Low-dose oral methotrexate for maintaining Crohn's disease remission: where we stand.
Methotrexate has been considered a second-line immunomodulating therapy, behind azathioprine (AZA) or its metabolite 6-mercaptopurine (6-MP), for the treatment of Crohn's disease (CD). Approximately 27% to 50% of patients with refractory CD are intolerant or resistant to AZA or 6-MP. Two well-designed randomized double-blind placebo-controlled trials have demonstrated that low-dose methotrexate (<25 mg/wk), given intramuscularly (IM), is effective in inducing and maintaining remission in CD. In clinical practice, IM injection involves an inconvenience for patients and higher costs. Furthermore, frequent IM injections increase the risk of complications such as peripheral nerve injury, local irritation, pain, bleeding, fibrosis, abscess formation, gangrene, and contractures. Alternatively, subcutaneous (SQ) injection has been advocated because it has been shown to have similar pharmacokinetics to IM injection. However, because of a recent and ongoing national shortage of parenteral methotrexate, patients who were receiving IM methotrexate had to switch to the oral form until the parenteral formulation becomes available. Oral methotrexate has been used with great success in treatment of rheumatoid arthritis and psoriasis for the past 50 years. However, the data on the usage of low-dose oral methotrexate in maintaining CD remission are scanty and controversial. The purpose of this article is to review the mechanism of action, absorption, and the objective evidence in supporting the use of oral methotrexate in maintaining CD remission.
Sun
John H
JH
Crohn's and Colitis Center of New Jersey, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA.
Das
Kiron M
KM
D000284:Administration, Oral; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D003424:Crohn Disease / Q000188:drug therapy* / Q000378:metabolism; D004334:Drug Administration Schedule; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007408:Intestinal Absorption; D008727:Methotrexate / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016032:Randomized Controlled Trials as Topic; D012074:Remission Induction
D018501:Antirheumatic Agents; D007166:Immunosuppressive Agents; D008727:Methotrexate