Efficacy and safety of different doses and retreatment of rituximab: a randomised, placebo-controlled trial in patients who are biological naive with active rheumatoid arthritis and an inadequate response to methotrexate (Study Evaluating Rituximab's Efficacy in MTX iNadequate rEsponders (SERENE))

Abstract

ObjectivesThis phase III study evaluated the efficacy and safety of rituximab plus methotrexate (MTX) in patients with active rheumatoid arthritis (RA) who had an inadequate response to MTX and who were naïve to prior biological treatment.MethodsPatients with active disease on stable MTX (10–25 mg/week) were randomised to rituximab 2×500 mg (n=168), rituximab 2×1000 mg (n=172), or placebo (n=172). From week 24, patients not in remission (Disease Activity Score (28 joints) ≥2.6) received a second course of rituximab; patients initially assigned to placebo switched to rituximab 2×500 mg. The primary end point was American College of Rheumatology 20 (ACR20) response at week 24. All patients were followed until week 48.ResultsAt week 24, both doses of rituximab showed statistically superior efficacy (p<0.0001) to placebo (ACR20: 54%, 51% and 23%; rituximab (2×500 mg) + MTX, rituximab (2×1000 mg) + MTX and placebo + MTX, respectively). Secondary end points were also significantly improved for both rituximab groups compared with placebo. Further improvements in both rituximab arms were observed from week 24 to week 48. Rituximab + MTX was well tolerated, demonstrating comparable safety to placebo + MTX through to week 24, and between rituximab doses through to week 48.ConclusionsRituximab (at 2×500 mg and 2×1000 mg) plus MTX significantly improved clinical outcomes at week 24, which were further improved by week 48. No significant differences in either clinical or safety outcomes were apparent between the rituximab doses.

Comparison of biosimilar CT-P10 and innovator rituximab in patients with rheumatoid arthritis: a randomized controlled Phase 3 trial

“…The proportions observed in this study are slightly lower than historical studies of RTX where the incidence of IRRs following the first infusion has ranged from 23–32%, and declined following the second infusion (6–9%). 5,7,18 However, the present results demonstrate a similar pattern of IRR predominantly occurring during the first infusion.…”

“…Data from four RCTs identified in this review were used to determine an appropriate equivalence margin. 5–7,18 All patients who received at least one full dose of study drug and provided at least one post-treatment PD result were included in the PD population. All patients that received study drug were included in the safety population.…”

Assessing Efficacy, Safety and Tolerability of Rituximab for Rheumatoid Arthritis: Meta-Analyses of Randomized Controlled Trials

“…Para a avaliação da eficácia do rituximabe na 24ª semana de tratamento, quatro estudos foram analisados (13,17,19,20 Uma alta heterogeneidade estatística foi observada somente para a meta-análise do ACR70. Essa alta heterogeneidade não pode ser explicada por diferenças clíni-cas ou metodológicas nos estudos.…”

“…These patients also had been using methotrexate for at least twelve weeks (except for Strand, 2006) before the randomization. Two studies (19,20) compared, besides rituximab versus placebo in the conventional dose, another dosage of rituximab (2 courses of 500 mg). A further two studies (13, 17) compared another scheme of intervention (rituximab + cyclophosphamide).…”

Systematic review of 2008-2012 literature and update of recommendations for the use of methotrexate in rheumatic diseases, with a focus on rheumatoid arthritis

“…The only combination with a better risk/benefit profile than MTX alone was MTX + Hydroxychloroquine + Sulfasalazine (44). Two recent studies have compared the efficacy and safety of this triple combination therapy to that of anti-TNF, revealing that the addition of a biological drug (not only anti-TNF) improves both clinical and radiological outcomes (45)(46)(47)(48). The recommendation was approved by 76.5% of participants.…”