Leflunomide or low-dose rituximab have similar benefit when added to methotrexate in RA
A leflunomide-methotrexate combination was as effective as, and more cost effective than, a low-dose rituximab-methotrexate combination for patients with rheumatoid arthritis (RA) refractory to conventional, first-line nonbiologic DMARDS*, according to a new study.
In this double-blind trial, researchers evaluated 40 patients who responded poorly to methotrexate (at least 10 mg/week) for more than 6 months (Disease Activity Score [DAS] >3.2). Participants were randomized to receive leflunomide (n=20, 10–20 mg/day) or low-dose rituximab (n=20, 500 mg on days 1 and 15) in addition to methotrexate (10–20 mg/week). [BMC Musculoskelet Disord 2017;doi:10.1186/s12891-017-1673-3]
At week 24, American College of Rheumatology (ACR) responses reflected a comparable efficacy between leflunomide and rituximab (84 percent vs 85 percent for ACR20#, 64 percent vs 60 percent for ACR50#, and 32 percent vs 35 percent for ACR70#).
“[Our results suggest that] both leflunomide and [two infusions of] low-dose rituximab were [successful] in controlling disease activity when added to methotrexate,” said the researchers.
There was also a significant reduction in disease activity at 24 weeks vs baseline (DAS <3.2 vs DAS 28 >5.1) in both leflunomide (42 percent vs 100 percent) and rituximab arms (40 percent vs 95 percent). European League Against Rheumatism (EULAR) good response rates were also similar to DAS (42 and 40 percent in the leflunomide and rituximab arms, respectively).
There was a significant reduction in memory B cells in both leflunomide and rituximab arms (p<0.01 and p<0.001, respectively) as well as pneumococcal antibody levels (p<0.05 for both) at week 24, the latter being a concern, as it increases the likelihood of reduced protection against pneumococcal infections, underscored the researchers.
Leflunomide is also a more cost-effective measure where a 20 mg/day dose costs an estimated US$ 192 for a one-year treatment vs US$ 2,850 for two infusions of low-dose rituximab. Although the findings favour leflunomide over low-dose rituximab in terms of cost, both are still relatively cheaper compared with standard high-dose rituximab (1,000 mg, US$ 5,700 for two infusions), said the researchers.
“[Overall, the] lower costs of both treatment options should enable more patients with refractory RA to be treated successfully in resource-limited settings,” they said, though they recommended use of the leflunomide-methotrexate combination first, given previous evidence showing the safety of leflunomide-methotrexate. [J Rheumatol 2013;40:228-235]