How to Treat Refractory Polymyalgia Rheumatica

Patients with polymyalgia rheumatica (PMR) who had relapsed while tapering glucocorticoid therapy were more likely to achieve sustained remission at one year and have a lower glucocorticoid exposure if they were treated with sarilumab (Kevzara) plus a rapid, 14-week glucocorticoid taper than if they received placebo plus a standard, 52-week glucocorticoid taper. This is according to a study published in The New England Journal of Medicine that supported the U.S. Food & Drug Administration’s (FDA) approval of the interleukin (IL) 6 receptor antagonist for the treatment of adults with PMR who have had an inadequate response to glucocorticoids or who cannot tolerate a glucocorticoid taper.^1-3

“PMR is among the most common inflammatory diseases, and although corticosteroids are extremely effective in controlling disease activity, flares, which generally necessitate raising the corticosteroid dose, are common, meaning that most patients have a prolonged course of treatment,” explains Robert Spiera, MD, professor of clinical medicine at Weill Cornell Medical College and director of the Scleroderma, Vasculitis, and Myositis Center at the Hospital for Special Surgery, New York City. “This results in many corticosteroid-related complications in this vulnerable group of patients. There is a major unmet need for an effective corticosteroid-sparing strategy in this disease, particularly in refractory patients.” Previous studies have implicated IL-6 in the pathophysiology of PMR and suggested that IL-6 inhibition may be clinically useful in treating the condition.^4,5

“It is exciting to see an understanding of disease pathophysiology ultimately result in the demonstration of a targeted therapy being effective in a rheumatic disease,” says Dr. Spiera. “This is truly a bench-to-bedside journey, as it has been for many of the other biologics and targeted therapies that have led to improved outcomes for patients with inflammatory and autoimmune diseases. Our improved sophistication in clinical trial design and execution also contributed enormously to the ability to prove this strategy as effective.”

The SAPHYR Trial

Dr. Spiera

The randomized, double-blind, placebo-controlled phase 3 SAPHYR trial was designed to assess the efficacy and safety of the IL-6 antagonist sarilumab in patients with PMR who had a disease flare while tapering glucocorticoid therapy.¹

The study, which had lower enrollment than planned because of the COVID-19 pandemic, included 118 patients with active PMR who had a disease flare while taking at least 7.5 mg prednisone or the equivalent daily within three months of screening. The patients’ median age was 69 years, 70% were women, and 83% were white. From October 2018 through July 2020, 60 patients were randomized to receive 200 mg of sarilumab subcutaneously every two weeks with a 14-week glucocorticoid taper and 58 patients were assigned to placebo plus a 52-week glucocorticoid taper.