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Drug News Abstracts - April 2024


Great Variation in Opioid Prescribing for High-Risk Infants in U.S. Hospitals

A study of nearly 150,000 infants admitted to 47 children's hospitals in the United States found that most of the high-risk infants received opioids during hospitalization, with wide variations across U.S. regions and between hospitals. It demonstrated significant hospital-level variations in opioid and methadone exposure and in the cumulative days of opioid use.

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Leptin Increase during Dexamethasone Use in Pediatric Acute Lymphoblastic Leukemia

High-dose dexamethasone, a common component of maintenance treatment in children with acute lymphoblastic leukemia (ALL), induces well-known side effects, including dyslipidemia, increased appetite, and consequent unhealthy eating behaviors, as well as increased fatigue and sleep problems. A study conducted within the Dexa Days-2 study, a Dutch national randomized controlled trial that analyzes dexamethasone-induced neurobehavioral problems in ALL patients, aimed to determine the influence of the 5-day dexamethasone course on changes in leptin, as well as fat mass, body mass index (BMI), hunger, sleep, and fatigue and to explore associations between these variables.

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Nirsevimab 90% Effective Against Hospitalization for RSV

Respiratory syncytial virus (RSV) is the leading cause of hospitalization for infants in the United States; 50,000 to 80,000 hospitalizations annually are attributed to the virus, with the highest rates of hospitalization occurring during the first months of life. The Centers for Disease Control and Prevention has taken a two-pronged approach to combatting the problem. In August 2023, the Advisory Committee on Immunization Practices recommended nirsevimab, a long-acting monoclonal antibody, to protect infants younger than age 8 months against lower respiratory infection during their first RSV season and to protect children ages 8 to 19 months at increased risk for severe RSV disease who are entering their second RSV season. In September 2023, the FDA made available a maternal RSV vaccine to provide protection to the youngest infants.

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Omalizumab Reduced Allergic Reactions Across Multiple Food Allergies

It's estimated that food-related anaphylactic reactions result in 30,000 emergency department visits in the United States annually; more than 40% of children and more than 50% of adults with food allergies will experience at least one severe reaction yearly. The prevalence of IgE-mediated food allergies has been on the rise; it now affects approximately 3.4 million children and 13.6 million adults in the United States.

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Drug News Abstracts Archive


Drug News Abstracts - April 2024
Great Variation in Opioid Prescribing for High-Risk Infants in U.S. HospitalsA study of nearly 150,000 infants admitted to 47 children's hospitals in the United States found that most of the high-risk infants received opioids during hospitalization, with wide variations across U.S. regions and between hospitals. It demonstrated significant hospital-level variations in opioid and methadone exposure and in the cumulative days of opioid use.READ MORE...Infants exposed to painful procedures experience acute physiologic responses and increased morbidity; opioids are often prescribed for these patients. However, extended opioid prescribing after surgery is associated with prolonged ventilation, total parenteral nutrition use, and hospitalization. Pain management in hospitalized infants needs to balance these two considerations to prevent long-term adverse health and developmental consequences.A retrospective cohort study examined data on high-risk infants younger than age 1 from January 2016 through December 2022 at 47 U.S. children's hospitals participating in the Pediatric Health Information System. The study identified 132,658 high-risk infants, median gestational age, 34 weeks; 54.5% male, with a median birth weight of 1,741 grams. Researchers identified high-risk infants by ICD-10 codes that enabled them to study newborns with substantial neonatal/perinatal morbidities, who needed to undergo multiple procedures and required prolonged intubation and therefore were at risk for prolonged opioid exposure. They included infants with congenital heart disease requiring surgery (CHD), necrotizing enterocolitis (NEC), extremely-low- or very-low-birthweight (ELBW or VLBW), hypoxemic-ischemic encephalopathy (HIE), and those requiring extracorporeal