Data From 11 Head-to-Head Trials Underscore Safety, Efficacy of Biosimilar Rituximab Products

While biosimilars of brand-name rituximab (Rituxan in the United States and MabThera in other regulatory territories) have been available in Europe for some time and have gained wide acceptance among stakeholders, in the United States context, rituximab biosimilars are relatively recent; Celltrion and Teva gained the FDA’s authorization for CT-P10, Truxima, in November of last year, and Pfizer’s biosimilar, PF‐05280586, Ruxience, was granted approval just last month.

To date, neither biosimilar has launched in the United States, and some providers have voiced skepticism about whether there will be broad acceptance of the products in cancer care, leading to some predictions that the biosimilars may be used largely in applications without curative intent in the oncology realm.

Complicating matters further for the rheumatology space is the fact that both Truxima and Ruxience carry so-called “skinny labels” in the United States, meaning that they are approved for fewer than all indications of the reference product, due to intellectual property and patent issues in the US market; while rituximab has become a widely used therapy for rheumatoid arthritis (RA), neither Truxima nor Ruxience carries an indication for RA, a fact that could lead stakeholders to mistakenly believe that the biosimilars have not been demonstrated to be safe or effective in treating inflammatory diseases.

A new paper published this month in BioDrugs, however, may help to allay some concerns that US providers may have about using FDA-approved biosimilar rituximab.¹ The paper reports on a systematic review and meta-analysis that sought to collate the available data on head-to-head randomized controlled trials of biosimilar rituximab agents compared with the reference in both RA and non-Hodgkin lymphoma (NHL).

The paper’s authors used the PubMed, EMBASE, Cochrane Library, and Google Scholar databases to identify a total of 11 head-to-head studies, with 3163 patients (1744 with RA and 1419 with NHL) that compared the efficacy and safety of biosimilar rituximab and the reference; the efficacy outcome for RA was the American College of Rheumatology criteria for 20% improvement (ACR20) and the outcome for NHL was the response rate.

Overall, the pooled risk ratio (RR) of achieving ACR20 in patients with RA at weeks 24 and 48 was 0.99 (P = .70; 95% CI, 0.92-1.06) and 1.04 (P = .73; 95% CI, 0.83-1.31), respectively. The pooled RR of the overall response at week 24 in patients with NHL was 1.02 (P = .31; 95% CI, 0.98-1.07).

There were no significant differences in terms of development of anti-drug antibodies to rituximab, nor were there significant differences in adverse events among patients receiving biosimilars and those receiving the reference drug.

These combined data from head-to-head studies, write the authors, “demonstrated the overall similarity of the long-term efficacy and safety of biosimilar rituximab to those of originator rituximab in RA and NHL.”

Reference

1. Lee S, Lee H, Kim E. Comparative efficacy and safety of biosimilar rituximab and originator rituximab in rheumatoid arthritis and non-Hodgkin’s lymphoma: a systematic review and meta-analysis [published online August 22, 2019]. BioDrugs. doi: 10.1007/s40259-019-00376-z.