Anti-adalimumab antibodies in psoriasis: lack of clinical utility and laboratory evidence

BMJ Open. 2016 Dec 9;6(12):e011941. doi: 10.1136/bmjopen-2016-011941.

Abstract

Objective: Adalimumab has proven effective in psoriasis; however, secondary failure may result from the drug's immunogenicity. Prevalence data on the immunogenicity of biologicals, and of adalimumab in particular, are highly variable. We investigated the prevalence of anti-adalimumab antibodies and the association with clinical indexes and tumour necrosis factor α (TNFα) serum levels in psoriatic patients.

Design: Case-control, longitudinal.

Setting: Single centre.

Participants: Patient groups: I (n=20) receiving biological therapies after switching from adalimumab; II (n=30) ongoing adalimumab therapy; III (n=30) novel adalimumab therapy; IV (n=15) biological therapies other than adalimumab.Healthy subjects: (group V; n=15) never treated with immunosuppressants or biologicals.

Interventions: All groups were tested at enrolment. Group II was also tested at 12 months, and group III at 1, 3, and 6 months.

Primary and secondary outcome measures: Standard clinical evaluations (Psoriasis Area Severity Index (PASI)), blood samples and two-site ELISA-based measurement of serum adalimumab trough levels, anti-adalimumab antibodies and TNFα.

Results: The false-positive rate was 23% for adalimumab detection and 22% for anti-adalimumab antibodies in patients naïve to adalimumab. Spurious positivity for anti-adalimumab antibodies (one-time-point positivity in group III during follow-up) accounted for 33% of the total. The prevalence of anti-drug antibodies was highest (87%) in group I patients. No correlations were found between the presence of anti-adalimumab antibodies or adalimumab levels and changes in PASI scores.

Conclusions: High variability of results, high prevalence of false-positives and lack of association between anti-adalimumab antibodies and TNFα level/PASI score limit this assay's usefulness. Accurate clinical evaluation is key to early identification of treatment failures.

Keywords: ELISA; adalimumab; anti-drug antibodies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adalimumab / immunology
  • Adalimumab / therapeutic use*
  • Adult
  • Anti-Inflammatory Agents / immunology
  • Anti-Inflammatory Agents / therapeutic use*
  • Antibodies / blood*
  • Biomarkers / blood
  • Case-Control Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Psoriasis / drug therapy*
  • Psoriasis / immunology
  • Severity of Illness Index
  • Treatment Failure
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Anti-Inflammatory Agents
  • Antibodies
  • Biomarkers
  • Tumor Necrosis Factor-alpha
  • Adalimumab