membrane oxygenation (ECMO) or abdominal surgery. They excluded infants with ICD-10 codes for neonatal opioid withdrawal syndrome, in utero exposure to opioids, or malignant tumors. The records of these infants were examined to determine opioid exposure during hospitalization. Researchers determined cumulative days of opioid exposure, methadone treatment after short-acting opioid exposure during hospitalization, and cumulative days of methadone exposure.During hospitalization, 76.5% of high-risk infants were exposed to opioids and 7.9% received methadone. Median length of any opioid exposure was 5 cumulative days (range, 2 to 12 days), and the median length of methadone treatment was 19 cumulative days (range, 7 to 46 days). The methadone use observed by researchers is in part attributable to its use while tapering opioids to minimize withdrawal signs and symptoms.When stratified by age at birth, premature infants had fewer days of opioid exposure than term infants (13% lower). Prematurity occurred in 30.3% of infants. Clinical factors associated with higher cumulative opioid days included mechanical ventilation and Intensive Care Unit stay. Cumulative opioid days were 104% higher with surgical NEC, 52% higher with medical NEC, 82% higher in those undergoing abdominal surgery, 25% higher in ELBW infants, 105% higher in those undergoing CHD-related procedures, and 177% higher in those receiving ECMO than in those without these conditions.Significant variability was noted in opioid and methadone exposure across regions and institutions. Opioid exposure among this cohort was 74.2% in the Northeast, 78.6% in the South, 71.6% in the Midwest, and 81.2% in the West; similarly, methadone exposure among this cohort was 4.6% in the Northeast, 10.3% in the South, 6.6% in the Midwest, and 7.1% in the West. Once the researchers controlled for hospital- and patient-level characteristics, only the variation in the Northeast was significant. An estimated 16% of the variability in opioid exposure and 20% of the variability in methadone exposure can be attributed to the individual hospital.The observed institutional-level variability in opioid and methadone prescribing in high-risk hospitalized infants underscores the need for standardized prescribing in this vulnerable population. Understanding the factors that result in these regional and institutional variations can inform best practices and encourage practitioners to carefully consider whether alternative pain management strategies may be an appropriate approach in some of these vulnerable patients.Hadland, S. E., & Schiff, D. M. (2024). Opioids in hospitalized infants–Managing pain and sedation while avoiding overuse. JAMA Netw Open, 7(3), Article e240523. Retrieved March 2024 from https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2815953Keane, O. A., et al. (2024). Institutional and regional variation in opioid prescribing for hospitalized infants in the US. JAMA Netw Open, 7(3), Article e240555. Retrieved March 2024 from https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2815949Released: April 2024Nursing Drug Handbook© 2024 Wolters KluwerLeptin Increase during Dexamethasone Use in Pediatric Acute Lymphoblastic LeukemiaHigh-dose dexamethasone, a common component of maintenance treatment in children with acute lymphoblastic leukemia (ALL), induces well-known side effects, including dyslipidemia, increased appetite, and consequent unhealthy eating behaviors, as well as increased fatigue and sleep problems. A study conducted within the Dexa Days-2 study, a Dutch national randomized controlled trial that analyzes dexamethasone-induced neurobehavioral problems in ALL patients, aimed to determine the influence of the 5-day dexamethasone course on changes in leptin, as well as fat mass, body mass index (BMI), hunger, sleep, and fatigue and to explore associations between these variables.READ MORE...The study included 105 children, median age, 5.4 years (range, 3.0 to 18.8 years) who were treated according to a Dutch ALL protocol; all had entered the maintenance phase of treatment after cessation of doxorubicin treatment. Dexamethasone (6 mg/m2/day) was administered for 5 days at the start of each 3-week cycle. Data and blood samples were collected before and after the 5-day course; BMI, fat mass, and leptin were measured, and parents completed questionnaires regarding hunger, fatigue, and sleep in the children.Leptin and fat mass, as well as hunger, fatigue, and sleep scores, deteriorated after 5 days of high-dose dexamethasone. After 5 days, mean leptin standardized deviation score (SDS) changed from −0.09 to 1.8, fat mass from 5.1 kg to 5.6 kg, fatigue score (median score on Pediatric