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Guselkumab, a novel interleukin-23p19 subunit monoclonal antibody, has been shown to effectively improve the diverse manifestations of active psoriatic arthritis (PsA) in two phase 3 trials (DISCOVER-1, DISCOVER-2). Serum concentrations of extracellular matrix (ECM) biomarkers at baseline and following treatment with guselkumab were evaluated in patients with active PsA, and the relationship of these biomarkers with baseline PsA characteristics and clinical response to guselkumab treatment was explored.Serum samples were collected at weeks 0, 4, 24, and 52 from a selected subset (N = 260) of the 739 biologic-naïve patients with PsA treated with guselkumab 100 mg every 4 or 8 weeks or placebo in DISCOVER-2. Demographically matched healthy controls (N = 76) were used for comparison. The samples were analyzed for ECM biomarkers associated with collagen degradation (C1M, C2M, C3M, C4M, C6M, C10C) and collagen formation (PRO-C1, PRO-C2, PRO-C3, PRO-C4, PRO-C6).Baseline concentrations of collagen degradation biomarkers C1M, C3M, C4M, and C6M and collagen formation biomarkers PRO-C3 and PRO-C6 were significantly higher (i.e., ≥ 1.25-fold and false discovery rate adjusted p 0.05) in PsA patients than in healthy controls. Serum C1M, C3M, C4M, and C6M levels declined from baseline in guselkumab-treated patients in both dosing regimens. In addition, guselkumab-treated ACR20 responders (≥ 20% improvement in American College of Rhematology response criteria) had significantly lower C1M levels than ACR20 nonresponders.These data demonstrate that serum collagen biomarkers are elevated in patients with PsA compared with healthy controls and that treatment with guselkumab decreases levels of C1M, C3M, C4M, and C6M. Importantly, C1M serves as a biomarker that associates with improvement of joint signs and symptoms.ClinicalTrials.gov identifier: NCT03158285.

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

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.

This post hoc analysis assessed efficacy and safety of intravenous (IV) golimumab in ankylosing spondylitis (AS) patients with early disease (ED) versus late disease (LD).The phase 3, double-blind, GO-ALIVE study randomized patients to IV golimumab 2 mg/kg at weeks 0 and 4 and then every 8 weeks through week 52, or placebo at weeks 0, 4, and 12 with crossover to IV golimumab at week 16. Clinical efficacy was assessed by ≥20% improvement in Assessment of Spondyloarthritis International Society response criteria (ASAS20), ≥50% improvement in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI 50), and Ankylosing Spondylitis Disease Activity Score (ASDAS)1.3 (inactive disease). Using self-reported duration of inflammatory back pain (IBP), patients were grouped into quartiles: first = ED and fourth = LD. Descriptive statistics summarized efficacy and safety findings through 1 year.Early disease patients (n = 60) were ~10 years younger and had shorter median AS (IBP) symptom duration (2-3 years) versus LD patients (n = 52; 21-24 years). At week 16, numerically higher proportions of golimumab- than placebo-treated patients achieved ASAS20 (ED: 71% vs. 32%; LD: 67% vs. 21%), BASDAI 50 (ED: 40% vs. 12%; LD: 33% vs. 7%), and ASDAS1.3 (ED: 17% vs. 4%; LD 8% vs. 0%) regardless of IBP duration. Efficacy was durable through 1 year of treatment; however, response rates were numerically higher in patients with ED versus LD. Through week 60, adverse events and serious adverse events, respectively, were reported by 46% and 3% of ED patients and 61% and 2% of LD patients.Prompt diagnosis of AS and early treatment with IV golimumab may yield more robust improvements in disease activity.

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.

Objective To assess performance of psoriatic arthritis (PsA) composite indices and evaluate guselkumab’s effect on achieving low disease activity or remission. Methods In this phase II trial, patients with active PsA (≥3 tender and ≥3 swollen joints, C‐reactive protein level ≥0.3 mg/dl, ≥3% body surface‐area with psoriasis involvement) were randomized 2:1 to subcutaneous guselkumab 100 mg (n = 100) or placebo (n = 49) at week 0, week 4, and every 8 weeks through week 44. At week 16, patients with

Evaluate the effect of intravenous golimumab on health-related quality of life (HRQoL) in patients with ankylosing spondylitis (AS) through week 28 of the phase III, multicenter, randomized, double-blind, placebo-controlled GO-ALIVE study.Adult patients (n = 208) were randomized to IV golimumab 2 mg/kg (n = 105) at weeks 0, 4, and 12 and every 8 weeks or placebo (n = 103) at weeks 0, 4, and 12, with crossover to golimumab 2mg/kg at weeks 16, 20, and every 8 weeks. General HRQoL was evaluated using the Short Form Health Survey (SF-36) Physical Component Summary/Mental Component Summary (PCS/MCS), and the EQ VAS, and AS disease-specific HRQoL was assessed using the Ankylosing Spondylitis Quality of Life (ASQoL) instrument.Mean improvements from baseline in SF-36 PCS were greater in the golimumab group versus the placebo group at weeks 8 and 16 (6.8 vs 2.1 and 8.5 vs 2.9, respectively; P.001); similar results were observed for SF-36 MCS (5.6 vs 1.7 and 6.5 vs 0.8, respectively; P.001). Mean improvement in each of 8 subscale scores of the SF-36 were also greater for golimumab-treated patients versus placebo at weeks 8 and 16. Mean improvements in EQ VAS and ASQoL were greater in the golimumab group versus placebo at week 8 and week 16. Greater proportions of golimumab-treated patients had clinically meaningful improvement in SF-36 PCS, SF-36 MCS, EQ VAS, and ASQoL at weeks 8 and 16; improvements in SF-36 PCS/MCS, EQ VAS, and ASQoL were maintained through week 28.Golimumab-treated patients had greater mean improvements in HRQoL measures compared with placebo through week 16. Clinically meaningful improvements were observed as early as week 8 and continued through week 28.

The effect of intravenous (IV) golimumab on health-related quality of life (HRQoL) and productivity in patients with ankylosing spondylitis (AS) was evaluated. Patients were randomized to IV golimumab 2 mg/kg (n = 105) at weeks 0, 4, then every 8 weeks (q8w) through week 52 or placebo (n = 103) at weeks 0, 4, 12, with crossover to golimumab 2 mg/kg at weeks 16, 20, then q8w through week 52. Changes from baseline in EuroQol-5 dimension-5 level (EQ-5D-5L) index and visual analog scale (EQ-VAS), daily productivity VAS, Work Limitations Questionnaire (WLQ), and Ankylosing Spondylitis Quality of Life (ASQoL) were assessed. Correlations between these outcomes and disease activity and patient functioning outcomes were evaluated post hoc. At week 16, changes from baseline (mean ± standard deviation) in EQ-5D-5L index (0.17 ± 0.16 vs 0.05 ± 0.14), EQ-VAS (20.3 ± 24.6 vs 4.8 ± 23.5), daily productivity VAS (− 2.9 ± − 2.9 vs − 1.1 ± − 2.5), WLQ productivity loss score (− 3.5 ± − 5.3 vs − 1.9 ± − 4.0), and ASQoL (− 5.4 ± − 5.0 vs − 1.8 ± − 4.5) were greater in the IV golimumab versus placebo group, respectively. At week 28, changes from baseline were similar between the IV golimumab and placebo-crossover groups (EQ-5D-5L index: 0.18 ± 0.17 and 0.16 ± 0.16, EQ-VAS: 20.5 ± 27.9 and 22.5 ± 23.1, daily productivity VAS: − 3.1 ± − 3.0 and − 3.1 ± − 2.8, WLQ productivity loss: − 3.9 ± − 5.5 and − 4.5 ± − 4.5, and ASQoL: − 5.3 ± − 5.2 and − 5.3 ± − 4.8, respectively); improvements were maintained through week 52. HRQoL and productivity outcomes were generally moderately correlated with disease activity and functioning outcomes. In patients with AS, IV golimumab produced sustained improvements in HRQoL and productivity through 1 year, which correlated with improvements in disease activity and functioning. ClinicalTrials.gov registry number is NCT02186873.

