FC 078REAL-WORLD EFFECTIVENESS OF ETELCALCETIDE VS. CINACALCET IN US HEMODIALYSIS PATIENTS: A FACILITY CALCIMIMETIC PREFERENCE APPROACH
Authors: Karaboyas Angelo , Muenz Daniel , Hwang Yunji , Goodman William , Cheng Sunfa , Desai Pooja , Fox Kathleen , Robinson Bruce , Pisoni Ronald 
Published: May 2021

Abstract

Background and Aims
Calcimimetic therapy, including oral cinacalcet and intravenous (IV) etelcalcetide, is often used to control parathyroid hormone (PTH) levels in hemodialysis (HD) patients. In a head-to-head clinical trial, etelcalcetide was superior to cinacalcet on PTH reduction. Given that oral administration of cinacalcet is susceptible to challenges of self-management and adherence, etelcalcetide may be even more effective in the real-world setting. To limit confounding by indication, we used a facility calcimimetic preference approach to investigate the comparative effectiveness of etelcalcetide vs. cinacalcet by estimating effects on PTH and other mineral and bone disorder (MBD) markers in a cohort of US HD patients.

Method
We used data from the US Dialysis Outcomes and Practice Patterns Study (US-DOPPS), a prospective cohort study of in-center HD patients. During a 6-month run-in period from March to August 2019, we evaluated facility calcimimetic preference by calculating the proportion of calcimimetic users in each facility who were prescribed etelcalcetide (vs. cinacalcet). Among patients with any prescription for a calcimimetic during the 6-month run-in period, we evaluated MBD marker outcomes (PTH, albumin-corrected serum calcium [Ca], serum phosphorus [P]), averaged over the subsequent 6 months, from September 2019 to February 2020. We compared HD facilities that treated &gt;75% of calcimimetic users with etelcalcetide (“Etel-first”) vs. those that treated &gt;75% of calcimimetic users with cinacalcet (“Cina-first”). Linear regression was used to model each continuous outcome. Modified Poisson regression was used to estimate the prevalence ratio (PR) of each MBD marker being out of target (PTH &gt;600 pg/mL, Ca &lt;8.4 mg/dL, P &gt;5.5 mg/dL). All models were adjusted for patient-level and facility-level confounders and accounted for facility clustering using GEE.

Results
We excluded 38 HD facilities with little-to-no calcimimetic use (&lt;10% use or &lt;5 total users) because calcimimetic preference could not be reliably defined, and 44 HD facilities with no clear calcimimetic preference (25-75% etelcalcetide use among calcimimetic users). The analysis included 2156 calcimimetic users: 969 patients from 45 Etel-first facilities and 1187 patients from 67 Cina-first facilities. In Etel-first (vs. Cina-first) HD facilities, the mean difference in PTH levels (primary outcome) was -99 pg/mL (95% CI: -179, -19) and the prevalence of PTH &gt;600 was lower (PR=0.75; 95% CI: 0.60, 0.94) in adjusted models. The adjusted mean levels of serum Ca and serum P (secondary outcomes) were slightly lower in Etel-first (vs. Cina-first) facilities [Table 1].

Conclusion
To our knowledge, this is the first large-scale comparison of IV etelcalcetide with oral cinacalcet in the real-world setting. Our unique approach resembles a natural experiment by leveraging practice variation across the US and isolating HD facilities with a clear preference for one calcimimetic. Thus, the prescribed calcimimetic type for included patients was more likely determined by facility preference than biased by patient indication. Our results indicate better PTH control (mean levels ∼100 pg/mL lower) in US HD facilities using etelcalcetide (vs. cinacalcet) as the primary calcimimetic therapy. Further research is needed to investigate the degree to which the greater real-world effectiveness of IV etelcalcetide (vs. oral cinacalcet) may be driven by adherence to the prescribed therapy, and how clinical outcomes may be affected.