Chronic hypoparathyroidism is linked to long-term renal and cardiovascular complications, and can have severe implications on patients’ health-related quality of life, according to data from several studies.
The data, presented by Takeda Pharmaceutical during the Endocrine Society’s 2019 Annual Meeting (ENDO) in New Orleans, also included the final outcomes regarding the long-term use of recombinant human parathyroid hormone, known as rhPTH(1-84).
Long-term safety and effectiveness of parathyroid hormone injections
Researchers presented data from the six-year, open-label, long-term safety and effectiveness RACE study (NCT01297309), regarding the continuous use of recombinant human parathyroid hormone, marketed as Natpara in the U.S. and Natpar in Europe.
The study, “Safety and Efficacy of Recombinant Human Parathyroid Hormone 1-84 for the Treatment of Adults with Chronic Hypoparathyroidism: Six-Year Results of the RACE study,” showed that treatment with rhPTH(1-84) can help manage chronic hypoparathyroidism in adults.
The trial enrolled 49 patients across 12 clinical sites in the U.S. They were treated with once-daily injections of 25 or 50 µg of the treatment. Stepwise dose adjustments of 25 µg, either up or down, up to a maximum of 100 µg per day, were administered as needed.
The levels of oral calcium and vitamin D were also adjusted as needed to maintain calcium levels in the target range of 8.0-9.0 mg/dL.
Clinical results collected from 34 patients (69.4%) who completed 72 months of treatment showed that rhPTH(1-84) could help reduce the amount of oral calcium needed by 40.4% and reduce the amount of vitamin D taken by 72.2%.
In general, 22 of 34 treated patients (64.7%) were able to sustain their calcium levels within the target range upon the final month of treatment. These patients also achieved stable mean blood creatinine levels, while phosphorus levels declined from above-normal values in the beginning of the study to within normal range at 72 months.
“We are committed to further investigating this rare condition and collecting more data on the long-term implications,” John Germak, global medical team lead at Takeda, said in a press release. “Gaining valuable insights directly from patients enhances our understanding of the complex nature of the disease and its management.”
Treatment with rhPTH(1-84) was found in general to be safe and well-tolerated during the six years that the study lasted, with no new issues being reported compared with previous studies.
Burden of chronic hypoparathyroidism on patients and caregivers
Three presentations, “Impact of Chronic Hypoparathyroidism on Health-Related Quality of Life: Findings from a 13-Country Patient Survey,” “Symptoms, Comorbidities and Treatment Satisfaction with Chronic Hypoparathyroidism: Findings from a 13-Country Patient Survey,” and “Impact of Chronic Hypoparathyroidism on Work, Productivity, and relationships: Findings from a 13-Country Patient and Caregiver Survey,” reported results from a global survey that provided new insights directly from patients with chronic hypoparathyroidism on their health status and quality of life.
The Burden of Illness Global Survey was conducted in 13 countries between October 2017 and March 2018. The anonymous survey included 398 patients with uncontrolled chronic hypoparathyroidism, as determined by patients’ report of persistent symptoms and/or poorly controlled calcium levels, as reported by their physicians. Patients who had received treatment with hormone replacement therapy were excluded from the study. The survey also enrolled 207 caregivers of patients with chronic hypoparathyroidism.
Participants’ answers revealed an inverse relationship between the severity of their disease symptoms and their health-related quality of life. In general, patients who had more severe hypoparathyroidism symptoms were found to have worse health-related scores.
Although most patients were taking standard therapies, such as oral calcium and vitamin D, “hypoparathyroidism was associated with burdensome symptoms that negatively affected health-related quality of life and health status,” the researchers said.
According to patients’ perspectives, 12% reported severe symptoms, while 85% had mild to moderate symptoms. Almost all patients (97%) reported experiencing physical fatigue. The most common physical manifestations were muscle cramps (present in 86% of cases), tingling (84%), and heaviness in limbs (82%).
Cognitive and behavioral symptoms were also reported as common occurrences. These included cognitive and mood symptoms of brain fog in 77% of patients, anxiety in 78%, and depression in 76%.
Analysis of secondary complications showed that 41% suffered from hypertension (high blood pressure); 29% had mental, behavioral, or neurodevelopmental disorders; 28% experienced arrhythmias; and 27% had kidney problems, among other metabolic and biochemical disorders.
Hypoparathyroidism manifestations were reported to have “somewhat” or “very much” impact on patients’ ability to exercise in 84% of cases; to sleep, in 78% of cases; to work, in 75% of cases. A total 63% of patients reported an impact of “somewhat” or “very much” on family relationships. In all cases, symptom severity was found to be associated with a reduced capacity to work or perform activities.
The survey showed the disease does not only affect patients’ lives. It can also put a burden on those caring for patients. Caregivers reported that the disease had “a major impact” on their relationship with spouse/partner (28%), with family (21%), and with friends (21%).
The survey also showed that the majority of patients (96%) believed that their disease was not controlled with current medications. Also, more than half (53%) disagreed with their physician’s perception of the effectiveness of their treatment regimen in controlling the disease.
“Findings from this global survey demonstrated that uncontrolled chronic hypoparathyroidism can be associated with substantial burdensome symptoms, comorbidities, and impact on various aspects of [patients’ and caregivers’] daily living,” the researchers said.
“Results from the Burden of Illness Global Survey in 13 countries reveal the extent of the impact hypoparathyroidism has on patients and their caregivers throughout their daily lives,” said John Bilezikian, MD, professor at the Columbia University Irving Medical Center, New York.
“This offers important insights and enables us to take a more holistic approach in the management of these patients due to a greater understanding of the potential cardiovascular risks patients may face, along with other complications of the kidneys,” he added.
Long-term cardiovascular and renal complications associated with chronic hypoparathyroidism
Results from another large-scale study, which included 8,097 patients with chronic hypoparathyroidism and 40,485 patients without the disease, provided further evidence of the cardiovascular and renal problems in this patient population.
The data showed that patients with chronic hypoparathyroidism have a 2.57 times greater risk of developing advanced chronic kidney disease (CKD). They were also found to have an increased risk of experiencing progressive renal disease and developing end-stage renal disease, compared with individuals without hypoparathyroidism.
Further analysis also revealed that patients with chronic hypoparathyroidism have a 1.64 times greater risk of developing cardiovascular problems, including atrial fibrillation, cerebrovascular disease, coronary artery disease, heart failure, peripheral vascular disease, and tachyarrhythmia.
Moreover, hypoparathyroidism patients were found to have a 1.81 times higher risk of nephrolithiasis (commonly known as kidney stones), and a 6.94 times greater risk of nephrocalcinosis (calcium deposits in the kidneys), compared with patients without hypoparathyroidism.
“Further research is warranted to understand the potential mechanisms for the relationship of chronic hypoparathyroidism and its management with these observed risks,” the researchers said.
These finding were discussed in four presentations titled, “Risk of Chronic Kidney disease (CKD) and Its Progression in Patients with Chronic Hypoparathyroidism (HypoPT),” “Risk of Decline in Estimated Glomerular Filtration Rate (eGFR) in Patients with Chronic Hypoparathyroidism (HypoPT),” “Risk of Cardiovascular (CV) Conditions in Patients with Chronic Hypoparathyroidism (HypoPT),” and “Risk of Nephrolithiasis and Nephrocalcinosis in Patients with Chronic Hypoparathyroidism (HypoPT).“