The IL-6 blocker sarilumab could broaden strategic options for managing polymyalgia rheumatica (PMR) through sustained remission and a lower reliance on glucocorticoids, researchers report.
In a phase 3 randomised trial, funded by Sanofi and Regeneron, sarilumab outperformed standard glucocorticoid tapering on remission while reducing cumulative glucocorticoid dose in patients whose PMR had relapsed during initial prednisone treatment.
The research team randomly assigned 118 patients who had relapsed during prednisone tapering to receive either 52 weeks of twice-monthly sarilumab injections (200mg) alongside a 14-week prednisone taper, or a placebo plus a 52-week prednisone taper.
The results, published in the New England Journal of Medicine, showed that after 52 weeks sustained remission was achieved in 28% of the sarilumab group and in 10% of the placebo group, marking a significant difference (p=0.02) of 18 percentage points (95% confidence interval, 4 to 32) between the two groups.
Among patients who had received concomitant methotrexate during the trial; 25% of the sarilumab group achieved sustained remission at 52 weeks versus 12% in the placebo arm.
Also of note, the proportion of patients with no signs or symptoms of PMR at 52 weeks who had not received rescue therapy during the study period was 45% (27 of 60) in the sarilumab group and 14% (8 of 58) in the placebo arm, “despite a more rapid prednisone taper in the sarilumab group,” the authors noted.
The median cumulative glucocorticoid dose was also significantly reduced in the sarilumab arm compared to placebo, with doses of 777 mg vs 2044 mg, respectively (p<0.001) after 52 weeks.
The sarilumab group also fared better than the placebo arm on other secondary outcomes, including bone health (loss of more than 3% in 22% and 49%, respectively) and reduction in CRP (-6.9mg versus 1.7mg).
On the downside, sarilumab was linked with a greater number of treatment-related discontinuations (12% versus 7%, respectively), and more frequent reports of neutropenia (15% vs 0%), arthralgia (15% vs 5%), and diarrhoea (12% vs 2%).
Also, a key limitation of the trial was its early termination with the advent of the COVID-19 pandemic, which led to a smaller than planned sample size and thus reduced statistical power, the researchers noted.
Nevertheless, the findings “indicate indicate a glucocorticoid-sparing and remission-maintenance effect of sarilumab,” the investigators concluded.
A broadening approach
In a linked editorial (link here), Dr Daniel Aletaha, Chair of Rheumatology and Head of the Division of Rheumatology at the Medical University of Vienna noted that study’s results, taken together with those of previous trials in both similar and different patient populations, “represent a broadening of the strategic approach toward the management of polymyalgia rheumatica according to the treat-to-target principle, even beyond the definition of remission.
“These additional treatment options allow for more flexibility in the tailoring of the right management strategy to achieve remission and minimise the risks of glucocorticoids”, he said.
However, he also emphasised that clinicians would need to balance the risk of the adverse events seen with sarilumab in the trial “against the expected benefits of control of inflammation, the potential sparing of risks associated with prolonged glucocorticoid therapy, medication affordability, and patient preferences regarding regimen complexity and route of administration”.