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News Capsules - February 2025

Condoliase Offers Less Invasive Treatment for Patients With Lumbar Disc Herniation

Lumbar disc herniation (LDH) is a spinal condition that causes nerve root compression, leading to radicular leg pain and affecting quality of life. Although many cases resolve with conservative treatments, approximately 10% of patients require more intensive interventions. Consequently, alternative treatments like condoliase, are being explored.

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Promising Treatment Combination for Cystic Fibrosis

Cystic fibrosis (CF) is a genetic disorder that's caused by mutations in the CFTR gene. The disease can manifest in early life, with symptoms such as pancreatic insufficiency and elevated chloride levels in sweat. Chronic respiratory infections and progressive lung damage are common, and poor nutrition exacerbates these issues, contributing to the overall decline in health.

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Updated Guidelines for Tuberculosis Treatment

Updated guidelines from the American Thoracic Society, the Centers for Disease Control and Prevention, the European Respiratory Society, and the Infectious Diseases Society of America now recommend shorter, fully oral treatment regimens for tuberculosis (TB) in both adults and children.

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Combination Metronomic Capecitabine and Aromatase Inhibitor as First-Line Treatment for Hormone Receptor-Positive, HER2-Negative Breast Cancer

Treating hormone receptor-positive, HER2-negative metastatic breast cancer (MBC) is challenging, especially as resistance to endocrine therapy develops in most patients over time. Metronomic chemotherapy, which uses lower doses of chemotherapy agents at more frequent intervals, offers potential as a less toxic alternative to traditional chemotherapy.

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Drug News Abstracts Archive

News Capsules - February 2025
Condoliase Offers Less Invasive Treatment for Patients With Lumbar Disc HerniationLumbar disc herniation (LDH) is a spinal condition that causes nerve root compression, leading to radicular leg pain and affecting quality of life. Although many cases resolve with conservative treatments, approximately 10% of patients require more intensive interventions. Consequently, alternative treatments like condoliase, are being explored.READ MORE...Condoliase is a glycosaminoglycan-degrading enzyme that reduces moisture retention and pressure within the intervertebral disc, alleviating nerve root compression, which is a key contributor to pain in LDH. A phase 3, multicenter, randomized, double-blind, sham-controlled trial focused on evaluating the safety and efficacy of condoliase in the United States.The study involved 352 participants ages 30 to 70 with radicular leg pain from LDH. Participants were randomized to receive either a single intradiscal injection (1.25 units) of condoliase or a sham injection. The primary endpoint was the change in worst leg pain score from baseline to Week 13, while secondary endpoints included changes in disability, herniation volume, and neurologic status. Results showed that the condoliase group had higher responder rates (50% or more reduction in pain) compared to the sham group. The condoliase group also showed improvements in disability and greater improvements in neurologic tests, such as the straight leg raise test, at Week 13.Although adverse events were reported more frequently in the condoliase group, including back pain and hypersensitivity reactions, no participants required discontinuation due to adverse events. Additionally, condoliase was associated with a lower rate of posttreatment surgery compared to the sham group, which is a promising result for patients looking for less invasive alternatives to surgery.This phase 3 trial supports condoliase as an effective treatment for radicular leg pain due to LDH, with improvements in pain relief and lower rates of surgery compared to sham treatment. Even though the drug was associated with some mild side effects, it provides a promising less-invasive option for patients who don't respond to conservative treatments. (Kim, K. D., et al. [2024]. A phase 3, randomized, double-blind, sham-controlled trial of SI-6603 [condoliase] in patients with radicular leg pain associated with lumbar disc herniation. The Spine Journal, 24[12], 2285–2296. Retrieved January 2025 from https://www.thespinejournalonline.com/article/S1529-9430(24)00936-7/fulltext)Released: February 2025Nursing Drug Handbook© 2025 Wolters Kluwer N.V., its subsidiaries and/or its licensors. All rights reserved.Promising Treatment Combination for Cystic FibrosisCystic fibrosis (CF) is a genetic disorder that's caused by mutations in the CFTR gene. The disease can manifest in early life, with symptoms such as pancreatic insufficiency and elevated chloride levels in sweat. Chronic respiratory infections and progressive lung damage are common, and poor nutrition exacerbates these issues, contributing to the overall decline in health.READ MORE...CFTR modulators are a therapeutic class designed to restore normal CFTR function, as individuals with healthy CFTR don't experience CF-related symptoms. Sweat chloride testing is a key diagnostic tool for CF, with elevated chloride levels indicating CFTR dysfunction. CFTR modulators, like vanzacaftor/tezacaftor/deutivacaftor, a new combination regimen, aim to normalize chloride transport and improve overall CFTR function.In a phase 3 trial for children ages 6 to 11 years, this combination was tested with 78 participants over a 24-week treatment period for safety, pharmacokinetics, and efficacy. In the trial, participants taking the combination therapy showed stable lung function, with no significant decline in forced expiratory volume in 1 second, a key measure of lung capacity. The treatment also led to a decrease in sweat chloride concentrations, with most children achieving sweat chloride levels below the 60 mmol/L threshold, a marker of improved CFTR function. Additionally, the Cystic Fibrosis Questionnaire-Revised respiratory domain scores improved, suggesting better respiratory health. As far as safety, the regimen was found to be well tolerated, with few serious adverse events.Overall, the 24-week trial demonstrated that vanzacaftor/tezacaftor/deutivacaftor treatment improves CFTR function in children ages 6 to 11, with a favorable safety profile. This next-generation CFTR modulator regimen offers hope for reducing the clinical burden of CF, potentially improving both quality of life and long-term health outcomes. (Hoppe, J. E., et al. [2025]. Vanzacaftor/tezacaftor/deutivacaftor for children aged 6–11 years with cystic fibrosis [RIDGELINE trial VX21-121-105]: An analysis from a single-arm, phase 3 trial. The Lancet Respiratory Medicine. Advance online publication. Retrieved January 2025 from https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(24)00407-7/fulltext)Released: February 2025Nursing Drug Handbook© 2025 Wolters Kluwer N.V., its subsidiaries and/or its licensors. All rights reserved.Updated Guidelines for Tuberculosis TreatmentUpdated guidelines from the American Thoracic Society, the Centers for Disease Control and Prevention, the European Respiratory Society, and the Infectious Diseases Society of America now recommend shorter, fully oral treatment regimens for tuberculosis (TB) in both adults and children.READ MORE...The push for shorter treatments comes after years of limited drug development. Recent studies have enabled the reduction of treatment durations to 4 months for drug-susceptible TB and 6 months for drug-resistant TB, providing a more efficient approach to managing the disease. However, not all patients qualify for these shortened regimens, and the existing recommendations for some patients from previous guidelines remain in place. The updated guidelines make the following suggestions:Children ages 3 months to 16 years old with nonsevere TB should receive a 4-month regimen of isoniazid, rifampin, pyrazinamide, and ethambutol for 2 months, followed by isoniazid and rifampin for the remaining 2 months.Patients age 12 and older with drug-susceptible TB should consider a 4-month regimen of isoniazid, rifapentine, moxifloxacin, and pyrazinamide.Patients age 14 and older with rifampin-resistant pulmonary TB and resistance to fluoroquinolones; and in cases of multidrug-resistant but fluoroquinolone-susceptible disease, a 6-month regimen of bedaquiline, pretomanid, linezolid, and moxifloxacin is recommended.Certain pediatric cases that don't meet the criteria for the shortened regimen should continue with the standard 6-month treatment, while children with severe TB forms may require alternative regimens. Some children may also be eligible for the 4-month rifapentine-moxifloxacin regimen. The guidelines stress that drug-susceptibility testing and close monitoring for safety and effectiveness remain essential, especially to prevent the emergence of drug resistance.The updated guidelines were largely adapted from the 2022 World Health Organization TB treatment recommendations, with a panel of 25 international experts contributing to the consensus. No new clinical trial data has emerged since the World Health Organization guidelines were published, and the U.S. guidelines align closely with the global recommendations. (Saukkonen, J. J., et al. [2025]. Updates on the treatment of drug-susceptible and drug-resistant tuberculosis: An official ATS/CDC/ERS/IDSA Clinical Practice Guideline. American Journal of Respiratory and Critical Care Medicine, 211[1], 15–33. Retrieved January 2025 from https://www.atsjournals.org/doi/full/10.1164/rccm.202410-2096ST)Released: February 2025Nursing Drug Handbook© 2025 Wolters Kluwer N.V., its subsidiaries and/or its licensors. All rights reserved.Combination Metronomic Capecitabine and Aromatase Inhibitor as First-Line Treatment for Hormone Receptor-Positive, HER2-Negative Breast CancerTreating hormone receptor-positive, HER2-negative metastatic breast cancer (MBC) is challenging, especially as resistance to endocrine therapy develops in most patients over time. Metronomic chemotherapy, which uses lower doses of chemotherapy agents at more frequent intervals, offers potential as a less toxic alternative to traditional chemotherapy.READ MORE...Capecitabine, an oral chemotherapy agent, is one such drug used in metronomic chemotherapy. The MECCA trial explored combining metronomic capecitabine with endocrine therapy, specifically an aromatase inhibitor (AI), as a first-line treatment for hormone receptor-positive, HER2-negative MBC. This phase 3 trial in China involved 254 patients and compared the combination of capecitabine and AI with AI alone in terms of progression-free survival (PFS) and other clinical outcomes.The primary endpoint was PFS, while secondary endpoints included overall survival (OS), objective response rate, disease control rate, and safety. Patients were randomly assigned to either the capecitabine (500 mg three times daily) plus AI group or the AI-only group. The study continued until disease progression, intolerable side effects, or patient withdrawal.After a median follow-up of 50.7 months, the combination group showed a meaningful improvement in PFS (20.9 months) compared to the AI-only group (11.9 months). The combination group also had an OS advantage, with a median OS not yet reached compared to 45.1 months in the AI-only group. The objective response and disease control rates were higher in the combination group as well, at 37.3% and 88.1%, respectively, compared to 25.0% and 75.8% for the AI-only group.In terms of safety, the combination therapy was generally well tolerated. Although adverse events like palmar-plantar erythrodysesthesia were more common in the capecitabine plus AI group, most side effects were mild to moderate.The MECCA trial supports metronomic capecitabine combined with AI as an effective first-line treatment for hormone receptor-positive, HER2-negative MBC, offering improvements in PFS and OS with manageable toxicity. Further research is needed to investigate its role alongside other therapies, including CDK4/6 inhibitors and targeted therapies. (Hong, R.-X., et al. [2025]. Metronomic capecitabine plus aromatase inhibitor as initial therapy in patients with hormone receptor–positive, human epidermal growth factor receptor 2–negative metastatic breast cancer. The phase III MECCA trial. Journal of Clinical Oncology. Advance online publication. Retrieved January 2025 from https://ascopubs.org/doi/10.1200/JCO.24.00938)Released: February 2025Nursing Drug Handbook© 2025 Wolters Kluwer N.V., its subsidiaries and/or its licensors. All rights reserved.
