Similarities in Postsurgical Vs Nonsurgical Patients with Hypoparathyroidism: Post Hoc Analysis from Recombinant Human Parathyroid Hormone (rhPTH[1-84], Parathyroid Hormone rDNA) Replace Study

Presentation Number: MON 343
Date of Presentation: April 3rd, 2017

Michael Mannstadt*1, Maria Luisa Brandi2, John P. Bilezikian3, Bart Lyman Clarke4, William D. Fraser5, Alan Krasner6, Hjalmar Lagast7, Hak-Myung Lee6, Lars Rejnmark8, Dolores M. Shoback9 and Tamara J. Vokes10
1Massachusetts General Hospital and Harvard Medical School, Boston, MA, 2University of Florence, Florence, Italy, 3College of Physicians and Surgeons, Columbia University, New York, NY, 4Mayo Clinic E18-A, Rochester, MN, 5University of East Anglia, Norwich, United Kingdom, 6Shire Human Genetic Therapies, Inc., Lexington, MA, 7Formerly NPS Pharmaceuticals, Inc. *A wholly owned indirect subsidiary of Shire, Lexington, MA, 8Aarhus University Hospital, Aarhus, Denmark, 9SF Department of Veterans Affairs Medical Center, University of California, San Francisco, CA, 10University of Chicago Medicine, Chicago, IL

Abstract

Hypoparathyroidism, a rare disorder characterized by absent or low levels of parathyroid hormone (PTH), often results from thyroid surgery. However, nonsurgical etiologies are present in >10% of patients. Data about this group of patients are limited. In this post hoc REPLACE (NCT00732615, EudraCT2008-005063-34) analysis, baseline characteristics and response to 50–100 µg/day rhPTH(1-84) in patients with postsurgical or nonsurgical hypoparathyroidism were evaluated. Demographic and baseline characteristics were compared between groups with chi-square tests for categorical variables and one-way analysis of variance with effect for continuous variables. Responders were defined as patients whose need for conventional treatment with oral calcium and active vitamin D was reduced by ≥50% while maintaining serum calcium at 2.00–2.25 mmol/L. Of 124 randomized patients, 89 (72%) had postsurgical and 35 (28%) had nonsurgical hypoparathyroidism. Interestingly per criteria in the 2015 ESE guidelines, ≥80% of patients within each subgroup were not well controlled pre-rhPTH(1-84) even after optimization with conventional treatment. Overall, there were more similarities than differences between the 2 groups. The only significant differences between groups were male gender (9/89 [10%] vs 17/35 [49%]; P<0.0001), age at onset (49.1 vs 42.9 years, P=0.014), and time since diagnosis (12.1 vs 17.5 years, P=0.008). At baseline, mean (SD) serum intact PTH levels were 0.8 (0.9) and 0.4 (0.5) pmol/L in the postsurgical and nonsurgical groups, respectively; healthy adult range is 1.5-7.6 pmol/L. In the postsurgical group, the 58% responder rate with rhPTH(1-84) (35/60) was significantly higher than the 3% rate with placebo (1/29; P<0.001). In the nonsurgical group, the 46% responder rate in the rhPTH(1-84) group (11/24) was numerically higher than the 0% placebo group rate (0/11; P=0.007). This post hoc analysis did not suggest any differences in response to PTH(1-84) based on etiology of hypoparathyroidism.

 

Disclosure: MM: Advisory Group Member, NPS-Shire. MLB: Speaker Bureau Member, NPS-Shire, Investigator, NPS-Shire. JPB: Investigator, NPS-Shire, Advisory Group Member, NPS-Shire. BLC: Investigator, NPS-Shire, Advisory Group Member, NPS-Shire. WDF: Advisory Group Member, NPS-Shire, Speaker Bureau Member, NPS-Shire. AK: Employee, Shire. HL: Employee, NPS-Shire. HML: Employee, Shire. LR: Investigator, NPS-Shire, Advisory Group Member, NPS-Shire. DMS: Investigator, NPS-Shire, Advisory Group Member, NPS-Shire. TJV: Advisory Group Member, NPS-Shire.