Mepolizumab a Good Choice in Chronic Rhinosinusitis with Comorbid Asthma
Results of the phase III SYNAPSE study demonstrated the effectiveness of mepolizumab in reducing nasal polyp size and nasal obstruction in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Mepolizumab is an MAb that prevents interleukin-5 from binding to its receptors on eosinophils, thus selectively inhibiting eosinophilic inflammation. The burden of disease in CRSwNP is greatest among those with comorbid asthma or aspirin-exacerbated respiratory disease (AERD) and in patients with eosinophilic infiltration. The researchers conducted a subgroup analysis targeting those patients that suggests that mepolizumab should be the treatment choice in CRSwNP in patients with comorbid asthma or AERD.
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SYNAPSE was a randomized, double-blind, 52-week study in patients with severe bilateral CRSwNP eligible for surgery despite intranasal corticosteroid treatment. Enrolled patients received subcutaneous mepolizumab 100 mg or placebo every 4 weeks plus standard of care (daily mometasone furoate nasal spray, saline nasal irrigations, and short courses of steroids or antibiotics, as needed) for 52 weeks. The patients had recurrent bilateral nasal polyps. The study reported the proportion of patients with greater than or equal to 1-point increase in total endoscopic nasal polyp score at week 52 and greater than or equal to 3-point improvement in nasal obstruction visual analog (VAS) score by weeks 49 to 52. Endoscopic nasal polyp score ranges from 0 (no polyps) to 4 (large polyps causing complete obstruction of inferior meatus) for each nostril, for a highest possible total score of 8. The nasal obstruction VAS score ranges from 0 to 10. This subgroup analysis included 407 patients; 289 had comorbid asthma, 108 had comorbid AERD, 371 had blood eosinophil cell (BEC) counts greater than or equal to 150 cells/f mm3, and 278 had BEC counts greater than or equal to 300 cells/f mm3.
In the intent-to-treat population, more patients who received mepolizumab had greater than or equal to 1-point improvement from baseline in endoscopic nasal polyp score—50.5% of patients vs. 28.4% in the placebo group. The proportions of patients with greater than or equal to 1-point improvement in endoscopic nasal polyp score was higher across the various subgroups with mepolizumab vs. placebo:
· Comorbid asthma: 52.9% vs. 29.5%
· Comorbid AERD: 51.1% vs. 20.6%
· BEC count greater than or equal to 150 cells/f mm3: 49.5% vs. 28.1%
· BEC count greater than or equal to 300 cells/f mm3: 50.4% vs. 28.1%
The proportion of patients who had a greater than or equal to 3-point improvement in nasal obstruction VAS score also differed greatly across these subgroups:
· Comorbid asthma: 60.0% vs. 34.9%
· Comorbid AERD: 64.4% vs. 30.2%
· BEC count greater than or equal to 150 cells/f mm3: 59.1% vs. 34.1%
· BEC count greater than or equal to 300 cells/f mm3: 59.0% vs. 32.4%
Among the other findings is that patients receiving mepolizumab had a lower risk of surgery than those receiving placebo. This reduction was greater in patients without asthma than those with asthma but was similar irrespective of the presence of AERD. This benefit may be an important consideration for patients who express concern over the risks associated with surgery. (Bachert, C., et al. (2022). Mepolizumab for chronic rhinosinusitis with nasal polyps: Treatment efficacy by comorbidity and blood eosinophil count. J Allergy Clin Immunol, 149(5), 1711-1721.E6.Retrieved June 2022 from https://www.jacionline.org/article/S0091-6749(22)00001-X/fulltext#fx1)
Released: June 2022
Nursing Drug Handbook
© 2022 Wolters Kluwer
Oral Antivirals for COVID-19
The best tool health care providers have to combat spread of COVID-19 disease is the vaccine program targeting the virus. However, research into treatments to mitigate the effects of the virus after infection are ongoing. In December 2021 two oral antiviral treatments were made available under an Emergency Use Authorization (EUA): ritonavir-boosted nirmatrelvir and molnupiravir.
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The Centers for Disease Control and Prevention has issued a health advisory with updates on the availability of and use of these treatments for mild to moderate COVID-19. When theseagents were first made available, ensuring adequate supplies to keep up with demand was challenging due to the rapid increase in omicron variant cases of COVID-19. These treatments are growing in importance as that highly transmissible variant continues as the predominant strain, with new subvariants emerging, and as mitigation strategies such as masking and social distancing are being phased out. The FDA has ensured that oral antivirals are widely available and can be accessed with a provider prescription at pharmacies and at Test-to-Treat locations.