Drug News Abstracts - January 2024
Adalimumab Effective after Resolution of Intra-Abdominal Abscess in Crohn DiseaseCrohn disease, a type of inflammatory bowel disease, is marked by acute flare-ups and periods of remission, and can be complicated by bowel perforation or obstruction, or intra-abdominal abscesses. Intra-abdominal abscesses occur in 10% to 30% of patients with Crohn disease; management of this complication is challenging; surgery is often necessary. A French study, GETAID, examined the role of anti-tumor necrosis factor (TNF) antibodies, such as adalimumab, in the management of those patients.READ MORE...GETAID was a prospective, multicenter, open-label observational study that enrolled 117 patients age 18 or older with a diagnosis of Crohn disease complicated by intra-abdominal or pelvic abscess. Before initiation of adalimumab, all patients had achieved complete resolution of sepsis and the abscess through administration of systemic antibiotics (median treatment length, 22 days) or percutaneous abscess drainage (median treatment length, 13 days). The study estimated the success rate of adalimumab in these patients at 24 weeks, defined as no need for steroids after week 12 and no need for intestinal resection, and no recurrence of abscess or clinical relapse. The study also sought to determine long-term success, defined as survival without abscess, relapse, or need for intestinal resection at week 104.At week 24, 87 patients (74%) achieved successful remission with the adalimumab treatment; of the 30 patients who failed to control their Crohn disease with adalimumab, 15 ultimately underwent surgery. At week 104, 72.9% of patients continued to have a successful response to adalimumab treatment, not experiencing any abscess recurrence or need for intestinal surgery. Of the 31 patients with treatment failure, 27 underwent surgical resection.In patients in whom abscesses were carefully managed before initiating treatment, the study showed the high efficacy of adalimumab in the short and long term. Researchers note that carefully preparing patients through administration of antibiotics, percutaneous drainage when feasible, and assessment of complete resolution of the abscess is mandatory to choosing the most suitable intervention (intestinal resection or anti-TNF treatment). (Bouhnik, Y, et al. (2023). Adalimumab in biologic-naïve patients with Crohn's disease after resolution of an intra-abdominal abscess: A prospective study from the GETAID. Clin Gastroenterol Hepatol, 21(13), 3365–3378.E5. Retrieved December 2023 from https://www.cghjournal.org/article/S1542-3565(23)00072-1/fulltext)Released: January 2024Nursing Drug Handbook© 2024 Wolters KluwerIncidence of Post-COVID Conditions Reduced in Vaccinated AdultsThe scale of the COVID-19 pandemic revealed the prevalence of postviral conditions. The syndrome associated with COVID-19 infection, known as long COVID or post-COVID-19 condition, is estimated to affect as many as 200 million individuals, with persistent symptoms that include fatigue, dyspnea, cognitive impairment, headache, muscle pains, and cardiac symptoms such as chest pain and palpitations.READ MORE...Studies demonstrate that receiving multiple doses of the COVID vaccine before an initial infection can dramatically reduce the risk of long COVID. A large population-based cohort study published in BMJ examined data from all adults in two regions of Sweden with a first COVID-19 infection between 27 December 2020 (start of vaccination in Sweden) and 9 February 2022 (end of full-population PCR testing). The study, which included 589,722 individuals, was part of the SCIFI-PEARL project (Swedish COVID-19 Investigation for Future Insights—A Population Epidemiology Approach using Register Linkage), a nationwide linked multiregister observational study of the pandemic. Individuals were followed from their first COVID infection until death, emigration, subsequent vaccination, reinfection, diagnosis of long COVID, or end of follow-up.Those who had received one or more COVID-19 vaccines before acute infection were 58% less likely to develop long COVID than unvaccinated individuals. Of 299,692 vaccinated individuals who were infected with COVID-19, 1,201 (0.4%) had a diagnosis of long COVID during follow-up, compared with 4,118 of 290,030 unvaccinated individuals (1.4%). Further analysis showed a dose-response relationship between vaccine exposure and the risk of long COVID:One dose decreased risk by 21%Two doses decreased risk by 59%Three or more doses decreased risk by 73%These results are similar to the cumulative protective effect of the COVID vaccines against outcomes of acute infection, such as severe illness or death.These findings underline the importance of timely vaccinations during pandemics. Future pandemic preparedness plans should continue to prioritize prompt manufacture, evaluation, and distribution of vaccines. (Lundberg-Morris, L., et al. (2023). Covid-19 vaccine effectiveness against post-covid-19 condition among 589 722 individuals in Sweden: Population based cohort study. BMJ, 383, Article e076990. Retrieved December 2023 from https://www.bmj.com/content/383/bmj-2023-076990; Sivan, M., et al. (2023). Does timely vaccination help prevent post-viral conditions? BMJ, 383, 2633. Retrieved December 2023 from https://www.bmj.com/content/383/bmj.p2633)Released: January 2024Nursing Drug Handbook© 2024 Wolters KluwerOnce-Weekly Somapacitan Is Effective Replacement for Growth Hormone in Children with GH DeficiencySomapacitan, a long-acting growth hormone (GH) derivative, has demonstrated sustained efficacy and tolerability over 2 years of treatment of GH deficiency in prepubertal children. GH deficiency is characterized by inadequate production or secretion of GH, resulting in reduced growth velocity and ultimately in reductions in adult height. The disorder can be treated by daily subcutaneous injections of recombinant GH, which can restore normal growth. But the daily injections can present a treatment burden, disrupting daily lives and family routines.READ MORE...In REAL4, a randomized, multinational, open-label, controlled parallel group phase 3 trial, consisting of a 52-week main phase and a 3-year safety extension, 200 treatment-naïve prepubertal patients in 85 sites in 20 countries were randomized 2:1 to somapacitan (0.16 mg/kg weekly; n = 132) or GH (0.034 mg/kg daily; n = 68). After 1 year, all patients were switched to somapacitan. The main outcome measured was height velocity (HV) in cm/yr at week 104; change in HV was calculated from week 0 in the first year and from week 52 in the second year.Height velocity was sustained in both groups between week 52 and week 104. Mean HV in the second year for those continuing to receive somapacitan treatment was 8.4 cm/yr; mean HV in the second year for those who switched from daily GH to somapacitan was 8.7 cm/yr. Other assessments, including changes in HV standard deviation score (SDS), changes in height SDS, bone age versus chronological age, and mean insulin-like growth factor-1 (IGF-I) SDS, were similar between the two groups and within the normal range. IGF-I release is stimulated by GH, and IGF-I SDS is commonly used as a surrogate marker for efficacy, adherence, and safety in long-term GH treatment. Mean IGF-I SDS during year 2, from baseline to week 104, in the continuous somapacitan group was 1.8, and in the group that switched from GH to somapacitan was 2.1.On a patient preference questionnaire, most parents or caregivers of patients who switched treatment preferred once-weekly somapacitan over daily GH treatment (45/50, 90%), with the vast majority (38/45) reporting a strong or very strong preference for somapacitan. The most common reasons given for this preference were:Decrease in the number of injections given: 27/45, 60%Parents less worried about remembering to give injections: 21/45, 46.7%Children less worried or annoyed about injections: 15/45, 33.3% each. Most respondents (35/45, 77.8%) said they would be more adherent to once-weekly somapacitan compared with daily GH treatment. These findings are encouraging because they indicate that somapacitan can overcome the poor treatment adherence associated with daily GH injections. (Miller, B. S., et al. (2023). Effective GH replacement with somapacitan in children with GHD: REAL4 2-year results and after switch from daily GH. J Clin Endocrinol Metab, 108(12), 3090–3099. Retrieved December 2023 from https://academic.oup.com/jcem/article/108/12/3090/7219888)Released: January 2024Nursing Drug Handbook© 2024 Wolters Kluwer
Drug News Abstracts - December 2023
Cardiovascular Benefits of Semaglutide Use for Weight ReductionAmong patients with a body mass index (BMI) of 27 or greater and preexisting CV disease but without diabetes, treatment with once-weekly semaglutide reduced the risk of a composite of death from CV causes, nonfatal MI, or nonfatal stroke by 20%. These results of SELECT (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity Trial) were presented at the 2023 American Heart Association's Scientific Sessions and were published simultaneously in the New England Journal of Medicine. Overweight and obesity are independently associated with an increased risk of CV events; semaglutide is known to reduce the risk of adverse CV events in adults with diabetes, but it's unknown if using the medication to treat overweight or obesity in the absence of diabetes will produce such effects.READ MORE...SELECT was a multicenter, double-blind, placebo-controlled trial conducted at 804 sites across 41 countries, and included 17,604 patients, mean age 61.6 years, 72.3% men, with mean BMI of 33.3 and mean Hb A1c of 5.8%; 71.5% of patients in the study were classified as having obesity (BMI of at least 30), and 67% met the criteria for prediabetes (Hb A1c 5.7% to 6.4%). Established CV disease was defined as previous MI, previous stroke, or symptomatic peripheral arterial disease. Patients were receiving other medications to manage their CV disease, including lipid-lowering medications, antiplatelet drugs, beta blockers, ACE inhibitors, and angiotensin receptor blockers. Patients were randomized to once-weekly semaglutide, titrated to a target dose of 2.4 mg (n = 8,803) or placebo (n = 8,801), while continuing their standard CV care.Use of semaglutide resulted in a 20% relative risk reduction in the composite endpoint of death from CV causes, nonfatal MI, and nonfatal stroke. A primary endpoint event occurred in 6.5% (n = 569) of those taking the GLP-1 receptor agonist and to 8.0% (n = 701) in placebo-treated patients. Findings for each element of the composite endpoint were:CV death: 2.5% with semaglutide versus 3.0% with placebo; hazard ratio (HR), 0.85Nonfatal MI: 2.7% with semaglutide versus 3.7% with placebo, HR, 0.72Nonfatal stroke: 1.7% with semaglutide versus 1.9% with placebo; HR, 0.93. Only the difference in nonfatal MI reached significance. Among secondary endpoints, heart failure events occurred in 3.4% with semaglutide versus 4.1% with placebo (HR, 0.82); all-cause death occurred in 4.3% with semaglutide versus 5.2% with placebo (HR, 0.81); and need for coronary revascularization was seen in 5.4% with semaglutide versus 6.9% with placebo (HR, 0.77). Patients receiving semaglutide were significantly less likely to progress to diabetes, defined as Hb A1c of 6.5% or higher (3.5% of patients receiving semaglutide versus 12.0% of those on placebo; HR, 0.27). Semaglutide reduced body weight by a mean of 15.2% among these patients. The mean change in body weight over 104 weeks was −9.39% with semaglutide vs. −0.88% with placebo, for an estimated treatment difference of −8.51 percentage points.What's important about the risk reduction seen with semaglutide is that the participants' CV disease was already reasonably well-controlled. Notably, the reduction in risk occurred early, before substantial weight loss could be achieved. It's worth exploring the mechanisms of such effects. (Neale, T. (2023). Full SELECT results affirm CV risk reduction with semaglutide in nondiabetics. tctMD.com. Retrieved November 2023 from https://www.tctmd.com/news/full-select-results-affirm-cv-risk-reduction-semaglutide-nondiabetics; Lincoff, A. M., et al. (2023). Semaglutide and cardiovascular outcomes in obesity without diabetes. New Engl J Med. Advanced online publication. Retrieved November 2023 from https://www.nejm.org/doi/10.1056/NEJMoa2307563?logout=true)Released: December 2023Nursing Drug Handbook© 2023 Wolters KluwerEffect of Adding Tirzepatide to Basal Insulin in Type 2 DiabetesIn patients with inadequately controlled type 2 diabetes mellitus treated with basal insulin, adding weekly tirzepatide as adjunctive treatment resulted in greater reduction in glycated hemoglobin (Hb A1c), accompanied by more weight loss and fewer incidents of hypoglycemia, than adding prandial insulin to the regimen. Basal insulins