Influence of trough serum levels and immunogenicity on long-term outcome of adalimumab therapy in Crohn's disease.
OBJECTIVE
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.
Karmiris
Konstantinos
K
Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium.
Paintaud
Gilles
G
Noman
Maja
M
Magdelaine-Beuzelin
Charlotte
C
Ferrante
Marc
M
Degenne
Danielle
D
Claes
Karolien
K
Coopman
Tamara
T
Van Schuerbeek
Nele
N
Van Assche
Gert
G
Vermeire
Severine
S
Rutgeerts
Paul
P
D000068879:Adalimumab; D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000276:immunology* / Q000493:pharmacokinetics*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D003424:Crohn Disease / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D004334:Drug Administration Schedule; D004351:Drug Resistance; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome; D055815:Young Adult
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D000069285:Infliximab; D000068879:Adalimumab