A phase 3 trial suggests IL-17A blockade may double sustained remission rates while cutting glucocorticoid exposure in relapsing polymyalgia rheumatica.
An IL-17A inhibitor commonly used in spondyloarthritis and psoriasis may soon expand into polymyalgia rheumatica, after phase 3 data showed secukinumab significantly improved sustained remission while reducing steroid exposure in patients with relapsing disease.
Results from the REPLENISH trial found that patients treated with secukinumab were roughly twice as likely to achieve sustained remission at 52 weeks compared with placebo when combined with a structured glucocorticoid taper.
Results were released in a presentation from Novartis Pharma.
Dr Claire Owen, deputy director of Rheumatology at Austin Health and honorary senior research fellow at The University of Melbourne, welcomed the study.
“The REPLENISH study represents a major milestone in PMR therapeutic development,” she told Rheumatology Republic.
“A significant difference between the treatment and placebo groups (for both secukinumab doses) reaffirms the role played by IL-17 in PMR pathogenesis and also points to certain differences in the inflammatory milleu between PMR and GCA given a successful outcome was not observed in the sister study, GCAPTAIN. O
“Of course, the publication is eagerly awaited for more details (especially PROM) but the early indicators look promising for secukinumab in relapsing PMR.”
Polymyalgia rheumatica remains one of the most common inflammatory rheumatic diseases in adults aged over 50 years, yet treatment still relies heavily on long-term glucocorticoids, which carry well-documented risks including osteoporosis, hypertension, infection and metabolic complications.
Relapse is also common, with around 40% of patients experiencing recurrence within the first year.
The multicentre, double-blind phase 3 study randomised 381 patients with recently relapsed PMR to secukinumab 300mg, secukinumab 150mg or placebo alongside a standardised 24-week prednisone taper.
Participants had previously received glucocorticoids for at least eight weeks and had relapsed during dose reduction.
At week 52, sustained remission was achieved in 41.2% of patients receiving secukinumab 300mg and 40.6% receiving the 150mg dose, compared with 20.4% in the placebo group. Both treatment arms showed statistically significant differences versus placebo (p<0.001).
More stringent complete sustained remission, defined by clinical remission with normal inflammatory markers, was also significantly higher with secukinumab, occurring in 28.2% and 24.5% of patients in the 300mg and 150mg groups respectively, compared with just 4.7% with placebo.
Importantly for clinicians trying to minimise long-term steroid toxicity, cumulative glucocorticoid exposure was markedly lower in both active treatment groups. The adjusted annual glucocorticoid dose was reduced by around 490mg with secukinumab 300mg and 410mg with the 150mg regimen compared with placebo.
Patients receiving secukinumab also went longer before requiring escape or rescue treatment. Median time to treatment escalation was 337 days with the higher dose and 282 days with the lower dose, compared with just 157 days in the placebo arm.
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Safety findings were broadly consistent with the established profile of secukinumab across immune-mediated diseases. Rates of adverse events and serious adverse events were similar across treatment groups, and serious infections occurred at comparable frequencies.
The researchers said the findings highlight a potential new therapeutic pathway in PMR, where targeted steroid-sparing options remain limited despite the disease’s high prevalence among older adults with comorbidities.
“There is a need for GC-sparing targeted therapies that can maintain remission,
prevent relapses, have a favourable safety profile, and improve QoL,” they wrote in their presentation.
If confirmed through regulatory review, secukinumab could become the first IL-17A inhibitor approved for PMR and provide clinicians with a biologic option capable of maintaining remission while reducing cumulative glucocorticoid exposure.
