To test the effectiveness of 6-mercaptopurine (6-MP) in the treatment of Crohn's disease, we entered 83 chronically ill patients into a two-year double-blind study comparing 6-MP with placebo. Crossover data showed that improvement occurred in 26 of 39 courses of 6-MP (67%) as compared with three of 39 courses of placebo (8%) (P less than 0.001). Non-crossover data likewise confirmed the superiority of 6-MP. The drug was more effective than placebo in closing fistulas (31 vs 6%) and in permitting discontinuation or reduction of steroid dosage (75 vs. 36%) (P less than 0.001). The onset of response to 6-MP was often delayed, with 32% of patients taking longer than three months to respond, and 19% taking longer than four months. Adverse side effects to 6-MP occurred in 10% of patients and were uniformly reversible. We conclude that 6-MP is an effective and useful agent in the management of Crohn's disease.
This article has been cited by other articles:
Valentine, J F, Fedorak, R N, Feagan, B, Fredlund, P, Schmitt, R, Ni, P, Humphries, T J
(2009). Steroid-sparing properties of sargramostim in patients with corticosteroid-dependent Crohn's disease: a randomised, double-blind, placebo-controlled, phase 2 study. Gut
58: 1354-1362
[Abstract][Full Text]
Schnitzler, F, Fidder, H, Ferrante, M, Noman, M, Arijs, I, Van Assche, G, Hoffman, I, Van Steen, K, Vermeire, S, Rutgeerts, P
(2009). Long-term outcome of treatment with infliximab in 614 patients with Crohn's disease: results from a single-centre cohort. Gut
58: 492-500
[Abstract][Full Text]
Yuan, B., Wang, Y.
(2008). Mutagenic and Cytotoxic Properties of 6-Thioguanine, S6-Methylthioguanine, and Guanine-S6-sulfonic Acid. J. Biol. Chem.
283: 23665-23670
[Abstract][Full Text]
Feagan, B. G., Sandborn, W. J., Mittmann, U., Bar-Meir, S., D'Haens, G., Bradette, M., Cohen, A., Dallaire, C., Ponich, T. P., McDonald, J. W. D., Hebuterne, X., Pare, P., Klvana, P., Niv, Y., Ardizzone, S., Alexeeva, O., Rostom, A., Kiudelis, G., Spleiss, J., Gilgen, D., Vandervoort, M. K., Wong, C. J., Zou, G. Y., Donner, A., Rutgeerts, P.
(2008). Omega-3 Free Fatty Acids for the Maintenance of Remission in Crohn Disease: The EPIC Randomized Controlled Trials. JAMA
299: 1690-1697
[Abstract][Full Text]
Poppe, D., Tiede, I., Fritz, G., Becker, C., Bartsch, B., Wirtz, S., Strand, D., Tanaka, S., Galle, P. R., Bustelo, X. R., Neurath, M. F.
(2006). Azathioprine Suppresses Ezrin-Radixin-Moesin-Dependent T Cell-APC Conjugation through Inhibition of Vav Guanosine Exchange Activity on Rac Proteins. J. Immunol.
176: 640-651
[Abstract][Full Text]
Cosnes, J, Nion-Larmurier, I, Beaugerie, L, Afchain, P, Tiret, E, Gendre, J-P
(2005). Impact of the increasing use of immunosuppressants in Crohn's disease on the need for intestinal surgery. Gut
54: 237-241
[Abstract][Full Text]
Sandborn, W J, Loftus, E V
(2004). Balancing the risks and benefits of infliximab in the treatment of inflammatory bowel disease. Gut
53: 780-782
[Full Text]
Sands, B. E., Anderson, F. H., Bernstein, C. N., Chey, W. Y., Feagan, B. G., Fedorak, R. N., Kamm, M. A., Korzenik, J. R., Lashner, B. A., Onken, J. E., Rachmilewitz, D., Rutgeerts, P., Wild, G., Wolf, D. C., Marsters, P. A., Travers, S. B., Blank, M. A., van Deventer, S. J.
(2004). Infliximab Maintenance Therapy for Fistulizing Crohn's Disease. NEJM
350: 876-885
[Abstract][Full Text]
Oh, K.-T., Anis, A. H., Bae, S.-C.
(2004). Pharmacoeconomic analysis of thiopurine methyltransferase polymorphism screening by polymerase chain reaction for treatment with azathioprine in Korea. Rheumatology (Oxford)
43: 156-163
[Abstract][Full Text]
Stallmach, A, Wittig, B M, Moser, C, Fischinger, J, Duchmann, R, Zeitz, M
(2003). Safety and efficacy of intravenous pulse cyclophosphamide in acute steroid refractory inflammatory bowel disease. Gut
52: 377-382
[Abstract][Full Text]
Podolsky, D. K.