Both ritonavir-boosted nirmatrelvir and molnupiravir work best early in the course of illness before SARS-CoV2 can have a chance to replicate and do damage. They are authorized for use within 5 days of symptom onset in nonhospitalized patients who have tested positive for SARS-CoV2 and are at high risk. High-risk patients include those over age 65 or those older than age 12 with an underlying condition that increases the risk of severe outcomes of COVID-19, such as cancer, heart disease, diabetes, and obesity. The preferred therapies are the oral antiviral ritonavir-boosted nirmatrelvir and the infusion remdesivir. The alternatives, molnupiravir and the monoclonal antibody bebtelovimab (available under EUA since February 2022) are to be used only when the preferred treatments are unavailable, not feasible, or not appropriate. Ritonavir-boosted nirmatrelvir produced an 89% reduction in the risk of hospitalization and death; molnupiravir is less efficacious, producing a 30% reduction in risk. There are numerous considerations that come into play when deciding on which oral antiviral to use. Ritonavir-boosted nirmatrelvir should be avoided by those with severe kidney or liver disease; in addition, because ritonavir acts to boost levels of nirmatrelvir by slowing down hepatic metabolism of the other drug through inhibition of CYP3A4, its use should be avoided with other drugs highly dependent on CYP3A enzymes for clearance. Its use should also be avoided with use of CYP3A inducers, which can result in low levels of ritonavir and therefore loss of virologic response. Molnupiravir use should be avoided in those who are, or are attempting to become, pregnant and in those under age 18; men with sexual contact with women of childbearing age should use a reliable method of contraception during molnupiravir treatment and for 3 months afterward.
In the battle against the pandemic, health care providers and their patients should be doing everything they can to avoid COVID-19 disease and disease progression in patients with risk factors: vaccinations, testing, isolation when positive, and these antiviral treatments. Providers should educate their patients at high risk not to overlook mild cases and to remember that accurate testing remains key to COVID-19 prevention. (Petty, L. A., & Malani, P. N. (2022). Oral antiviral medications for COVID-19. JAMA Patient Page. Retrieved June 2022 from https://jamanetwork.com/journals/jama/fullarticle/2791780#:~:text=Two%20new%20oral%20antiviral,US%20under%20emergency%20use%20authorization;Katella, K. (2022).13 things to know about Paxlovid, the latest COVID-19 pill. Yale Medicine. Retrieved June 2022 from https://www.yalemedicine.org/news/13-things-to-know-paxlovid-covid-19; U.S. Food & Drug Administration. (2021, December 22). Coronavirus (COVID-19) update: FDA authorizes first oral antiviral for treatment of COVID-19. [Press Release]. Retrieved June 2022 from https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-first-oral-antiviral-treatment-covid-19;Centers for Disease Control and Prevention. (2022, April 25). Updated information on availability and use of treatments for outpatients with mild to moderate COVID-19 who are at increased risk for severe outcomes of COVID-19. [Press release]. Retrieved June 2022 from https://emergency.cdc.gov/han/2022/han00463.asp;National Institutes of Health. COVID-19 Treatment Guidelines. (2022). Ritonavir-boosted nirmatrelvir (Paxlovid). Retrieved June 2022 from https://www.covid19treatmentguidelines.nih.gov/therapies/antiviral-therapy/ritonavir-boosted-nirmatrelvir--paxlovid-/)
Released: June 2022
Nursing Drug Handbook
© 2022 Wolters Kluwer
Polypharmacy and Disability in Older Adults
A new Japanese study published in Geriatrics and Gerontology International evaluated the relationship between high-risk prescribing practices and the risk for disability in people age 65 and older. These practices include polypharmacy (the use of five or more prescription drugs) and the use of drugs with sedative or anticholinergic properties, including antipsychotics, benzodiazepines, and antiparkinsonian drugs. These prescribing practices have been previously shown to be associated with physical frailty among older adults.
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The researchers for the University of Tsukuba conducted a population-based, case-control study, the study cohort nested within a cohort of older adults in a Japanese city. Using combined medical claims and long-term care (LTC) needs certification database, researchers identified 2,123 individuals who received a first LTC needs certification and matched them to 40,295 controls (accounting for 89% of the over-65 population) based on age, sex, residence, and the observation period. In Japan, people age 65 and older with a functional disability are eligible for LTC services; an LTC needs certification is needed to access these services, so the researchers were able to use it as a proxy for disability.
