Methotrexate Use in Polymyalgia Rheumatica
Methotrexate is conditionally recommended for PMR at a dose of 7.5-10 mg/week, particularly in patients at high risk for relapse, prolonged glucocorticoid therapy, or those with comorbidities where glucocorticoid-related adverse events are more likely. 1
When to Consider Methotrexate
Consider early introduction of methotrexate in addition to glucocorticoids for:
- High-risk patients for relapse/prolonged therapy: Female patients with high initial peripheral inflammatory arthritis 1
- Patients with glucocorticoid-related risk factors: Those with diabetes, osteoporosis, glaucoma, hypertension, cardiovascular disease, or chronic infections 1
- During follow-up: Patients experiencing relapse, inadequate response to glucocorticoids alone, or developing glucocorticoid-related adverse events 1
Dosing Regimen
The standard methotrexate dose for PMR is 7.5-10 mg/week orally. 1
- Clinical trials have consistently used this dose range with moderate to high quality evidence 1
- Clinical improvement should be noted after 2 weeks, with almost complete response expected after 4 weeks 1
- No specific recommendations exist for dose adjustments of methotrexate in PMR 1
- Folic acid supplementation of at least 5 mg/week is strongly recommended when prescribing methotrexate 1
Evidence for Efficacy
Methotrexate demonstrates glucocorticoid-sparing benefits with moderate to high quality evidence:
- Increased glucocorticoid-free remission at week 44 (RR=5.22) 1
- Reduced relapse rate at week 76 (RR=0.64) 1
- Higher rates of glucocorticoid discontinuation at weeks 48 (RR=1.74) and 76 (RR=1.64) 1
- Lower cumulative glucocorticoid doses at 12 months 1
- In one randomized trial, 88% of patients in the methotrexate group versus 53% in placebo group discontinued prednisone by week 76 2
Important Caveats
Methotrexate does not reduce most glucocorticoid-related adverse events - the quality of evidence for this outcome is very low, and studies were not adequately powered to detect differences in adverse events 1
The decision to use methotrexate should be individualized based on:
- Risk of relapse (female sex, peripheral inflammatory arthritis) 1
- Presence of comorbidities that increase glucocorticoid toxicity risk 1
- Patient response to initial glucocorticoid therapy 1
Discontinuation
Once glucocorticoids have been successfully withdrawn in patients on combination therapy, discontinuation of methotrexate may be considered. 1
Monitoring
Standard methotrexate monitoring applies: ALT/AST, creatinine, and complete blood count should be performed every 1-1.5 months until stable dose is reached, then every 1-3 months thereafter 1