Polymyalgia rheumatica is a common inflammatory condition characterized by pain and stiffness of the shoulders and hips. Standard initial therapy consists of glucocorticoids, but relapses are frequent and long-term glucocorticoid use is associated with substantial toxic effects. There is an unmet need for effective steroid-sparing treatments. Secukinumab is a fully human monoclonal antibody that selectively inhibits interleukin-17A (IL-17A) and was investigated as an adjunct to a scheduled glucocorticoid taper in relapsing polymyalgia rheumatica.
This Phase 3, randomized, double-blind trial enrolled patients with recently relapsed polymyalgia rheumatica. Participants were assigned in a 1:1:1 ratio to one of three groups: secukinumab 300 mg (SEC-300), secukinumab 150 mg (SEC-150), or placebo, administered for 52 weeks. All patients received prednisone according to a predefined tapering schedule for 24 weeks.
The trial's primary outcome was sustained remission at week 52, defined as clinical remission with absence of signs or symptoms attributable to polymyalgia rheumatica and no new diagnosis of giant-cell arteritis that required escape or rescue therapy; sustained remission required that remission be present from week 12 through week 52. A key secondary outcome was the annual cumulative glucocorticoid dose. Safety was assessed throughout the 52-week treatment period. The study is reported under the REPLENISH program and is registered at ClinicalTrials.gov (NCT05767034).
A total of 381 patients underwent randomization, with 127 patients assigned to each of the three groups (SEC-300, SEC-150, and placebo). The source does not provide additional baseline demographic or disease-characteristic details in the abstract.
The primary efficacy endpoint was the proportion of patients achieving sustained remission from week 12 until week 52. The main secondary efficacy measure reported was the mean adjusted annual cumulative glucocorticoid dose. Safety endpoints included the incidence of serious adverse events and prespecified adverse event categories.
At week 52, sustained remission rates were:
Both secukinumab doses met the primary endpoint, with each dose showing a statistically significant higher rate of sustained remission compared with placebo (P<0.001 for each comparison). The reported definition of sustained remission required absence of disease-attributable signs or symptoms and no new giant-cell arteritis that required escape or rescue treatment.
The mean adjusted annual cumulative glucocorticoid doses reported were:
Both secukinumab groups had lower annual cumulative glucocorticoid exposure than the placebo group when used in combination with the same 24-week prednisone taper.
Serious adverse events occurred in similar proportions across groups: 13.5% in the SEC-300 group, 15.9% in the SEC-150 group, and 14.2% in the placebo group. Specific adverse events that were more frequent in the secukinumab groups compared with placebo included nasopharyngitis, hypersensitivity reactions, urinary tract infections, fungal infections, and back pain. The abstract does not detail the severity grading or the relationship of individual serious adverse events to study drug beyond the aggregated numbers reported.
In this randomized Phase 3 trial of patients with relapsed polymyalgia rheumatica, adding secukinumab (either 300 mg or 150 mg) to a 24-week glucocorticoid taper increased the proportion of patients achieving sustained remission at 52 weeks and reduced cumulative glucocorticoid exposure compared with a glucocorticoid taper plus placebo. The incidence of serious adverse events was similar across groups, although some infections and hypersensitivity-type events were more common with secukinumab.
The trial was funded by Novartis and reported under the REPLENISH clinical program (ClinicalTrials.gov NCT05767034). These results position IL-17A inhibition with secukinumab as an effective option to increase remission rates and decrease glucocorticoid burden in relapsing polymyalgia rheumatica, based on the data presented in the abstract.
The source material is the trial abstract and provides key outcomes but omits several granular details. The abstract does not report baseline characteristics, detailed statistical methods beyond the primary comparisons, subgroup or per-protocol analyses, long-term outcomes beyond 52 weeks, or specific descriptions of serious adverse events and their causality assessments. Where such details are not included in the abstract, they are not reported in this summary.