (n=585)BionaïveNon-BionaïveBionaïveNon-BionaïveNo MTX UseMTXUseNo MTX UseMTX UseInfusion Reactions6/242(2.5%)21/443(4.7%)36/251(14.3%)47/334(14.1%)15/265(5.7%)12/420(2.9%)44/229(19.2%)39/356(11.0%)Medication for Infusion Reactions33.3%59.1%78.9%73.6%50.%58.3%73.6%77.6%MTX=methotrexateConclusion:Whether bionaïve, non-bionaïve, MTX non-user or MTX user at baseline, the incidence of infusion reactions was notably lower among GLM- vs IFX-treated pts. Serious and/or severe infusion reactions did not occur among GLM pts and were rare among IFX pts. IFX was more commonly administered mediation for an infusion reaction compared to GLM. Infusion reactions accounted for almost four times the number of discontinuations related to adverse events in IFX pts compared to GLM pts.Disclosure of Interests: :Sergio Schwartzman Grant/research support from: Janssen Research & Development, LLC, Consultant of: AbbVie, Crescendo Bioscience, Dermtech, Eli Lilly and Company, Gilead Sciences, Janssen Pharmaceutica, Myriad Genetics, Novartis, Regeneron, Samsung, Sanofi, UCB, Speakers bureau: AbbVie, Eli Lilly and Company, Genentech, Janssen Pharmaceutica, Novartis, Pfizer, Regeneron, Sanofi, UCB, Aaron Broadwell Grant/research support from: Janssen Research & Development, LLC, Janssen, Eli Lilly, Consultant of: AbbVie, Amgen, AstraZeneca, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Sandoz, Speakers bureau: AbbVie, Amgen, Celgene, GSK, Horizon, Janssen, Mallinckrodt, Novartis, Pfizer, Radius, Sanofi-Regeneron, UCB, Alan Kivitz Shareholder of: AbbVie, Amgen, Gilead, GSK, Pfizer Inc, Sanofi, Consultant of: AbbVie, Boehringer Ingelheim,,Flexion, Genzyme, Gilead, Janssen, Novartis, Pfizer Inc, Regeneron, Sanofi, SUN Pharma Advanced Research, UCB, Paid instructor for: Celgene, Genzyme, Horizon, Merck, Novartis, Pfizer, Regeneron, Sanofi, Speakers bureau: AbbVie, Celgene, Flexion, Genzyme, Horizon, Merck, Novartis, Pfizer Inc, Regeneron, Sanofi, Shawn Black Employee of: Janssen Research & Development, LLC, Janssen Scientific Affairs, LLC, Stephen Xu Employee of: Janssen Research & Development, LLC, Wayne Langholff Employee of: Janssen Research & Development, LLC, Shelly Kafka Employee of: Janssen Scientific Affairs, LLC

Background:Intra-articular therapies (IAT) are widely used in clinical practice to treat patients with rheumatic and musculoskeletal diseases (RMDs). Many factors influence their efficacy and safety. There is a wide variation in the way IATs are delivered by health professionals. In an attempt to standardise these procedures, evidence-based recommendations are the right way forward.Objectives:To establish evidence-based recommendations to guide health professionals using IAT in adult patients with peripheral arthropathies.Methods:At a first face-to-face meeting, the results of an overview of systematic reviews were presented to the multidisciplinary task force of members from 8 countries. The aim, scope and outline of the taskforce were also established at this meeting. Thirty-two clinical questions ranked for priority (relevance for practice plus feasibility) drove the systematic reviews performed by two fellows. In addition, two surveys addressed to physicians, health professionals and patients throughout Europe were agreed to acquire more background information. At the second face-to-face meeting, the evidence for each research question was discussed, and each recommendation shaped and voted in a first Delphi round. Level of agreement was numerically scored 0 to 10 (0 completely disagree, 10 completely agree). All panellists voted anonymously using a sli.do app. Agreement needed to be greater than 80% to be included in a second Delphi round, which also allowed reformulation of statements. Finally, a third Delphi round was sent to the taskforce. The level of evidence was assigned to each recommendation according to the EULAR SOP for establishing recommendations.Results:Recommendations focus on practical aspects for daily practice to guide health professionals before, during and after IAT in adult patients with peripheral arthropathies. Five overarching principles were established, together with 11 recommendations that address the following issues: (1) patient information; (2) procedure and setting; (3) accuracy issues; (3) routine and special antiseptic care; (4) safety issues and precautions to be addressed in special populations; (5) efficacy and safety of repeated joint injections; (6) the usage of local anaesthetics; and (7) aftercare. The document includes the supporting evidence and results from the surveys, level of evidence and agreement.Conclusion:We have developed the first evidence and expert opinion based recommendations to guide health professionals using IAT.Acknowledgments:Eular Taskforce grant CL109Disclosure of Interests:Jacqueline Uson Jaeger: None declared, Esperanza Naredo: None declared, Sebastian C Rodriguez-García Speakers bureau: Novartis Farmaceutica, S.A., Merck Sharp & Dohme España, S.A., Sanofi Aventis, UCB Pharma, Raul Castellanos-Moreira: None declared, Terence O’Neill: None declared, Hemant Pandit Grant/research support from: Glaxo Smith Kline (GSK) for work on Diclofenac Gel, Speakers bureau: Bristol Myers Squibb for teaching their employees about hip and knee replacement, Michael Doherty Grant/research support from: AstraZeneca funded the Nottingham Sons of Gout study, Consultant of: Advisory borads on gout for Grunenthal and Mallinckrodt, Mikael Boesen Consultant of: AbbVie, AstraZeneca, Eli Lilly, Esaote, Glenmark, Novartis, Pfizer, UCB, Paid instructor for: IAG, Image Analysis Group, AbbVie, Eli Lilly, AstraZeneca, esaote, Glenmark, Novartis, Pfizer, UCB (scientific advisor)., Speakers bureau: Eli Lilly, Esaote, Novartis, Pfizer, UCB, Ingrid Möller: None declared, Valentina Vardanyan: None declared, Jenny de la Torre-Aboki: None declared, Lene Terslev: None declared, Francis Berenbaum Grant/research support from: TRB Chemedica (through institution), MSD (through institution), Pfizer (through institution), Consultant of: Novartis, MSD, Pfizer, Lilly, UCB, Abbvie, Roche, Servier, Sanofi-Aventis, Flexion Therapeutics, Expanscience, GSK, Biogen, Nordic, Sandoz, Regeneron, Gilead, Bone Therapeutics, Regulaxis, Peptinov, 4P Pharma, Paid instructor for: Sandoz, Speakers bureau: Novartis, MSD, Pfizer, Lilly, UCB, Abbvie, Roche, Servier, Sanofi-Aventis, Flexion Therapeutics, Expanscience, GSK, Biogen, Nordic, Sandoz, Regeneron, Gilead, Sandoz, Maria Antonietta D’Agostino Consultant of: AbbVie, BMS, Novartis, and Roche, Speakers bureau: AbbVie, BMS, Novartis, and Roche, Willm Uwe Kampen: None declared, Elena Nikiphorou: None declared, IRENE Pitsillidou: None declared, Loreto Carmona Grant/research support from: Novartis Farmaceutica, SA, Pfizer, S.L.U., Merck Sharp & Dohme España, S.A., Roche Farma, S.A, Sanofi Aventis, AbbVie Spain, S.L.U., and Laboratorios Gebro Pharma, SA (All trhough institution)

Background:Rheumatoid arthritis (RA) has been shown a strong genetic association with particularHLA–DRB1alleles containing shared epitope (SE). However, whether SE is clinically useful in treatment choices is insufficiently investigated1and previous studies have presented mixed findings in the role of SE in the response of TNFi therapies2,3.Objectives:To assess the role of SE in response to TNFi treatment in real-world RA patients (pts).Methods:Pts enrolled in a large RA registry, Brigham and Women’s Hospital RA Sequential Study, with known SE and received TNFi therapies were included for the analysis. TNFi pts were identified by the first-time use of the drugs between March 2003 to June 2018. For this analysis, all pts were followed up to 1 year. Summary statistics are reported for demographics, serostatus and disease activity (DA) at baseline and follow-up, stratified by SE status. Given the strong association of SE and anti-citrullinated protein antibody (ACPA), the analysis was further stratified by ACPA status. The effect of SE on change in DA was assessed using linear regression model with age, gender, RA disease duration, baseline DA, smoking status, SE, ACPA and ACPA-SE interaction as covariates.Results:Of the 484 TNFi pts included in the study, 68.8% were SE+. SE+ pts (vs SE-) were more likely to be rheumatoid factor positive, have erosive disease and a higher disease duration, irrespective of ACPA status. No difference in the change of DA was observed by SE. In SE- pts, ACPA+ pts had a greater reduction of DA than ACPA- pts (Table 1). After accounting for baseline differences, there was no significant effect of SE status on the mean change from baseline in any of the 3 DA measures.(Figure 1) The change in DA was not associated with ACPA but was significantly affected by disease duration and baseline DA.Table 1.Disease Activity in TNFi Patients, Stratified by SE and ACPA StatusParameterSE+ (1 & 2 alleles, n=333)SE- (n=151)ACPA+ACPA–OverallACPA+ACPA-Overall(n=264)(n=69)(n=333)(n=90)(n=61)(n=151)Baseline, Mean (SD)DAS28 CRP3.94 (1.69)3.57 (1.61)3.86 (1.67)3.85 (1.49)3.45 (1.65)3.69 (1.57)CDAI23.06 (18.13)18.95 (15.96)22.25 (17.78)21.91 (15.96)17.72 (17.06)20.26 (16.48)SDAI24.08 (18.82)19.96 (16.59)23.27 (18.45)22.58 (16.34)18.55 (17.87)20.99 (17.01)Follow-up, Mean (SD)DAS28 CRP3.42 (1.55)2.69 (1.32)3.27 (1.53)3.19 (1.43)3.11 (1.53)3.16 (1.47)CDAI17.61 (15.53)12.11 (12.65)16.51 (15.14)15.15 (13.35)14.94 (14.73)15.07 (13.84)SDAI18.35 (15.73)12.45 (12.78)17.15 (15.34)15.31 (13.81)15.71 (15.45)15.46 (14.38)Change, Mean (SD)DAS28 CRP-0.48 (1.31)-0.65 (1.53)-0.52 (1.36)-0.52 (1.50)-0.24 (0.93)-0.42 (1.34)CDAI-4.29 (13.16)-4.79 (13.13)-4.39 (13.12)-6.45 (13.56)-2.63 (9.58)-4.99 (12.28)SDAI-4.74 (14.13)-5.07 (13.90)-4.80 (14.05)-6.87 (14.21)-2.97 (10.32)-5.41 (12.98)Figure 1.Linear Regression Model for Change in Disease Activity*Estimates, p-values are shown as data labels on the graphs; The above model is adjusted for age, gender, RA duration, smoking status, SE status, baseline DA, ACPA and ACPA*SE statusConclusion:This real-world study validates the finding from previous studies conducted in clinical settings that SE does not differentiate treatment response for TNFi therapies.References:[1]Saruhan-Direskeneli G, et al.Rheumatology (Oxford) 2007;46(12):1842-44[2]Skapenko A, et al.Clin Exp Rheumatol2019;37(5):783-790[3]Rigby W, et al.Annals of the Rheumatic Diseases2019;78(2):263-264Disclosure of Interests:Joe Zhuo Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Joshua Bryson Shareholder of: I own shares of Bristol-Myers Squibb Company, Employee of: I am a paid employee of Bristol-Myers Squibb Company, Qian Xia Shareholder of: I own shares of Bristol-Myers Squibb Company, Employee of: I am a paid employee of Bristol-Myers Squibb Company, Niyati Sharma Consultant of: I work as a consultant for Bristol-Myers Squibb Company, Chidananda Samal Consultant of: I work as a consultant for Bristol-Myers Squibb Company, Sonie Lama Shareholder of: I own shares of Bristol-Myers Squibb Company., Employee of: I am a paid employee of Bristol-Myers Squibb Company., Michael E. Weinblatt Grant/research support from: BMS, Amgen, Lilly, Crescendo and Sonofi-Regeneron, Consultant of: Horizon Therapeutics, Bristol-Myers Squibb, Amgen, Abbvie, Crescendo, Lilly, Pfizer, Roche, Gilead, Nancy Shadick Grant/research support from: Mallinckrodt, BMS, Lilly, Amgen, Crescendo Biosciences, and Sanofi-Regeneron, Consultant of: BMS

