Overview
This review details current and emerging strategies for managing polymyalgia rheumatica (PMR), focusing on traditional glucocorticoid therapy and the expanding role of glucocorticoid-sparing agents, especially biologics targeting IL-6. Key studies, ongoing trials, and future therapeutic directions are discussed to optimize remission and reduce treatment-related risks.
Epidemiology, Pathophysiology, and Diagnosis
- PMR mainly affects individuals aged 50+, more common in women and those of Northern European descent.
- Key symptoms include bilateral muscle pain and stiffness, particularly in shoulders, hips, and neck.
- Diagnosis is clinical, using 2012 ACR/EULAR criteria, supported by elevated ESR/CRP, and imaging for bursitis or synovitis.
- Subclinical giant cell arteritis (GCA) may coexist and requires vigilant monitoring.
Relapses and Risk Factors
- Relapses affect 20–60% of patients, mostly in the first year, often during glucocorticoid tapering.
- Elevated CRP and persistent IL-6 are strong relapse predictors.
- Risk is increased by rapid steroid taper, certain HLA alleles, and sustained inflammation.
- Definitions of relapse/remission are inconsistent; tools like PMR-AS require further validation.
Standard Treatment Approaches
- Prednisone/prednisolone (12.5–25 mg/day) remains first-line, with slow individualized taper to prevent relapse.
- Modified-release prednisone shows slight advantage over immediate-release formulations.
- Glucocorticoid injections and NSAIDs offer limited benefit and are not generally recommended.
Glucocorticoid-Sparing Agents: Conventional DMARDs
- Methotrexate (MTX) is the recommended DMARD, shown to reduce cumulative steroid exposure in some studies, but results are inconsistent.
- Leflunomide may be more effective than MTX for steroid tapering, but evidence is limited and longer follow-up is needed.
- Alternatives like azathioprine and hydroxychloroquine have either limited efficacy or safety concerns.
Biologic Therapies and New Agents
- Anti-TNF agents (e.g., infliximab, etanercept) failed to provide additional benefit in clinical trials.
- Anti-IL-6 therapies (tocilizumab, sarilumab) demonstrate significant efficacy in reducing relapses, steroid burden, and achieving remission.
- Sarilumab is FDA-approved for PMR, with a favorable safety profile despite some increased risks (e.g., neutropenia).
- Research on other agents (secukinumab, canakinumab, rituximab, abatacept, JAK inhibitors) is ongoing, with mixed early results.
Discussion and Future Perspectives
- Optimal management requires balancing remission induction with minimizing glucocorticoid-related side effects.
- Individualized treatment and shared decision-making between physicians and patients are emphasized.
- Biosimilars may improve biologic access and reduce costs.
- Emerging therapies include selective glucocorticoid receptor modulators (SEGRMs), liposome-based steroids, and immune checkpoint strategies, though clinical evidence is preliminary.
- Weight management is advised, particularly for obese patients due to worse outcomes.
Recommendations / Advice
- Early consideration of MTX for patients at high risk of relapse or prolonged steroid use.
- Consider anti-IL-6 therapy for refractory or relapsing PMR, especially when glucocorticoids are contraindicated.
- Monitor for side effects and individualized risks with biologics due to higher costs and potential adverse events.
- Ongoing research and patient stratification are essential for evolving treatment paradigms.