are typically the first injectable treatment option for patients with type 2 diabetes mellitus who have inadequate glycemic control on oral antidiabetic medications. Current guidelines, however, suggest adding an injectable incretin-related treatment: a glucagon-like peptide-1 receptor agonist such as tirzepatide.READ MORE...SURPASS-6, a 52-week, open-label, multicenter, phase 3b trial conducted at 135 sites in 15 countries, enrolled 1,248 adults with type 2 diabetes mellitus. Patients were randomized to once-weekly (subcutaneous injections of tirzepatide in three dosage strengths:5 mg (n = 243), 10 mg (n = 238), and 15 mg (n = 236)–or to twice daily prandial insulin lispro (n = 708). Eligible participants had Hb A1c levels of 7.5% to 11% at visit 1 and body mass index of 23 to 45. Patients were instructed to switch their diabetes treatment to insulin glargine and to discontinue other glucose-lowering medications, except for metformin, 10 weeks before randomization. At randomization, the insulin glargine dose was reduced by 30% to lower the risk of hypoglycemia, then titrated to meet an early-morning blood glucose target of 100 to 125 mg/dL.The mean change from baseline Hb A1c at week 52 with tirzepatide (pooled data) was −2.1%, and with insulin lispro was −1.1%. Final mean Hb A1c levels were 6.7% versus 7.7%, an estimated treatment difference of −0.98%. This difference was statistically significant. The mean change and estimated treatment difference compared to insulin lispro with each dosage strength was as follows:5-mg tirzepatide: −1.9%; treatment difference −0.79%10-mg tirzepatide: −2.2%; treatment difference −1.01%15-mg tirzepatide: −2.3%; treatment difference −1.13% Estimated mean change in body weight was −9.0 kg with tirzepatide and +3.2 kg with insulin lispro, a treatment difference of −12.2 kg. Mean change in body weight was −6.7 kg with 5-mg tirzepatide, −9.2 kg with 10-mg tirzepatide, and −11.0 kg with 15-mg tirzepatide. The percentage of patients reaching the target of Hb A1c <7.0% was 68% for tirzepatide and 36% for insulin lispro, for an odds ratio of 4.2. The percentage reaching Hb A1c <6.5% was 56% for tirzepatide and 22% for insulin lispro; for <5.7% was 56% for tirzepatide and 22% for insulin lispro.In addition, these effects on glycemic control enabled a decrease in the mean daily basal insulin dose, from a baseline of 46 IU to the following:13 IU with pooled tirzepatide20 IU with 5 mg tirzepatide12 IU with 10 mg tirzepatide8 IU with 15 mg tirzepatide. Depending on the tirzepatide dosage, 8% to 19% of patients were able to completely discontinue insulin glargine treatment by week 52.The most common adverse events were mild to moderate GI symptoms. The most serious was hypoglycemia. Rates of hypoglycemic events (blood glucose level <54 mg/dL) were 0.4 events/patient-year with tirzepatide and 4.4 events/patient-year with insulin lispro. Severe hypoglycemia was reported in 30 insulin lispro-treated patients and in 3 tirzepatide-treated patients. The incidence of clinically significant hypoglycemia was 12% in the 5-mg group, 9% in the 10-mg group, and 11% in the 15-mg group compared to 48% in the prandial insulin lispro group.The researchers hypothesized that the body weight loss induced by tirzepatide may have led to an improvement in insulin sensitivity. Sustained weight loss of more than 10% has known disease-modifying effects, including remission of type 2 diabetes. In exploratory analysis of the data, 32% to 57% of tirzepatide users met that goal. (Rosenstock, J., et al. (2023). Tirzepatide vs insulin lispro added to basal insulin in type 2 diabetes: The SURPASS-6 randomized clinical trial. JAMA, 330(17), 1631–1640. Retrieved November 2023 from https://jamanetwork.com/journals/jama/fullarticle/2810386)Released: December 2023Nursing Drug Handbook© 2023 Wolters KluwerFirst Fixed-Dose Triple Combination Therapy for AcneAcne pathogenesis follows multiple pathways, including abnormal keratinization, increased inflammation and sebum production, and follicular proliferation of Cutibacterium acnes (Propionibacterium acnes). Fixed-dose combination treatments that target those multiple pathways can provide better efficacy and adherence in patients with moderate to severe acne. IDP-126, a fixed-dose, triple-combination topical gel, was demonstrated to be effective and well tolerated in two clinical studies discussed in the Journal of the American Academy of Dermatology.READ MORE...The topical gel contains clindamycin phosphate 1.2%, adapalene 1.15%, and benzoyl peroxide 3.1%. Clindamycin is a lincosamide antibiotic; adapalene is a retinoid that modulates cellular differentiation, proliferation, and keratinization; and benzoyl peroxide is an antibacterial with keratolytic and mild comedolytic effects. In the phase 3 double-blind studies, each enrolling approximately 180 participants aged at least 9 years with moderate to severe acne, participants were randomized to IDP-126 gel or vehicle gel, applied once daily for 12 weeks (Study 1: IDP-126 [n = 122], vehicle gel [n = 61]; Study 2: IDP-126 [n = 120], vehicle gel [n = 60]). Treatment success was defined as achieving at least a 2-grade reduction from baseline on the Evaluator's Global Severity Score.At week 12, about half of those using IDP-126 achieved treatment success: 49.6% and 50.5% of those using the triple-combination gel reported such improvement compared to 24.9% and 20.5% using the vehicle gel in the two studies, respectively. IDP-126 also provided significantly greater reductions in lesion counts compared to the vehicle gel: 72.7% and 80.1% versus 47.6% and 59.6%, respectively, in the two studies. IDP-126 gel showed rapid reductions in lesion counts as early as week 4 and was superior to the vehicle gel in all efficacy assessments at week 12.In addition, in both studies, mean cutaneous safety and tolerability scores with the triple-combination gel were below 1 (mild) for all assessments at all visits. Most treatment-emergent adverse events were mild to moderate in severity. (Stein Gold, L., et al. (2023). Clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% gel for moderate-to-severe acne: Efficacy and safety results from two randomized phase 3 trials. J Am Acad Dermatol, 89(5), 927–935. Retrieved November 2023 from https://www.jaad.org/article/S0190-9622(23)01201-X/fulltext)Released: December 2023Nursing Drug Handbook© 2023 Wolters Kluwer
Drug News Abstracts - November 2023
Enzalutamide–Leuprolide Combination in Recurrent Prostate CancerA phase 3 study has demonstrated that in patients with prostate cancer with high-risk biochemical disease resurgence, combination treatment with enzalutamide plus leuprolide was superior to leuprolide alone in producing metastasis-free survival. Approximately 20% to 50% of patients who have undergone definitive treatment for prostate cancer experience such biochemical disease resurgence, characterized by a rise in prostate-specific antigen (PSA) levels. Patients whose PSA levels double in less than a 9-month period are at high risk for rapid disease progression.READ MORE...The EMBARK trial evaluated the efficacy and safety of enzalutamide plus leuprolide and enzalutamide monotherapy as compared with leuprolide alone in patients with prostate cancer who had high-risk biochemical resurgence. Patients were randomly assigned to enzalutamide plus leuprolide (combination group, n = 355), placebo plus leuprolide (leuprolide-only group, n = 358), and placebo plus enzalutamide (monotherapy group, n = 355). Enzalutamide (160 mg) and placebo were given orally once daily; leuprolide (2.25 mg) as a single IM or subut injection every 12 weeks. Patients were recruited from 244 sites in 17 countries; eligible patients had confirmed adenocarcinoma of the prostate, with high-risk disease, defined as PSA doubling time of 9 months or less and PSA levels of more than 2 ng/mL above nadir after radiation treatment or at least 1 ng/mL after radical prostatectomy.At 5 years, metastasis-free survival was 87.3% in the combination group, 71.4% in the leuprolide-only group, and 80.0% in the monotherapy group. Combination treatment had a 57.6% lower risk of metastasis or death (hazard ratio [HR], 0.42); monotherapy was also superior to leuprolide alone, with a 36.9% lower risk (HR, 0.63). These differences were statistically significant. Death or disease progression on imaging occurred in 45 patients (12.7%) in the combination group, 92 patients (25.7%) in the leuprolide-only group, and 63 patients (17.7%) in the monotherapy group. Those free from PSA progression at 5 years numbered 97.4% of those on combination therapy, 70% of those receiving leuprolide only, and 88.9% of those on enzalutamide monotherapy.Treatment was suspended at week 37 if PSA reached undetectable levels (less than 0.2 ng/mL). In the combination group, 90.9% of patients (321/353) had reached undetectable PSA levels; treatment was suspended for a median of 20.2 months in that group. In the leuprolide-only group, 67.8% of patients (240/354) had achieved undetectable PSA levels; treatment was suspended for a median of 16.8 months. In the monotherapy group, 85.9% of patients (304/354) had achieved undetectable PSA levels; treatment was suspended for a median of 11.1 months.The median duration of treatment was 38.7 months, with no new safety issues reported. The most common adverse events were hot flashes, fatigue, and (in monotherapy group) gynecomastia. Most were less than grade 3 in severity. Treatment was discontinued due to adverse events in 20.7% in the combination group, 10.2% in the leuprolide-only group, and 17.8% in the monotherapy group. The most common cause leading to discontinuation was fatigue.The magnitude of risk reduction for metastases and death seen in this study is consistent with the additional benefit provided by the addition of enzalutamide to treatment for metastatic hormone-sensitive prostate cancer. (Freedland, S. J., et al. (2023). Improved outcomes with enzalutamide in biochemically recurrent prostate cancer. New Engl J Med, 389, 1453–1465 https://www.nejm.org/doi/full/10.1056/NEJMoa2303974?logout=true)Released: November 2023Nursing Drug Handbook© 2023 Wolters KluwerInsulin Pumps and Intensive Education Program Improve Hb A1c in Pediatric DiabetesCompared with matched persons receiving other forms of intensive insulin treatment, pediatric patients with type 1 diabetes mellitus on insulin pumps have lower glycosylated hemoglobin (Hb A1c) levels. A longitudinal study published in Archives of Disease in Childhood examined the impact, not only of intensive insulin treatment, but also of multidisciplinary team input, on glycemic control. Use of intensive insulin treatment, including insulin pumps and multiple daily injections (MDIs), has replaced the use of fixed-dose regimens in the management of diabetes. This study compared these two regimens and further analyzed the effectiveness of an active intervention program (AIP), a diabetes nurse specialist-led service that offered contact, extra support, and education to any patient with poor or deteriorating glycemic control.READ MORE...The study examined a prospectively maintained database of clinical encounters from a large tertiary pediatric diabetes center in Ireland over a 13-year period; that center has a long-standing history of improved access to insulin pump treatment complemented by multidisciplinary team support. The dataset consisted of 25,865 encounters for 1,359 patients; the study examined data only for patients with type 1 diabetes mellitus; after excluding encounters that did not include measurement of Hb A1c and those without a certain date of diagnosis, the study ultimately examined 15,284 encounters with 995 patients.A sustained improvement in Hb A1c was observed in the insulin pump cohort that was evident as early as 6 months. By 1 year, relative to the MDI cohort, the Hb A1c with insulin pump use was 7.47% versus 8.00%, a decrease of 0.53%. This improvement was sustained over 8 years (Hb A1c 7.8% versus 8.32%, a decrease of 0.53%). The Hb A1c in patients who were assigned to receive AIP along with the intensive insulin therapy was an average 0.95% higher than otherwise identical patients. After 6 months of the AIP sessions, Hb A1c dropped by a mean of 0.81%, a finding that was consistent no matter which forms of intensive insulin therapy were used.Results of this study demonstrate that, although new technologies for delivery of insulin therapy have a significant role to play in glycemic control, so too does the action of the diabetes nurse educator and the multidisciplinary team. This study was limited by its focus on Hb A1c alone, as other factors can influence the development of long-term diabetes complications. The authors stress that the multidisciplinary team will continue to need support and resources to meet the needs of their pediatric patients. (Foran, J., et al. (2023). Close