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Comparative Effectiveness of Calcimimetic Agents for Secondary Hyperparathyroidism in Adults: A Systematic Review and Network Meta-analysis.
Am J Kidney Dis. 2020 09; 76(3):321-330.AJ

Abstract

RATIONALE & OBJECTIVE

Comparative benefits and harms of calcimimetic agents used for the treatment of secondary hyperparathyroidism have not been well characterized. We sought to compare the effectiveness of 3 calcimimetic agents using published data.

STUDY DESIGN

Systematic review of randomized controlled trials and network meta-analysis.

SETTING & STUDY POPULATION

Adults with chronic kidney disease enrolled in a clinical trial of a calcimetic agent.

SEARCH STRATEGY & SOURCES

MEDLINE, EMBASE, CENTRAL (from February 7, 2013, to November 21, 2019), and a published meta-analysis.

DATA EXTRACTION

Two reviewers independently extracted the study data, assessed risk of bias, and rated evidence certainty using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria.

ANALYTICAL APPROACH

Frequentist network meta-analysis was conducted. The primary review outcomes were achievement of a target reduction in serum parathyroid hormone (PTH) levels and hypocalcemia. Additional outcomes were nausea, vomiting, serious adverse events, all-cause mortality, cardiovascular mortality, heart failure, and fracture.

RESULTS

36 trials (11,247 participants) were included. All except 4 trials involved dialysis patients. Median follow-up was 26 weeks (range, 1 week to 21.2 months). Compared with placebo, calcimimetic agents had higher odds of achieving target PTH levels with high or moderate certainty. Etelcalcetide had the highest odds of achieving a PTH target compared with evocalcet (OR, 4.93; 95% CI, 1.33-18.2) and cinacalcet (OR, 2.78; 95% CI, 1.19-6.67). Etelcalcetide appeared to cause more hypocalcemia than cinacalcet and evocalcet. Cinacalcet and to a lesser extent etelcalcetide appeared to cause more nausea than placebo. Differences in risk for mortality, cardiovascular end points, or fractures across calcimimetic agents could not be discerned with sufficient certainty.

LIMITATIONS

Lack of longer-term data; heterogeneous end point definitions.

CONCLUSIONS

Evidence of the benefits of calcimimetic therapy is limited to short-term assessment of a putative surrogate outcome (serum PTH). Although etelcalcetide was associated with the largest reduction in PTH levels, side-effect profiles differed across the 3 calcimimetic agents, making it not possible to identify 1 preferred agent.

Authors+Show Affiliations

University of Otago Christchurch, Christchurch, New Zealand.Department of Primary Education, University of Ioannina, Greece; Paris Descartes University, Paris, France.University of Queensland at the Princess Alexandra Hospital, Queensland, Australia.Cumming School of Medicine, University of Calgary, Calgary, Canada.Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy.Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy; Sydney School of Public Health, The University of Sydney, NSW, Australia. Electronic address: gfmstrippoli@gmail.com.

Pub Type(s)

Comparative Study
Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Systematic Review

