Methotrexate Dosing in Pulmonary Sarcoidosis
For patients with pulmonary sarcoidosis, methotrexate should be started at 10-15 mg once weekly, with potential escalation by 5 mg every 2-4 weeks up to 20-30 mg weekly, depending on clinical response and tolerability. 1
Initial Dosing and Administration
- Starting dose: 10-15 mg once weekly 1
- Administration route: Oral is typically first-line
- Consider parenteral administration (subcutaneous or intramuscular) if:
- Inadequate clinical response to oral therapy
- Gastrointestinal intolerance to oral formulation 1
Dose Escalation Protocol
- Increase by 5 mg every 2-4 weeks if needed 1
- Maximum target dose: 20-30 mg weekly 1
- Allow 4 weeks after dose increases to assess clinical response 1
- If minimal efficacy is achieved after 12-16 weeks at doses ≥15 mg/week, consider switching to alternative medication 1
Monitoring and Adjustments
Required Laboratory Monitoring:
- Before starting: Complete blood count (CBC), liver function tests (AST/ALT), renal function (creatinine), chest X-ray 1
- During treatment:
- First 1-1.5 months: CBC, liver function, renal function every 1-1.5 months until stable dose
- Maintenance: Every 1-3 months thereafter 1
Efficacy Assessment:
- Pulmonary function tests (especially FVC, DLCO)
- Radiological improvement on chest imaging
- Symptom improvement (dyspnea, cough, fatigue)
- Ability to reduce corticosteroid dose 2
Folic Acid Supplementation
- Strongly recommended: At least 5 mg folic acid per week 1
- Administration: Daily except on the day of methotrexate 1
- Benefits: Reduces gastrointestinal side effects, minimizes risk of hematologic toxicity 1
Safety Considerations
The safety profile of methotrexate in pulmonary sarcoidosis is generally favorable. In a large cohort study over six years, only 1.6% of patients experienced moderate liver enzyme elevations and serious hematologic toxicity was rare 3.
Common Side Effects:
- Gastrointestinal: Nausea, anorexia, stomatitis (most common)
- Hepatotoxicity: Monitor liver enzymes regularly
- Myelosuppression: Leukopenia, thrombocytopenia (uncommon)
- Pulmonary: Methotrexate pneumonitis (rare but serious) 1
Contraindications:
- Significant renal impairment (creatinine clearance <20 mL/min) 1
- Severe hepatic disease
- Active infection
- Pregnancy or planning pregnancy
Treatment Duration and Discontinuation
- Treatment duration: Typically long-term (months to years) for chronic pulmonary sarcoidosis
- Discontinuation strategy: Once disease stability is achieved, consider gradual dose reduction
- Relapse rate: Relatively low in complete responders after discontinuation 4
Clinical Evidence of Efficacy
Methotrexate has demonstrated effectiveness in approximately 80% of pulmonary sarcoidosis patients 4. Studies show significant improvements in vital capacity and reduction in bronchoalveolar lavage lymphocyte percentages, comparable to effects seen with corticosteroids 5. In a prospective study, 55% of patients showed significant improvement in pulmonary function parameters after methotrexate therapy 6.
Methotrexate also demonstrates important steroid-sparing effects, allowing for reduction or elimination of corticosteroids in many patients with chronic sarcoidosis 2.