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ObjectiveAssess pooled safety results through the end of the phase II/III studies of guselkumab (GUS; ≤ 2 years) in tumor necrosis factor inhibitor (TNFi)-naïve and -experienced patients with psoriatic arthritis (PsA).MethodsData were pooled from the Phase 2 and DISCOVER-1 (both TNFi-naïve and -experienced), DISCOVER-2 (TNFi-naïve), and COSMOS (TNFi-experienced) studies. Patients with active PsA were randomized to GUS 100 mg every 4 or 8 weeks (Q4W + Q8W = Combined GUS) or placebo (PBO) with crossover to GUS Q4W or Q8W at week 24. Time-adjusted adverse event (AE) rates (events/100 patient-years [PY]) and clinical laboratory findings were assessed during the PBO-controlled period and through end of study (≤ 2 years).ResultsOf 1554 randomized patients (n = 373 [GUS Q4W], 664 [GUS Q8W], and 517 [PBO]), 1138 (73.23%) were TNFi-naïve and 416 (26.77%) were TNFi-experienced. Respective AE rates through week 24 were 220.8/100 PY (TNFi-naïve) and 251.6/100 PY (TNFi-experienced) in the Combined GUS group and 196.1/100 PY (TNFi-naïve) and 303.0/100 PY (TNFi-experienced) in the PBO group. Among all GUS-treated patients (including those who crossed over from PBO), low AE rates were maintained during long-term evaluation in both TNFi-naïve (139.7/100 PY) and TNFi-experienced (174.0/100 PY) patients. Rates/100 PY of AEs leading to treatment discontinuation, serious AEs, and other AEs of interest, as well as occurrence of elevated hepatic transaminase levels and decreased neutrophil counts were consistent between PBO and GUS-treated patients through week 24 regardless of prior TNFi use and remained low through the end of the studies.ConclusionThe safety profile of GUS in TNFi-experienced patients was consistent with that in TNFi-naïve patients, which remained favorable for up to 2 years. [ClinicalTrials.gov: Phase 2 (NCT02319759), DISCOVER-1 (NCT03162796), DISCOVER-2 (NCT03158285), and COSMOS (NCT03796858)]

Background/Aims Guselkumab, a human monoclonal antibody targeting the interleukin-23 p19 subunit, demonstrated joint and skin efficacy in patients with PsA in the Phase III DISCOVER-1/-2 trials. MDA, a multi-domain composite outcome, is a clinically relevant measure of therapeutic response in PsA. However, response dynamics and the effect of individual domains on achieving MDA are not well understood. This analysis aimed to characterise MDA response clusters according to domain changes over time and identify potential baseline predictors in patients with PsA receiving guselkumab. Methods Data from bio-naïve patients with active PsA receiving guselkumab 100 mg every 4 or 8 weeks were pooled across DISCOVER-1/-2. Unsupervised machine learning using the time-series K-means clustering algorithm was performed to identify clusters according to MDA domain responses over 52 weeks. Missing data were not imputed. Results This analysis included 571 of 669 patients receiving guselkumab and distinguished four response clusters (C1-4; Table 1). Mean age and body mass index were similar across clusters; C3 had a lower proportion of female patients vs. other clusters. Relative to C3, a high burden of baseline disease was observed in C4 across clinical measures and PROs, and across PROs only in C2. Through Week 52, mean values for all MDA domains showed continuous improvement across clusters (Table 1). MDA response rates were highest in C3, in which all individual domain thresholds were rapidly approached, and lowest in C4. In C1 and C2, improvement in clinical measures paralleled that of C3; both met the PASI threshold and showed substantial reduction in SJC. PROs appeared to take longer to improve but did so earlier in C1 than C2. Improvements were slowest in C4, though still substantial given the high baseline disease burden. Conclusion Machine learning differentiated four clusters of patients with PsA receiving guselkumab based on response patterns in individual MDA domains. Response may differ due to baseline disease burden, especially in patients with high pain, PtGA and functional disability scores. These results offer an innovative, complementary approach to identifying treatment response patterns across diverse clusters of bio-naïve patients with PsA, which may facilitate clinical decision-making. Disclosure A. Zabotti: Member of speakers’ bureau; AbbVie, Amgen, Janssen, Lilly, Novartis and UCB. Grants/research support; Novartis. S. Ohrndorf: Other; Speaker fees or travel expense reimbursements from AbbVie, BMS, Janssen, Novartis and Pfizer. W. Tillett: Other; Research funding, consulting, speaker fees and/or honoraria from AbbVie, Amgen, Celgene, GlaxoSmithKline, Janssen, Lilly, MSD, Novartis, Pfizer and UCB. M. Neuhold: Other; Former employee of Janssen and is now an employee of Takeda Pharmaceuticals International AG. M. van Speybroeck: Shareholder/stock ownership; Employee of Janssen and owns stocks in Johnson & Johnson. E. Theander: Other; Former employee of Janssen. C. Contré: Other; Former employee of Janssen and is now an employee of Chiesi. M. Sharaf: Shareholder/stock ownership; Employee of Janssen and owns stocks in Johnson & Johnson. M. Shawi: Shareholder/stock ownership; Employee of Janssen and owns stocks in Johnson & Johnson. M. Perate: Shareholder/stock ownership; Employee of Janssen and owns stocks in Johnson & Johnson. A. Kollmeier: Shareholder/stock ownership; Employee of Janssen and owns stocks in Johnson & Johnson. P. Richette: Other; Received fees from AbbVie, Amgen, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer and UCB.

Background/Aims Guselkumab is a monoclonal antibody approved to treat moderate-to-severe plaque psoriasis and active psoriatic arthritis (PsA). In this analysis, safety data from 11 Phase 2/3 studies of guselkumab were pooled to evaluate guselkumab safety in a large population of patients with psoriatic disease. Methods Guselkumab was generally administered as 100-mg injections at Week (W)0, W4, then Q8W in 7 psoriasis studies and at W0, W4, then Q4W or Q8W in 4 PsA studies. Patients randomized to placebo crossed over to guselkumab Q8W at W16 in 5 PsO studies and to guselkumab Q4W or Q8W at W24 in all PsA studies. Safety data were summarized for the placebo-controlled period (W0-W16 in PsO; W0-W24 in PsA) and through the end of the reporting period (up to 5 years in PsO; up to 2 years in PsA). Incidence rates of key safety events were integrated post-hoc, adjusted for duration of follow-up, and reported per 100 patient-years (PY). Results During the placebo-controlled periods, 1061 patients received placebo (395 PY) and 2257 received guselkumab (856 PY). Through the long-term reporting periods, 4399 guselkumab-treated patients (PsO: 2891; PsA: 1508) contributed 10787 PY of follow-up (PsO: 8662 PY; PsA: 2125 PY). In PsO and PsA studies, pooled incidence rates of overall adverse events (AEs) were similar between guselkumab- and placebo-treated patients. Rates of serious AEs, AEs leading to discontinuation, serious infections, malignancy, and major adverse cardiovascular events were low and generally similar between guselkumab- and placebo-treated patients. Rates of safety events remained consistent through the long-term reporting period for guselkumab-treated patients (Table). No cases of Crohn’s disease or ulcerative colitis were reported in guselkumab-treated patients. No serum sickness-like or anaphylactic reactions related to guselkumab were reported. No opportunistic infections were reported in any guselkumab-treated PsO patient. Three cases of opportunistic infection were reported in pooled PsA studies (0.14/100 PY; all post-W52 in DISCOVER-2). No cases of active tuberculosis were reported across all studies. Conclusion In the most comprehensive analysis of guselkumab safety to date, AE rates in guselkumab-treated patients were similar to those observed with placebo and were stable throughout long-term follow-up. Disclosure B. Strober: Grants/research support; AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, Eli Lilly, Meiji Seika Pharma, Novartis, Pfizer, UCB Pharma, Sun Pharma, Regeneron, Dermira, Leo Pharma, Inc, Arcutis, Are. L. Coates: Grants/research support; AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Novartis, Pfizer, and UCB; grant/research support from AbbVie, Amgen, Celgene, Eli Lilly, Jan. J. Yu: Shareholder/stock ownership; Janssen Research & Development, LLC, Johnson & Johnson. K. Rowland: Shareholder/stock ownership; Janssen Scientific Affairs, LLC, Johnson & Johnson; E. Leibowitz, Janssen Scientific Affairs, LLC, Johnson & Johnson. E. Leibowitz: Shareholder/stock ownership; Janssen Scientific Affairs, LLC, Johnson & Johnson; E. Leibowitz, Janssen Scientific Affairs, LLC, Johnson & Johnson. M. Miller: Shareholder/stock ownership; Janssen Scientific Affairs, LLC, Johnson & Johnson; E. Leibowitz, Janssen Scientific Affairs, LLC, Johnson & Johnson. A. Kollmeier: Shareholder/stock ownership; Janssen Scientific Affairs, LLC, Johnson & Johnson; E. Leibowitz, Janssen Scientific Affairs, LLC, Johnson & Johnson. S. Li: Shareholder/stock ownership; Janssen Scientific Affairs, LLC, Johnson & Johnson; E. Leibowitz, Janssen Scientific Affairs, LLC, Johnson & Johnson. Y. Wang: Shareholder/stock ownership; Janssen Scientific Affairs, LLC, Johnson & Johnson; E. Leibowitz, Janssen Scientific Affairs, LLC, Johnson & Johnson. D. Chan: Shareholder/stock ownership; Janssen Scientific Affairs, LLC, Johnson & Johnson. S. Chakravarty: Shareholder/stock ownership; Janssen Scientific Affairs, LLC, Johnson & Johnson; Y. Yang, Janssen Pharmaceutical Companies, Johnson & Johnson. Y. Yang: Shareholder/stock ownership; Janssen Pharmaceutical Companies, Johnson & Johnson. M. Shawi: Shareholder/stock ownership; Janssen Pharmaceutical Companies of Johnson and Johnson. M. Lebwohl: Grants/research support; Arcutis, Boehringer Ingelheim, Bristol Myers Squibb, Verrica, AbbVie, Amgen, Eli Lilly, Janssen, Ortho Dermatologics, Pfizer, UCB Pharma, Avotres Therapeutics, AnaptysBio, Aristea Therapeutics, BioMX, Cara Therapeutics, Castle Biosciences, Dermavant, Evommune, Facilitatation of International Dermatology Education, Forte Biosciences, Foundation for Research and Education in Dermatology, Hexima, Meiji Seika Pharma, Mindera Health, Regeneron, Seanergy, Incyte, Arrive Technologies, Dr Reddy's Laboratories, Evelo Biosciences, Helsinn Therapeutics, LEO Pharma, Mount Sinai, CorEvitas (formerly Cor. P. Rahman: Shareholder/stock ownership; Janssen, Novartis, AbbVie, Eli Lilly and Company, Pfizer.

