ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2018) 56 GP178 | DOI: 10.1530/endoabs.56.GP178

The global, prospective, observational PARADIGHM™ registry for patients with chronic hypoparathyroidism was expanded to capture recombinant human parathyroid hormone, rhPTH(1-84), use under routine clinical care

Bart L Clarke1, Lars Rejnmark2, Maria Luisa Brandi3, John Germak4, Stefanie Hahner5, Pascal Houillier6, Olle Kampe7, Christian Kasperk8, Aliya Khan9, Michael A Levine10, Michael Mannstadt11, Rebecca Piccolo12, Dolores M Shoback13, Tamara J Vokes14 & Neil Gittoes15

1Mayo Clinic, Rochester, Minnesota, USA; 2Aarhus University Hospital, Aarhus, Denmark; 3University Hospital of Careggi, Florence, Italy; 4Shire International GmbH, Zug, Switzerland; 5University of Würzburg, Würzburg, Germany; 6Georges Pompidou Hospital and Paris Descartes University, Paris, France; 7Karolinska Institutet, Stockholm, Sweden; 8Medical University, Heidelberg, Germany; 9McMaster University, Hamilton, Ontario, Canada; 10Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; 11Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; 12Shire Human Genetic Therapies, Inc., Lexington, Massachusetts, USA; 13SF Department of Veterans Affairs Medical Center, University of California, San Francisco, California, USA; 14University of Chicago Medicine, Chicago, Illinois, USA; 15University of Birmingham, Birmingham, UK.

PARADIGHM, a global, prospective, observational registry of patients with chronic hypoparathyroidism (HPT), began enrolment in 2013 to collect data on the natural history of chronic HPT ( NCT01922440). Since initiation, recombinant human PTH, rhPTH(1-84), has been approved in the United States and Europe as an adjunctive treatment for adult patients with HPT. The protocol for the registry (now a European Medicines Agency–designated postmarketing commitment) was amended to capture rhPTH(1-84) use in HPT patients under routine clinical care (EUPAS16927). Patient recruitment continues with a global enrolment goal of ≥900 patients, including ≥300 receiving rhPTH(1-84). Follow-up data collection on each patient is planned for ≥10 years. Patients with a diagnosis of HPT of ≥6 months are eligible for inclusion; exclusions include inability to provide informed consent, enrolment in any interventional study, or active PTH(1-34) therapy. Treatment regimens are determined by the patients’ physician, per usual clinical practice, and can be conventional calcium/vitamin D supplements and/or rhPTH(1-84). Primary outcome variables are HPT lab tests, including renal function; renal and cardiovascular events; soft tissue calcification or bone fractures; presence of cataracts; and adverse events, including those considered to be related to rhPTH(1-84) treatment. Secondary outcome variables include health-related quality of life, disease-specific patient-reported measures, and hospitalisations and emergency room visits. Additional data to be collected include demographics, medical history, HPT management, and concomitant medications. Data are collected every 6 months, and the database uploads are via electronic data capture. A steering committee reviews scientific reports and evaluates requests for analyses. Prior to starting the new protocol, a registry data cut on December 1, 2016, was completed. Forty-one investigator sites and 492 patients (49±17 years of age; 30±9 kg/m2 body mass index) had been enrolled. Notably, 93% of patients reported ≥1 symptom within the previous 6 months despite prescribed conventional therapy of calcium (91%) and vitamin D (84%). Only 7% were recorded as receiving rhPTH(1-84) in a clinical trial setting (ie, data capture was prior to US Food and Drug Administration approval). Data from PARADIGHM will provide physicians with needed information on the natural history of HPT in patients prescribed conventional treatment and in those prescribed rhPTH(1-84).