Emergence of Crohn's disease during treatment with the anti-tumor necrosis factor agent etanercept for ankylosing spondylitis: possible mechanisms of action.
OBJECTIVE
To report on the clinical evolution of a patient with ankylosing spondylitis (AS) treated with etanercept who subsequently developed Crohn's disease, to review the literature for similar cases, and to discuss possible mechanisms responsible for these observations.


METHODS
We describe the medical history, diagnostic tests, and disease progression of a 26-year-old man with AS who developed the clinical manifestations of Crohn's disease after 16 months of successful treatment of his rheumatologic symptoms with etanercept. A Medline search, as well as cases presented in abstract form at European Leaque Against Rheumatism (EULAR) and American College of Rheumotology (ACR) meetings, describing emergent bowel symptoms in patients treated with etanercept was undertaken.


RESULTS
Eight other cases were identified, with gastrointestinal symptoms appearing after a few weeks to several years, while receiving etanercept treatment. These observations raise the possibility that etanercept unmasks inflammatory bowel disease in patients with AS whose gastrointestinal symptoms were silent.


CONCLUSIONS
The reactivation or the unmasking of gastrointestinal symptoms during etanercept treatment raises the issue of differences between etanercept and the other antitumor necrosis factor monoclonal antibodies in their molecular structure, tumor necrosis factor neutralizing effect, mode of administration, and pharmacokinetics that may account for these observations.
Haraoui
Boulos
B
University of Montréal, Rheumatology, Centre Hospitalier de l'Université de Montréal, Hôpital Notre Dame, Montreal, Canada. boulos.haraoui@ssss.gouv.qc.ca
Krelenbaum
Marilyn
M
D000328:Adult; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003424:Crohn Disease / Q000175:diagnosis* / Q000209:etiology*; D018450:Disease Progression; D000068800:Etanercept; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D013167:Spondylitis, Ankylosing / Q000150:complications / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept