Polymyalgia rheumatica is a chronic inflammatory condition characterized by pain and stiffness in the shoulders, along with fatigue, weight loss, loss of appetite, and depression. Mainly affecting patients over 50 years of age, patients with polymyalgia rheumatica experience a silent type of suffering. Although many are diagnosed in their late 60s and 70s, patients diagnosed with the condition are often diagnosed with giant cell arteritis, which causes temporal headaches, jaw pain while chewing, scalp tenderness, and occasionally visual symptoms.

"Polymyalgia rheumatica can be an incapacitating disease, causing painful disease flares in multiple parts of the bodies that leave people fatigued and unable to fully perform everyday activities,” George D. Yancopolous, MD, PhD, president and chief scientific officer at Regeneron, stated.¹

While the prevalence of polymyalgia is low, with less than 1% of the population affected, on average, 2 out of 5 patients with polymyalgia may need to be treated with steroids for more than 2 years, which can create additional issues for patients, such as weight gain, mood swings, and increased risk of infection.

Current Treatments for Polymyalgia Rheumatica

Treatment for polymyalgia rheumatica generally involves an initial dosing of corticosteroids. In the United Kingdom, where Arvind Nune, MRCP, consultant rheumatologist at Southport and Ormskirk Hospital NHS Trust, practices, the standard therapy is 15 milligrams of prednisone for up to 3-4 weeks, depending on symptom remission and inflammatory markers such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR).

Once the symptoms improve and the markers decrease, steroids are gradually tapered. Nune explained the prognosis for polymyalgia rheumatica is one where 3 in 5 patients achieve remission after 18 months to 2 years of corticosteroid therapy. However, half of these patients relapse during the first year and 1 in 4 patients require treatment for 4-8 years.²

“Corticosteroids have been the primary treatment to date, many patients do not adequately respond to steroids or cannot be tapered off steroids, which puts such patients at risk of complications from long-term steroid therapy,” Yancopolous continued.¹

“In rheumatology, 2 types of therapies are commonly used: steroid-based and non-steroid based disease modifying drugs,” explained Nune, in an interview with HCPLive. “While steroids have been an older staple drug, newer non-steroid based drugs, such as methotrexate and leflunomide, but unfortunately, they do not seem to be effective for polymyalgia patients.”

Nune added biologic drugs, such as tumor necrosis factor inhibitors (TNFs) and rituximab, have also been tested for the treatment of the condition but have not been proven to be significantly beneficial.

In addition to pharmaceutical treatments, patients are often prescribed calcium and vitamin D supplements to prevent potential bone loss from long-term steroid therapy. They are also encouraged to eat a healthy diet, engage in regular exercise, ensure proper sleeping habits, and use assistive devices if necessary.³

Tocilizumab as a Potential Treatment Option

Although many pharmacologic options have been examined, none have been found to be as effective as steroids for treating polymyalgia rheumatica. However, the interleukin-6 (IL-6) inhibitor, tocilizumab, has shown some promise in recent trials examining the drug’s efficacy and safety in this patient population.

“The IL-6 blocker tocilizumab is a promising drug, especially since it has been found to work well in its sister disease, giant cell arthritis, which falls within a similar disease spectrum,” Nune said. “It is expected that tocilizumab should have some benefit for polymyalgia patients as well.”

In the double-blind, multicenter, phase 2/3 PMR-SPARE trial, 39 patients with new onset polymyalgia rheumatica who were undergoing rapid glucocorticoid tapering, which was defined as tapering from 20 mg to 0 mg over the course of 11 weeks, were given either weekly subcutaneous tocilizumab (n = 19) or placebo (n = 17). Results of the trial indicated tocilizumab was superior to placebo in terms of sustained glucocorticoid-free remission, time to relapse, and cumulative glucocorticoid dose.⁴

At week 16, glucocorticoid-free remission was achieved in 62.2% (n = 12/19) patients receiving tocilizumab compared with only 11.8% (n = 2/17) of those in the placebo cohort. The mean time to first relapse was 130 days in the tocilizumab cohort compared with 82 days in the placebo cohort and the mean cumulative dose of tocilizumab was lower for those receiving tocilizumab (727 mg vs 935 mg, respectively). Further, serious adverse events occurred in 5 patients in the placebo group compared with only 1 in the tocilizumab group.

