Summary

Methotrexate and infliximab are commonly used together in treating autoimmune conditions like rheumatoid arthritis. While this combination can be highly effective, it significantly increases immunosuppression and the risk of serious infections and malignancies.

Introduction

Methotrexate is a disease-modifying antirheumatic drug (DMARD) and antimetabolite that inhibits folate metabolism, commonly used to treat rheumatoid arthritis, psoriasis, and certain cancers. Infliximab is a tumor necrosis factor (TNF) alpha inhibitor, a biologic medication used to treat inflammatory conditions including rheumatoid arthritis, Crohn's disease, and ankylosing spondylitis. Both medications work by suppressing the immune system through different mechanisms.

Mechanism of Interaction

The interaction between methotrexate and infliximab is pharmacodynamic, involving additive immunosuppressive effects. Methotrexate inhibits dihydrofolate reductase, reducing folate-dependent cellular processes and suppressing T-cell activation. Infliximab blocks TNF-alpha, a key inflammatory cytokine involved in immune responses. When used together, these medications create profound immunosuppression by targeting different pathways of the immune system, potentially enhancing therapeutic efficacy but also increasing susceptibility to infections and malignancies.

Risks and Symptoms

The primary risks of combining methotrexate and infliximab include significantly increased susceptibility to serious bacterial, viral, fungal, and opportunistic infections, including tuberculosis reactivation. There is an elevated risk of lymphomas and other malignancies. Additional concerns include hepatotoxicity, bone marrow suppression, and potential for severe skin reactions. Patients may experience increased gastrointestinal toxicity and delayed wound healing. The combination may also increase the risk of progressive multifocal leukoencephalopathy (PML), though this is rare.

Management and Precautions

Close monitoring is essential when using methotrexate and infliximab together. Patients should undergo tuberculosis screening before initiating therapy and regular monitoring for signs of infection. Complete blood counts, liver function tests, and kidney function should be monitored regularly. Folic acid supplementation is recommended with methotrexate to reduce toxicity. Live vaccines should be avoided during treatment. Patients should be educated about infection symptoms and advised to seek immediate medical attention for fever, unusual fatigue, or signs of infection. Regular dermatologic examinations are recommended to monitor for skin malignancies.

Methotrexate interactions with food and lifestyle

Alcohol consumption should be avoided or strictly limited while taking methotrexate due to increased risk of liver toxicity and hepatotoxicity. Both methotrexate and alcohol can cause liver damage, and their combination significantly increases this risk. Patients should also maintain adequate hydration and avoid excessive sun exposure, as methotrexate can increase photosensitivity. Folic acid supplementation is commonly recommended to reduce certain side effects, though this should be discussed with a healthcare provider as timing and dosing are important.

Infliximab interactions with food and lifestyle

Live vaccines should be avoided during Infliximab treatment and for several months after discontinuation due to increased risk of serious infections. Patients should avoid exposure to individuals with active infections when possible. Alcohol consumption should be limited or avoided, especially in patients with concurrent hepatitis B or C, as Infliximab may increase the risk of liver toxicity. Close contact with individuals who have received live vaccines (such as oral polio vaccine, nasal flu vaccine, or rotavirus vaccine) should be avoided when possible.