What is the best approach to manage diarrhea in a patient with rheumatoid arthritis (RA) taking methotrexate (MTX) 15 mg by mouth once weekly and folic acid (FA) 1 mg by mouth once daily?

Managing Methotrexate-Induced Diarrhea in Rheumatoid Arthritis

Changing methotrexate from oral to subcutaneous administration at the same dose (15 mg weekly) while continuing folic acid 1 mg daily is the most appropriate strategy to mitigate diarrhea in this patient with rheumatoid arthritis.

Rationale for Switching to Subcutaneous Administration

Gastrointestinal side effects, including diarrhea, are common with oral methotrexate and can significantly impact a patient's quality of life and work performance. The evidence supports several key points:

• Subcutaneous administration of methotrexate has higher bioavailability compared to oral administration and is associated with fewer gastrointestinal side effects 1
• Switching from oral to subcutaneous methotrexate is recommended when patients experience intolerable side effects at the highest tolerable oral dose 1, 2
• This approach maintains the therapeutic dose needed for disease control while reducing gastrointestinal toxicity 1

Why Other Options Are Less Appropriate

1. Reducing methotrexate to 10 mg orally weekly:

   • While dose reduction might decrease side effects, it could compromise disease control in a newly diagnosed patient
   • The primary goal in early RA is achieving adequate disease control, which requires optimal dosing 1

2. Stopping methotrexate and starting adalimumab:

   • Switching to biologics is only indicated after failure of conventional DMARDs at optimal doses 1
   • This would be premature in a newly diagnosed patient experiencing side effects that can be managed with route modification

3. Continuing current regimen and waiting:

   • Gastrointestinal side effects often persist rather than resolve with continued oral administration
   • This approach would unnecessarily prolong the patient's symptoms and potentially affect work performance

Role of Folic Acid Supplementation

Folic acid supplementation is crucial in mitigating methotrexate toxicity:

• Folic acid reduces gastrointestinal side effects without reducing methotrexate efficacy 2, 3
• A meta-analysis showed a 26% relative risk reduction in gastrointestinal side effects with folate supplementation 3
• Continuing folic acid is essential when switching to subcutaneous methotrexate 2

Implementation Strategy

1. Maintain the same weekly dose: Keep methotrexate at 15 mg weekly but change to subcutaneous administration
2. Continue folic acid: Maintain daily folic acid 1 mg to help prevent other potential side effects
3. Patient education: Provide instruction on subcutaneous self-administration
4. Monitoring: Schedule follow-up within 4-6 weeks to assess response to route change

Important Considerations

• If gastrointestinal symptoms persist despite switching to subcutaneous administration, consider increasing folic acid dosage to 5 mg daily (except on the day of methotrexate) 2
• Regular monitoring of complete blood count, liver function, and renal function should continue as per standard protocol 2
• Subcutaneous methotrexate may cause injection site reactions, but these are generally mild and transient compared to the impact of gastrointestinal side effects

By switching to subcutaneous administration while maintaining the same dose, this patient has the best chance of achieving disease control with improved tolerability, allowing her to remain effective at work.