title: Infliximab-induced autoantibodies: a multicenter study.
abstract: The purpose of this study was to assess autoantibody incidence in patients treated with infliximab for various diseases, and the development of autoimmune diseases using a multicenter, longitudinal, open-label, phase IV observational study. All patients received anti-tumor necrosis factor (anti-TNF) according to local treatment guidelines. The autoantibodies assessed before and after infliximab treatment were ANA, anti-Sm, anti-dsDNA, anticardiolipin IgM/IgG, anti-Scl70, anti-centromere B, anti-chromatin, anti-ribosomal P, anti-Sm-RNP, anti-RNP A, anti-RNP 68 kD, anti-La/SSB, anti-Ro/SSA 52 kD and 60 kD, and anti-Jo1. ANA was determined by indirect immunofluorescence on HEp-2 cells (INOVA); the remaining was assessed using BioPlexTM 2200. The Fisher exact test, Wilcoxon test, and the McNemar were used when appropriate.Two hundred eighty-six patients were included (139 with rheumatoid arthritis, 77 with ankylosing spondylitis, 29 with inflammatory bowel disease, 27 with psoriatic arthritis, and 14 with psoriasis), 167 females and 119 males, with mean age of 46.3 years. Subjects received at least five infusions of infliximab (6-month treatment). A significant difference was observed in antinuclear antibody (ANA) detection between samplings (p = 0.001). Among patients that had ANA before treatment (n = 92), six became ANA-negative, 48 had increased titers, 29 maintained, and nine decreased titers after treatment; a total of 186 patients had a positive ANA after treatment. Fine speckled nuclear pattern was most commonly observed (both before and after infliximab treatment). The number of patients with anti-dsDNA had a statistically significant increase (p = 0.003). No significant differences were noted for anticardiolipin and the remaining autoantibodies tested. Among the 286 patients included in the study, only one (0.35 %) showed clinical signs of drug-induced lupus, presenting elevated ANA and anti-dsDNA titers that normalized once treatment was discontinued. Infliximab induced the formation of autoantibodies in the combined population (ANA and anti-dsDNA with no apparent clinical importance).
authors.affiliation: Departamento de Reumatologia, Universidade Federal do Estado Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: João Luiz Pereira
authors.initials: JL
authors.lastname: Vaz
authors.affiliation: Departamento de Reumatologia, Universidade de Cuiabá, Cuiabá, Brazil.
authors.forename: Vander
authors.initials: V
authors.lastname: Fernandes
authors.affiliation: Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Felipe
authors.initials: F
authors.lastname: Nogueira
authors.affiliation: Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Adriano
authors.initials: A
authors.lastname: Arnóbio
authors.affiliation: Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil. roger.a.levy@gmail.com.|Centro de Imunoterapia de Ipanema-CITIPA, Rio de Janeiro, Brazil. roger.a.levy@gmail.com.|Rua Rodolfo Dantas 16/1004, Rio de Janeiro, BR, 22002040, Brazil. roger.a.levy@gmail.com.
authors.forename: Roger A
authors.initials: RA
authors.lastname: Levy
mesh_terms: D018501:Antirheumatic Agents / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D005260:Female; D006801:Humans; D000069285:Infliximab / Q000276:immunology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged
chemical_list: D018501:Antirheumatic Agents; D001323:Autoantibodies; D000069285:Infliximab
keywords: Autoantibodies; Biomarkers; Diagnostic tests; Infliximab; Pharmacovigilance