Sarilumab for polymyalgia rheumatica led to sustained remission and fewer flares

Nearly 30% of participants receiving IL-6 inhibition in the randomised, phase 3 SAPHYR study achieved sustained remission. Furthermore, participants on sarilumab had a significant reduction of flares compared with those receiving placebo.

Elevated IL-6 levels in polymyalgia rheumatica (PMR) have been linked to relapse and increased need for corticosteroids [1–3]. This led to the exploration of IL-6 inhibition with sarilumab as a potential therapeutic agent [1]. The phase 3, randomised, double-blind SAPHYR trial (NCT03600818) included patients with PMR ≥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 recruitment halted at 118 participants due to the COVID-19 pandemic.

The participants were allocated to either placebo plus 52-week glucocorticoid taper or sarilumab 200 mg every 2 weeks plus a 14-week of glucocorticoid taper. The primary endpoint was defined as the rate of participants achieving sustained remission at week 52. This included disease remission at week 12 plus the absence of flares, CRP normalisation, and adherence to glucocorticoid taper from weeks 12–52.

The mean age of the participants was about 70 years, and they were mostly women. The median PMR duration was 292 days in the sarilumab arm and 310 days in the placebo arm. “The median number of previous 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, United Kingdom) 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, respectively. 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 the light of the study protocol, the researcher expected a higher use of glucocorticoid in the placebo arm. “But we saw a 200 mg difference between the actual and the expected use in the placebo arm, which 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.

“We were very excited to particularly concentrate on patient-reported outcomes because we know from our previous studies that patient-reported outcomes in terms of PMR quality-of-life are actually lower at onset than what we see with rheumatoid arthritis,” Prof. Dasgupta mentioned. In the current trial, sarilumab demonstrated an overall positive influence on quality-of-life for patients with PMR.

1. Dasgupta B, et al. Sarilumab in patients with relapsing polymyalgia rheumatica: a phase 3, multicenter, randomised, double-blind, placebo-controlled trial (SAPHYR). LB0006, EULAR 2022 Congress, 1–4 June, Copenhagen, Denmark.
2. Pulsatelli L, et al. Arthritis Rheum. 2008;59:1147–1154.
3. Martinez-Taboada VM, et al. 2008;44:207–220.

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Posted on 21 July, 202216 February, 2024