Use of Methotrexate in the Treatment of Inflammatory Bowel Diseases

Abstract

Low-dose methotrexate (MTX) therapy is a well-recognized therapy for many inflammatory conditions such as rheumatoid arthritis (RA), psoriatic arthritis and psoriasis. More than 20 years ago the clinical efficacy of MTX was also established for steroid dependent Crohn’s disease (CD), but it was never broadly adapted as a treatment modality. More recently, MTX has become increasingly used in the pediatric CD population, both as a single agent as well as a concomitant therapy with anti-tumor necrosis factor-alpha (anti-TNF) treatment. This review outlines important pharmacological aspects for the therapeutic application of MTX and the current status of MTX as mono- or combination therapy in both pediatric and adult patients with IBD including new results of MTX monotherapy in steroid dependent ulcerative colitis (UC).

Understanding the Cautions and Contraindications of Immunomodulator and Biologic Therapies for Use in Inflammatory Bowel Disease

“…In circulation, it is albumin-bound; thus, hypoalbuminemia or the presence of concomitant medications that competitively bind albumin (e.g., tetracyclines) cause the accumulation of free MTX in the serum, increasing the risk of the hepatic, hematological, and the aforementioned pulmonary toxicity. 94,95 A creatinine clearance of less than 20 mL/min is a contraindication to MTX treatment, 96 as are medications that competitively inhibit the renal excretion of MTX (e.g., sulfonamides and commonly-used NSAIDs). 95 …”

“…This includes suspected or undiagnosed liver disease, as in patients who are heavy alcohol users and obese (body mass index >30 kg/m 2 ), diabetic and hyperlipidemic patients, of whom the latter three are at increased risk of nonalcoholic fatty liver disease. 94,98 Known chronic liver diseases, particularly chronic viral hepatitis B (HBV) and C (HCV) are also contraindications. Although rare and more often associated with anti-TNF-α agents, reactivation of resolved HBV infection in MTX-treated patients has been reported, 99 although a recent report claimed no reactivation in an HBV-infected population with rheumatological diseases in Thailand.…”

“…101 For MTX-treated psoriasis patients, current guidelines recommend a surveillance liver biopsy after a cumulative dose of 1000–1500 mg in patients with a baseline risk of liver disease and 3500–4000 mg for those without such risk factors. 94 No similar guidelines exist for IBD patients. Moreover, Dawwas et al report that because MTX-induced hepatotoxicity is so rarely associated with need for liver transplant, in the absence of the abovementioned risk factors, the use of MTX should not be discouraged.…”

Methotrexate for Inflammatory Bowel Diseases - New Developments

“…Currently liver biopsies are only recommended in the setting of reproducible elevations of liver function tests, however, liver fibrosis or cirrhosis may also develop in the absence of abnormal liver values. 10, 14 Thus a non-invasive method to monitor patients on long term MTX therapy would be desirable. Possibilities to monitor for liver toxicity in a non-invasive manner might be the use of transient elastography (TE; Fibroscan).…”

“…However, more recently, MTX therapy is becoming more in vogue in pediatric patients and is also investigated as a potential therapeutic approach in patients with UC. 8-10 …”