Objective The present study was undertaken to evaluate the safety and efficacy of intravenous (IV) golimumab in patients with active psoriatic arthritis (PsA) through 1 year. Methods GO-VIBRANT was a phase III, randomized, placebo-controlled trial of 480 adults with active PsA. Patients were randomized to receive IV placebo (n = 239) or golimumab 2 mg/kg (n = 241) at weeks 0, 4, and every 8 weeks, with placebo crossover to golimumab at weeks 24, 28, and every 8 weeks thereafter. Efficacy through week 52 was assessed using the American College of Rheumatology (ACR) ≥20%, 50%, or 70% improvement criteria (ACR20/50/70), and the Psoriasis Area and Severity Index ≥75% improvement criteria (PASI75). Radiographic progression was measured using the PsA-modified Sharp/van der Heijde score (SHS). Adverse events (AEs) were monitored through week 60. Results The primary and major secondary end points through week 24 were achieved. At week 52, 76.8% of patients in the golimumab group and 77.0% in the placebo-crossover group achieved an ACR20 response, 58.1% and 53.6%, respectively, achieved an ACR50 response, and 38.6% and 33.9%, respectively, achieved an ACR70 response. Among patients with ≥3% body surface area affected, 71.9% in the golimumab group and 60.6% in the placebo-crossover group achieved a PASI75 response at week 52. Mean change from baseline in total SHS at week 52 was -0.5 in the golimumab group and 0.8 in the placebo-crossover group. Through week 60, 50.9% of all golimumab-treated patients had ≥1 AE, and 5.2% had ≥1 serious AE. There were no opportunistic infections, 2 malignancies, and 1 death in patients treated with golimumab. Conclusion Sustained improvements in joint and skin disease in patients with PsA were maintained through 1 year in the GO-VIBRANT study. No new safety signals for IV golimumab were identified.

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

Background Intravenous (IV) golimumab, a TNFi, is approved for treating rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). We analyzed pooled safety results from three phase 3 IV golimumab trials in these rheumatologic diseases and hypothesized that the safety profile of IV golimumab would be similar to that established for other TNFi, including subcutaneous golimumab. Methods Data from three double-blind, randomized trials of IV golimumab in patients with RA, PsA, and AS, each with a placebo-controlled period and an extension of active treatment, were included. Golimumab 2 mg/kg was administered at weeks 0 and 4, then every 8 weeks through week 100 (RA) or week 52 (PsA, AS). Concomitant low-dose, oral corticosteroids were permitted. Concomitant methotrexate was required in the RA trial and permitted in the PsA and AS trials; placebo patients crossed over to golimumab at weeks 24 (RA, PsA) and 16 (AS), respectively. Adverse events (AEs), including infections, serious infections, malignancies, and major adverse cardiovascular events (MACE), were assessed through week 112 (RA) or week 60 (PsA, AS). Results In total, 539 patients were randomized to placebo, and 740 patients were randomized to golimumab; 1248 patients received ≥ 1 golimumab administration. Among the placebo and golimumab patients, respectively, during the placebo-controlled periods, 40.6% and 50.3% had an AE, 2.4% and 3.8% had a serious AE, and 0.4% and 0.8% had a serious infection. Among all golimumab-treated patients, the numbers of events/100 patient-years (95% CI) were as follows: AEs, 175.2 (169.0, 181.6); serious AEs, 12.7 (11.0, 14.5); serious infections, 3.4 (2.5, 4.4); active tuberculosis, 0.4 (0.1, 0.8); opportunistic infection, 0.2 (0.1, 0.6); malignancies, 0.4 (0.2, 0.9), and MACE, 0.5 (0.2, 1.0). There were no cases of lymphoma. Three (0.6%) placebo-treated patients and 6 (0.5%) golimumab-treated patients died during the studies. Concomitant methotrexate was associated with increased occurrence of elevated alanine transaminase levels and lower incidence of antibodies to golimumab. During the placebo-controlled periods, serious infections in the placebo and golimumab groups were more common in patients receiving concomitant low-dose oral corticosteroids vs. those not receiving corticosteroids. Conclusions IV golimumab demonstrated a safety profile that was broadly consistent across these rheumatologic indications and with other TNFi, including subcutaneous golimumab. Concomitant methotrexate or corticosteroids were associated with an increase in specific AEs. Trial registrations ClinicalTrials.gov, NCT00973479. Registered on September 9, 2009. ClinicalTrials.gov, NCT02181673. Registered on July 4, 2014. ClinicalTrials.gov, NCT02186873. Registered on July 10, 2014.

Objective To evaluate the safety and efficacy of intravenous golimumab + methotrexate (MTX) in patients with active rheumatoid arthritis (RA) aged

Objective Golimumab immunogenicity was extensively studied during clinical development. As anti-drug antibody (ADA) detection with the standard bridging EIA (original-EIA) can yield false-negative results or underestimate ADA incidence and titres due to drug interference, a more sensitive assay was needed to determine clinical impact. Methods A highly sensitive drug-tolerant EIA (DT-EIA) was developed and cross-validated against the original-EIA. Samples from phase-3 subcutaneous golimumab rheumatological trials (GO-FORWARD-rheumatoid arthritis, GO-REVEAL-psoriatic arthritis, GO-RAISE-ankylosing spondylitis) were then retested. Associations between ADAs and golimumab pharmacokinetics, efficacy and safety were assessed. Results The DT-EIA was more sensitive than the original-EIA and capable of detecting ADAs amid golimumab concentrations far exceeding those in immunogenicity test samples. Consequently, an 8-fold increase in the incidence of ADAs was observed with the DT-EIA (31.7%) vs original-EIA (4.1%) in the studies. Most ADA-positive patients identified by the DT-EIA had lower antibody titres, while most with higher titres were previously identified as ADA-positive by the original-EIA. With the DT-EIA, ADA-positive patients generally had lower trough serum golimumab concentrations than ADA-negative patients; however, ADA impact on serum golimumab concentrations was more notable at higher ADA titres (⩾100). No impact of ADAs on clinical efficacy or injection-site reactions was evident. Conclusion ADA incidence was expectedly higher using the DT-EIA vs original-EIA; newly detected ADAs were characterized mostly by low titres, with no impact on clinical efficacy or injection-site reactions, consistent with previously observed original-EIA results. Golimumab immunogenicity with the DT-EIA is consistent with existing knowledge regarding the clinical relevance of ADAs detected with the original-EIA in patients with rheumatological disorders. Trial registration NCT00264550, NCT00265096, NCT00265083.

Objective Guselkumab, a human monoclonal antibody specific to interleukin-23p19, demonstrated efficacy and safety versus placebo through week 24 of the phase III DISCOVER-2 trial in biologic-naive patients with psoriatic arthritis (PsA). Here we report 1-year DISCOVER-2 findings.Methods Adults with active PsA (>= 5 swollen and >= 5 tender joints; C-reactive protein level >= 0.6 mg/dl) despite standard nonbiologic treatment were randomized to receive subcutaneous injections of guselkumab 100 mg every 4 weeks, guselkumab 100 mg at week 0, week 4 and every 8 weeks thereafter, or placebo with crossover to guselkumab 100 mg every 4 weeks at week 24. We primarily evaluated clinical efficacy through week 52 by imputing missing data (nonresponse for categorical end points; no change/using multiple imputation for continuous end points). Observed radiographic scores and adverse events (AEs) were summarized.Results Of 739 randomized, treated patients, 93% completed week 52. The proportions of patients in whom a >= 20% improvement from baseline in American College of Rheumatology criteria (ACR20) was achieved were maintained after week 24, reaching 71% (173 of 245) and 75% (185 of 248) for patients randomized to receive treatment every 4 weeks or every 8 weeks, respectively, by week 52. The proportions of patients in whom ACR50/ACR70 and skin responses, minimal or very low disease activity, and dactylitis or enthesitis resolution were achieved at week 24 were also maintained through week 52. Further, low levels of radiographic progression, along with improvements in physical function and health-related quality of life, were sustained through week 52 with continued guselkumab treatment. Few patients experienced serious infections through week 52, with no evidence of a dosing regimen response or increase from weeks 0-24 (4 of 493 [0.8%]) to weeks 24-52 (3 of 493 [0.6%]) among guselkumab-randomized patients. No patient developed an opportunistic infection or died.Conclusion In biologic-naive PsA patients, guselkumab provided sustained improvements across diverse manifestations and maintained a favorable risk-benefit profile through week 52.

Introduction/objectives To evaluate changes in health-related quality of life (HRQoL) and productivity following treatment with intravenous (IV) golimumab in patients with psoriatic arthritis (PsA). Methods Patients were randomized to IV golimumab 2 mg/kg (n=241) at Weeks 0, 4, then every 8 weeks (q8w) through Week 52 or placebo (n=239) at Weeks 0, 4, then q8w, with crossover to IV golimumab 2 mg/kg at Weeks 24, 28, then q8w through Week 52. Change from baseline in EuroQol-5 dimension-5 level (EQ-5D-5L) index and visual analog scale (EQ-VAS), daily productivity VAS, and the Work Limitations Questionnaire (WLQ) was assessed. Relationships between these outcomes and disease activity and patient functional capability were evaluated post hoc. Results At Week 8, change from baseline in EQ-5D-5L index (0.14 vs 0.04), EQ-VAS (17.16 vs 3.69), daily productivity VAS (−2.91 vs −0.71), and WLQ productivity loss score (−2.92 vs −0.78) was greater in the golimumab group versus the placebo group, respectively. At Week 52, change from baseline was similar in the golimumab and placebo-crossover groups (EQ-5D-5L index: 0.17 and 0.15; EQ-VAS: 21.61 and 20.84; daily productivity VAS: −2.89 and −3.31; WLQ productivity loss: −4.49 and −3.28, respectively). HRQoL and productivity were generally associated with disease activity and functional capability, with continued association from Week 8 through Week 52. Conclusion IV golimumab resulted in early and sustained improvements in HRQoL and productivity from Week 8 through 1 year in patients with PsA. HRQoL and productivity improvements were associated with improvements in disease activity and patient functional capability. Key Points• In patients with active psoriatic arthritis (PsA), intravenous (IV) golimumab improved health-related quality of life (HRQoL) and productivity as early as 8 weeks and maintained improvement through 1 year• Improvements in HRQoL and productivity outcomes in patients with PsA treated with IV golimumab were associated with improvements in disease activity and patient functional capability outcomes• IV golimumab is an effective treatment option for PsA that can mitigate the negative effects of the disease on HRQoL and productivity

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)

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

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.

