Methotrexate Dose Reduction When Starting Rituximab

Introduction to Methotrexate Dose Management

The British Association of Dermatologists recommends that adjuvant systemic immunosuppressive drugs can be continued with concomitant use of rituximab, but dose reduction should be considered to decrease the risk of infections and other adverse effects related to immunosuppression 1, 2

For vasculitis (GPA/MPA), rituximab is conditionally recommended over methotrexate or azathioprine for remission maintenance, suggesting these agents serve different roles rather than being used simultaneously 3
For pemphigus, rituximab has been used with concomitant corticosteroids and immunosuppressants (including methotrexate) in 79-97% of cases 1, 2

Patients with risk factors for infection, such as advanced age 4, diabetes or other comorbidities 5, history of recurrent infections 6, or impaired renal function, may require methotrexate dose reduction 6
The American Academy of Dermatology suggests considering methotrexate dose reduction to 10-15 mg/week when adding rituximab, especially in patients on high-dose methotrexate (≥15-20 mg/week) 5

Enhanced surveillance is essential when combining rituximab and methotrexate, including complete blood count every 2-4 weeks initially after starting rituximab, liver function tests, and renal function monitoring 7
The British Association of Dermatologists recommends watching for signs of methotrexate toxicity, such as mucositis, fever, diarrhea, skin reactions, and ensuring adequate folic acid supplementation (1-5 mg daily except on methotrexate day) 7, 8

Both rituximab and methotrexate impair vaccine responses, with rituximab having a greater effect, and vaccinations should ideally be completed before starting rituximab 9, 4, 10
The combination of rituximab and methotrexate increases infection risk beyond either agent alone, and methotrexate should be temporarily discontinued if serious infection develops requiring antibiotics 8
Methotrexate toxicity risk increases dramatically with renal impairment, and dose reduction or avoidance is recommended in patients with impaired renal function 6, 7