Six-year treatment with Natpara reduced supplemental calcium and calcitriol requirements, stabilized serum calcium concentration and reduced urinary calcium excretion in hypoparathyroidism, according to study findings.
Natpara (recombinant human parathyroid hormone[1-84], Shire Pharmaceuticals) was approved by the FDA in January 2105.
Mishaela R. Rubin, MD, assistant professor of clinical medicine at Columbia University College of Physicians and Surgeons, and colleagues evaluated 33 adults (mean age, 47 years; 79% women) with hypoparathyroidism to determine the long-term effect of rhPTH(1-84) treatment for up to 6 years. Treatment was started at 100 µg every other day for 6 years, and the dose may have been adjusted due to the availability of new doses during the study period.
Main outcome measures included supplemental calcium and vitamin D requirements, serum and urinary calcium (monthly for 6 months then biannually), serum phosphorus, bone turnover markers and bone mineral density biannually.
There were decreases in supplemental calcium requirements within 1 year after beginning of treatment (P < .001), and requirements remained lower than baseline throughout the study. There was a 53% average reduction in calcium supplementation from baseline to 6 years (P < .0001). Requirements for 1,25-hydroxyvitamin D requirements also decreased within 1 year of treatment (P = .001) and continued to fall at year 6 (P = .02 vs. year 1). There was a 67% reduction in 1,25-hydroxyvitamin D requirements from baseline to the end of the study (P < .0001).
Throughout the 6-year period, serum calcium levels remained in the lower end of normal (P = .53). There were decreases in urinary calcium secretion at years 1, 3 and 6 (P = .007). From baseline, serum phosphate decreased at years 4 and 5 (P = .01) but returned to near baseline levels at year 6. There were decreases in serum magnesium from baseline to year 1 (P < .0001) and levels remained lower than baseline through the study (P = .002).
There were increases in lumbar spine BMD at 24 months (P = .01) with a mean gain from baseline of 3.8% at year 6 (P = .004). At year 6, femoral neck BMD did not differ from baseline. There were increases in total hip BMD from baseline to year 6 (P = .02).
At year 1, bone turnover markers were threefold above baseline and subsequently declined throughout the study but remained higher than baseline.
“This study has demonstrated that rhPTH(1-84) is safe and effective as a long-term treatment of hypoparathyroidism for at least 6 years,” the researchers wrote. “It permits major reductions in the need for supplemental calcium and active vitamin D while maintaining normal calcium levels. Longer-term studies are needed to help determine whether the major comorbidities associated with hypoparathyroidism on the kidney and bone are reduced or reversed with long-term rhPTH(1-84) therapy.” – by Amber Cox
Rubin reports receiving research support from Shire Pharmaceuticals. Please see the full study for a list of all other authors’ relevant financial disclosures.