Can methotrexate (MTX) improve arm pain in polymyalgia rheumatica (PMR) that does not respond to prednisolone?

Methotrexate for Arm Pain in Polymyalgia Rheumatica Unresponsive to Prednisolone

Yes, methotrexate can effectively improve arm pain in polymyalgia rheumatica (PMR) patients who do not respond adequately to prednisolone, as recommended by EULAR/ACR guidelines specifically for patients with insufficient response to glucocorticoids. 1, 2

When to Consider Methotrexate in PMR

Methotrexate (MTX) should be considered in the following clinical scenarios:

1. Insufficient response to prednisolone (lack of improvement within 2 weeks of adequate dosing)
2. Relapse during prednisolone tapering
3. Patients experiencing glucocorticoid-related adverse events
4. High-risk patients:
   • Female sex (higher risk of relapse and steroid-related adverse events)
   • Peripheral inflammatory arthritis
   • Comorbidities that may be exacerbated by glucocorticoid therapy

Evidence for Methotrexate Efficacy in Prednisolone-Resistant PMR

The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) guidelines conditionally recommend MTX for patients with PMR who have an insufficient response to glucocorticoids 1. Clinical studies have demonstrated that:

• MTX allows for reduced cumulative prednisolone doses while maintaining disease control 3
• Clinical improvement with MTX typically begins after 2 weeks, with almost complete response expected after 4 weeks 1
• In a randomized controlled trial, significantly more patients in the MTX group (28/32,88%) were able to discontinue prednisolone compared to the placebo group (16/30,53%) 3
• MTX-treated patients experienced fewer disease flare-ups (15/32 vs 22/30 in placebo) 3

Dosing and Administration

• Recommended dose: 7.5-10 mg/week orally 1, 2
• Higher doses (up to 25 mg/week) may be more effective, similar to dosing in other inflammatory rheumatic conditions 4
• Consider folate supplementation to reduce side effects

Management Algorithm for Prednisolone-Resistant PMR

1. Confirm diagnosis and adequate prednisolone dosing

   • Ensure prednisolone dose is 12.5-25 mg/day
   • Verify symptoms have persisted >2 weeks despite adequate dosing

2. Add methotrexate

   • Start at 7.5-10 mg weekly
   • Consider higher doses (up to 25 mg weekly) for more severe cases

3. Monitor response

   • Assess for clinical improvement at 2 and 4 weeks
   • Monitor ESR and CRP to track inflammatory response

4. Adjust prednisolone

   • Once response is achieved, gradually taper prednisolone
   • Target reduction to 10 mg/day within 4-8 weeks
   • Then taper by 1 mg every 4 weeks until discontinuation

5. Long-term follow-up

   • Follow up every 4-8 weeks in first year
   • Continue MTX even after prednisolone discontinuation
   • Consider MTX discontinuation only after sustained remission

Important Caveats

• Verify diagnosis: Persistent arm pain despite prednisolone may indicate an alternative diagnosis
• Avoid TNFα blocking agents: Strongly recommended against by EULAR/ACR 1, 2
• Consider exercise program: An individualized exercise program is recommended to maintain muscle mass and function 1
• Monitor for MTX side effects: Regular liver function tests and complete blood counts are essential

MTX has shown steroid-sparing effects and can reduce the risk of glucocorticoid-related adverse events, which is particularly important in elderly PMR patients who are at increased risk for complications like osteoporosis 5.