Background:Anifrolumab treatment resulted in improved British Isles Lupus Assessment Group (BILAG)–based Composite Lupus Assessment (BICLA) response rates in patients with systemic lupus erythematosus (SLE) in the phase 3 TULIP-2 and TULIP-1 trials.1,2In addition, annualized flare rates were lower among the groups treated with anifrolumab compared with placebo.1,2Objectives:TULIP-2 and TULIP-1 data were analyzed to assess the effects of anifrolumab on the number of SLE flares and time to first flare during 52 weeks of treatment.Methods:The randomized, double-blind, placebo-controlled TULIP-2 and TULIP-1 trials evaluated efficacy and safety of intravenous anifrolumab 300 mg vs placebo every 4 weeks for 48 weeks, with the primary endpoints assessed at Week 52, in patients with moderate to severe SLE despite standard-of-care treatment. Flares were defined as ≥1 new BILAG-2004 A or ≥2 new (worsening) BILAG-2004 B domain scores compared with the prior month’s visit. Time to first flare was evaluated using a Cox proportional hazards model. Annualized flare rate was analyzed using a negative binomial regression model.Results:In TULIP-2 (anifrolumab, n=180; placebo, n=182) and TULIP-1 (anifrolumab, n=180; placebo, n=184), fewer patients experienced ≥1 BILAG-2004 flare in the anifrolumab groups (TULIP-2: 31.1%, n=56; TULIP-1: 36.1%, n=65) compared with the placebo groups (TULIP-2: 42.3%, n=77; TULIP-1: 43.5%, n=80; Figure 1). Results favoring anifrolumab were observed in time to first flare (TULIP-2: hazard ratio [HR] 0.65, 95% confidence interval [CI] 0.46–0.91 and TULIP-1: HR 0.76, 95% CI 0.55–1.06; Figure 2) and BILAG-based annualized flare rates (TULIP-2: adjusted rate ratio 0.67, 95% CI 0.48–0.94 and TULIP-1: rate ratio 0.83, 95% CI 0.60–1.14) across both trials.Conclusion:Across 2 phase 3 trials, we observed reductions in the total number of flares and annualized flare rates, as well as prolongation of time to first flare with anifrolumab treatment compared with placebo. These results support the potential of anifrolumab to reduce disease activity and reduce flares, benefiting patients with SLE.References:[1]Morand EF, et al.N Engl J Med. 2020;382:211–221.[2]Furie RA, et al.Lancet Rheumatol.2019;1:e208–e219.Disclosure of Interests:Richard Furie Grant/research support from: AstraZeneca, Biogen, Consultant of: AstraZeneca, Biogen, Eric F. Morand Grant/research support from: AstraZeneca, Consultant of: AstraZeneca, Speakers bureau: AstraZeneca, Anca Askanase Grant/research support from: Regeneron and Pfizer, Consultant of: AbbVie and BMS, Employee of: GSK, AstraZeneca, Janssen, Lilly, and Mallinckrodt, Edward Vital Grant/research support from: AstraZeneca, Roche/Genentech, and Sandoz, Consultant of: AstraZeneca, GSK, Roche/Genentech, and Sandoz, Speakers bureau: Becton Dickinson and GSK, Rubana Kalyani Employee of: AstraZeneca, Gabriel Abreu Employee of: AstraZeneca, Lilia Pineda Employee of: AstraZeneca, Raj Tummala Employee of: AstraZeneca

Background:Multimorbidity (≥2 chronic conditions) escalates the risk of adverse health outcomes. However, its burden in people with osteoarthritis (OA) remains largely unknown.Objectives:To identify the clusters of patients with multimorbidity and associated factors in OA and non-OA populations and to estimate the risk of developing multimorbidity clusters after the index date (after diagnosis).Methods:The study used the Clinical Practice Research Datalink – a primary care database from the UK. Firstly, age, sex and practice matched OA and non-OA people aged 20+ were identified to explore patterns and associations of clusters of multimorbidity within each group. Non-OA controls were assigned with same index date as that of matched OA cases. Secondly, multimorbidity trajectories for 20 years after the index date were examined in people without any comorbidities at baseline in both OA and non-OA groups. Latent class analysis was used to identify clusters and latent class growth modelling was used for cluster trajectories. The associations between clusters and age, sex, body mass index (BMI), alcohol use, smoking habits at baseline were quantified through multinomial logistic regression.Results:In total, 47 long-term conditions were studied in 443,822 people (OA- 221922; non-OA- 221900), with a mean age of 62 years (standard deviation ± 13 years), and 58% being women. The prevalence of multimorbidity was 76.6% and 68.9% in the OA and non-OA groups, respectively. In the OA group five clusters were identified including relatively healthy (18%), ‘cardiovascular (CVD) and musculoskeletal (MSK)’ (12.3%), metabolic syndrome (28.2%), ‘pain and psychological (9.1%), and ‘musculoskeletal’ (32.4%). The non-OA group had similar patterns except that the ‘pain+ psychological’ cluster was replaced by ‘thyroid and psychological’. (Figure 1) Among people with OA, ‘CVD+MSK’ and metabolic syndrome clusters were strongly associated with obesity with a relative risk ratio (RRR) of 2.04 (95% CI 1.95-2.13) and 2.10 (95% CI 2.03-2.17), respectively. Women had four times higher risk of being in the ‘pain+ psychological’ cluster than men when compared to the gender ratio in the healthy cluster, (RRR 4.28; 95% CI 4.09-4.48). In the non-OA group, obesity was significantly associated with all the clusters.Figure 1: Posterior probability distribution of chronic conditions across the clusters in Osteoarthritis (OA, n=221922) and Non-Osteoarthritis (Non-OA, n=221900) group. COPD- Chronic Obstructive Pulmonary Disease; CVD- Cardiovascular; MSK- MusculoskeletalOA (n=24139) and non-OA (n=24144) groups had five and four multimorbidity trajectory clusters, respectively. Among the OA population, 2.7% had rapid onset of multimorbidity, 9.5% had gradual onset and 11.6% had slow onset, whereas among the non-OA population, there was no rapid onset cluster, 4.6% had gradual onset and 14.3% had slow onset of multimorbidity. (Figure 2)Figure 2: Clusters of multimorbidity trajectories after index date in OA (n=24139) and Non-OA (n=24144)Conclusion:Distinct identified groups in OA and non-OA suggests further research for possible biological linkage within each cluster. The rapid onset of multimorbidity in OA should be considered for chronic disease management.Supported by:Acknowledgments:We would like to thank the University of Nottingham, UK, Beijing Joint Care Foundation, China and Foundation for Research in Rheumatology (FOREUM) for supporting the study.Disclosure of Interests:Subhashisa Swain: None declared, Carol Coupland: None declared, Victoria Strauss: None declared, Christian Mallen Grant/research support from: My department has received financial grants from BMS for a cardiology trial., Chang-Fu Kuo: None declared, Aliya Sarmanova: None declared, Michael Doherty Grant/research support from: AstraZeneca funded the Nottingham Sons of Gout study, Consultant of: Advisory borads on gout for Grunenthal and Mallinckrodt, Weiya Zhang Consultant of: Grunenthal for advice on gout management, Speakers bureau: Bioiberica as an invited speaker for EULAR 2016 satellite symposium

