Overview
This review provides an in-depth evaluation of traditional and emerging strategies for managing polymyalgia rheumatica (PMR), focusing on glucocorticoid therapy, glucocorticoid-sparing agents (such as methotrexate and leflunomide), and the growing role of biologics, especially IL-6 inhibitors.
Epidemiology and Pathogenesis of PMR
- PMR affects mainly those over 50, with higher prevalence in women and individuals of Northern European descent.
- Clinical features include symmetrical muscle pain and stiffness, especially in the shoulders and hips.
- Diagnosis is based on age, bilateral shoulder pain, raised CRP/ESR, and exclusion of similar conditions.
- Genetic predisposition and environmental triggers, such as infections, contribute to disease onset.
- Subclinical large-vessel vasculitis may occur, necessitating vigilance for giant cell arteritis (GCA).
Relapse and Disease Monitoring
- Relapses affect 20-60% of patients, typically during glucocorticoid tapering.
- Persistent elevation of inflammatory markers, especially CRP and IL-6, predicts relapse risk.
- The speed of glucocorticoid tapering is a key factor in relapse likelihood.
- PMR activity score (PMR-AS) is a promising tool to distinguish relapses and guide therapy.
Glucocorticoid Therapy
- Prednisone/prednisolone at 12.5–25 mg/day is standard, with lower doses for at-risk patients.
- Glucocorticoids achieve rapid symptom relief, but prolonged use leads to significant side effects.
- Modified-release prednisone may offer improved response compared to immediate-release formulations.
- Injections and NSAIDs offer limited additional benefit.
Glucocorticoid-Sparing Agents
- Methotrexate is recommended for patients with high relapse risk or comorbidities, showing reduced glucocorticoid burden in some studies.
- Leflunomide may be more effective than methotrexate in glucocorticoid tapering, but further validation is needed.
- Alternatives like azathioprine and hydroxychloroquine lack robust supporting evidence.
Biologic Therapies
- Anti-TNF agents (e.g., infliximab, etanercept) have not shown benefit in isolated PMR.
- IL-6 receptor blockers (tocilizumab, sarilumab) reduce relapses, lower glucocorticoid use, and promote remission.
- Sarilumab is FDA-approved for PMR and effective during glucocorticoid tapering.
- Other biologics (secukinumab, canakinumab, rituximab, abatacept) are under investigation, with early results prompting further research.
Janus Kinase Inhibitors
- Tofacitinib and baricitinib have shown promise in early studies, but require more evidence before routine use.
Future Directions
- Treatment should be individualized with shared decision-making, especially considering comorbidities.
- Biosimilar biologics may improve access due to lower cost.
- Research focuses on optimizing glucocorticoid benefit/risk ratio, including new agents like SEGRMs and targeted delivery systems.
- Weight management and comorbidity assessment are important in patient care.
- Immuno-checkpoint inhibitors and innovative drug delivery methods represent emerging research areas.
Recommendations / Advice
- Use glucocorticoids as first-line treatment, minimizing duration and dose to reduce adverse effects.
- Consider early methotrexate or leflunomide in high-risk or relapsing patients.
- Employ IL-6 inhibitors in refractory or frequently relapsing cases, especially where rapid glucocorticoid discontinuation is needed.
- Monitor for GCA in PMR patients, especially with atypical symptoms or poor response to therapy.
- Make treatment decisions through patient-physician collaboration, accounting for comorbidities and patient preferences.
Questions / Follow-Ups
- Ongoing trials will clarify the role of leflunomide, rituximab, baricitinib, and other novel agents in PMR treatment.
- Long-term safety and cost-effectiveness of biologic therapies remain areas for further study.