intervention sessions complement intensive insulin therapy in paediatric diabetes: A longitudinal study. Arch Dis Child, 108, 818–823. https://adc.bmj.com/content/108/10/818)Released: November 2023Nursing Drug Handbook© 2023 Wolters KluwerCurrent Therapies for Nonhospitalized COVID-19 PatientsAntivirals for nonhospitalized patients with COVID-19 infection prevent progression to severe illness, hospitalization, and death, but utilization of these therapies remains low. A viewpoint published in JAMA summarizes the available antivirals, and discusses which patients are most likely to benefit from them. Clinical trials conducted before widespread SARS-CoV2 vaccination and before the widespread circulation of the omicron variants demonstrated the effectiveness of these treatments in preventing progression to severe COVID-19. After widespread immunization campaigns, the lower hospitalizations and death rates have made it difficult to assess current benefits. Recent retrospective analyses have, however, suggested that nirmatrelvir–ritonavir continues to have value in older persons and others who develop the infection.READ MORE...The combination antiviral nirmatrelvir–ritonavir (marketed as Paxlovid) was approved by the FDA in May 2023 for treatment of mild to moderate COVID-19 in adults at high risk of progression. The oral SARS-CoV2 protease inhibitor is given within 5 days of symptom onset and is taken twice daily for 5 days; it has been shown to reduce hospitalization and death by 86%. It's considered safe to use in pregnant patients, and its use is limited only by the action of ritonavir on cytochrome P3A4, which results in numerous potential drug interactions.Remdesivir, a nucleotide prodrug that inhibits viral RNA polymerase, has been approved for use in adult and pediatric patients 28 days or older at high risk for progression to severe COVID-19. It's given as soon as possible after diagnosis, within 7 days of symptom onset, via IV infusion once daily for 3 days. It also was shown in trials to reduce hospitalization or death by 87% compared with placebo. Its use in pregnancy is not recommended; in general, the need to administer remdesivir IV limits its accessibility for many patients.Molnupiravir, an oral agent that inhibits viral replication by inducing viral RNA mutagenesis, is given twice daily for 5 days. It's substantially less effective than other antivirals, reducing hospitalizations by 30% compared to placebo in clinical trials. It is not recommended for use in children or during pregnancy, but it is an option for adults at risk for progression to more severe COVID-19 infection for whom the other treatment options are inappropriate or are unavailable.When choosing between these options, the prescriber must take patient characteristics into consideration. Although nirmatrelvir–ritonavir is the preferred agent, it may not be possible to use it because of serious drug interactions or in patients with severe kidney disease. Remdesivir is the next preferred choice, although administering 3 days of IV treatment presents challenges for many patients. Molnupravir should only be used if the other antivirals aren't accessible or are inappropriate, and only with patient counseling. (Chew, K. W., et al. (2023). COVID-19 therapeutics for nonhospitalized patients–Updates and future directions. JAMA, 330(16), 1519–1520. https://jamanetwork.com/journals/jama/article-abstract/2810358)Released: November 2023Nursing Drug Handbook© 2023 Wolters Kluwer
Drug News Abstracts - October 2023
Aroxybutynin and Atomoxetine Combination Effective in Treatment of Obstructive Sleep ApneaContinuous positive airway pressure (CPAP) is a highly efficacious treatment for obstructive sleep apnea (OSA), but it's often not well tolerated; a pharmacologic alternative has been sought. Combination treatment with the antimuscarinic aroxybutynin added to the norepinephrine reuptake inhibitor atomoxetine demonstrated clinically significant improvement over a 4-week period in adults with mild to severe OSA in a phase 2, randomized, double-blind trial.READ MORE...The trial randomized participants into 4 groups, comparing two dosage strengths of the combination drug (2.5 mg aroxybutynin/75 mg atomoxetine and 5 mg aroxybutynin/75 mg atomoxetine), atomoxetine alone (75 mg), and placebo. Participants were adults with OSA and an apnea-hypopnea index (using the greater than or equal to 4% desaturation criterion for hypopnea; AHI4) of 10 to 45 based on polysomnography. Those using CPAP or other devices were included in the study if they had discontinued use more than 2 weeks before the baseline polysomnogram.Both doses of the combination therapy showed clinically meaningful improvements over the 1-month period in patients with mild to severe OSA. The AHI4 was reduced from a median of 20.5 to 10.8 with the 2.5/75 mg dose, a 47.1% reduction, and from a median of 19.4 to 9.5 with the 5/75 mg dose, a 42.9% reduction, compared to a decrease from a median of 19.0 to 11.8 with atomoxetine alone (−38.8%) and from a median of 20.1 to 16.3 with placebo (−18.9%). The improvement in AHI4 was seen during both rapid-eye-movement (REM) sleep and non-REM sleep; it was statistically significant in non-REM sleep and in either the supine or lateral positions. Compared to placebo, the hypoxic burden was reduced by 12.7 on the 2.5/75 mg dose and by 16.6 on the 5/75 mg dose of aroxybutynin/atomoxetine. A significant improvement in the PROMIS fatigue score was seen with the smaller dose versus placebo (−3.56) and atomoxetine alone (−3.49). The combination didn't affect total sleep time or sleep latency, but did reduce REM sleep, although the decrease was smaller than that seen in single-night studies, suggesting that the effect on REM sleep may ease over time.Aroxybutynin/atomoxetine didn't differ significantly from atomoxetine alone in its effect for most respiratory parameters, suggesting that the noradrenergic activity of atomoxetine is the primary reason for its effect on upper airway obstruction. However, atomoxetine alone was more likely to disturb sleep than either dose (23.93 fewer minutes of sleep compared to the 2.5/75 mg dose and 16.09 fewer minutes compared to the 5/75 mg dose). The current study suggests that the optimal dosage of the combination may be 2.5/75 mg; higher doses increase the antimuscarinic side effects. It does not eliminate sleep-disordered breathing, as can occur with CPAP. Its lower effectiveness must be balanced against the lower adherence to CPAP, or the practice of using CPAP only part of the night.The combination demonstrated meaningful improvements in OSA and was generally well tolerated over the 1-month study period, suggesting that it may be an effective treatment option for some patients. Further study in larger populations for longer durations will help identify those populations who will have the best response to aroxybutynin/atomoxetine treatment. (Schweitzer, P. K., et al. (2023). The combination of aroxybutynin and atomoxetine in the treatment of obstructive sleep apnea (MARIPOSA): A randomized controlled trial. Am J Respir Crit Care Med. Advance online publication. Retrieved October 2023 from https://www.atsjournals.org/doi/10.1164/rccm.202306-1036OC?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed)Released: October 2023Nursing Drug Handbook© 2023 Wolters KluwerLevodopa–Carbidopa Intestinal Gel Effective Long-Term in Advanced Parkinson DiseaseTreatment with levodopa–carbidopa intestinal gel improves motor and nonmotor symptoms in patients with advanced Parkinson disease; use of the gel demonstrated OFF time improvements above the minimal clinically important difference (MCID) of 1 hour in this population, improvements that were maintained over 3 years. These are the results from DUOGLOBE, an international, prospective, long-term, real-world, observational study of patients with advanced Parkinson disease initiating levodopa–carbidopa intestinal gel in routine clinical care.READ MORE...Levodopa–carbidopa intestinal gel provides levodopa, the gold standard treatment for Parkinson disease, in a continuous daytime infusion to patients with advanced Parkinson disease, allowing levodopa levels to be maintained at a constant level within the therapeutic window. This bypasses the usual diminishment of effectiveness of levodopa that occurs as the disease progresses.DUOGLOBE was conducted in 55 sites in 10 countries. Patients enrolled in the study had no prior exposure to levodopa–carbidopa intestinal gel, a Mini-Mental State Exam score of at least 24, no prior surgery for Parkinson disease, and no current use of subcutaneous apomorphine infusion to treat their Parkinson disease. Dosage was individualized, and other Parkinson medications were permitted at the discretion of the treating practitioner. One-year interim results of the study had indicated significant improvements in motor symptoms (including OFF time and dyskinesia) and nonmotor symptoms (including sleep), health-related quality of life (QOL), and caregiver burden.The study included 195 patients in the 3-year analysis, 61.5% male, with a mean age of 70.2 years and a mean disease duration of 11.2 years. Mean treatment duration was 923.5 days, with median daily duration of 16 hours. The daily dose of the intestinal gel remained stable from Day 1 (1,241 mg/day) through Month 36 (1,365.4 mg/day). Results of the study have demonstrated beneficial effects on motor symptoms: decrease in OFF time and increase in ON time without troublesome dyskinesia. Mean daily hours spent in the OFF state significantly decreased from baseline and remained decreased through Month 36 (−3.3 hours at Month 36). Significant improvements were seen in other measures: United Dyskinesia Rating Scale total scores were significantly reduced from baseline at all visits through Month 36 (mean reduction in score at month 36: −5.9). The subscore of ON dyskinesia was significantly reduced from baseline through Month 24, above the MCID of −2.1, and the subscore of OFF dystonia was significantly reduced through Month 36, above the MCID of −1.8. These parallel improvements (significant decrease in OFF time coupled with significant improvements in ON dyskinesia) are likely due to the continuous delivery afforded by levodopa–carbidopa intestinal gel. Nonmotor total scores also demonstrated significant, sustained improvements from baseline to Month 36 (mean, −14.3), as did scores on three of the nine subdomains (sleep and fatigue, mean −3.7; GI tract, mean −2.5; and miscellaneous nonmotor symptoms, mean −3.9). Finally, health-related QOL significantly improved through Month 24 (score −6.0 on the 8-item Parkinson Disease Questionnaire) and caregiver burden significantly improved through Month 30 (score of −2.3 on Modified Caregiver Strain index).Slightly more than half of patients (n = 107) experienced a serious adverse event, with event frequency and type as could be expected in this patient population of advanced age with multiple comorbidities. The most common serious adverse events were falls (n = 8), worsening of Parkinson disease (n = 8), and UTI (n = 7).These findings contribute to our understanding of long-term management of patients with advanced Parkinson disease. Of particular interest is that improvements above the MCID in OFF time, dyskinesia, nonmotor symptoms, sleep, and health-related QOL were maintained long-term in a population with an otherwise progressive disease.(Chaudhuri, K. R., et al. (2023). Levodopa carbidopa intestinal gel in advanced Parkinson's disease: DUOGLOBE final 3-year results. J Parkinson's Dis, 13(5), 769–783. Retrieved October 2023 from https://content.iospress.com/articles/journal-of-parkinsons-disease/jpd225105)Released: October 2023Nursing Drug Handbook© 2023 Wolters Kluwer
Drug News Abstracts - September 2023
