Background: The interleukin-23/Th17 pathway is implicated in psoriatic arthritis pathogenesis. Guselkumab, a an interleukin-23-inhibitor that specifically binds the IL23p19-subunit, human anti-interleukin-23p19-subunit monoclonal antibody, significantly and safely improved psoriatic arthritis in a Phase-2 study. Methods: This Phase-3, double-blind, placebo-controlled study (118 sites in 13 countries) enrolled biologic-naïve patients with active psoriatic arthritis (≥5 swollen, ≥5 tender joints, C-reactive-protein ≥0•6mg/dL) despite standard therapies. Patients were randomised (1:1:1; computer-generated permuted blocks; stratified by baseline disease-modifying antirheumatic drug use and C-reactive-protein) to subcutaneous guselkumab 100mg every-4-weeks (q4w); guselkumab 100mg at Weeks 0, 4, every-8-weeks (q8w); or placebo. The primary endpoint was ACR20 response at Week24 among randomized and treated patients. Clinicaltrials.gov identifier-NCT03158285 (active-not recruiting). Findings: From 07/13/2017-03/06/2019, 739 randomised patients received guselkumab q4w (N=245), q8w (N=248), or placebo (N=246); 716 patients continued treatment through Week24. Significantly greater proportions of guselkumab q4w-(156 [63•74%] of 245; 95% confidence interval: 57%, 70%) and q8w-(159 [64•1%] of 248; 95% confidence interval: 58%, 70%) than placebo-(81 [32•93%] of 246; 95% confidence interval: 27%, 39%) treated patients achieved Week24 ACR20 response (% differences [95% confidence intervals]: 30•81 (22•4, 39•1) and 31•2 (22•93, 39•540), respectively; both p<0•0001). Both guselkumab regimens significantly improved psoriasis, enthesitis, dactylitis, physical function, and quality-of-life vs. placebo at Week24. Mean changes in total modified van der Heijde-Sharp scores at Week24 were 4 significantly (0•29) and numerically (0•52) lower with guselkumab q4w and q8w, respectively, than placebo (0•95; p=0.011 and p=0.07). Through Week24, serious adverse events, and specifically serious infections, occurred in eight (3•3%) and three (1•2%) of 245 patients receiving guselkumab q4w, three (1•2%) and one (0•4<1%) of 248 receiving guselkumab q8w, and seven (2•83%) and one (0•4<1%) of 246 receiving placebo, respectively. No deaths occurred. Interpretation: Guselkumab, a human anti-interleukin-23p19-subunit monoclonal antibody that specifically inhibits interleukin-23 by binding the cytokine's p19-subunit, was efficacious and well tolerated in patients with active psoriatic arthritis who were biologic naive. These data support the further development of guselkumab for treating psoriatic arthritis.

Objective:The phase III GO-FORWARD study examined the efficacy and safety of golimumab in patients with active rheumatoid arthritis (RA) despite methotrexate therapy.Methods:Patients were randomly assigned in a 3 : 3 : 2 : 2 ratio to receive placebo injections plus methotrexate capsules (group 1, n  =  133), golimumab 100 mg injections plus placebo capsules (group 2, n  =  133), golimumab 50 mg injections plus methotrexate capsules (group 3, n  =  89), or golimumab 100 mg injections plus methotrexate capsules (group 4, n  =  89). Injections were administered subcutaneously every 4 weeks. The co-primary endpoints were the proportion of patients with 20% or greater improvement in the American College of Rheumatology criteria (ACR20) at week 14 and the change from baseline in the health assessment questionnaire-disability index (HAQ-DI) score at week 24.Results:The proportion of patients who achieved an ACR20 response at week 14 was 33.1% in the placebo plus methotrexate group, 44.4% (p = 0.059) in the golimumab 100 mg plus placebo group, 55.1% (p = 0.001) in the golimumab 50 mg plus methotrexate group and 56.2% (p<0.001) in the golimumab 100 mg plus methotrexate group. At week 24, median improvements from baseline in HAQ-DI scores were 0.13, 0.13 (p = 0.240), 0.38 (p<0.001) and 0.50 (p<0.001), respectively. During the placebo-controlled portion of the study (to week 16), serious adverse events occurred in 2.3%, 3.8%, 5.6% and 9.0% of patients and serious infections occurred in 0.8%, 0.8%, 2.2% and 5.6%, respectively.Conclusion:The addition of golimumab to methotrexate in patients with active RA despite methotrexate therapy significantly reduced the signs and symptoms of RA and improved physical function.

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This is a repository copy of Guselkumab in patients with active psoriatic arthritis who were biologic-naive or had previously received TNFα inhibitor treatment (DISCOVER-1): a double-blind, randomised, placebo-controlled phase 3 trial.