Methotrexate in inflammatory bowel disease: A primer for gastroenterologists

Abstract

Methotrexate is an antineoplastic agent that is also used at lower doses for anti-inflammatory properties. Along with thiopurines (azathioprine and 6-mercaptopurine), it has historically been an important part of pharmacological treatment for patients with inflammatory bowel disease. Despite an increase in therapeutic options, these immunomodulators continue to play important roles in the management of inflammatory bowel disease, used either as a monotherapy in mild to moderate cases or in combination with monoclonal antibodies to prevent immunogenicity and maintain efficacy. In light of data linking the use of thiopurines with the risk of malignancies, methotrexate has regained attention as a potential alternative. In this article, we review data on the pharmacology, safety, and efficacy of methotrexate and discuss options for the positioning of methotrexate alone, or in combination, in therapeutic algorithms for Crohn's disease and ulcerative colitis.

Methotrexate injection: An old drug with a newly developing landscape

“…MTX has also been used in the field of gastroenterology for the treatment of inflammatory bowel disease (IBD) 13,18,19 It is recommended that MTX be administered via subcutaneous injection at a dose level of 25 mg/wk for induction therapy and 15 mg/wk for maintenance therapy 19 . In dermatology, MTX is a classic medication for psoriasis and psoriatic arthritis and is also used in the treatment of atopic dermatitis, 20 refractory alopecia areata, 21 generalized granuloma annulare, 22 and reactive inflammatory lesions of leprosy 23 …”

Interplay between inflammatory bowel disease therapeutics and the gut microbiome reveals opportunities for novel treatment approaches

“…Parenterally-administered methotrexate can also interact with the intestinal microbiota due to biliary secretion [ 51 , 52 ] . Within the cells, methotrexate undergoes polyglutamation through the addition of varying numbers of glutamic acid molecules, resulting in a much more active version of the drug, methotrexate-polyglutamate (methotrexate-PG), where the longer-chain methotrexate-PGs are more potent [ 53 , 54 ] . Because of its ability to inhibit nucleic acid synthesis in rapidly proliferating cells, it was initially used in oncology [ 53 ] .…”

“…Within the cells, methotrexate undergoes polyglutamation through the addition of varying numbers of glutamic acid molecules, resulting in a much more active version of the drug, methotrexate-polyglutamate (methotrexate-PG), where the longer-chain methotrexate-PGs are more potent [ 53 , 54 ] . Because of its ability to inhibit nucleic acid synthesis in rapidly proliferating cells, it was initially used in oncology [ 53 ] . However, it is used at lower concentrations to treat IBD, where it exerts an anti-inflammatory response through inhibition of the enzyme 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/inosine monophosphate cyclohydrolase (ATIC) [ 55 ] .…”

Are immunomodulatory therapies safe in patients with inflammatory bowel disease? 23 years of single center experience

“…İmmünmodülatör ilaçlardan olan AZA toksisitesi; idiyosenkratik (halsizlik, gastrointestinal yakınmalar, hepatotoksisite, enfeksiyon, pankreatit, cilt toksisitesi ve artralji), doz bağımlı (hepatotoksisite, kemik iliği toksisitesi), immünsüpresyon ilişkili (bakteriyel, parazitik ve viral enfeksiyonlar) ve kanserler olarak sınıflandırılabilir (6). Bir diğer sıklıkla kullanılan immünmodülatör ajan olan MTK'nın yan etkileri arasında hepatotoksisite, karaciğer fibrozisi, gastrointestinal sistem ve kemik iliği toksisitesi yer almaktadır (7,8). Literatürdeki…”