Methotrexate for induction of remission in refractory Crohn's disease

Robarts Clinical Trials, Robarts Research Institute, P.O. Box 5015, 100 Perth Drive, London, Ontario, Canada, N6A 5K8.
Cochrane database of systematic reviews (Online) (Impact Factor: 6.03). 12/2012; 12(12):CD003459. DOI: 10.1002/14651858.CD003459.pub3
Source: PubMed


Although corticosteroids are effective for induction of remission of Crohn's disease, many patients relapse when steroids are withdrawn or become steroid dependent. Furthermore, corticosteroids exhibit significant side effects. Methotrexate is an immunosuppressive drug that is used to treat active treatment resistant Crohn's disease. This review includes seven randomized trials with a total of 495 participants. There is evidence from one large study which suggests that methotrexate (25 mg/week) injected intramuscularly for 16 weeks among patients with active treatment resistant Crohn's disease may provide a benefit for induction of remission and complete withdrawal from steroids. This reduction in steroid use could reduce steroid-induced side effects for people with chronic Crohn's disease. Although side effects are more common with high dose methotrexate therapy, no serious side effects have been observed. Common side effects associated with methotrexate therapy include nausea and vomiting, abdominal pain, diarrhea, skin rash and headache. Studies comparing lower dose oral methotrexate (12.5 to 15 mg/week) to placebo (e.g. sugar pill) or other active drugs (e.g. azathioprine or 6-mercaptopurine) indicate that lower dose oral methotrexate does not appear to provide any benefit for treatment of active treatment resistant Crohn's disease. However, these trials were small in size and further studies of oral methotrexate may be justified. Two studies looked at the combination of methotrexate and infliximab (a biological drug) compared to infliximab therapy alone. These studies indicated that the addition of methotrexate to infliximab therapy does not appear to provide any additional benefit over infiximab. 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.

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    • "IFX trough concentrations in the combination group were higher compared with the mono-therapy group, but this difference was not statistically significant (6.35 μg/mL vs 3.75 μg/mL; P=0.08). In a Cochrane review, the combination of methotrexate with IFX therapy did not provide any additional benefit over IFX monotherapy, although more data are needed.41 "
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    ABSTRACT: Dovepress 359 R E v i E w open access to scientific and medical research Open Access Full Text Article Abstract: Infliximab (IFX) is an effective treatment for inducing and maintaining response in Crohn's disease and ulcerative colitis patients. Some patients present lack of response or loss of response to IFX during maintenance therapy. Empirical management with combination therapy with an immunomodulator, IFX dose escalation, or switching IFX for another antitumor necrosis factor-α drug, mainly adalimumab, is common in clinical practice. Selecting the best choice with the help of serum drug concentrations and trough IFX antibody concentrations could be a very interesting approach. In addition to surgery, a broad spectrum of new drugs has been tested and could expand treatment options in the near future.
    Clinical and Experimental Gastroenterology 09/2014; 7. DOI:10.2147/CEG.S45297
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    • "Historically, corticosteroids were used as first-line therapy to manage symptoms, but were associated with a high incidence of steroid dependency and unacceptable rates of adverse events.1 Furthermore, while corticosteroids are useful to induce symptomatic remission, they do not promote mucosal healing and are not useful for maintenance of remission.1,2 Methotrexate and thiopurines (6-mercaptopurine and azathioprine) were found to be effective as steroid-sparing agents and for maintenance of remission in CD,3–5 but have a delayed onset of action and are only effective in 60%–70% of patients who receive them.4,5 More recently, the tumor necrosis factor (TNF)-α antagonists infliximab and adalimumab have been shown to be effective for the induction and maintenance of remission in patients with moderate-to-severe CD, while certolizumab pegol is effective for the maintenance of remission in patients who have responded to certolizumab-induction therapy.6–12 "
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    ABSTRACT: The advent of anti-tumor necrosis factor (TNF)-α therapy has been a major advance in the medical management of Crohn's disease (CD). However, a significant proportion of patients with CD do not respond adequately to treatment with these agents. Primary and secondary nonresponse to anti-TNFα therapy represents a common clinical challenge, and highlights the need for the development of additional medication options for CD. The proinflammatory cytokines interleukin (IL)-12 and IL-23 are thought to play a key role in the pathogenesis of CD, and serve as a potential target for additional biologic therapies. Monoclonal antibodies targeting IL-12/23 have shown efficacy in animal models of colitis, and are currently being studied in Phase III clinical trials of CD. This review focuses on ustekinumab, a fully human immunoglobulin G1 monoclonal antibody, which blocks activity of IL-12 and IL-23 through binding the p40 subunit, and describes the current efficacy and safety data for ustekinumab in patients with CD.
    Clinical and Experimental Gastroenterology 05/2014; 7(1):173-179. DOI:10.2147/CEG.S39518
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    ABSTRACT: To assess the efficacy and safety of mycophenolate mofetil (MMF) prospectively in inflammatory bowel disease (IBD) patients intolerant or refractory to conventional medical therapy. Crohn's disease (CD) or ulcerative colitis/IBD unclassified (UC/IBDU) patients intolerant or refractory to conventional medical therapy received MMF (500-2000 mg bid). Clinical response was assessed by the Harvey Bradshaw index (HBI) or colitis activity index (CAI) after 2, 6 and 12 mo of therapy, as were steroid usage and adverse effects. Fourteen patients (9 CD/5 UC/IBDU; 8M/6F; mean age 50.4 years, range 28-67 years) were treated and prospectively assessed for their response to oral MMF. Of the 11 patients who were not in remission on commencing MMF, 7/11 (63.6%) achieved remission by 8 wk. All 3 patients in remission on commencing MMF maintained their remission. Ten patients were still on MMF at 6 mo with 9/14 (64.3%) in remission, while of 12 patients followed for 12 mo, 8 were in remission without dose escalation (66.7%). Three patients were withdrawn from the MMF due to drug intolerance. There were no serious adverse events attributed due to the medication. MMF demonstrated efficacy in the management of difficult IBD. MMF appeared safe, well tolerated and efficacious for both short and long-term therapy, without the need for dose escalation. Further evaluation of MMF comparing it to conventional immunosuppressants is required.
    World Journal of Gastroenterology 05/2009; 15(13):1594-9. · 2.37 Impact Factor
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