Bimekizumab Efficacy for Psoriasis Persists Long-TermBimekizumab produces dual inhibition of interleukin-17A and -17F (IL-17A/F). BE RADIANT, a phase 3b, randomized clinical trial, showed that such dual inhibition with bimekizumab was superior to IL-17A inhibition alone with secukinumab. In the open-label extension of BE RADIANT, in which all patients received bimekizumab, the high levels of clinical response seen through the first 48 weeks of treatment were generally sustained through 96 weeks.READ MORE...In BE RADIANT, patients received bimekizumab (320 mg every 4 weeks or every 8 weeks) or secukinumab (300 mg weekly to week 4, then every 4 weeks). Results from Year 1 showed that bimekizumab produced high rates of complete skin clearance (100% improvement on the Psoriasis Area and Severity Index, or PASI 100). At baseline, 743 patients were randomized to bimekizumab (n = 373) or secukinumab (n = 370); of those, 336 (90.1%) and 318 (85.9%), respectively, entered the open-label extension. They were randomized as follows:All patients who had not achieved PASI 90 by week 48 were assigned to receive bimekizumab every 4 weeks.Those who had achieved PASI 90 on an every-8-week schedule continued receiving bimekizumab on that schedule.Those who had achieved PASI 90 on an every-4-week schedule or on secukinumab were randomized to receive bimekizumab on either schedule; at week 64, when phase 3 data demonstrated similar efficacy for the two schedules, those still receiving the drug on an every-4-week schedule were switched to every 8 weeks. At week 48, more patients had achieved complete skin clearance (PASI 100) with bimekizumab than secukinumab (74.8% versus 52.8%). The proportions of patients with PASI 100 responses were maintained to week 96 in patients who had continuously received bimekizumab (70.8%), and the proportion increased in patients who switched from secukinumab to bimekizumab (76.6%). Results were consistent for patients who received bimekizumab by either schedule. Improvements on other measures were also sustained in patients receiving continuous bimekizumab and improved in those who switched from secukinumab at week 48. For example, the proportions of patients achieving improvements in at least two categories from baseline in the Investigator's Global Assessment were 94.0% with bimekizumab at week 48 and 90.9% at week 96, and 85.1% with secukinumab at week 48, improving to 90.7% in those who switched to bimekizumab. In addition, the proportions of patients achieving clear skin so that less than 1% of BSA was affected by psoriasis at week 48 for bimekizumab was 88.4%, maintained at week 96 in 86.9%, and 75.9% at week 48 for secukinumab, rising to 87.4% at week 96 in those who switched to bimekizumab.Adverse effects on the open-label extension generally decreased or stayed consistent relative to 1-year data. The most common adverse events were nasopharyngitis, oral candidiasis, and UTI. Despite the expected increased risk of oral candidiasis with dual therapy against IL-17A/F, most cases were mild or moderate. Only one complex case of systemic candidiasis was seen. Note that the 2-year safety data includes a greater proportion of patients receiving every-8- week dosing than in Year 1. (Strober, B., et al. (2023). Bimekizumab efficacy and safety in patients with moderate to severe plaque psoriasis: Two-year interim results from the open-label extension of the randomized BE RADIANT phase 3b trial. J Am Acad Dermatol. 2023; 89(3), 486–495. Retrieved October 2023 from https://www.jaad.org/article/S0190-9622(23)00782-X/fulltextReleased: September 2023Nursing Drug Handbook© 2023 Wolters KluwerHow Did the COVID-19 Pandemic Affect Adherence to Psychotropic Medications?The COVID-19 pandemic and associated public health measures shifted the ways people accessed health care. Canadian public health measures in response to the pandemic included social distancing, travel bans, reduced physical contact, and restrictions on nonessential services. A retrospective, population-wide observational cohort study, conducted at the Manitoba Center for Health Policy, looked to determine the effects of the challenges posed by the pandemic, from difficulty getting to pharmacies and clinics to overall supply chain problems, on adherence rates for various psychotropic medications.READ MORE...The researchers hypothesized that the proportion of patients achieving a medication possession ratio (MPR) of at least 80% (0.80) would decrease compared to expected, and that the rates of drug discontinuation would increase. MPR, the most used measure of adherence involving administrative data, is calculated by determining the days' supply for all fills of a given medication prescription and dividing it by the number of days in the same period. The study monitored adherence for the last three quarters of 2019 and all of 2020 and compared the magnitude of change in adherence in each quarter in 2020 to the previous quarter and to its respective quarter in 2019. In addition, quarterly discontinuation rates were determined by counting those who had good adherence in the preceding two quarters who then failed to fill their prescription.As expected with the implementation of the public health measures to combat the pandemic in 2020-Q2, antidepressant adherence was lower in that quarter compared to the previous quarter. But they rebounded in Q3 and Q4, surpassing the adherence rates of the previous year. Compared with the expected trend, the proportion of individuals adherent to antidepressants and stimulants increased in 2020-Q4 and of anxiolytics and cannabinoids in 2020-Q3. The difference in adherence rates for antidepressants in 2020-Q4 was approximately twofold higher than expected (2.27). Adherence to anxiolytics was 1.39 times greater than expected in 2020-Q3. The proportion of individuals adherent to stimulants decreased in 2020-Q3 (−3.28), and no changes were observed for adherence to antipsychotics.All drug classes except lithium showed decreases in drug discontinuation during the pandemic compared to 2019, possibly due to the increased mental health burden brought on by the pandemic causing a reluctance to discontinue psychotropic medications. The odds of discontinuing antidepressants in each quarter of 2020 were compared to the respective quarter in 2019; odds ratios (ORs) were 0.81, 0.88, and 0.86 for Q2, Q3, and Q4, respectively. This was also true for anxiolytics/sedative-hypnotics, with ORs of 0.85, 0.86, and 0.90 for Q2, Q3, and Q4, respectively. For cannabinoids, the odds of discontinuing were lower in two quarters of 2020: OR, 0.53 and 0.62 for Q2 and Q3, respectively, and the odds of discontinuing stimulants was lower in Q2 and Q4 of 2020 compared with 2019, with ORs of 0.92 and 0.74, respectively.By the time of the second wave of COVID-19 that was predominant in the final quarter of 2020, patients had adjusted. Although accessing in-person clinics was still restricted, patients were able to access medication during the pandemic. Further study of the impact of the pandemic on adherence long-term and in differences in access for specific populations, such as urban or rural populations, is ongoing. In addition, it will be necessary to determine whether the higher adherence to certain medications will have an impact on future health service use and long-term outcome. (Froese, B., et al. (2023). Adherence to psychotropic medication before and during COVID-19: A population-wide retrospective observational study J Clin Psychopharmacol, 43(4), 313–319. Retrieved October 2023 from https://journals.lww.com/psychopharmacology/fulltext/2023/07000/adherence_to_psychotropic_medication_before_and.3.aspxReleased: September 2023Nursing Drug Handbook© 2023 Wolters KluwerProton Pump Inhibitor Use and the Risk of DementiaProton pump inhibitors (PPIs; lansoprazole, omeprazole, pantoprazole, rabeprazole, esomeprazole), available by prescription and OTC, are currently a first-line option for short-term treatment (4 to 8 weeks) of gastroesophageal reflux disease and peptic ulcers. Although they have not been approved for longer-term use, such use is still common; long-term use of PPIs has been linked to numerous health conditions, including stroke, CV disease, chronic kidney disease, and dementia. Studies on the links between PPI use and the risk of dementia have produced mixed results, with little information on the effects of cumulative use.READ MORE...Using data from the Atherosclerosis Risk in Communities (ARIC) study, a community-based cohort, from the time of enrollment (1987 to 1989) through 2017, a trial published in Neurology demonstrated a significantly higher risk of dementia in patients who used PPIs for more than 4½ years. The ARIC cohort originally numbered 15,792; participants attended multiple in-person visits over the years. Visit 5, which occurred between 2011 and 2013 and was attended by 6,538 participants, was the first in which PPI use was common. Analysis, using Visit 5 as baseline, included 5,712 participants who were dementia-free at that point. To track medication use, participants were asked to bring to in-person clinic visits all OTC and prescription medications they had taken in the previous 2 weeks or to report that same information on annual phone calls.Current PPI use was defined as actively using the drugs at Visit 5; cumulative PPI use was defined as duration prior to that visit, sorted according to exposure (1 day to 2.8 years, more than 2.8 years to 4.4 years, and more than 4.4 years). Cumulative PPI use ranged from 112 days to 20.3 years by 2011; median use was 3.8 years and mean use was 4.4 years. Dementia status was determined by exam at in-person visits 6 and 7; for those only reached by phone, the Six-Item Screening tool was conducted, with follow-up as appropriate. The researchers identified 585 cases of dementia over median follow-up (10.2%).Current users of PPIs at Visit 5 (n = 1,450) were not associated with a significantly higher risk of developing dementia during follow-up than those not using PPIs (HR, 1.05). Among cumulative users (n = 1,490), participants who had used PPIs for more than 4.4 years by Visit 5 were at a 38% higher risk of developing dementia later in life (HR, 1.38) compared to those who had never used PPIs. Short-term (1 day to 2.8 years) and intermediate cumulative use (2.8 years to 4.4 years) were not associated with a significant risk of dementia.The long-term nature of ARIC enabled these researchers to consider the long latency of dementia. Further studies are needed to enable us to understand possible pathways for the development of dementia related to this long-term cumulative use of PPIs. (Northuis, C., et al. (2023). Cumulative use of proton pump inhibitors and risk of dementia: The Atherosclerosis Risk in Communities study. Neurology. Advanced online publication. Retrieved October 2023 from https://n.neurology.org/content/neurology/early/2023/08/09/WNL.0000000000207747.full.pdfReleased: September 2023Nursing Drug Handbook© 2023 Wolters Kluwer
Drug News Abstracts - August 2023
Active Monitoring Demonstrates Safety of COVID-19 Vaccination in ChildrenResults from near-real-time monitoring of health outcomes after BNT162b2 (Pfizer/BioNTech) COVID-19 vaccination provide additional evidence of vaccine safety in the pediatric population. In the population-based cohort study of more than 3 million children ages 5 to 17 who received the BNT162b2 COVID-19 vaccine, the first approved for use in the pediatric population, through mid-2022, active monitoring of 20 health outcomes was performed.READ MORE...The study enrolled 3,017,352 health plan members, using data from three commercial claims databases after administration of the BNT162b2 COVID-19 vaccine (5,901,825 doses). It included persons ages 5 to 17 who received the vaccine from the earliest dates of its Emergency Use Authorization through June 2022 and divided the study population into three age groups: ages 5 to 11, 12 to 15, and 16 to 17. Conducted under the FDA's public health surveillance mandate, the study used a near-real-time monitoring framework that enables early detection of potential safety signals, including rare outcomes that may not be identified in other trials.They conducted monthly sequential testing and generated incidence rate ratios of observed outcome rates compared with expected rates. The health outcomes the study monitored for included cardiac outcomes, including myocarditis/pericarditis and MI; thrombotic complications, including deep vein thrombosis and stroke; neurologic reactions such as Guillain-Barré and other reactions, including anaphylaxisOnly myocarditis/pericarditis met the statistical threshold for safety after vaccination. Safety signal was observed after the primary series of vaccines in all three databases for age groups 12 to 15 and 16 to 17. In dose-specific analysis, it was detected after dose 2 in these age groups. There was no evidence of this outcome in the youngest age group (ages 5 to 11 years). Of the 153 cases of myocarditis/pericarditis that this monitoring found, medical records review was conducted on 37 cases. Of these, 73.0% (n = 27) were confirmed as myocarditis/pericarditis, of whom 25 were male; 19 patients were hospitalized for it, with a mean length of stay of 2.8 days.These results provide reassuring real-world evidence of vaccine safety. They also provide evidence in support of reports in peer-reviewed journals that suggested increased risk for myocarditis/pericarditis with mRNA vaccines, especially among young males. It's still a very rare event, with an average incidence of 39.4 cases per million doses administered to children ages 5 to 17. (Hu, M., et al. (2023). Safety of the BNT162b2 COVID-19 vaccine in children aged 5 to 17 years. JAMA Pediatr, 177(7), 710–717. Retrieved July 2023 from https://jamanetwork.com/journals/jamapediatrics/fullarticle/2805184Released: August 2023Nursing Drug Handbook© 2023 Wolters KluwerEarly Treatment Initiation Beneficial