— New findings resulted in boxed caution on drug’s labeling for sophisticated CKD clients
by
Kristen MonacoSenior Staff Writer, MedPage Today
January 19, 2024
Lots of females on dialysis rapidly established extreme hypocalcemia after beginning denosumab (Prolia) for osteoporosis, Medicare information revealed.
Throughout the very first 12 weeks of treatment, 41.1% of females on denosumab established serious hypocalcemia compared to 2.0% of those taking oral bisphosphonates, reported a group of mostly FDA scientists led by Steven Bird, PhD, PharmD, of the firm workplaces in Silver Spring, Maryland.
This equated to more than a 20-times greater threat for occurrence serious hypocalcemia with denosumab (weighted danger ratio 20.7, 95% CI 13.2-41.2), according to the retrospective friend research study in JAMA
Supported by these brand-new findings, the FDA on Friday included a boxed caution over the danger of extreme hypocalcemia in clients with innovative persistent kidney illness (CKD) taking denosumab for osteoporosis.
The research study exposed a sharp decrease in calcium levels within the very first week of denosumab administration that continued for approximately 10 weeks after.
The exact same was seen in concerns to the 12-week weighted cumulative occurrence of really extreme hypocalcemia, which happened in 10.9% of denosumab-treated clients versus just 0.4% of those on oral bisphosphonates (weighted RR 26.4, 95% CI 9.7-449.5).
“Stable serum calcium levels observed in this friend throughout the 6 months prior to denosumab administration, combined with the quick start and high occurrence of extreme hypocalcemia post administration, recommend that this association may be causal,” they presumed. Since of this, the authors stated denosumab must just be administered “after cautious clients choice and with prepare for regular tracking.”
“This might be because of a confluence of nephrology practice patterns, insufficient interaction in between doctors, and absence of assistance on osteoporosis management in clients going through dialysis,” commented accompanying editorial authors Pascale Khairallah, MD, of Baylor College of Medicine in Houston, and Thomas Nickolas, MD, MS, of Columbia University Irving Medical Center in New York.
These findings likewise weren’t absolutely unanticipated, Khairallah and Nickolas stated, as other international research studies reported rates of denosumab-related hypocalcemia of as much as 42%.
“The absence of assistance on handling osteoporosis in CKD is shared in between the nephrology neighborhood and drug regulative firms,” the editorialists argued. “The broad series of anti-fracture medications being utilized in clients and the emerging postmarketing negative occasion information need to trigger medical societies, in combination with the … FDA, to produce appropriate assistance on management methods, consisting of constraints on drug class use if necessitated by drug security profiles.”
The FDA had actually released a security alert back in November 2022 over denosumab’s prospective hypocalcemia threat in dialysis-dependent females. Because security alert, the firm described interim arise from maker Amgen’s continuous security research study of denosumab, which recommended an increased danger of hypocalcemia in clients with innovative kidney illness. That security research study– needed upon denosumab’s preliminary approval– was performed in guys and postmenopausal ladies with osteoporosis.
Bird’s group took a look at Medicare information on females 65 and older who started treatment with denosumab 60 mg (n=1,523) or oral bisphosphonates (n=1,281) consisting of alendronate (Fosamax), risedronate (Actonel, Atelvia), or ibandronate (Boniva) from 2013 through 2020. All ladies were going through long-lasting hemodialysis or peritoneal dialysis and had a medical diagnosis of osteoporosis or were getting treatment for low bone mass after treatment with aromatase inhibitors, gonadotropin-releasing hormonal agent agonists, or high-intensity glucocorticoids. Almost all had osteoporosis and hyperparathyroidism.
The huge bulk of these drugs were recommended by medical care clinicians, followed by endocrinologists and rheumatologists. Less than 3% of scripts were composed by nephrologists.
Serious hypocalcemia was specified as overall albumin-corrected serum calcium listed below 7.5 mg/dL (1.88 mmol/L) or a main health center or emergency situation department hypocalcemia medical diagnosis, while extremely extreme hypocalcemia was thought about a serum calcium listed below 6.5 mg/dL (1.63 mmol/L) or emerging care. Nearly all extreme hypocalcemia cases were determined based upon albumin-corrected serum calcium levels instead of based upon emergency situation department or medical facility medical diagnosis.
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Kristen Monaco is a senior personnel author, concentrating on endocrinology, psychiatry, and nephrology news. Based out of the New York City workplace, she’s operated at the business considering that 2015.
Disclosures
The research study was moneyed by the FDA through an interagency arrangement with the Centers for Medicare & & Medicaid Services.
Bird and co-authors reported work with the FDA and relationships with Acumen, which is the specialist for this research study’s interagency financing arrangement in between the FDA and the Centers for Medicare & & Medicaid Services.
Nickolas reported grants from Amgen and clinical board of advisers subscription for Pharmacosmos.
Khairallah divulged no appropriate relationships with market.
Main Source
JAMA
Source Reference: Bird ST, et al “Severe hypocalcemia with denosumab amongst older female dialysis-dependent clients” JAMA 2024; DOI: 10.1001/ jama.2023.28239.
Secondary Source
JAMA
Source Reference: Khairallah P, Nickolas TL “Managing osteoporosis in dialysis– a medical Catch-22” JAMA 2024; DOI: 10.1001/ jama.2023.24072.