Background:The use of a specific and widely used type of intravenous ferrotherapy, ferric carboxymaltose (FCM), has been linked to the development of an asymptomatic and transient hypophosphataemia. However, in recent years it has been published that it can generate a severe hypophosphataemic osteomalacia (HPO) mediated by fibroblast growth factor 23 (FGF23) that is associated with high morbidity1. It is a potentially serious adverse effect whose prevalence is unknown and that clinicians may know little about.Objectives:To know the clinical and biochemical characteristics of this adverse effect and make it visible in the medical community.Methods:Observational descriptive study of three cases of patients assessed in the Rheumatology department of our hospital who were referred for study of recurrent fractures and diagnosed of FGF23-mediated HPO due to FCM. Demographic, clinical and laboratory data of the patients are described.Results:The clinical and laboratory characteristics of the patients are shown in table 1. All patients presented clinical and biochemical features compatible with FGF23-mediated HPO (mean of FGF levels 240 kRU/L, NR 0-145). All had multiple insufficiency fractures (Fx) and/or avascular necrosis (AN), with hip involvement in all 3 cases. Other causes of HPO were ruled out in all of them using PET18F-FDG, octreotide scintigraphy, abdominal magnetic resonance and PET68Ga-DOTATOC, and a genetic study of hypophosphataemic rickets was also performed in case 1. In all patients FCM was discontinued and phosphate levels were progressively normalized allowing the withdrawal of oral phosphate and calcitriol replacement therapy. After metabolic normalization, none presented new Fx or AN.Table 1.Clinical and biochemical characteristics of the patientsCase 1Case 2Case 3Age (years)a367543Medical historyCrohn’s disease (CD), right hemicolectomy. CD-associated spondyloarthritisSmall bowel angiodysplasiasAntisintetase syndrome. Uterine fibroids.Cause of anemiaGastrointestinal bleeding and malabsorptionGastrointestinal bleedingGynecological bleedingFe-CBX start date10/201008/201302/2018Fe-CBX discontinuation date10/201811/201806/2018Total time Fe-CBX (months)96634FracturesAN: left calcaneus posterior tuberosity, astragaline dome, right femoral headFx: left talus, tibial pylon, tibia-astragaline and ischiopubial branch; right 2nd metatarsal, distal tibia, posterior tuberosity of calcaneusFx both femoral necks and right sacral wingAN both femoral headsBone densitometryLS: Z-score-2.4FN: Z-score -2.4LS: Z-score -0.5FN: Z-score -1.3Phosphate, mg/dL (NR 2.5-4.5)a1.81.61.3Calcium, mg/dL (NR 8.6-10.2)a9.18.39.01,25(OH)zD3, ng/ml (NR 30-100)a54127PTH, pg/ml (NR 12-65)a71223104AP, UI/L (NR 46-116)a11314086Ph-exc, mg/24h (NR 400-1300)a16091630489TPR, % (NR 73-87)a58.350.270.7FGF-23, kRU/L (NR 0-145)a183335201Time to normalizationb1048aDuring treatment with FCM.bOf serum phosphate levels since FCM discontinuation in months. LS: Lumbar spine. FN: Femoral neck. NR: Normality range..PTH: Parathyroid hormone. AP: Alkaline phosphatase. Ph-exc: 24-hour urine phosphate excretion. Ph-cl: phosphate clearance. TPR: Tubular phosphate reabsorption. Data highlighted in bold indicate altered values.Conclusion:Treatment with FCM can cause severe FGF23-mediated HPO, multiple fractures and a great decrease in the quality of life. Since it can be potentially serious and easily reversible, it is important to favor the dissemination of these new cases and the knowledge of this disease. The need to monitor phosphate and/or FGF23 levels in patients receiving this intravenous iron therapy should be evaluated.References:[1]Bishay RH, Ganda K, Seibel MJ. Long-term iron polymaltose infusions associated with hypophosphataemic osteomalacia: a report of two cases and review of the literature. Ther Adv Endocrinol Metab. 2017;8(1-2):14–19. doi:10.1177/2042018816678363Disclosure of Interests:Elisa Fernández: None declared, Carolina Tornero: None declared, Victoria Navarro-Compán Consultant of: Abbvie, Lilly, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, MSD, Lilly, Novartis, Pfizer, UCB, Gemma Bonilla: None declared, Chamaida Plasencia: None declared, Alejandro Balsa Grant/research support from: BMS, Roche, Consultant of: AbbVie, Gilead, Lilly, Pfizer, UCB, Sanofi, Sandoz, Speakers bureau: AbbVie, Lilly, Sanofi, Novartis, Pfizer, UCB, Roche, Nordic, Sandoz, Pilar Aguado: None declared

Background:Intra-articular therapies (IAT) are routinely used in rheumatic and musculoskeletal diseases (RMDs); however large variability exists regarding current practice of delivery amongst health professionals.Objectives:To inquire about common practice aspects to inform the EULAR Taskforce for the IAT of arthropathies.Methods:A steering committee prepared a 160-item questionnaire based on the information needs of the Taskforce. The survey was disseminated via EULAR professional associations and social media and it was open to any health professional treating persons with RMDs, regardless of using IAT personally.Results:The survey was answered by 186 health professionals from 26 countries, the large majority of whom (77%) were rheumatologists, followed by nurses (12%), general practitioners (2%) and orthopaedic surgeons (2%). The two collectives that perform IAT routinely are rheumatologists (97%) and orthopaedic surgeons (89%), with other professionals Conclusion:Although often performed in clinical practice for RMDs, there is apparent variability in several elements related to delivery of this treatment. This information, together with patient input, will help design current recommendations where research evidence is not available.Acknowledgments:Eular Taskforce grant CL109Disclosure of Interests:Jenny de la Torre-Aboki: None declared, IRENE Pitsillidou: None declared, Jacqueline Uson Jaeger: None declared, Esperanza Naredo: None declared, Lene Terslev: None declared, Mikael Boesen Consultant of: AbbVie, AstraZeneca, Eli Lilly, Esaote, Glenmark, Novartis, Pfizer, UCB, Paid instructor for: IAG, Image Analysis Group, AbbVie, Eli Lilly, AstraZeneca, esaote, Glenmark, Novartis, Pfizer, UCB (scientific advisor)., Speakers bureau: Eli Lilly, Esaote, Novartis, Pfizer, UCB, Hemant Pandit Grant/research support from: Glaxo Smith Kline (GSK) for work on Diclofenac Gel, Speakers bureau: Bristol Myers Squibb for teaching their employees about hip and knee replacement, Ingrid Möller: None declared, Maria Antonietta D’Agostino Consultant of: AbbVie, BMS, Novartis, and Roche, Speakers bureau: AbbVie, BMS, Novartis, and Roche, Willm Uwe Kampen: None declared, Terence O’Neill: None declared, Michael Doherty Grant/research support from: AstraZeneca funded the Nottingham Sons of Gout study, Consultant of: Advisory borads on gout for Grunenthal and Mallinckrodt, Francis Berenbaum Grant/research support from: TRB Chemedica (through institution), MSD (through institution), Pfizer (through institution), Consultant of: Novartis, MSD, Pfizer, Lilly, UCB, Abbvie, Roche, Servier, Sanofi-Aventis, Flexion Therapeutics, Expanscience, GSK, Biogen, Nordic, Sandoz, Regeneron, Gilead, Bone Therapeutics, Regulaxis, Peptinov, 4P Pharma, Paid instructor for: Sandoz, Speakers bureau: Novartis, MSD, Pfizer, Lilly, UCB, Abbvie, Roche, Servier, Sanofi-Aventis, Flexion Therapeutics, Expanscience, GSK, Biogen, Nordic, Sandoz, Regeneron, Gilead, Sandoz, Valentina Vardanyan: None declared, Elena Nikiphorou: None declared, Sebastian C Rodriguez-García Speakers bureau: Novartis Farmaceutica, S.A., Merck Sharp & Dohme España, S.A., Sanofi Aventis, UCB Pharma, Raul Castellanos-Moreira: None declared, Loreto Carmona Grant/research support from: Novartis Farmaceutica, SA, Pfizer, S.L.U., Merck Sharp & Dohme España, S.A., Roche Farma, S.A, Sanofi Aventis, AbbVie Spain, S.L.U., and Laboratorios Gebro Pharma, SA (All trhough institution)

Background:Anti-PM/Scl antibodies are associated to systemic sclerosis (SSc) but are not specific to SSc. The true prevalence of anti-PM/Scl antibodies in SSc is unknown, ranging from 2.5% to 12.5%. An association between anti-PM/Scl antibodies with muscular involvement, pulmonary fibrosis, calcinosis, and a relatively benign prognosis have been described.Objectives:To compare the clinical manifestations and prognosis of SSc patients according the presence of anti-PM/Scl antibodies in the cohort of RESCLE (Spanish Scleroderma Registry).Methods:From the Spanish Scleroderma Study Group database, we selected patients in whom anti-PM/Scl antibodies had been tested. We compared demographic features, clinical manifestations, laboratory characteristics, and survival data between patients according the anti-PM/Scl antibodies status.Results:72 out of 947 (7%) patients tested positive for anti-PM/Scl antibodies. As presenting SSc manifestations, patients with anti-PM/Scl antibodies had higher prevalence of puffy fingers (11% versus 2%; p=0.002) and arthralgias (11% versus 4%; p=0.03), and lower prevalence of Raynaud’s phenomenon (65% versus 82%, p=0.002). Regarding cumulative manifestations, myositis (51% versus 15%; pWe did not find differences in terms of death rate nor in the causes of death (SSc and non-SSc related) according to the anti-PM/Scl antibodies profile.The 5- and 10-years survival rates of patients with anti-PM/Scl antibodies were 91% and 82% respectively, without differences with those without these antibodies (93% and 85%, respectively).Conclusion:In Spanish SSc patients, the presence of anti-PM/Scl antibodies confer a distinctive clinical profile. However, anti-PM/Scl antibodies do not play a role in the prognosis of these patients.References:[1]Stochmal A, Czuwara J, Trojanowska M, Rudnicka L. Antinuclear antibodies in systemic sclerosis: an update. Clin Rev Allergy Immunol 2020;58(1):40-51. doi: 10.1007/s12016-018-8718-8.Acknowledgments:We gratefully acknowledge all investigators who are part of the RESCLE Registry. We also thank the RESCLE Registry Coordinating Centre, S&H Medical Science Service, for their quality control data, logistic and administrative support and Prof. Salvador Ortiz, Universidad Autónoma de Madrid and Statistical Advisor S&H Medical Science Service for the statistical analysis of the data presented in this paper.Disclosure of InterestsNerea Iniesta-Arandia: None declared, Gerard Espinosa Speakers bureau: Glaxo-Smith-Kline, Janssen, Boehringer, Rovi, Alfredo Guillen del Castillo: None declared, Carles Tolosa Consultant of: Actelion pharmaceuticals, GSK, MSD., Gema Maria Lledó: None declared, Dolores Colunga Argüelles Consultant of: Actelion pharmaceuticals, GSK, MSD., Cristina González-Echávarri: None declared, Luis Sáez-Comet: None declared, Norberto Ortego: None declared, Jose Antonio Vargas-Hitos: None declared, Manuel Rubio-Rivas: None declared, Mayka Freire: None declared, Juan José Rios: None declared, Monica Rodriguez-Carballeira: None declared, Luis Trapiella Martínez: None declared, Vicent Fonollosa Pla Speakers bureau: Actelion, Carmen Pilar Simeón-Aznar Consultant of: Actelion pharmaceuticals, GSK, MSD., on behalf of RESCLE Investigators, Autoimmune Diseases Study Group (GEAS): None declared