Quality of Life Inventory SDS) from −0.5 to −3.5. BMI remained stable, from 17.3 to 17.7. However, no significant correlations were found between the change in leptin SDS and changes in these other measures.Because children with ALL are at increased risk for metabolic adverse events, it's important to understand the mechanisms behind these changes. These results hint that a dexamethasone-induced state of leptin resistance might play a role.van Hulst, A. M., et al. (2024). Leptin increase during dexamethasone and its association with hunger and fat in pediatric acute lymphoblastic leukemia. J Clin Endocrinol Metab, 109(3), 631–640. Retrieved March 2024 from https://academic.oup.com/jcem/article/109/3/631/7329845Released: April 2024Nursing Drug Handbook© 2024 Wolters KluwerNirsevimab 90% Effective Against Hospitalization for RSVRespiratory syncytial virus (RSV) is the leading cause of hospitalization for infants in the United States; 50,000 to 80,000 hospitalizations annually are attributed to the virus, with the highest rates of hospitalization occurring during the first months of life. The Centers for Disease Control and Prevention has taken a two-pronged approach to combatting the problem. In August 2023, the Advisory Committee on Immunization Practices recommended nirsevimab, a long-acting monoclonal antibody, to protect infants younger than age 8 months against lower respiratory infection during their first RSV season and to protect children ages 8 to 19 months at increased risk for severe RSV disease who are entering their second RSV season. In September 2023, the FDA made available a maternal RSV vaccine to provide protection to the youngest infants.READ MORE...The New Vaccine Surveillance Network (NVSN), a population-based, prospective surveillance platform for acute respiratory illnesses in infants, children, and adolescents, evaluated the effectiveness of nirsevimab among infants in their first RSV season, from October 1, 2023, through February 29, 2024. NVSN collected demographic, clinical, and immunization data through parent interviews, medical records, and state information systems. Among 1,036 eligible infants, 699 met the inclusion criteria (verified nirsevimab status, reported gestational age at birth, and a medical record review to assess for underlying medical conditions), and were designated as case patients (n = 407; 58%) or control patients (n = 292; 42%) based on a positive RSV result on PCR testing.Administration of nirsevimab was shown to be 90% effective against RSV-associated hospitalizations in infants in their first RSV season. Ultimately, 6 case patients (1%) and 53 control patients (18%) received nirsevimab. The median time from receipt of nirsevimab to symptom onset was 45 days (range, 7 to 127 days).This early effectiveness estimate supports the current recommendations for prevention of severe RSV disease in infants and has implications for public health practice. Adding use of nirsevimab in infants to the protocol that includes maternal RSV vaccination will reduce the risk of RSV-associated hospitalizations. The researchers note that the 90% efficacy seen in this study may be higher than expected in a real-world setting, as nirsevimab effectiveness is expected to decrease with increasing time after receipt over a full RSV season because of antibody decay. Median duration of RSV season in the United States is 189 days. Still, in clinical trials it did remain effective through 150 days after receipt.Moline, H. L., et al. (2024). Early estimate of nirsevimab effectiveness for prevention of respiratory syncytial virus-associated hospitalization among infants entering their first respiratory syncytial virus season—new vaccine surveillance network, October 2023–February 2024. MMWR, 73(9), 209–214. Retrieved March 2024 from https://www.cdc.gov/mmwr/volumes/73/wr/mm7309a4.htm?s_cid=mm7309a4_wReleased: April 2024Nursing Drug Handbook© 2024 Wolters KluwerOmalizumab Reduced Allergic Reactions Across Multiple Food AllergiesIt's estimated that food-related anaphylactic reactions result in 30,000 emergency department visits in the United States annually; more than 40% of children and more than 50% of adults with food allergies will experience at least one severe reaction yearly. The prevalence of IgE-mediated food allergies has been on the rise; it now affects approximately 3.4 million children and 13.6 million adults in the United States.READ MORE...Report of a study examining the effectiveness of the monoclonal anti-IgE antibody omalizumab was published in the New England Journal of Medicine and was featured in a symposium at the 2024 American Academy of Allergy, Asthma, and Immunology annual meeting. OUtMATCH (Omalizumab