medwireNews: Add-on rituximab treatment may improve some clinical outcomes for patients with rheumatoid arthritis (RA) and an inadequate response to leflunomide, suggest findings from the AMARA trial.
However, rates of the primary endpoint of an ACR50 response at week 24 were not significantly different among patients treated with the combination versus those given add-on placebo, report Frank Behrens (Goethe University, Frankfurt, Germany) and co-investigators.
The phase 3 investigator-initiated study included 140 patients with active RA despite at least 3 months of leflunomide treatment who were randomly assigned to receive rituximab – given as intravenous infusions at a dose of 1000 mg on days 1 and 15 – or placebo, in addition to ongoing leflunomide.
At the 24-week follow-up, 26.9% of the 93 participants given rituximab achieved an ACR50 response, compared with 14.9% of the 47 given placebo, a nonsignificant difference.
The researchers note, however, that “analyses of secondary endpoints supported a benefit in adding rituximab to leflunomide.”
For instance, ACR50 response rates were significantly higher in the rituximab than the placebo arm at week 16 (32.3 vs 14.9%), as were ACR20 response rates at weeks 12 (55.9 vs 25.5%), 16 (53.8 vs 23.4%), and 24 (51.6 vs 27.7%). Average DAS28 scores were significantly lower among rituximab- versus placebo-treated patients from weeks 12 to 24.
The researchers say that their study “was likely underpowered for the predefined primary outcome of ACR50 response at week 24.” They suggest that this was due to lower enrolment rates and higher dropout rates than expected, which they attribute to a study reporting an unconfirmed association between rituximab and pancreatic cancer, as well as the manufacturer’s decision not to apply for a first-line biologic indication for rituximab.
Behrens and team report that the combination therapy was “generally well tolerated” in the AMARA study, with no unexpected adverse events (AEs). Rates of AEs were comparable in the rituximab and placebo groups (71.0 vs 70.2%), but patients given rituximab had higher rates of serious AEs (20.4 vs 2.1%), most commonly infections and musculoskeletal disorders.
Taken together, the trial results suggest that rituximab plus leflunomide “may be an effective treatment regimen for some patients with active RA and an inadequate response to leflunomide alone,” write the researchers in Rheumatology.
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