ObjectiveTo evaluate the effect of guselkumab on enthesitis and dactylitis in a phase II trial of patients with active psoriatic arthritis (PsA).MethodsThis was a phase II, randomised, placebo-controlled, double-blind trial of adults with active PsA (≥3 swollen and ≥3 tender joints and C reactive protein ≥0.3 mg/dL) despite conventional synthetic disease-modifying anti-rheumatic drug, non-steroidal anti-inflammatory drug, and/or oral corticosteroid therapy. Patients were randomised to subcutaneous injections of guselkumab 100 mg or placebo at weeks 0, 4 and every 8 weeks, with placebo crossover to guselkumab at week 24. Dactylitis was scored on a scale of 0–3 on each digit; enthesitis was assessed using the Leeds Enthesitis Index (0–6). Other assessments included American College of Rheumatology (ACR) and Psoriasis Area and Severity Index responses.ResultsOf 149 randomised patients, 107 patients had enthesitis (mean score=2.7) and 81 patients had dactylitis (mean dactylitis score=5.7) at baseline. Mean improvements in enthesitis and dactylitis at week 24 were greater in the guselkumab group versus placebo and sustained through week 56. Similar results were observed for the proportions of patients with resolution of enthesitis and dactylitis. At week 56, mean improvements in enthesitis and dactylitis among patients who switched from placebo to guselkumab treatment were similar to those in the guselkumab group. In the guselkumab group, ACR20 responders had greater improvements in enthesitis and dactylitis versus non-responders (week 24).ConclusionsAt week 24, the guselkumab group had greater mean improvements in enthesitis and dactylitis and greater proportions of patients with resolution of enthesitis and dactylitis versus placebo. ACR20 response was associated with improvements in enthesitis and dactylitis.Trial registration numberClinicalTrials.gov: NCT02319759.URL: https://clinicaltrials.gov/ct2/show/NCT02319759; Registered 18 December 2014.

The effect of intravenous (IV) golimumab on health-related quality of life (HRQoL) and productivity in patients with ankylosing spondylitis (AS) was evaluated.Patients were randomized to IV golimumab 2 mg/kg (n = 105) at weeks 0, 4, then every 8 weeks (q8w) through week 52 or placebo (n = 103) at weeks 0, 4, 12, with crossover to golimumab 2 mg/kg at weeks 16, 20, then q8w through week 52. Changes from baseline in EuroQol-5 dimension-5 level (EQ-5D-5L) index and visual analog scale (EQ-VAS), daily productivity VAS, Work Limitations Questionnaire (WLQ), and Ankylosing Spondylitis Quality of Life (ASQoL) were assessed. Correlations between these outcomes and disease activity and patient functioning outcomes were evaluated post hoc.At week 16, changes from baseline (mean ± standard deviation) in EQ-5D-5L index (0.17 ± 0.16 vs 0.05 ± 0.14), EQ-VAS (20.3 ± 24.6 vs 4.8 ± 23.5), daily productivity VAS (- 2.9 ± - 2.9 vs - 1.1 ± - 2.5), WLQ productivity loss score (- 3.5 ± - 5.3 vs - 1.9 ± - 4.0), and ASQoL (- 5.4 ± - 5.0 vs - 1.8 ± - 4.5) were greater in the IV golimumab versus placebo group, respectively. At week 28, changes from baseline were similar between the IV golimumab and placebo-crossover groups (EQ-5D-5L index: 0.18 ± 0.17 and 0.16 ± 0.16, EQ-VAS: 20.5 ± 27.9 and 22.5 ± 23.1, daily productivity VAS: - 3.1 ± - 3.0 and - 3.1 ± - 2.8, WLQ productivity loss: - 3.9 ± - 5.5 and - 4.5 ± - 4.5, and ASQoL: - 5.3 ± - 5.2 and - 5.3 ± - 4.8, respectively); improvements were maintained through week 52. HRQoL and productivity outcomes were generally moderately correlated with disease activity and functioning outcomes.In patients with AS, IV golimumab produced sustained improvements in HRQoL and productivity through 1 year, which correlated with improvements in disease activity and functioning. ClinicalTrials.gov registry number is NCT02186873. Key Points • Intravenous (IV) golimumab resulted in clinically important improvement in general and ankylosing spondylitis-specific health-related quality of life (HRQoL) and productivity outcomes in patients with ankylosing spondylitis (AS) as early as week 8 and maintained improvement through 1 year • Improvements in HRQoL and productivity outcomes in these patients with AS were correlated with improvements in measures of disease activity and patient functional capability • IV golimumab is an effective treatment option for AS that can help mitigate the negative effects of the disease on HRQoL and productivity.

Background Guselkumab (GUS), an anti-interleukin-23p19 monoclonal antibody, is approved to treat psoriasis (PsO). We evaluated GUS efficacy and safety in a Phase 3, double-blind, placebo (PBO)-controlled trial in patients with active PsA who were biologic-naïve or prior TNFα inhibitor (TNFi)-treated (DISCOVER-1). Methods Adults with active PsA (≥3 swollen + ≥3 tender joints; CRP ≥0.3mg/dL) despite standard therapies (eg, non-biologic DMARDs, apremilast, or NSAIDs) were eligible. ∼30% of patients previously could have received or have had inadequate response to 1-2 TNFi. Patients were randomised 1:1:1, stratified by Week [W]0 DMARD use and prior TNFi use, to GUS 100mg Q4W; GUS 100mg at W0, W4, Q8W (Q8W); or PBO. Concomitant stable use of select non-biologic DMARDs, oral corticosteroids, and NSAIDs was allowed. At W16, patients with Results 381 patients were treated and analyzed; baseline characteristics were consistent with moderate-to-severe disease (mean BSA involved with PsO: 13.4%, patients with IGA=3-4: 42.5%; mean swollen/tender joint counts: 9.8/19.3). Significantly more patients receiving GUS Q4W (58.6%) and Q8W (52.8%) vs PBO (22.2%, both p < 0.001) achieved ACR20 response at W24. Consistent response rates were observed in the subgroups of patients with or without prior TNFi use. Significantly greater improvements in HAQ-DI and SF-36 PCS scores were seen in GUS- vs PBO-treated patients from W0 to W24. Among 249 patients with ≥3% BSA PsO and IGA ≥2 at W0, significantly more GUS- vs PBO-treated patients achieved IGA response. Higher proportions of patients achieved ACR20 response at W16, ACR50 response at W16/24, ACR70 response at W24, and PASI75/90/100 responses at W24. More GUS Q4W- or Q8W- vs PBO-treated patients achieved MDA response at W24. Serious AEs, serious infections, and death occurred in 9/381 (2.4%), 2/381 (0.5%), and 1/381 (0.3%) patients, respectively. Conclusion In patients with active PsA who were biologic-naïve or had been treated with TNFi, both GUS Q4W and Q8W demonstrated efficacy for joint and skin symptoms, physical function, and quality of life relative to PBO. Observed AEs were consistent with GUS safety established in PsO. Disclosures A. Deodhar: Other; A.D. has been a study investigator for Janssen clinical trials. P. Helliwell: Other; P.H. has been a research investigator for Janssen. W. Boehncke: Other; W.B. has been a study investigator for Janssen. E.C. Hsia: Other; E.H. is a Janssen employee. A.P. Kollmeier: Other; A.K. is a Janssen employee. R.A. Subramanian: Other; R.S. is a Janssen employee. X.L. Xu: Other; X.X. is a Janssen employee. S. Sheng: Other; S.S. is a Janssen employee. B. Zhou: Other; B.Z. is a Janssen employee. P.C. Gorecki: Other; P.G. is a Janssen employee. C. Ritchlin: Other; C.R. has been a study investigator for Janssen.

