Methotrexate

Methotrexate is an immunomodulator that can help control Crohn’s disease. It is used most often to maintain remission after a steroid response, or as a partner to biologics to lower the chance of antibody formation. It is given once weekly, usually by subcutaneous injection, with folic acid to reduce side effects. Careful lab monitoring and pregnancy prevention are essential. (journals.lww.com)

Key takeaways

• Works for Crohn’s maintenance, and sometimes as induction when steroids are needed. It has not shown clear benefit in ulcerative colitis. (cochrane.org)

• Typical plan: 25 mg once weekly by injection to induce, then 15 mg weekly to maintain. Oral dosing is less reliable in Crohn’s. (journals.lww.com)

• Expect onset in about 8 to 12 weeks. Keep weekly dosing consistent. Never take it daily. (crohnsandcolitis.org.uk)

• Folic acid is recommended to reduce nausea, mouth sores, and liver test bumps. Common regimens are 1 mg daily or 5 mg once weekly on a different day. (sps.nhs.uk)

• Labs are checked at 2, 4, 8, and 12 weeks, then every 8–12 weeks once stable. (sps.nhs.uk)

What methotrexate is and when it is used

• Methotrexate calms the immune system by blocking folate pathways that drive inflammation.

• In Crohn’s disease, methotrexate can maintain remission after a steroid response. Evidence supports parenteral dosing. It is less effective for induction than modern biologics, but may help in steroid‑dependent cases. (cochrane.org)

• In ulcerative colitis, randomized trials and reviews have not shown clear benefit for induction or maintenance, so it is not routinely used. (cochrane.org)

Combination with biologics

• Adding methotrexate to an anti‑TNF can reduce anti‑drug antibodies in some settings, which may help drug levels. Evidence is mixed. The COMMIT trial found no added benefit of infliximab plus methotrexate over infliximab alone, while observational work shows lower antibody rates with an immunomodulator. Combination is considered when thiopurines are not tolerated. (pubmed.ncbi.nlm.nih.gov)

How it is taken

• Route and dose

• Induction: 25 mg once weekly by subcutaneous or intramuscular injection.

• Maintenance: 15 mg once weekly.

• Oral dosing can be considered in those without malabsorption, but injections are preferred in Crohn’s. (journals.lww.com)

• Time to effect

• Many people notice benefit after about 8 to 12 weeks. Continue weekly doses as prescribed. (crohnsandcolitis.org.uk)

• Folic acid

• Reduces mouth sores, nausea, and abnormal liver tests. Typical options are folic acid 1 mg daily or 5 mg once weekly, on a different day from methotrexate. (sps.nhs.uk)

Safety and required lab monitoring

• Baseline screening before the first dose

• Complete blood count, liver enzymes, albumin, and kidney function.

• Hepatitis B surface antigen, core antibody, and surface antibody. Vaccinate if nonimmune.

• Hepatitis C testing as clinically indicated.

• Tuberculosis risk assessment and testing if indicated.

• Pregnancy test when relevant, and contraception planning.

• Consider lung history or imaging if respiratory disease is suspected. (sps.nhs.uk)

• Ongoing lab schedule for gastroenterology use

Monitor more often if results trend abnormal, doses change, or risks are high. (sps.nhs.uk)

• What to watch for

• Common: nausea, fatigue, headache, mouth sores, mild hair thinning, and abnormal liver tests.

• Serious but uncommon: liver injury, bone marrow suppression, severe infections, and lung inflammation that causes cough or shortness of breath. Seek urgent care for fever, heavy bleeding, severe breathlessness, or jaundice. (journals.lww.com)

Who should not take methotrexate

• Pregnancy or breastfeeding, or trying to conceive soon.

• Significant chronic liver disease or heavy alcohol use.

• Severe kidney impairment.

• Pre‑existing blood count disorders or uncontrolled active infection. Decisions are individualized by the care team. (drugs.com)

Drug and vaccine interactions

• Avoid trimethoprim‑sulfamethoxazole when possible, because together they can cause dangerous drops in blood counts. If no alternative exists, close monitoring is required. Use NSAIDs cautiously. Limit or avoid alcohol. (pubmed.ncbi.nlm.nih.gov)

• Live vaccines are generally avoided during immunosuppression. Update routine inactivated vaccines before starting therapy when possible. (journals.lww.com)

Practical tips

• Take it once weekly on the same day. Never daily.

• Injections are commonly used. A nurse or pharmacist can teach safe self‑injection.

• If nausea is a problem, ask about nighttime dosing, splitting the weekly dose, an anti‑nausea medicine, or switching route.

• Keep folic acid on a different day from methotrexate.

FAQs

Does methotrexate work for ulcerative colitis

Trials have not shown clear benefit for induction or maintenance in ulcerative colitis, so other therapies are preferred. (cochrane.org)

Can someone plan pregnancy while taking methotrexate

No. Methotrexate is teratogenic. It should be stopped in advance of conception planning. Many experts advise at least 3 months for both females and males. Discuss timing and folate needs with the care team. Avoid during breastfeeding. (academic.oup.com)

Why is monitoring so important

Regular blood tests catch early liver, kidney, or bone marrow problems, so dosing can be adjusted safely. The usual schedule is at 2, 4, 8, and 12 weeks, then every 8–12 weeks once stable. (sps.nhs.uk)

Can methotrexate be used with biologics

Sometimes. It may lower antibody formation to anti‑TNF medicines, though benefits vary by drug and study. The decision balances potential gains with added monitoring. (pubmed.ncbi.nlm.nih.gov)