SO034CINACALCET DISCONTINUATION AND ITS PREDICTORS IN HEMODIALYSIS PATIENTS: RESULTS FROM 7 EUROPEAN COUNTRIES

Abstract

INTRODUCTION AND AIMS: High parathyroid hormone (PTH) levels have been associated with adverse outcomes in hemodialysis (HD) patients. PTH levels in Europe have increased during the last two decades despite increased use of vitamin D analogs and cinacalcet, an oral calcimimetic indicated for secondary hyperparathyroidism (SHPT) in patients on dialysis. Rates and predictors of cinacalcet discontinuation in the US have been published, but results for Europe are lacking. METHODS: Using monthly prescription (Rx) data from 613 patients in the international Dialysis Outcomes and Practice Patterns Study (DOPPS) phases 4 and 5 (2008-2015), we estimated cumulative incidence functions (CIFs) and predictors of cinacalcet discontinuation for HD patients in 7 European countries (Belgium, France, Germany, Italy, Spain, Sweden, and the United Kingdom). Eligible patients began a cinacalcet Rx after no cinacalcet Rx in the prior 3 months. Patients with prior parathyroidectomy were excluded. We used last-observation-carried-forward to impute single months with missing cinacalcet Rx data. Patients were censored at departure from DOPPS (e.g. due to death, transplant, or transfer) or if consecutive months with missing data were encountered. We used univariate Cox regression to identify predictors of discontinuation. RESULTS: 172 patients (28%) discontinued cinacalcet. CIF values at 6, 12, and 22 months (maximum follow-up) were 21%, 35%, and 45%, respectively. CIF values by country were 17-33% at 6 months and 21-46% at 12 months. Higher discontinuation was observed in patients with history of cardiovascular disease (hazard ratio [HR]: 1.46; 95% confidence interval [CI]: 1.07-2.00) and cerebrovascular disease (HR: 1.52; CI: 1.02-2.27), but not with age (HR: 1.05 per 10 years older; CI: 0.95-1.15), female sex (HR: 1.03 vs male; CI: 0.77-1.38), or years with end-stage renal disease (HR: 0.99 per 1 year longer; CI: 0.96-1.01). In time-dependent analyses, higher cinacalcet discontinuation was associated with both high and low levels of PTH and calcium (Figure) but not serum phosphorus (HR: 1.00 per 0.5 mg/dl higher; CI: 0.95-1.05). CONCLUSIONS: Cinacalcet discontinuation is common in European countries, occurring in 35% of patients within a year from initiation. CIF values in our study are lower compared to prior reports in the US using administrative claims data but similar to those using Rx data consistent with the discontinuation definition in these analyses. As anticipated, discontinuation was associated with lower PTH and calcium levels, which are both direct effects of cinacalcet therapy. Discontinuation was also more likely at higher PTH levels, perhaps reflecting poor compliance to cinacalcet that was not captured in our data. Given the recent increases in PTH levels, there is a need to improve management of SHPT in European HD patients. One important aspect is to optimize prescription and discontinuation patterns of available drugs, including cinacalcet.