Switching among multiple infliximab biosimilars does not cause immunogenicity

Immunogenicity does not constitute a barrier to interchangeability between biosimilars infliximab in chronic inflammatory diseases. “There are still consequences of immunogenicity that are not negligible with increased risk of allergic reactions, even though they were quite low in our cohort,” concluded Dr Jéróme Avouac (Paris Descartes University, France) [1].

The use of biosimilars has taken off in the past few years and is expected to increase further. The debate on the use of biosimilars and the switching from reference biologic medicines to biosimilars in rheumatology focuses on the clinical outcomes, including enhanced immunogenicity, compromised safety, or diminished efficacy for patients.

Dr Avouac et al. aimed to determine whether the successive switches from innovator infliximab to a first then second biosimilar increased the risk of immunogenicity during a 3-year observation period. This was done as a prospective, single-centre, observational study in France [1,2]. A total of 265 patients were included. Of these, 135 had axial spondyloarthritis, 64 had inflammatory bowel disease, 31 rheumatoid arthritis, 21 had psoriatic arthritis, 8 had uveitis, and 6 had other inflammatory diseases. These patients were all treated with the reference infliximab, then were switched to a biosimilar and followed for 3 years. Prior to the switch, 29 patients had anti-drug antibodies (ADAs). At year 2, 140 patients were switched to a second biosimilar infliximab, while 26 remained on the first biosimilar and 55 patients switched back to the reference product.
Among the 236 patients with no ADAs before the first switch, 20 developed ADAs during the observation period, corresponding to a rate of 3 per 100 patient-years. The mean time to ADA detection was 21.2 months.

Kaplan Meier Survival analysis showed that the number of patients that received biosimilars did not impact the development of ADAs. Among the 20 patients who developed new ADAs, 4 were taking the reference product at the time of detection, while 10 had been exposed to the first biosimilar only, and 6 had been exposed to both biosimilars. No predictive factors, including age, disease state, sex, body mass index, or concomitant drug therapy, were identified for immunogenicity.

The retention rate for biosimilar infliximab was 58% at the end of the observation period, including 131 patients treated with the second biosimilar and 23 patients treated with the first biosimilar. These real-world data may provide reassurance that switches to different biosimilars do not pose a risk with respect to increased immunogenicity.

1. Avouac J, et al. Abstract OP0227. EULAR 2019
2. Gisondi P, et al. Abstract P049. SPIN 2019.

Posted on 4 September 201917 March 2021