Monotherapy and as Adjunct Therapy to Multi-Allergen Oral Immunotherapy in Food-Allergic Children and Adults) demonstrated that use of omalizumab increased the amount of foods containing allergens (peanuts, tree nuts, eggs, milk, and wheat) that individuals as young as 1 year with multifood allergies could consume without an allergic reaction.OUtMATCH has three stages; this report describes stage 1, which aims to evaluate the efficacy and safety of omalizumab in patients allergic to peanuts and at least two other common foods. Researchers enrolled 180 patients ages 1 to 55 who were unable to tolerate 100 mg of peanut protein and 300 mg of at least two other food proteins (milk, eggs, cashews, walnuts, hazelnuts, or wheat). Each participant completed four separate blended food challenges (including a placebo challenge) to assess their ability to consume a single dose of at least 600 mg of peanut protein (primary endpoint) and a single dose of at least 1,000 mg of the other proteins (secondary endpoint) without experiencing moderate to severe allergic reactions. Patients were assigned to subcutaneous omalizumab or placebo, with dose based on weight and IgE levels every 2 to 4 weeks for 16 to 20 weeks, after which the food challenges were repeated.Compared to placebo, a statistically significantly higher proportion of patients receiving omalizumab were able to consume a greater quantity of peanuts, milk, eggs, and cashews without moderate to severe reactions. Although not statistically significant, a higher proportion of patients on omalizumab were able to consume at least 1,000 mg of walnuts, hazelnuts, and wheat. For peanuts, 67% of treated patients were able to consume the target quantity versus 7% on placebo; for cashews, 41% versus 3%; for eggs, 67% versus 0%; for milk, 66% versus 10%. The values for walnuts were 64% versus 13%, for hazelnuts were 65% versus 14%, and for wheat were 75% versus 13%. Treatment for 16 weeks was superior to placebo in increasing the reaction threshold for peanut and other common food allergies.Results of this study show that anti-IgE therapy could significantly reduce the occurrence of allergic reactions across multiple foods in the event of accidental exposure, and thereby improve nutrition, quality of life, personal finances, and health care utilization.Genentech. (2024, February 25). New England Journal of Medicine publishes phase III data showing Xolair significantly reduced allergic reactions across multiple foods in people with food allergies [Press release]. Retrieved March 2024 from https://www.gene.com/media/press-releases/15020/2024-02-25/new-england-journal-of-medicine-publisheWood, R. A., et al. (2024). Omalizumab for the treatment of multiple food allergies. N Engl J Med, 390, 889–899. Retrieved March 2024 from https://www.nejm.org/doi/full/10.1056/NEJMoa2312382Released: April 2024Nursing Drug Handbook© 2024 Wolters Kluwer
Drug News Abstracts - March 2024
Concerns Raised about Cardiovascular Safety of Therapeutic Cannabis UseRecreational use of cannabis has been linked with cardiovascular adverse effects. In response to the rise in use of medical cannabis to treat chronic pain, Danish researchers designed a study, published in the European Heart Journal, to investigate whether these associations with new-onset arrhythmias would hold true for medical cannabis use.READ MORE...The nationwide cohort study identified 5,391 patients with a prescription for medical cannabis (63.2% women, median age 59) and matched them 1:5 to 26,941 controls based on age, sex, chronic pain diagnosis, and concomitant use of other pain medications. The patients were followed from the index date of the initial prescription (or corresponding date for control patients) until either new-onset arrhythmia, death, or 180 days of observation. The study, based on 4 years of nationwide data from an established cannabis pilot program that allowed any Danish health care provider to prescribe it for chronic pain, allowed use of a combination product containing both cannabidiol (CBD) and tetrahydrocannabinol (THC), as well as products containing only CBD or THC as an option. Of the patients who initiated medical cannabis treatment, 29% received a CBD/THC combination product, 24% CBD only, and 47% THC only. The study reported the absolute risk of first-time arrhythmia, including atrial fibrillation or flutter, conduction disorder, paroxysmal tachycardia, and ventricular arrhythmia, and of acute coronary syndrome; these findings were determined from hospitalizations or outpatient visits coded with any of the arrhythmias.Arrhythmia was observed in 42 of the 5,391 patients on medical cannabis and in 104 of the 26,941 control individuals. The