Background/Aims Although continuous composite measures of disease activity for PsA assessment exist, more feasible abbreviated measures are needed for routine screening. The 3VAS and 4VAS scores, developed by abridging the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) Composite Exercise (GRACE) measure, are the first short multidimensional composite measures specifically for routine PsA care. 3VAS/4VAS showed superior performance vs. several established composite measures using small datasets. However, GRAPPA members recommended further testing of 3VAS/4VAS in observational and trial datasets. Methods This post hoc analysis used pooled data through W24 from all treatment groups in the DISCOVER 1/2 and COSMOS studies. Correlation of 3VAS/4VAS with DAPSA, PASDAS, PhGA and PtGA was assessed with Pearson’s correlation coefficient, minimal important difference (MID) with four distribution-based methods and minimal detectable change (MDC) with the standard formula (Table 1). Clinically relevant thresholds for low, moderate and high disease activity were estimated with receiver operating characteristic analysis and DAPSA (≤4, >4-≤14, >14-≤28, >28), PASDAS (≤1.9, >1.9-≤3.2, >3.2-1-≤3, >3-≤6, >6 cm) as anchors. Results This analysis included 1405 patients: 51.3% were male, with a mean (sd) age of 47.1 (11.8) and PsA duration of 6.4 (6.5) years. The mean baseline 3VAS, 4VAS, DAPSA, PASDAS, PhGA and PtGA scores reflected high disease activity levels (Table 1). Through W24, 3VAS and 4VAS showed very strong correlation with PtGA (r3VAS=0.92, r4VAS=0.94) and PASDAS (r3VAS=0.81, r4VAS=0.82), strong with PhGA (r3VAS=0.77, r4VAS=0.74) and moderate-to-strong with DAPSA (r3VAS=0.59, r4VAS=0.61). Calculated MIDs were 0.9 for 3VAS and 0.9 for 4VAS; MDCs were 3.3 for 3VAS and 3.2 for 4VAS (Table 1). Cut-off values for low, moderate and high disease activity were 2.0, 3.4 and 4.9 for 3VAS, and 2.1, 3.5 and 5.1 for 4VAS. Conclusion Using a large pooled clinical trial dataset of patients with active PsA, we have calculated clinically relevant thresholds for improvement, as well as disease activity thresholds, for 3VAS and 4VAS. These estimates are generally comparable to those previously reported and may facilitate setting treatment targets and screening disease activity in routine care when resources are limited or in remote patient monitoring. Disclosure W. Tillett: Other; Received research funding, consulting, speaker fees and/or honoraria from AbbVie, Amgen, Celgene, GlaxoSmithKline, Janssen, Lilly, MSD, Novartis, Pfizer and UCB. L. Coates: Consultancies; AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Novartis, Pfizer and UCB. Member of speakers’ bureau; AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Medac, Novartis, Pfizer and UCB. Grants/research support; AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB. Other; National Institute for Health Research (NIHR) Clinician Scientist award. The research was supported by the NIHR Oxford Biomedical Research Centre, The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health, We acknowledge the support of the NIHR Clinical Research Network. M. Vis: Other; Received research grants and consulting or speaker fees from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, UCB and the Dutch Arthritis Foundation. J. Merola: Consultancies; Consultant and/or investigator for AbbVie, Arena, Biogen, Bristol Myers Squibb, Dermavant, Lilly, Janssen, Novartis, Pfizer, Sun Pharma and UCB Pharma. E. Soriano: Consultancies; AbbVie, Janssen, Novartis and Roche. Member of speakers’ bureau; AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, Roche and UCB. Grants/research support; AbbVie, Janssen, Novartis, Pfizer, Roche and UCB. M. Perate: Shareholder/stock ownership; Employee of Janssen and owns stocks in Johnson & Johnson. M. Shawi: Shareholder/stock ownership; Employee of Janssen and owns stocks in Johnson & Johnson. M. Zimmermann: Shareholder/stock ownership; Employee of Janssen and owns stocks in Johnson & Johnson. E. Rampakakis: Consultancies; Employee of JSS Medical Research; paid consultant of Janssen. M. Sharaf: Shareholder/stock ownership; Employee of Janssen and owns stocks in Johnson & Johnson. P. Nash: Other; Received grants for research and clinical trials and honoraria for advice and lectures on behalf of AbbVie, Boehringer-Ingelheim, Gilead/Galapagos, GSK, Janssen, Lilly, MSD, Novartis, Pfizer, Samsung,. P.S. Helliwell: Consultancies; AbbVie, Amgen, Novartis and Janssen. Other; Fees for educational services from AbbVie, Amgen, Novartis and Janssen.

ObjectivesPsoriatic arthritis (PsA) phenotypes are typically defined by their clinical components, which may not reflect patients’ overlapping symptoms. This post hoc analysis aimed to identify hypothesis-free PsA phenotype clusters using machine learning to analyse data from the phase III DISCOVER-1/DISCOVER-2 clinical trials.MethodsPooled data from bio-naïve patients with active PsA receiving guselkumab 100 mg every 8/4 weeks were retrospectively analysed. Non-negative matrix factorisation was applied as an unsupervised machine learning technique to identify PsA phenotype clusters; baseline patient characteristics and clinical observations were input features. Minimal disease activity (MDA), disease activity index for psoriatic arthritis (DAPSA) low disease activity (LDA) and DAPSA remission at weeks 24 and 52 were evaluated.ResultsEight clusters (n=661) were identified: cluster 1 (feet dominant), cluster 2 (male, overweight, psoriasis dominant), cluster 3 (hand dominant), cluster 4 (dactylitis dominant), cluster 5 (enthesitis, large joints), cluster 6 (enthesitis, small joints), cluster 7 (axial dominant) and cluster 8 (female, obese, large joints). At week 24, MDA response was highest in cluster 2 and lowest in clusters 3, 5 and 6; at week 52, it was highest in cluster 2 and lowest in cluster 5. At weeks 24 and 52, DAPSA LDA and remission were highest in cluster 2 and lowest in clusters 4 and 6, respectively. All clusters improved with guselkumab treatment over 52 weeks.ConclusionsUnsupervised machine learning identified eight PsA phenotype clusters with significant differences in demographics, clinical features and treatment responses. In the future, such data could help support individualised treatment decisions.

INTRODUCTION: The phase 3 DISCOVER-2 trial evaluated the effect of guselkumab on impaired work productivity and nonwork activity in biologic-naïve patients with psoriatic arthritis (PsA).METHODS: Adults with active PsA were randomized (1:1:1) to guselkumab 100 mg every 4 weeks (Q4W), guselkumab 100 mg at weeks 0 and 4 and then every 8 weeks (Q8W), or placebo (with crossover to guselkumab Q4W at week 24). Least squares mean change from baseline in Work Productivity and Activity Impairment Questionnaire for PsA (WPAI-PsA) domains and employment were assessed by treatment group. Multivariate analysis of data from weeks 0 through 24 assessed independent associations between PsA clinical features and WPAI-PsA domains.RESULTS: In total, 738 patients were evaluated (guselkumab Q4W n = 245; guselkumab Q8W n = 248; placebo n = 245). At week 24, improvements (reduced impairment) in presenteeism (Q4W -20.1%, Q8W -19.6%, placebo -10.5%), work productivity (Q4W -20.1%, Q8W -19.2%, placebo -10.6%), and nonwork activity (Q4W -20.5%, Q8W -21.2%, placebo -9.9%) were greater in guselkumab-treated versus placebo-treated patients. At week 52, following placebo crossover at week 24, improvements were similar among groups. Baseline absenteeism was minimal and did not change in any group. By week 52, 23.1-25.9% of guselkumab-treated patients who were unemployed at baseline were employed. All WPAI-PsA domains were positively associated with C-reactive protein level, fatigue, and pain. All domains except absenteeism were positively associated with enthesitis and Psoriasis Area and Severity Index score. Age was negatively associated with presenteeism and work productivity loss, female sex and tender joint count were positively associated with nonwork activity impairment, and dactylitis was positively associated with presenteeism.CONCLUSION: Both guselkumab regimens reduced work productivity loss and nonwork activity impairment in patients with active PsA. Association of work productivity loss and nonwork activity impairment with PsA joint and skin features suggests that improvement in both features is beneficial for optimizing improved work productivity loss and nonwork activity impairment.TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03158285.

Aim: Estimate the cost-per-remitter with esketamine nasal spray plus an oral antidepressant (ESK + oral AD) versus oral AD plus nasal placebo (oral AD + PBO) among patients with treatment-resistant depression. Patients & methods: An Excel-based model was developed to estimate the cost-per-remitter for ESK + oral AD versus oral AD + PBO over 52 weeks from multiple US payer perspectives. Clinical end points and cost inputs were derived from clinical trials and the literature, respectively. Results: Under the base-case scenario, the cost-per-remitter for ESK + oral AD and oral AD + PBO were as follows: Commercial: US$85,808 versus US$100,198; Medicaid: US$76,236 versus US$96,067; Veteran’s Affairs: US$77,765 versus US$104,519; and Integrated Delivery Network: US$103,924 versus US$142,766. Conclusion: The findings suggest that ESK + oral AD is a cost-efficient alternative treatment for treatment-resistant depression compared with oral AD + PBO.