Background:Physical function is a core domain to be measured in randomized controlled trials (RCTs) of psoriatic arthritis (PsA). The discriminative performance of patient reported outcome measures (PROMs) for physical function (PF) in RCTs has not been evaluated systematically.Objectives:In this systematic review, the GRAPPA-OMERACT working group aimed to evaluate the clinical trial discrimination of PF-PROMs in PsA RCTs.Methods:We searched PubMed and Scopus databases in English to identify all original RCTs conducted in PsA. We limited the review to RCTs of biologic and targeted synthetic DMARDs. Groups of two researchers extracted data independently for PF-PROMs. We assessed quality in each article using the OMERACT good method checklist. Effect sizes (ES) for the PF-PROMs were calculated and appraised usinga priorihypotheses. Evidence supporting clinical trial discrimination for each PF-PROM was summarized to derive recommendations.Results:32 articles were included (Figure 1). Four PF-PROMs had data for evaluation: HAQ-Disability Index (DI), HAQ-Spondyloarthritis (S), Short Form 36-item Health Survey Physical Component Summary (SF-36 PCS), and the Physical Functioning domain (SF-36 PF) (Table 1). The ES for intervention versus (vs.) control arms for HAQ-DI ranged from -0.55 to -1.81 vs. 0.24 to -0.52; and for SF-36 PCS ranged from 0.30 to 1.86 vs. -0.02 to 0.63.Table 1.Summary of Measurement Properties Table for clinical trial discriminationArticlesHAQ-DIHAQ-SSF-36 PCSSF-36 PFAntoni 2005 (IMPACT); Gottlieb 2009 (UST)+Antoni 2005 (IMPACT2)++Kavanaugh 2006 (IMPACT2)+Mease 2005 (ADEPT); Genovese 2007 (ADA); Mease 2010 (ETN); Kavanaugh 2009 (GO-REVEAL); Kavanaugh 2017 (GO-VIBRANT); Gladman 2014 (RAPID-PsA); Mease 2015 (FUTURE1); McInnes 2015 (FUTURE2); Kavanaugh, 2016 (FUTURE2)-subgroup; Nash 2018 (FUTURE3); Mease 2017 (SPIRIT-P1); Nash 2017 (SPIRIT-P2); Deodhar 2018 (GUS); Mease 2016 (CLZ)++Mease 2000 (ETN); McInne, 2013 (PSUMMIT 1); Ritchlin 2014 (PSUMMIT 2); Araugo 2019 (ECLIPSA)++Gniadecki 2012 (PRESTA)+Mease 2019 (SEAM-PsA)+/-+McInnes 2014 (SEC)++Mease 2014 (BRO)++Mease 2011 (ABT)+/-+Mease 2017 (ASTRAEA)++Mease 2006 (ALC)+/-Mease 2017 (OPAL Broaden); Gladman 2017 (OPAL Beyond)++Mease 2018 (EQUATOR)++Mease 2018 (ABT-122)+Total available articles311244Total articles for evidence synthesis291232Overall rating+++Color code in each box indicate study quality by OMERACT good methods. GREEN: “likely low risk of bias”; AMBER: “some cautions but can be used as evidence”; RED: “don’t use as evidence”. WHITE (empty boxes): absence of information from that study. (+): findings had adequate performance of the instrument; (+/-): equivocal performance; (-): poor performance (less than adequate).Conclusion:Clinical trial discrimination was supported for HAQ-DI and SF-36 PCS in PsA with low risk of bias; and for SF-36 PF with some caution. More studies are required for HAQ-S.Disclosure of Interests:Ying Ying Leung Speakers bureau: Novartis, Janssen, Eli Lilly, Richard Holland: None declared, Ashish Mathew: None declared, Christine Lindsay Employee of: Previously employed (worked) for pharmaceutical company., Niti Goel Shareholder of: UCB and Galapagos, Consultant of: VielaBio, Mallinckrodt, and IMMVention, Alexis Ogdie Grant/research support from: Novartis, Pfizer – grant/research support, Consultant of: AbbVie, BMS, Eli Lilly, Novartis, Pfizer, Takeda – consultant, Ana-Maria Orbai Grant/research support from: Abbvie, Eli Lilly and Company, Celgene, Novartis, Janssen, Horizon, Consultant of: Eli Lilly; Janssen; Novartis; Pfizer; UCB. Ana-Maria Orbai was a private consultant or advisor for Sun Pharmaceutical Industries, Inc, not in her capacity as a Johns Hopkins faculty member and was not compensated for this service., Pil Hoejgaard: None declared, Jeffrey Chau: None declared, Laura C Coates: None declared, Vibeke Strand: None declared, Dafna D Gladman Grant/research support from: AbbVie, Amgen Inc., BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB – grant/research support, Consultant of: AbbVie, Amgen Inc., BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB – consultant, Robin Christensen: None declared, William Tillett: None declared, Philip J Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/research support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau

Background:The pharmacologic management of OA is centred around optimising pain control but first-line analgesics only have modest efficacy1. Findings from several studies suggest thatβ-adrenoreceptor blocking drugs (β-blockers) have anti-nociceptive effects2 3. However, evidence for the benefits of β-blockers in the context of OA pain is scarce. We recently demonstrated, for the first time, an association between beta-blockers and lower pain severity, and less opioid analgesic use in a secondary analysis of data for community dwelling adults with large-joint lower OA4. This association, however, was not confirmed in a hospital-based study5.Objectives:We examined [1] the association betweenβ-blocker prescription and first primary care consultation for knee OA, hip OA, knee pain, and hip pain and [2] the classes ofβ-blocker drugs that reduce the risk of these outcomes.Methods:This was a cohort study using data from the UK Clinical Practice Research Datalink. Participants aged ≥40 years, in receipt of ≥2 β-blocker prescriptions within 60 days were matched by age, sex, and propensity score (PS) for β-blocker prescription to one control using greedy nearest neighbour matching. Participants with chronic painful conditions, contra-indications to β-blockers, maintenance analgesic prescriptions, and with Results:Data for 223,436 PS-matched exposed and un-exposed participants were included. β-blocker prescription associated with a significantly reduced risk of knee OA, knee pain, and hip pain consultations with aHR(95%CI) 0.90(0.83–0.98), 0.88(0.83–0.92), 0.85(0.79–0.90) respectively. The reduction in hip OA lacked statistical significance (aHR 95%CI 0.94; 0.83-1.07) (Table 1). On stratified analysis, propranolol and atenolol had a statistically significant protective effect on knee OA and knee pain consultations with aHRs between 0.78 and 0.91 (Figure 1).Table 1.The association between β-blocker prescription and incident osteoarthritis and joint painOutcomesExposedEvents (n)Person-timeEvent rate (95% CI)*HR (95% CI)1Knee OANo986262,0033.76 (3.54 – 4.01)1.00Yes1,101307,2313.58(3.38 – 3.80)0.90(0.83 – 0.98)Hip OANo451263,7531.71(1.56– 1.87)1.00Yes530310,0451.71(1.57 – 1.86)0.94(0.83 – 1.07)Knee painNo3,074255,00312.06(11.64 – 12.49)1.00Yes3,560297,02711.99(11.60 – 12.37)0.88(0.83 – 0.92)Hip painNo1,767259,5156.81 (6.50 – 7.13)1.00Yes1,981304,4546.51 (6.23 - 6.80)0.85(0.79 – 0.90)OA; osteoarthritis, *1,000 person-years,1PS matched and, additionally adjusted for age, number of GP consultations, hospital out-patient referrals, hospital admissions in the 12 month period preceding cohort entry, total number of GP consultations for knee or hip injury prior to cohort entry and non-osteoporotic fractures.Figure 1.The association between individual β-adrenoreceptor blocking drugs and incident knee osteoarthritis and knee pain11Comparison group is unexposed to β-blockers; size of the square is proportional to number of events.Conclusion:β-blockers appear to reduce consultations for knee OA, and knee or hip pain. Our results imply that, atenolol might be used preferentially for the treatment of people with cardiovascular comorbidities, while, propranolol with its’ anti-anxiety effect may be a suitable analgesic in people with OA and comorbid anxiety.References:[1] McAlindon TE, et al. Osteoarthritis and Cartilage 2014;22(3):363-88.[2] Harkanen L, et al. Journal of anesthesia 2015;29(6):934-43. doi: 10.1007/s00540-015-2041-9[3] Light KC, et al. The journal of pain 2009;10(5):542-52. doi: 10.1016/j.jpain.2008.12.006[4] Valdes AM, et al. Arthritis Care Res (Hoboken) 2017;69(7):1076-81. doi: 10.1002/acr.23091[5] Zhou L,et al. Osteoarthritis and Cartilage 2019 doi:https://doi.org/10.1016/j.joca.2019.08.008Acknowledgments:This work was funded by the National Institute for Health Research (grant numbers: PB-PG-0816-20025 and NIHR-RP-2014-04-026).Disclosure of Interests:Georgina Nakafero: None declared, Matthew Grainge: None declared, Ana Valdes Grant/research support from: Pfizer Inc, Consultant of: Consultant for Heel GmBH, Nick Townsend: None declared, Christian Mallen Grant/research support from: My department has received financial grants from BMS for a cardiology trial., Weiya Zhang Consultant of: Grunenthal for advice on gout management, Speakers bureau: Bioiberica as an invited speaker for EULAR 2016 satellite symposium, Michael Doherty Grant/research support from: AstraZeneca funded the Nottingham Sons of Gout study, Consultant of: Advisory borads on gout for Grunenthal and Mallinckrodt, Mamas Mamas: None declared, Abhishek Abhishek Consultant of: Consulting for Inflazome, and Royalties from Uptodate and Springer

