A minority of patients with polymyalgia rheumatica (PMR) who were new to rheumatology practice were prescribed steroid-sparing agents through two years of follow-up. This is according to a large, U.S.-based cohort study, published in Arthritis Care & Research, which also found that nearly two-thirds of the patients remained on glucocorticoids beyond one year.1
“Our study shows current contemporary practice, indicating that glucocorticoid-sparing agents are still used in a minority of patients despite the need for prolonged use of glucocorticoids,” says Sebastian E. Sattui, MD, MS, an assistant professor of medicine and director of the UPMC Vasculitis Center at the University of Pittsburgh School of Medicine. “Although these decisions in clinical practice are guided by a shared decision-making process (e.g., balancing low-dose glucocorticoids vs. methotrexate or similar agent), it possibly also reflects the lack of evidence to better guide clinicians on the use of glucocorticoid-sparing agents with regard to value, timing and balancing risks and benefits.”
Background
Dr. Sattui
Historically, the treatment of patients with PMR—one of the most common systemic rheumatic diseases in older adults—relied on the long-term use of glucocorticoids, but treatment relapses occur in up to half of the patients. Recent studies showed the efficacy of steroid-sparing agents for PMR, including rituximab and the interleukin (IL) 6 inhibitors tocilizumab and sarilumab.2-4 In February 2023, the U.S. Food & Drug Administration (FDA) approved sarilumab (Kevzara) for the treatment of adults with glucocorticoid-resistant or relapsing PMR.5
“Our study is quite timely given the recent publication of trials using biologic drugs for the treatment of PMR and even more so with the recent FDA approval of sarilumab for the treatment of refractory/relapsing PMR,” says Dr. Sattui. “Data included in our analysis was up to 2022, so less likely to be affected by the publication of these new trials and even more so the FDA approval.”
Dr. Sattui explains, “Our goal was to better describe the current treatment patterns of individuals with PMR under rheumatology care. We focused on trying to understand these patients who are being seen by rheumatologists, as well as the duration of glucocorticoid treatment and current use—as well as factors—of glucocorticoid-sparing agents.”
Cohort Study
A total of 26,102 patients with PMR were identified in the ACR Rheumatology Informatics System for Effectiveness (RISE) registry from 2016 to 2022, of which 16,703 patients were new to rheumatology practice and presumed to have new-onset PMR.1 To assess treatment patterns over time, the majority of the analysis of this electronic health record data focused on the new patients. The researchers looked at the use of glucocorticoids and immunomodulatory drugs employed as steroid-sparing agents. They aimed to identify factors associated with prolonged glucocorticoid use and the persistent use of steroid-sparing agents beyond one year.
For the entire cohort, patients were predominantly women (60.2%) and white (56.1%), with a mean age of 73 years. The demographic characteristics were similar in the patients new to rheumatology practice: 55.8% were women; 46.7% were white, with a mean age of 72 years. The most common comorbidities were hypertension (81.2%), congestive heart failure (52.4%), hyperlipidemia (41.3%) and ischemic heart disease (36%). On average, patients received medications for six to seven comorbidity categories. At baseline, 92.3% of the patients were on glucocorticoids and 13.1% were on a steroid-sparing agent, of which methotrexate (6.9%) and hydroxychloroquine (4.4%) were the most frequently used. At 13 to 24 months, 63.8% of the patients remained on glucocorticoids. The use of steroid-sparing agents increased to 39%, but this remained primarily conventional immunomodulatory drugs, such as methotrexate (19.5%) and hydroxychloroquine (11.1%). The use of IL-6 inhibitors and rituximab past one year was reported in 2.5% and 0.3% of patients, respectively.
Persistent glucocorticoid use was associated with female sex, a higher number of comorbidities and use of a steroid-sparing agent at 24 months. The use of a steroid-sparing agent was associated with obesity and a higher number of comorbidities. In contrast, a lower use of steroid-sparing agents was associated with older age and private insurance.
