Vaccines for COVID-19 Prevention in School-Age Children
Pediatricians, health officials, and schools are awaiting rollout of COVID-19 vaccines for younger children amid concerns about the effect of the pandemic on children’s mental health and development. As of early November, the Advisory Committee on Immunization Practices (ACIP) has recommended emergency use authorization of a two-dose regimen of 10-mcg apiece, 21 days apart, for the Pfizer-BioNTech mRNA COVID-19 vaccine. The Moderna vaccine could be made available to children and teens by the end of the year.
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The decision on the Pfizer vaccine was supported by results of a phase 2/3 study that enrolled 3,109 participants ages 5 to 11 who received the vaccine and 1,528 who received placebo. The trial demonstrated efficacy of 90.7%, with 3 COVID cases in the vaccine group and 16 in the placebo group, none of those cases severe.
On October 25th, Moderna announced interim data from its phase 2/3 study, KidCOVE, that examined the company’s vaccine candidate against COVID-19 in children ages 6 to 12. KidCOVE showed a robust neutralizing antibody response after two 50-mcg doses. The SARS neutralizing antibody geometric mean ratio comparing the response in the 4,753 participants in the study to that of young adults for the phase 3 COVE study was 1.5, with a seropositive rate of 99.3%.
The new vaccines are being made available in an atmosphere of controversy, with a recent poll finding that 25% of parents with school-age children said they would “definitely not” get their child vaccinated. At the same time, other parents are looking to protect their children with vaccines in regions where mask mandates aren’t enforced. As a result of this contentious atmosphere, health care providers are an important source of accurate information. They need to be prepared to counter myths and misconceptions about the vaccine’s risks and benefits. (Walker, M. (2021). FDA panel: High marks for Pfizer’s kid-dose COVID vaccine. MedPage Today. Retrieved November 2021 from https://www.medpagetoday.com/infectiousdisease/covid19vaccine/95278; Moderna. (2021). Moderna announces positive top line data from phase 2/3 study of COVID-19 vaccine in children 6 to 11 years of age. [Press release]. Retrieved November 2021 from https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-positive-top-line-data-phase-23-study-covid-19; Walker, M. (2021). Kids 5-11 can now get Pfizer's COVID vaccine. MedPage Today. Retrieved November 2021 from https://www.medpagetoday.com/infectiousdisease/covid19vaccine/95410)
Released: November 2021
Nursing Drug Handbook
© 2021 Wolters Kluwer
Weekly Lonapegsomatropin in Growth Hormone Deficiency
Since 1987, children with growth hormone (GH) deficiency have been treated with daily injections of somatropin. Although safe, daily injection carries a high treatment burden, which can lead to poor adherence and suboptimal outcomes. Development of a long-acting form of GH aims to create a more convenient treatment, thus improving adherence. Lonapegsomatropin is a once-weekly, long-acting prodrug consisting of the parent drug somatropin, an inert PEG (polyethylene glycol) carrier, and a linker.
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The phase 3 heiGHt trial of weekly lonapegsomatropin demonstrated superior annualized height velocity (AHV) and statistically greater change in height standard deviation score (SDS) from baseline compared to equivalent doses of daily somatropin. The study, conducted in 73 sites across 15 countries, enrolled 161 prepubertal patients (Tanner stage 1) with GH deficiency, defined as peak GH level ≤10 ng/mL confirmed via two GH stimulation tests. The subjects had a height SDS ≤−2.0, insulin-like growth factor-1 SDS ≤−1.0, and BMI within + 2.0 standard deviation of the mean, as well as bone age ≥6 months behind chronological age. By week 52, 13.8% of all subjects had entered the pubertal transition.
The primary endpoint for the study was AHV at week 52; a secondary endpoint was the change from baseline in height SDS. The least squares mean AHV at 52 weeks was 11 cm/year for weekly lonapegsomatropin vs. 10.3 cm/year for daily somatropin. The increase from baseline in least-square mean height SDS was 1.10 SDS for lonapegsomatropin vs. 0.96 SDS for daily somatropin. The study therefore met its goal of demonstrating that the weekly formulation performed at least as well as the daily dose.
The AHV range observed was between 5.9 and 18.0 cm/year for lonapegsomatropin and between 4.7 and 16.3 cm/year for somatropin. The treatment difference favoring the weekly formulation started at week 5 and continued throughout the study. There were no serious adverse events related to the study drug, and none led to treatment discontinuation or death. (Thornton, P. S., et al. (2021).Weekly lonapegsomatropin in treatment-naïve children with growth hormone deficiency: The phase 3 heiGHt trial. J Clin Endocrinol Metab, 106(11), 3184–3195. Retrieved November 2021 from https://academic.oup.com/jcem/article/106/11/3184/6323258?searchresult=1)
Released: November 2021
Nursing Drug Handbook
© 2021 Wolters Kluwer
Mitigating Medication Complacency in Epilepsy
The STEP Survey (Seize the Truth of Epilepsy Perceptions), discussed in Neurology Clinical Practices, examined the perceptions of adult patients with epilepsy, along with those of caregivers and health care providers, on treatments for seizuresand treatment decisions. Findings of the surveypoint to potential strategies to mitigate treatment complacency: increased reporting of all seizure occurrences and frequent discussion of and education about possible treatment changes.