Objectives To evaluate the efficacy of guselkumab for the treatment of active PsA utilizing composite indices. Methods Data were pooled from the phase 3 DISCOVER-1 (n = 381) and DISCOVER-2 (n = 739) studies. In both studies, patients were randomized 1:1:1 to subcutaneous guselkumab 100 mg every 4 weeks (Q4W); guselkumab 100 mg at week 0, week 4, then Q8W; or placebo Q4W with crossover to guselkumab 100 mg Q4W at week 24. Composite indices used to assess efficacy through week 52 included Disease Activity Index for Psoriatic Arthritis (DAPSA), Psoriatic Arthritis Disease Activity Score (PASDAS), minimal disease activity (MDA), and very low disease activity (VLDA). Through week 24, treatment failure rules were applied. Through week 52, non-responder imputation was used for missing data. Results Greater proportions of guselkumab- than placebo-treated patients achieved DAPSA low disease activity (LDA) and remission, PASDAS LDA and VLDA, MDA, and VLDA at week 24 vs placebo (all unadjusted P Conclusion Treatment with guselkumab provided robust and sustained benefits across multiple PsA domains through 1 year, indicating that guselkumab is an effective therapy for the diverse manifestations of PsA. Trial registration NCT03162796; NCT03158285

The phase 3 DISCOVER-2 trial evaluated the effect of guselkumab on impaired work productivity and nonwork activity in biologic-naïve patients with psoriatic arthritis (PsA).Adults with active PsA were randomized (1:1:1) to guselkumab 100 mg every 4 weeks (Q4W), guselkumab 100 mg at weeks 0 and 4 and then every 8 weeks (Q8W), or placebo (with crossover to guselkumab Q4W at week 24). Least squares mean change from baseline in Work Productivity and Activity Impairment Questionnaire for PsA (WPAI-PsA) domains and employment were assessed by treatment group. Multivariate analysis of data from weeks 0 through 24 assessed independent associations between PsA clinical features and WPAI-PsA domains.In total, 738 patients were evaluated (guselkumab Q4W n = 245; guselkumab Q8W n = 248; placebo n = 245). At week 24, improvements (reduced impairment) in presenteeism (Q4W -20.1%, Q8W -19.6%, placebo -10.5%), work productivity (Q4W -20.1%, Q8W -19.2%, placebo -10.6%), and nonwork activity (Q4W -20.5%, Q8W -21.2%, placebo -9.9%) were greater in guselkumab-treated versus placebo-treated patients. At week 52, following placebo crossover at week 24, improvements were similar among groups. Baseline absenteeism was minimal and did not change in any group. By week 52, 23.1-25.9% of guselkumab-treated patients who were unemployed at baseline were employed. All WPAI-PsA domains were positively associated with C-reactive protein level, fatigue, and pain. All domains except absenteeism were positively associated with enthesitis and Psoriasis Area and Severity Index score. Age was negatively associated with presenteeism and work productivity loss, female sex and tender joint count were positively associated with nonwork activity impairment, and dactylitis was positively associated with presenteeism.Both guselkumab regimens reduced work productivity loss and nonwork activity impairment in patients with active PsA. Association of work productivity loss and nonwork activity impairment with PsA joint and skin features suggests that improvement in both features is beneficial for optimizing improved work productivity loss and nonwork activity impairment.ClinicalTrials.gov identifier, NCT03158285.

Background/Aims Guselkumab (GUS), a human monoclonal antibody targeting the interleukin-23p19-subunit, has demonstrated efficacy at Week 24 (W24) in the Phase IIIb COSMOS clinical trial of patients with active psoriatic arthritis (PsA) and inadequate response or intolerance to one or two tumour necrosis factor inhibitors (TNFis). This post hoc analysis aimed to identify predictors of minimal disease activity (MDA) with GUS at W24 in this population. Methods Multiple logistic regression analysis was performed to identify potential predictors of MDA with GUS at W24 in TNFi-refractory patients with PsA; odds ratios, 95% confidence intervals and p-values were calculated. Baseline characteristics assessed as predictors included sex, body mass index (BMI), C-reactive protein (CRP), other medication use and disease duration; clinical features included tender and swollen joint counts (TJC/SJC), affected joint location, dactylitis, enthesitis, spondylitis, Psoriasis Area Severity Index (PASI) score and psoriasis (PsO) localisation (Table). Missing data for MDA at W24 were imputed as non-response; missing baseline values were imputed for two patients. Results Patients (n = 187; female, 54.6%; mean disease duration, 8.3 years) had mean TJC 0-68 and SJC 0-66 of 21.0 and 10.3, respectively, mean PASI score of 11.6, and mean BMI of 28.9; 67.9% had enthesitis and 35.8% had dactylitis at baseline. One prior TNFi had been received by 88.2% of patients, with two received by 11.8%. At W24, 17.1% (32/187) of patients achieved MDA. Wrist involvement (p = 0.031) and scalp PsO (p = 0.049) were positive predictors of MDA. Women were significantly less likely to achieve MDA vs. men; other negative predictors included hand small joints or shoulder involvement and hand/foot PsO (all p < 0.05). Age, BMI, CRP, TJC/SJC, HAQ-DI, PASI, spondylitis, enthesitis, dactylitis, other medication and number of prior TNFis were not predictive of MDA (Table). Conclusion Baseline characteristics and clinical features may be positively (wrist involvement, scalp PsO) or negatively (female sex, hand small joints or shoulder involvement, hand/foot PsO) associated with achieving MDA with GUS at W24 in a TNFi-refractory population. Though the low patient number limits the generalisability of this analysis, assessment of Week 48 data may further elucidate potential predictors of MDA after longer-term treatment. Disclosure W. Tillett: Other; William Tillett has received research grants and consulting or speaker fees from AbbVie, Amgen, Celgene, Eli Lilly, Janssen, MSD, Novartis, Pfizer and UCB. S. Ohrndorf: Other; Sarah Ohrndorf has received fees from AbbVie, BMS, Janssen, Novartis and Pfizer. J. Ramírez: Other; Julio Ramírez has received consulting or speaker fees from AbbVie, Amgen, Eli Lilly, Janssen, Novartis and UCB. M. Neuhold: Other; Marlies Neuhold is an employee of Janssen and owns stocks in Johnson & Johnson. R. Wapenaar: Other; Robert Wapenaar is an employee of Janssen and owns stocks in Johnson & Johnson. E. Theander: Other; Elke Theander is an employee of Janssen and owns stocks in Johnson & Johnson. C. Contre: Other; Christine Contre is an employee of Janssen and owns stocks in Johnson & Johnson. M. Sharaf: Other; Mohamed Sharaf is an employee of Janssen and owns stocks in Johnson & Johnson. M. Shawi: Other; May Shawi is an employee of Janssen and owns stocks in Johnson & Johnson. M. Vis: Other; Marijn Vis has received research grants and consulting or speaker fees from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, UCB and the Dutch Arthritis Foundation.

Carmela Benson,1 David Singer,2 Colleen M Carpinella,3 May Shawi,4 Larry Alphs4 1Real-World Value & Evidence, Janssen Scientific Affairs, LLC, Titusville, NJ, USA; 2Jefferson College of Population Health, Thomas Jefferson University, Philadelphia, PA, USA; 3Real-World Evidence Health Division, Kantar Health, San Mateo, CA, USA; 4Neuroscience Medical Affairs, Janssen Scientific Affairs, LLC, Titusville, NJ, USACorrespondence: Carmela Benson Director, Real-World Value & Evidence, Janssen Scientific Affairs, LLC, 1125 Trenton-Harbourton Road, Titusville, NJ 08560, USAEmail CBenson5@its.jnj.comBackground: Suicidal ideation (SI) is a cardinal aspect of major depressive disorder (MDD); however, patient-reported outcomes data from large-scale surveys are limited concerning SI in the context of MDD. This study aims to understand the association between varying levels of SI and health-related quality of life (HRQoL), work productivity, healthcare resource utilization (HRU), and associated costs in patients with moderately severe/severe MDD.Methods: This was a retrospective, cross-sectional analysis of 2013 national survey data. Patients who self-reported moderately severe or severe MDD and completed the Short Form Survey Version 2 (SF-36v2), Work Productivity Loss and Activity Impairment questionnaire (WPAI), and questions related to HRU were analyzed. Direct and indirect costs were calculated. Patients were categorized and analyzed by the level of SI (no SI, low, moderate, and high) based on their response to Item 9 of the Patient Health Questionnaire-9.Results: Among 75,000 respondents, 15.3% self-reported receiving a physician diagnosis of moderately severe or severe MDD and 2.8% of the total sample endorsed some level of SI. Patients with high SI showed a higher burden than patients with no SI, reporting lower mean SF-36v2 mental component summary scores (p< 0.001), higher work productivity loss (p=0.039), and higher numbers of per patient per month hospitalizations (p=0.002) and emergency room visits (p=0.011). High SI was associated with greater per patient per month direct costs ($1220 vs $796; p=0.002) and indirect costs ($1449 vs $1058; p=0.001) compared with no SI. When patients with low or moderate SI were compared with patients with no SI, the results were mixed.Conclusion: Higher levels of SI were associated with lower HRQoL, greater HRU, and more work impairment resulting in higher direct and indirect costs compared with patients with MDD but no SI. These results highlight the need to implement effective treatment models and interventions in the employed population.Keywords: major depression, suicidal ideation, economic burden, health-related quality of life

