Study Underlines Potential of IL-6 Inhibitors for Polymyalgia Rheumatica

Jeffrey Curtis, MD, MS, MPH
Credit: University of Alabama at Birmingham Medicine

An analysis of data from Medicare beneficiaries is underlining the potential benefits of interleukin-6 (IL-6) inhibition in treatment of polymyalgia rheumatica as second- or third-line treatment relative to conventional immunomodulators.

Leveraging data from more than 650 patients with steroid-refractory polymyalgia rheumatica, results of the study suggest IL-6 inhibition, with either sarilumab or tocilizumab, was a more effective steroid-sparing agent than conventional immunomodulator therapy, with more patients in the IL-6 groups discontinuing glucocorticoid use than their counterparts receiving conventional immunomodulators.

“In the real-world, IL-6 receptor inhibition was a more effective steroid sparing agent than conventional immunomodulators in steroid refractory polymyalgia rheumatica,” wrote investigators.

Regeneron and Sanofi made history in late February 2023 with the announcement of the US Food and Drug Administration approval of sarilumab for the treatment of polymyalgia rheumatica. Indicated as a treatment for adults who have an inadequate response to corticosteroids or who cannot tolerate corticosteroid taper, approval of the IL-6 inhibitor marked the first FDA-approved biologic indicated for patients with polymyalgia rheumatica. Although not currently approved, a randomized trial published in 2022 examining tocilizumab as a treatment for patients with glucocorticoid-dependent polymyalgia rheumatica returned results indicatinguse was associated with significantly greater percentage of patients with a CRP PMR-AS less than 10 with reduced prednisone requirements at week 24.²

With this in mind, a team of investigators led by Jeffrey Curtis, MD, MS, MPH, of the University of Alabama at Birmingham, designed their study, which was presented at the Congress of Clinical Rheumatology (CCR) East 2023 annual meeting, as a retrospective analysis of patients aged 50 years or older with steroid-refractory polymyalgia rheumatica obtained from national fee-for-service Medicare data. Using March 29, 2016-June 30, 2020, as a period of interest, investigators limited their study to those with at least 1 inpatient or 2 outpatient claims with a polymyalgia rheumatic diagnosis at least 30 days apart. Additional inclusion criteria included 180 days of continuous enrollment prior to index, to be receiving 25 mg or less prednisone equivalent glucocorticoid, and to have been initiated on an IL-6 inhibitor or conventional immunomodulators as a second- or third-line therapy.¹

A total of 409 and 251 patients were identified for each arm of the propensity score-matched third line and second line cohorts, respectively. Investigators highlighted post direct- and propensity score-matched patient characteristics were generally balanced between the groups.¹

Investigators pointed out the index date for the third line cohort was the start date of IL-6 inhibitor use or new conventional immunomodulator after prior conventional immunomodulator and the index date for the second line cohort was the start date of IL-6 inhibitor use or conventional immunomodulator with no prior use of IL-6 inhibitor use or conventional immunomodulator.¹

The primary outcomes of interest for the study were discontinuation of glucocorticoids and minimal glucocorticoid use or no glucocorticoid use at 52 weeks. Of note, minimal glucocorticoid use was defined as 2 mg or less per day. Investigators estimated adjusted hazard ratios (aHR) for outcomes of interest using Cox proportional hazards models.¹

In adjusted analysis, results indicated users of IL-6 inhibitors were more likely to discontinue glucocorticoid use (aHR, 1.32 [95% confidence interval [CI], 1.09-1.58]) and achieve minimal dose or no glucocorticoid use (aHR, 1.30 [95% CI, 1.09-1.54]) relative to conventional immunomodulator use.¹

Among those in the third line group, the proportion of those who discounted glucocorticoid use was 45% among users of IL-6 inhibitors and 30.1% among conventional immunomodulators users. Among those in the second line group, the proportion of those who discontinued glucocorticoid use was 49.0% among users of IL-6 inhibitors and 32.7% among conventional immunomodulators users. Further analysis of indicated the proportion of users of IL-6 inhibitors and conventional immunomodulators achieving minimal or no glucocorticoid use were 49.6% and 34.7%, respectively in the third line cohort and 55.4% and 39.4%, respectively in the second line cohort.¹

References:

1. Curtiss JR, Ford K, Fiore S, et al. Real-world Effectiveness of Interleukin-6 Receptor Inhibitors in Patients with Steroid Refractory Polymyalgia Rheumatica . Paper presented at: Paper presented at: Congress of Clinical Rheumatology (CCR) East 2023 Annual Meeting. Destin, FL. May 4 – 7, 2023.
2. Pine L. Uncovering the mystery: Advancements in the treatment of polymyalgia rheumatica. HCP Live. https://www.hcplive.com/view/uncovering-the-mystery-advancements-treatment-polymyalgia-rheumatica. Published April 18, 2023. Accessed May 7, 2023.