Efficacy and safety of Cinacalcet on secondary hyperparathyroidism in Chinese chronic kidney disease patients receiving hemodialysis

Abstract

Introduction Secondary hyperparathyroidism (SHPT) develops in patients with chronic renal failure. Cinacalcet hydrochloride has been used successfully in U.S., Europe, and Japan in the treatment of SHPT, while maintaining serum levels of calcium and phosphorus. The efficacy and safety profile of Cinacalcet treatment vs. conventional treatments has been of great interest in clinical practice. In this recent phase III study conducted in China, efficacy and safety of a calcimimetic agent, Cinacalcet (Kyowa Hakko Kirin Co., Ltd.), were assessed for SHPT treatment in stable chronic renal disease patients on hemodialysis. Methods In this double-blind, multicenter, placebo-controlled, randomized phase III study, 238 subjects were enrolled in 12 centers and randomly divided into a Cinacalcet group and a placebo group. The percentage of patients achieving a serum parathyroid hormone (PTH) level ≤250 pg/mL was the primary efficacy end point. Serum calcium and phosphorus levels were measured. Adverse events and serious adverse events were recorded, and causal analysis performed. Findings In primary analysis, 25.4% of the Cinacalcet group and 3.5% of the placebo group achieved the primary end point (PTH ≤250 pg/mL). Calcium and phosphorus levels and calcium-phosphorus product were lower in the Cinacalcet group compared with the placebo group. Eleven serious adverse events were reported and considered to be not related to study drugs. Mild to moderate hypocalcemia and reduced calcium levels were reported and considered to be Cinacalcet related. Discussion This phase III study demonstrated that Cinacalcet is effective and well tolerated in treating SHPT in Chinese chronic kidney disease patients on hemodialysis, and in a patient population with much higher baseline PTH levels.

Targeted surgical parathyroidectomy in end‐stage renal disease patients and long‐term metabolic control: A single‐center experience in the current era

“…7 All these measures lead to an excessive utilization of phosphorus binders, pill burden, gastrointestinal side effects and cost. [8][9][10] Calcium-sensing receptor (CSR) agonists (e.g., cinacalcet [CNC]) lower PTH levels without escalating the calcium-phosphorus product, [11][12][13] albeit only to a limited degree; additionally, they are expensive and their impact on bone fractures and survival remains unclear. 14 An alternative approach to the escalating pill burden of expensive medication is the timely consideration of surgical parathyroidectomy (PTX), historically involving the removal of 3 1 = 2 or all 4 glands and autotransplanting some of the removed tissues.…”

Cinacalcet for Treatment of Chronic Kidney Disease-Mineral and Bone Disorder: A Meta-Analysis of Randomized Controlled Trials

“…Fifty-six articles were retrieved for detailed evaluation, of which 24 RCTs with 10,031 participants fulfilled eligibility criteria, and were included in the meta-analysis (Fig. 1) [8-10, 19-39]. …”

“…Five studies were conducted in Asia [10, 27, 30, 34, 39], 1 study in Europe [9], 6 studies in America [19, 20, 22, 24, 29, 38], and 12 in multiple countries [8, 21, 23, 25, 26, 28, 31-33, 35-37]. There were 15 trials comparing cinacalcet to placebo [8, 19-28, 30, 31, 33, 39], 3 trials comparing cinacalcet to standard treatment (i.e., a phosphate binder and/or vitamin D compound) [9, 10, 38], and 6 trials comparing cinacalcet and a vitamin D compound to a vitamin D compound alone [29, 32, 34-37]. Twenty-one trials involved hemodialysis patients [8, 10, 19-24, 26-33, 35-39], 1 trial involved peritoneal dialysis patients [34], and 2 trials enrolled patients on a combination of hemodialysis and peritoneal dialysis [9, 25].…”

“…There were 15 trials comparing cinacalcet to placebo [8, 19-28, 30, 31, 33, 39], 3 trials comparing cinacalcet to standard treatment (i.e., a phosphate binder and/or vitamin D compound) [9, 10, 38], and 6 trials comparing cinacalcet and a vitamin D compound to a vitamin D compound alone [29, 32, 34-37]. Twenty-one trials involved hemodialysis patients [8, 10, 19-24, 26-33, 35-39], 1 trial involved peritoneal dialysis patients [34], and 2 trials enrolled patients on a combination of hemodialysis and peritoneal dialysis [9, 25]. The mean age ranged from 46 to 65 years, and duration of treatment spanned from 7 days to 12 months.…”

A Bayesian network analysis on comparative efficacy of treatment strategies for dialysis patients with secondary hyperparathyroidism

“…Moe et al, In the present analysis, 3,552 patients were males (65.7%). Among the 20 trials, 14 (70.0%) (6,11,13,20,22,(24)(25)(26)(27)(29)(30)(31)(32)34) had detailed records on withdrawals and dropouts and 14 (70.0%) (6,11,13,20,22,(24)(25)(26)(27)(29)(30)(31)(32)34) had Jadad scores ≥3 points. A total of 17 (85.0%) (6,10,13,20-22,24-34) t r ials were repor ted as multicenter studies and 10 (50.0%) (6,20,24-28,31-33) were multinational.…”