Polymyalgia Rheumatica (PMR) is an inflammatory disorder primarily affecting older adults, causing pain and stiffness, particularly in the shoulders and hips. Symptoms often appear suddenly, are typically worse in the morning, and can make simple daily activities difficult. Since PMR is a long-term condition requiring extended medication, there has been a continuous search for modern therapies that are less toxic and more effective than traditional options. This search recently yielded a significant new biologic approval, shifting the treatment landscape.
The Foundation of PMR Treatment
The standard approach for managing PMR has long centered on the use of systemic corticosteroids, such as prednisone. These medications are highly effective because they rapidly reduce the systemic inflammation driving the symptoms. Patients often experience complete resolution of their pain and stiffness within days of starting treatment.
However, PMR requires a long course of treatment, often lasting two to three years or more, which presents substantial challenges. Sustained, low-dose corticosteroid use exposes patients to serious long-term side effects. These complications include an increased risk of bone loss (osteoporosis), weight gain, diabetes, and higher susceptibility to infections.
The high rate of relapse often occurs when patients attempt to taper their corticosteroid dose. This dependency on the medication establishes a cycle of treatment and relapse, highlighting the limitations of corticosteroids as a sole long-term solution. Therefore, the primary goal of modern PMR research is to find effective agents that can minimize or eliminate the reliance on long-term steroid regimens.
The Newest Approved Biologic Therapy
The most recent significant development in PMR treatment is the approval of sarilumab (brand name Kevzara). In 2023, the U.S. Food and Drug Administration (FDA) approved this biologic for the treatment of adults with PMR. This is a milestone because sarilumab is the first biologic agent specifically approved by the FDA for the PMR indication.
Sarilumab functions as an interleukin-6 (IL-6) receptor blocker. IL-6 is a pro-inflammatory cytokine that plays a major role in driving the widespread inflammation seen in PMR. By binding to and blocking the IL-6 receptor, sarilumab inhibits the signaling pathway that fuels the disease, thereby reducing inflammation and symptoms.
The FDA approval was based on the results of the Phase 3 SAPHYR clinical trial. This trial focused on patients whose condition had not responded adequately to corticosteroids or who struggled to taper their steroid dose. The trial demonstrated that a significantly higher percentage of patients receiving sarilumab achieved sustained remission compared to those on placebo. Sustained remission required achieving remission by week 12, maintaining C-reactive protein (CRP) normalization, and adhering to a rapid corticosteroid taper protocol.
Patients in the sarilumab group completed a rapid 14-week corticosteroid taper, compared to the standard 52-week taper for the placebo group. The median cumulative corticosteroid dose was substantially lower for the sarilumab group, demonstrating its ability to spare patients from high, long-term steroid exposure. Sarilumab is administered via injection, typically every two weeks. Like all biologics, it carries risks, including potential for serious infections and changes in blood counts, such as neutropenia.
Current Research and Steroid-Sparing Strategies
Beyond the newest biologic therapy, other strategies are used or under investigation to reduce the burden of long-term corticosteroid use. One long-established method involves methotrexate, a traditional Disease-Modifying Antirheumatic Drug (DMARD). Methotrexate is often co-prescribed with corticosteroids to help facilitate the tapering process and prevent relapse.
While some studies indicate that methotrexate can reduce the total cumulative steroid dosage and lower the rate of flare-ups, its overall effectiveness as a steroid-sparing agent in PMR remains a topic of debate. Nevertheless, it continues to be a common therapeutic option for patients who require assistance in weaning off corticosteroids or who experience frequent relapses.
Research is also exploring other targeted medications, including Janus Kinase (JAK) inhibitors, which target intracellular signaling pathways involved in inflammation. Early studies using JAK inhibitors like tofacitinib have shown promise in achieving effects comparable to corticosteroids for newly diagnosed PMR patients. However, these agents do not yet have specific FDA approval for PMR, and further validation is required.
Another promising direction is the development of personalized medicine through the identification of specific biomarkers. Researchers are working to find measurable biological factors, such as specific inflammatory protein levels or unique inflammatory scores, that can predict which patients will respond best to particular treatments. This approach aims to optimize the therapeutic pathway for each individual patient, moving closer to sustained, drug-free remission.