Another trial evaluated disease activity in patients with polymyalgia rheumatica receiving either tocilizumab (n=51) or placebo (n=50).⁵ The randomized clinical trial enrolled patients with active polymyalgia rheumatica despite receiving glucocorticoid therapy. A low disease activity score in conjunction with a prednisone dose to ≤5 mg per day or a decrease ≥10 mg per day was achieved by 63.7% of patients in the tocilizumab group at 24 weeks compared with only 31.4% of those receiving placebo.

While these results are promising, investigators noted, “further research is needed to confirm efficacy and to determine the balance of potential benefits and harms.”⁵

Sarilumab: The First FDA-Approved Biologic

In February 2023, Sanofi and Regeneron Pharmaceuticals, Inc announced the US Food and Drug Administration (FDA) approval of sarilumab (Kevzara), which made the agent the first biologic to treat adult patients with polymyalgia rheumatica who had inadequate response to corticosteroids or could not tolerate a corticosteroid taper.¹

The decision to approve the injectable IL-6 receptor inhibitor was based on data from the phase 3 SAPHYR trial, which showed that treatment with sarilumab resulted in nearly 3 times as many patients achieving sustained remission when compared with placebo. For the trial, sustained remission was defined as remission by week 12, CRP normalization from weeks 12 to 52, absence of disease flare, and adherence to the corticosteroid tapering protocol from weeks 12 to 52.

Per trial protocol, patients received 200 mg of sarilumab every 2 weeks in conjunction with a 14-week taper of steroids or placebo with a 52-week taper of steroids.

At the end of the trial, 28% of patients treated with sarilumab met the primary endpoint of sustained remission compared with 10% in the placebo cohort. As in previous tocilizumab studies, the patients in the tocilizumab group had lower median cumulative steroid doses when compared with placebo (777 mg vs 2044 mg, respectively).

“Until now, people living with polymyalgia rheumatica have had limited treatment options for this serious rheumatic condition which causes significant pain and discomfort,” wrote Bill Sibold, executive vice president, head of Specialty Care at Sanofi.¹ “The approval is a new option for patients and the healthcare professionals who treat them.”

Despite the recent advancements in the treatment of polymyalgia rheumatica, a need for more research focused on finding non-steroidal treatment options remains. While research is constantly evolving, at present, only a handful of drugs have been shown to effectively treat this condition.

“Because polymyalgia rheumatica is a common condition, and patients should be aware of symptoms such as prolonged pain and stiffness in the shoulders and thigh girdles,” Nune stressed. “If they experience these symptoms, they should take them seriously. It is important to treat patients in a timely manner because if left untreated, they may suffer from irreversible visual loss and other complications, such as reduced daily living activities and systemic symptoms.”

References

^{1. Press room - press releases. (n.d.). Retrieved April 14, 2023, from https://www.news.sanofi.us/2023-03-01-Kevzara-R-sarilumab-approved-by-FDA-as-first-and-only-biologic-indicated-for-patients-with-polymyalgia-rheumatica}

^{2. Kremers HM, Reinalda MS, Crowson CS, Zinsmeister AR, Hunder GG, Gabriel SE. Relapse in a population based cohort of patients with polymyalgia rheumatica. J Rheumatol. 2005;32(1):65-73}

^{3. Mayo Foundation for Medical Education and Research. (2022, June 16). Polymyalgia Rheumatica. Mayo Clinic. Retrieved April 14, 2023, from https://www.mayoclinic.org/diseases-conditions/polymyalgia-rheumatica/diagnosis-treatment/drc-20376545}

^{4. Bonelli M, Radner H, Kerschbaumer A, et al. Tocilizumab in patients with new onset polymyalgia rheumatica (PMR-SPARE): a phase 2/3 randomised controlled trial. Ann Rheum Dis. 2022;81(6):838-844. doi:10.1136/annrheumdis-2021-221126}

^{5. Devauchelle-Pensec V, Carvajal-Alegria G, Dernis E, et al. Effect of Tocilizumab on Disease Activity in Patients With Active Polymyalgia Rheumatica Receiving Glucocorticoid Therapy: A Randomized Clinical Trial. JAMA. 2022;328(11):1053-1062. doi:10.1001/jama.2022.15459}