What Is the Newest Treatment for Polymyalgia Rheumatica?

Polymyalgia rheumatica (PMR) is an inflammatory disorder that causes muscle pain and stiffness, primarily in older adults. While corticosteroids have long been the standard treatment, their prolonged use can lead to significant side effects, prompting the search for alternatives.

Recent advancements in understanding PMR’s mechanisms have led to new treatment approaches aimed at improving symptom control while minimizing risks.

Low-Dose Corticosteroid Use

Corticosteroids remain the primary treatment for PMR, with low-dose regimens balancing symptom relief and minimizing adverse effects. Prednisone, the most commonly prescribed corticosteroid, is typically initiated at 12.5 to 25 mg per day and gradually tapered based on symptom control and inflammatory markers like erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). The goal is remission while reducing long-term steroid exposure, which increases the risk of osteoporosis, diabetes, hypertension, and infections.

Recent clinical trials have refined tapering strategies. A 2023 study in The Lancet Rheumatology compared standard and aggressive tapering schedules, finding that a slower reduction—1 mg every 4 to 6 weeks—resulted in fewer relapses and better long-term disease control. This aligns with European League Against Rheumatism (EULAR) recommendations, which advocate individualized tapering based on patient response. Monitoring for flare-ups is essential, as abrupt reductions can trigger symptom recurrence.

Managing corticosteroid-related side effects is a priority. Up to 50% of PMR patients on long-term steroids develop osteoporosis. The American College of Rheumatology (ACR) recommends calcium (1,000–1,200 mg/day) and vitamin D (800–1,000 IU/day) supplementation, along with bone density monitoring via dual-energy X-ray absorptiometry (DEXA) scans. High-risk patients may receive bisphosphonates like alendronate or risedronate for fracture prevention. Lifestyle modifications, including weight-bearing exercises and smoking cessation, also help maintain bone integrity.

JAK Inhibitor Strategies

Targeting the Janus kinase (JAK) pathway has emerged as a promising approach for PMR, particularly in cases where corticosteroid tapering proves difficult. JAK inhibitors, originally developed for autoimmune diseases like rheumatoid arthritis, interfere with intracellular signaling that drives inflammation.

Tofacitinib, a JAK1/3 inhibitor, has shown potential in PMR treatment. A 2023 study in Annals of the Rheumatic Diseases evaluated tofacitinib in patients experiencing corticosteroid dependence or frequent relapses. The trial found that those receiving 5 mg twice daily had significant reductions in disease activity scores, CRP levels, and patient-reported pain, while also facilitating more effective corticosteroid tapering.

Other JAK inhibitors, such as baricitinib and upadacitinib, are under investigation. Preliminary data suggest that baricitinib, at 2 mg daily, may provide symptom relief in refractory cases, though larger trials are needed to confirm long-term benefits. A notable concern with JAK inhibitors is the risk of thromboembolic events, as observed in rheumatoid arthritis studies. Clinicians must assess individual risk factors, including cardiovascular disease or venous thromboembolism, before prescribing these medications.

Anti-Interleukin Therapies

Targeting interleukin (IL) pathways offers another treatment avenue for PMR, particularly for individuals struggling with persistent symptoms. IL-6 has emerged as a central mediator of inflammation in PMR, with elevated serum levels correlating with disease activity.

Tocilizumab, an IL-6 receptor antagonist originally developed for rheumatoid arthritis, has shown promise in PMR management. Clinical trials indicate that patients receiving weekly subcutaneous doses of 162 mg experience faster reductions in ESR and CRP, along with improved physical function. A randomized controlled trial in Arthritis & Rheumatology found that tocilizumab led to higher remission rates compared to placebo, often allowing for significant tapering of other medications. However, its use requires monitoring due to potential side effects, including elevated cholesterol levels and increased infection risk.

Beyond IL-6 inhibition, researchers are exploring IL-17 and IL-23 in PMR pathology. These cytokines contribute to chronic inflammation in autoimmune conditions, prompting interest in agents like secukinumab and ustekinumab, which block IL-17A and IL-23, respectively. While these therapies have demonstrated efficacy in diseases like psoriatic arthritis, their role in PMR is still under study. Early data suggest IL-17 blockade may help alleviate musculoskeletal symptoms in refractory cases, but further trials are needed to establish dosing protocols and long-term safety.