FDA Approves Sarilumab for Adults with Glucocorticoid-Resistant Polymyalgia Rheumatica

On Feb. 28, 2023, the U.S. Food & Drug Administration (FDA) approved sarilumab (Kevzara) for the treatment of adults with polymyalgia rheumatica (PMR) for whom glucocorticoids have proved inadequate or who cannot tolerate a glucocorticoid taper.^1,2 Sarilumab is an interleukin (IL) 6 receptor antagonist. In May 2017, the FDA initially approved the agent for the treatment of adults with moderate to severe, active rheumatoid arthritis (RA) who cannot tolerate one or more disease-modifying anti-rheumatic drugs (DMARDs) or for whom one or more DMARDs have proved inadequate.³

In patients with PMR, the recommended sarilumab dose is 200 mg given as a subcutaneous injection once every two weeks in combination with a tapering course of glucocorticoids. Sarilumab can also be used alone after the discontinuation of glucocorticoids. The treatment should not be prescribed for patients with an absolute neutrophil count (ANC) of less than 2,000/mm3, a platelet count of less than 150,000/mm3 or liver transaminases of more than 1.5 times the upper limit of normal.

Background

The FDA approval was based on results from the 52-week SAPHYR trial. The phase 3 clinical trial enrolled patients with active, glucocorticoid-resistant PMR who experienced disease flares while taking at least 7.5 mg prednisone daily, or the equivalent, during a glucocorticoid taper. They were randomized to receive 200 mg of sarilumab every two weeks with a 14-week glucocorticoid taper (n=59) or placebo (n=58).⁴

The primary study end point was the proportion of patients who achieved sustained remission at week 52. This outcome was defined as being in disease remission by week 12 and the absence of disease flare, C-reactive protein normalization from weeks 12–52, as well as adherence to the study glucocorticoid taper from weeks 12–52.

The Results

The patients had similar demographics, and were mostly white women, with a median age of 70 years. At week 52, 28% of patients who received sarilumab and only 10% of patients who received placebo attained the study’s primary end point (P=0.0193). In patients who received sarilumab, the proportion of those without the signs and symptoms of PMR increased at week 2 and continued to increase over time through the end of the study period. Additionally, patients who received sarilumab were less likely to experience disease flare after achieving clinical remission than those who received placebo (16.7% vs. 29.3%; hazard ratio [HR] 0.56; 95% confidence interval [CI] 0.35–0.90; P=0.0158). (Note: The study was cut short due to the COVID-19 pandemic.)