Language

eng

PubMed ID

32475604

Citation

Palmer, Suetonia C., et al. "Comparative Effectiveness of Calcimimetic Agents for Secondary Hyperparathyroidism in Adults: a Systematic Review and Network Meta-analysis." American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, vol. 76, no. 3, 2020, pp. 321-330.
Palmer SC, Mavridis D, Johnson DW, et al. Comparative Effectiveness of Calcimimetic Agents for Secondary Hyperparathyroidism in Adults: A Systematic Review and Network Meta-analysis. Am J Kidney Dis. 2020;76(3):321-330.
Palmer, S. C., Mavridis, D., Johnson, D. W., Tonelli, M., Ruospo, M., & Strippoli, G. F. M. (2020). Comparative Effectiveness of Calcimimetic Agents for Secondary Hyperparathyroidism in Adults: A Systematic Review and Network Meta-analysis. American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, 76(3), 321-330. https://doi.org/10.1053/j.ajkd.2020.02.439
Palmer SC, et al. Comparative Effectiveness of Calcimimetic Agents for Secondary Hyperparathyroidism in Adults: a Systematic Review and Network Meta-analysis. Am J Kidney Dis. 2020;76(3):321-330. PubMed PMID: 32475604.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparative Effectiveness of Calcimimetic Agents for Secondary Hyperparathyroidism in Adults: A Systematic Review and Network Meta-analysis. AU - Palmer,Suetonia C, AU - Mavridis,Dimitris, AU - Johnson,David W, AU - Tonelli,Marcello, AU - Ruospo,Marinella, AU - Strippoli,Giovanni F M, Y1 - 2020/05/28/ PY - 2019/08/18/received PY - 2020/02/13/accepted PY - 2020/6/2/pubmed PY - 2020/10/9/medline PY - 2020/6/2/entrez KW - Calcimimetic KW - PTH target KW - cardiovascular disease (CVD) KW - cinacalcet KW - dialysis KW - end-stage renal disease (ESRD) KW - etelcalcetide KW - evidence-based medicine (EBM) KW - evocalcet KW - fracture KW - gastrointestinal side effects KW - hypocalcemia KW - mortality KW - nausea KW - network meta-analysis KW - parathyroid hormone (PTH) KW - randomized controlled trials (RCTs) KW - renal failure KW - secondary hyperparathyroidism KW - systematic review KW - vomiting SP - 321 EP - 330 JF - American journal of kidney diseases : the official journal of the National Kidney Foundation JO - Am J Kidney Dis VL - 76 IS - 3 N2 - RATIONALE & OBJECTIVE: Comparative benefits and harms of calcimimetic agents used for the treatment of secondary hyperparathyroidism have not been well characterized. We sought to compare the effectiveness of 3 calcimimetic agents using published data. STUDY DESIGN: Systematic review of randomized controlled trials and network meta-analysis. SETTING & STUDY POPULATION: Adults with chronic kidney disease enrolled in a clinical trial of a calcimetic agent. SEARCH STRATEGY & SOURCES: MEDLINE, EMBASE, CENTRAL (from February 7, 2013, to November 21, 2019), and a published meta-analysis. DATA EXTRACTION: Two reviewers independently extracted the study data, assessed risk of bias, and rated evidence certainty using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. ANALYTICAL APPROACH: Frequentist network meta-analysis was conducted. The primary review outcomes were achievement of a target reduction in serum parathyroid hormone (PTH) levels and hypocalcemia. Additional outcomes were nausea, vomiting, serious adverse events, all-cause mortality, cardiovascular mortality, heart failure, and fracture. RESULTS: 36 trials (11,247 participants) were included. All except 4 trials involved dialysis patients. Median follow-up was 26 weeks (range, 1 week to 21.2 months). Compared with placebo, calcimimetic agents had higher odds of achieving target PTH levels with high or moderate certainty. Etelcalcetide had the highest odds of achieving a PTH target compared with evocalcet (OR, 4.93; 95% CI, 1.33-18.2) and cinacalcet (OR, 2.78; 95% CI, 1.19-6.67). Etelcalcetide appeared to cause more hypocalcemia than cinacalcet and evocalcet. Cinacalcet and to a lesser extent etelcalcetide appeared to cause more nausea than placebo. Differences in risk for mortality, cardiovascular end points, or fractures across calcimimetic agents could not be discerned with sufficient certainty. LIMITATIONS: Lack of longer-term data; heterogeneous end point definitions. CONCLUSIONS: Evidence of the benefits of calcimimetic therapy is limited to short-term assessment of a putative surrogate outcome (serum PTH). Although etelcalcetide was associated with the largest reduction in PTH levels, side-effect profiles differed across the 3 calcimimetic agents, making it not possible to identify 1 preferred agent. SN - 1523-6838 UR - https://wwww.unboundmedicine.com/medline/citation/32475604/Comparative_Effectiveness_of_Calcimimetic_Agents_for_Secondary_Hyperparathyroidism_in_Adults:_A_Systematic_Review_and_Network_Meta_analysis_ DB - PRIME DP - Unbound Medicine ER -