Biosimilar Etanercept Associated With Fewer Injection Site Reactions, Less Immunogenicity Than Reference Enbrel

A recent research letter, published in the British Journal of Dermatology, reports that a biosimilar etanercept, SB4 (approved as Benepali in the European Union and Brenzys in The Republic of Korea, Canada, and Australia), is associated with fewer injection-site reactions (ISRs) and less immunogenicity than reference etanercept (Enbrel), while maintaining equivalent efficacy.

ISRs are a common adverse reaction in the use of biologic drugs. The symptoms associated with such reactions can consist of itching, erythema, and induration at the injection site. ISRs usually appear within 24 to 48 hours after an injection, and subside within a few days. Though ISRs rarely lead to a discontinuation of treatment, they do remain a safety concern for patients using biologic drugs.

Discussed in the research letter is a study that showed results of therapeutic equivalence of etanercept biosimilar, SB4, and the reference etanercept, demonstrated in patients with moderate to severe rheumatoid arthritis. The study being addressed in the research letter also noted that ISRs were observed less frequently with the biosimilar compared with reference etanercept up to week 52. Results showed that 22 cases of ISRs were reported in 3.7% of patients (n = 11/299) treated with SB4, and 157 cases of ISRs were reported in 17.5% of patients (n = 52/297) taking reference etanercept. In this study, patients were treated with a 50-mg once-weekly dose, which resulted in an incidence of ISRs resulting from reference etanercept injection (17.5%) comparable to the incidence of such ISRs in previously conducted studies (19%). Researchers stated that, historically, ISRs in the use of etanercept have appeared in to be in the range of 10% to 49%, and more frequent dosing was also associated with a higher incidence of ISRs.

The correlation of ISRs with the presence of anti-drug antibodies (ADAs) was also assessed in this study. Incidence of ADA development was lower with the biosimilar etanercept compared with the reference (1.0% [n = 3/399] versus 13.1% [n = 39/297]; P <.001). The reported incidence of ISRs in ADA-negative patients treated with biosimilar SB4 was 3.4% (n = 10/296), and 17.5% (n = 45/257) in those treated with reference etanercept.

In ADA-positive groups, patients treated with the biosimilar SB4 reported a 33.3% (n = 1/3) incidence of ISRs, and those treated with reference etanercept reported an incidence of 17.9% (n = 7/39). However, assessing ISRs in ADA-positive patients treated with the biosimilar is limited by the small number of patients in the group.

The research letter reports that, overall, biosimilar SB4 has equivalent efficacy to the reference etanercept, and is in fact associated with fewer ISRs and less immunogenicity than the reference.