Rituximab for rheumatoid arthritis refractory to anti–tumor necrosis factor therapy: Results of a multicenter, randomized, double‐blind, placebo‐controlled, phase III trial evaluating primary efficacy and safety at twenty‐four weeks

Abstract

Objective. To determine the efficacy and safety of treatment with rituximab plus methotrexate (MTX) in patients with active rheumatoid arthritis (RA) who had an inadequate response to anti-tumor necrosis factor (anti-TNF) therapies and to explore the pharmacokinetics and pharmacodynamics of rituximab in this population.Methods. We evaluated primary efficacy and safety at 24 weeks in patients enrolled in the Random- Results. Patients assigned to placebo (n ‫؍‬ 209) and rituximab (n ‫؍‬ 311) had active, longstanding RA. At week 24, significantly more (P < 0.0001) rituximabtreated patients than placebo-treated patients demonstrated ACR20 (51% versus 18%), ACR50 (27% versus 5%), and ACR70 (12% versus 1%) responses and moderate-to-good EULAR responses (65% versus 22%).

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

“…5–7 The findings of the present study demonstrate not only that the efficacy of CT-P10 is comparable to RTX, but that it is of similar magnitude to that reported in the pivotal RCTs of RTX in combination with MTX. 5–7 …”

“…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.…”

“…The 95% confidence intervals (CI; −0.29, 0.21) of the estimated treatment difference between CT-P10 and RTX (−0.04) were entirely within a systematic literature review-derived statistical equivalence margin of ±0.5, as well as the margin of ±0.6 derived from the pivotal REFLEX study 5 and European League Against Rheumatism (EULAR) response criteria. The treatment difference (95% CI) was highly similar in the all-randomized population (−0.04 [−0.28, 0.21]).…”

“…5–7 These studies reported variable proportions of RTX-treated patients achieving ACR and EULAR responses at 24 weeks (ACR20, 51–73%; ACR50, 27–43%; ACR70, 12–23%; and EULAR moderate-to-good, 65–83%), and changes from baseline in DAS28-ESR at 24 weeks (−1.90 to −2.60). 5–7 The findings of the present study demonstrate not only that the efficacy of CT-P10 is comparable to RTX, but that it is of similar magnitude to that reported in the pivotal RCTs of RTX in combination with MTX. 5–7 …”

“…2–4 The efficacy of RTX in combination with methotrexate (MTX) in patients with active RA was established in randomized controlled trials (RCTs) published over a decade ago. 5–7 …”