ObjectiveEvaluate relationship between radiographic progression and clinical outcomes in post hoc analyses of patients with psoriatic arthritis (PsA) receiving up to 2 years of guselkumab therapy in the phase 3, placebo-controlled, randomised trial, DISCOVER-2.MethodsBiologic-naïve adults with active PsA (≥5 swollen joints /≥5 tender joints ; C reactive protein ≥0.6 mg/dL) were randomised to guselkumab 100 mg every 4 weeks (Q4W); guselkumab 100 mg at week 0, week 4, then every 8 weeks (Q8W); or placebo→guselkumab 100 mg Q4W (week 24). Radiographs (hands/feet) at week 0, week 24, week 52 and week 100 were scored via PsA-modified van der Heijde-Sharp (vdH-S) methodology. In these post hoc analyses, mean changes in vdH-S scores were summarised according to achievement of American College of Rheumatology 20/50/70 response; low disease activity (LDA) defined by Disease Activity in Psoriatic Arthritis (DAPSA) ≤14 or Psoriatic ArthritiS Disease Activity Score (PASDAS) ≤3.2, or minimal/very low disease activity (MDA/VLDA); and normalised physical function (Health Assessment Questionnaire-Disability Index (HAQ-DI) ≤0.5). Response rates for achieving MDA/VLDA and each component were determined among patients with and without radiographic progression (change in total vdH-S score >0.5). No formal hypothesis testing was performed.Results664 of 739 treated patients in DISCOVER-2 continued study treatment at week 52 and were included in these analyses. Mean changes in vdH-S scores from weeks 0 to 100 among all patients in the Q4W and Q8W groups were 1.7 and 1.5, respectively. Among all guselkumab-randomised patients, those who achieved ACR20/50/70, DAPSA LDA, PASDAS LDA, MDA, VLDA and HAQ-DI ≤0.5 (normalised physical function) had smaller mean changes in vdH-S scores than did non-responders at week 52 (0.2–1.2 vs 1.7–4.1) and week 100 (0.3–1.2 vs 2.0–4.6). Relative to patients with radiographic progression, those without progression were more likely to achieve the MDA criteria related to swollen and tender joint counts, patient-reported pain and global assessment, and normalised physical function through week 100.ConclusionIn these post hoc analyses, the achievement of low levels of disease activity, including MDA, was associated with diminished rates of radiographic progression observed in patients receiving up to 2 years of guselkumab. Radiographic non-progressors were more likely to achieve patient-reported MDA criteria of minimal pain and normalised physical function compared with radiographic non-responders.Trial registration numberNCT03158285.

ObjectivesTo evaluate the efficacy through 52 weeks of guselkumab, an interleukin 23-p19 subunit inhibitor, in subgroups of pooled psoriatic arthritis (PsA) patients from the DISCOVER-1 and DISCOVER-2 trials defined by baseline patient characteristics.MethodsAdults with active PsA despite standard therapies were enrolled in DISCOVER-1 (≥3 swollen and ≥3 tender joints, C reactive protein (CRP) level ≥0.3 mg/dL) and DISCOVER-2 (≥5 swollen and ≥5 tender joints, CRP ≥0.6 mg/dL, biological-naïve). Randomised patients received 100 mg guselkumab at weeks 0, 4, and then every 4 or 8 weeks (Q4W/Q8W) or placebo. Guselkumab effects on joint (ACR20/50/70), skin (IGA 0/1, IGA 0), patient-reported outcome (Health Assessment Questionnaire Disability Index/Functional Assessment of Chronic Illness Therapy-Fatigue) and disease severity (minimal disease activity/PsA Disease Activity Score low disease activity) endpoints were evaluated by patient sex, body mass index, PsA duration, swollen/tender joint counts, CRP level, percent body surface area with psoriasis, Psoriasis Area and Severity Index score, and conventional synthetic disease-modifying antirheumatic drug use at baseline.ResultsBaseline patients characteristics in DISCOVER-1 (N=381) and DISCOVER-2 (N=739) were well balanced across randomised groups. At week 24, 62% (232/373) and 60% (225/375), respectively, of guselkumab Q4W-treated and Q8W-treated patients pooled across DISCOVER-1 and DISCOVER-2 achieved the primary endpoint of ACR20 response versus 29% (109/372) of placebo-treated patients. Guselkumab treatment effect at week 24 was observed across patient subgroups. Within each patient subgroup, response rates across all disease domains were sustained or increased at week 52 with both guselkumab regimens.ConclusionsGuselkumab Q4W and Q8W resulted in robust and sustained improvements in PsA signs and symptoms consistently in subgroups of patients defined by diverse baseline characteristics.Trial registration numbersNCT03162796, NCT03158285.

Background Guselkumab was efficacious in reducing signs and symptoms of psoriatic arthritis in the phase 3 DISCOVER-1 and DISCOVER-2 studies. We aimed to evaluate the efficacy of guselkumab in post-hoc analyses of patients with psoriatic arthritis with imaging-confirmed sacroiliitis consistent with axial involvement. Methods In DISCOVER-1, 381 patients with active psoriatic arthritis (defined as 03 swollen joints, 03 tender joints, and C-reactive protein [CRP] 00middot3 mg/dL) and in DISCOVER-2, 739 patients with active psoriatic arthritis (defined as 05 swollen joints, 05 tender joints, and CRP 00middot6 mg/dL) were randomly allocated to receive guselkumab 100 mg every 4 weeks, guselkumab 100 mg every 8 weeks (week 0, week 4, then every 8 weeks), or placebo. These pooled, post-hoc analyses included patients with axial disease documented by previous imaging or pelvic radiography at screening consistent with sacroiliitis (confirmed by investigator). Efficacy assessments included least squares mean changes, with 95% CIs, in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score, modified BASDAI (mBASDAI; excluding peripheral joint pain), spinal pain, and Ankylosing Spondylitis Disease Activity Score (ASDAS), and proportions of patients achieving at least a 50% improvement in BASDAI score (BASDAI50) and achieving ASDAS responses of inactive disease (score

To assess long-term efficacy and safety of guselkumab, an interleukin-23 p19 subunit (IL-23p19) inhibitor, in patients with active psoriatic arthritis (PsA) from the phase III DISCOVER-2 trial.In the DISCOVER-2 trial, patients with active PsA (≥5 swollen joints and ≥5 tender joints; C-reactive protein level ≥0.6 mg/dl) despite prior nonbiologic therapy were randomized to receive the following: guselkumab 100 mg every 4 weeks; guselkumab 100 mg at weeks 0 and 4 and then every 8 weeks; or placebo with crossover to guselkumab 100 mg every 4 weeks, beginning at week 24. Efficacy assessments included American College of Rheumatology ≥20%/50%/70% improvement criteria (ACR20/50/70), Investigator's Global Assessment (IGA) of psoriasis score of 0 (indicating complete skin clearance), resolution of enthesitis (Leeds Enthesitis Index) and dactylitis (Dactylitis Severity Score), and changes in the Sharp/van der Heijde modified radiographic scores for PsA. Clinical data (imputed as no response/no change from baseline if missing) and observed radiographic data were summarized through week 100; safety assessments continued through week 112.Of the 739 randomized and treated patients, 652 (88%) completed treatment through week 100. Across groups of guselkumab-treated patients (including those in the placebo-guselkumab crossover group), the following findings at week 100 indicated that amelioration of arthritis signs/symptoms and extraarticular manifestations was durable through 2 years: ACR20 response (68-76%), ACR50 response (48-56%), ACR70 response (30-36%), IGA score of 0 (55-67%), enthesitis resolution (62-70%), and dactylitis resolution (72-83%). Mean changes in the Sharp/van der Heijde modified score for PsA from weeks 52 to week 100 (range 0.13-0.75) indicated that the low rates of radiographic progression observed among guselkumab-treated patients at earlier time points extended through week 100. Through week 112, 8% (5.8 per 100 patient-years) and 3% (1.9 per 100 patient-years) of the 731 guselkumab-treated patients had a serious adverse event or serious infection, respectively; 1 death occurred (road traffic accident).In biologic-naive PsA patients, guselkumab provided durable improvements in multiple disease domains with no unexpected safety findings through 2 years.

BackgroundThe interleukin-23p19-subunit inhibitor guselkumab effectively treats signs and symptoms of psoriatic arthritis (PsA). We evaluated the effect of guselkumab on fatigue.MethodsAcross two phase 3 trials of guselkumab (DISCOVER-1, DISCOVER-2), patients with active PsA despite standard therapy were randomized to subcutaneous injections of guselkumab 100 mg every 4 weeks (Q4W,N= 373); guselkumab 100 mg at week 0, week 4, and then Q8W (N= 375); or placebo (N= 372) through week 24, after which patients in the placebo group crossed over to guselkumab Q4W. Fatigue was measured as a secondary endpoint using the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue instrument (range 0–52, higher scores indicate less fatigue). Least-squares mean changes in FACIT-Fatigue scores were compared between treatments using a mixed-effect model for repeated measures. Mediation analysis was used to adjust for indirect effects on fatigue deriving from improvement in other outcomes, including ≥20% improvement in American College of Rheumatology criteria (ACR20; prespecified), minimal disease activity (MDA; post hoc), or C-reactive protein (CRP; post hoc).ResultsBaseline mean (SD) FACIT-Fatigue scores in DISCOVER-1 (N= 381) and DISCOVER-2 (N= 739), ranging from 29.1 (9.5) to 31.4 (10.1), indicated substantial levels of fatigue relative to the United States general population (43.6 [9.4]). Across studies, mean improvements, and proportions of patients with ≥4-point improvements, in FACIT-Fatigue scores at week 24 with guselkumab Q4W and Q8W (5.6–7.6 and 54–63%, respectively) were larger vs placebo (2.2–3.6 and 35–46%). Improvement in FACIT-Fatigue scores with guselkumab was sustained from week 24 to week 52, with moderate-to-large effect sizes (Cohen’sd= 0.52–0.81 at week 24; 0.66–0.91 at week 52). Mediation analyses demonstrated that substantial proportions of the effects of guselkumab vs placebo on fatigue were direct effect, after adjusting for achievement of ACR20 (Q4W 69–70%, Q8W 12–36% direct effect) or MDA (72–92% across dosing regimens) response or for change in serum CRP concentrations (82–88% across dosing regimens).ConclusionsIn patients with active PsA, guselkumab 100 mg Q4W or Q8W led to clinically meaningful and sustained improvements in fatigue through 1 year. A substantial portion of the improvement in FACIT-Fatigue scores induced by guselkumab was independent of effects on the achievement of other select outcomes.Trial registrationName of the registry: ClinicalTrials.govTrial registrations: DISCOVER-1, NCT03162796; DISCOVER-2, NCT03158285Date of registration: DISCOVER-1, May 22, 2017; DISCOVER-2, May 18, 2017URLs of the trial registry record:DISCOVER-1,https://clinicaltrials.gov/ct2/show/NCT03162796?term=NCT03162796&draw=1&rank=1DISCOVER-2,https://clinicaltrials.gov/ct2/show/NCT03158285?term=NCT03158285&draw=2&rank=1