in Multiple SclerosisA study published in Neurology demonstrated that early treatment for multiple sclerosis (MS) is linked with lower risk of disability than seen in patients who begin treatment later. MS, which affects 2.8 million people worldwide, is an autoimmune condition that results in damage to the myelin sheaths that cover and protect nerve cells, resulting in disability, including loss of balance, weakness, and paresthesia. The study identified 580 patients with MS with a first demyelinating event recorded between 1994 and 2021 who had received treatment with at least one disease-modifying drug. Patients were categorized into three groups according to the time frame between that first demyelinating event and the first use of a disease-modifying drug, from very early treatment group (less than 6 months; n = 194), to middle treatment group (6.1 to 16 months; n = 192), to latest treatment group (greater than 16 months; n = 194). Researchers assessed the association of receiving very early treatment with the risk of long-term disability, including the magnetic resonance score (MRS), for an average follow-up of 11 years.READ MORE...By starting treatment earlier, the study shows, patients may be able to prevent or minimize further damage. Those in the earliest treatment group had a 45% lower risk of disability progression to a score of 3 on the 10-point Expanded Disability Status Score (EDSS) by the end of the study compared to those treated latest. A score of 3 on the EDSS reflects a patient who can walk unassisted but has either moderate disability in one of eight areas (muscle weakness, balance and coordination, speech and swallowing, numbness, bowel and bladder function, visual function, thinking skills) or mild disability in three or four of those eight areas. In addition, those in the earliest treatment group were 60% less likely to progress to secondary progressive MS compared with those who began treatment latest. Those treated earliest were also 50% more likely to remain stable a year after initial treatment than those in the latest treatment group.Previous studies haven't integrated magnetic resonance (MR) findings when evaluating outcomes. To confirm the role of MR findings in treatment decisions, researchers in this study also determined the time elapsed from the first demyelinating event to treatment initiation in all patients with available radiologic information. A 5-point MRS was determined, according to the sum of these indications:more than 9 brain lesions (1 point)at least 1 infratentorial lesion (1 point)at least 1 spinal cord lesion (1 point)at least 1 contrast-enhancing brain lesion (1 point)at least 1 contrast-enhancing spinal cord lesion (1 point). They found a 62.4% reduction in median time between the first demyelinating event and the first ever treatment initiation from patients with an MRS of 5 versus an MRS of 1.  This study contributes to the understanding of how treating MS at different stages affects disability and can improve treatment strategies as well as the patient's quality of life. (Lennon, A. (2023). Multiple sclerosis: Early treatment may slow disease progression. Med News Today. Retrieved July 2023 from https://www.medicalnewstoday.com/articles/starting-treatment-at-first-sign-of-ms-symptoms-could-slow-down-progression; Cobo-Calvo, A., et al. (2023). Association of very early treatment initiation with the risk of long-term disability in patients with a first demyelinating event. Neurology, 10, Article 207664. Retrieved July 2023 from https://n.neurology.org/content/early/2023/07/19/WNL.0000000000207664)Released: August 2023Nursing Drug Handbook© 2023 Wolters KluwerDetermining Effectiveness of Long-Term Beta Blocker Therapy after Acute MIBeta blockers are known to improve quality of life and reduce deaths in patients after MI, but current guidelines, both from the American Heart Association/American College of Cardiology and the European Society of Cardiology, don't provide clear answers as to the usefulness of long-term beta blocker treatment or the optimal duration of such use. A study published in the Journal of the American Heart Association examined the associations between the duration of beta blocker therapy and outcomes and showed that among patients post-MI who are stable after undergoing percutaneous coronary intervention (PCI), longer maintenance therapy with beta blockers, especially for longer than 36 months, was associated with better clinical outcomes.READ MORE...The retrospective study analyzed data from COREA-AMI, a nationwide PCI registry, collected from consecutive admissions for MI at tertiary care hospitals in Korea from January to August 2014. All patients underwent PCI within 48 hours after admission; then were prescribed dual antiplatelet therapy (100 mg of aspirin plus a P2Y12 inhibitor, either 75 mg clopidogrel, 10 mg prasugrel, or 90 mg ticagrelor b.i.d.) for at least 1 year. The patients received further therapy, including statins, beta blockers, and renin-angiotensin-aldosterone inhibitors, according to guidelines. The most widely used beta blockers were carvedilol (52.7%), bisoprolol (35.2%), and nebivolol (9.0%). The 7,159 patients enrolled were event-free for 3 months after MI; patients were divided into four groups according to the duration of beta blocker use; less than 12 months (n = 1,729), 12 to less than 24 months (n = 809), 24 to less than 36 months (n = 864), and greater than or equal to 36 months (n = 3,757). The study compared the clinical benefits of beta blocker maintenance use stratified by duration of use, examining for a composite outcome of all-cause death, recurrent MI, heart failure, or hospitalization for unstable angina. In addition, researchers specifically evaluated the efficacy of beta blocker use beyond 36 months.During the mean 5 years of follow-up, 1,788 primary outcomes occurred (in 25% of patients overall), including these components:1,112 all-cause deaths333 recurrent MIs175 cases of heart failure695 hospitalizations for unstable angina. In addition, 805 cardiac deaths were seen in the overall population of patients. Significant stepwise decreases in the incident rate of three outcomes were seen.  The composite outcome occurred in: 34.1% of patients using beta blockers for less than 12 months (n = 590/1,729)33.6% of patients using beta blockers for 12 to less than 24 months (n = 272/809)29.3% of patients using beta blockers for 24 to less than 36 months (n = 253/864)17.9% of patients using beta blockers for greater than or equal to 36 months (n = 673/3,757)All-cause death occurred in: 26.7% of patients using beta blockers for less than 12 months (n = 461/1,729)24.8% of patients using beta blockers for 12 to less than 24 months (n = 201/809)19.9% of patients using beta blockers for 24 to less than 36 months (n = 172/864)7.4% of patients using beta blockers for greater than or equal to 36 months (n = 278/3,757)Cardiac death occurred in: 20.5% of patients using beta blockers for less than 12 months (n = 354/1,729)17.3% of patients using beta blockers for 12 to less than 24 months (n = 140/809)14.0% of patients using beta blockers for 24 to less than 36 months (n = 121/864)5.1% of patients using beta blockers for greater than or equal to 36 months (n = 190/3,757). More than half (52.5%) of patients continued beta blocker treatment for longer than 36 months. In the 3-year landmark analysis of 5,918 patients who remained event-free for 36 months, the 2,593 patients who received beta blocker treatment for less than 36 months exhibited considerably higher risks, not only of the primary composite outcome (adjusted hazard ratio [HR], 1.59), but also of all-cause death (adjusted HR, 1.88), cardiac death (adjusted HR, 2.25), recurrent MI (adjusted HR, 1.57), and heart failure (adjusted HR, 1.95), compared to those using beta blockers for greater than or equal to 36 months.These results have clinical implications regarding the efficacy of long-term maintenance therapy after reperfusion. Further trials can help determine the optimal duration of such maintenance. (Abbott, J. D., & Goldberger, J. J. (2023). β-blocker therapy after myocardial infarction: A little goes a long way. J Am Heart Assoc, 12(15), Article e030867. Retrieved July 2023 from https://www.ahajournals.org/doi/10.1161/JAHA.123.030867; Lee, M., et al. (2023). Comparative effectiveness of long-term maintenance beta-blocker therapy after acute myocardial infarction in stable, optimally treated patients undergoing percutaneous coronary intervention. J Am Heart Assoc, 12(15), Article e028976. Retrieved July 2023 from https://www.ahajournals.org/doi/10.1161/JAHA.122.028976)Released: August 2023Nursing Drug Handbook© 2023 Wolters KluwerMirikizumab Can Induce Remission in Ulcerative ColitisUlcerative colitis is a chronic disease of the colon and rectum in which inflammation of the mucosa leads to rectal bleeding, increased stool frequency, urgency of bowel movements, and abdominal pain. Treatments include anti-inflammatory agents, biologics, and immunomodulators; these target the pro-inflammatory cytokine interleukin-23. Mirikizumab is a humanized IgG variant Mab that specifically binds to the p19 subunit against IL-23. A study published in the New England Journal of Medicine demonstrated the effectiveness of mirikizumab across clinical, symptomatic, endoscopic, and histologic measures of ulcerative colitis, even in patients who had previous treatment failure with conventional immunosuppressants, biologics, or tofacitinib.READ MORE...The study included two phase 3 double-blind, placebo-controlled trials totaling 52 weeks of treatment. Lucent-1 lasted 12 weeks and enrolled 1,162 adults with moderately to severely active ulcerative colitis; 868 patients were randomly assigned to mirikizumab 300 mg IV every 4 weeks for 12 weeks and 294 patients to placebo. Lucent-2, the maintenance phase, enrolled 544 responders to Lucent-1 (365 from the mirikizumab group and 179 from the placebo group), who were then rerandomized 2:1 to mirikizumab 200 mg subcutaneous every 4 weeks for 40 weeks or placebo. Patients who didn't respond to either arm of the induction trial (Lucent-1) received open-label extended induction treatment with an additional 3 doses of mirikizumab IV every 4 weeks for an additional 12 weeks. If they responded to that extended trial, they were added to the cohort for the maintenance trial; if there was no response after this extended induction, the patients were withdrawn from the trial.Researchers determined clinical remission at week 12 in Lucent-1 and at week 40 (52 weeks overall) in Lucent-2. They also examined the patients for clinical response, endoscopic remission, and increase in bowel-movement urgency. The severity of ulcerative colitis was assessed by means of a modified Mayo score (scale, 0 to 9); those enrolled in the study had a score from 4 to 9, with an endoscopic subscore (range, 0 to 3) of 2 to 3. Clinical remission was defined as 0 on the stool-frequency subscore, or a stool-frequency subscore of 1 with a decrease of at least 1 point from baseline, a rectal-bleeding subscore of 0, and an endoscopic subscore of 0 to 1.Mirikizumab was shown to be more effective than placebo both in inducing and maintaining clinical remission in patients with ulcerative colitis. Significant differences were seen in clinical response, endoscopic remission, and bowel-movement urgency than with placebo. A significantly higher percentage of patients in the mirikizumab group than the placebo group had clinical remission at week 12 of the induction trial (Lucent-1): 24.2% versus 13.3% (difference, 11.1 percentage points) and at week 40 of the maintenance trial (Lucent-2): 49.9% versus 25.1% (difference, 23.2 percentage points). Results also favored the mirikizumab group for the major secondary endpoints of clinical response, remission of symptoms at weeks 4 and 12, clinical response in patients who had previous treatment failures, and histologic-endoscopic mucosal improvement. Among the 272 patients in the open-label induction extension, 53.7% had clinical response and 11.4% had clinical remission by week 12; of the 144 patients in this group who went on to receive mirikizumab in the maintenance trial, clinical remission was maintained in 72.2%. Overall incidence of adverse events was similar in the mirikizumab and placebo groups during both phases of the trial, although nasopharyngitis and arthralgia were reported more frequently with mirikizumab than with placebo. Among the 1,217 patients treated with mirikizumab at any time during the two Lucent trials, 15 experienced an opportunistic infection, including 6 with herpes zoster, and 8 had cancer, including 3 with colorectal cancer; among those receiving placebo, 1 had herpes zoster and none had cancer.This report presents another option for people with ulcerative colitis, especially those who didn't respond to other medications. Longer trials are ongoing to assess more prolonged efficacy and safety of mirikizumab in ulcerative colitis. (D'Haens, G., et al. (2023). Mirikizumab as induction and maintenance therapy for ulcerative colitis. New Engl J Med, 388, 2444–2455. Retrieved July 2023 from https://www.nejm.org/doi/full/10.1056/NEJMoa2207940; Bailey, E. (2023). New drug mirikizumab shows promise in ulcerative colitis remission. Medical News Today. Retrieved July 2023 from https://www.medicalnewstoday.com/articles/new-drug-mirikizumab-shows-promise-in-ulcerative-colitis-remission)Released: August 2023Nursing Drug Handbook© 2023 Wolters Kluwer
