Optimum duration of treatment with 6-mercaptopurine for Crohn's disease.
OBJECTIVE
6-Mercaptopurine (6MP) and azathioprine are immunomodulators used in the treatment of refractory Crohn's disease. Studies have confirmed their efficacy and value in maintenance of remission, but it is our purpose to determine how long 6MP/azathioprine should be continued once remission has been accomplished.


METHODS
Careful follow-up was accomplished in patients with Crohn's disease seen at one medical center who were treated with 6MP for > or = 6 months, who achieved remission within 1 yr of initiation of therapy, and who were in prolonged clinical remission (> or = 6 months without steroids). The time-to-relapse was calculated in those who continued treatment, in those who stopped treatment for reasons other than a relapse, and in the whole sample, taking into account that they could be treated with the drug, or could not, as a function of time. The influence of concomitant variables on the time-to-relapse rate was evaluated.


RESULTS
A total of 120 patients met the inclusion criteria. The cumulative probabilities of relapse at 1, 2, 3, and 5 yr for those who continued to take 6MP and for those who stopped the therapy for reasons other than a relapse are as follows: Patients maintained on 6MP (n = 84): 1 yr, 29%; 2 yr, 45%; 3 yr, 55%; 5 yr, 61%. Patients who terminated 6MP (n = 36): 1 yr, 36%; 2 yr, 71%; 3 yr, 85%; 5 yr, 85%. Sex, distribution of disease, duration of disease, time to remission on 6MP, and concomitant 5-ASA use did not influence the relapse rates. Younger age was associated with a higher rate of relapse in patients who were maintained on 6MP. A higher daily dose of 6MP was associated with a higher relapse rate.


CONCLUSIONS
Discontinuation of 6MP, while Crohn's disease is in remission, leads to higher relapse rates and continuation of 6MP reduces the likelihood of relapse. Therefore, we favor the indefinite use of 6MP once remission has been achieved.
Kim
P S
PS
Department of Medicine, Lenox Hill Hospital and the New York University School of Medicine, New York 10021, USA.
Zlatanic
J
J
Korelitz
B I
BI
Gleim
G W
GW
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001379:Azathioprine / Q000627:therapeutic use; D016001:Confidence Intervals; D003424:Crohn Disease / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage / Q000627:therapeutic use*; D019804:Mesalamine / Q000627:therapeutic use; D008875:Middle Aged; D011336:Probability; D016016:Proportional Hazards Models; D012008:Recurrence; D012074:Remission Induction; D012737:Sex Factors; D013997:Time Factors
D000276:Adjuvants, Immunologic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007166:Immunosuppressive Agents; D019804:Mesalamine; D015122:Mercaptopurine; D001379:Azathioprine