Therapy of hypoparathyroidism with PTH(1-84): A prospective six year investigation of efficacy and safety

Abstract

Context: Human recombinant (rh)PTH(1-84) was recently approved for the treatment of refractory hypoparathyroidism, based upon a short-term phase 3 clinical trial. Long-term data are needed, because no time limit was placed on the treatment period. Objective: We studied the effect of long-term rhPTH(1-84) treatment in hypoparathyroidism for up to 6 years. Design: Prospective open-label study. Setting: Referral center. Patients: A total of 33 subjects with hypoparathyroidism. Interventions: rhPTH(1-84) treatment was initiated at a starting dose of 100 μg every other day for 6 years. Due to the availability of new dosages during the 6-year time period of the study, the dose could be and was adjusted for most patients to a daily dosing regimen. Main Outcome Measures: Supplemental calcium and vitamin D requirements, serum and urinary calcium (monthly for 6 mo and then biannually), serum phosphorus, bone turnover markers, and bone mineral density (BMD) biannually. Results: Treatment with rhPTH(1-84) progressively reduced supplemental calcium requirements over 6 years by 53% (P μ.0001) and 1,25-dihydroxyvitamin D requirements by 67% (P μ.0001). Sixteen subjects (48%) were able to eliminate 1,25-dihydroxyvitamin D supplementation completely. Serum calcium concentration remained stable, and urinary calcium excretion fell. Lumbar spine BMD increased (3.8-1%, P