Drug News Abstracts - July 2023
Fruquintinib Prolongs Survival in Metastatic Colorectal CancerNealy 50% of patients with colorectal cancer will develop distant metastases, and the overall survival rate for these patients is about 15%. An international, randomized, double-blind, placebo-controlled, phase 3 study published in The Lancet demonstrated that fruquintinib, a selective inhibitor of vascular endothelial growth factor receptors 1, 2, and 3 is effective as a treatment for such metastatic colorectal cancer.READ MORE...FRESCO-2 was conducted at 124 hospitals and cancer centers across 14 countries. It enrolled 691 patients with documented metastatic colorectal adenocarcinoma who had progressed on or been intolerant to cytotoxic and targeted therapies. They were randomly assigned to fruquintinib 50 mg (n = 461) or placebo (n = 230) once daily on days 1 to 21 in 28-day cycles. The patients had received a median of four lines of previous systemic therapy for the disease; 73% of patients had received more than three lines of therapy.The use of fruquintinib resulted in meaningful improvements in overall and progression-free survival among patients who had progressed or been intolerant to multiple previous therapies. At 6 months, 24% of the patients in the treatment group demonstrated progression-free survival, compared to 1% in the placebo group. The treatment group also had longer overall survival than the placebo group, with a 34% reduced risk of death. The median survival of patients in the fruquintinib group was 7.4 months, compared with 4.8 months in the placebo group (hazard ratio, 0.66).Adverse events were generally manageable, with minimal discontinuation due to treatment-related toxicity. Grade 3 or worse adverse events occurred in 286 (63%) who received fruquintinib and 116 (50%) who received placebo. The most common of these were hypertension (n = 62 [14%]), asthenia (n = 35 [8%]), and hand-foot syndrome (n = 29 [6%]). One treatment-related death occurred in each group.These data support the use of fruquintinib as a treatment option for patients with refractory metastatic colorectal cancer. Future research is needed, both to assess patient quality of life after fruquintinib therapy and the safety of the drug, and to determine the optimal sequencing strategy for patients with metastatic colorectal cancer who have failed at least two lines of therapy. (Dasari, A., et al. (2023). Fruquintinib versus placebo in patients with refractory metastatic colorectal cancer (FRESCO-2): An international, multicentre, randomised, double-blind, phase 3 study. The Lancet, 402(10395): 41–53. Retrieved June 2023 from – https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00772-9/fulltext#%20; Norris, J. (2023). New therapy may be on the horizon for metastatic colorectal cancer. Medical News Today. Retrieved June 2023 from https://www.medicalnewstoday.com/articles/new-therapy-may-be-on-the-horizon-for-metastatic-colorectal-cancerReleased: July 2023Nursing Drug Handbook© 2023 Wolters KluwerExamining Possible Association between Menopausal Hormone Therapy and DementiaIn a Danish nationwide, nested case-control study, exposure to menopausal hormonal therapy with estrogen and progestin was positively associated with development of all-cause dementia and Alzheimer disease, even with short-term usage around the age of menopause onset. The study identified 5,589 incident cases of dementia and 55,890 age-matched controls in Danish women ages 50 to 60 with no history of dementia or contraindications for menopausal hormone therapy. For all included participants, researchers assessed the history of menopausal hormone therapy in each patient starting from ages 45 to 55 up to 2 years before study initiation or dementia diagnosis. Using the program Medicin Macro, they were able to calculate probable daily dose and duration of medication use.READ MORE...The study examined the cohort for development of dementia, defined by first-time diagnosis or first-time use of dementia-specific medications. Compared with people who had never used estrogen-progestin therapy, those who did had an increased rate of all-cause dementia (hazard ratio [HR], 1.24). Increasing duration of use produced higher HRs, ranging from 1.21 for 1 year or less of use to 1.74 for more than 12 years of hormonal therapy. Both continuous (HR, 1.31) and cyclical (HR, 1.24) treatment regimens were associated with the development of dementia. This association persisted in women who received estrogen-progestin therapy at age 55 or younger (HR, 1.24); for those who initiated therapy at ages 45 to 50, HR was 1.26 and for those who initiated therapy at ages 51 to 60 years, HR was 1.21. It also held for either late-onset (HR, 1.21) or Alzheimer disease (HR, 1.22).Before the index date, 1,782 (31.9%) of patients with dementia and 16,154 (28.9%) of those in the control group had received menopausal treatment with estrogen-progestin. Among all users of estrogen-progestin, 66.2% had their last treatment day more than 8 years before the index date; 8.7% were still users at diagnosis or matching. Median age at initiation of estrogen-progestin was 53 years for both case and control groups; the median duration of use was 3.8 years for cases and 3.6 years for controls. Among those in the case group, 25.7% received continuous progestin, 38.9% received cyclical progestin, and 30.4% received both continuous and cyclical treatment before the index date. In the control group, among those who received hormonal therapy, 24.3% received continuous progestin, 38.9% received cyclical progestin, and 31.5% received both continuous and cyclical progestin.Further studies are necessary to determine whether these findings represent an actual effect of menopausal hormone therapy on dementia risk or whether they reflect an underlying predisposition in women in need of these therapies. In addition, the effect of short-term use of hormone therapy around the age of menopause remains to be fully explained. (Kantarci, K., & Manson, J. E. (2023). Menopausal hormone therapy and dementia. BMJ, 381, 1404. Retrieved June 2023 from https://www.bmj.com/content/381/bmj.p1404; Pourhadi, N., et al. (2023). Menopausal hormone therapy and dementia: Nationwide, nested case-control study. BMJ, 381, Article e072770. Retrieved June 2023 from https://www.bmj.com/content/bmj/381/bmj-2022-072770.full.pdf)Released: July 2023Nursing Drug Handbook© 2023 Wolters KluwerTezepelumab Effective in a Range of Severe Asthma TypesPost hoc pooled analysis of two studies of patients with severe asthma suggest that treatment with tezepelumab resulted in clinically meaningful reductions in asthma exacerbations, including those associated with hospitalization or an emergency department (ED) visit, across patient subgroups. Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin, which is released by airway epithelial cells in response to allergens or other triggers and drives airway inflammation. The two studies analyzed were PATHWAY, a phase 2 dose-finding study of tezepelumab in adults with inadequately controlled severe asthma, and NAVIGATOR, a phase 3 study of subcutaneous tezepelumab in adults and adolescents with severe asthma.READ MORE...The pooled analysis included patients ages 18 to 75 years in PATHWAY and ages 12 to 80 years in NAVIGATOR who had received tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. Overall, 1,334 patients were included (665 tezepelumab, 669 placebo). All patients had experienced at least two exacerbations of their asthma in the year before enrollment. The annualized asthma exacerbation rate (AAER) over 52 weeks was calculated both in the overall population and in subgroups defined by inflammatory biomarkers or clinical characteristics. To examine the reduction of AAER in patients across the spectrum of T2 inflammation, AAER reduction was assessed in patients grouped by combinations of baseline blood eosinophil counts (BEC), functional exhaled nitric oxide (FENO) levels, and perennial allergy status. Patients were grouped by combinations of low and high BEC (less than 150 cells/microliter, or greater than or equal to 150 cells/microliter) and low and high FENO levels (less than 25 ppb, or greater than or equal to 26 ppb).In both studies, treatment with tezepelumab reduced the AAER; in the pooled population, tezepelumab reduced AAER by 60% compared with placebo; clinically meaningful reductions in exacerbations were observed in patients with type 2-low disease, defined by low (less than 300 cells/microliter) or very low (less than 150 cells/microliter) baseline BEC, low FENO levels (less than 25 ppb), and negative perennial allergy status in the absence of maintenance corticosteroid use at baseline. Reductions in exacerbations ranged from 37% in type 2-low disease (BEC less than 300 cells/microliter, FENO levels less than 25 ppb) to 77% in type 2-high disease (BEC greater than or equal to 300 cells/microliter, FENO levels greater than or equal to 25 ppb). In the triple T2-low subgroup (BEC less than 150 cells/microliter, FENO levels less than 25 ppb, no perennial allergies), the AAER over 52 weeks was 34% lower with tezepelumab compared with placebo. Use of tezelepumab reduced rate of exacerbations requiring hospitalization or ED visit by 79% in the total population and by 60% in type 2-low disease and by 91% in type 2-high disease subgroups. The AAER among these patients remained consistent across baseline BECs but increased as baseline FENO levels increased. Exacerbations associated with hospitalizations or ED visit was decreased by 80% in patients with perennial allergies and by 74% in those without.Tezepelumab also improved lung function, asthma control, and asthma-related quality of life. In the overall population, the incidence of adverse events was similar between the two groups: in 75% of patients receiving tezepelumab and in 77% of patients receiving placebo. Serious adverse events were seen in 9% of patients receiving tezepelumab and in 13% of patients receiving placebo.Capturing a clear picture of the efficacy of tezepelumab in different subgroups is important as it represents the first in a new class of asthma medications. Real-world studies are warranted to further illuminate the drug's safety and its optimal use. (Brusselle, G., & Riemann, S. (2023). Is efficacy of Tezepelumab independent of severe asthma phenotype. Am J Respir Crit Care Med, 208(1), 1–3. Retrieved June 2023 from https://www.atsjournals.org/doi/epdf/10.1164/rccm.202304-0700ED?role=tab; Corren, J., et al. (2023). Efficacy of tezepelumab in severe, uncontrolled asthma: Pooled analysis of the PATHWAY and NAVIGATOR clinical trials. Am J Respir Crit Care Med, 208(1): 13–24. Retrieved June 2023 from https://www.atsjournals.org/doi/full/10.1164/rccm.202210-2005OC)Released: July 2023Nursing Drug Handbook© 2023 Wolters Kluwer
Drug News Abstracts - June 2023
