Many ladies on dialysis rapid developed extreme hypocalcemia after starting denosumab (Prolia) for osteoporosis, Medicare knowledge confirmed.
Correct throughout the principle 12 weeks of therapy, 41.1% of girls on denosumab developed extreme hypocalcemia in comparison with 2.0% of those taking oral bisphosphonates, reported a neighborhood of largely FDA researchers led by Steven Bird, PhD, PharmD, of the company locations of work in Silver Spring, Maryland.
This translated to larger than a 20-times better possibility for incident extreme hypocalcemia with denosumab (weighted possibility ratio 20.7, 95% CI 13.2-41.2), per the retrospective cohort behold in JAMA.
Supported by these unusual findings, the FDA on Friday added a boxed warning over the likelihood of extreme hypocalcemia in sufferers with evolved chronic kidney illness (CKD) taking denosumab for osteoporosis.
The behold published a interesting decline in calcium levels throughout the principle week of denosumab administration that continued for as a lot as 10 weeks after.
The an identical modified into seen with regard to the 12-week weighted cumulative incidence of very extreme hypocalcemia, which came about in 10.9% of denosumab-treated sufferers versus only 0.4% of those on oral bisphosphonates (weighted RR 26.4, 95% CI 9.7-449.5).
“Stable serum calcium levels noticed in this cohort all the way throughout the 6 months ahead of denosumab administration, coupled with the snappy onset and high incidence of extreme hypocalcemia post administration, counsel that this association may presumably well furthermore very well be causal,” they posited. Thanks to this, the authors acknowledged denosumab may presumably well furthermore aloof only be administered “after cautious sufferers alternative and with plans for frequent monitoring.”
“This would be due to a confluence of nephrology practice patterns, insufficient verbal replace between physicians, and absence of guidance on osteoporosis administration in sufferers present process dialysis,” commented accompanying editorial authors Pascale Khairallah, MD, of Baylor College of Remedy in Houston, and Thomas Nickolas, MD, MS, of Columbia University Irving Scientific Heart in New York.
These findings furthermore weren’t fully surprising, Khairallah and Nickolas acknowledged, as other global reports reported rates of denosumab-related hypocalcemia of as a lot as 42%.
“The shortcoming of guidance on managing osteoporosis in CKD is shared between the nephrology neighborhood and drug regulatory companies,” the editorialists argued. “The massive fluctuate of anti-atomize medications being fashioned in sufferers and the rising postmarketing antagonistic tournament knowledge may presumably well furthermore aloof fast scientific societies, alongside with the … FDA, to fabricate related guidance on administration systems, alongside side restrictions on drug class utilization if warranted by drug safety profiles.”
The FDA had issued a security alert back in November 2022 over denosumab’s doable hypocalcemia possibility in dialysis-dependent ladies. In that safety alert, the company referred to meantime results from maker Amgen’s ongoing safety behold of denosumab, which fast an increased possibility of hypocalcemia in sufferers with evolved kidney illness. That safety behold — required upon denosumab’s preliminary approval — modified into performed in men and postmenopausal ladies with osteoporosis.
Bird’s neighborhood checked out Medicare knowledge on ladies 65 and older who initiated therapy with denosumab 60 mg (n=1,523) or oral bisphosphonates (n=1,281) alongside side alendronate (Fosamax), risedronate (Actonel, Atelvia), or ibandronate (Boniva) from 2013 through 2020. All ladies had been present process long-timeframe hemodialysis or peritoneal dialysis and had a diagnosis of osteoporosis or had been receiving therapy for low bone mass after therapy with aromatase inhibitors, gonadotropin-releasing hormone agonists, or high-depth glucocorticoids. Nearly about all had osteoporosis and hyperparathyroidism.
The sizable majority of these medicine had been prescribed by predominant care clinicians, adopted by endocrinologists and rheumatologists. No longer as a lot as 3% of scripts had been written by nephrologists.
Severe hypocalcemia modified into defined as total albumin-corrected serum calcium below 7.5 mg/dL (1.88 mmol/L) or a predominant well being facility or emergency division hypocalcemia diagnosis, whereas very extreme hypocalcemia modified into concept of a serum calcium below 6.5 mg/dL (1.63 mmol/L) or emergent care. Nearly about all extreme hypocalcemia circumstances had been identified in accordance with albumin-corrected serum calcium levels in preference to in accordance with emergency division or well being facility diagnosis.
Kristen Monaco is a senior workers creator, focusing on endocrinology, psychiatry, and nephrology news. Essentially based fully out of the New York City pickle of job, she’s labored at the corporate since 2015.
The behold modified into funded by the FDA through an interagency agreement with the Centers for Medicare & Medicaid Providers and products.
Bird and co-authors reported employment with the FDA and relationships with Acumen, which is the contractor for this behold’s interagency funding agreement between the FDA and the Centers for Medicare & Medicaid Providers and products.
Nickolas reported grants from Amgen and scientific advisory board membership for Pharmacosmos.
Khairallah disclosed no related relationships with industry.
Source Reference: Bird ST, et al “Severe hypocalcemia with denosumab amongst older female dialysis-dependent sufferers” JAMA 2024; DOI: 10.1001/jama.2023.28239.
Source Reference: Khairallah P, Nickolas TL “Managing osteoporosis in dialysis — a scientific Take-22” JAMA 2024; DOI: 10.1001/jama.2023.24072.