Guselkumab in biologic-naive patients with active psoriatic arthritis (DISCOVER-2): a double-blind, randomised, placebo-controlled phase 3 trial
| Autor: | Mease, P.J., Rahman, P., Gottlieb, A.B., Kollmeier, A.P., Hsia, E.C., Xu, X.L., Sheng, S.H., Agarwal, P., Zhou, B., Zhuang, Y.L., Heijde, D. van der, McInnes, I.B., Discover-2 Study Grp |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Male medicine.medical_specialty Phases of clinical research 030204 cardiovascular system & hematology Antibodies Monoclonal Humanized Placebo Severity of Illness Index Double blind Therapy naive 03 medical and health sciences Psoriatic arthritis 0302 clinical medicine Double-Blind Method Internal medicine medicine Clinical endpoint Humans 030212 general & internal medicine business.industry Arthritis Psoriatic General Medicine Middle Aged medicine.disease Rheumatology Treatment Outcome Guselkumab Antirheumatic Agents Female business |
| Zdroj: | The Lancet, 395(10230), 1126-1136. ELSEVIER SCIENCE INC |
| ISSN: | 0140-6736 |
| DOI: | 10.1016/s0140-6736(20)30263-4 |
| Popis: | Background:\ud The interleukin-23 (IL-23)/T-helper 17 cell pathway is implicated in psoriatic arthritis pathogenesis. Guselkumab, an IL-23 inhibitor that specifically binds the IL-23 p19 subunit, significantly and safely improved psoriatic arthritis in a phase 2 study. DISCOVER-2 was a phase 3 trial to assess guselkumab in biologic-naive patients with psoriatic arthritis.\ud \ud Methods:\ud This phase 3, double-blind, placebo-controlled study was done at 118 sites in 13 countries across Asia, Europe, and North America. We enrolled biologic-naive patients with active psoriatic arthritis (at least five swollen joints, at least five tender joints, and C-reactive protein ≥0·6 mg/dL) despite standard therapies. Patients were randomly assigned (1:1:1, computer-generated permuted blocks; stratified by baseline disease-modifying antirheumatic drug use and C-reactive protein concentration) to subcutaneous injections of guselkumab 100 mg every 4 weeks; guselkumab 100 mg at weeks 0, 4, then every 8 weeks; or placebo. The primary endpoint was American College of Rheumatology 20% improvement (ACR20) response at week 24 in all patients per assigned treatment group. Safety was assessed in all patients per treatment received. This trial is registered at ClinicalTrials.gov, NCT03158285 (active, not recruiting).\ud \ud Findings:\ud From July 13, 2017, to Aug 3, 2018, 1153 patients were screened, of whom 741 were randomly assigned to receive guselkumab every 4 weeks (n=246), every 8 weeks (n=248), or placebo (n=247). One patient in the every 4 weeks group and one in the placebo group did not start treatment, and the remaining 739 patients started treatment; 716 patients continued treatment up to week 24. Significantly greater proportions of patients in the guselkumab every 4 weeks group (156 [64%] of 245 [95% CI 57–70]) and every 8 weeks group (159 [64%] of 248 [58–70]) than in the placebo group (81 [33%] of 246 [27–39]) achieved an ACR20 response at week 24 (percentage differences vs placebo 31% [95% CI 22–39] for the every 4 weeks group and 31% [23–40] for the every 8 weeks group; both p |
| Databáze: | OpenAIRE |
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