Objective To further characterize the effect of guselkumab, a selective IL-23p19-subunit inhibitor approved for PsA, on enthesitis and assess relationships between enthesitis resolution and patient status/outcomes. Methods Adults with active PsA despite standard therapies in the phase 3 DISCOVER-1 and DISCOVER-2 studies were randomized 1:1:1 to guselkumab 100 mg every 4 weeks (Q4W); guselkumab 100 mg at week 0, week 4, Q8W; or placebo through week 20 followed by guselkumab 100 mg Q4W. Independent assessors evaluated enthesitis using the Leeds Enthesitis Index (LEI; total score 0–6). Enthesitis findings through week 24 were pre-specified to be pooled across studies; post hoc and week 52 analyses also employed pooled data. Results Among 1118 randomized, treated patients in DISCOVER-1 and 2 who had ≥1 LEI site evaluated, 65% had enthesitis at baseline. These patients exhibited numerically more swollen and tender joints, systemic inflammation and impaired physical function than patients without enthesitis. Guselkumab Q4W and Q8W were superior to placebo in resolving pre-existing enthesitis at week 24 (45 and 50% vs 29%; both adjusted P = 0.0301). Enthesitis resolution rates continued to rise; 58% of guselkumab-randomized patients achieved resolution at week 52, including patients with mild (LEI = 1; 70–75%), moderate (LEI = 2; 69–73%) or severe (LEI = 3–6; 42–44%) enthesitis at baseline. Among guselkumab-randomized patients with resolved enthesitis at week 24, 42% achieved minimal disease activity at week 52, vs 17% of patients with unresolved enthesitis. Conclusion Guselkumab resulted in higher proportions of PsA patients with resolved enthesitis by week 24, with maintenance of resolution rates through 1 year. As enthesitis confers greater disease burden, sustained resolution could portend better patient outcomes. Clinical trial registration DISCOVER 1 (NCT03162796) and DISCOVER 2 (NCT03158285)

ObjectiveEvaluation of the efficacy and safety of guselkumab, a human monoclonal antibody targeting the interleukin-23p19 subunit, in patients with psoriatic arthritis (PsA) through 1 year.MethodsAdults who met ClASsification criteria for Psoriatic ARthritis, with active disease (≥3 swollen and ≥3 tender joints; C reactive protein ≥0.3 mg/dL) despite standard treatment (31% previously received ≤2 tumour necrosis factor inhibitors (TNFi)), were randomised (1:1:1) to guselkumab 100 mg every 4 weeks (Q4W); guselkumab 100 mg at Week0, Week4, then Q8W; or placebo with cross-over to guselkumab 100 mg Q4W at Week24 (PBO→Q4W) through Week48. Clinical efficacy through Week52 (employing non-responder imputation) and adverse events (AEs) through Week60 were evaluated.ResultsOf 381 treated patients, 90% completed the study. Numerical increases in the proportions of patients achieving ≥20% improvement in ACR criteria (ACR20) were observed post-Week24, reaching 73% (94/128) and 60% (76/127) for Q4W-randomised and Q8W-randomised patients, respectively, by Week52. Proportions of patients achieving ACR50/ACR70/skin responses and minimal/very low disease activity were maintained, as were improvements in physical function and health-related quality of life, through Week52 in guselkumab-randomised patients. Response to guselkumab was maintained in both TNFi-naïve and TNFi-experienced patients. Serious AEs and serious infections occurred in similar proportions of guselkumab Q4W-randomised (3% and 0%) and Q8W-randomised (6% and 2%) patients through Week60, with no new safety concerns versus observations through Week24. No guselkumab-treated patient and two patients receiving placebo died; no study participant developed opportunistic infection or inflammatory bowel disease.ConclusionGuselkumab provided sustained improvement across multiple clinical manifestations of PsA, maintaining a favourable benefit-risk profile, through 1 year regardless of prior TNFi exposure.

Background:In patients (pts) with psoriatic arthritis (PsA), fatigue is a major driver of perceived impact of disease and has been identified as an important domain to be assessed in clinical trials.1,2 The association between fatigue and other PsA domains (eg, physical function) or clinical response is not well understood.Objectives:Fatigue was measured with the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue questionnaire in the pivotal DISCOVER-1 and DISCOVER-2 Phase 3 studies of guselkumab (GUS) vs placebo (PBO). This post hoc analysis explores the correlation between FACIT-Fatigue and physical function and clinical response in the DISCOVER program.Methods:This analysis used pooled data from pts (N=1120) treated with GUS or PBO. In DISCOVER-1 and DISCOVER-2, 381 pts with active PsA (swollen joint count [SJC] ≥3, tender joint count [TJC] ≥3, C-reactive protein [CRP] ≥0.3 mg/dL) and 739 pts with active PsA (SJC ≥5, TJC ≥5, CRP ≥0.6 mg/dL) and inadequate response to standard therapies, respectively, were randomized 1:1:1 to GUS 100 mg Q4W; GUS 100 mg at W0, W4, then Q8W; or PBO. PBO pts switched to GUS 100 mg Q4W at W24. The FACIT-Fatigue questionnaire has 13 items that assess self-reported fatigue/tiredness over the last 7 days. Items are scored from 0 (very much fatigued) to 4 (not at all fatigued). FACIT-Fatigue response was defined as an increase of ≥4 points from baseline. Physical function was evaluated with the Health Assessment Questionnaire-Disability Index (HAQ-DI). HAQ-DI response was defined as a decrease of ≥0.35 points from baseline. Clinical response was defined as achievement of ≥20% improvement in the American College of Rheumatology (ACR 20) criteria. Relationships between FACIT-Fatigue and HAQ-DI at W8/16/24 were assessed by Pearson correlation coefficients. Mean changes in HAQ-DI scores at W8/16/24 were summarized in FACIT-Fatigue responders and nonresponders. A logistic regression model was applied to estimate odds ratios (ORs) for achievement of HAQ-DI and ACR 20 response by FACIT-Fatigue response status at each visit. A multiple linear regression model was used to evaluate the association between FACIT-Fatigue and HAQ-DI at W24 after adjusting for SJC, TJC, CRP, and pt assessment of pain.Results:FACIT-Fatigue and HAQ-DI scores and changes from baseline were negatively correlated at W8, W16, and W24 (Table 1). Mean changes in HAQ-DI were −0.31, −0.43, and −0.48 at W8, W16, and W24, respectively, in FACIT-Fatigue responders and −0.06, −0.07, and −0.09, respectively, in FACIT-Fatigue nonresponders. FACIT-Fatigue responders were significantly more likely than nonresponders to achieve HAQ-DI and ACR 20 response (OR [95% CI] at W8, 2.8 [2.2-3.7] and 2.4 [1.9-3.1]; at W16, 3.6 [2.8-4.7] and 2.9 [2.3-3.7]; and at W24, 4.4 [3.4-5.7] and 3.2 [2.5-4.2], respectively; Figure 1). Correlations between FACIT-Fatigue and HAQ-DI remained significant after adjusting for SJC, TJC, CRP, and pt assessment of pain.Conclusion:In pts with PsA, fatigue response is a clinically meaningful predictor of improvements in physical function and achievement of ACR 20 response, reinforcing the importance of assessing fatigue in PsA disease management.References:[1]Leung YY et al. J Rheumatol. 2020;96:46-9.[2]Gudu T et al. Joint Bone Spine. 2016;83:439-43.Table 1.Correlation* of FACIT-Fatigue and HAQ-DIVisitHAQ-DI and FACIT Fatigue ScoresChanges From Baseline in HAQ-DI and FACIT-Fatigue ScoresW8−0.61 (p−0.42 (pW16−0.60 (p−0.47 (pW24−0.62 (p−0.50 (p*Determined by Pearson correlation coefficient; p-values derived from hypothesis tests of correlation ρ=0 (ie, no correlation).Figure 1Disclosure of Interests:Arthur Kavanaugh Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Genentech, Janssen, Eli Lilly, Merck, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Genentech, Janssen, Eli Lilly, Merck, Novartis, Pfizer and UCB, Yan Liu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Atul Deodhar Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, GSK, Janssen, Novartis, Pfizer, UCB, Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB, Philip J Mease Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, SUN, and UCB; and personal fees from Boehringer Ingelheim and GlaxoSmithKline, Philip Helliwell Consultant of: Galapagos, Janssen, Novartis, Grant/research support from: Abbvie, Janssen, Pfizer, Laure Gossec Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Biogen, Celgene, Gilead, Janssen, Eli Lilly, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis, UCB, Grant/research support from: Amgen, Galapagos, Janssen, Eli Lilly, Pfizer, Sandoz, Sanofi, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Elizabeth C Hsia Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, Chenglong Han Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Proton Rahman Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Grant/research support from: Janssen and Novartis.

