Sarilumab Effective for Polymyalgia Rheumatica in Phase 3 Trial

PHILADELPHIA — Therapy with the interleukin-6 receptor antagonist sarilumab (Kevzara), together with a 14-week taper of glucocorticoids, proved to have vital efficacy in sufferers with relapsing polymyalgia rheumatica (PMR) who had been proof against glucocorticoids in a part 3 trial.

No new security considerations had been discovered with sarilumab, within the multicenter, randomized, double-blind, placebo-controlled SAPHYR trial. Sarilumab is permitted in america for the therapy of reasonable to extreme energetic rheumatoid arthritis in adults who’ve had an insufficient response or intolerance to a number of disease-modifying antirheumatic medication.

The outcomes, offered on the American School of Rheumatology 2022 Annual Assembly by Robert Spiera, MD, director of the Scleroderma, Vasculitis, and Myositis Middle at Hospital for Particular Surgical procedure in New York Metropolis, included clinically significant enchancment in quality-of-life scores.

The illness, which primarily impacts folks over age 65, could cause widespread aching and stiffness. It’s one of the vital widespread inflammatory ailments amongst older adults.

PMR is comparatively straightforward to deal with with glucocorticoids, however relapses are widespread, which implies lengthy programs of glucocorticoid remedy and the unwanted effects that include them.

Want for a Steroid-Sparing Remedy

“We acknowledge {that a} steroid-sparing drug in polymyalgia rheumatica appears to be an unmet want,” Spiera mentioned on the assembly.

The trial, sponsored by Sanofi, included energetic, refractory PMR sufferers who flared inside 3 months of examine entry whereas on at the very least 7.5 mg/day of prednisone or the equal. They had been randomly assigned (1:1) to 52 weeks of therapy with subcutaneous sarilumab 200 mg each 2 weeks plus the speedy 14-week glucocorticoid tapering routine or got placebo each 2 weeks plus a extra conventional 52-week tapering of glucocorticoids.

COVID Hampered Recruitment

Recruitment was stopped early due to issues in the course of the COVID-19 pandemic, so between October 2018 and July 2020, 118 of the meant 280 sufferers had been recruited, and 117 had been handled (sarilumab = 59, placebo = 58). Median age was 69 years within the therapy group and 70 amongst these taking placebo.

Of the 117 handled, solely 78 sufferers (67%) accomplished therapy (sarilumab = 42, placebo = 36). The principle causes for stopping therapy had been hostile occasions — together with 7 with sarilumab and 4 with placebo — and lack of efficacy (sarilumab = 4, placebo = 9).

The first final result was the proportion of sufferers who reached sustained remission at 52 weeks, outlined as illness remission by week 12 and no illness flare, regular C-reactive protein (CRP), and adherence to the glucocorticoid taper throughout weeks 12 to 52.

The researchers discovered that sustained remission was considerably increased within the sarilumab arm vs the management group (28.3% vs 10.3%; P = .0193).

IL-6 inhibitors decrease CRP, however when you take CRP out of the definition, Spiera mentioned, “we nonetheless noticed this distinction: 31.7% of sufferers handled with sarilumab and 13.8% handled with placebo and an extended taper achieved that endpoint.”

44% Decrease Threat of Flare With Sarilumab

Sufferers within the sarilumab group additionally had 44% decrease threat of getting a flare after reaching medical remission vs. the comparator group (16.7% vs 29.3%; HR, 0.56; 95% CI, 0.35 – 0.90; P = .0153).

Affected person-reported outcomes, which included bodily and psychological well being scores and incapacity index outcomes, favored sarilumab.

The incidence of treatment-emergent hostile occasions (TEAEs) was numerically increased within the sarilumab group, in contrast with the management group (94.9% vs 84.5%). TEAEs included neutropenia (15.3%) and arthralgia (15.3%) within the sarilumab group and insomnia (15.5%) within the comparator arm.

Nonetheless, the frequency of great AEs was increased within the management group, in contrast with the sarilumab arm (20.7% vs 13.6%). No deaths had been reported, and, importantly on this age group handled with concurrent glucocorticoids and an IL-6 inhibitor, Spiera mentioned, “there have been no instances of diverticulitis requiring intervention.”

Spiera was requested a few seemingly low remission price. He answered that the bar was very excessive for remission on this examine.

Sufferers needed to obtain remission by week 12 and with the speedy 14-week taper. “Which means by week 12 the sarilumab arm sufferers had been solely on 2 mg of every day prednisone or its equal,” he mentioned.

Sufferers needed to keep that for an additional 40 weeks, he famous, including, “I feel particularly within the context of high quality of life and performance indices, these had been necessary outcomes.”

Sebastian E. Sattui, MD, director of the College of Pittsburgh Medical Middle Vasculitis Clinic, Pittsburgh, Pennsylvania, informed Medscape Medical Information that extended use of glucocorticoids in sufferers with PMR stays an necessary concern and the necessity for different choices is crucial.

Dr Sebastian Sattui

“Round 30% of sufferers with PMR stay on prednisone 5 years after analysis,” he mentioned. “Low-dose glucocorticoids are nonetheless related to vital morbidity. Till not too long ago, there was a paucity of high-quality knowledge relating to using steroid-sparing brokers in PMR. “

He famous that the SAPHYR trial knowledge are promising “with sarilumab being profitable in reaching remission whereas minimizing glucocorticoids in sufferers with relapsing PMR.” The clinically significant enchancment in patient-reported outcomes was simply as necessary, he added.

The principle unanswered query is whether or not the disease-modifying capability of sarilumab will proceed after it’s stopped, Sattui mentioned.

Spiera is a marketing consultant for Sanofi, which funded the trial. He additionally disclosed monetary relationships with GlaxoSmithKline, Boehringer Ingelheim, Corbus, InflaRx, AbbVie/Abbott, Novartis, Chemocentryx, Roche, and Vera. Sattui has acquired analysis help from AstraZeneca and has accomplished unpaid consulting work for Sanofi.

American School of Rheumatology (ACR) 2022 Annual Assembly: Summary 1676. Introduced November 14, 2022.

Marcia Frellick is a contract journalist based mostly in Chicago. She has beforehand written for the Chicago Tribune, Science Information, and, and was an editor on the Chicago Solar-Occasions, the Cincinnati Enquirer, and the St. Cloud (Minnesota) Occasions. Comply with her on Twitter at @mfrellick.

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