Incidence and risk factors for adalimumab and infliximab anti-drug antibodies in rheumatoid arthritis: A European retrospective multicohort analysis

Objectives: To evaluate the incidence of anti-drug antibody (ADA) occurrences and ADA-related risk factors under adalimumab and infliximab treatment in rheumatoid arthritis (RA) patients. Methods: The study combined retrospective cohorts from the ABIRISK project totaling 366 RA patients treated with adalimumab (n = 240) or infliximab (n = 126), 92.4% of them anti-TNF naive (n = 328/355) and 96.6% of them co-treated with methotrexate (n = 341/353) with up to 18 months follow-up. ADA positivity was measured by enzyme‐linked immunosorbent assay. The cumulative incidence of ADA was estimated, and potential bio-clinical factors were investigated using a Cox regression model on interval-censored data. Results: ADAs were detected within 18 months in 19.2% (n = 46) of the adalimumab-treated patients and 29.4% (n = 37) of the infliximab-treated patients. The cumulative incidence of ADA increased over time. In the adalimumab and infliximab groups, respectively, the incidence was 15.4% (5.2–20.2) and 0% (0–5.9) at 3 months, 17.6% (11.4–26.4) and 0% (0–25.9) at 6 months, 17.7% (12.6–37.5) and 34.1% (11.4–46.3) at 12 months, 50.0% (25.9–87.5) and 37.5% (25.9–77.4) at 15 months and 50.0% (25.9–87.5) and 66.7% (37.7–100) at 18 months. Factors associated with a higher risk of ADA development were: longer disease duration (1–3 vs. < 1 year; adalimumab: HR 3.0, 95% CI 1.0–8.7; infliximab: HR 2.7, 95% CI 1.1–6.8), moderate disease activity (DAS28 3.2–5.1 vs. < 3.2; adalimumab: HR 6.6, 95% CI 1.3–33.7) and lifetime smoking (infliximab: HR 2.7, 95% CI 1.2–6.3). Conclusions: The current study focusing on patients co-treated with methotrexate for more than 95% of them found a late occurrence of ADAs not previously observed, whereby the risk continued to increase over 18 months. Disease duration, DAS28 and lifetime smoking are clinical predictors of ADA development.