OBJECTIVE To evaluate whether intravenous (IV) golimumab produces improvements in skin and nail symptoms that are concomitant with improvements in quality of life (QoL) and joint symptoms in patients with psoriatic arthritis. METHODS Patients were randomized to either IV golimumab 2 mg/kg at weeks 0, 4, then every 8 weeks (q8w) through week 52 or placebo at weeks 0, 4, then q8w, with crossover to IV golimumab 2 mg/kg at weeks 24, 28, and then q8w through week 52. Assessments included Psoriasis Area and Severity Index (PASI), modified Nail Psoriasis Severity Index (mNAPSI), Dermatology Life Quality Index (DLQI), and American College of Rheumatology (ACR) rheumatoid arthritis response criteria. RESULTS Through week 24, achievement of PASI 75/90/100 responses (P ≤ .0098) and mean improvements in mNAPSI (-11.4 vs -3.7; P < .0001) and DLQI (-9.8 vs -2.9; P < .0001) were significantly greater with golimumab versus placebo. Responses were maintained in patients treated with golimumab through week 52. In placebo-crossover patients, increases in the proportion of patients achieving PASI 75/90/100 responses were observed from weeks 24 to 52, and mean improvements in mNAPSI (from -3.7 to -12.9) and DLQI (from -2.9 to -7.8) increased from weeks 24 to 52. Simultaneous achievement of PASI and DLQI responses, PASI and ACR responses, and mNAPSI and DLQI responses were also observed. Similar responses were observed for all assessments regardless of concomitant methotrexate use. CONCLUSION Improvements in skin and nail psoriasis symptoms with IV golimumab in patients with psoriatic arthritis were concomitant with improvements in QoL and arthritis disease activity through 1 year.

Objective.To evaluate the efficacy, safety, pharmacokinetics, and immunogenicity of CNTO6785, a fully human monoclonal antibody that binds to human interleukin 17A, in patients with active rheumatoid arthritis (RA) with inadequate response to methotrexate (MTX) therapy.Methods.This randomized, double-blind, placebo-controlled, dose-ranging study enrolled patients aged 18 to 80 years (inclusive) with active RA (≥ 6/66 swollen and ≥ 6/68 tender joints) who were refractory to MTX treatment (7.5–25 mg weekly, inclusive). The study duration was 38 weeks, containing a 10-week safety followup. Patients were randomized 1:1:1:1:1 to receive CNTO6785 15, 50, 100, or 200 mg every 4 weeks + MTX or placebo + MTX. The primary endpoint was American College of Rheumatology 20 (ACR20) response at Week 16.Results.There were no significant differences from placebo in the proportion of patients treated with CNTO6785 in the primary endpoint of ACR20 response at Week 16. There were no significant findings in any additional efficacy variables through Week 32. No dose-response relationships or specific patterns were observed in adverse event profiles among CNTO6785 treatment groups. Infections occurred with similar frequency across all groups, and injection site reactions were mild or moderate and did not demonstrate a dose-response relationship. Median serum CNTO6785 concentration increases through Week 38 were about dose-proportional; the incidence of neutralizing antidrug antibodies was 19.4% and was not associated with study drug dose level.Conclusion.CNTO6785 was well tolerated, but did not demonstrate clinical efficacy in patients with active RA with inadequate response to MTX.

Objective The American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) have defined remission using Boolean- or index-based criteria (i.e., a Simplified Disease Activity Index [SDAI] score of ≤3.3). We undertook this study to compare definitions of remission to inform choice of end points for future rheumatoid arthritis (RA) clinical trials, and we also included in our comparison the remission criterion of a score of ≤2.8 on the Clinical Disease Activity Index (CDAI). Methods We performed post hoc analyses on clinical remission rates using data from 2 infliximab trials (the ASPIRE [Active-Controlled Study of Patients Receiving Infliximab for the Treatment of Rheumatoid Arthritis of Early Onset] and ATTRACT [Anti–Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy] trials) and 1 golimumab trial (the GO-FORWARD trial). We investigated stringency of the different remission definitions, their power to discriminate between active drug and comparator, and aspects of their internal and external validity. We also investigated population determinants of discriminatory power for a particular remission end point. Results In patients with early RA (the ASPIRE trial), ACR/EULAR Boolean, CDAI, and SDAI remission rates at 6–7 months were 4–6% for methotrexate (MTX) alone versus 11–14% for infliximab plus MTX. In patients with MTX-refractory active RA (the ATTRACT and GO-FORWARD trials), remission rates were ≤1% for comparator (add-on of placebo) versus 4–6% for add-on of infliximab in the ATTRACT trial and ≤3% for comparator (add-on of placebo) versus 11–13% for add-on of golimumab in the GO-FORWARD trial. Existing remission cut points of different measures were generally comparable, with the Boolean criteria being somewhat more stringent than the SDAI and CDAI criteria. Remission rates were similar across definitions, as was average statistical power (CDAI, 55.6%; Boolean, 59.9%; SDAI, 62.6%). Conclusion Remission is an ambitious primary end point for RA clinical trials, to be reserved for selected scenarios based on power considerations. The ACR/EULAR definitions are interchangeable, with slightly higher stringency of Boolean criteria over index-based criteria.

Background:Guselkumab (GUS), a monoclonal antibody that specifically binds to the p19-subunit of IL-23, is approved to treat PsO. At Week24 (W24) of the Phase 3, double-blind, PBO-controlled trial in pts with active PsA who were biologic-naïve or prior TNFα inhibitor (TNFi)-treated (DISCOVER-1), GUS 100 mg, given every 4/8 weeks (Q4W/Q8W), demonstrated efficacy for joint & skin symptoms, physical function & quality of life vs PBO; AEs were consistent with GUS safety in PsO.Objectives:Assess GUS efficacy & safety in PsA through 1 year.Methods:Adults with active PsA (≥3 swollen+≥3 tender joints; CRP ≥0.3mg/dL) despite standard therapies were eligible. Approx. 30% of pts could have previously received ≤2 TNFi. Pts were randomized 1:1:1, stratified by W0 DMARD [Y/N] & prior TNFi (Y/N) use, to GUS 100mg Q4W; GUS 100 mg at W0, W4 & Q8W; or PBO. At W24, PBO pts crossed over to GUS 100 mg Q4W (PBO X Q4W). W48 marked the last dose of study agent. ACR response rates at W52, based on nonresponder imputation (NRI) for missing data and as observed in pts still on study agent at W24, are shown. Observed data for additional endpoints are shown. AEs through W60 are reported.Results:362/381 (95%) randomized pts continued study agent at W24 (125 Q4W, 123 Q8W, 114 PBO X Q4W), 347/381 (91%) pts completed treatment & 343/381 (90%) completed study. NRI ACR20 response rates were maintained at W52 (Q4W 73%, Q8W 60%; Fig 1A). Similar responses patterns were seen for the more stringent ACR50/70 criteria (Fig 1C,E). Observed ACR responses, overall (Fig, 1B,D,F) and in pts with (Fig 2A,C,E) & without (Fig 2B,D,F) prior TNFi use, were also maintained at W52. Improvements in other clinical outcomes were also maintained at W52, and responses for pts crossing over from PBO X Q4W at W24 were generally consistent with other GUS-treated pts by W52 (Table 1). Through W24, 4 (2%) GUS- and 5 (4%) PBO-treated pts had serious AEs; no GUS-treated and 2 (2%) PBO-treated pts had a serious infection. Through W60, serious AEs and serious infections occurred in 4% & 1%, respectively, of all 369 GUS-treated pts; no GUS-treated pt died or had IBD, opportunistic infections or active TB, or anaphylactic or serum sickness-like reactions.Table 1.Observed Efficacy1GUSQ4WGUSQ8WPBO(W0-24) XQ4W(W24-52)Data are % unless otherwise statedW24W52W24W52W24W52Dactylitis at W0,n373749444743Resolution64.978.467.379.561.781.4Enthesitis at W0,n717071647163Resolution49.362.940.856.331.069.8≥3% BSA psoriasis, IGA ≥2 at W0,n888881756866IGA 0/1 + ≥2-grade decrease76.183.058.069.317.681.52PASI7587.594.376.580.020.684.8PASI9063.676.150.666.713.272.7PASI10045.564.825.948.07.462.1HAQ-DI,n125124123114114104Mean change-0.4-0.5-0.3-0.4-0.1-0.4SF-36 scores,n (mean change)124124123114114104Physical Component - PCS6.68.56.57.32.76.9Mental Component - MCS3.84.93.05.11.84.2MDA, n125124123112114103MDA response31.240.323.633.912.331.1VLDA,n125124123114113104VLDA response9.616.94.112.31.814.41Randomized pts still on study agent at W24;2n=65Conclusion:GUS Q4W & Q8W maintained improvements in joint symptoms through 1 year in pts with active PsA who were biologic-naïve or previously TNFi-treated. In pts continuing in the study, improvements in skin symptoms, dactylitis, enthesitis, physical function & quality of life were also maintained through 1 year. GUS 100 mg Q4W & Q8W were safe and well-tolerated through study completion and consistent with GUS safety in PsO.1References:[1]https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/TREMFYA-pi.pdf.Acknowledgments:NoneDisclosure of Interests:Christopher T. Ritchlin Grant/research support from: UCB Pharma, AbbVie, Amgen, Consultant of: UCB Pharma, Amgen, AbbVie, Lilly, Pfizer, Novartis, Gilead, Janssen, Philip Helliwell: None declared, Wolf-Henning Boehncke Grant/research support from: Janssen Research & Development, LLC, Consultant of: Janssen, 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, Ramanand A Subramanian Employee of: Janssen Research & Development, LLC, Xie L Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Shihong Sheng Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Yusang Jiang: None declared, Bei Zhou Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Atul Deodhar Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB

