Polymyalgia rheumatica is one of the more common inflammatory diseases of older adults, and for decades its treatment rested on a single, problematic pillar: glucocorticoids. They work, but relapses are frequent and the cumulative steroid burden carries its own toll. The field has begun to move past that. The interleukin-6 receptor inhibitor sarilumab (Kevzara) was the first biologic shown in a phase 3 trial, SAPHYR, to help in relapsed disease. REPLENISH, a Novartis-sponsored phase 3 trial published in The New England Journal of Medicine, is the first to show that selectively blocking interleukin-17A also works in patients who have already relapsed. Secukinumab (Cosentyx) is not approved for polymyalgia rheumatica; this is the first phase 3 trial of the drug in the disease, and the results are an efficacy signal, not a green light for clinical use.
The trial randomized 381 patients with recently relapsed disease in a 1:1:1 ratio to secukinumab 300 mg, secukinumab 150 mg, or placebo for 52 weeks, with 127 patients in each group. Every patient also received prednisone on a 24-week tapering schedule, so the comparator was an active steroid taper, not nothing.
The remission gap
The primary endpoint was sustained remission at week 52: remission achieved by week 12 and maintained through week 52 without escape or rescue treatment and with no new diagnosis of giant-cell arteritis. Sustained remission was reached by 41.2% of patients on 300 mg (95% CI, 32.8 to 49.7) and 40.6% on 150 mg (95% CI, 32.2 to 49.0), versus 20.4% on placebo (95% CI, 13.6 to 27.2). Each dose beat placebo at P<0.001. Put the other way, even on the active doses roughly 6 in 10 patients did not reach sustained remission.
Both doses roughly doubled the one-year sustained-remission rate over a steroid taper alone — and the two doses landed within a percentage point of each other.
The steroid-sparing signal followed, but as a secondary endpoint. The mean adjusted annual cumulative glucocorticoid dose was 1603.7 mg on 300 mg and 1683.2 mg on 150 mg, against 2093.0 mg on placebo — roughly a 400-to-490 mg reduction over the year, on this defined 24-week taper and in this relapsed population.
Safety looked broadly balanced. Serious adverse events occurred in 13.5% of patients on 300 mg, 15.9% on 150 mg, and 14.2% on placebo. Consistent with the IL-17 class, more secukinumab-treated than placebo-treated patients had nasopharyngitis, hypersensitivity reactions, urinary tract infections, fungal infections, and back pain.
Two caveats temper the enthusiasm. The trial enrolled patients who had already relapsed while tapering glucocorticoids, so the findings speak to harder-to-control disease rather than first-line use. And the near-identical performance of the two doses, while convenient, leaves the dose-response question open. This is a regulatory-grade efficacy signal for the first IL-17A-targeted therapy in PMR — not, on its own, a treatment recommendation.