Background:Osteoarthritis (OA) is a leading cause of disability worldwide. Currently, exercise is recognised to be one of the core treatments for OA (NICE, 2014). Convincing evidence shows that exercise can have positive effects on pain and function in people with OA (Fransen et al., 2015). However, a standardised exercise regimen may not suit all patients and adherence to exercise is always an issue. Therefore, several international guidelines recommended individualisation of the exercise regimen according to individual patient characteristics (e.g. pain severity, personal goals and co-morbidities), as this may enhance take up and adherence, hence treatment effect of the intervention (Fernandes et al., 2013).Objectives:The aims of this systematic review were: (1) to evaluate the current evidence for efficacy in randomised controlled trials (RCTs) of individualised exercise (IE) interventions for people with hip or knee OA; and (2) compare this to the efficacy of non-individualised exercise (NIE).Methods:A systematic search was carried out, up until March 6th2018, on the following databases: MEDLINE, CINAHL, AMED, PsycINFO and EMBASE. RCTs of IE interventions, or with subgroup analysis based on specific patient characteristics, were searched. Standardised mean difference and 95% confidence interval (CI) were calculated using random effects model. Risk of bias was evaluated using the modified Cochrane tool. Pain was the primary outcome of interest. Results of IE interventions were then compared to the NIE interventions identified from a previous systematic review (Goh et al., 2019).Results:We reviewed titles of 1,766 records in the systematic search. The screening process (Figure) identified 15 studies (1,826 participants) that met the inclusion criteria, of which 7 were included in a meta-analysis. Most included studies had high risk of bias. Blinding was a consistent problem due to the nature of the intervention. Within the trials exercise was individualised according to factors including severity of symptoms, exercise performance, lower limb muscle strength and presence of co-morbidities (e.g. heart failure, chronic obstructive pulmonary disease (COPD) and diabetes mellitus (DM) type 2).The analysis showed that IE significantly improved pain, physical function, performance and quality of life outcomes (Table). When compared to NIE interventions, IE showed greater effect size for all outcomes but their 95% CIs were overlapping.Figure showing Summary of screening processTable 1.Summary of resultsOutcomeType of exercise programES95% CINumber of studies (Number of patients)PainIE1.040.32 - 1.777 (991)NIE0.570.44 - 0.6965 (4,723)FunctionIE1.370.50 - 2.247 (991)NIE0.510.38 - 0.6463 (4,829)PerformanceIE2.000.07 - 3.932 (291)NIE0.51038 - 0.6366 (4,889)QoLIE1.30-0.52 - 3.122 (226)NIE0.320.15 - 0.4934 (2,545)ES= Effect size. CI= Confidence Interval. IE= Individualised Exercise. NIE= Non-Individualised Exercise. QoL= Quality of LifeConclusion:The results of this review show that IE may have better outcomes on people with hip or knee OA compared to NIE. However, the small study effect may inflate the estimates of the individualised exercise group, and further head to head comparisons are required.References:[1] FERNANDES L., HAGEN K. B., BIJLSMA J. W., ANDREASSEN O., CHRISTENSEN P., CONAGHAN P. G., DOHERTY M., GEENEN R., HAMMOND A. & KJEKEN I. 2013. EULAR recommendations for the non-pharmacological core management of hip and knee osteoarthritis.Annals of the rheumatic diseases,72, 1125-1135.[2] FRANSEN M., MCCONNELL S., HARMER A. R., VAN DER ESCH M., SIMIC M. & BENNELL K. L. 2015. Exercise for osteoarthritis of the knee.The Cochrane Library.[3] GOH S.-L., PERSSON M. S., STOCKS J., HOU Y., WELTON N. J., LIN J., HALL M. C., DOHERTY M. & ZHANG, W. 2019. Relative efficacy of different exercises for pain, function, performance and quality of life in knee and hip osteoarthritis: Systematic review and network meta-analysis.Sports Medicine,49, 743-761.[4] NICE 2014. Osteoarthritis: care and management in adults.https://www.nice.org.uk/guidance/cg177/chapter/1-Recommendations#non-pharmacological-management-2[Accessed 02/12 2019]Disclosure of Interests:Khalid Yaseen: None declared, Burak Kundakci: None declared, Siew Li Goh: None declared, Michael Doherty Grant/research support from: AstraZeneca funded the Nottingham Sons of Gout study, Consultant of: Advisory borads on gout for Grunenthal and Mallinckrodt, Weiya Zhang Consultant of: Grunenthal for advice on gout management, Speakers bureau: Bioiberica as an invited speaker for EULAR 2016 satellite symposium, Abhishek Abhishek Grant/research support from: AstraZeneca and OxfordImmunotech, Speakers bureau: Menarini pharmaceuticals, Michelle Hall: None declared

Background:Gout is one of the most common inflammatory arthropathies. By searching a large administrative data base (Symphony Integrated Dataverse), we found that persons with acute gout see a rheumatologist infrequently, whereas less than 50% of advanced gout patients are seen by a rheumatologist. Notably, however, gout patients seen by rheumatologists have more frequent urate measurements and are prescribed urate lowering therapy more frequently. This study sought to determine whether involvement of a rheumatologist in gout care had a positive impact on health outcomesObjectives:To determine whether involvement of a rheumatologist had a positive impact on health outcomes of patients with gout.Methods:We carried out a retrospective analysis to identify persons with gout over an approximately 3-year period from October 2015 to December 2018. This study used data from the Truven Marketscan®database, an administrative database covering over 190 million patients across the United States and based on fully adjudicated and paid insurance claims. Patients were identified as having gout if they were >18 years of age and had at least two medical claims for the diagnosis of gout on different days, separated by at least 3 months. Patients with acute gout were identified by ICD-10 code M10.*, chronic nontophaceous gout (M1A.***0), tophaceous gout (M1A.***1) and uncontrolled gout (M10.*, M1A.*), the latter manifested by three gout codes (any) in the primary diagnosis position and three urate measurements within the same calendar year. Particular attention was placed on Emergency Room (ER) visits by individuals in each category and by individuals who had been evaluated by a rheumatologist.Results:We identified 284,877 gout patients. The median age was 59.2 years and 79.0% were male. Of the 230,998 persons coded as acute gout, 10.7% were seen by a rheumatologist, whereas 26.9% of the 32,942 coded as chronic nontophaceous gout, 47.2% of the 7,723 coded as tophaceous gout and 43.6% of the13,514 coded as uncontrolled gout were seen by a rheumatologist. In each gout category, the frequency of ER visits was significantly reduced in persons who had been seen by a rheumatologist (Table 1). In acute gout, the frequencies of ER visits in those with and without rheumatologist care were 5.6% vs 6.6% (pTable 1.Rheumatology BreakdownEmergency Room VisitsPopulationOverall NW/ RheumatologyPatients%With Gout ER Visit (%)p-value (comparing %)ER Visits* Per PatientAcute Gout230,698Yes24,63810.68%1373 (5.57%)1.47No206,06089.32%13632 (6.62%)1.53Non-Tophaceous Chronic32,942Yes8,86326.90%486 (5.48%)1.95No24,07973.10%1601 (6.65%)2.39Tophaceous Chronic7,723Yes3,64847.24%376 (10.31%)2.78No4,07552.76%597 (14.65%)2.89Uncontrolled13,514Yes5,88643.55%753 (12.79%)2.06No7,62856.45%1452 (19.04%)2.56* ER Visits are only included in this analysis if the primary diagnosis code on the claim is a gout code (M10.X, M1A.X)Conclusion:There appears to be a positive impact of rheumatologist involvement in the care of gout patients, manifested by a significant decrease in the frequency of ER visits. Considering the inconvenience and cost of ER visits, rheumatologist care may have a significant impact on the well-being of gout patients and on the overall cost of their care.Disclosure of Interests:Naomi Schlesinger Grant/research support from: Pfizer, Amgen, Consultant of: Novartis, Horizon Therapeutics, Selecta Biosciences, Olatec, IFM Therapeutics, Mallinckrodt Pharmaceuticals, N. Lawrence Edwards Consultant of: Horizon Therapeutics, Takeda Pharmaceuticals US, Aclaris Therapeutics, Atom Biosciences, Sanders Clark: None declared, Peter Lipsky Consultant of: Horizon Therapeutics

