Time Course and Clinical Implications of Development of Antibodies Against Adalimumab in Patients With Inflammatory Bowel Disease

J Clin Gastroenterol. 2016 Jul;50(6):483-9. doi: 10.1097/MCG.0000000000000375.

Abstract

Background: Antibodies (Abs) against adalimumab (ADL) have been associated with low ADL levels and treatment failure.

Aim: To characterize the temporal characteristics of anti-ADL Ab appearance and possible disappearance, and determine the clinical significance on drug efficacy and disease course.

Methods: Cohort study including inflammatory bowel disease patients in whom anti-ADL Abs had been assessed by radioimmunoassay (RIA) and, in case of disappearance, by enzyme immunoassay, and functional reporter gene assay.

Results: Anti-ADL Abs were evaluated in 133 serum samples from 72 patients. Seventeen patients (24%) tested positive after median of 194 days, interquartile range of 66 to 361. The proportion with anti-ADL Abs was 22% after 1 year, and 32% from 21 months onwards. Anti-ADL Abs generally persisted at repeat assessments during continued ADL therapy (n=8). Disappearance of anti-ADL Abs during therapy (n=3) was presumably caused by methodological biases due to detection of nonfunctional nonpersistent anti-ADL Abs by RIA, or false-negative measurement at reassessment by RIA and reporter gene assay. Anti-ADL Abs appeared pharmacologically active as judged by a median ADL concentration below limit of detection versus 7.4 μg/mL in anti-ADL Ab-negative samples (P<0.0001). Anti-ADL Abs associated with loss of response (odds ratio estimated 67, P<0.0001), and shorter treatment duration (P<0.0001).

Conclusions: Abs against ADL appear in approximately one fourth of inflammatory bowel disease patients with decreasing frequency over time and usually within 1 year of therapy. Anti-ADL Abs generally persist during continued ADL therapy, and are associated with elimination of drug and treatment failure. Therefore, ADL cessation should be considered when anti-ADL Abs are detected and supported by clinical observations.

MeSH terms

  • Adalimumab / immunology
  • Adalimumab / therapeutic use*
  • Adolescent
  • Adult
  • Anti-Inflammatory Agents / immunology
  • Anti-Inflammatory Agents / therapeutic use*
  • Antibodies / immunology*
  • Cohort Studies
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Follow-Up Studies
  • Genes, Reporter
  • Humans
  • Inflammatory Bowel Diseases / drug therapy*
  • Inflammatory Bowel Diseases / immunology
  • Male
  • Radioimmunoassay
  • Retrospective Studies
  • Time Factors
  • Treatment Failure
  • Young Adult

Substances

  • Anti-Inflammatory Agents
  • Antibodies
  • Adalimumab