Results from a Phase 3 clinical trial reported in The New England Journal of Medicine,[1] have highlighted the significant unmet need for effective long-term treatments for those battling polymyalgia rheumatica.
Polymyalgia rheumatica is an inflammatory disease that primarily affects older adults, and causes stiffness and muscle pain, particularly in the hips and shoulders. For years, glucocorticoids have been the primary treatment for polymyalgia rheumatica, providing rapid relief from symptoms. However, although they can be life-changing, more than half of patients are unable to successfully taper off glucocorticoids and experience relapse or disease flare.
Previous studies have suggested that targeting interleukin-6 may be a promising approach. The SAPHYR study was designed to investigate whether sarilumab, an innovative human monoclonal antibody designed to block interleukin-6, could induce and maintain remission for one year.
During the trial, patients were divided into two groups: one receiving sarilumab injections every two weeks along with a rapid 14-week prednisone taper, and the other receiving a placebo with a 52-week prednisone taper.
The results for the sarilumab group were somewhat underwhelming, with 28% of the sarilumab arm achieving sustained remission. However, the results for the prednisone group were even worse - with only 10% in the prednisone group achieving sustained remission.
Fewer patients in the sarilumab arm required emergency glucocorticoid treatment compared to the placebo group, and even after achieving clinical remission, fewer experienced a disease relapse.
Study data analyzed using the Steritas GTI showed sarilumab was effective in reducing steroid-toxicity, with significant improvements to both the Cumulative Worsening and Aggregate Improvement Scores. The study also suggests that patients in the sarilumab group had better quality-of-life scores than those in the placebo group.
Notably, half of the patients in the prednisone group suffered a loss in bone mineral density of more than 3% - highlighting that even the relatively low doses of glucocorticoids used to treat polymyalgia rheumatica cause a significant risk of fracture.
The researchers caution that while the safety data collected is consistent with the known safety profile of sarilumab, the premature termination of the trial due to the COVID-19 pandemic reduced the sample size and statistical power of the trial. Nevertheless, the results are striking and highlight the urgent need for new therapies to treat polymyalgia rheumatica.
Reference
- Spiera R.F et al. Sarilumab for Relapse of Polymyalgia Rheumatica during Glucocorticoid Taper, N Engl J Med 2023; 389:1263-1272, DOI: 10.1056/NEJMoa2303452