Background:DISCOVER 1 & 2 are phase 3 psoriatic arthritis (PsA) trials investigating guselkumab (GUS), an IL-23 inhibitor that specifically binds the IL-23p19 subunit. In both studies, GUS showed significant improvement vs placebo (PBO) through week (W) 24 in the PBO-controlled period.1,2Objectives:To present integrated safety results of DISC 1 & 2 through the PBO-controlled periods.Methods:Adult patients (pts) with active PsA despite standard therapy were enrolled. All pts were biologic-naïve, except ~30% in DISC 1 with previous exposure to 1-2 TNF inhibitors. Pts were randomized to SC GUS 100 mg Q4W; GUS 100 mg at W0, W4, then Q8W; or PBO. Adverse events (AEs) and lab results were analyzed from pooled data.Results:The rates of pts experiencing ≥1 AE, serious AE, infection, serious infection, and discontinuation due to an AE were similar between GUS and PBO (Table 1). There were 2 deaths, 3 malignancies, 2 Major Adverse Cardiac Events (MACE), and no opportunistic infections (treatment group not shown to prevent unblinding). Among the AEs reported by ≥5% pts in any group (Table 1), nasopharyngitis and elevated serum hepatic aminotransferases were more common with GUS vs PBO. Laboratory ALT and AST elevations were mostly mild, transient, and not associated with significant bilirubin elevation. There was a trend to decreased neutrophil count (mostly Grade 1, transient, and not associated with infection) with GUS vs PBO (Table 2). Low rates of injection-site reactions were seen with GUS vs PBO. Anti-drug antibody development was also low (Table 1).Table 1.Patient Reported AEs, n (%)GUS100 mgQ8WGUS100 mgQ4WPBON375373372≥1 AE182 (48.5)182 (48.8)176 (47.3)≥1 Serious AE7 (1.9)8 (2.1)12 (3.2)Discontinuation due to AE5 (1.3)8 (2.1)7 (1.9)≥1 Infection73 (19.5)80 (21.4)77 (20.7)≥1 Serious infection1 (0.3)3 (0.8)3 (0.8)≥1 Opportunistic Infection (including Candida)000Active Tuberculosis000≥1 Injection-site reaction5 (1.3)4 (1.1)1 (0.3)Anti-GUS antibody +, n/N (%)6/373 (1.6)9/371 (2.4)--AEs* reported by ≥5% of patients in any treatment groupNasopharyngitis26 (6.9)19 (5.1)17 (4.6)Upper respiratory tract infection13 (3.5)23 (6.2)17 (4.6)Increased ALT23 (6.1)28 (7.5)14 (3.8)Increased AST23 (6.1)14 (3.8)9 (2.4)*Medical Dictionary for Regulatory Activities (MedDRA) preferred termTable 2.Lab Results*GUS100 mgQ8WGUS100 mgQ4WPBON373371370ALT Increased (%)Grade 128.235.030.121.12.71.43-40.81.10.8Neutrophil Count Decreased (%)Grade 15.65.93.221.61.60.83-400.30.3*NCI toxicity gradeALT=Alanine aminotransferaseConclusion:GUS was safe and well tolerated through the PBO-controlled period in 2 randomized, phase 3 trials of patients with active PsA. There were no meaningful safety differences between the Q8W and Q4W groups, no significant safety issues identified when comparing GUS to PBO, and no safety signals with regards to infections, malignancy, and MACE. The safety profile of GUS Q4W and Q8W in PsA pts was generally consistent with that in the Phase 3 trials of GUS Q8W for psoriasis.3,4References:[1]Deodhar et al. ACR 2019 (#807). Arth Rheum 2019;71 S10:1386[2]Mease et al. ACR 2019 (#L13). Arth Rheum 2019;71 S10:5247[3]Blauvelt et al. J Am Acad Derm 2017;76:405[4]Reich et al. J Am Acad Derm 2017;76:418Acknowledgments:NoneDisclosure of Interests:Proton Rahman Grant/research support from: Janssen and Novartis, Consultant of: Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, and Pfizer., Speakers bureau: Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, Pfizer, Christopher T. Ritchlin Grant/research support from: UCB Pharma, AbbVie, Amgen, Consultant of: UCB Pharma, Amgen, AbbVie, Lilly, Pfizer, Novartis, Gilead, Janssen, Philip Helliwell: None declared, Wolf-Henning Boehncke Grant/research support from: Janssen Research & Development, LLC, Consultant of: Janssen, 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, Alice B Gottlieb Grant/research support from:: Research grants, consultation fees, or speaker honoraria for lectures from: Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB., Consultant of:: Research grants, consultation fees, or speaker honoraria for lectures from: Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB., Speakers bureau:: Research grants, consultation fees, or speaker honoraria for lectures from: Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB., Shelly Kafka Employee of: Janssen Scientific Affairs, LLC, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Elizabeth C Hsia Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Xie L Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Shihong Sheng Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Prasheen Agarwal Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Bei Zhou Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Paraneedharan Ramachandran Employee of: Janssen Research & Development, LLC, Iain McInnes Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer, and UCB

Background:Guselkumab (GUS), an interleukin-23 inhibitor, was efficacious in reducing signs and symptoms of active psoriatic arthritis (PsA) in patients (pts) in two phase 3 trials (DISCOVER-1 and DISCOVER-2).Objectives:To evaluate the efficacy of GUS in PsA pts with imaging-confirmed axial involvement consistent with sacroiliitis in DISCOVER-1&2.Methods:In DISCOVER-1, 381 pts with active PsA (≥ 3 swollen joints, ≥ 3 tender joints; C-reactive protein ≥ 0.3mg/dL despite standard therapies) and in DISCOVER-2, 739 pts with active PsA (≥ 5 swollen joints, ≥ 5 tender joints, CRP ≥ 0.6mg/dL despite standard therapies) were randomized 1:1:1 to GUS 100mg Q4W, GUS 100mg Q8W (Wk0, Wk4, then Q8W), or PBO. This analysis included pts with sacroiliitis at baseline who had either documented imaging confirmation of sacroiliitis in the past or pelvic X-ray confirmation of sacroiliitis at screening (pooled data from DISCOVER-1&2) based on investigators’ judgment of presence/absence of sacroiliitis. Efficacy was assessed by BASDAI score, BASDAI50, modified BASDAI (mBASDAI; excludes Q#3), spinal pain (BASDAI Q#2), ASDAS-CRP score, and ASDAS responses of inactive disease (Results:312 pts presented with axial involvement (PBO, n= 118; GUS q8w, n = 91; GUS q4w, n = 103). The LS mean changes from baseline to wk24 in BASDAI, spinal pain, mBASDAI, and ASDAS-CRP were greater in the two GUS groups vs PBO (Table). Greater proportions of GUS-treated pts achieved BASDAI50 (Table) and ASDAS responses of inactive disease, major improvement, and clinically important improvement (Figure) at wk24 vs PBO.Conclusion:GUS improved axial symptoms over 24 weeks in active PsA patients with imaging-confirmed sacroiliitis.Table.Efficacy of GUS in PsA patients with axial involvement at week 24.aPBO(n=118)GUS 100 mg every 8 weeks(n=91)GUS100 mg every 4 weeks(n=103)LS Mean change in BASDAI-1.35-2.67*-2.68*LS Mean change in spinal painb-1.30-2.73*-2.48*BASDAI50c, %21/110 (19.1%)34/84 (40.5%)**36/95 (37.9%)**LS Mean change in modified BASDAId-1.13-2.16*-2.18*LS Mean change in ASDAS-CRP-0.71-1.43*-1.46*aPts with axial involvement consistent with sacroiliitis at baseline and either a history of imaging confirmation or pelvic X-ray at screening (pooled data from DISCOVER-1 & 2)bQuestion 2 of the BASDAI.cPts with BASDAI > 0 at baseline.dExcludes question 3 of the BASDAI.Unadjusted p-values as noted: *p < 0.001, ** p < 0.01Acknowledgments:NoneDisclosure of Interests:Philip Helliwell: 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, Denis Poddubnyy Grant/research support from: AbbVie, MSD, Novartis, and Pfizer, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB, Philip J Mease Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Janssen, Eli Lilly, Novartis, Pfizer, Sun Pharma, UCB Pharma, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Galapagos, Gilead, Novartis, Pfizer, Sun Pharma, UCB Pharma, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Genentech, Janssen, Novartis, Pfizer, UCB Pharma, Xenofon Baraliakos Grant/research support from: Grant/research support from: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Consultant of: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, 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, Xie L Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Shihong Sheng Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Prasheen Agarwal Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Bei Zhou Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Soumya D Chakravarty Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Chetan Karyekar Shareholder of: Johnson & Johnson, Consultant of: Janssen, Employee of: Janssen Global Services, LLC. Previously, Novartis, Bristol-Myers Squibb, and Abbott Labs., Atul Deodhar Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli-Lilly, Galapagos, Gilead Sciences, Inc., Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma; Director of Imaging Rheumatology BV

