OP0227 EFFECTS OF SUCCESSIVE SWITCHES TO DIFFERENT BIOSIMILARS INFLIXIMAB ON IMMUNOGENICITY IN CHRONIC INFLAMMATORY DISEASES IN DAILY CLINICAL PRACTICE
Authors: Ambre Lauret, Anna Moltó, Vered Abitbol, Loriane Gutermann, Ornella Conort, Francois Chast, Claire Goulvestre, Claire Le Jeunne, Stanislas Chaussade, Christian Roux, Frédéric Batteux, Maxime Dougados, Yannick Allanore, Jérôme Avouac
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> <h3>Objectives</h3> To determine whether the successive switches from innovator infliximab to a first then a second biosimilar infliximab increase the risk of immunogenicity during a 3-year observation period. <h3>Methods</h3> This is a usual care study performed in Cochin Hospital, Paris, France. First switch from innovator infliximab to a first biosimilar infliximab occurred in October/December 2015 and the second switch from the first to the second biosimilar infliximab started in December 2017. The end of the observation period was December 2018. Immunogenicity was defined by the detection of positive anti-drug antibodies (ADA &gt;10 ng/mL), at least at two consecutive time points. The primary outcome of the study was the development of immunogenicity during the observation period. Secondary outcomes were i) the point prevalence of positive ADA at baseline, ii) the influence of the successive switches to biosimilars on the risk of immunogenicity and iii) the retention rate of biosimilar infliximab at the end of the observation period. <h3>Results</h3> Our prospective cohort consisted on 265 patients on maintenance therapy with innovator infliximab (135 axSpA, 64 with inflammatory bowel diseases, IBD, 31 with RA, 21 with PsA, 8 with uveitis and 6 with other chronic inflammatory diseases) who switched to biosimilar infliximab. Then, 140 patients switched to the second biosimilar infliximab, 26 remained treated with the first biosimilar, and innovator infliximab was re-established in 55 patients. 29 patients (15 females, 14 males) had positive ADA at baseline (point prevalence: 12.4%), before the switch to biosimilar infliximab. Among these 29 patients, 15 had axSpA (11%), 6 RA (19%), 6 IBD (9%) and 2 PSa (10%). Among the 236 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 21.2±13.7 months. Kaplan Meyer curve showed no influence of the number of biosimilars infliximab received on immunogenicity (Figure 1A). Among the 20 patients with positive ADA, 4 were back to innovator infliximab at the time of ADA detection, 10 patients were exposed to the first biosimilar and 6 to the second. The risk of treatment discontinuation was significantly higher in patients with positive ADA at baseline or during follow-up compared to patients without ADA (Figure 1B, Hazard Ratio 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 DMARD intake). The retention rate of biosimilar infliximab (Figure 1C) was 58% (154/265) at the end of observation period, including 131 patients treated with the second biosimilar and 23 who remained treated with the first biosimilar. <h3>Conclusion</h3> In this usual care study with a 3-year observation period, the development of immunogenicity was low (3 for 100 patient years) and not favored by the switch to biosimilars infliximab. Thus, immunogenicity does not constitute a barrier to interchangeability between biosimilars infliximab in chronic inflammatory diseases. <h3>Disclosure of Interests</h3> Ambre Lauret: None declared, Anna Moltó: None declared, Vered Abitbol: None declared, Loriane Gutermann: None declared, Ornella Conort: None declared, Francois Chast: None declared, Claire Goulvestre: None declared, Claire Le Jeunne: None declared, Stanislas Chaussade: None declared, Christian Roux Grant/research support from: Alexion, Amgen, UCB, Frédéric Batteux: None declared, maxime dougados Grant/research support from: Eli Lilly and Company, Pfizer, AbbVie, and UCB Pharma, Consultant for: Eli Lilly and Company, Pfizer, AbbVie, and UCB Pharma, Yannick Allanore Grant/research support from: Inventiva, F Hoffman La-Roche, Sanofi, BMS, Pfizer, Consultant for: Actelion, Bayer, BMS, Boehringer, Roche, Sanofi, Jérôme Avouac Grant/research support from: research grant from Pfizer