Background:In the Phase 3 DISCOVER-11 & DISCOVER-22 trials, guselkumab (GUS), a human monoclonal antibody targeting the IL-23p19-subunit, was effective in psoriatic arthritis (PsA) across joint & skin endpoints. At Week 24 (W24), GUS benefit was consistent regardless of baseline (BL) demographic & disease characteristics.3Objectives:We assessed whether GUS efficacy was sustained through W52 in pooled DISCOVER-1 & -2 patients (pts) across select BL subgroups.Methods:Adults with active PsA despite standard therapies were enrolled in DISCOVER-1 (swollen [SJC] ≥3 & tender joint count [TJC] ≥3, C-reactive protein [CRP] ≥0.3 mg/dL) & DISCOVER-2 (SJC ≥5 & TJC ≥5, CRP ≥0.6 mg/dL). 31% of DISCOVER-1 pts had received 1-2 prior tumor necrosis factor inhibitors; DISCOVER-2 pts were biologic naïve. Pts were randomized 1:1:1 to GUS 100 mg every 4 weeks (Q4W); GUS 100 mg at W0, W4, then Q8W; or placebo (PBO). Pts randomized to PBO received GUS 100 mg Q4W starting at W24 & were excluded from these analyses assessing maintenance of effect from W24 to W52. GUS effects on joint (American College of Rheumatology [ACR]20/50/70) & skin (Investigator’s Global Assessment [IGA=0/1 + ≥2-grade reduction from W0] in pts with ≥3% body surface area [BSA] with psoriasis & IGA ≥2 at W0) endpoints were evaluated by pt BL SJC, TJC, conventional synthetic disease-modifying antirheumatic drug (csDMARD) use, body mass index (BMI), PsA duration, & % BSA with psoriasis. Missing data were imputed as nonresponse through W52.Results:BL pt characteristics in DISCOVER-1 (N=381) & DISCOVER-2 (N=739) were well balanced across randomized groups.1,2 Among 1120 pooled pts, mean SJC was 11, mean TJC was 21, & 68% used csDMARDs (primarily methotrexate [MTX]). At W24, 62% (232/373) & 60% (225/375), respectively, of GUS Q4W- & Q8W-treated pts achieved ACR20 vs 29% (109/372) of PBO, with GUS effect consistently observed across pt BL subgroups (Figure 1). ACR20 response rates were sustained or increased at W52 in the GUS Q4W (72%) & Q8W (70%) groups & across SJC (61-79%), TJC (68-76%), & csDMARD use (68-80%) subgroups (Table 1) & pt subgroups defined by BL BMI, PsA duration, & % BSA with psoriasis (data not shown). ACR50 & 70 response patterns were similar to ACR20 (Table 1). In pts with ≥3% BSA psoriasis & IGA ≥2 at BL, 71% (193/273) & 66% (171/258) of GUS Q4W- & Q8W-treated pts, respectively, vs 18% (47/261) of PBO, achieved IGA 0/1 at W24, with GUS effect consistently observed across pt BL subgroups (Figure 1). IGA 0/1 response rates were also sustained or increased at W52 in the GUS Q4W (80%) & Q8W (71%) groups & across % BSA with psoriasis (67-87%) & csDMARD use (68-87%) subgroups (Table 1) & pt subgroups defined by BL BMI and PsA duration (data not shown).Conclusion:Treatment with GUS 100 mg Q4W & Q8W resulted in sustained improvement in signs & symptoms of active PsA through W52 regardless of pt BL characteristics.References:[1]Deodhar A, et al. Lancet 2020;395:1115-25;[2]Mease P, et al. Lancet 2020;395:1126-36;[3]Deodhar A, et al. American College of Rheumatology 2020; Poster P0908.Figure 1Figure 1Table 1.ACR & IGA Responses at Weeks 24 & 52 & by Select BL CharacteristicsGuselkumab Q4WGuselkumab Q8WN=373N=375Week 24Week 52Week 24Week 52ACR20, %62726070 SJC (15)68/59/5379/61/6757/66/6068/68/76 TJC (15)74/67/5673/76/6962/60/6075/68/68 csDMARD use (none/any/MTX)66/60/6380/68/6862/59/5773/68/68ACR50, %34493145 SJC (15)41/32/2058/39/3834/28/2646/40/49 TJC (15)51/41/2458/53/4340/33/2652/46/43 csDMARD use (none/any/MTX)36/33/3553/46/4836/29/2751/42/40ACR70, %16271627 SJC (15)22/10/732/20/2418/10/1930/23/26 TJC (15)29/19/934/32/2227/15/1435/28/24 csDMARD use (none/any/MTX)21/13/1430/26/2721/14/1434/24/23N=273N=258IGA 0/1, %71806671 BSA % with psoriasis(≥3-61/71/8076/87/7962/64/7267/72/74 csDMARD use (none/any/MTX)84/64/6787/77/7872/63/6477/68/68Disclosure of Interests:Christopher T. Ritchlin Consultant of: AbbVie, Amgen, Gilead, Janssen, Eli Lilly, Novartis, Pfizer, and UCB Pharma, Grant/research support from: AbbVie, Amgen, and UCB Pharma, Philip J Mease Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN, and UCB Pharma, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, SUN, and UCB Pharma, Wolf-Henning Boehncke Speakers bureau: AbbVie, Almirall, Celgene, Janssen, Leo, Eli Lilly, Novartis, UCB Pharma, Consultant of: AbbVie, Almirall, Celgene, Janssen, Leo, Eli Lilly, Novartis, UCB Pharma, Grant/research support from: Pfizer, John Tesser Speakers bureau: AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Crescendo Biosciences/Myriad, GlaxoSmithKline, Genentech, Janssen, Eli Lilly, and Pfizer, Consultant of: AbbVie, AstraZeneca, Bristol Myers Squibb, Gilead, Janssen, Eli Lilly, Novartis, and Pfizer, Grant/research support from: AbbVie, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Horizon, Janssen, Eli Lilly, Merck KG, Novartis, Pfizer, Sandoz, Sun Pharma, Setpoint, and UCB Pharma, Elena Schiopu Consultant of: Janssen, Grant/research support from: Janssen, Soumya D Chakravarty Shareholder of: Johnson & Johnson, of which Janssen Research & Development is a wholly owned subsidiary, Employee of: Janssen Scientific Affairs, LLC, Alexa Kollmeier Shareholder of: Johnson & Johnson, of which Janssen Research & Development is a wholly owned subsidiary, Employee of: Janssen Research & Development, LLC, Elizabeth C Hsia Shareholder of: Johnson & Johnson, of which Janssen Research & Development is a wholly owned subsidiary, Employee of: Janssen Research & Development, LLC, Xie L Xu Shareholder of: Johnson & Johnson, of which Janssen Research & Development is a wholly owned subsidiary, Employee of: Janssen Research & Development, LLC, May Shawi Shareholder of: Johnson & Johnson, of which Janssen Research & Development is a wholly owned subsidiary, Employee of: Janssen Global Services, LLC, Yusang Jiang Employee of: Cytel, Inc., providing statistical support (funded by Janssen), Shihong Sheng Shareholder of: Johnson & Johnson, of which Janssen Research & Development is a wholly owned subsidiary, Employee of: Janssen Research & Development, LLC, Joseph F. Merola Consultant of: AbbVie, Arena, Biogen, Bristol Myers Squibb, Dermavant, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, and UCB Pharma, Iain McInnes Consultant of: AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB Pharma, Grant/research support from: Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, and UCB Pharma, Atul Deodhar Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, UCB Pharma, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, GlaxoSmithKline, Janssen, Novartis, Pfizer, UCB Pharma, Grant/research support from: AbbVie, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer, UCB Pharma.

Background:Guselkumab (GUS), a selective monoclonal antibody targeting the interleukin-23p19 subunit, has demonstrated efficacy in 2 pivotal Ph3 psoriatic arthritis (PsA) studies (DISCOVER-1,1 DISCOVER-22).Objectives:Evaluate GUS efficacy and safety in PsA patients (pts) with inadequate response (IR) to tumor-necrosis-factor inhibition (TNFi) through Week24 (W24) of the Ph3b COSMOS study.Methods:In this randomized, double-blind, placebo (PBO)-controlled trial, 285 pts with active PsA (≥3 swollen & ≥3 tender joints) who demonstrated lack of benefit or intolerance to 1-2 TNFi were randomized 2:1 to subcutaneous GUS 100mg (n=189) or PBO (n=96) at W0, W4, then every 8 weeks (Q8W) through W44 (with PBO crossover to GUS at W24). At W16, pts who met early escape (EE) criteria (Results:Baseline characteristics were similar across GUS and PBO pts, though a higher proportion of females and more severe joint symptoms were seen in the GUS group. At W24, 44.4% of GUS vs 19.8% of PBO pts achieved ACR20 (pTable 1.Baseline characteristics of, and adverse events reported by, randomized and treated COSMOS ptsGUS 100 mg Q8W (N=189)PBO (N=96) Age, y4949 Sex, Female54%46% Duration of PsA, y8.38.7 Body mass index, kg/m22931a Swollen (0-66) / tender (0-68) joint count10 / 219 / 18 Pt pain / Pt global arthritis / Physician global disease, 0-10 cm VAS6.5 / 6.5 / 6.96.0 / 6.2 / 6.4 Health Assessment Questionnaire-Disability Index, 0-31.3b1.2 C-reactive protein, mg/dL1.2b1.2 Methotrexate use at baseline56%53% Psoriatic body surface area, %17.913.4 Number of prior TNFi: 1 / 288% / 12%89% / 11% Reason for prior TNFi discontinuation: Efficacy / Safety84% / 16%* 81% / 19%*Pts with ≥1 AE / SAE37% / 3%48% / 3%Pts with ≥1 infection / serious infection18% / 0%20% / 0%Pts with ≥1 AE leading to study agent discontinuation2%2%Pts with ≥1 malignancy0.4%0Pts with ≥1 injection-site reaction2%1%Data shown are mean or %. aN=95; bN=188. *Missing for 1 pt. SAE – serious adverse events; VAS – visual analog scaleConclusion:In this Ph3b, placebo-controlled study of PsA pts with IR to 1-2 TNFi, GUS 100 mg Q8W elicited a significantly higher ACR20 response rate vs. PBO at W24; results of prespecified sensitivity and subgroup analyses were consistent. GUS safety in TNF-IR PsA pts through W24 is consistent with the favorable GUS safety profile in psoriasis and biologic-naïve PsA pts.3References:[1]Deodhar A. Lancet 2018;391: 2213–24.[2]Mease PJ. Lancet 2020;395: 1126–36.[3]Guselkumab Prescribing Information. Janssen Biotech, Inc.Disclosure of Interests:Laura C Coates Consultant of: AbbVie, Amgen, Biogen, BMS, Boehringer Ingelehim, Celgene, Domain, Eli Lilly, Gilead, Janssen, Medac, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Gilead, Novartis, Pfizer, Laure Gossec Consultant of: AbbVie, Amgen, BMS, Biogen, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis, UCB, Grant/research support from: Amgen, Eli Lilly, Galapagos, Janssen, Pfizer, Sandoz, Sanofi, Elke Theander Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC, Paul Bergmans Shareholder of: Johnson & Johnson, Employee of: Janssen, Marlies Neuhold Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC, Chetan Karyekar Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, Wim Noel Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC, Georg Schett: None declared, Iain McInnes Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, and UCB

