Tumor necrosis factor inhibitors (TNFis) have been a mainstay in the treatment of rheumatoid arthritis (RA) since 1998. These biological agents directly target molecules and cells involved in the pathogenesis of RA, leading to a better prognosis and clinical remission, especially in patients who are not well controlled with traditional disease-modifying antirheumatic drugs alone [Weaver AL et al. Curr Med Res Opin. 2006].

Because TNFis are expensive, however, there is currently much interest in lower-cost biosimilars—biological products that are highly similar to a licensed reference biological product with no clinically meaningful differences in safety, potency, and purity. Because they are not exact replicas of the reference drug, each biosimilar must be tested against its reference drug to determine its efficacy and safety in a particular therapeutic area.

Jonathan Kay, MD, University of Massachusetts Medical School, Worcester, Massachusetts, USA, presented results of a phase 3, randomized, double-blind, active comparator trial of the biosimilar BOW015 to its reference drug infliximab in patients with active RA. The trial originally enrolled 199 patients at 23 study sites in India. Almost 90% of the patients were female with a median age of 46 and a median disease duration of 3 years. All patients received a stable dose of either oral methotrexate or corticosteroids for at least 4 weeks prior to randomization, and no patient had previously used a biologic agent. No patient had active or latent tuberculosis.

Patients were randomized to receive infliximab (n = 62) or the biosimilar drug (n = 127) dosed at 3 mg/kg at baseline and at weeks 2, 6, and 14. The primary outcome of the study was the proportion of patients in either treatment group who achieved an American College of Rheumatology 20% improvement response (ACR20) at week 16.

Of the original patients, 181 completed the double-blind portion of the study (weeks 0 to 22). At 22 weeks, patients who responded to the biosimilar continued with the treatment; responders to infliximab were crossed over to the biosimilar group (n = 157, both groups). All of the responders then continued on BOW015 every 8 weeks through week 46. Nonresponders were followed only to week 26 (n = 24). The last efficacy measure was at week 54, and safety follow-up extended to week 58.

By week 16, ACR20 responses were seen in 89.8% of patients receiving infliximab and in 86.4% of those taking the biosimilar (95% CI, −19.3% to 12.6%). The durability of the response was maintained at weeks 24 and 54.

During the double-blind phase of the study, at least 1 treatment-emergent adverse event (AEs) occurred in 40.94% of the BOW015 group and in 48.39% of the infliximab group. Serious AEs were reported by 7.1% and 6.5% of the BOW015 and infliximab groups, respectively. No deaths were reported. At week 58, 53.5% of the patients in the initial BOW015 group had developed antidrug antibodies compared with 56.5% of the patients who initially received infliximab.

In conclusion, these data suggest that BOW015 was well tolerated and efficacious both as monotherapy and following an initial 12-week regimen of infliximab, with a durability of clinical response that extended over a total of 54 weeks.