new-onset arrhythmias observed included atrial fibrillation or flutter (76%), paroxysmal tachycardia (12%), and other arrythmias (12%) in the users of medical cannabis and atrial flutter or fibrillation (79%), conduction disorders (14%), and other arrythmias (7%) in the control group. Medical cannabis use was associated with an elevated risk of new-onset arrhythmia. The 180-day absolute risk was 0.8% compared with 0.4% in control individuals (absolute risk difference, 0.4%), with a risk ratio of 2.07. No significant association was found between use of medical cannabis and risk of hospitalization for acute coronary syndrome (180-day absolute risk difference of 0.04% and 180-day risk ratio of 1.20). Including concomitant treatment with opioids, antiepileptics, and NSAIDs yielded similar results: risk ratios of 1.97 and 1.14 for new-onset arrhythmias and acute coronary syndrome, respectively.The interest in new treatments for chronic pain, including medical cannabis, is substantial. This study provides evidence of an elevated risk of new-onset arrhythmias, although the incidence is relatively small. Further studies can better identify those at most risk. (Holt, A., et al. (2024). Cannabis for chronic pain: Cardiovascular safety in a nationwide Danish study. Eur Heart J, 45(6), 475–484. Retrieved March 2024 from https://academic.oup.com/eurheartj/article/45/6/475/7500071; Page, II, R. L. (2024). Cannabis by any name does not smell as sweet: Potential cardiovascular events with medical cannabis. Eur Heart J, 45(6), 485–487. Retrieved March 2024 from https://academic.oup.com/eurheartj/article/45/6/485/7500073)Released: March 2024Nursing Drug Handbook© 2024 Wolters KluwerZinc Supplementation Decreases Hand-Foot Skin Reaction in Patients Treated With RegorafenibHand-foot skin reaction (HFSR), characterized by abnormalities of the skin on the palms of the hands and soles of the feet, occurs in approximately 35% of cancer patients treated with vascular endothelial growth factor receptor—tyrosine kinase inhibitors (VEGFR-TKIs). But despite its prevalence, effective interventions for HFSR are lacking.READ MORE...Because zinc deficiency has been associated with the dermatologic toxicity related to these agents, a phase 2 randomized trial published in the Journal of the American Academy of Dermatology investigated whether zinc supplementation could reduce the severity of HFSR induced by the oral multikinase inhibitor regorafenib within the first 8 weeks of treatment. The trial enrolled 65 patients with metastatic colorectal cancer being treated with regorafenib from March 2016 to March 2019 into a zinc supplementation group (n = 32; zinc gluconate, 78 mg PO twice daily) or a control group (n = 33).The median serum zinc concentrations at baseline were similar between the zinc supplementation (67.75 mcg/dL) and control groups (65.7 mcg/dL). After 4 weeks of regorafenib treatment, both zinc supplementation and control groups had a similar incidence of grade 2/3 HFSR (21.8% [n = 7 of 32] and 30.3% [n = 10 of 33], respectively). But after 4 weeks, the incidence of grade 2/3 HFSR dropped in the zinc supplementation group, to 12.5% (n = 4 of 23) while remaining similar in the control group (33.3% [n = 11 of 33]). The researchers noted that 6 of the 7 patients who had grade 2/3 HFSR at 4 weeks had improved to grade 0/1 by week 8.The researchers note the limitations of the study, including the small sample size, lack of data on the patients' quality of life, and the potential influence of skin care measures taken during the study period on the severity of the HFSR. To combat that final problem, patients were assigned to the same dermatologist to minimize differences in the management of skin toxicity. The underlying mechanism of the serum zinc decrease in patients with HSFR caused by VEGFR-TKI treatment remains unclear; it's possible that GI side effects of the treatment may influence zinc intake or that the VEGFR-TKI may directly chelate zinc ions.Based on this data and other cohort data, clinicians should consider zinc supplementation for those undergoing VEGFR-TKI therapy who develop HFSR. This approach can facilitate quicker recovery from HFSR and allow cancer patients to continue treatment with VEGFR-TKI at optimal doses. (Huang, W-K., et al. (2024). Zinc supplementation decreased incidence of grade ≥2 hand-foot skin reaction induced by regorafenib: A phase II randomized clinical trial. J Am Acad Dermatol, 90(2), 368—369. Retrieved March 2024 from https://www.jaad.org/article/S0190-9622(23)02383-6/fulltext; Lu, C-W. (2023). Zinc supplementation is associated with improvement in hand-foot skin reaction in patients on vascular endothelial growth factor