Background:Tanezumab, a monoclonal antibody against nerve growth factor, was recently evaluated in an 80 week placebo and tramadol-controlled trial in patients with chronic low back pain (CLBP) and a history of inadequate response to standard-of-care analgesics (NSAIDs, opioids, etc). Primary endpoint was change in Low Back Pain Intensity (LBPI) at week 16 vs placebo. Key secondary endpoints were the proportion of patients with ≥50% improvement in LBPI at week 16, change in Roland Morris Disability Questionnaire score at week 16, and change in LBPI at week 2 (all vs placebo). Tanezumab 10mg met the primary and all key secondary endpoints. Tanezumab 5mg did not meet the primary endpoint, but improved 2 of 3 key secondary endpoints. Due to the primary endpoint result and the statistical gate-keeping approach to control for multiple comparisons, a conclusion of superiority over placebo could not be made for the 5mg dose.Objectives:To further characterize tanezumab’s effects on pain and function in this trial through analysis of Brief Pain Inventory-short form (BPI-sf) scores.Methods:Patients received placebo (n=406), subcutaneous (SC) tanezumab 5mg (every 8 weeks; n=407), SC tanezumab 10mg (every 8 weeks; n=407) or oral tramadol prolonged-release (100-300mg/day; n=605). Pre-specified secondary endpoints included BPI-sf worst pain, average pain, the overall pain interference index, and selected individual domains of the index (general activity, walking ability, sleep, and normal work). Least squares (LS) mean (standard error [SE]) changes from baseline in BPI-sf scores were compared between groups (unadjusted for multiplicity) at week 16 using an analysis of covariance model. Scores range from 0-10 with higher scores indicating greater pain severity or functional impairment.Results:LS mean (SE) differences from placebo for worst pain were -0.52 (0.19) for tanezumab 5mg (p≤0.01), -0.54 (0.19) for tanezumab 10mg (≤0.01), and -0.24 (0.17) for tramadol (p=0.17). LS mean (SE) differences from placebo for average pain were -0.37 (0.18) for tanezumab 5mg (p=0.04), -0.46 (0.18) for tanezumab 10mg (≤0.01), and -0.17 (0.16) for tramadol (p=0.29). LS mean (SE) differences from placebo for the pain interference index were -0.41 (0.18) for tanezumab 5mg (p=0.03), -0.58 (0.18) for tanezumab 10mg (≤0.01), and -0.15 (0.17) for tramadol (p=0.39). Effects of tanezumab were not statistically different (p>0.05) from tramadol for worst pain, average pain, and the pain interference index, with exception of the pain interference index for tanezumab 10mg (p=0.01). Mean dose of tramadol was 203mg/day at week 16.Tanezumab 10mg significantly (pConclusion:Tanezumab 5mg and 10mg significantly improved worst pain, average pain, and overall pain interference index scores vs placebo in patients with CLBP. Tanezumab 10mg also significantly improved the overall pain interference index vs tramadol. Tanezumab 5mg significantly improved most individual domains of the pain interference index vs placebo, while tanezumab 10mg significantly improved all domains assessed vs placebo and vs tramadol.Disclosure of Interests:John Markman Consultant of: Consultant: Trigemina, Editas Medicine, and Plasma Surgical; Advisory board: Clexio Biosciences, Flexion Therapeutics, Quark Pharmaceuticals, Quartet Medicine, Collegium Pharmaceutical, Purdue Pharma, Biogen, Novartis, Aptinyx, Nektar, Allergan, Grünenthal, Eli Lilly and Company, Depomed, Janssen Pharmaceuticals, Teva Pharmaceutical Industries, KemPharm, Abbott Laboratories, Plasma Surgical, Chromocell, Convergence Pharmaceuticals, Inspirion, Pfizer, Sanofi, Daiichi Sankyo, and Trevena; Data safety monitoring boards for Novartis and Allergan, Serge Perrot Consultant of: Grunenthal, Pfizer, Lilly, MSD, Sanofi, Menarini, Seiji Ohtori: None declared, Thomas Schnitzer Consultant of: Pfizer, Lilly, AstraZeneca, GSK, Said Beydoun Grant/research support from: Argenx, Catalyst Pharma, Mallinckrodt, Pfizer, UCB, Consultant of: Alexion, Akcea, Alnylam, CSL, Takeda, Mitsubishi Tanabe, Speakers bureau: Alexion, Akcea, Alnylam, CSL, Takeda, Mitsubishi Tanabe, Lars Viktrup Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Ruoyong Yang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Candace Bramson Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Christine West Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Ken Verburg Shareholder of: Pfizer Inc, Employee of: Pfizer Inc

Background:The Addressing Lupus Pillars for Health Advancement (ALPHA) Project is a global consensus initiative to identify, prioritize and address top barriers in lupus drug development, clinical care and access to care. The Lupus Foundation of America convenes ALPHA with Tufts Center for the Study of Drug Development and a Global Advisory Committee of lupus experts representing clinician-scientists, industry and patients.Objectives:Collect global patient input to determine alignment with the lupus clinician-scientist community on prior published consensus of top lupus barriers.Methods:A 23-question online Qualtrics survey was developed to identify challenges across lupus diagnosis, clinical care and research participation. The survey, available in English, Spanish, Korean and simplified Chinese, was fielded in November 2019 to people with lupus and caregivers of children Results:Analysis included only consented responses with ≥ 68% survey completion (n=3,447) received across 83 countries. 95% were female with a mean age of 45. Respondents reported being White (57%), Black or of African descent (14%), Hispanic or Latino (18%) and Asian (10%). 65% resided in the US while 35% resided in countries outside of the US. 97% were people with lupus while 3% were caregivers to children Highest ranked challenges were similar globally and across children and adults: medication side effects, lack of treatment options and high out-of-pocket costs. Managing side effects ranked significantly higher (pConclusion:This global survey revealed that medication side effects and lack of effective treatments are top challenges for people with lupus, including children. Most respondents were never asked by their doctors to participate in a clinical trial, which may explain difficulties in trial recruitment. These barriers are consistent with prior published barriers identified by the clinician-scientist community.Acknowledgments:ALPHA sponsors: EMD Serono, GSK, Aurinia, MallinckrodtDisclosure of Interests:Karin Tse: None declared, Yaritza Peña: None declared, Kathleen Arntsen: None declared, Sang-Cheol Bae: None declared, Lauren Bloch Consultant of: Faegre Drinker Consulting is a division of Faegre Drinker Biddle & Reath, a law and consulting firm that represents patient advocacy organizations and sponsors developing drugs, Ian N. Bruce Grant/research support from: Genzyme Sanofi, GSK, and UCB, Consultant of: Eli Lilly, AstraZeneca, UCB, Iltoo, and Merck Serono, Speakers bureau: UCB, Karen Costenbader Grant/research support from: Merck, Consultant of: Astra-Zeneca, Bradley Dickerson Employee of: Aurinia, Thomas Dörner Grant/research support from: Janssen, Novartis, Roche, UCB, Consultant of: Abbvie, Celgene, Eli Lilly, Roche, Janssen, EMD, Speakers bureau: Eli Lilly, Roche, Samsung, Janssen, Kenneth Getz: None declared, Amy Kao Employee of: EMD Serono, Susan Manzi: None declared, Eric F. Morand Grant/research support from: AstraZeneca, Consultant of: AstraZeneca, Speakers bureau: AstraZeneca, Sandra Raymond: None declared, Brad H Rovin Grant/research support from: GSK, Consultant of: GSK, Laura Schanberg Grant/research support from: Sobi, BMS, Consultant of: Aurinia, UCB, Sanofi, Victoria Werth Grant/research support from: Biogen, Celgene, Gilead, Janssen, Viela, Consultant of: Biogen, Gilead, Janssen, Abbvie, GSK, Resolve, AstraZeneca, Amgen, Eli Lilly, EMD Serono, BMS, Viela, Kyowa Kirin, Joan Von Feldt Shareholder of: GSK, Employee of: GSK, David Zook Consultant of: Faegre Drinker Consulting is a division of Faegre Drinker Biddle & Reath, a law and consulting firm that represents patient advocacy organizations and sponsors developing drugs, Leslie Hanrahan: None declared

Background:Real-world data from electronic health records (EHR) allow examination of treatment patterns and clinical practice behaviors for psoriatic arthritis (PsA).Objectives:To describe physician and patient characteristics, and treatment patterns of patients with PsA who initiated secukinumab and other biologics using data from the Columbus Repository.Methods:EHR data from adult patients with PsA who were prescribed a new biologic therapy between January 2018 and March 2019 (index date) were included from the Columbus Repository, which collects clinical records from a network of US rheumatology providers. Demographics, disease characteristics, and treatment patterns, as well as physicians’ characteristics, were reported for patients who were prescribed secukinumab vs other biologics (abatacept, adalimumab, etanercept, certolizumab pegol, golimumab, infliximab, infliximab-dyyb, infliximab-abda, ustekinumab, and ixekizumab). Treatment groups were mutually exclusive and only the most recently prescribed biologic was represented. Categorical variables were summarized using frequency counts and percentages and continuous variables were presented using means and standard deviations.Results:As of March 2019, 234 patients initiated secukinumab and 806 initiated other biologics for PsA treatment; 62 physicians prescribed biologics for PsA. Overall, 73% of physicians’ offices had a single provider contributing patients to the analysis, and 76% of physicians were located in the South US region. Secukinumab initiators were younger (55.2 vs 57.3 years), more likely to be male (44% vs 31%), and had higher BMI (34.0 vs 31.9 kg/m2) vs other biologic initiators. Almost all disease activity measures evaluated had a large proportion (> 80%) of missing data; among those with nonmissing data, secukinumab initiators had numerically higher mean (SD) RAPID3 score vs other biologic initiators (12.6 [6.5] vs 11.6 [7.1]). Overall, 70% of secukinumab initiators and 48% of other biologic initiators were biologic experienced (Figure 1). Comorbidities were similar between groups (Figure 2). The most common reasons for discontinuation of prior biologic were the biologic was no longer required and lack of efficacy (Table 1).Table 1.Treatment Patterns Among Patients With PsA at the Index DateSecukinumab(N = 234)Other Biologic(N = 806)SMD*PValueReason for discontinuing prior biologic treatment, n (%)N = 164N = 3850.200.67No longer required64 (39)136 (35)Lack of efficacy28 (17)75 (19)Cost or administrative5 (3)10 (3)Side effects5 (3)9 (2)Lack of tolerability03 (1)Patient fear of side effects1 (1)0Other25 (15)63 (16)Missing36 (22)89 (23)Prior medication use, n (%)NSAIDs109 (47)365 (45)0.030.78Opioids89 (38)252 (31)0.140.06Steroids68 (29)265 (33)0.080.31DMARDsMethotrexate83 (35)340 (42)0.140.08Sulfasalazine25 (11)93 (12)0.030.81Apremilast53 (23)104 (13)0.26< 0.01Tofacitinib10 (4)36 (4)0.011.00No. of prior biologics, mean (SD)0.95 (0.82)0.62 (0.77)0.41< 0.01SMD, standardized mean difference.* Comparisons with SMD > 0.1 were suggestive of clinically relevant differences.Conclusion:Secukinumab initiators with PsA were more likely to be male and biologic experienced, have a higher BMI and higher RAPID3 scores indicative of more active disease vs those initiating other biologics. Additional structured and unstructured elements may need to be captured on EHR platforms to gain clarity on disease activity and treatment decisions.Acknowledgments:This study was funded by Novartis Pharmaceuticals Corporation, East Hanover, NJ. Support for third-party writing assistance for this abstract, furnished by Kheng Bekdache, PhD, of Health Interactions, Inc, was provided by Novartis Pharmaceuticals Corporation, East Hanover, NJ.Disclosure of Interests:Howard Busch Speakers bureau: AbbVie, Amgen, Crescendo, Exagen, Genentech, Mallinckrodt, Novartis, Primus, Sanofi/Regeneron, and UCB, Jeffrey Curtis Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Lilly, Myriad, Pfizer, Regeneron, Roche, UCB, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Lilly, Myriad, Pfizer, Regeneron, Roche, UCB, Peter Hur Employee of: Novartis Pharmaceuticals Corporation

