Influence of trough serum levels and immunogenicity on long-term outcome of adalimumab therapy in Crohn's disease.

نویسندگان

  • Konstantinos Karmiris
  • Gilles Paintaud
  • Maja Noman
  • Charlotte Magdelaine-Beuzelin
  • Marc Ferrante
  • Danielle Degenne
  • Karolien Claes
  • Tamara Coopman
  • Nele Van Schuerbeek
  • Gert Van Assche
  • Severine Vermeire
  • Paul Rutgeerts
چکیده

BACKGROUND & AIMS Adalimumab is an efficacious therapy for active Crohn's disease, but long-term data are scarce. We conducted an observational study to assess the long-term clinical benefit of adalimumab in patients who failed to respond to infliximab, specifically focusing on the influence of trough serum concentration and antibodies against adalimumab on clinical outcome. METHODS A total of 168 patients with Crohn's disease treated with adalimumab in a tertiary center were included in a prospective follow-up program. Trough serum concentration and antibodies against adalimumab were measured at predefined time points using enzyme-linked immunosorbent assays. RESULTS A total of 71% and 67% of patients responded by weeks 4 and 12, respectively; among them, 61.5% demonstrated sustained clinical benefit until the end of follow-up (median [interquartile range], 20.4 [11.7-30.0] months). Of the 156 patients receiving maintenance therapy, 102 (65.4%) had to step up to 40 mg weekly and 60 (38.5%) eventually stopped adalimumab therapy mainly due to loss of response. Significantly lower adalimumab trough serum concentrations were measured throughout the follow-up period in patients who discontinued therapy as compared with patients who stayed on adalimumab. Antibodies against adalimumab were present in 9.2% of the patients and affected trough serum concentration. Serious adverse events occurred in 12% of the patients. CONCLUSIONS Introduction of adalimumab after failure of infliximab therapy resulted in a sustained clinical benefit in two thirds of patients during a median follow-up period of almost 2 years. Discontinuation was directly related to low adalimumab trough serum concentration, which was observed more frequently in patients who developed antibodies against adalimumab.

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عنوان ژورنال:
  • Gastroenterology

دوره 137 5  شماره 

صفحات  -

تاریخ انتشار 2009