(2002). Inflammatory Bowel Disease. NEJM
347: 417-429
[Full Text]
Lennard, L
(2002). TPMT in the treatment of Crohn's disease with azathioprine. Gut
51: 143-146
[Abstract][Full Text]
Farthing, M J G
(2002). Ileal Crohn's disease is best treated by surgery. Gut
51: 13-14
[Full Text]
Schwartz, D. A., Pemberton, J. H., Sandborn, W. J.
(2001). Diagnosis and Treatment of Perianal Fistulas in Crohn Disease. ANN INTERN MED
135: 906-918
[Abstract][Full Text]
SANDBORN, W J
(2001). Rational dosing of azathioprine and 6-mercaptopurine. Gut
48: 591-592
[Full Text]
Cuffari, C, Hunt, S, Bayless, T
(2001). Utilisation of erythrocyte 6-thioguanine metabolite levels to optimise azathioprine therapy in patients with inflammatory bowel disease. Gut
48: 642-646
[Abstract][Full Text]
Feagan, B. G., Fedorak, R. N., Irvine, E. J., Wild, G., Sutherland, L., Steinhart, A. H., Greenberg, G. R., Koval, J., Wong, C. J., Hopkins, M., Hanauer, S. B., McDonald, J. W.D., The North American Crohn's Study Group Investigato,
(2000). A Comparison of Methotrexate with Placebo for the Maintenance of Remission in Crohn's Disease. NEJM
342: 1627-1632
[Abstract][Full Text]
Sartor, R. B.
(2000). New Therapeutic Approaches to Crohn's Disease. NEJM
342: 1664-1666
[Full Text]
Present, D. H., Rutgeerts, P., Targan, S., Hanauer, S. B., Mayer, L., van Hogezand, R.A., Podolsky, D. K., Sands, B. E., Braakman, T., DeWoody, K. L., Schaible, T. F., van Deventer, S. J.H.
(1999). Infliximab for the Treatment of Fistulas in Patients with Crohn's Disease. NEJM
340: 1398-1405
[Abstract][Full Text]
Neurath, M F, Wanitschke, R, Peters, M, Krummenauer, F, zum Buschenfelde, K-H M., Schlaak, J F
(1999). Randomised trial of mycophenolate mofetil versus azathioprine for treatment of chronic active Crohn's disease. Gut
44: 625-628
[Abstract][Full Text]
Wyllie, R., Sarigol, S.
(1998). The Treatment of Inflammatory Bowel Disease in Children. CLIN PEDIATR
37: 421-425
Gross, V, Andus, T, Ecker, K W, Raedler, A, Loeschke, K, Plauth, M, Rasenack, J, Weber, A, Gierend, M, Ewe, K, Scholmerich, J, Budesonide Study Group,
(1998). Low dose oral pH modified release budesonide for maintenance of steroid induced remission in Crohn's disease. Gut
42: 493-496
[Abstract][Full Text]
Ballow, M., Nelson, R.
(1997). Immunopharmacology: Immunomodulation and Immunotherapy. JAMA
278: 2008-2017
[Abstract]
Hanauer, S. B.
(1996). Inflammatory Bowel Disease. NEJM
334: 841-848
[Full Text]
Korelitz, B. I., Present, D. H., Feagan, B. G., McDonald, J. W.D., The North American Crohn's Study Group investigato,
(1995). Methotrexate for Crohn's Disease. NEJM
333: 600-601
[Full Text]
Feagan, B. G., McDonald, J., Rochon, J., Laupacis, A., Fedorak, R. N., Kinnear, D., Saibil, F., Groll, A., Archambault, A., Gillies, R., Valberg, B., Irvine, E. J., The Canadian Crohn's Relapse Prevention Trial Inve,
(1994). Low-Dose Cyclosporine for the Treatment of Crohn's Disease. NEJM
330: 1846-1851
[Abstract][Full Text]
Peppercorn, M. A.
(1990). Advances in Drug Therapy for Inflammatory Bowel Disease. ANN INTERN MED
112: 50-60
[Abstract]
Present, D. H., Meltzer, S. J., Krumholz, M. P., Wolke, A., Korelitz, B. I.
(1989). 6-Mercaptopurine in the Management of Inflammatory Bowel Disease: Short- and Long-Term Toxicity. ANN INTERN MED
111: 641-649
[Abstract]
Kozarek, R. A., Patterson, D. J., Gelfand, M. D., Botoman, V. A., Ball, T. J., Wilske, K. R.
(1989). Methotrexate Induces Clinical and Histologic Remission in Patients with Refractory Inflammatory Bowel Disease. ANN INTERN MED
110: 353-356
[Abstract]
