From the Guidelines
Methotrexate is recommended as a concomitant immunomodulator with infliximab in pediatric Crohn's disease to reduce the formation of anti-infliximab antibodies, as it has been shown to reduce immunogenicity and improve long-term treatment outcomes 1. The typical dosing is 15 mg/m² (maximum 25 mg) given subcutaneously once weekly. This combination therapy should be initiated at the start of infliximab treatment and continued for at least 6-12 months, with many specialists recommending longer-term use if well-tolerated. Some key points to consider when using methotrexate in pediatric Crohn's disease include:
- Supplementation with folic acid (1 mg daily) is important to reduce side effects 1
- Regular monitoring should include complete blood counts, liver function tests, and renal function every 1-3 months
- Methotrexate works by suppressing the immune response that leads to antibody formation against infliximab, thereby improving drug retention and therapeutic efficacy
- Patients should be counseled about potential side effects including nausea, hepatotoxicity, bone marrow suppression, and the absolute contraindication in pregnancy The use of methotrexate in combination with infliximab has been supported by recent guidelines, including the British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults, which suggest that combination therapy of infliximab with methotrexate may be used in Crohn’s disease to reduce immunogenicity 1. Additionally, a pediatric registry study of 502 Crohn’s disease patients found that concomitant methotrexate, taken for more than 6 months, increased the likelihood of remaining on infliximab, both compared with non-use of immunomodulators and compared with thiopurine use 1. However, it is essential to weigh the benefits and risks of combination therapy, as the evidence is not yet conclusive, and some studies have raised concerns about the potential for increased toxicity 1. In clinical practice, the decision to use methotrexate in combination with infliximab should be made on a case-by-case basis, taking into account the individual patient's needs and risk factors.
From the Research
Role of Methotrexate in Managing Infliximab Antibodies
- Methotrexate (MTX) is used as an immunomodulator therapy in pediatric Crohn's disease, often in combination with other treatments such as Infliximab (IFX) 2
- The use of MTX in managing IFX antibodies is not directly addressed in the provided studies, but it is mentioned as a part of the treatment regimen for some patients 2
- IFX is effective in inducing remission in severe forms of pediatric Crohn's disease, and its efficacy and safety as maintenance therapy have been demonstrated in several studies 2, 3, 4, 5, 6
Efficacy and Safety of Infliximab
- IFX has been shown to be effective in inducing and maintaining remission in pediatric Crohn's disease, with response rates ranging from 50% to 85.7% 2, 3, 5, 6
- The safety profile of IFX in pediatric patients is generally favorable, with common adverse events including infusion reactions and infections 3, 5, 6
- The duration of effect of IFX maintenance treatment is limited, with 50% of patients losing their therapeutic response after 5 years 4
Treatment Strategies
- Scheduled maintenance therapy with IFX every 2 months has been shown to be more effective than "on demand" treatment in maintaining remission in pediatric Crohn's disease 2
- Dose adjustments, including increasing the dose to 10 mg/kg, may be necessary to regain therapeutic benefit in patients who lose response to IFX 3, 4