Background:Guselkumab (GUS), an anti-interleukin-23p19-subunit monoclonal antibody, demonstrated efficacy vs placebo (PBO) in achieving American College of Rheumatology 20% improvement (ACR20) response in patients (pts) with active psoriatic arthritis (PsA) in two phase 3 trials, DISCOVER-1 & 2.1,2Objectives:To assess the differential treatment effects of GUS across individual components of ACR response in PsA pts participating in the DISCOVER-1 & 2 trials.Methods:In DISCOVER-1 & 2, 1120 pts were randomized & treated with GUS 100 mg every 4 weeks (Q4W; N=373); GUS 100 mg at Week (W)0 and W4, then Q8W (N=375); or matching PBO (N=372). Pts were evaluated by independent joint assessors at study visits. ACR20 response is defined as ≥20% improvement from baseline in both tender joint count (0-68 [TJC68]) and swollen joint count (0-66 [SJC66]) and ≥20% improvement from baseline in ≥3 of 5 assessments: Patient Assessment of Pain [Pt Pain], Patient Assessment of Global Disease Activity (arthritis) [PtGA], Physician Assessment of Global Disease Activity [PGA], Patient assessment of physical function as measured by Disability Index of the Health Assessment Questionnaire (HAQ-DI), and C-reactive protein (CRP). For each ACR component, achievement of ≥20% improvement from baseline was assessed over time through W24 for the combined (Q4W+Q8W) GUS groups, and median time to onset of treatment effect was determined with Kaplan-Meier curves by randomized group.Results:Median time to response for all components except SJC66 occurred earlier with GUS than PBO. Time to onset of ACR20 treatment effect is shown in Figure 1. CRP data show 56% of GUS-treated pts had diminution of systemic inflammation by W4 (Table 1). Reduction in systemic inflammation was accompanied or rapidly followed by GUS-related improvement in both PtGA and PGA (median W4-8). Although SJC66/TJC68 data showed similar patterns, there was also a high PBO response (data not shown). Consistent with early reductions in systemic inflammation, 48-61% of GUS-treated pts had ≥20% improvement in TJC68/SJC66/PGA at W4 (Table 1), and 45-48% had ≥20% improvement in HAQ-DI, PtGA, and Pt Pain by W8. By W24, >80% of GUS-treated pts had ≥20% improvement in SJC66/TJC68/PGA, followed by 63-64% with this degree of improvement in PtGA, CRP, and Pt Pain, and 57% for HAQ-DI.Conclusion:GUS demonstrated ACR20 improvements with separation from PBO in ACR components as early as W4, which is consistent with reduced inflammation by GUS and prior serological studies.3 At early study time points, both pts and physicians were able to discern improvements in signs and symptoms of arthritis that rapidly followed reductions in systemic inflammation (CRP). The predominant drivers of ACR20 response rates at W24 in GUS pts were SJC66/TJC68/PGA.References:[1]Deodhar A et al. Lancet. 2020;395:1115-25[2]Mease P et al. Lancet. 2020;395:1126-36[3]Siebert S et al. EULAR 2020. Presentation OP0229Table 1.W4W8W12W16W20W24ACR20203950566061HAQ-DI score364552545657SJC66617484868788TJC68486575798081PGA506774788181PtGA354858596264Pt Pain324855586163CRP566062636464Figure 1Disclosure of Interests:Peter Nash Consultant of: AbbVie, Bristol Myers Squibb, Boehringer, Celgene, Gilead, Eli Lilly, Janssen, Novartis, Pfizer, Roche, Sandoz, Sun, Grant/research support from: AbbVie, Bristol Myers Squibb, Boehringer, Celgene, Gilead, Eli Lilly, Janssen, Novartis, Pfizer, Roche, Sandoz, Sun, Iain McInnes Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, Christopher T. Ritchlin Consultant of: AbbVie, Amgen, Janssen, Eli Lilly, Gilead, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, and UCB, Wen-Chan Tsai Consultant of: AbbVie, Eli Lilly, Janssen, Pfizer, and Novartis, Ying Ying Leung Consultant of: Abbvie, Eli Lilly, Janssen, and Novartis, Lai-Shan Tam Consultant of: AbbVie, Boehringer Ingelheim, Janssen, Lilly, Pfizer, and Sanofi, Grant/research support from: Amgen, Boehringer Ingelheim, Janssen, GSK, Novartis, and Pfizer, Daniel Furtner Employee of: Janssen, a division of Johnson & Johnson Pte. Ltd., May Shawi Employee of: Janssen Research and Development, LLC, Stephen Xu Employee of: Janssen Research and Development LLC, Shihong Sheng Employee of: Janssen Research and Development, LLC, Alexa Kollmeier Employee of: Janssen Research and Development, LLC, Atul Deodhar Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, GlaxoSmithKline, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer, and UCB.

Background:Psoriatic arthritis (PsA), a chronic inflammatory disease characterized by peripheral arthritis, axial inflammation, dactylitis, enthesitis & skin/nail psoriasis, causes impaired physical function, disability & loss of work productivity.Objectives:Evaluate associations between PsA clinical characteristics & outcomes including fatigue & work productivity using Work Productivity & Activity Impairment Questionnaire: PsA (WPAI-PsA).Methods:The Phase 3 DISCOVER-2 trial assessed guselkumab (GUS), an anti-IL-23p19 subunit monoclonal antibody, in bio-naïve adults with active PsA (swollen joint count [SJC] ≥5 & tender joint count [TJC] ≥5, C-reactive protein [CRP] ≥0.6 mg/dL) despite standard therapies.1 Patients (Pts) were randomized 1:1:1 to GUS 100 mg Q4W; GUS 100 mg at W0, W4, then Q8W; or placebo (PBO). WPAI-PsA assesses PsA-related work time missed (absenteeism), impairment while working (presenteeism), productivity loss (absenteeism+presenteeism), & daily activity during the previous week. Spearman correlation testing evaluated relationships between pt demographics & disease characteristics of PsA & WPAI domain scores based on observed values at baseline. Univariate linear regression assessed associations between WPAI & these variables based on observed data at W0 & at W24. Variables with pResults:As reported elsewhere,2 least-squares mean % changes from baseline at W24 were -3.8/-19.5/-20.0/-20.5 for GUS Q4W, -3.1/-19.4/-19.7/-21.5 for GUS Q8W, & -3.5/-10.2/-10.9/-10.3 for PBO for absenteeism, presenteeism, absenteeism+presenteeism, & daily activity impairment, respectively. Among 738 pts, WPAI domain scores were moderately to strongly correlated (ie, ≥0.4) with pt-reported pain (0-10 visual analog scale), physical function (Health Assessment Questionnaire Disability Index [HAQ-DI]), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F] scale) & 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) score, but weakly correlated with other variables (Figure 1). Based on univariate analyses & evaluation of collinearity between variables, attributes included in multivariate models were age, body mass index (BMI), gender, CRP, FACIT-F, pain, Psoriasis Area Severity Index (PASI), TJC, SJC, enthesitis & dactylitis. In final model, CRP, FACIT-F, & pain were statistically significantly associated with all WPAI domains (Table 1). Presence of enthesitis & higher PASI score were significantly associated with higher loss of work productivity & activity outside work.Conclusion:In PsA pts, extra-articular symptoms, fatigue, pain & elevated CRP were significantly associated with WPAI-assessed work & activity impairment. Treating all major clinical manifestations of PsA is needed to help pts improve work & activity impairment. GUS effectively treats all major clinical manifestations1 & improves work & activity impairment in PsA.2References:[1]Mease P. Lancet 2020;395:1126-36.[2]Curtis J. ACR 2020; Poster 0332.Table 1.Multivariate analysis of clinical characteristics/outcomes & WPAI domains at W0 & W24ParameterAbsenteeismaPresenteeismaProductivity LossaActivity ImpairmentbEstimatep-valueEstimatep-valueEstimatep-valueEstimatep-valueAge-0.050.42-0.27-0.28-0.060.17Female0.910.46-1.540.22-1.740.202.380.02CRP0.730.040.970.011.010.010.89FACIT-F-0.31-0.67-0.73-0.75Pain1.034.154.254.02PASI0.060.360.160.020.140.050.150.003SJC0.080.48-0.050.61-0.050.660.030.75TJC-0.100.130.110.090.090.190.100.04Dactylitis (Y/N)-1.100.392.470.052.580.050.540.57Enthesitis (Y/N)1.520.202.380.042.990.012.400.01aPts working at baselinebAll pts in studyDisclosure of Interests:Jeffrey Curtis Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Eli Lilly, Myriad, Pfizer, Regeneron, Roche, and UCB, Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Eli Lilly, Myriad, Pfizer, Regeneron, Roche, and UCB, Iain McInnes Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, and UCB, Dafna D Gladman Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer and UCB, Feifei Yang Shareholder of: Janssen, Employee of: Janssen, Steve Peterson Shareholder of: Janssen, Employee of: Janssen, Prasheen Agarwal Shareholder of: Janssen, Employee of: Janssen, Alexa Kollmeier Shareholder of: Janssen, Employee of: Janssen, Elizabeth C Hsia Shareholder of: Janssen, Employee of: Janssen, Chenglong Han Shareholder of: Janssen, Employee of: Janssen, May Shawi Shareholder of: Janssen, Employee of: Janssen, William Tillett Speakers bureau: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, MSD, Pfizer, and UCB, Grant/research support from: AbbVie, Celgene, Eli Lilly, Janssen, and Novartis, Philip J Mease Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, SUN, and UCB, Proton Rahman Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Grant/research support from: Janssen and Novartis

