Immunogenicity negatively influences the outcome of adalimumab treatment in Crohn's disease.
BACKGROUND
Adalimumab is an effective treatment in patients with Crohn's disease; as it is a humanized anti-tumour necrosis factor monoclonal antibody, immunogenicity is thought not to be of any significance.


OBJECTIVE
To assess whether antibodies to adalimumab (ATAs) affect adalimumab treatment outcome in patients with Crohn's disease previously treated with infliximab.


METHODS
A retrospective study was performed. Patients with active Crohn's disease and who had lost response or were intolerant to infliximab were treated with adalimumab. Clinical response and side effects were assessed as were serum ATAs and antibodies to infliximab (ATIs).


RESULTS
In total 30 patients [M/F (7/23)], median age 36 years (range 21-73) were treated with adalimumab for 318 days (median range 83-632). Clinical response was 77% (23/30), a dose escalation was necessary in eight (27%) patients and side effects were observed in 47% (14/30). In five patients (17%) ATAs were detected; of these patients, four were nonresponders. The presence of ATAs was related to nonresponse to adalimumab (P = 0.006). ATIs were positive in 57% of patients (17/30) and serum levels were significantly increased in adalimumab nonresponders (P = 0.01).


CONCLUSIONS
Immunogenicity plays a role in adalimumab treatment because of the development of ATAs.
West
R L
RL
Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands. r.west@erasmusmc.nl
Zelinkova
Z
Z
Wolbink
G J
GJ
Kuipers
E J
EJ
Stokkers
P C F
PC
van der Woude
C J
CJ
D000068879:Adalimumab; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology; D061067:Antibodies, Monoclonal, Humanized; D003424:Crohn Disease / Q000188:drug therapy* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage* / Q000276:immunology; D055815:Young Adult
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab