What’s New in Polymyalgia Rheumatica?

EULAR 2024 (VIENNA)—What’s new in polymyalgia rheumatica (PMR)? That’s the question Frank Buttgereit, MD, senior consultant and deputy head of the Department of Rheumatology and Clinical Immunology, University Medicine, Berlin, set out to answer at EULAR 2024. Harry Spiera, MD, is credited with describing the first American case series of PMR in the 1970s.¹ Since then, we have come to recognize PMR as the most common inflammatory disease in people aged 50 and older.² In this WIN session, Dr. Buttgereit summarized the latest advances in the diagnosis and treatment of PMR.

Assessing Patients

When screening a patient for PMR, Dr. Buttgereit said rheumatologists should also screen for giant cell arteritis (GCA), a frequently overlapping condition whose co-occurrence has implications for patient management. Subclinical GCA in PMR—based on imaging or biopsy—has a pooled prevalence of about 23%, yet the clinical implications of these findings are unclear.³

In a study conducted by De Miguel et al., 150 patients with PMR and without clinical symptoms of GCA were stratified into two groups: 1) those with isolated PMR and 2) those with subclinical GCA, based on ultrasound imaging. These groups were followed for two years. The study found patients with PMR and subclinical GCA have a fourfold higher rate of relapse than patients with isolated PMR. Additionally, they found a lower starting dose and rapid taper of glucocorticoids in the first three months of treatment increases the risk of relapse in these patients.⁴

These findings raise the question: Should all patients with PMR have a vascular ultrasound assessment? Dr. Buttgereit believes that such an evaluation should be considered at the time of diagnosis, particularly if clinician sonographers are accessible.

Treatment

Dr. Buttgereit noted that the 2015 Recommendations for the Management of PMR, jointly published by EULAR and the ACR, remains a helpful guideline for practicing rheumatologists.⁶ This guideline recommends clinicians begin treatment with prednisone in a dose ranging from 12.5–25 mg daily. For patients with a high risk or relapse and low risk of adverse events, the dose can be up to 30 mg of prednisone daily. Conversely, doses as low as 7.5 mg of prednisone daily can be prescribed for patients with comorbidities (i.e., diabetes, osteoporosis or glaucoma).^5,6

The initial tapering of glucocorticoids should allow the patient to reach a dose of 10 mg of prednisone daily four to eight weeks after therapy is initiated. Subsequent tapering should be in increments of 1 mg every four weeks.^5,6

If the patient experiences a relapse, the prednisone dose can be increased to the pre-relapse level and then decreased gradually over four to eight weeks to the dose at which relapse occurred. Dr. Buttgereit noted that, within the context of these recommendations, it’s important for physicians and patients to participate in shared decision making and routinely discuss the goals of care, which most commonly focus on maximizing health-related quality of life.^5,6

Next, Dr. Buttgereit discussed recent clinical trials demonstrating the effectiveness of interleukin (IL) 6 receptor inhibition in the treatment of PMR. These studies include the PMR-SPARE trial of tocilizumab, the SEMAPHORE trial of tocilizumab and the SAPHYR trial of sarilumab.^7–9 Although the PMR-SPARE and SEMAPOHORE trials demonstrated positive results for tocilizumab, the SAPHYR trial may be more familiar to rheumatologists in the U.S. because its findings influenced the 2023 U.S. Food & Drug Administration’s approval of sarilumab for the treatment of patients with PMR for whom glucocorticoids have proved inadequate or who cannot tolerate glucocorticoid tapering.¹⁰

The SAPHYR trial enrolled 118 patients with PMR, all of whom had:⁹ 1) at least one episode of disease flare during glucocorticoid tapering (at a dose of ≥7.5 mg of prednisone per day) within 12 weeks of screening, and 2) a history of at least eight weeks of glucocorticoid treatment. the investigators randomly assigned patients to receive 200 mg of sarilumab twice per month over 52 weeks plus a 14-week prednisone taper or placebo plus a 52-week prednisone taper. The primary outcome at 52 weeks was sustained remission, defined as the absence of PMR signs/symptoms by week 12, sustained C-reactive protein (CRP) normalization, absence of disease flare and adherence to the prednisone taper from weeks 12 through 52. At week 52, sustained remission occurred in 28% of participants in the sarilumab group and in 10% in the placebo group; this significant difference held true even when ESR and CRP were removed from the analysis. The cumulative glucocorticoid dose at week 52 was lower in the sarilumab group than in the placebo group (777 mg vs. 2,044 mg, respectively). Fewer disease flares occurred after clinical remission at week 12 in the sarilumab group than in the placebo group (24% vs. 57%, respectively). Finally, patients treated with sarilumab had lower glucocorticoid toxicity index scores during 52 weeks (52.32 vs. 57.22) and larger mean improvement in disease activity score from baseline to week 52 (−15.57 vs. −10.27) than those receiving placebo.

Dr. Buttgereit also highlighted several studies evaluating the effectiveness and safety of tofacitinib and rituximab for treating patients with PMR.

In the EAST PMR study, researchers randomized patients to receive either tofacitinib or glucocorticoids for 24 weeks. The study showed no difference in the primary end point—defined as the proportion of patients with PMR-AS score ≤10 at weeks 12 and 24—between the two groups.¹¹

In 2023, Bolhuis et al. published a follow up to the BRIDGE-PMR study, a randomized controlled trial of rituximab for the treatment of PMR. BRIDGE-PMR was a proof-of-concept clinical trial that suggested B cell depletion with rituximab may have glucocorticoid-sparing effects in patients with PMR. The researchers assessed the rates of glucocorticoid-free remission up to one year after infusion of rituximab in an extension of the BRIDGE-PMR trial. They found the proportion of patients in remission remained stable at one year after infusion and a glucocorticoid-sparing effect was demonstrated.¹²

Jason Liebowitz, MD, is an assistant professor of medicine in the Division of Rheumatology at Columbia University Vagelos College of Physicians and Surgeons, New York.

References

1. Ullman K. Dr. Harry Spiera retires after 60 years in rheumatology. The Rheumatologist. 28 Sep 2023.
2. Lundberg IE, Sharma A, Turesson C, et al. An update on polymyalgia rheumatica. J Intern Med. 2022 Nov;292(5):717–732.
3. Hemmig AK, Gozzoli D, Werlen L, et al. Subclinical giant cell arteritis in new onset polymyalgia rheumatica A systematic review and meta-analysis of individual patient data. Semin Arthritis Rheum. 2022 Aug;55:152017.
4. De Miguel E, Karalilova R, Macchioni P, et al. Subclinical giant cell arteritis increases the risk of relapse in polymyalgia rheumatica. Ann Rheum Dis. 2024 Feb 15;83(3):335–341.
5. Dejaco C, Singh PY, 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.
6. 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. Ann Rheum Dis. 2015 Oct;74(10):1799–1807.
7. 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 Jun;81(6):838–844.
8. 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 Sep 20;328(11):1053–1062.
9. 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.
10. Kaufman, MB. FDA approves sarilumab for the treatment of adults with glucocorticoid-resistant PMR. The Rheumatologist. 2023 Mar 14.
11. Ma X, Yang F, Wu J, et al. Efficacy and safety of tofacitinib in patients with polymyalgia rheumatica (EAST PMR): An open-label randomized controlled trial. PLoS Med. 2023 Jun 29;20(6):e1004249.
12. Bolhuis TE, Marsman DE, den Broeder AA, et al. 1-year results of treatment with rituximab in polymyalgia rheumatica: An extension study of a randomised double-blind placebo-controlled trial. Lancet Rheumatol. 2023 Apr;5(4):e208–e214.