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The self-administered online survey was completed by 400 patients, 200 caregivers, and 258 health care providers. Patient participants were older than age 18, had been diagnosed with epilepsy, and were receiving one or more antiseizure medications. More than half of patients were on their third or more antiseizure medication regimen (58%). In the survey, 61% of patients reported at least 1 seizure with impaired awareness in the past year, 52% reported 1 to 9 seizures, 15% reported 10 to 20 seizures, and 17% reported no seizures in the past year. Eligible caregivers included a patient’s partner (23%), parent (25%), adult child (13%), another family member (27%), and friend (18%). Health care providers surveyed included neurologists (n = 112), epileptologists (n = 96), and nurse practitioners/physician assistants (NPs/PAs; n = 50), who saw at least 20 patients with epilepsy in their practice. The average percentage of patients these providers saw who had focal seizures was 67% for neurologists, 66% for epileptologists, and 55% for NPs/PAs.
Treatment complacency was common among all these surveyed groups, despite many patients with uncontrolled seizures. Survey responses point to several factors underlying that complacency. Significantly, according to patients in the survey, they report less than half their seizures (45%) to their health care providers, and caregivers and health care providers aren’t aware of this; caregivers estimate that patients report 83% of their seizures, and health care providers estimate that patients report 73% of their seizures. This disconnect likely contributes to delays in discussions of changes in antiseizure medication treatments.
All groups agreed that health care providers were most likely to be the ones to initiate such discussions: 73% of patients, 66% of caregivers, and 77% of health care providers report this. Patients become complacent with their current antiseizure medication regimen, since they are expecting the health care provider to bring the subject up. To close the gap between seizures experienced and those reported, the reasons given by patients for not reporting them—not considering the seizure as serious enough, forgetting, fear of losing their driver’s license, or because health care providers didn’t ask—should be addressed. (Penovich, P. E., et al. (2021). Epilepsy treatment complacency in patients, caregivers, and health care professionals. Neurol Clin Pract, 11(5), 377–384. Retrieved November 2021 from https://cp.neurology.org/content/11/5/377)
Released: November 2021
Nursing Drug Handbook
© 2021 Wolters Kluwer
Sacituzumab Govitecan Effective against Metastatic Triple-Negative Breast Cancer
Future Oncology published a summary of findings of the ASCENT study, which demonstrated the effectiveness of the antibody-drug conjugate sacizutumab govitecan against metastatic triple-negative breast cancer. The antibody-drug conjugate is made up of an antibody that targets the human trophoblast cell-surface antigen-2 (Trop-2) coupled to a topoisomerase-1 inhibitor (SV-38). In triple-negative breastcancer, the tumor cells lack expression of estrogen, progesterone, and human epidermal growth factor 2 (HER2) receptors. Because most treatments for breast cancer depend on them being positive for one of these receptors, treating this form of breast cancer is challenging.
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The randomized, phase 3 ASCENT trial compared the antibody-drug conjugate with single-therapy chemotherapy, the standard treatment for metastatic triple-negative breast cancer. The study included 529 people with metastatic triple-negative breast cancer, all of whom had progressed on two previous chemotherapies and had tumors that could be measured by computed tomography scan or magnetic resonance imaging. They were randomized to Group A (n = 267), receiving IV injections of sacituzumab govitecan on days 1 and 18 of a 21-day cycle, or to Group B (n = 262), chemotherapy determined by the treating health care practitioner: either eribulin (54%), vinorelbine (20%), capecitabine (13%), or gemcitabine (12%).
Treatment was continued until disease progression, unacceptable toxic effects, withdrawal from the trial, or death. Those with brain metastases were included in the study only if there was evidence that the tumor had stopped growing for at least 4 weeks. But the primary endpoint was progression-free survival among patients without brain metastases. Progression-free survival in those without brain metastases was 5.6 months in Group A, compared to 1.7 months in Group B; in the total population, progression-free survival was 4.8 months in Group A and 1.7 months in Group B. Overall survival in those without brain metastases was 12.1 months in Group A compared to 6.7 months in Group B; in the total population, it was 11.8 months in Group A and 6.9 months in Group B. Decrease in tumor size was seen in 35% of patients without brain metastases (82/235) in Group A and in 5% of patients (11/233) in Group B; in the total population, decrease in tumor size was seen in 31% of patients (83/267) in Group A and in 4% of patients (11/262) in Group B. The duration of response in patients without brain metastases was 6.3 months in Group A and 3.6 months in Group B; in the overall population, it was 6.3 months in Group A and 3.6 months in Group B.
Side effects were seen in 98% of patients receiving sacituzumab govitecan and 86% of those receiving chemotherapy. The most common adverse effects were neutropenia (63% with sacituzumab govitecan and 43% with chemotherapy), diarrhea (59% with sacituzumab govitecan and 12% with chemotherapy), and nausea (57% with sacituzumab govitecan and 26% with chemotherapy). (Bardia, A., et al. (2021). A plain language summary of the ASCENT study: Sacituzumab govitecan for metastatic triple-negative breast cancer. Future Oncol, 17(30), 3911–3924. Retrieved November 2021 from https://www.futuremedicine.com/doi/pdf/10.2217/fon-2021-0868; Bardia, A., et al. (2021). Sacituzumab govitecan in metastatic triple-negative breast cancer. NEJM, 384: 1529–1541. Retrieved November 2021 from https://www.nejm.org/doi/full/10.1056/NEJMoa2028485)
Released: November 2021
Nursing Drug Handbook
© 2021 Wolters Kluwer