The study demonstrated a dose-response relationship between both polypharmacy and the use of drugs with sedative or anticholinergic properties with the risk for LTC needs certification. Adjusted odds ratios (OR) of this outcome were as follows:
· Polypharmacy (5 to 9 prescription drugs): OR, 1.32
· Hyperpolypharmacy (greater than or equal to 10 prescription drugs): OR, 1.87
· Cumulative doses of drugs with sedative or anticholinergic properties, in terms of defined daily dose:
o defined daily dose 1–364: OR, 1.07
o defined daily dose 365–729: OR, 1.25
o defined daily dose greater than 730: OR, 1.33
Further study should examine whether adjusting prescribing patterns in these patients could reduce the risk of LTC needs certification in older adults and reduce the LTC burden for the public. (University of Tsukuba. (2022, May 18). Potential pitfalls of high-risk prescribing practices in older adults. AlphaGalileo. Retrieved June 2022 from https://www.alphagalileo.org/en-gb/Item-Display/ItemId/221191?returnurl=https://www.alphagalileo.org/en-gb/Item-Display/ItemId/221191;Kuroda, N., et al. (2022). Associations of polypharmacy and drugs with sedative or anticholinergic properties with the risk of long-term care needs certification among older adults in Japan: A population-based, nested case–control study. Geriatr Gerontol Int. Advanced online publication. Retrieved June 2022 from https://onlinelibrary.wiley.com/doi/full/10.1111/ggi.14393)
Released: June 2022
Nursing Drug Handbook
© 2022 Wolters Kluwer
Risdiplam Effective Long-Term for Spinal Muscular Atrophy
Genentech presented long-term data from the FIREFISH study, including one-year data for the open-label extension, at the European Paediatric Neurology Society Conference, held April 28 through May 2, 2022. FIREFISH is a phase II/III, 2-part, multicenter trial that examined the long-term efficacy and safety of risdiplam in infants with symptomatic Type 1 spinal muscular atrophy (SMA). SMA is a group of severe, progressive neuromuscular diseases that is the leading cause of infant mortality. It’s caused by a mutation of the SMN1 gene that leads to a deficiency of the SMN protein, resulting in cellular imbalance in motor neurons that in turn causes the motor neuron endplates to not properly connect to muscle and leads to death of the motor neurons. Without treatment, depending on the type of SMA, the patients can lose physical strength; and the ability to walk, eat, or breathe can be significantly diminished or lost. Untreated infants with type 1 SMA typically don’t survive past age 2. Risdiplam is a survival motor neuron 2 splicing modifier that allows production of full-length SMN protein and thereby can affect the progression of SAM.
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The original study evaluated efficacy and safety in infants ages 1 to 7 months at the time of trial enrollment. Part 1 of the trial was a dose-finding study; in part 2, the patients received liquid risdiplam orally or via feeding tube once daily. After 24 months, the trial entered a 3-year open-extension phase. At 36 months after trial enrollment, 91% (n = 58) of children treated with risdiplam were alive. The marker chosen to demonstrate efficacy was the percentage of children able to sit without support for 5 seconds, as assessed by the Bayley Scale of Infant Development at month 12. Without treatment, infants with type 1 SMA are never able to sit without support. At this 36-month follow-up, among the 48 children who could be assessed, 32 maintained that ability and 4 gained it between months 24 and 36, and no child who had gained the ability to sit without support for 5 seconds lost that ability. Further, 20 children maintained and 15 gained the ability to sit without support for at least 30 seconds. The children had other successes in the improvement or maintenance of skills measured on the Hammersmith Infant Neurological Examination between 24 and 36 months on treatment:
· Ability to hold head up: 36 maintained, 3 gained, 0 lost this ability
· Pivot while sitting: 15 maintained, 11 gained, 0 lost this ability
· Stand with support: 6 maintained, 5 gained, 1 lost this ability
· Walk while holding on: 1 maintained, 2 gained, 0 lost this ability
The study showed overall continued reduction in serious adverse events and hospitalization over time. The rate of serious adverse events decreased by approximately 50% after each 12-month treatment period and a 78% reduction between the first and third year of treatment. The rate of hospitalization decreased from 1.24 per patient per year over 12 months to 0.70 hospitalizations per patient per year over 36 months. (Genentech. (2022, April 28). New three-year data for Genentech’s Evrysdi (risdiplam) show long-term improvements in survival and motor milestones in babies with type 1 spinal muscular atrophy (SMA). [Press Release]. Retrieved June 2022 from https://www.gene.com/media/press-releases/14950/2022-04-28/new-three-year-data-for-genentechs-evrys)
Released: June 2022
Nursing Drug Handbook
© 2022 Wolters Kluwer