Objective.Assess 5-year golimumab (GOL) safety in rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS).Methods.Subcutaneous (SC) GOL (50 mg or 100 mg every 4 weeks) was evaluated in phase 3 trials of patients with active RA, PsA, and AS. Safety data through Year 5 were pooled across 3 RA trials [1 each evaluating methotrexate (MTX)-naive, MTX-experienced, and antitumor necrosis factor (TNF)-experienced patients], 1 PsA trial, and 1 AS trial. Data summarized was derived from both placebo-controlled (through weeks 24–52) and uncontrolled study periods. For adverse events (AE) of special interest [serious infections (SI), opportunistic infections (OI), deaths, malignancies, demyelination, tuberculosis (TB)], incidence per 100 patient-years (pt-yrs) was determined.Results.Across all trials, 639 patients received placebo and 2228 received SC GOL 50 mg only (n = 671), 50 mg and 100 mg (n = 765), or 100 mg only (n = 792). Safety followup extended for averages of 28.5 and 203.2 weeks for placebo and GOL, respectively. Respective placebo and GOL AE incidence/100 pt-yrs (95% CI) through Year 5 were 4.86 (2.83–7.78) and 3.29 (2.92–3.69) for SI, 0.00 (0.00–0.86) and 0.23 (0.14–0.35) for TB, 0.00 (0.00–0.86) and 0.22 (0.13–0.34) for OI, 0.00 (0.00–0.86) and 0.10 (0.05–0.20) for lymphoma, 0.00 (0.00–0.86) and 0.08 (0.03–0.17) for demyelination, and 0.29 (0.01–1.59) and 0.41 (0.29–0.57) for death. TB, OI, lymphoma, and demyelination incidence appeared to be higher among patients receiving GOL 100 mg only.Conclusion.SC GOL safety through Year 5 remained consistent with previously reported Year 3 findings and with other TNF antagonists. Numerically higher incidences of TB, OI, lymphoma, and demyelination were observed with 100 mg versus 50 mg. Clinicaltrials.gov identifiers: NCT00264537 (GO-BEFORE), NCT00264550 (GO-FORWARD), NCT00299546 (GO-AFTER), NCT00265096 (GO-REVEAL), and NCT00265083 (GO-RAISE).

Background In the GO-VIBRANT trial of intravenous golimumab in psoriatic arthritis (PsA), golimumab significantly inhibited radiographic progression. In post hoc analyses, we evaluated changes in total PsA-modified Sharp/van der Heijde scores (SHS) across levels of composite index-defined disease activity following treatment. Methods In this phase-3, double-blind, placebo-controlled trial, 480 bio-naïve patients with active PsA randomly received intravenous golimumab 2 mg/kg (N = 241; week 0, week 4, every 8 weeks [q8w]) or placebo (N = 239; week 0, week 4, week 12, week 20) followed by golimumab (week 24, week 28, q8w) through week 52. Week 24 and week 52 SHS changes in patient subgroups, defined by levels of disease activity as assessed by several composite measures (minimal disease activity [MDA], very low disease activity [VLDA], Psoriatic ArthritiS Disease Activity Score [PASDAS], Disease Activity in Psoriatic Arthritis [DAPsA], Clinical Disease Activity Index [CDAI]), were evaluated post hoc in 474 patients with evaluable radiographic data. Partially (last-observation-carried-forward methodology) and completely (nonresponder methodology) missing data were imputed. Results Across indices, golimumab-treated patients demonstrated less radiographic progression than placebo-treated patients, regardless of disease activity state achieved via golimumab, from week 0 to 24 (e.g., mean changes in PsA-modified SHS were − 0.83 vs. 0.91, respectively, in patients achieving MDA and − 0.05 vs. 1.49, respectively, in those not achieving MDA). Treatment differences observed at week 24 persisted through week 52, despite placebo-randomized patients crossing over to golimumab at week 24 (e.g., mean changes in PsA-modified SHS from week 0 to 52 for golimumab- vs. placebo→golimumab-treated patients achieving MDA were − 1.16 vs. 1.19, respectively) and regardless of whether low disease activity was achieved (0.03 vs. 1.50, respectively, in those not achieving MDA). Consistent patterns were observed for disease activity assessed using VLDA, PASDAS, DAPsA, and CDAI composite endpoints. Conclusions The extent of structural damage inhibition afforded by up to 1 year of intravenous golimumab treatment paralleled levels of PsA activity, with greater progression of structural damage observed in patients with sustained higher disease activity. Among patients not achieving low levels of disease activity across several composite indices, golimumab-randomized patients appeared to exhibit far less progression of structural damage than placebo-randomized PsA patients, illustrating a potential disconnect between responses, wherein golimumab can inhibit structural damage independent of clinical effect. Trial registration ClinicalTrials.gov. NCT02181673. Registered 04 July 2014.

Objectives Evaluate the effects of intravenous golimumab 2 mg/kg on multiple domains of health-related quality of life (HRQoL) in adult patients with active psoriatic arthritis (PsA). Methods In this phase III, randomized, double-blinded, placebo-controlled study, adults with active PsA were randomized in a 1:1 ratio to receive intravenous (IV) infusions of placebo (n = 239) or golimumab 2 mg/kg (n = 241) at weeks 0, 4, 12, and 20. Physical function was assessed using the Health Assessment Questionnaire-Disability Index (HAQ-DI). HRQoL was assessed using the 36-item Short-Form Health Survey Physical and Mental Component Summary (SF-36 PCS/MCS) scores, the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue, EQ VAS, and the Dermatology Life Quality Index (DLQI). Results Patients in the golimumab group had greater mean changes from baseline in HAQ-DI compared with placebo at weeks 8 (−0.52 vs −0.10), 14 (−0.60 vs −0.12), and 24 (−0.63 vs −0.14). Mean improvements from baseline in SF-36 PCS (8.0 vs 1.7), SF-36 MCS (5.0 vs 1.2), EQ VAS (17.2 vs 3.7), FACIT-Fatigue (7.9 vs 2.0), and DLQI (−7.2 vs −1.7) were also greater in the golimumab group versus placebo at week 8 and were maintained or increased through week 24. Greater proportions of golimumab-treated patients had improvements greater than or equal to the minimal clinically important difference (MCID) for HAQ-DI, SF-36 PCS/MCS, EQ VAS, FACIT-Fatigue, and DLQI scores at weeks 14 and 24. Conclusion Improvements in HRQoL were greater in the IV golimumab group compared with placebo and were evident at week 8 and sustained through week 24.

ObjectiveTo evaluate the efficacy of ustekinumab by prior treatment exposure and disease duration in tumour necrosis factor inhibitor (TNF)-naïve patients with psoriatic arthritis (PsA) in the PSUMMIT 1 and PSUMMIT 2 studies.MethodsIn the phase 3, randomised, placebo-controlled PSUMMIT 1 and PSUMMIT 2 studies, adults with active PsA for ≥6 months despite conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and/or non-steroidal anti-inflammatory drugs (NSAIDs) (PSUMMIT 1) or csDMARDs, NSAIDs and/or anti-TNF agents (PSUMMIT 2) were enrolled. Patients were randomised to subcutaneous injections of placebo, ustekinumab 45 mg or ustekinumab 90 mg at weeks 0 and 4 and every 12 weeks. Efficacy was assessed at week 24 using the American College of Rheumatology criteria and 28-joint count disease activity score using C reactive protein (DAS28-CRP); radiographical progression, enthesitis, and dactylitis were also assessed in this post hoc analysis.ResultsA total of 747 patients were included; all 747 were TNF-naïve, of which, 179 were methotrexate-naïve and TNF-naïve, and 146 were all csDMARD-naïve and TNF-naïve. At week 24, greater proportions of ustekinumab-treated patients had ≥20%/50%/70% improvement in American College of Rheumatology criteria (ACR20/ACR50/ACR70) responses, DAS28-CRP response and DAS28-CRP remission versus placebo in all three prior-treatment populations, with similar differences between treatment groups. Greater proportions of ustekinumab-treated patients also had complete resolution of enthesitis and dactylitis at week 24 across the three prior-treatment populations. Mean changes from baseline in total van der Heijde-Sharp Score at week 24 were generally smaller for ustekinumab-treated patients versus placebo but were statistically significant only in the full TNF-naïve population. Response rates for ACR20/ACR50/ACR70 were similar for TNF-naïve patients with PsA durations of ConclusionUstekinumab-treated patients demonstrated greater clinical response at week 24 compared with placebo regardless of prior treatment exposure and PsA disease duration.

