Background/Purpose: Anti-adalimumab antibody (AAA) production may lead to reduced adalimumab (ADA) serum levels and therapy failure. There are, however, scarce and conflicting data regarding ADA immunogenicity in juvenile idiopathic arthritis (JIA) patients. Importantly, none of these three studies performed AAA production kinetics nor they have evaluated predictors of therapy response. Thereby, our objectives were to assess the longitudinal production of AAA and baseline risk factors for this antibody development in JIA patients initiating ADA.

Methods: From June 2010 to October 2016, 30 consecutive JIA patients under ADA therapy were prospectively followed in the biologic therapy center of Rheumatology Division of a tertiary university hospital. JIA clinical/laboratorial/treatment data and sera for ADA and AAA assays (ELISA and bridging ELISA) were obtained at baseline (BL), 2 months (2M), 3 months (3M), 6 months (6M) and 12 months (12M). Patients with therapy failure requiring ADA withdrawn had their sera evaluated at their last medical visit prior to biologic switch (blinded to ADA and AAA levels).

Results: The mean age at ADA start was 14.5±56.4 years, 67% were females and the mean disease duration until biologic therapy initiation was 8.4±5.8 years. Subtype distribution was 43% polyarticular subtype, 27% systemic, 20% oligoarticular, 7% enthesitis related arthritis and 3% psoriatic arthritis. In 20% patients, active uveitis was the indication for ADA. AAA was absent at BL, first detected at 2M after ADA initiation in 2/30 (7%) patients with a significant increase at 3M [10/29 (34%), p=0.013] and no major change in 6M [11/30 (37%)] and 12M [9/26 (35%)]. Of note, at 3M AAA levels correlated negatively with ADA levels (r=-0.781, p=0.0001). Analysis of BL predictors revealed a significantly higher risk of developing AAA in patients with female gender (odds ratio [OR] 21; 95%confidence interval [CI], 1.08-406.57, p=0.044), ESR >30mm/1^sthour (OR 5.44; 95%CI, 1.04-28.53, p=0.045) and leflunomide use (OR 9.33; 95%CI, 1.51-57.66, p=0.016). In contrast, concomitant use of methotrexate was protective for AAA appearance (OR 0.08; 95%CI, 0.01-0.53, p=0.009). At 3M evaluation, AAA positive patients showed higher disease activity parameters: patient VAS [4.5 (0-7) vs. 1 (0-5), p=0.043], physician VAS [3 (0-6) vs. 0 (0-5), p=0.035] and JADAS-71 [9.8 (0-31.8) vs. 2.7 (0-14.9), p=0.005]. After 12M of ADA, 60% of AAA-positive patients required drug switch for drug failure compared to 15% in AAA-negative group (p=0.03).

Conclusion: This study provides novel evidence of AAA production kinetics demonstrating a timely significant increase starting at 3M and stable throughout 12M. We also identified female gender, increased ESR and leflunomide use as relevant risk factors for AAA production at BL, whereas methotrexate was protective. Early systematic monitoring of AAA from 3M to 6M may therefore, guide drug switching in these patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-adalimumab-antibodies-kinetics-an-early-guide-for-juvenile-idiopathic-arthritis-jia-switching/