Ultra-low dosing of rituximab in RA is a viable treatment option

Rituximab showed non-inferior efficacy of longer-term treatment of rheumatoid arthritis (RA) with an ultra-low dose. Dosing regimens of 500 mg and 200 mg led to comparable results to the 1,000 mg dose when following patients for up to 4 years.

As rituximab was originally developed for lymphoma, special dose-finding investigations for RA are limited [1]. “The optimal dose of rituximab in RA is unknown,” said Mr Nathan den Broeder (Sint Maartenskliniek, the Netherlands) [1]. It has been however demonstrated that a low dose of 1,000 mg (or 2x500 mg) is equivalent to the registered high dose of 2x1,000 mg per 6 months [2]. Furthermore, the previous REDO trial (NTR6117) data showed on intention-to-treat analysis that an ultra-low dose of rituximab (i.e. 500 mg and 200 mg) was non-inferior to a standard low dose (1,000 mg) at 6 months, although the same conclusion failed in per-protocol analysis. Long-term data is lacking however. An extension trial of up to 4 years aimed to close this knowledge gap.

Of 142 patients in REDO, 118 entered the extension study that included outcomes like disease activity (using DAS28-CRP), quality of life, and adverse events. The mean age of the study participants was 64 years and 66% were women. The disease duration was about 14 years and approximately 90% were positive for rheumatoid factor or anti-citrullinated protein antibody (ACPA). The mean follow-up of 3.2 years equalled 377 evaluated patient years. The study treatment was decided by the treating rheumatologist and was either 1,000 mg, 500 mg, or 200 mg rituximab. Patients who had a good response in the REDO trial were encouraged to continue on ultra-low dosing. Of note, only 7 patients were switched to a different disease-modifying antirheumatic drug (DMARD) during the trial.

With regard to disease activity, both ultra-low dose groups demonstrated non-inferiority to the 1,000 mg group (non-inferiority margin 0.6). Interestingly, the analysis on received dose that was adjusted for medication use and rheumatoid factor/ACPA-positivity revealed only a slightly higher DAS28-CRP in the ultra-low dosing group. Overall, the median yearly dose that patients received in the trial was 978 mg. At the end, dosing intervals were all around 6 months and the final dosage of rituximab was 200 mg in 31% of patients, 500 mg in 40%, and 1,000 mg in 29% of participants.

Adverse events, most commonly infections and planned surgeries, were similar between groups. The lower infection rate on ultra-low-dose rituximab that was seen in REDO was not confirmed in this extension trial. However, the researchers believe there has been a lot of underreporting as adverse events were not as closely followed as in REDO.

“In summary, I believe we can conclude that ultra-low-dose rituximab is a good option for patients responding well to 1,000 mg of rituximab,” Mr den Broeder stressed.

1. Den Broeder N. Long-term effectiveness of ultra-low doses of rituximab in rheumatoid arthritis. Abstract 1443, ACR Convergence 2021, 3–10 November.
2. Bredemeier M, et al. Clin Rheumatol. 2015 Oct;34(10):1801-5.

 

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Posted on 14 January 2022