Low-Dose Oral Methotrexate for Maintaining Crohn??s Disease Remission

Abstract

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.

A role for Drosophila in understanding drug-induced cytotoxicity and teratogenesis

“…These changes to the structure are sufficient to make MTX a potent inhibitor of DHFR, and thus a valuable pharmaceutical (McGuire 2003). Indeed, MTX is used for the treatment of a wide variety of cancers (Huennekens 1994) as well as for the treatment of ectopic pregnancy (Fernandez et al 1998), inflammatory skin disease (Goujon et al 2006), Crohn's disease (Sun and Das 2005), rheumatoid arthritis (Nakazawa et al 2001), and systemic lupus (Wise et al 1996). However, MTX is a well known teratogen and therefore must be prescribed with caution to women of reproductive age (Lloyd et al 1999;Lewden et al 2004).…”

Methotrexate in the treatment of inflammatory bowel disease

“…leczenia, a wg niektórych autorów nawet później [1]. Niestety, u części chorych (wg niektórych zestawień nawet u 20-40%) leki te są nieskuteczne lub powodują wystąpienie działań niepożądanych (nudności, wymioty, uszkodzenie wątroby, szpiku, zapalenie trzustki) prowadzących do przerwania leczenia [2,3]. U tych chorych można rozważyć kilka terapii alternatywnych.…”

“…Spowodowało to szybkie wprowadzenie tych leków do praktyki dermatologicznej i reumatologicznej -MTX stał się podstawowym lekiem systemowym w łuszczycy o ciężkim przebiegu oraz jednym z tzw. leków modyfikujących przebieg choroby w RZS [2]. Skuteczność MTX w innych chorobach autoimmunologicznych doprowadziła w 1989 r. do zastosowania go w NChZJ [4].…”

“…Dzia łając poprzez monocyty i makrofagi, MTX hamuje produkcję TNF-α oraz prozapalnych interleukin 6 i 8 (IL-6 i IL-8) i jednocześnie pobudza syntezę działającej przeciwzapalnie IL-10 oraz antagonisty receptora IL-1 [1,5]. Innym prawdopodobnym mechanizmem przeciwzapalnego działania MTX jest zapobieganie aktywacji i nasilanie apoptozy aktywowanych limfocytów T [6] oraz hamowanie ekspresji cząsteczek przylegania na komórkach śródbłonka (E-selektyny i VCAM-1), prowadzące do osła-bienia chemotaksji neutrofilów [1,2,5]. Leki, które podobnie jak MTX ingerują w metabolizm kwasu foliowego (np.…”

Low dosages: new chemotherapeutic weapons on the battlefield of immune-related disease

“…40 To treat RA, the starting dose is usually 7.5-10 mg per week, and this can be increased to 20-25 mg per week, if a positive response has not occurred within 4-8 weeks after MTX initiation and there has been no toxicity. 41 Aside from RA, MTX has also been tested in other 44 In a retrospective study of 12 cutaneous lupus erythematosus patients treated with weekly low-dose MTX at 10-25 mg, six and four of these patients showed complete and partial remission, respectively. Five of the 10 responding patients presented with a long-term remission.…”