Background GO-VIBRANT is a Phase 3 trial of intravenous (IV) golimumab (GLM) in adult patients (pts) with active psoriatic arthritis (PsA). Clinically meaningful improvements in skin and nail psoriasis (PsO) and in Dermatology Life Quality index (DLQI) that were significantly greater than placebo (PBO) at weeks (wks) 14 & 24 were previously reported.1 Objectives To evaluate improvement in skin and nail PsO and DLQI with IV GLM through wk52. Methods Adult bio-naive PsA pts with active disease(≥5 swollen & tender joints, CRP ≥0.6mg/dL, active plaque psoriasis or documented history), despite treatment w/csDMARDs &/or NSAIDs, were randomized to IV GLM 2mg/kg at wks 0/4 & every 8 wks thereafter or PBO at wks 0/4/12/20 with crossover to GLM at wk24. Pts with ≥3% body surface area (BSA) psoriasis at baseline (BL) were assessed using Psoriasis area and Severity index (PASI, 0-72) of 75/90/100% improvement scale, modified Nail Psoriasis Severity index (mNAPSI, 0-130) in pts with mNAPSI >0 at BL, and DLQI (0-30) scale. Results 394 pts (PBO:n=198; GLM:n=196) had ≥3% BSA psoriasis at BL; 76.5% had mNAPSI>0 at BL(mean 18.6). Pts on IV GLM achieved a greater PASI 75 response rate (RR) vs PBO at wk24 (64.8% vs 13.1%, p 1 at baseline, rate of simultaneous achievement of both PASI 50 response & improvement in DLQI ≥5 was greater at wk24 with IV GLM (59.2%) vs PBO (8.1%, p Conclusion Clinically meaningful improvements in skin and nail psoriasis and psoriasis quality of life after IV GLM treatment of PsA pts were maintained from 24 to 52 weeks of treatment. References [1] Mease P, et al. EULAR. June2018, amsterdam, NL. Disclosure of interests M Elaine Husni Grant/research support from: Janssen, Philip J Mease Grant/research support from: abbVie, amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, SUN and UCB, Consultant for: abbVie, amgen, BMS, Galapagos, Gilead Sciences, inc., Janssen, Lilly, Novartis, Pfizer, SUN and UCB, Speakers bureau: abbVie, amgen, BMS, Celgene, Genentech, Janssen, Lilly, Novartis, Pfizer and UCB, Soumya D Chakravarty Shareholder of: Johnson & Johnson, Employee of: Johnson & Johnson, Shelly Kafka Shareholder of: J&J, Employee of: J&J, Diane D Harrison Employee of: Janssen Research & Development, LLC, Dennis Parenti Employee of: Janssen Research & Development, LLC, Lilianne Kim Employee of: Janssen Research & Development, LLC, Kim Hung Lo Employee of: Janssen Research & Development, LLC, Elizabeth C Hsia Employee of: Employee of Janssen Research & Development, LLC, arthur Kavanaugh Grant/research support from: UCB Pharma

Background: Psoriatic arthritiS Disease activity Score (PASDAS), GRAppa Composite scorE (GRACE) index, modified Composite Psoriatic Disease activity index (mCPDAI), and Disease activity index for PSoriatic arthritis (DAPSA) are composite indices recently developed to assess disease activity in psoriatic arthritis (PsA).1,2 Guselkumab (GUS) is a monoclonal antibody targeting interleukin-23 that has demonstrated efficacy in a phase 2 PsA trial.3 Objectives: To compare the effect of GUS on disease activity in psoriatic arthritis (PsA) as measured by these composite indices. Methods: In this Phase-2 trial, patients with active PsA (≥3 tender, ≥3 swollen joints, C-reactive protein ≥3 mg/L, ≥3% body surface area) were randomized 2:1 to subcutaneous GUS 100mg (n=100) or placebo (PBO, n=49) at Wk0, Wk4, and every 8 wks through Wk44. At Wk16, patients with Results: Changes in SF-36 PCS score were consistent with disease activity states at Wk24 for each PsA composite index in guselkumab-treated patients. The SMD, ES and SRM indicated that guselkumab elicited a substantial effect in treating the diverse manifestations of PsA compared with placebo, regardless of composite index employed (Figure). PASDAS and GRACE indices appeared to be more sensitive than mCPDAI and DAPSA in detecting changes upon treatment and distinguishing guselkumab treatment effects relative to placebo. Residual disease activities among guselkumab-treated patients who achieved low disease activity at Week24 based on each PsA composite index are summarized in the Table. Conclusion: Regardless of the PsA-specific composite index employed, GUS significantly improved disease activity and achieved clinically meaningful therapeutic targets such as low/minimal disease activity or remission. PASDAS and GRACE indices were more sensitive than mCPDAI and DAPSA in detecting changes in disease activity by guselkumab treatment. References [1] Helliwell PS, et al. JRheumatol2014;41:1212-1217. [2] Scholes MM, et al. AnnRheumDis2016;75:811-818. [3] Deodhar a, et al. Lancet2018;391: 2213–24. Disclosure of interests: Philip Helliwell Grant/research support from: Paid to charity: from abbVie, Janssen and Novartis, Consultant for: Paid to charity: from abbVie, amgen, Pfizer, and UCB and Celgene. Paid to self: from Celgene and Galapagos, atul Deodhar Grant/research support from: abbVie, amgen, Eli Lilly, GSK, Janssen, Novartis, Pfizer, and UCB, Consultant for: abbVie, amgen, BMS, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, alice B Gottlieb Grant/research support from: PI: incyte Corporation, Janssen-Ortho inc., Lilly ICOS LLC, Novartis, UCB, XBiotech, Consultant for: abbVie, Dermira, incyte Corporation, Lilly ICOS LLC, Novartis, Sun Pharmaceutical industries Ltd., avotres (unpaid), XBiotech (unpaid), Speakers bureau: abbVie, Eli Lilly and Company, Janssen Biotech; advisory board: Bristol-Myers Squibb, Celgene Corporation, Janssen Biotech, Janssen-Ortho inc., LEO Pharma, Novartis, UCB, Wolf-Henning Boehncke Consultant for: Pfizer inc, Speakers bureau: Pfizer inc, Xie L Xu Employee of: Employee of Janssen Research & Development, LLC, Stephen Xu Employee of: Employee of Janssen Research & Development, LLC, Yuhua Wang Employee of: Employee of Janssen Research & Development, LLC, Elizabeth C Hsia Employee of: Employee of Janssen Research & Development, LLC, Dafna D Gladman Grant/research support from: abbVie, amgen, Celgene, Lilly, Novartis, Pfizer, and UCB, Consultant for: abbVie, amgen, BMS, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB, Christopher T. Ritchlin Grant/research support from: abbVie, amgen, UCB Pharma, Consultant for: abbVie, amgen, Lilly, Novartis, Pfizer, UCB Pharma

Background Guselkumab (GUS) is a monoclonal antibody targeting interleukin-23 that has demonstrated efficacy in a phase 2 trial of psoriatic arthritis (PsA).1 Objectives Here subgroup analyses were conducted to evaluate the consistency of efficacy on the primary endpoint, ACR20 response. Methods In this randomized, double-blind, placebo-controlled, Phase-2 trial, pts with active PsA (≥3 tender, ≥3 swollen joints, C-reactive protein ≥3 mg/L, ≥3% body surface area [BSA] of plaque psoriasis) despite current or previous treatment with standard-of-care therapies were randomized 2:1 to subcutaneous GUS 100 mg (n=100) or placebo (PBO, n=49) at Wk0, Wk4, and every 8 wks (q8w) through Wk44. At Wk16, pts with Results At Wk24, 58/100 (58·0%) of pts in the GUS vs 9/49 (18.4%) in the PBO group achieved an ACR20 response (p 10%, tender joint count ≤10 or swollen joint count ≤10 appeared to have numerically higher ACR20 response rate than those corresponding subgroups defined otherwise, although the sample size is small and the data should be interpreted with caution. Conclusion In this phase 2 trial of patients with PsA, GUS demonstrated efficacy consistently across subgroups of pts according to baseline demographics, disease characteristics, and PsA-medication use. The relationship between baseline characteristics and clinical outcome will be further explored in phase 3 studies with a larger PsA population. Reference [1] Deodhar A, et al. Lancet 2018;391: 2213–24. Disclosure of Interests Iain McInnes Grant/research support from: AstraZeneca, Celgene, Compugen, Novartis, Roche, UCB Pharma, Consultant for: AbbVie, Celgene, Galvani, Lilly, Novartis, Pfizer, UCB Pharma, Philip Helliwell Grant/research support from: Paid to charity: from AbbVie, Janssen and Novartis, Consultant for: Paid to charity: from AbbVie, Amgen, Pfizer, and UCB and Celgene. Paid to self: from Celgene and Galapagos, Alice B Gottlieb Grant/research support from: PI: Incyte Corporation, Janssen-Ortho Inc., Lilly ICOS LLC, Novartis, UCB, XBiotech, Consultant for: AbbVie, Dermira, Incyte Corporation, Lilly ICOS LLC, Novartis, Sun Pharmaceutical Industries Ltd., Avotres (unpaid), XBiotech (unpaid), Speakers bureau: AbbVie, Eli Lilly and Company, Janssen Biotech; advisory board: Bristol-Myers Squibb, Celgene Corporation, Janssen Biotech, Janssen-Ortho Inc., LEO Pharma, Novartis, UCB, Wolf-Henning Boehncke Consultant for: Pfizer Inc, Speakers bureau: Pfizer Inc, Xie L Xu Employee of: Employee of Janssen Research & Development, LLC, Stephen Xu Employee of: Employee of Janssen Research & Development, LLC, Yuhua Wang Employee of: Employee of Janssen Research & Development, LLC, Elizabeth C Hsia Employee of: Employee of Janssen Research & Development, LLC, Atul Deodhar Grant/research support from: AbbVie, Amgen, Eli Lilly, GSK, Janssen, Novartis, Pfizer, and UCB, Consultant for: AbbVie, Amgen, BMS, Eli Lilly, Janssen, Novartis, Pfizer, and UCB

