Are Ultra-low Rituximab Doses Effective in RA?

A study published in The Lancet Rheumatology compared the efficacy of different doses of rituximab in patients with rheumatoid arthritis (RA).

Rituximab, a biological [disease-modifying antirheumatic drug] DMARD targeting CD20 on B cells, improves the symptoms of patients with rheumatoid arthritis and can prevent disease progression,” the study authors wrote. They added, “The US Food and Drug Administration and European Medicines Agency recommend two doses of 1000 mg rituximab (2 weeks apart) every 6 months, and this dosing scheme was used in the first randomised controlled trial in patients with rheumatoid arthritis. However, findings of a systematic review showed that low-dose rituximab (two doses of 500 mg 2 weeks apart or one dose of 1000 mg every 6 months) was as effective as the higher dose.”

Here, the researchers compared two ultra-low doses of rituximab—500 mg and 200 mg—to a standard low dose of 1,000 mg in RA patients with adequate response to standard doses.

The study, REDO, was a randomized, double-blind, multicenter study that took place in the Netherlands. Adult RA patients were randomized 1:2:2 to intravenous rituximab in one of three doses: 1,000 mg, 500 mg, or 200 mg. Researchers compared three- and six-month outcomes between 500 mg versus 1,000 mg doses and 200 mg versus 1,000 mg doses. Outcomes included change from baseline in the 28-joint disease activity score based on C-reactive protein levels (DAS28-CRP).

A total of 142 patients were randomized to receive 1,000 mg (n = 29), 500 mg (n = 58), or 200 mg (2 = 55) doses. At three months, the 500 mg dose group did not have significantly different outcomes compared to the 1,000 mg group (mean change from baseline in DAS28-CRP, –0.07; 95% CI –0.41–0.27), but by six months the 500 mg group was no longer non-inferior (mean change from baseline in DAS28-CRP, 0.29; 95% CI –0.08–0.65). Serious adverse events occurred in 13 patients—three (10%) in the 1000 mg group, six (10%) in the 500 mg group, and four (7%) in the 200 mg group—the most common of which were cardiovascular. The ultra-low dose groups had a significantly lower infection rate than the standard group (1,000 mg dose, 1.24 infections per patient-year; 500 mg dose, 0.52; 200 mg dose, 0.55, rate ratio, 0.42; 95% CI 0.21–0.83; P=0.013 for 500 mg vs. 1,000 mg; rate ratio, 0.44; 95% CI 0.22–0.88; P=0.019 for 200 mg vs. 1,000 mg). No deaths were reported.

The authors stated, “Our study did not show non-inferiority of ultra-low doses of rituximab for continued treatment of patients with rheumatoid arthritis. Nonetheless, in clinical practice, a strategy with an ultra-low dose of rituximab might be considered after evaluation of risks and benefits, although further studies are needed to establish non-inferiority.”