As IL-6 plays an important role in PMR, IL-6 inhibition with sarilumab was worth exploring1. By now, research has advanced to the phase 3, randomised, double-blind SAPHYR (NCT03600818) trial. The study included PMR patients ≥50 years who had at least 1 flare within 12 weeks before the trial while being on ≥7.5 mg of prednisolone. The study aimed to enrol 280 patients but recruited halted at 118 participants due to the COVID-19 pandemic.
Participants were allocated to either placebo plus 52-week glucocorticoid [GC] taper or sarilumab 200 mg every 2 weeks plus 14-week taper of GC. The primary endpoint was defined as the rate of patients achieving sustained remission at week 52. This included disease remission at week 12 plus the absence of flares, CRP normalisation, and adherence to GC taper from weeks 12–52.
The mean age of the participants was about 70 years, and they were mostly women. The median duration of PMR was 292 days in the sarilumab arm and 310 days in the placebo group. “The median number of flares per patient was 2 and that was similar between the 2 groups, and many of these patients had received prior immunosuppression,” Prof. Bhaskar Dasgupta (Anglia Ruskin University, UK) further specified.
At week 52, a statistically significant difference was seen between sarilumab and placebo with 28.3% versus 10.3% (P=0.0193) attaining sustained remission. Prof. Dasgupta further highlighted that all the components of sustained remission showed a better result for the sarilumab arm compared with the control arm. The study drug also clearly delayed the time to the first flare and the risk of having a flare on sarilumab versus placebo was determined with a hazard ratio of 0.56 (95% CI 0.35–0.90).
In light of the study protocol, the researcher expected a higher use of GC in the placebo arm. “But when we looked at the discrepancy between the actual and the expected use, there was a 200 mg difference between the actual and the expected in the placebo arm and this is related to a higher incidence of flares in the placebo arm,” Prof. Dasgupta stated. The safety profile of sarilumab observed in SAPHYR was consistent with earlier findings.
Reference:
1. Dasgupta B, et al. Sarilumab in patients with relapsing polymyalgia rheumatica: a phase 3, multicenter, randomised, double-blind, placebo controlled trial (SAPHYR). LB0006, 1–4 June, Copenhagen, Denmark.