Background Psoriatic ArthritiS Disease Activity Score (PASDAS), GRAppa Composite scorE (GRACE) Index, modified Composite Psoriatic Disease Activity Index (mCPDAI), and Disease Activity Index for PSoriatic Arthritis (DAPSA) are composite indices recently developed to assess disease activity in psoriatic arthritis (PsA).1,2 Objectives The effect of guselkumab (GUS) on these indices was evaluated in a phase 2 study in patients with active PsA. Methods Patients with ≥3 tender and ≥3 swollen joints, C-reactive protein ≥3 mg/L, and ≥3% body surface area (BSA) of plaque psoriasis despite treatment were randomized 2:1 to receive GUS 100 mg subcutaneously (N=100) or placebo (PBO, N=49) at Weeks 0, 4, and every 8 weeks thereafter through Week44. At Week16, patients with Results Baseline PASDAS, GRACE, mCPDAI, and DAPSA showed moderate to high disease activity (mean (SD): 6.53 (1.079), 6.08 (1.208), 7.6 (2.15), and 46.65 (20.391), respectively), and were generally comparable between PBO and GUS. At Week24, GUS significantly decreased PASDAS, GRACE, mCPDAI, and DAPSA scores (mean (SD) change from baseline: -2.50 (1.59), -2.73 (1.76), -3.8 (2.72), -23.08 (20.21), respectively) vs PBO (mean (SD) change from baseline: -0.49 (1.33), -0.35 (1.39), -0.8 (2.16), -4.97 (20.11), respectively, all p Conclusion GUS demonstrated consistent improvements based on all PsA composite indices evaluated, and efficacy was maintained through Week44. References [1] Helliwell PS, FitzGerald O, and Fransen J. JRheumatol2014;41:1212-1217. [2] Scholes MM, Aletaha D, Alasti F, Smolen JS. AnnRheumDis2016;75:811-818. Disclosure of Interests Dafna D Gladman Grant/research support from: AbbVie, Amgen, Celgene, Lilly, Novartis, Pfizer, and UCB, Consultant for: AbbVie, Amgen, BMS, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB, Philip Helliwell Grant/research support from: Paid to charity: from AbbVie, Janssen and Novartis, Consultant for: Paid to charity: from AbbVie, Amgen, Pfizer, and UCB and Celgene. Paid to self: from Celgene and Galapagos, Atul Deodhar Grant/research support from: AbbVie, Amgen, Eli Lilly, GSK, Janssen, Novartis, Pfizer, and UCB, Consultant for: AbbVie, Amgen, BMS, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Alice B Gottlieb Grant/research support from: PI: Incyte Corporation, Janssen-Ortho Inc., Lilly ICOS LLC, Novartis, UCB, XBiotech, Consultant for: AbbVie, Dermira, Incyte Corporation, Lilly ICOS LLC, Novartis, Sun Pharmaceutical Industries Ltd., Avotres (unpaid), XBiotech (unpaid), Speakers bureau: AbbVie, Eli Lilly and Company, Janssen Biotech; advisory board: Bristol-Myers Squibb, Celgene Corporation, Janssen Biotech, Janssen-Ortho Inc., LEO Pharma, Novartis, UCB, Wolf-Henning Boehncke Consultant for: Pfizer Inc, Speakers bureau: Pfizer Inc, Xie L Xu Employee of: Employee of Janssen Research & Development, LLC, Stephen Xu Employee of: Employee of Janssen Research & Development, LLC, Yuhua Wang Employee of: Employee of Janssen Research & Development, LLC, Elizabeth C Hsia Employee of: Employee of Janssen Research & Development, LLC, Christopher T. Ritchlin Grant/research support from: AbbVie, Amgen, UCB Pharma, Consultant for: AbbVie, Amgen, Lilly, Novartis, Pfizer, UCB Pharma

Background The GO-FURTHER, GO-VIBRANT, and GO-ALIVE randomized controlled trials evaluated the efficacy and safety of intravenous (IV) golimumab (GLM) in patients (pts) with active rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS), respectively. Objectives This integrated analysis assessed safety events across indications in pts who received IV GLM. Methods Integrated safety data from 3 Phase 3, double-blind, placebo (PBO)-controlled trials were analyzed up to week (WK) 112 in RA pts and up to WK 60 in PsA and AS pts. Pts received either IV PBO or IV GLM (2 mg/kg) at 0, 4, 12, and 20 WKS. PBO pts crossed over to IV GLM at WK 24, except RA pts randomized to PBO who met early escape criteria crossed over at WK 16 and AS pts randomized to PBO who crossed over at WK 16. Cumulative adverse events (AEs) were reported by indication and pooled by treatment. Anti-drug antibodies (ADAs) were evaluated. Results Overall, 1248 pts were treated with IV GLM across indications. A numerically greater proportion (%) of IV GLM pts with RA reported safety events than pts with PsA or AS (Table 1): SAEs (18.2 vs 5.2 vs 3.4), infections (49.1 vs 22.8 vs 32.8), serious infections (6.2 vs 2.2 vs 1.5), and infusion reactions (4.6 vs 0.9 vs 1.5). Incidence (per 100 pt-years) of opportunistic infections, malignancy, active tuberculosis, and death with IV GLM was low (≤0.5) across indications (Table 2). Infections were the most commonly reported type of SAE among pooled IV GLM pts; the most frequent was pneumonia (10 [0.8%]). Incidence (per 100 pt-years) of serious infections was similar among IV GLM pts with and without corticosteroid use (3.35 vs 3.37, respectively). Overall, 1 IV GLM pt (PsA) experienced a demyelination event. A numerically greater proportion of IV GLM pts discontinued due to an AE than PBO pts (5.0% vs 0.9%, respectively). In IV GLM pts with baseline alanine aminotransferase (ALT) ≤ upper limit of normal (ULN), 1.2% had post-baseline ALT elevations ≥5X ULN. The proportion of IV GLM and PBO pts with post-baseline ALT elevations ≥5X ULN was 2.1% vs 0% with methotrexate and 0.7% vs 1.4% without methotrexate use at baseline, respectively. Using a drug-tolerant enzyme immunoassay, the incidence of ADAs was 22% through WK 52 across indications, which primarily consisted of low titer ADAs. Conclusion IV GLM demonstrated a consistent safety profile across indications in the PBO-controlled (up to WK 24) and uncontrolled study periods. Similar to WK 24 (1), more safety events occurred in RA pts, who represented the largest study population with older pts, longer disease duration, and more concomitant medication use. References [1] Husni ME, et al. Presented at EULAR 2018, Amsterdam, the Netherlands. Disclosure of Interests Atul Deodhar Grant/research support from: AbbVie, Amgen, Eli Lilly, GSK, Janssen, Novartis, Pfizer, and UCB, Consultant for: AbbVie, Amgen, BMS, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, M Elaine Husni Grant/research support from: Janssen, Sergio Schwartzman Shareholder of: Amgen, Boston Scientific, Gilead, Medtronic, and Pfizer, Consultant for: AbbVie, Crescendo, Dermtech, Janssen, Gilead, Lilly, Myriad, Novartis, Regeneron, Samsung, Sanofi, and Union Chimique Belge, Speakers bureau: Abbott/AbbVie, Genentech, Janssen, Lilly, Novartis, Pfizer, Regeneron, Sanofi, and Union Chimique Belge, Shelly Kafka Shareholder of: J&J, Employee of: J&J, Soumya D Chakravarty Shareholder of: Johnson & Johnson, Employee of: Johnson & Johnson, Elizabeth C Hsia Employee of: Employee of Janssen Research & Development, LLC, Diane D Harrison Employee of: Janssen Research & Development, LLC, Jocelyn H Leu Employee of: Janssen Research & Development, LLC, Yiying Zhou Employee of: Janssen Research & Development, LLC, Kim Hung Lo Employee of: Janssen Research & Development, LLC, Arthur Kavanaugh Grant/research support from: UCB Pharma