receptor-tyrosine kinase inhibitors: A cohort study. J Am Acad Dermatol. Advanced online publication. Retrieved March 2024 from https://www.jaad.org/article/S0190-9622(23)03272-3/fulltext)Released: March 2024Nursing Drug Handbook© 2024 Wolters KluwerResmetirom Helps Resolve Nonalcoholic Steatohepatitis and Improves Liver FibrosisNonalcoholic steatohepatitis (NASH) is a progressive liver disease, with a global prevalence of 4% to 6%. NASH is characterized by 5% or greater hepatic steatosis with hepatocellular damage and inflammation. Once it progresses to clinically meaningful fibrosis, the risk of adverse outcomes increases, especially among patients with type 2 diabetes. MAESTRO-NASH is an ongoing phase 3 trial evaluating the safety and efficacy of resmetirom, an oral, liver-directed thyroid hormone receptor beta (THRβ)-selective agonist, in adults with biopsy-confirmed NASH and fibrosis. In NASH, THRβ formation in the liver is impaired, which leads to a reduction in mitochondrial function and beta oxidation of fatty acids in association with increasing fibrosis. The double-blind, placebo-controlled trial is being conducted at 245 sites in 15 countries with a planned duration of 54 months. A report in the New England Journal of Medicine describes results of the primary biopsy end points at week 52.READ MORE...The trial included 966 patients who were randomized to 80-mg (n = 322) or 100-mg (n = 323) resmetirom or placebo (n = 321). Patients were age 18 or older and had three of five risk factors for metabolic syndrome. Baseline biopsies and repeat biopsies at week 52 were used to determine NASH resolution and improvement in fibrosis. NASH resolution was shown by a hepatocellular ballooning score of 0, lobular inflammation score of 0 to 1, and reduction in nonalcoholic fatty liver disease (NAFLD) activity score by at least 2 points with no worsening of fibrosis. Improvement in fibrosis was indicated by a reduction by at least one stage (scale F0 for no fibrosis to F4 for cirrhosis) with no worsening of the NAFLD activity score.Demographic and clinical characteristics were similar across groups; 89.3% were white, with a high incidence of metabolic risk factors (78.1% had hypertension, 71.3% dyslipidemia, and 67.0% type 2 diabetes). The mean age of patients was 56.6 years, and the mean body mass index was 35.7. On baseline biopsy, 83.5% of patients had an NAFLD activity score of 5 or more, 5.1% had F1B fibrosis, 33.0% had F2 fibrosis, and 61.9% had F3 fibrosis. NASH resolution with no worsening of fibrosis was achieved in significantly more patients receiving resmetirom than placebo: 25.9% in the 80-mg group and 29.9% in the 100-mg group, compared with 9.7% in the placebo group. Improvement in fibrosis with no worsening of NAFLD score was also achieved in significantly more patients receiving resmetirom than placebo: 24.2% in the 80-mg group and 25.9% in the 100-mg group, compared with 14.2% in the placebo group.The percentage change from baseline in LDL cholesterol level at week 24, a key secondary endpoint, was −1.36% in the 80-mg resmetirom group, −16.3% in the 100-mg resmetirom group and 0.1% in the placebo group; the decreases with resmetirom use seemed to be maintained at week 52. Most adverse events were mild to moderate and were most frequently GI events; diarrhea and nausea were more frequent with resmeritom. The incidence of serious adverse events was similar across all trial groups: 10.9% in the 80-mg group, 12.7% in the 100-mg group, and 11.5% in the placebo group. (Harrison, S. A., et al. (2024). A phase 3, randomized, controlled trial of resmetirom in NASH with liver fibrosis. New Engl J Med, 390, 497–509. Retrieved March 2024 from https://www.nejm.org/doi/full/10.1056/NEJMoa2309000)Released: March 2024Nursing Drug Handbook© 2024 Wolters Kluwer
Drug News Abstracts - February 2024
Selecting First-Line Chemotherapy Protocols for Metastatic Pancreatic CancerDoes the chemotherapy protocol NALIRIFOX (fluorouracil, leucovorin, liposomal irinotecan, and oxaliplatin) confer survival benefit as a first-line treatment in patients with metastatic pancreatic cancer, especially in reference to the other accepted chemotherapy protocols used for the condition? A systematic review and meta-analysis published in JAMA allowed comparison between NALIRIFOX and the protocols FOLFIRINOX (fluorouracil, leucovorin, irinotecan, and oxaliplatin) and GEM-NABP (gemcitabine with nab-paclitaxel).READ MORE...The study examined results of phase 3 clinical trials that tested these protocols as first-line treatment of metastatic pancreatic ductal adenocarcinoma (PDAC) and included in their reports overall survival and progression-free survival. There have been few direct