Immunogenicity constitutes an important concern since it is associated with lower clinical responses and more adverse events. Biosimilars of Infliximab (e.g., CT-P13, SB2), one of the most immunogenic antibodies against TNF-α, have recently entered the market with the same indications to the innovator drug and are of use in clinical practice.1 According to previous clinical studies, anti-drug antibodies (ADA) directed against innovator Infliximab recognise and bind CT-P13, illustrating that these two treatments may have common immunodominant epitopes. The authors’ aim was to determine whether the successive switches from innovator infliximab to a first, and then second, biosimilar infliximab increase the risk of immunogenicity during a 3-year observation period.
This study was a usual care study performed in the Rheumatology, Gastroenterology, and Internal Medicine departments of Cochin Hospital, Paris, France. The first switch from innovator infliximab to CT-P13 occurred in October/December 2015, and the second switch from CT-P13 to SB2 started in December 2017. The end of the observation period was December 2018. Immunogenicity was defined by the detection of positive ADA >10 ng/mL, at least at two consecutive time points.
The authors prospective cohort consisted of 265 patients on maintenance therapy with innovator infliximab (135 with axial spondyloarthritis, 64 with inflammatory bowel diseases, 31 with rheumatoid arthritis, 21 with psoriatic arthritis, 8 with uveitis, and 6 with other chronic inflammatory diseases) who switched to CT-P13. Following this, 140 patients switched to SB2, 26 remained treated with CT-P13, and innovator infliximab was re-established in 55 patients. 30 patients (16 females) had positive ADA at baseline (point prevalence: 11.3%), before the switch to CT-P13. These patients were more likely to have a BMI >30 (45% versus 17%, p<0.001) and received less innovator infliximab infusions (28±20 versus 40±25 infusions, p=0.012) than patients without ADA. Among the 235 patients with no ADA at baseline, 20 patients developed ADA during the observation period, corresponding to a rate of 3 for 100 patient years. The mean time to positive ADA detection was 21.19±13.70 months (range: 1–37 months). Kaplan Meyer analysis, illustrating immunogenicity-free survival, showed no influence by the number of biosimilars infliximab received on immunogenicity. Among the 20 patients with positive ADA, 4 were back to innovator infliximab at the time of ADA detection. Positive ADA were detected in 10 patients during exposition to CT-P13, and 6 during exposition to SB2. The risk of treatment discontinuation was significantly higher in patients with positive ADA at baseline or during follow-up compared to patients without ADA ([HR: 2.27; 95% confidence interval: 1.33–3.89]). No predictive factor of immunogenicity was identified (including type of disease, age, sex, BMI, or concomitant disease-modifying antirheumatic drug intake). The retention rate of biosimilar infliximab was 58% (154/265) at the end of the observation period, including 131 patients treated with SB2 and 23 who remained treated with CT-P13.
In this usual care study with a 3-year observation period, the development of immunogenicity was low (3 for 100 patient years) and not favoured by the switch to biosimilars infliximab. Thus, immunogenicity does not constitute a barrier to interchangeability between biosimilars infliximab in chronic inflammatory diseases.