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

Bella Ungar*, Tal Engel, Doron Yablecovitch, Adi Lahat, Alon Lang, Benjamin Avidan, Ofir Har-Noy, Dan Carter, Nina Levhar, Limor Selinger, Sandra Neuman, Ola Haj Natour, Miri Yavzori, Ella Fudim, Orit Picard, Uri Kopylov, Yehuda Chowers, Timna Naftali, Efrat Broide, Eyal ShacharRami Eliakim, Shomron Ben-Horin

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)890-898
Number of pages9
JournalAmerican Journal of Gastroenterology
Volume113
Issue number6
DOIs
StatePublished - 1 Jun 2018

Funding

FundersFunder number
Chaim Sheba Medical Center
AbbVie
Leona M. and Harry B. Helmsley Charitable Trust
Takeda Pharmaceutical Company
Janssen Pharmaceuticals
Canadian Thoracic Society
Ferring Pharmaceuticals

    Fingerprint

    Dive into the research topics of 'Prospective Observational Evaluation of Time-Dependency of Adalimumab Immunogenicity and Drug Concentrations: The Poetic Study'. Together they form a unique fingerprint.

    Cite this