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

  • Juliana Barbosa Brunelli
  • Clovis Almeida Silva
  • Sandra Gofinet Pasoto
  • Carla Gonçalves Schahin Saa
  • Katia Tomie Kozu
  • Claudia Goldenstein-Schainberg
  • Elaine Pires Leon
  • Margarete B. G. Vendramini
  • Nicole Fontoura
  • Eloisa Bonfa
  • Nádia Emi AikawaEmail author
Original Article

Abstract

Objective

To 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).

Method

Thirty 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 Patients with therapy failure requiring ADA withdrawn had their sera evaluated at their last medical visit prior to biologic switch (blinded to ADA and AAA levels).

Results

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 (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).

Conclusions

This 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

Keywords

Juvenile idiopathic arthritis Adalimumab Anti-adalimumab antibody Immunogenicity 

Notes

Funding information

This study was supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP 2015/03756-4 to NEA, CAS, SGP and EB), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq 303422/2015-7 to CAS and 305068/2014-8 to EB), and by Núcleo de Apoio à Pesquisa “Saúde da Criança e do Adolescente” da USP (NAP-CriAd) to CAS.

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest.

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Copyright information

© International League of Associations for Rheumatology (ILAR) 2019

Authors and Affiliations

  • Juliana Barbosa Brunelli
    • 1
  • Clovis Almeida Silva
    • 1
  • Sandra Gofinet Pasoto
    • 2
  • Carla Gonçalves Schahin Saa
    • 2
  • Katia Tomie Kozu
    • 1
  • Claudia Goldenstein-Schainberg
    • 2
  • Elaine Pires Leon
    • 2
  • Margarete B. G. Vendramini
    • 2
  • Nicole Fontoura
    • 2
  • Eloisa Bonfa
    • 2
  • Nádia Emi Aikawa
    • 1
    • 2
    Email author
  1. 1.Pediatric Rheumatology Unit, Hospital das Clinicas HCFMUSP, Faculdade de MedicinaUniversidade de Sao PauloSão PauloBrazil
  2. 2.Division of Rheumatology, Hospital das Clinicas HCFMUSP, Faculdade de MedicinaUniversidade de Sao PauloSão PauloBrazil

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