Background:Despite the high prevalence of gout, there has been little investigation into the relationship between physical activity and gout.Objectives:To investigate whether physically active gout patients, as assessed by the International Physical Activity Questionnaire (IPAQ) long form, have lower pain scores, decreased inflammation, assessed by C-reactive protein (CRP) levels and less flares.Methods:During scheduled appointments, gout patients not experiencing a flare at the time of visit were recruited from our clinics and consented to participate in the study. IPAQ were completed. Clinical data collected during the visit included age, years since diagnosis, flares per year, perceived pain at the time of visit and in the past 4 weeks, and C-reactive protein (CRP) levels.Results:Thirty gout patients were recruited. Ages 31-86 (mean 61); duration of gout: one- 43 years (mean 9). IPAQ, separated gout patients into physically active (n=16) and physically inactive cohorts (n=14) (pConclusion:This is the first study using a validated physical activity tool, IPAQ, to assess physical activity in gout patients. In this study, physically active gout patients were found to have lower CRP levels, less flares per year, and decreased pain perception compared to those that are not physically active, highlighting, the importance of incorporating physical activity as a possible adjunct treatment option during intervals between flares.References:[1]Benatti FB, Pedersen BK. Exercise as an anti-inflammatory therapy for rheumatic diseases-myokine regulation. Nat Rev Rheumatol 2015;11:86-97.[2]Hagströmer M, Oja P, Sjöström M. The International Physical Activity Questionnaire (IPAQ): a study of concurrent and construct validity. Public Health Nutr 2006;9:755-62.[3]Young NA, Jablonski K, Sharma J, Thomas E, Snoad B, Hampton J, et al. Low and Moderate Intensity Exercise Suppresses Inflammatory Responses in an Acute Mouse Model of Gout and Suggests Therapeutic Efficacy [abstract]. Arthritis Rheumatol. 2017;69 (suppl 10).Disclosure of Interests:Naomi Schlesinger Grant/research support from: Pfizer, AMGEN, Consultant of: Novartis, Horizon Pharma, Selecta Biosciences, Olatec, IFM Therapeutics, Mallinckrodt Pharmaceuticals, Speakers bureau: Takeda, Horizon, Kyle jablonski: None declared, Emmy schwarz: None declared, Nicholas Young: None declared

Background:Gout is a painful inflammatory arthritis caused by persistently elevated serum uric acid (sUA) levels. Pegloticase, an infused recombinant PEGylated uricase, rapidly lowers sUA levels by converting uric acid to allantoin, a water-soluble molecule that is readily excreted by the kidneys. In the phase 3 clinical trials, 42% of patients1dosed with pegloticase every two weeks maintained sUA levels below 6.0 mg/dL during months 3 and 6 of pegloticase treatment. The loss of pegloticase efficacy has been attributed to the development of anti-drug antibodies (ADAs)1-3and these ADAs have been associated with infusion reactions (IRs).1,2Case reports4and prospective case series5, 6indicate that methotrexate (MTX) may allow patients to attain more complete therapeutic benefits, presumably through attenuation of pegloticase immunogenicity. The current study prospectively examines the efficacy and safety of MTX-pegloticase co-therapy in patients with uncontrolled gout.Objectives:To assess efficacy and safety of concomitant pegloticase and MTX therapy in patients with uncontrolled gout.Methods:Adult patients with uncontrolled gout who were beginning pegloticase therapy were considered for enrollment in this ongoing multicenter, open-label, efficacy and safety study of pegloticase with MTX co-treatment (NCT03635957). Patients were administered oral MTX (15 mg/week) and folate (1 mg/day) 4 weeks prior to the first pegloticase infusion (Day 1) and throughout the pegloticase treatment period. Blood was drawn prior to each infusion to measure sUA level, monitor clinical parameters, and examine for ADA development. All patients followed typical IR prophylaxis protocols (fexofenadine one day before and the morning of each infusion and acetaminophen and IV corticosteroid the morning of each infusion). Patients also received gout flare prophylaxis with either NSAIDs, colchicine or prednisone initiated at least 1 week prior to Day 1. The primary study outcome was the proportion of responders, defined as sUA Results:A total of 17 patients were screened and 14 patients (all men, average age: 49.3 ± 8.7 years) were enrolled. On Day 1, mean sUA was 9.2 ± 2.5 mg/dL and 12 of the 14 patients had visible tophi. At the 6 months timepoint, 11/14 (78.6%, 95%CI 49.2-95.3%) met the responder definition, with 3 patients discontinuing after meeting stopping rules (pre-infusion sUA values greater than 6 mg/dL at 2 consecutive scheduled visits). All patients tolerated MTX. One serious AE of bacterial sepsis occurred (resolved). AEs that occurred in >1 patient during the co-treatment period were: diarrhea and upper respiratory tract infection in 3 patients each, sinusitis, muscle strain, and hypertension in 2 patients each. Gout flares occurred in 12/14 (85.7%) patients. No new safety concerns were identified.Conclusion:An increased proportion of patients maintained therapeutic response at 6 months when treated concomitantly with MTX and pegloticase (78.6%) when compared to the previously reported 42% using pegloticase alone.1These results support and reflect the improved response rates demonstrated in two prior case series.5,6A definitive randomized double-blinded trial evaluating pegloticase with MTX vs. pegloticase with placebo is ongoing.References:[1]Sundy JS et al.JAMA2011;306:711-20.[2]Baraf HS et al.J Clin Rheumatol2014;20:427-32.[3]Lipsky PE et al.Arthritis Res Ther2014;16:R60.[4]Bessen SY et al.Semin Arthritis Rheum2019;49:56-61.[5]Botson J, Peterson J.Ann Rheum Dis2019;78:A1289.[6]Albert JA et al.Arthritis & Rheumatology2019;71(S10):A1236.Disclosure of Interests: :John Botson Grant/research support from: Horizon Therapeutics (PI and study site), Radius Health (study site), Consultant of: Horizon Therapeutics, Speakers bureau: Celgene, Eli Lilly, Horizon Therapeutics, Mallinckrodt, Novartis, Pfizer, Paul M. Peloso Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics, Katie Obermeyer Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics, Brian LaMoreaux Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics, Michael E. Weinblatt Grant/research support from: BMS, Amgen, Lilly, Crescendo and Sonofi-Regeneron, Consultant of: Horizon Therapeutics, Bristol-Myers Squibb, Amgen, Abbvie, Crescendo, Lilly, Pfizer, Roche, Gilead, Jeff Peterson Grant/research support from: Abbvie, UCB, Smith Klein, Horizon Therapeutics, Consultant of: Lilly, Norvartis, Horizon Therapeutics, Speakers bureau: Lilly, Novartis, Horizon Therapeutics, Abbvie, Genentech

Background Despite the availability of therapeutic options for RA, including DMARDs and biologic agents, there are many patients who are resistant to current therapy and remain inadequately controlled. We hypothesized that 12-week repository corticotropin injection (RCI) treatment may provide relief of RA and acute exacerbations in patients refractory to treatment with DMARDs and at least three biologics (including 1 tumor necrosis factor inhibitor). Objectives The objective of this study was to assess the efficacy and safety of RCI in this patient population. Methods This was a 12-week prospective, multicenter, open-label study with 9 patients. Patients were maintained on stable doses of a biologic, other DMARD therapies and prednisone of at least 7.5 mg daily; RCI was adjunctive therapy. RCI 40 U was given subcutaneously daily for 7 days. If an adequate response (>1.2 point reduction in the Disease Activity Score 28 using C-Reactive Protein [DAS28-CRP]) was achieved, the dose was decreased to 40 U twice weekly through week 12. If the response was inadequate, patients received 80 U once daily for 7 days, followed by 80 U twice weekly through week 12. The primary endpoint was >1.2 point reduction in DAS28-CRP at week 12. Secondary endpoints included improvements in American College of Rheumatology 20%, 50%, and 70% (ACR20, 50 and 70), decrease in Health Assessment Questionnaire Disease Index (HAQ-DI) score, and improvement in Functional Assessment of Chronic Illness Therapy (FACIT) and health-related quality of life (HRQOL) questionnaires. Results We report results for 9 patients (44–60 years). A total of 66% (6/9) of patients met the primary endpoint. The mean DAS improvement at 12 weeks on 40 U of therapy was numerically greater than that in patients increasing their dose to 80 U. Improvements were also noted in secondary endpoints, particularly over the first 4–8 weeks of treatment. Five of 9 patients maintained improvement in HAQ-DI and in the FACIT fatigue scale at week 12 (Table). There did not appear to be a clear pattern or association between cortisol levels and RCI response. No serious adverse events (AEs) occurred. Mild AEs included Cushingoid features (n=2), mild hyperglycemia (n=1), herpes zoster (n=1), and pedal edema (n=1). Conclusions RCI produced a rapid and clinically meaningful reduction in markers of disease activity and improved quality of life. RCI demonstrated a favorable safety profile; there were no serious adverse events and cortisol levels did not increase for most patients. For patients who are refractory to common RA therapies, the response rate to RCI was substantial and shows great promise in this difficult to treat population. Disclosure of Interest P. Fischer Grant/research support from: Mallinckrodt, Genetech, Paid instructor for: Mallinckrodt, R. Rapoport Paid instructor for: Amgen, Abbvie, Union Chimique Belge, Exagen

