(286) Real-world effectiveness of interleukin-6 receptor inhibitors compared to methotrexate in steroid-refractory frail patients with polymyalgia rheumatica

Background: : A previous post hoc analysis of frail (defined by claims-based frailty index (CFI) ≥0.2) patients with PMR on second-line (2L)- and 3L-treatment found IL-6 receptor inhibitors (IL-6Ri) initiators were >twice (HR 2.32) as likely to discontinue GC vs. conventional synthetic immunomodulators (csIM: methotrexate [MTX], azathioprine, and leflunomide) initiators, ~double the effect size in overall cohort (HR 1.28). This study builds on prior analysis by comparing IL-6Ri to MTX as 2L-treatment, with frailty (CFI ≥0.25) as inclusion criteria and propensity score (PS)-match covariate, minimizing pre-frailty patient inclusion.

Objective: : To compare effectiveness of IL-6Ri to MTX in GC-refractory frail patients with PMR.

Methods: : This observational retrospective comparative cohort study used US Medicare claims data (10/2016–12/2022). Inclusions: ≥50 years with ≥1 inpatient/≥2 outpatient PMR diagnosis codes ≥30 days apart, ≤25 mg prednisone equivalent dose (PED), CFI ≥0.25, IL-6Ri/MTX initiation (index), no prior IL-6Ri/csIM and continuous enrollment ≥180 days prior (baseline) to 1 day. Exclusions: patients initiating IL-6Ri and csIM on same day and patients with seropositive RA, other systemic rheumatic disease (except giant cell arteritis), organ transplant, multiple sclerosis or active malignancy treatment during baseline. Patients were direct matched on select characteristics, then PS matched on demographic, treatment and clinical characteristics. Outcomes were primary: time to GC discontinuation (>60-day gap), key secondary: time to minimal (≤2 mg/day PED) or no GC.

Results: : Overall, 29% and 18.3% of patients in IL-6Ri and MTX groups, respectively, had CFI ≥0.25. Of these, 86 matched pairs with 2L-treatment with no prior IL-6Ri were identified. Patient characteristics were balanced, though mean time from first PMR diagnosis to index date (1025 vs. 799 days) and seronegative RA occurrence (32.6% vs. 22.1%) were higher in IL-6Ri vs. MTX groups. About 1/4th of the patients were moderately-severely frail (CFI ≥0.35, 20.9% vs. 26.7%). Time to GC discontinuation and time to minimal or no GC up to 1 year were significantly shorter for IL-6Ri vs. MTX groups (HR [95% CI] 1.75 [1.05, 2.93]; p=0.033) and (HR [95% CI] 1.86 [1.15, 3.00]; p=0.011), respectively.

Conclusions: : IL-6Ri therapy enabled rapid GC discontinuation or achieving minimal GC in frail patients with PMR, suggesting that this vulnerable population may benefit more from IL-6Ri vs. MTX.

Sponsorship:: Foundation for Advancing Science, Technology, Education and Research, funded by Sanofi and Regeneron.