Baclofen and Risk of EncephalopathyThe 30-day risk of encephalopathy was at least two times as high in patients treated with the muscle relaxant baclofen when compared with other muscle relaxants, tizanidine or cyclobenzaprine. This was demonstrated in an active comparator study conducted using new user data from the Geisinger Health System, a large tertiary health care system in Pennsylvania.READ MORE...Baclofen is a GABA agonist, and case reports and recent population-based studies have linked its use to encephalopathy in patients with kidney disease. It's thought that this encephalopathy is related to baclofen's effect on GABAB receptors, that excessive activation can reduce the release of neurotransmitters, resulting in disorientation and other cognitive impairments, and can also decrease cerebral blood flow and metabolic activity, leading to more severe symptoms.The study examined results in patients age 18 and older who were studied in two separate paired cohorts; cohort 1 compared baclofen and tizanidine, and cohort 2 compared baclofen and cyclobenzaprine. It balanced the cohorts on 45 patient characteristics and conducted subgroup analyses based on age, estimated GFR, sex, and concomitant opioid use.In cohort 1, the 30-day risk of encephalopathy was 64.7 per 1,000 person-years with baclofen compared to 28.3 per 1,000 person-years with tizanidine. The 30-day risk in cohort 2 was 52.6 per 1,000 person-years with baclofen compared to 22.3 per 1,000 person-years with cyclobenzaprine. The elevated risk, apparent as early as 30 days, persisted through the first year of treatment. In cohort 1, the subdistribution hazard ratio (SHR) of elevated encephalopathy risk at 30 days was 2.29; at 1 year, SHR with baclofen was 1.32. In cohort 2, the SHR at 30 days was 2.35; at 1 year, SHR with baclofen was 1.94. This increased risk remained consistent in all subgroup analyses.These findings may inform shared treatment decisions between patients and prescribers. Doctors and other prescribers could consider the use of alternative muscle relaxants or initiate baclofen at a lower dose, especially in patients with kidney disease. Patients should be educated to watch for the signs of the toxic effects, and health care providers should monitor for them. Finally, it might be appropriate for regulatory agencies to consider issuing warning labels about the potential risk, particularly in patients with chronic kidney disease. (Hwang, Y. J., et al. (2023). Baclofen and the risk of encephalopathy: A real-world, active-comparator cohort study. Mayo Clin Proceed, 98(5), 676&en688. Retrieved June 2023 from https://www.mayoclinicproceedings.org/article/S0025-6196(22)00649-8/fulltext; Muanda, F. T., et al. (2023). Reviewing the evidence of the association between baclofen and encephalopathy. Mayo Clin Proceed, 98(5), 647–649. Retrieved June 2023 from https://www.mayoclinicproceedings.org/article/S0025-6196(23)00134-9/fulltext)Released: June 2023Nursing Drug Handbook© 2023 Wolters Kluwer   Dupilumab Appears to be Superior Biologic for AsthmaA study using data from a single integrated health system suggests that dupilumab has the lowest overall risk of asthma-related exacerbations when compared with omalizumab and mepolizumab. Multiple biologics have been approved for treatment of asthma, but head-to-head comparisons of these biologics are lacking. Researchers conducted a retrospective cohort study that emulated a hypothetical randomized trial, a target trial to compare the effectiveness of these biologics in reducing asthma exacerbations and improving lung function.READ MORE...The agents in the analysis were omalizumab, an anti-IgE biologic approved for allergic asthma with sensitivity to perennial allergens and IgE levels between 30 and 700 kU/L; mepolizumab, an anti-IL-5 biologic effective in eosinophilic asthma with blood eosinophil counts of at least 150 cells/microliter; and dupilumab, an anti-IL-4 receptor biologic effective in both allergic and eosinophilic asthma. Using the integrated health records from the Massachusetts General Bingham Research Patient Data Registry, the study examined results for adults with moderate to severe asthma and no other chronic lung diseases; participants included 68 patients receiving dupilumab, 68 omalizumab, and 65 mepolizumab. Researchers examined for incidence of asthma-related exacerbations and change in baseline FEV1 value over 12 months of follow-up. Clinically significant exacerbations were defined as emergency department visits or hospitalizations with a primary diagnostic code for asthma or an outpatient prescription for corticosteroids in patients with asthma. Over 12 months of follow-up, asthma-related exacerbations occurred in 17 patients in the dupilumab group (25.0%), 28 patients in the mepolizumab group (43.1%), and 27 patients in the omalizumab group (39.7%). The number of exacerbations recorded and their incidence were as follows:dupilumab: 31 exacerbations (0.46 per person-year)omalizumab: 63 exacerbations (0.93 per person-year)mepolizumab: 86 exacerbations (1.32 per person-year)The adjusted incidence rate ratios (IRR) were 0.28 for dupilumab versus mepolizumab, 0.36 for dupilumab versus omalizumab, and 0.78 for omalizumab versus mepolizumab. Results were similar for adjusted IRR in patients with eosinophil counts of at least 300 cells/microliter: 0.26 for dupilumab versus mepolizumab and 0.33 for dupilumab versus omalizumab.At 12 months' follow-up, change from baseline in prebronchodilator FEV1 values was greater in patients receiving dupilumab than in those receiving mepolizumab (mean difference, 0.11 L) or in those receiving omalizumab (mean difference, 0.082 L), but were not statistically significant. (Akenroye, A. T., et al. (2023). Comparative effectiveness of omalizumab, mepolizumab, and dupilumab in asthma: A target trial emulation. J Allergy Clin Immunol, 151(5), 1269–1276. Retrieved June 2023 from https://www.jacionline.org/article/S0091-6749(23)00144-6/fulltext)Released: June 2023Nursing Drug Handbook© 2023 Wolters KluwerProphylactic Antiemetics before Apomorphine to Treat Parkinson Disease May Be UnnecessaryPost hoc analysis of data from the dose optimization phase of an open-label, long-term safety and efficacy study of sublingual apomorphine (SL-APO) in patients with Parkinson disease demonstrated rates of nausea and vomiting similar to those seen with other dopaminergic medications and with other apomorphine preparations. Nausea is common in patients with Parkinson disease, and many Parkinson disease medications in particular, levodopa and dopamine agonists can exacerbate nausea and vomiting. Because prophylactic antiemetics were used in clinical trials of apomorphine but not in trials of other dopamine agonists, the FDA recommends their use. This study evaluated the need for such antiemetics. U.S. prescribing information recommends prophylactic use of trimethobenzamide, but it has been in short supply and the alternative, domperidone, is not approved for use in the United States.READ MORE...Eligible patients had idiopathic Parkinson disease, were responsive to and were receiving stable doses of carbidopa-levodopa (with or without adjunctive medications), and had experienced at least one OFF episode per day with at least 2 hours of daily OFF time. During sequential office visits, patients underwent dose optimization (10 to 35 mg at 5-mg increments) when in an OFF state to determine the individualized dose that resulted in a tolerable FULL ON within 45 minutes. FULL ON was considered to be achieved when SL-APO treatment produced benefits in mobility, stiffness, and slowness; achieved adequate motor function to perform normal activities of daily living; and resulted in a response comparable or better than the patient's former responses to Parkinson disease medications. Once such a tolerable FULL ON dose was identified for the individual patient, the patient progressed into an open-label maintenance phase.The dose optimization population in the study included 449 patients; most were male (66.4%), white (96.0%), and had a mean age of 64.3 years. Of these 449 patients, 82.2% were new patients with no prior exposure to SL-APO, and all patients were also receiving carbidopa-levodopa. In the dose optimization phase of the trial, 88.4% (n = 397) successfully achieved an effective and tolerable dose; of these patients, 12.3% (n = 49) and 1.3% (n = 5) experienced vomiting during the optimization phase. Among those who had nausea and vomiting during dose optimization and continued into the long-term maintenance phase of the study, nausea occurred in 44.9% (22/49) and vomiting in 40.0% (2/5) during maintenance. Among those who had not experienced nausea and vomiting during dose optimization, 19.1% went on to report nausea and vomiting during maintenance.Of the patients in the dose optimization phase, 43.7% (n = 196) didn't use an antiemetic during that phase of the study; most of these patients (169/196) achieved an effective and tolerable SL-APO dose. Nausea and vomiting were uncommon in these patients: 12.2% (n = 24) had nausea, and 0.5% (n = 1) experienced vomiting. Nausea and vomiting were also seen among the 56.3% (n = 253) of patients who had used an antiemetic at any time during that phase of the study: 17.0% (n = 43) had nausea, and 2.4% (n = 6) experienced vomiting. Of the 67 patients who did experience nausea and the 7 who experienced vomiting, all events were mild to moderate, except for 1 severe occurrence of each.Importantly, less than half of all patients in this analysis who experienced nausea and vomiting went on to experience these events again during maintenance treatment, suggesting that patients can develop tolerance to those side effects over time. The choice of using prophylactic antiemetics should be made based on the individual's risks and benefits, as there may be patients who find it lessens their symptoms, but this research demonstrates that it's not necessary for most patients initiating SL-APO for treatment of OFF episodes in Parkinson disease. (Hauser, R. A., et al. (2023). Dose optimization of apomorphine sublingual film for OFF episodes in Parkinson's Disease: Is the prophylactic use of an antiemetic necessary? J Parkinson Dis, 13(3), 403–414. Retrieved June 2023 from https://content.iospress.com/articles/journal-of-parkinsons-disease/jpd223537)Released: June 2023Nursing Drug Handbook© 2023 Wolters KluwerSpironolactone for Acne VulgarisThe Spironolactone for Adult Female Acne (SAFA) trial evaluated the effectiveness of the potassium-sparing diuretic against persistent facial acne in adult women in the UK when given in addition to standard topical treatments. Treatment guidance for acne recommends fixed-combination topical preparations containing retinoids, benzoyl peroxide, and antibiotics as first-line treatments. One-third of people under care for acne in the UK receive secondary treatment with long courses of oral antibiotics; given the increasing prevalence of antibiotic resistance, looking for an alternative is important. Spironolactone, which has been used off-label to treat acne, has been suggested as that alternative.READ MORE...In the pragmatic, multicenter, phase 3, double-blind, randomized controlled trial, study participants were older than age 18 with facial acne for at least 6 months, with acne of sufficient severity to warrant treatment by oral antibiotics, as judged by a clinician, and with an IGA of at least 2; 342 participants were included in the primary analysis. They were randomly assigned to either 50 mg/day spironolactone (n = 176) or matched placebo (n = 166) for 6 weeks, increasing to 100 mg/day up to week 24. At 24 weeks, the study was unblinded, and patients could choose to continue or start spironolactone. The mean age at baseline was 29.2 years; 46% had mild acne, 40% had moderate acne, and 13% had severe acne. Each participant underwent baseline assessments, including pregnancy tests, blood tests to exclude abnormal kidney function or hyperkalemia, a baseline photo, and contraceptive counseling. They were followed up at 6 weeks and 12 weeks, with a primary outcome assessment at 12 weeks, and longer-term follow-up by questionnaires from 24 weeks up to 52 weeks.Researchers measured effectiveness through the Acne-Specific Quality of Life questionnaire (Acne-QOL), which contains 19 questions organized into four domains (self-perception, social role, emotional role, and acne symptoms); each subscale has a range of 0 to 30, in which higher scores reflect improved QOL. Mean Acne-QOL acne symptoms subscale score was 13.2 for spironolactone at baseline and 12.9 for placebo. At week 12, scores had improved to 19.2 in the spironolactone group and 17.8 in the placebo group. The difference, 1.27, was small, but was statistically significant. At 24 weeks, the difference was greater: 3.45 (acne symptom subscale score 2.12 with spironolactone and 17.4 with placebo). More participants in the spironolactone group self-reported acne improvement than in the placebo group. No significant differences were noted at week 12 (72% of participants versus 68%), but the difference at week 24 (82% versus 63%) was significant (odds ratio, 1.16). The IGA of treatment success was demonstrated in 31/168 (19%) of those given spironolactone and in 9/160 (6%) of those given placebo. Most adverse reactions were mild; they were slightly more common in the spironolactone group, with more headaches reported than with placebo (20% versus 12%).Spironolactone improved acne on all outcomes tested, with significant differences at 24 weeks. It offers a useful alternative to oral antibiotics for women with persistent acne when first-line topical treatments have not worked. (Santer, M., et al. (2023). Effectiveness of spironolactone for women with acne vulgaris (SAFA) in England and Wales: Pragmatic, multicentre, phase 3, double blind, randomised controlled trial. BMJ; 381, e074349. Retrieved June 2023 from https://www.bmj.com/content/381/bmj-2022-074349; Santer, M., & Layton, A. (2023). What do we know about prescribing spironolactone for acne? BMJ, 381, 1114. Retrieved June 2023 from https://www.bmj.com/content/381/bmj.p1114)Released: June 2023Nursing Drug Handbook© 2023 Wolters Kluwer
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