Methotrexate has been used to treat CD for some 25 years. Research has found that a weekly dose of 25 mg by injection may induce remission in CD, while a lower dose of 15 mg per week can maintain remission.

There is some evidence that taking methotrexate by injection is more effective and may cause fewer side effects than tablets when treating CD. However, some people prefer to use oral preparations because they are more convenient, and some doctors prescribe the oral tablets to maintain remission once remission has been induced by the injections.

Research on the use of methotrexate for UC is limited, partially because many of the studies looked at a very low oral dose of methotrexate. However, medical experience suggests that it can be beneficial for some people with UC.

Sometimes methotrexate is used in combination with biological drugs such as infliximab or adalimumab. However, the evidence for this is mixed, some studies suggest that methotrexate reduces the risk of developing antibodies to the biological drug and makes it work better, but other studies do not show any benefit.