Journal Article

Anti-adalimumab antibodies kinetics: an early guide for juvenile idiopathic arthritis (JIA) switching

Brunelli, Juliana Barbosa, Vendramini, Margarete B, Fontoura, Nicole, Aikawa, Nádia Emi, Bonfa Eloisa, Kozu Katia Tomie, Pires, Leon Elaine, Silva Clovis Almeida, Pasoto, Sandra Gofinet, Goldenstein-Schainberg Claudia, Saa Carla Gonçalves Schahin

2020

Overview

ObjectiveTo assess the longitudinal production of anti-adalimumab antibody (AAA) and baseline risk factors for this antibody development in juvenile idiopathic arthritis (JIA) patients initiating adalimumab (ADA).MethodThirty consecutive JIA patients under ADA therapy were prospectively followed. 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), 12 months (12M), and 24 months (24M). Patients with therapy failure requiring ADA withdrawn had their sera evaluated at their last medical visit prior to biologic switch (blinded to ADA and AAA levels).ResultsAAA was absent at BL, first detected at 2M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 (OR 21; 95% CI 1.08–406.57; p = 0.044), ESR > 30 mm/1st hour (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). After 12M of ADA, 60% of AAA-positive patients required drug switch for drug failure compared with 15% in AAA-negative group (p = 0.03).ConclusionsThis study provides novel evidence of AAA production kinetics demonstrating a timely significant increase starting at 3M and stable throughout 24M. 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 at 3M may, therefore, guide drug switching in these patients.Key Points• Anti-adalimumab antibodies (AAA) production kinetics demonstrated a timely significant increase starting at 3M in juvenile idiopathic arthritis (JIA) patients under adalimumab therapy• Female gender, increased ESR, and leflunomide use were identified as relevant risk factors for AAA production in JIA, whereas methotrexate was protective

• Publisher: Springer Nature B.V
• Subject: Arthritis / Enzyme-linked immunosorbent assay / Gender / Immunomodulators / Immunotherapy / Leflunomide / Methotrexate / Monoclonal antibodies / Patients / Risk factors / TNF inhibitors