Background:DISCOVER 1&2 (PsA) and VOYAGE 1&2 (PsO) are Phase 3 trials of guselkumab (GUS).Objectives:Compare safety results through up to 1yr of GUS in PsA and PsO pts.Methods:In DISCOVER, 1120 pts with active PsA despite standard therapy were treated. Most pts were biologic-naïve; ~30% in DISCOVER 1 had previous exposure to 1-2 TNFi. Concomitant MTX (57%), oral corticosteroids (17%), and NSAIDs (64%) were permitted. Pts were randomized to SC GUS 100mg at W0, W4, then Q8W; GUS 100mg Q4W; or PBO. At W24, PBO patients were switched to GUS 100mg Q4W. In VOYAGE, in which concomitant MTX use was prohibited, 1245 pts with moderate to severe PsO were treated and randomized to SC GUS 100 mg at W0, W4, W12, then Q8W; or PBO at W0, W4, W12, with crossover to GUS at W16, W20, then Q8W. AEs and laboratory parameters, analyzed by National Cancer Institute-Common Terminology Criteria for AEs [NCI-CTCAE] toxicity grades, were summarized through the PBO-controlled periods and 1yr.Results:Safety profiles were generally consistent across the GUS PsO and PsA clinical programs (Table 1). Time-adjusted incidence rates for numbers of AEs, serious AEs, serious infections, malignancy, MACE and AEs leading to d/c were generally similar between PsO and PsA. No cases of anaphylaxis or opportunistic infections were reported. Proportions of pts with decreased neutrophil counts and elevations in hepatic transaminases were slightly higher in PsA vs PsO. These abnormalities were mostly of NCI-CTCAE Grade 1 or 2 (3 for neutrophils; Conclusion:The GUS safety profile was generally consistent in PsA and PsO GUS-treated pts through 1yr of the DISCOVER and VOYAGE trials.Table 1.Treatment-Emergent AEs During PBO-controlled Period and Through 1Yr: VOYAGE & DISCOVER TrialsPooled VOYAGE 1&2Pooled DISCOVER 1&2Time PeriodW0-16Through 1YrW0-24bThrough 1Yr(N=)PBO(422)GUS Q8W(823)Combined GUSa(1221)PBOc(372)GUS Q8W(375)GUS Q4W (373)GUS Q8W(375)GUS Q4W (373)Combined GUS† (1100)Total pt-yrs of follow-up128255974173173172384385973Incidence/100 pt-yrs (95% CI)dAEs317 (287,349)330 (308,353)259 (249, 270)219 (198,243)256 (232,281)221 (200, 245)218 (203,233)177 (164,191)191 (182, 199)SAEs5 (2, 10)6 (4, 10)6 (5, 8)9 (5, 15)4 (2, 8)5 (2, 10)6 (4, 9)4 (2, 7)6 (4, 7)AEs leading to study agent d/c3 (0.9, 8)4 (2, 8)2 (2, 4)4 (2, 8)3 (1, 7)7 (4, 12)2 (1, 4)4 (2, 6)3 (2, 5)Infections86 (71, 104)98 (86, 111)98 (92, 104)58 (48, 71)58 (47, 71)63 (51, 76)58 (50, 66)53 (46, 61)55 (50, 60)Serious Infections0. 8 (0, 4)0.4 (0, 2)1 (0.5, 2)4 (2, 8)0.6 (0, 3)2 (0.4, 5)2 (0.6, 3)1 (0, 2)2 (0.9, 3)All Malignancy0 (0, 2)0.4 (0, 2)1 (0.4, 2)0.6 (0, 3)1 (0, 4)0 (0, 2)0.5 (0, 2)0 (0, 0. 8)0 (0, 1)MACE0 (0, 2)0.4 (0, 2)0.4 (0, 1)0.6 (0, 3)0 (0, 2)0.6 (0, 3)0 (0, 0.8)0.3 (0, 1.4)0.1 (0, 0.6)% pts with ≥1 injection site rxn3.14.55.00.31.31.11.62.41.7aPlacebo crossover pts were included in the combined GUS column after crossover to GUSbFor all pts who d/c study treatment early with the last dose of PBO/GUS prior to W24 and who did not receive any PBO/GUS at or after Wk24, all data including the final safety follow-up visit collected through 1yr were includedcFor pts in PBO group who switched to GUS due to cross-over or inadvertently, only data prior to first administration of GUS were included.dCI based on an exact method assuming observed number of events follows a Poisson distributionDisclosure of Interests:Alice B Gottlieb Consultant of: Anaptyps Bio, Avotres Therapeutics, Beiersdorf, Boehringer Ingelheim, Bristol-Myers-Squibb, Eli Lilly, Janssen, LEO Pharma, Novartis, Sun Pharmaceuticals, UCB, and Xbiotech, Grant/research support from: Boehringer Ingelheim, Janssen, Novartis, Sun Pharmaceuticals, UCB, and Xbiotech, Joseph F. Merola Consultant of: AbbVie, Arena, Biogen, BMS, Dermavant, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, UCB, April Armstrong Consultant of: AbbVie, Janssen, Lilly, Leo, Novartis, UCB, Ortho Dermatologics, Dermira, KHK, Sanofi, Regeneron, Sun Pharma, BMS, Dermavant, and Modernizing Medicine, Richard Langley Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, LEO Pharma, Merck, Novartis, Pizer, Sun Pharmaceutical, and UCB Pharma, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, LEO Pharma, Merck, Novartis, Pizer, Sun Pharmaceutical, and UCB Pharma, Mark Lebwohl Consultant of: Aditum Bio, Allergan, Almirall, Arcutis, Inc., Avotres Therapeutics, BirchBioMed Inc., BMD skincare, Boehringer-Ingelheim, Bristol-Myers Squibb, Cara Therapeutics, Castle Biosciences, Corrona, Dermavant Sciences, Evelo, Evommune, Facilitate International Dermatologic Education, Foundation for Research and Education in Dermatology, Inozyme Pharma, Kyowa Kirin, LEO Pharma, Meiji Seika Pharma, Menlo, Mitsubishi, Neuroderm, Pfizer, Promius/Dr. Reddy’s Laboratories, Serono, Theravance, and Verrica., Grant/research support from: Abbvie, Amgen, Arcutis, Boehringer Ingelheim, Dermavant, Eli Lilly, Evommune, Incyte, Janssen, Leo Pharmaceutucals, Ortho Dermatologics, Pfizer, and UCB, Christopher E.M. Griffiths Speakers bureau: AbbVie, Amgen, Almirall, BMS, Boehringer Ingelheim Celgene, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, Sun Pharma, UCB Pharma., Consultant of: AbbVie, Amgen, Almirall, BMS, Boehringer Ingelheim Celgene, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, Sun Pharma, UCB Pharma., Grant/research support from: AbbVie, Amgen, Almirall, BMS, Boehringer Ingelheim Celgene, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, Sun Pharma, UCB Pharma., May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, Ya-Wen Yang Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, Elizabeth C Hsia Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Xie L Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Miwa Izutsu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Paraneedharan Ramachandran Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Shihong Sheng Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Yin You Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Megan Miller Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Christopher T. Ritchlin Consultant of: AbbVie, Amgen, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB Pharma, Grant/research support from: AbbVie, Amgen, and UCB Pharma, Iain McInnes Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, and Janssen, Novartis, Pfizer, and UCB, Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, Proton Rahman Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Grant/research support from: Janssen and Novartis.

Objective To use the Clinical Global Impression‐Severity (CGI‐S) scale to estimate clinically meaningful and clinically substantial changes as measured using the Montgomery‐Åsberg Depression Rating Scale (MADRS), the Sheehan Disability Scale (SDS), and the Patient Health Questionnaire‐9 (PHQ‐9) in patients with treatment‐resistant depression (TRD). Methods Pooled data were derived from two 4‐week, randomized, active‐controlled studies evaluating esketamine nasal spray (ESK) plus oral antidepressant (OAD) or OAD plus placebo nasal spray (PBO) in adults with TRD (N = 565). CGI‐S, MADRS, SDS, and PHQ‐9 scores were obtained at baseline and over 4 weeks of treatment. In this post hoc analysis, change scores on the MADRS, SDS, and PHQ‐9 that corresponded to a clinically meaningful (1‐point) or clinically substantial (2‐point) change on the CGI‐S scale were identified. Results Clinically meaningful changes in CGI‐S scores after 28 days corresponded to 6‐, 4‐, and 3‐point changes from baseline on the MADRS, SDS, and PHQ‐9, respectively. Similarly, a 2‐point CGI‐S score change (clinically substantial change) corresponded to a 12‐, 8‐, and 6‐point change on the MADRS, SDS, and PHQ‐9, respectively. The proportion of patients showing substantial clinical improvement in the ESK plus OAD group versus the OAD plus PBO group after 28 days of treatment favored ESK plus OAD: 69.0% vs 55.3% (MADRS), 64.5% vs 48.9% (SDS), and 77.1% vs 64.7% (PHQ‐9). Conclusion We provide a basis for identifying clinically meaningful and clinically substantial changes as assessed with commonly used outcome measures for depression to facilitate the translation of clinical trial results into clinical practice.