Should azathioprine and 5-aminosalicylates be coprescribed in inflammatory bowel disease?: an audit of adverse events and outcome.
BACKGROUND
An interaction between azathioprine and 5-aminosalicylates may exist, but the mechanism remains unclear.


OBJECTIVE
To investigate the occurrence of adverse events and efficacy of azathioprine with or without mesalazine.


METHODS
Retrospective study of 199 patients. In all, 95 patients received azathioprine alone (monotherapy); 104 received combination of 5-aminosalicylates and azathioprine (dual therapy). Data were recorded on adverse events, azathioprine dose and thiopurine methyl transferase (TPMT) level. In 85 of the patients, relapse rate was compared in the two groups.


RESULTS
Adverse events were more common in dual therapy group, 50/104, than in monotherapy group, 29/95; chi=6.4, P=0.05. Most patients had normal TPMT activity. No relationship between TPMT activity and adverse events was observed. A total of 105 patients took (>or=2 mg/kg) azathioprine; adverse events occurred in 26% compared with 54% taking less than 2 mg/kg (chi=15.8, P<0.0001). Discontinuation of azathioprine owing to adverse events was found to be higher in dual therapy group, 26/50, than in monotherapy group, 7/29 (chi=5.0, P<0.01). Relapse rate was higher in the dual therapy group (29/49) than with monotherapy (12/36) (chi=5.5, P<0.02).


CONCLUSIONS
Adverse events are more common in patients taking dual therapy than azathioprine monotherapy. Adverse events are unrelated to dose of azathioprine. Patients receiving dual therapy are more likely to relapse than patients receiving monotherapy.
Shah
Jayshri A
JA
Bristol Royal Infirmary, Bristol, UK.
Edwards
Cathryn M
CM
Probert
Chris S
CS
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001379:Azathioprine / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008485:Medical Audit; D019804:Mesalamine / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D008780:Methyltransferases / Q000097:blood; D012008:Recurrence; D012189:Retrospective Studies; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007166:Immunosuppressive Agents; D019804:Mesalamine; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine