Dynamics of cinacalcet use and biochemical control in hemodialysis patients: a retrospective New-user cohort design

BMC Nephrology

M. Alan Brookhart¹  Abhijit V. Kshirsagar²  Brian D. Bradbury⁴  Susan V. Yue⁴  Thy P. Do⁴  Paul J. Dluzniewski⁴  B. Diane Reams³ 

[1] Department of Epidemiology, UNC Gillings School of Global Public Health, UNC Chapel Hill, Chapel Hill, NC, USA;University of North Carolina Kidney Center, UNC School of Medicine, Chapel Hill, NC, USA;Cecil G. Sheps Center for Health Services Research, University of North Carolina, Chapel Hill, NC, USA;Amgen, Inc, Thousand Oaks, CA, USA

关键词: Hemodialysis;    Secondary hyperparathyroidism;    Cinacalcet;   

Others  :  1231085
DOI  :  10.1186/s12882-015-0174-6

 received in 2015-05-26, accepted in 2015-10-19,  发布年份 2015

【 摘 要 】

Background

Cinacalcet is used to treat secondary hyperparathyroidism among hemodialysis patients. Large-scale epidemiologic studies describing patterns of cinacalcet use, effects on parathyroid hormone (PTH), calcium, and phosphorous levels, and predictors of discontinuation have not been previously reported.

Methods

This retrospective cohort study used a clinical database of a large U.S. dialysis provider (2007–2010) merged with administrative data from the United States Renal Data System. Among new users of cinacalcet with Medicare coverage, trends in PTH, calcium, and phosphorus were measured in 30-day intervals following cinacalcet initiation.

Results

Seventeen thousand seven hundred sixty-three eligible initiators contributed 111,047 30-day follow-up intervals. Of these, 56 % discontinued cinacalcet by month 4. Of those discontinuing, 76.3 % reinitiated. Mean values of PTH, calcium, and phosphorus decreased to recommended levels within 4 months following initiation. Proximal PTH levels <150 pg/mL were associated with discontinuation: HR = 1.23 (95 % CI: 1.12, 1.36), whereas low calcium (<7.5 mg/dL) was suggestive of an association, HR = 1.09 (95 % CI 0.91, 1.32). Being in the Part D gap period increased discontinuation risk: HR = 1.09 (95 % CI: 1.03, 1.16). Low-income subsidy status decreased discontinuation risk: HR = 0.77 (95 % CI 0.69, 0.86). Predictors of reinitiation included low-income subsidy, HR = 1.32 (95 % CI 1.22, 1.43); higher albumin level, HR = 1.23 (95 % CI 1.10, 1.36) and higher calcium level, HR = 1.26 (95 % CI 1.19, 1.33).

Conclusions

Substantial and expected declines in laboratory values occurred following cinacalcet initiation. Early discontinuation and reinitiation of cinacalcet were common and may have occurred for clinical and economic reasons.

