All 3 calcimimetic drugs – cinacalcet, etelcalcetide, and evocalcet – successfully reduce parathyroid hormone (PTH) levels to within target range in patients with secondary hyperparathyroidism (SHPT), according to new study findings. Benefits and harms vary among agents, however.

Giovanni F.M. Strippoli, MD, PhD, of the University of Bari in Bari, Italy, and colleagues conducted an updated systematic review and network meta-analysis of 36 randomized trials involving 11,247 patients with SHPT. The vast majority of patients received hemodialysis, but some trials enrolled patients on peritoneal dialysis, patients with chronic kidney disease, and kidney transplant recipients.

Etelcalcetide, cinacalcet, and evocalcet users, respectively, had 28.6, 10.3, and 5.8 greater odds of achieving  target PTH levels over a median 26 weeks compared with placebo recipients Furthermore, etelcalcetide users had 4.9- and 2.8-fold greater odds of achieving target PTH compared with evocalcet and cinacalcet users, respectively, Dr Strippoli’s team reported in the American Journal of Kidney Diseases. Parathyroidectomy appeared the most efficacious for PTH control overall, with odds of success ranging 20- to 100-fold higher compared with calcimimetics, according to results from a single trial. The surgery is not definitive therapy, however, and some patients on dialysis cannot undergo surgery on the neck.

Etelcalcetide was associated with 1.5- and 2.3-fold greater odds of hypocalcemia than cinacalcet and evocalcet, respectively. In a ranking, cinacalcet and to a lesser extent etelcalcetide caused more nausea than placebo, according to the authors. Etelcalcetide does not cross the blood-brain barrier, so the cause of the gastrointestinal effects are still unknown.


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Due to a lack of long-term data, the investigators could not sufficiently assess differences in risk for mortality, cardiovascular end points, or fractures.

“At present, the benefits of calcimimetic agents are limited to lowering serum PTH levels during short-term follow-up,” Dr Strippoli’s team wrote. “Longer-term effects of treatment on cardiovascular and bone complications are uncertain.”

In an accompanying editorial, James B. Wetmore, MD, MS, of Hennepin Healthcare Research Institute in Minneapolis, Minnesota, lauded the review:

“In conclusion, Palmer et al, in their rigorous study of all known calcimimetic trials, have provided convincing evidence that these drugs are generally highly effective at lowering PTH levels,” Dr Wetmore wrote. “They are not as effective as parathyroidectomy, but are obviously far less invasive with lower risk. However, as Palmer et al demonstrate, hypocalcemia and nausea are daunting untoward effects that pose the greatest clinical threats to routine use of these agents.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

References

Palmer SC, Mavridis D, Johnson DW, Tonelli M, Ruospo M, and Strippoli GFM. Comparative effectiveness of calcimimetic agents for secondary hyperparathyroidism in adults: a systematic review and network meta-analysis. Am J Kidney Dis. 76(3):321-330. doi:10.1053/j.ajkd.2020.02.439

Wetmore JB. Calcimimetics: a promise unfulfilled. Am J Kidney Dis. 76(3):309-310. doi:10.1053/j.ajkd.2020.03.018