Chronic Hypoparathyroidism Disease Profile: Initial Analysis from the Paradighm™ Natural History Global Registry

Presentation Number: OR06-4
Date of Presentation: April 4th, 2017

Steven Wai Ing*1, Bart Lyman Clarke2, Aliya Aziz Khan3, Michael Mannstadt4, Michael T. McDermott5, Rebecca Piccolo6, Michael Howard Shanik7, Tamara J. Vokes8 and John Germak9
1Ohio State University Wexner Medical Center, Columbus, OH, 2Mayo Clinic E18-A, Rochester, MN, 3McMaster University, ON, Canada, 4Massachusetts General Hospital and Harvard Medical School, Boston, MA, 5University of Colorado Hospital, Aurora, CO, 6Shire Human Genetic Therapies, Inc., Lexington, MA, 7Endocrine Associates of Long Island, Smithtown, NY, 8University of Chicago Medicine, Chicago, IL, 9Shire International GmbH, Zug, Switzerland

Abstract

PARADIGHM is a global, prospective registry (ClinicalTrials.gov NCT01922440) of patients with chronic hypoparathyroidism (HPT) managed under conditions of normal clinical practice. The aim of this registry is to provide currently unavailable information on natural history and response to therapy in this rare disease. Patients with a diagnosis of HPT ≥6 months are eligible for inclusion regardless of HPT etiology and management. Routine medical care data was entered using electronic case report forms. The short form 36 (SF-36v2) health survey was completed at baseline and follow-up by patients aged ≥18 years to assess health-related quality of life outcomes. In this initial analysis, we report the baseline-recorded data from the first 210 patients enrolled as of December 2014 from US centers. At baseline, 75% were women, mean (SD) HPT duration was 10 (11) years, age was 49 (16) years and BMI was 29.9 (7.6) kg/m2. The reported causes of HPT were surgery (73%), idiopathic (10%), genetic (9%), autoimmune (2%; all APS1 diagnosis), other (1%; congenital, velocardiofacial syndrome, natural), unknown/missing (6%). Patients’ medical histories included mood disorder (30%), arthritis (17%), chronic renal disease (6%), kidney stones (5%), fractures (5%), and hypercalciuria (4%). 88% of patients had baseline symptom data captured for the previous 6 months and 74% of these patients reported ≥1 symptom. The most common were fatigue (37%), paresthesia (25%), muscle twitching (24%), anxiety(24%), muscle weakness (15%), back pain (14%), headache (14%), brain fog (12%), and disturbances to bowel movements (12%). HPT management included oral calcium in 89% (calcium carbonate, 59%) and active vitamin D in 81% (calcitriol, 99%) of patients. 95% of patients were taking ≥1 concomitant medication (63% thyroid hormone, 5% hydrochlorothiazide, 2% psycholeptics, 1% magnesium supplements). 13% of patients had been treated with recombinant parathyroid hormone (1-84) in a clinical trial. Key laboratory mean (SD) values were PTH 10.6 (8.2) pg/mL, n=62; albumin-corrected total serum calcium 8.4 (1.1) mg/dL, n=150; 24-hour urinary calcium 291.1 (179.7) mg/24 hour, n=41; phosphate 4.6 (0.9) mg/dL, n=122; and magnesium 1.9 (0.4) mg/dL, n=81. Calcifications recorded during imaging tests were reported in 16 patients (8%; kidney (n=5), cardiovascular (n=3), brain (n=2), and other sites (n=6). Medical service utilization due to HPT in the past 12 months reported 50% of patients had 2–3 doctor’s visits and 48% had ≥1 emergency room visit. The mean summary scores (SD; range) from the SF-36 survey for physical components were 46.1 (10.9; 11.3–64.3) and mental components 48.9 (11.2; 17.6–70.3). This real world data from the first 210 patients enrolled in the prospective PARADIGHMregistry provides valuable insight into the disease variability, symptom burden, and treatment approach to HPT in the US.

 

Disclosure: SWI: Consultant, Shire, Investigator, Shire. BLC: Investigator, NPS-Shire, Advisory Group Member, NPS-Shire. AAK: Advisory Group Member, Shire. MM: Advisory Group Member, Shire. MTM: Advisory Group Member, Shire. RP: Employee, Shire. MHS: Investigator, Shire, Advisory Group Member, Shire, Speaker, Shire. TJV: Advisory Group Member, Shire. JG: Employee, Shire.