The PARADIGHM (physicians advancing disease knowledge in hypoparathyroidism) registry for patients with chronic hypoparathyroidism: study protocol and interim baseline patient characteristics

Abstract

Background: The PARADIGHM registry of adult and pediatric patients with chronic hypoparathyroidism evaluates the long-term safety and effectiveness of treatment with recombinant human parathyroid hormone, rhPTH(1-84), and describes the clinical disease course under conditions of routine clinical practice. In this first report, we detail the registry protocol and describe the baseline characteristics of two adult patient cohorts from an interim database analysis. One cohort after study entry were prescribed rhPTH(1-84), and the other cohort received conventional therapy of calcium and active vitamin D.

Methods: An observational study of patients with chronic hypoparathyroidism in North America and Europe, collecting data for ≥10 years per patient. Main outcome measures were baseline patient demographics, clinical characteristics, medications, and disease outcome variables of symptoms, biochemical parameters, and health assessments. Baseline is the enrollment assessment for all variables except biochemical measurements in patients treated with rhPTH(1-84); those measurements were the most recent value before the first rhPTH(1-84) dose. Exclusion criteria applied to the analysis of specified outcomes included pediatric patients, patients who initiated rhPTH(1-84) prior to enrollment, and those who received rhPTH(1-34). Clinically implausible biochemical outlier data were excluded.

Results: As of 30 June 2019, data of 737 patients were analyzed from 64 centers; 587 (80%) were women, mean ± SD age 49.1±16.45 years. At enrollment, symptoms reported for patients later prescribed rhPTH(1-84) (n=60) and those who received conventional therapy (n=571), respectively, included fatigue (51.7%, 40.1%), paresthesia (51.7%, 29.6%), muscle twitching (48.3%, 21.9%), and muscle cramping (41.7%, 33.8%). Mean serum total calcium, serum phosphate, creatinine, and estimated glomerular filtration rate were similar between cohorts. Health-related quality of life (HRQoL) 36-item Short Form Health Survey questionnaire scores for those later prescribed rhPTH(1-84) were generally lower than those for patients in the conventional therapy cohort.

Conclusions: At enrollment, based on symptoms and HRQoL, a greater percentage of patients subsequently prescribed rhPTH(1-84) appeared to have an increased burden of disease than those who received conventional therapy despite having normal biochemistry measurements. PARADIGHM will provide valuable real-world insights on the clinical course of hypoparathyroidism in patients treated with rhPTH(1-84) or conventional therapy in routine clinical practice.

Trial registration: EUPAS16927, NCT01922440.

Keywords: Chronic hypoparathyroidism; parathyroid hormone, patient registry; quality of life, rhPTH(1-84); symptoms.

Conflict of interest statement

NG and SH have served as an advisory board member and consultant for Shire, a Takeda company. LR has served as an advisory board member, research investigator, and speaker for Shire, a Takeda company. SWI has served as an advisory board member and research investigator for Shire, a Takeda company, and served as research investigator for Amgen Inc., Chugai Pharmaceutical Co., Ltd, Radius Health Inc., and Ultragenyx Pharmaceutical. SB and AAK have served as research investigators for Shire, a Takeda company. MLB has served as a research investigator and speaker for Shire, a Takeda company. LCH has served as a research investigator and received honoraria for advisory boards from Shire, a Takeda company, and received honoraria for advisory boards from Ascendis Pharma, Alexion Pharmaceuticals Inc., Amgen Inc., Kyowa Kirin International, and USB. PH has served as an advisory board member, consultant, research investigator, and speaker for Shire, a Takeda company. MAL, DMS, and TV have served as an advisory board member, consultant, and research investigator for Shire, a Takeda company. PZ and JG are employed by Shire Human Genetic Therapies, Inc., a Takeda company, Lexington, MA, USA. MM has served as an advisory board member, consultant, and research investigator for Shire, a Takeda company, as consultant and research investigator for Chugai Pharmaceutical Co., Ltd, and as consultant for Amolyt Pharma. CM is employed by Takeda Pharmaceuticals International AG, Zurich, Switzerland. BLC has served as consultant and research investigator for Shire, a Takeda company, and has received grant funding from Ascendis Pharma and Chugai Pharmaceutical Co., Ltd.

© 2021. The Author(s).