Prospective Observational Evaluation of Time-Dependency of Adalimumab Immunogenicity and Drug Concentrations: The POETIC Study

Am J Gastroenterol. 2018 Jun;113(6):890-898. doi: 10.1038/s41395-018-0073-0. Epub 2018 Jun 5.


Objectives: Adalimumab is usually self-injected at home, making prospective serial-sampling studies challenging and scarce. This has led to a gap in knowledge about evolution of anti-adalimumab antibodies (AAAs) over time and its correlation with clinical and inflammatory outcomes.

Methods: A program for home visits by physicians at induction, every 3 months and at event of relapse, was established prospectively for Crohn's disease (CD) patients. At each visit, patients' clinical scores were determined and sera were obtained for C-reactive protein, drug, and AAA levels. This cohort was compared to a parallel prospective cohort of infliximab-treated CD patients. In a subgroup of 29 patients, trough and in-between-trough levels were compared, to elucidate the importance of timing of sampling during the injection cycle.

Results: Ninety-eight CD patients starting adalimumab were prospectively followed (median follow-up 44 weeks) and 621 serum samples were analyzed. Thirty-three patients (32%) developed AAA; 18/33 (55%) of them as early as week 2, and 26/33 (79%) by week 14. Induction period AAAs were strongly associated with primary non-response (odds ratio (OR) = 5.4, 95% confidence interval (CI): 1.6-17.8, p = 0.005). As compared to antibodies-to-infliximab (ATI), AAA formation rate over time was significantly lower (p = 0.01) and AAA were much more specific-85% of AAA events were associated with loss-of-response compared with 58% rate for ATI (p = 0.01). In 29 patients sampled serially during an injection cycle, levels of drug and AAA seemed comparable between four time-points during a single cycle both in patients with or without AAA (n = 8, n = 21, respectively).

Conclusions: When followed prospectively and serially, AAAs are found to arise earlier than previously appreciated and their impact may be more pronounced for primary rather than secondary, non-response. Drug and AAA levels were similar both at trough and in-between injections, enabling to simplify therapeutic drug monitoring of adalimumab.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adalimumab / administration & dosage
  • Adalimumab / blood
  • Adalimumab / immunology*
  • Adult
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / blood
  • Anti-Inflammatory Agents / immunology*
  • C-Reactive Protein / analysis
  • Crohn Disease / blood
  • Crohn Disease / drug therapy*
  • Crohn Disease / immunology
  • Drug Monitoring / statistics & numerical data*
  • Female
  • Follow-Up Studies
  • Humans
  • Infliximab / administration & dosage
  • Infliximab / blood
  • Infliximab / immunology
  • Male
  • Prospective Studies
  • Time Factors
  • Treatment Outcome


  • Anti-Inflammatory Agents
  • C-Reactive Protein
  • Infliximab
  • Adalimumab