Evaluating Real-World Use of Cinacalcet and Biochemical Response to Therapy in US Hemodialysis Patients

Abstract

Background/Aims: Data describing real-world use and effectiveness of cinacalcet are limited. We aimed to characterize predictors of treatment and changes in secondary hyperparathyroidism (SHPT) biochemistry after cinacalcet initiation. Methods: We studied 25,250 in-center hemodialysis patients from a large dialysis provider, alive through November 2004, with no prior cinacalcet prescription. Patients were followed until initiation of cinacalcet, censoring, death, or July 31, 2007. Initiators were further followed for dose titration and discontinuation. Predictors of these events were evaluated using Cox proportional hazards modeling. Biochemical parameters and other SHPT medication use were compared between baseline, pre-initiation, and post-initiation time points. Results: Over an average of 1.25 years of follow-up, 30% of patients initiated cinacalcet therapy. Between baseline and initiation (mean of 386 days), parathyroid hormone (PTH) and phosphorus levels increased 78 and 7%, respectively, in these patients. After adjustment, cinacalcet initiation was associated with higher SHPT severity, younger age, African-American race, higher phosphorus levels, and more comorbidity. Within 1 month of initiation, median PTH was reduced by 15-30% and phosphorus by 3-5%. Reductions were sustained or increased over 12 months, depending on initiating PTH level and whether dose up-titration occurred. Discontinuation was common, although many patients reinitiated. Conclusions: A substantial proportion of patients experienced SHPT progression and initiated cinacalcet treatment. Reductions in biochemistry varied by disease severity and whether doses were titrated.

Rates and Outcomes of Parathyroidectomy for Secondary Hyperparathyroidism in the United States

“…The latter is plausible in that the EVOLVE Trial protocol specified titration of cinacalcet to a maximum daily dose of 180 mg during the first 20 weeks of the trial. Observational studies in which the dose of cinacalcet was recorded suggests that relatively few patients are titrated to doses .60 or 90 mg daily (7,20,21). The relative frequency of gastrointestinal side effects seen with cinacalcet therapy-principally nausea and vomitingmay be limiting the observed benefit, at least vis-à-vis parathyroidectomy-a potential example of efficacy versus effectiveness.…”

Variability in Cinacalcet Prescription across US Hemodialysis Facilities

“…Etelcalcetide was approved by the US Food and Drug Administration in 2017 (15), and thus realworld utilization data are not yet suitable for analysis. Previous studies have identified patient characteristics that are associated with cinacalcet use; examples include more severe secondary hyperparathyroidism (higher PTH, calcium, and phosphate levels), longer dialysis vintage, younger age, black race, female sex, and comorbidities (16)(17)(18). However, there are no studies describing the distribution of calcimimetic use across facilities or assessing the extent to which patient and facility factors contribute to facility variation in calcimimetic use.…”

Management of serum calcium reductions among patients on hemodialysis following cinacalcet initiation

“…[9][10][11] Interventional trials and noninterventional studies have shown that serum calcium reductions following cinacalcet initiation are common but typically occur without associated clinical manifestations. [12][13][14][15][16][17][18] However, there have been no large-scale investigations into the frequency, type, and effectiveness of clinical therapeutic intervention for patients who experience cinacalcet-induced calcium reductions.…”