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Prospective Observational Evaluation of Time-Dependency of Adalimumab Immunogenicity and Drug Concentrations: The POETIC Study.
Ungar, Bella; Engel, Tal; Yablecovitch, Doron; Lahat, Adi; Lang, Alon; Avidan, Benjamin; Har-Noy, Ofir; Carter, Dan; Levhar, Nina; Selinger, Limor; Neuman, Sandra; Natour, Ola Haj; Yavzori, Miri; Fudim, Ella; Picard, Orit; Kopylov, Uri; Chowers, Yehuda; Naftali, Timna; Broide, Efrat; Shachar, Eyal; Eliakim, Rami; Ben-Horin, Shomron.
Afiliação
  • Ungar B; Department of Gastroenterology, Sheba Medical Center Tel Hashomer, Ramat Gan, Israel. Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Rambam Health Care Campus and Bruce Rappaport School of Medicine, Haifa, Israel. Technion Israel Institute of Technology, Haifa, Israel. Department
  • Engel T; Department of Gastroenterology, Sheba Medical Center Tel Hashomer, Ramat Gan, Israel. Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Rambam Health Care Campus and Bruce Rappaport School of Medicine, Haifa, Israel. Technion Israel Institute of Technology, Haifa, Israel. Department
  • Yablecovitch D; Department of Gastroenterology, Sheba Medical Center Tel Hashomer, Ramat Gan, Israel. Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Rambam Health Care Campus and Bruce Rappaport School of Medicine, Haifa, Israel. Technion Israel Institute of Technology, Haifa, Israel. Department
  • Lahat A; Department of Gastroenterology, Sheba Medical Center Tel Hashomer, Ramat Gan, Israel. Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Rambam Health Care Campus and Bruce Rappaport School of Medicine, Haifa, Israel. Technion Israel Institute of Technology, Haifa, Israel. Department
  • Lang A; Department of Gastroenterology, Sheba Medical Center Tel Hashomer, Ramat Gan, Israel. Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Rambam Health Care Campus and Bruce Rappaport School of Medicine, Haifa, Israel. Technion Israel Institute of Technology, Haifa, Israel. Department
  • Avidan B; Department of Gastroenterology, Sheba Medical Center Tel Hashomer, Ramat Gan, Israel. Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Rambam Health Care Campus and Bruce Rappaport School of Medicine, Haifa, Israel. Technion Israel Institute of Technology, Haifa, Israel. Department
  • Har-Noy O; Department of Gastroenterology, Sheba Medical Center Tel Hashomer, Ramat Gan, Israel. Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Rambam Health Care Campus and Bruce Rappaport School of Medicine, Haifa, Israel. Technion Israel Institute of Technology, Haifa, Israel. Department
  • Carter D; Department of Gastroenterology, Sheba Medical Center Tel Hashomer, Ramat Gan, Israel. Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Rambam Health Care Campus and Bruce Rappaport School of Medicine, Haifa, Israel. Technion Israel Institute of Technology, Haifa, Israel. Department
  • Levhar N; Department of Gastroenterology, Sheba Medical Center Tel Hashomer, Ramat Gan, Israel. Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Rambam Health Care Campus and Bruce Rappaport School of Medicine, Haifa, Israel. Technion Israel Institute of Technology, Haifa, Israel. Department
  • Selinger L; Department of Gastroenterology, Sheba Medical Center Tel Hashomer, Ramat Gan, Israel. Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Rambam Health Care Campus and Bruce Rappaport School of Medicine, Haifa, Israel. Technion Israel Institute of Technology, Haifa, Israel. Department
  • Neuman S; Department of Gastroenterology, Sheba Medical Center Tel Hashomer, Ramat Gan, Israel. Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Rambam Health Care Campus and Bruce Rappaport School of Medicine, Haifa, Israel. Technion Israel Institute of Technology, Haifa, Israel. Department
  • Natour OH; Department of Gastroenterology, Sheba Medical Center Tel Hashomer, Ramat Gan, Israel. Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Rambam Health Care Campus and Bruce Rappaport School of Medicine, Haifa, Israel. Technion Israel Institute of Technology, Haifa, Israel. Department
  • Yavzori M; Department of Gastroenterology, Sheba Medical Center Tel Hashomer, Ramat Gan, Israel. Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Rambam Health Care Campus and Bruce Rappaport School of Medicine, Haifa, Israel. Technion Israel Institute of Technology, Haifa, Israel. Department
  • Fudim E; Department of Gastroenterology, Sheba Medical Center Tel Hashomer, Ramat Gan, Israel. Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Rambam Health Care Campus and Bruce Rappaport School of Medicine, Haifa, Israel. Technion Israel Institute of Technology, Haifa, Israel. Department
  • Picard O; Department of Gastroenterology, Sheba Medical Center Tel Hashomer, Ramat Gan, Israel. Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Rambam Health Care Campus and Bruce Rappaport School of Medicine, Haifa, Israel. Technion Israel Institute of Technology, Haifa, Israel. Department
  • Kopylov U; Department of Gastroenterology, Sheba Medical Center Tel Hashomer, Ramat Gan, Israel. Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Rambam Health Care Campus and Bruce Rappaport School of Medicine, Haifa, Israel. Technion Israel Institute of Technology, Haifa, Israel. Department
  • Chowers Y; Department of Gastroenterology, Sheba Medical Center Tel Hashomer, Ramat Gan, Israel. Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Rambam Health Care Campus and Bruce Rappaport School of Medicine, Haifa, Israel. Technion Israel Institute of Technology, Haifa, Israel. Department
  • Naftali T; Department of Gastroenterology, Sheba Medical Center Tel Hashomer, Ramat Gan, Israel. Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Rambam Health Care Campus and Bruce Rappaport School of Medicine, Haifa, Israel. Technion Israel Institute of Technology, Haifa, Israel. Department
  • Broide E; Department of Gastroenterology, Sheba Medical Center Tel Hashomer, Ramat Gan, Israel. Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Rambam Health Care Campus and Bruce Rappaport School of Medicine, Haifa, Israel. Technion Israel Institute of Technology, Haifa, Israel. Department
  • Shachar E; Department of Gastroenterology, Sheba Medical Center Tel Hashomer, Ramat Gan, Israel. Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Rambam Health Care Campus and Bruce Rappaport School of Medicine, Haifa, Israel. Technion Israel Institute of Technology, Haifa, Israel. Department
  • Eliakim R; Department of Gastroenterology, Sheba Medical Center Tel Hashomer, Ramat Gan, Israel. Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Rambam Health Care Campus and Bruce Rappaport School of Medicine, Haifa, Israel. Technion Israel Institute of Technology, Haifa, Israel. Department
  • Ben-Horin S; Department of Gastroenterology, Sheba Medical Center Tel Hashomer, Ramat Gan, Israel. Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Rambam Health Care Campus and Bruce Rappaport School of Medicine, Haifa, Israel. Technion Israel Institute of Technology, Haifa, Israel. Department
Am J Gastroenterol ; 113(6): 890-898, 2018 06.
Article em En | MEDLINE | ID: mdl-29867175
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doença de Crohn / Monitoramento de Medicamentos / Adalimumab / Anti-Inflamatórios Tipo de estudo: Clinical_trials / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Female / Humans / Male Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doença de Crohn / Monitoramento de Medicamentos / Adalimumab / Anti-Inflamatórios Tipo de estudo: Clinical_trials / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Female / Humans / Male Idioma: En Ano de publicação: 2018 Tipo de documento: Article