“At the 13- to 24-month follow-up, close to two-thirds of patients remained on glucocorticoids, while less than half of patients were receiving a glucocorticoid-sparing agent,” Dr. Sattui says. “Even low doses of glucocorticoids are associated with toxicity—more so in this population (e.g., older age, higher burden of comorbidities).
“Methotrexate, as one would expect given the 2015 existing recommendations, was the most frequent choice of glucocorticoid-sparing agent, followed by hydroxychloroquine, leflunomide, and then IL-6 inhibitors.6 Although trials do exist for methotrexate, there are no rigorous studies (until recent IL-6 inhibitor trials) that support their use,” Dr. Sattui says.
With the FDA approval of a biologic for the treatment of PMR, adds Dr. Sattui, “I would expect to see changes in the treatment practices. However, this will most likely take some time given the usual delay in uptake of new treatments and because as promising as the results of the recently published SAPHYR trial are, these only apply to a select population.”4
Future Research
Dr. Sattui notes that we need to better understand the benefits of glucocorticoid-sparing agents, including glucocorticoid-free and drug-free remission. Efforts should also focus on identifying patients who could benefit from these agents and for whom earlier consideration is needed. He also recommends prospective analyses that include treatments used and patient-reported outcomes relevant to these individuals and this age group, such as physical function and mobility.
“In PMR, unlike many of the other conditions we treat as rheumatologists, we can actually talk about drug-free disease remission and theoretically talk about disease-modifying agents,” Dr. Sattui concludes.7 “Use of glucocorticoid-sparing agents could potentially open the door for this, and this needs to be a focus of trial and treatment. This will also require the need for earlier assessment of all individuals with a diagnosis of PMR.”
Dr. Owen
Claire Owen, MBBS (Hons), PhD, deputy director of rheumatology at Austin Health and senior research fellow at the University of Melbourne, Victoria, Australia, calls the study a welcome addition to the PMR literature, given the large size of the patient cohort and the focus on management by rheumatologists, rather than primary care providers.
The finding that “a minority of patients [is] being prescribed a steroid-sparing agent in the first 24 months following their PMR diagnosis speaks to how underresearched and misunderstood this common rheumatic disease has been,” Dr. Owen says. “This work is a reminder that we may be underutilizing cheaper, readily available synthetic DMARDs in a more recently diagnosed PMR population. Future research efforts should therefore not be limited to novel therapies but also revisit improved utilization of drugs like methotrexate in well-designed clinical trial settings.”
Katie Robinson is a medical writer based in New York.
References
- Sattui SE, Xie F, Wan Z, Clinton C, Domsic RT, Curtis JR. Treatment of polymyalgia rheumatica by rheumatology providers: Analysis from the ACR Rheumatology Informatics System for Effectiveness registry [published online ahead of print, 2023 Aug 10]. Arthritis Care Res (Hoboken). 2023;10.1002/acr.25216.
- Marsman DE, den Broeder N, van den Hoogen FHJ, et al. Efficacy of rituximab in patients with polymyalgia rheumatica: a double-blind, randomised, placebo-controlled, proof-of-concept trial. Lancet Rheumatol. 2021 Sept;3(11):e758–e766.
- 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.
- Spiera RF, Unizony S, Warrington KJ, et al. Sarilumab for relapse of polymyalgia rheumatica during glucocorticoid taper. N Engl J Med. 2023 Oct 5;389(14):1263-1272.
- Highlights of prescribing information: Kevzara (sarilumab) injection for subcutaneous use. U.S. Food & Drug Administration. 2023 Feb 28.
- Dejaco C, Singh YP, Perel P, et al. 2015 recommendations for the management of polymyalgia rheumatica: A European League Against Rheumatism/American College of Rheumatology collaborative initiative. Arthritis Rheumatol. 2015 Oct;67(10):2569–2580.
- Dejaco C, Kerschbaumer A, Aletaha D, et al. Treat-to-target recommendations in giant cell arteritis and polymyalgia rheumatica [published online ahead of print, 2023 Feb 24]. Ann Rheum Dis. 2023;ard-2022-223429.
