Supporting Evidence for the Efficacy of MabThera® (rituximab) in RA
The aim of DANCER was to examine the efficacy and safety of different MabThera doses plus methotrexate, with or without the administration of glucocorticoids, in patients with active RA who were resistant to DMARDS, including tumour necrosis factor (TNF) inhibitors. There were nine treatment groups in total: three MabThera groups (placebo, 500 mg and 1000 mg), each also taking placebo glucocorticoids, intravenous glucocorticoid premedication, or intravenous glucocorticoid pretreatment plus oral glucocorticoids for 2 weeks. At Week 24, 55% and 54% of patients receiving MabThera 2 x 500 mg and 2 x 1000 mg achieved an American College of Rheumatology (ACR) 20 response, respectively, compared with only 28% of patients in the placebo arm (p<0.0001). Of patients receiving MabThera 2 x 500 mg or 2 x 1000 mg, 33% and 34%, respectively, achieved ACR50, compared with only 13% in the placebo group (p<0.001 for comparisons of the placebo and active arms). This response rate was achieved despite the fact that 30–40% of patients had been exposed to TNF inhibitor therapy at baseline (Emery et al. 2006).
The highest response level (ACR70) was attained by 20% of patients who received MabThera 2 x 1000 mg and 13% of patients who received MabThera 2 x 500 mg, compared with only 5% of patients in the placebo arm (p≤0.001 and p=0.029 for comparison of the placebo group with each active group, respectively). Although no dose–response relationship was established based on ACR20 for the two MabThera doses studied, there was an overall trend towards a higher proportion of patients achieving ‘high efficacy’ endpoints (ACR70, ACRn, EULAR [European League Against Rheumatism] good response, EULAR remission, and EULAR low disease) in patients treated with MabThera 2 x 1000 mg, compared with those receiving MabThera 2 x 500 mg (Emery et al. 2006).
Evidence for the maintenance of efficacy of MabThera with repeated treatment courses comes from an open-label extension study. Patients with an inadequate response to DMARDs who had previously received MabThera in Phase II studies, including DANCER, were eligible to receive a subsequent treatment course of two infusions of MabThera if they had shown a predefined improvement after the first course of treatment but still had residual disease activity (Emery et al. 2006 ). When assessed for clinical signs and symptoms of RA after 24 weeks, a higher proportion of patients receiving their second MabThera treatment course achieved ACR20, ACR50 or ACR70 responses, low disease activity (DAS28≤3.2) and remission (DAS28<2.6), compared with their first MabThera course. These data are consistent with that seen for TNF inhibitor IR patients (Keystone et al. 2006), indicating that there is a trend towards further improvement in response with subsequent MabThera treatment courses.