【 授权许可】

   
2015 Reams et al.

【 图 表 】

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【 参考文献 】

• [1]Cunningham J. Management of secondary hyperparathyroidism. Ther Apher Dial. 2005; 9 Suppl 1:S35-40.
• [2]Goodman WG, Quarles LD. Development and progression of secondary hyperparathyroidism in chronic kidney disease: lessons from molecular genetics. Kidney Int. 2008; 74(3):276-88.
• [3]Cunningham J, Locatelli F, Rodriguez M. Secondary hyperparathyroidism: pathogenesis, disease progression, and therapeutic options. Clin J Am Soc Nephrol. 2011; 6(4):913-21.
• [4]KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral Bone Disorder (CKD-MBD). Kidney Int Suppl. 2009; 113:S1-130.
• [5]Block GA, Martin KJ, de Francisco AL, Turner SA, Avram MM, Suranyi MG et al.. Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis. N Engl J Med. 2004; 350(15):1516-25.
• [6]Lindberg JS, Culleton B, Wong G, Borah MF, Clark RV, Shapiro WB et al.. Cinacalcet HCl, an oral calcimimetic agent for the treatment of secondary hyperparathyroidism in hemodialysis and peritoneal dialysis: a randomized, double-blind, multicenter study. J Am Soc Nephrol. 2005; 16(3):800-7.
• [7]Kilpatrick RD, Newsome BB, Zaun D, Liu J, Solid CA, Nieman K et al.. Evaluating real-world use of cinacalcet and biochemical response to therapy in US hemodialysis patients. Am J Nephrol. 2013; 37(4):389-98.
• [8]Smrzova J, Urbanek T. Cinacalcet - clinical and laboratory effectiveness, concomitant treatment patterns and treatment cost: could we do better and how? Kidney Blood Press Res. 2010; 33(5):333-42.
• [9]Urena P, Jacobson SH, Zitt E, Vervloet M, Malberti F, Ashman N et al.. Cinacalcet and achievement of the NKF/K-DOQI recommended target values for bone and mineral metabolism in real-world clinical practice--the ECHO observational study. Nephrol Dial Transplant. 2009; 24(9):2852-9.
• [10]Gincherman Y, Moloney K, McKee C, Coyne DW. Assessment of adherence to cinacalcet by prescription refill rates in hemodialysis patients. Hemodial Int. 2010; 14(1):68-72.
• [11]Lee A, Song X, Khan I, Belozeroff V, Goodman W, Fulcher N et al.. Association of cinacalcet adherence and costs in patients on dialysis. J Med Econ. 2011; 14(6):798-804.
• [12]Pruijm M, Teta D, Halabi G, Wuerzner G, Santschi V, Burnier M. Improvement in secondary hyperparathyroidism due to drug adherence monitoring in dialysis patients. Clin Nephrol. 2009; 72(3):199-205.
• [13]Strippoli GF, Palmer S, Tong A, Elder G, Messa P, Craig JC. Meta-analysis of biochemical and patient-level effects of calcimimetic therapy. Am J Kidney Dis. 2006; 47(5):715-26.
• [14]Ray WA. Evaluating medication effects outside of clinical trials: new-user designs. Am J Epidemiol. 2003; 158(9):915-20.
• [15]R: A Language and Environment for Statistical Computing. In. Vienna, Austria: R Foundation for Statistical Computing; 2014.
• [16]Newsome BB, Kilpatrick RD, Liu J, Zaun D, Solid CA, Nieman K et al.. Racial differences in clinical use of cinacalcet in a large population of hemodialysis patients. Am J Nephrol. 2013; 38(2):104-14.
• [17]Schmid H, Hartmann B, Schiffl H. Adherence to prescribed oral medication in adult patients undergoing chronic hemodialysis: a critical review of the literature. Eur J Med Res. 2009; 14(5):185-90. BioMed Central Full Text
• [18]Investigators ET, Chertow GM, Block GA, Correa-Rotter R, Drueke TB, Floege J et al.. Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis. N Engl J Med. 2012; 367(26):2482-94.
• [19]Park H, Rascati KL, Lawson KA, Barner JC, Richards KM, Malone DC. Adherence and persistence to prescribed medication therapy among Medicare part D beneficiaries on dialysis: comparisons of benefit type and benefit phase. J Manag Care Pharm. 2014; 20(8):862-76.
• [20]Chiu YW, Teitelbaum I, Misra M, de Leon EM, Adzize T, Mehrotra R. Pill burden, adherence, hyperphosphatemia, and quality of life in maintenance dialysis patients. Clin J Am Soc Nephrol. 2009; 4(6):1089-96.
• [21]Manley HJ, Garvin CG, Drayer DK, Reid GM, Bender WL, Neufeld TK et al.. Medication prescribing patterns in ambulatory haemodialysis patients: comparisons of USRDS to a large not-for-profit dialysis provider. Nephrol Dial Transplant. 2004; 19(7):1842-8.
• [22]Li X, Sturmer T, Brookhart MA. Evidence of sample Use among New users of statins: implications for pharmacoepidemiology. Med Care. 2014.
• [23]Lauffenburger JC, Balasubramanian A, Farley JF, Critchlow CW, O’Malley CD, Roth MT et al.. Completeness of prescription information in US commercial claims databases. Pharmacoepidemiol Drug Saf. 2013; 22(8):899-906.
• [24]Brouwer ES, Napravnik S, Eron Jr JJ, Simpson Jr RJ, Brookhart MA, Stalzer B, et al. Validation of medicaid claims-based diagnosis of myocardial infarction using an HIV clinical cohort. Med Care. 2013.