Methotrexate compared to placebo for induction of remission in refractory Crohn’s disease.
Related articles (Crohn):
*Infliximab in Crohn (ACCENT I)
*Infliximab with Azathiopurine (Crohn)
*Infliximab with Methotrexate (Crohn)
*Infliximab switch to Adalimumab in Crohn (GAIN/ADHERE trial)
*Adalimumab (CLASSIC & CHARM trial – Crohn)
*Adalimumab with immunomodulator (Crohn)
*Ustekinumab (UNITI trial – Crohn – 2016)
*Vedolizumab (GEMINI II – Crohn – 2013)
For the evidence on maintenance see end of page.
Cochrane meta-analysis conclusion.
There is evidence from a single large randomized trial which suggests that intramuscular methotrexate (25 mg/week) provides a benefit for induction of remission and complete withdrawal from steroids in patients with refractory Crohn’s disease. Lower dose oral methotrexate does not appear to provide any significant benefit relative to placebo or active comparator. However, these trials were small and further studies of oral methotrexate may be justified. Comparative studies of methotrexate to drugs such as azathioprine or 6‐mercaptopurine would require the randomization of large numbers of patients. The addition of methotrexate to infliximab therapy does not appear to provide any additional benefit over infliximab monotherapy. However these studies were relatively small and further research is needed to determine the role of methotrexate when used in conjunction with infliximab or other biological therapies.
Methotrexate for maintenance of remission in Crohn’s disease
Conclusions of Cochrane review
Moderate quality evidence indicates that intramuscular methotrexate at a dose of 15 mg/week is superior to placebo for maintenance of remission in Crohn’s disease. Intramuscular methotrexate appears to be safe. Low dose oral methotrexate (12.5 to 15 mg/week) does not appear to be effective for maintenance of remission in Crohn’s disease. Combination therapy (methotrexate and infliximab) does not appear to be any more effective for maintenance of remission than infliximab monotherapy. The results for efficacy outcomes between methotrexate and 6‐mercaptopurine and methotrexate and 5‐aminosalicylic acid were uncertain. Large‐scale studies of methotrexate given orally at higher doses for maintenance of remission in Crohn’s disease may provide stronger evidence for the use of methotrexate in this manner.
Feagan 2000 NEJM: A COMPARISON OF METHOTREXATE WITH PLACEBO FOR THE MAINTENANCE OF REMISSION IN CROHN’S DISEAS
McDonald JWD, Wang Y, Tsoulis DJ, MacDonald JK, Feagan BG. Methotrexate for induction of remission in refractory Crohn’s disease. Cochrane Database of Systematic Reviews 2014, Issue 8. Art. No.: CD003459. DOI: 10.1002/14651858.CD003459.pub4
Patel V, Wang Y, MacDonald JK, McDonald JWD, Chande N. Methotrexate for maintenance of remission in Crohn’s disease. Cochrane Database of Systematic Reviews 2014, Issue 8. Art. No.: CD006884. DOI: 10.1002/14651858.CD006884.pub3
Feagan BG, Fedorak RN, Irvine EJ, et al. A comparison of methotrexate with placebo for the maintenance of remission in Crohn’s disease. North American Crohn’s Study Group Investigators. N Engl J Med 2000;342:1627–32.