Background Repository corticotropin injection (RCI), a melanocortin peptide preparation, is FDA approved as adjunctive therapy for short term administration to tide patients over acute episodes or exacerbations of rheumatoid arthritis (RA), but has not been studied in an animal model of arthritis flare. Objectives To test the efficacy of RCI in a Streptococcal cell wall-induced model of arthritis flare in rats [1]. Methods Dark Agouti rats were primed on day 0 by an intra-articular injection of a proteoglycan/polysaccharide (PGPS) preparation from Streptococcal cell wall into the right ankle and vehicle (phosphate buffered saline) into the left. On days 14 and 28, transient arthritic flares were induced in the ankle by intravenous injection of PGPS. Caliper measurements of the right and left paw diameters were made daily beginning on the day of induction of the first flare. RCI was administered subcutaneously at doses of 40, 160, and 400 U/kg beginning day 1 after induction of the first flare and dosed every other day until animals were sacrificed on day 35, after recovery from the second flare. Arthritis was assessed by measuring the diameter difference between the right (PGPS injected) and left ankles. Histologic analysis was performed on the paws obtained at sacrifice (day 35). Results RCI dose-dependently inhibited paw swelling in rats after induction of both the first and second arthritic flares. Doses of 160 U/kg and 400 U/kg inhibited physical signs of the first flare by 69% (p Conclusions These preclinical results demonstrate the efficacy of RCI in an animal model of RA flare and support the potential clinical benefit of the drug for the treatment of inflammatory arthritis exacerbations. References Schopf L, Anderson K, Jaffee B. Rat models of arthritis: Similarities, differences, advantages, and disadvantages in the identification of novel therapeutics. In: C Stevenson, L Marshall, D Morgan (eds): In Vivo Models of Inflammation. 2006 Birkhauser Verlag, Basel. 1–34. Disclosure of Interest P. Higgins Employee of: Mallinckrodt, D. Decker Employee of: Mallinckrodt, P. Becker Employee of: Mallinckrodt

Background We recently reported results from a pilot 8-week randomized double-blind placebo (PBO)-controlled study of RCI in subjects with persistently active SLE involving skin and/or joints despite moderate dose corticosteroids for ≥4 weeks a . Although the primary endpoint of this study (resolution of disease active for SLEDAI rash or arthritis with no worsening of other organ systems by BILAG) was not met, RCI therapy (40U daily or 80U every other day SC) led to improvement in several measures of disease activity, including total hybrid SLEDAI (hSLEDAI), total BILAG, CLASI Activity scores, and Tender and swollen joint count, as compared with PBO. Objectives To describe the topline results of a 44-week open-label extension (OLE) of this study of RCI in persistently active SLE. Methods 33/38 subjects completed the double-blind phase of the study and opted to enroll in the OLE. Of these 33, 22 had received RCI and 11 PBO during the prior 8 weeks. The dose of RCI could be adjusted beginning at week 9, with the goal of achieving a stable dose (16, 40 or 80U SC, 1–3x/week) to control disease activity no later than Week 28. Beginning at Week 20, investigators were encouraged to taper background prednisone. Disease activity was assessed monthly by hSLEDAI, BILAG, CLASI, Tender & swollen joint counts, and physician9s global assessment (PGA). Results 20 subjects completed the OLE, 13/22 from the RCI/RCI and 7/11 from the PBO/RCI groups. No unexpected adverse events were observed. Conclusions These data demonstrate that subjects in the RCI/RCI group had a durable response to therapy over 52 weeks, whereas those in the PBO/RCI group experienced improvements in disease activity during the OLE that were generally comparable to the improvements seen with RCI treatment from the blinded phase of the trial. References Furie R, Das M, Li D, Smythe S, Mathura E, Becker P. Repository Corticotropin Injection (H.P. Acthar® Gel) Attenuates Disease Activity in Patients with Persistently Active Systemic Lupus Erythematosus (SLE) Requiring Corticosteroids [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). Disclosure of Interest P. Becker Shareholder of: Mallinckrodt Pharmaceuticals Inc, Employee of: Mallinckrodt Pharmaceuticals Inc, R. Furie: None declared, M. Mitrane Consultant for: Mallinckrodt Pharmaceuticals Inc, E. Zhao Employee of: Mallinckrodt Pharmaceuticals Inc

Background Although there are many types of treatment for rheumatoid arthritis (RA) currently available, some patients have disease that is refractory to treatment and thus fail to achieve remission. Acthar Gel may have a potential role in enabling refractory RA patients to reach their treatment goals. Objectives To assess the efficacy and safety of subcutaneous injections of Acthar Gel as adjunctive therapy in patients with active RA. Methods This is an ongoing, 17-week, prospective, single-center, open-label study with planned enrollment of 10 patients (≥18 years) with RA, as confirmed by a full count of 68 joints, who are currently not responding sufficiently to a biological agent and have previously inadequately responded to ≥2 biologic agents with different modes of action. Patients are administered 80 U Acthar Gel subcutaneously every 72 hours for 12 weeks, with assessments conducted at screening (Week -1), baseline (Week 0), and Weeks 2, 6, 12, 14, and 16. Primary outcome measures are tender joint count and swollen joint count (ACR Core Data Set 66/68-joint count) and 20-item Health Assessment Questionnaire (HAQ). Secondary outcome measures are acute erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels, Patient Global Visual Analogue Scale (VAS), and Physician Global VAS. Disease Activity Score for RA (DAS28) is also being calculated. Results Six patients (aged 54-80; 9-39 years since diagnosis of RA) have completed the trial so far. At end of treatment (Week 12), all had reductions from baseline in tender and swollen joint counts; 3 showed improvement in HAQ and 3 showed no change. Improvements in DAS28 (6 of 6 patients), ESR (4/6), CRP (4/6), and Patient (5/6) and Physician (6/6) Global VAS were also seen at end of treatment, with improvements in all measures generally receding 4 weeks post-treatment (Week 16). One patient experienced a mild skin reaction at the injection site, and 1 had hypoglycemic episodes. A third patient was hospitalized for hip pain unrelated to Acthar Gel. All resolved and no patients withdrew from treatment due to adverse events. Conclusions It is extremely difficult to provide effective treatment for patients with active RA who have not responded adequately to biological agents with 3 different mechanisms of action. This interim report of an ongoing trial indicates that 80 U Acthar Gel administered subcutaneously every 72 hours for 12 weeks may provide a treatment option for such patients. Acknowledgements This study is supported by an investigator-initiated research grant from Autoimmune and Rare Diseases Business (formerly Questcor) Mallinckrodt Pharmaceuticals. Disclosure of Interest T. Gillis Grant/research support from: received study drug and study funding from Autoimmune and Rare Diseases Business (formerly Questcor) Mallinckrodt Pharmaceuticals, M. Crane Grant/research support from: received study drug and study funding from Autoimmune and Rare Diseases Business (formerly Questcor) Mallinckrodt Pharmaceuticals, C. Hinkle Grant/research support from: received study drug and study funding from Autoimmune and Rare Diseases Business (formerly Questcor) Mallinckrodt Pharmaceuticals, N. Wei Grant/research support from: received study drug and study funding from Autoimmune and Rare Diseases Business (formerly Questcor) Mallinckrodt Pharmaceuticals

Background Acthar Gel has been approved for use in multiple rheumatic/inflammatory conditions since the early 1950s, yet the current literature remains sparse on its real-world clinical efficacy and safety. In addition to the well-established steroid-dependent effects of Acthar Gel, research suggests it has direct steroid-independent immunomodulatory effects in a variety of tissues due to its ability to bind to multiple melanocortin receptors. Clinical reports on the real-world efficacy and safety of Acthar Gel are needed. Objectives This is an assessment of the efficacy and tolerability of Acthar Gel among patients with systemic lupus erythematosus (SLE). Methods This is a retrospective analysis of 4 African American female patients with SLE, all of whom had continued disease activity despite receiving standard therapy (see Table for previous treatments). They were all on chronic maintenance cortisone at an equivalent dosage of 5 mg of prednisone per day. Each patient received 80 U of Acthar Gel subcutaneously twice weekly as adjunctive treatment. Patients 1, 2, 3, and 4 were treated for 9, 1.5, 6, and 3.5 months, respectively. Outcome measures included protein/creatinine ratio, double-stranded DNA (dsDNA), lymphocyte count, white blood cell count, platelet count, and hemoglobin level. Results The SLE patients had a mean disease duration of 7.85 years. Results are presented below (Table). There was a substantial decline in protein/creatinine ratio among 3 patients, especially patient 3, who decreased from 7628 mg/g to 1311 mg/g in approximately 11 months. The first patient had extremely elevated dsDNA, which can occur among patients with SLE, but it declined substantially after treatment initiation with Acthar Gel. Patient 4 had diffuse skin hyperpigmentation. There were no other treatment-related adverse events. Conclusions Acthar Gel was well tolerated and reduced proteinuria in this small subset of patients. These results support those from previous SLE studies. Acthar Gel provided clinical benefits for 3 of 4 patients despite the fact that they had not responded adequately to prior treatments. The substantial improvements in protein/creatinine ratio among those 3 patients all began within the first month of initiation of 80 U Acthar Gel twice weekly and were sustained throughout the duration of treatment. Although there were only 4 subjects included in this analysis, of the 3 patients that showed improved disease activity, 2 of these patients (66%) showed improved lymphocyte counts, not unexpected in patients with autoimmune disease. Melanocortin receptors are also found on lymphocytes, and therefore it is possible that Acthar Gel provided beneficial effects on certain T cell populations among these patients with active disease who had not responded adequately to previous treatments. Additional clinical research is necessary in order to establish the optimal dosage, optimal duration, and efficacy, safety, and tolerability of therapy with Acthar Gel. Acknowledgements Funding to support the preparation of this abstract for submission was provided by Mallinckrodt Pharmaceuticals. Disclosure of Interest S. Pegram Speakers bureau: Compensation originally provided by Questcor Pharmaceuticals, Inc. and continued by Mallinckrodt Pharmaceuticals while serving as a speaker.