Sustained inhibition of progressive joint damage with rituximab plus methotrexate in early active rheumatoid arthritis: 2-year results from the randomised controlled trial IMAGE

Abstract

BackgroundIn the IMAGE study, rituximab plus methotrexate (MTX) inhibited joint damage and improved clinical outcomes at 1 year in MTX-naïve patients with early active rheumatoid arthritis.ObjectiveThe aim of this study was to assess joint damage progression and clinical outcomes over 2 years.MethodsPatients (n=755) were randomised to receive rituximab 2×500 mg+MTX, 2×1000 mg+MTX or placebo+MTX. The placebo-controlled period continued to week 104. Two-year end points were defined as secondary or exploratory and included change in total Genant-modified Sharp score (mTSS), total erosion score and joint space narrowing score from baseline to week 104. Clinical efficacy and physical function end points were also assessed.ResultsAt 2 years, rituximab 2×1000 mg+MTX maintained inhibition of progressive joint damage versus MTX alone (mTSS change 0.41 vs 1.95; p<0.0001 (79% inhibition)), and a higher proportion of patients receiving rituximab 2×1000 mg+MTX had no radiographic progression over 2 years compared with those receiving MTX alone (57% vs 37%; p<0.0001). Contrary to 1-year results, exploratory analysis of rituximab 2×500 mg+MTX at 2 years showed that progressive joint damage was slowed by ∼61% versus placebo+MTX (mTSS, exploratory p=0.0041). Improvements in clinical signs and symptoms and physical function seen after 1 year in rituximab-treated patients versus those receiving placebo were maintained at year 2. Safety profiles were similar between groups.ConclusionsTreatment with rituximab 2×1000 mg+MTX was associated with sustained improvements in radiographic, clinical and functional outcomes over 2 years.Clinical trials.gov identifier NCT00299104.

Animal models of rheumatoid arthritis: How informative are they?

“…Another validated approach in human RA is anti-B cell (anti-CD20) mAb therapy, which is administered primarily to anti-TNF non-responders (Tak et al, 2012). Although anti-CD20 treatment has not been tested specifically in animal models, B cell deletion or depletion is known to protect against arthritis (Svensson et al, 1998;Yanaba et al, 2007) and anti-CD19 mAb therapy was found to effective in CIA, without depleting B cells (Cemerski et al, 2010).…”

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

“…Most adverse events tar a artrite reumatoide (22)(23)(24). Estudos clínicos também evidenciaram que essas drogas são seguras (17,19,20 De acordo com um estudo denominado "IMAGE trial" (27,28), não incluído em nossas meta-análises por apresentar dados após 52 semanas de tratamento, mas delineado de forma a se encaixar nos demais critérios de inclusão do nosso estudo, aproximadamente 42 % dos pacientes usando placebo atingiram o ACR50, e 65 % dos pacientes usando rituximabe 1,0 g x 2 atingiram esse resultado. Isso significa que houve uma melhora dos pacientes considerando esse parâmetro clínico.…”

“…there was no difference between rituximabtreated patients and the control group. According to a large study called "IMAGE trial" (27,28), which was not included in our meta-analyses because it presents data after 52 weeks of treatment although it fits the other criteria, approximately 42 % of the patients on placebo achieved ACR50, and 65 % of the patients on rituximab 1,0 g x 2 achieved this parameter. This means that there was an improvement in this clinical outcome.…”

The Efficacy and Safety of Rituximab Biosimilar (Acellbia®) in Rheumatoid Arthritis as the First Biological Agent: Results of Phase Iii (Alterra) Clinical Trial

“…Результаты крупномасштабных РКИ свиде-тельствуют о сходной эффективности двух инфузий РТМ в дозах 500 и 1000 мг [36][37][38][39][40][41][42][43][44][45][46] (табл. 3).…”

“…По критерию «non-inferiority» (эффективность/безо-пасность/переносимость метода лечения не ниже, чем у ак-тивного контроля) низкие дозы РТМ не уступают высоким дозам по ACR20, ACR50 и динамике DAS28 через 24 и 48 нед. Представляют интерес отдаленные результаты ис-следования IMAGE, согласно которым сходная эффектив-ность и безопасность низких и высоких доз РТМ сохраня-лись в течение 104 нед [44]. Достоверных различий разных доз РТМ в отношении подавления прогрессирования дест-рукции суставов по данным рентгенологического исследо-вания отмечено не было.…”