SAPHYR Trial Highlights Kevzara’s Ability To Prevent Relapse in Polymyalgia Rheumatica During Steroid Taper

Polymyalgia rheumatica is an inflammatory disease that causes pain and morning stiffness in the shoulders and pelvic girdles. Typically, this condition is treated with glucocorticoids; however, more than half of patients on this treatment are unable to successfully taper their therapy without relapse.

Robert F. Spiera, M.D.

In this Managed Healthcare Executive Between the Lines video series, Dana McCormick, RPh, spoke with Robert Spiera, M.D., about the results of the phase 3, multicenter, randomized, double-blind, placebo-controlled SAPHYR trial evaluating the safety and efficacy of using Kevzara (sarilumab) to manage relapse during glucocorticoid tapers in patients with polymyalgia rheumatica. McCormick is the director of pharmacy for Blue Cross and Blue Shield of Illinois, Montana, New Mexico, Oklahoma and Texas, and Spiera is the director of the Scleroderma, Vasculitis and Myositis Center at the Hospital for Special Surgery in New York.

On Feb. 28, 2023, the FDA approved Kevzara, an interleukin-6 receptor inhibitor, to treat polymyalgia rheumatica in adults for whom glucocorticoids are an inadequate treatment or who cannot tolerate a glucocorticoid taper. Kevzara was previously approved in 2017 to treat certain adults with moderate to severe, active rheumatoid arthritis who either could not tolerate disease-modifying antirheumatic drugs (DMARDs) or had an inadequate response on DMARDs.

Polymyalgia rheumatica commonly occurs in people aged 50 years or older, and the stiffness they feel can cause severe pain and make them “miserably uncomfortable,” Spiera said. Early in the disease, treatment is easy with glucocorticoids and patients are very responsive and begin to
feel much better.

“The challenge is that a prolonged course of steroids [is] often required,” he said. Guidelines recommend trying to taper the steroids over one year, but in clinical practice, steroids can be required for up to six years. This length of treatment comes with a price, with side effects and significant steroid-related toxicity.

SAPHYR results

The SAPHYR trial included patients who had failed to taper their steroids without a disease flare.The goal was to see whether adding Kevzara would allow these patients to achieve a clinically meaningful sustained remission over the course of one year. “The study design was meant to truly test whether Kevzara was an effective therapy in a very substantial way,” Spiera said.

Patients were randomly assigned to receive either200 milligrams (mg) of Kevzara every two weeks plus prednisone that was supposed to be tapered off entirely by week 14 or a placebo injection plus prednisone that was tapered during a standard 52 weeks. The primary outcome was sustained remission at 52 weeks. However, Spiera said some of the secondary outcomes may be even more meaningful than sustained remission. For instance, the study looked at cumulative glucocorticoid dose, time to flare, glucocorticoid toxicity index and safety.

For the primary outcome, approximately three times as many patients who were treated with Kevzara as those on placebo achieved a sustained remission. At week 52,28% of patients on Kevzara and 10% of patients on placebo achieved sustained remission.

“Despite the fact that [patients in the Kevzara arm] only had 14 weeks of steroids and had to be in remission by week [52], where they were down to maybe 1 or 2 [mg] of prednisone, those patients were threefold more likely to … have achieved remission,” Spiera said.

Those patients on Kevzara were exposed to lower amounts of steroids but also had a lower likelihood of having a flare after remission, he added. Patients on Kevzara also had a lower score on the Glucocorticoid Toxicity Index, which measures glucocorticoid-related morbidity over time. Patients who received Kevzara also were much less likely to need rescue therapy by week 52: 84% of patients did not need treatment with other steroids during the trial.

Spiera noted that the patients who were treated with Kevzara also fared better in almost every domain evaluating quality of life.

It isn’t clear what would be a meaningful difference in glucocorticoid total dose, Spiera said, but this trial does provide information that as little as 1,500 mg of prednisone, cumulatively, over the course of a year is clinically important for a group of older patients.

From a safety standpoint, there are no major safety signals in the trial. The most common side effect among patients receiving Kevzara was neutropenia (15%) versus none in the placebo group.None of the side effects resulted in study discontinuation for any of the patients; instead, the researchers were able to adjustthe doses.

Kevzara will fit very easily into the American College of Rheumatology’s treatment guidelines for polymyalgia rheumatica, Spiera said, although they were last updated in 2015. Spiera was involved in that update. The goal of those guidelines has been to strike a balance between avoiding overtreated with steroids and making sure the disease was treated appropriately. When those guidelines were last updated, there was an attempt to include anything that might get patients off steroids faster, including trying methotrexate, despite the fact that it didn’t have a lot of evidence. “I think the way the use of [Kevzara] will be incorporated into the guidelines will be straightforward in patients … who have failed steroid tapers, patients who are very susceptible to steroid side effects, [and] I would even imagine that, potentially, patients who are very high risk for steroid side effects even if they haven’t failed a steroid taper,” Spiera said.

Although the FDA approval is specifically for patients who have been refractory to a steroid taper or who are intolerant of a taper, Spiera believes the guideline writers could consider the use of Kevzara as a first-line treatment for patients who anticipated to have steroid-related side effects, although the evidence for that is not conclusive right now.

Without updated guidelines, there may be concerns about delayed treatment with Kevzara due to payer prior authorization requirements. Spiera recommended that policies be set up that align with the FDA approval for the drug. He also recommended recognizing that there is evidence that in patients who have experienced a steroid taper failure resulting in disease flare that patients will be intolerant to a steroid taper or develop significant steroid-related side effects. In these cases, it will not only be better for the patient’s quality of life to have access to a steroid-sparing agent, but it will also save the payer a lot of money in the long term by avoiding those side effects, he said.

For patients who haven’t experienced disease flare when tapering steroids, some of the factors to consider for who might be at risk of unacceptable corticosteroid-related toxicity are those who could experience severe exacerbation of diabetes; skin fragility, bruising, breakdown and infections; psychosis; and fractures.

“But essentially, your whole population with polymyalgia rheumatica is at high risk,” Spiera said.

Relevance for physicians, payers and patients

Having a nonsteroid treatment option for patients with polymyalgia rheumatica who are refractory to or intolerant of a steroid taper is exciting, Spiera said, because it’s an important area of unmet need. “It’s also really important to recognize that there is a better path for patients, and, ultimately, it’s in everyone’s [best] interests for patients to be as healthy as possible,” he said. “The kind of chronic problems that develop from long-term corticosteroid use are huge burdens on the healthcare system.”