Artikel
Rituximab in combination with Leflunomide: Results from a multicenter randomized placebo controlled investigator initiated clinical trial in active Rheumatoid Arthritis (AMARA-Study)
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Veröffentlicht: | 29. August 2016 |
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Background: Use of biologicals such as Rituximab (RTX) in Rheumatoid Arthritis (RA) is effective and often only licensed in combination with Methotrexate (MTX). In cases of contraindications to or intolerances of MTX, other cDMARDs are frequently used in routine care without data from RCTs.
Methods: A total of 189 patients with active RA (DAS28 > 3.2 and at least 3 SJC and 3 TJC) despite stable leflunomide (LEF) treatment were screened for a 52-weeks randomized double-blind placebo (PLA) controlled multicenter clinical trial in Germany. Patients were randomized to receive either two times 1000mg RTX i.v. or PLA, followed by a second course of RTX of either two times 500 or 1000 mg at week 24. Superiority of RTX in ACR20 and 50 responses vs. PLA during 24-weeks treatment period was defined as primary endpoint. Disease activity as well as patient reported outcomes were measured at each visit until week 52. For safety evaluation, frequency and severity of adverse events were documented.
Results: 148 patients were randomized (mean age 56 years, mean body weight 76 kg, 74% female, DAS28 at baseline 5.57 for RTX, 5.54 for PLA). RTX demonstrated significant superiority compared to PLA at week 16 in ACR 20 and ACR 50 response. ACR 20 response was significant superior for RTX at weeks 12, 16 and 24 in per protocol and modified intention to treat analysis. DAS28 levels in the RTX treatment-group decreased to 3.69 at week 24 (PLA 4.51) and to 3.01 at week 52. A total of 372 adverse events (AE) were observed during the one-year study period, only 14 were classified as severe (10 in RTX and 4 in PLA). 43 serious adverse events were reported, 28 of them in the RTX treatment group during the placebo controlled period.
Conclusion: Here we report for the first time data of a RCT of combination of RTX with LEF. The treatment with RTX in combination with LEF demonstrated significant efficacy compared to PLA for ACR20 and ACR50 response as well as reduction in DAS28. The highest level of response was seen at week 16. Combination of RTX and LEF demonstrated a reasonable safety profile.