What are the recommended steroid-sparing agents for polymyalgia rheumatica?

Steroid-Sparing Agents for Polymyalgia Rheumatica

Methotrexate is the recommended steroid-sparing agent for polymyalgia rheumatica (PMR), particularly for patients at high risk for relapse, those requiring prolonged glucocorticoid therapy, or those with risk factors for glucocorticoid-related adverse events. 1

First-Line Treatment

• Glucocorticoids remain the initial treatment for PMR
  • Recommended starting dose: 12.5-25 mg prednisone equivalent daily
  • Tapering schedule: Individualized over 1-2 years based on clinical response and risk factors
  • Single daily doses preferred over divided doses

When to Consider Steroid-Sparing Agents

Methotrexate should be considered in the following scenarios:

• Patients at high risk for relapse
• Patients requiring prolonged glucocorticoid therapy
• Patients with risk factors for glucocorticoid-related adverse events
• Patients with insufficient response to glucocorticoids
• Patients experiencing disease flares during glucocorticoid tapering

Methotrexate Dosing and Administration

• Initial dose: 7.5-10 mg/week orally 1
• Higher doses (up to 25 mg/week) may be more effective for severe cases 1
• Consider folic acid supplementation of at least 5 mg per week to reduce toxicity 2
• Methotrexate can be continued for long-term use based on its acceptable safety profile 2

Evidence Supporting Methotrexate Use

• Methotrexate has demonstrated effectiveness as a steroid-sparing agent in PMR 2
• In a randomized, double-blind, placebo-controlled trial, patients receiving methotrexate (10 mg weekly) plus prednisone were more likely to discontinue prednisone at 76 weeks compared to those receiving placebo plus prednisone (87.5% vs 53.3%) 3
• The same study showed fewer disease flares and lower cumulative prednisone doses in the methotrexate group 3
• A more recent study in routine clinical care showed that methotrexate was associated with significant reductions in inflammatory markers (ESR and CRP) and prednisolone dose after 6 months 4

Monitoring and Safety Considerations

• Before starting methotrexate:

  • Clinical assessment of risk factors for methotrexate toxicity (including alcohol intake)
  • Laboratory tests: AST, ALT, albumin, CBC, creatinine
  • Chest X-ray (obtained within the previous year)
  • Consider serology for HIV, hepatitis B/C, fasting glucose, lipid profile, and pregnancy test 2

• Monitoring during treatment:

  • ALT with or without AST, creatinine, and CBC every 1-1.5 months until a stable dose is reached
  • Then every 1-3 months thereafter
  • Clinical assessment for side effects at each visit 2

• Contraindications:

  • Pregnancy planning (should not be used for at least 3 months before planned pregnancy)
  • Pregnancy and breastfeeding 2

Important Caveats and Pitfalls

• Not all studies show benefit: Some earlier research found no benefit of methotrexate in PMR 5, highlighting the importance of appropriate patient selection
• TNF-α blocking agents are strongly discouraged for PMR treatment 1
• NSAIDs are not recommended as primary treatment for PMR 1
• Methotrexate should be stopped if there is a confirmed increase in ALT/AST greater than three times the upper limit of normal, but may be reinstituted at a lower dose following normalization 2
• Approximately 50% of patients may discontinue methotrexate, with adverse effects being a common reason 4

Alternative Approaches

• Anti-IL-6 receptor agents have shown promise in reducing relapse frequency and lowering cumulative glucocorticoid burden, although these are not currently included in EULAR/ACR guidelines 1
• For patients who cannot tolerate methotrexate, consider specialist referral for alternative management strategies 1

Methotrexate remains the most evidence-based steroid-sparing agent for PMR, with demonstrated benefits in reducing glucocorticoid requirements and improving outcomes in appropriately selected patients.