comparisons of these protocols. The NAPOL3 trial showed the superiority of NALIRIFOX over GEM-NABP in metastatic PDAC, but NALIRIFOX and FOLFIRINOX, because they are so similar, are unlikely to be directly compared in a study on efficacy and tolerability.In the seven trials included in the meta-analysis, 383 patients with metastatic PDAC were treated with NALIRIFOX, 433 with FOLFIRINOX, and 1,756 with GEM-NABP. Median follow-up was 18.8 months overall, with a significantly shorter follow-up for NALIRIFOX (16.2 months versus 20.3 months for GEM-NABP and 18.8 months for FOLFIRINOX).NALIRIFOX and FOLFIRINOX showed superior progression-free and overall survival compared with GEM-NABP. Using NALIRIFOX as the reference, GEM-NABP had worse progression-free survival (5.7 months versus 7.4 months; hazard ratio [HR], 1.45), with no statistical significance observed for differences with FOLFIRINOX (7.3 months versus 7.4 months; HR, 1.21). In addition, GEM-NABP had poorer overall survival compared with NALIRIFOX (10.4 months versus 11.1 months; HR, 1.18), while no difference was observed between FOLFIRINOX and NALIRIFOX (11.7 months versus 11.1 months; HR, 1.06). There were no statistically significant differences in overall response rate (ORR) among the three chemotherapy protocols: NALIRIFOX 41.8%, FOLFIRINOX 31.6%, and GEM-NABP 35.0%.NALIRIFOX had the most favorable toxicity profile compared to the other two regimens, with a lower incidence of hematologic effects and peripheral neuropathy, both of which can lead to discontinuation of the other regimens. For example, the platelet count decreased by 1.6% with NALIRIFOX versus 11.8% with FOLFIRINOX and 10.8% with GEM-NABP. NALIRIFOX did have a higher rate of diarrhea compared with GEM-NABP (20.3% versus 15.7%).Treatment of metastatic PDAC is challenging, as the results of this study show. The most used regimens have only moderate efficacy, with progression-free survival and overall survival of less than 1 year. Because it has fewer toxic effects, GEM-NABP is preferred, whereas FOLFIRINOX has been reserved for carefully selected patients. The question then arises, how does the newer regimen, NALIRIFOX, compare with the very similar FOLFIRINOX? Its tolerable toxicity profile and high ORR are encouraging, but the high cost of liposomal irinotecan may limit use of NALIRIFOX. Patient selection should be based on the regimens' toxicity profiles. Liposomal irinotecan, and therefore NALIRIFOX, should be avoided in patients at risk of grade 3 or greater diarrhea. But it should be the choice for patients who need tumor shrinkage and in whom peripheral neuropathy could compromise adherence. (Nichetti, F., et al. (2024). NALIRIFOX, FOLFIRINOX, and gemcitabine with nab-paclitaxel as first-line chemotherapy for metastatic pancreatic cancer: A systematic review and meta-analysis. JAMA Network Open, 7(1), Article e2350756. Retrieved February 2024 from https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2813517)Released: February 2024Nursing Drug Handbook© 2024 Wolters KluwerLamotrigine Prevents Depressive Episodes in Bipolar I Disorder in Females of Childbearing AgeA meta-analysis using patient-level data from four randomized, placebo-controlled trials showed that maintenance lamotrigine delayed relapse or recurrence of mood episodes in females of childbearing age who had bipolar I disease. It produced this effect largely by preventing depressive episodes in these patients.READ MORE...The meta-analysis investigated data from studies of patients with bipolar I disorder, differing in whether they included patients who had experienced a current or recent depressive episode, manic episode, or either. After trial with open-label lamotrigine (up to 16 weeks), those who responded to that treatment were randomized to a double-blind maintenance phase. Of the 717 females of childbearing age included in the open-label phase, 287 responded to the initial treatment and were assigned to 100 to 400 mg/day lamotrigine (n = 153) or placebo (n = 134) for up to 76 weeks.The primary outcome was median time to intervention for any mood episode, which was 323 days with lamotrigine treatment and 127 days with placebo, with the hazard ratio (HR) significantly favoring lamotrigine (HR, 0.69). In the lamotrigine group, 65/152 patients (43%) had interventions for a mood episode, compared with 73/133 patients (55%) in the placebo group. On further analysis, it was shown that lamotrigine delayed time to intervention for any depressive episode (HR, 0.59) with no treatment difference shown for manic episodes (HR, 0.91). It was found that 38/152 (25%) participants had a depressive episode requiring intervention compared with 50/133 (38%) participants in the placebo group. The median time to a depressive episode could not be estimated for the lamotrigine group; the lower level was 137 days, but the upper limit was not reached.In the open-label phase, 2/717 patients (less than 1%) experienced serious risk-related adverse events; 127 (18%) experienced adverse events leading to study withdrawal or permanent discontinuation of the study drug during that phase, with similar incidence in both arms. Adverse events leading to permanent discontinuation or withdrawal from the study in the double-blind phase occurred in 12/152 patients (8%) in the lamotrigine arm and 18/133 (14%) in the placebo arm.Given the high incidence of unplanned pregnancies among females of childbearing age with bipolar 1 disorder, treatment decisions should always consider the possibility of pregnancy in this group. Lamotrigine has a more favorable safety profile during pregnancy; its use is also associated with a lower risk of ovulatory dysfunction, hyperandrogenism, and polycystic ovary syndrome than valproate. In addition, the efficacy of lamotrigine in delaying depressive symptoms has important clinical implications for the treatment of bipolar disorder in females of childbearing age, who are more likely than males to have a predominant depressive polarity. (Vieta, E., et al. (2024). Lamotrigine efficacy, safety, and tolerability for women of childbearing age with bipolar I disorder: Meta-analysis from four randomized, placebo-controlled maintenance studies. Eur Neuropsychopharmacol, 78, 81–92. Retrieved February 2024 from https://www.sciencedirect.com/science/article/pii/S0924977X23006715)Released: February 2024Nursing Drug Handbook© 2024 Wolters KluwerOral Simnotrelvir Effectively Treats Mild to Moderate COVID-19In a Chinese study, early administration of simnotrelvir plus ritonavir shortened time to resolution of symptoms among adult patients with mild to moderate coronavirus disease 2019 (COVID-19). Vaccination can lessen the effects of COVID-19 in high-risk groups but is less effective in preventing infections caused by SARS-CoV2 variants. More drug options are needed to accelerate the resolution of symptoms among patients who, despite vaccination, develop mild to moderate COVID-19. In this phase 2/3 double-blind, randomized, placebo-controlled trial, patients with mild to moderate COVID-19 infection were randomized within 3 days of symptom onset to 750 mg of simnotrelvir plus 100 mg of ritonavir or placebo twice daily for 5 days.READ MORE...The study enrolled 1,208 patients, defining the intent-to-treat population as all patients who received at least one dose of the trial drug or placebo and had a diagnosis of SARS-CoV2 infection confirmed by RCT-PCR, no concomitant influenza infection, and at least one COVID-related symptom at baseline. They were followed to determine time to sustained resolution of symptoms, defined as absence of 11 COVID-related symptoms for 2 consecutive days. Symptom severity was scored on a 4-point scale, from 0 (no symptoms) to 3 (severe symptoms). The most frequent COVID-19 symptoms at baseline were sore or dry throat (76.2%), cough (73.4%), stuffy or runny nose (55.9%), headache (52.9%), and fever (52.9%).Among patients who received the first dose of treatment within 72 hours of symptom onset, time to sustained resolution of symptoms (symptom score, 0) was significantly shorter with simnotrelvir plus ritonavir than placebo (180.1 hours versus 216.0 hours; median difference, −35.8 hours). In the subgroup of patients with risk factors for severe COVID-19, the median time to sustained resolution was even longer: −60.4 hours. Among patients who had sustained resolution of symptoms by day 14, symptom rebound occurred in 1/425 patients (0.2%) in the simnotrelvir plus ritonavir group and in 2/420 patients (0.5%) in the placebo group.The median time to sustained alleviation of symptoms (symptom score of 1 or less) was also significantly shorter in the simnotrelvir group than the placebo group (120.4 hours versus 168.3 hours; median difference, −47.9 hours). Simnotrelvir plus ritonavir treatment significantly accelerated the alleviation of respiratory symptoms (median difference, −41.4 hours).The baseline viral load was similar in the two groups. By day 3, the mean additional change in viral load with simnotrelvir as compared with placebo was −1.10 log10 copies/mL; by day 5, it was −1.51 log10 copies/mL. The most pronounced antiviral effect occurred at day 5. Of the 750 patients who had respiratory samples available, viral rebound occurred in 18/379 participants (4.7%) on simnotrelvir and 18/371 patients (4.9%) in the placebo group. No patients had both viral and symptom rebound. (Cao, B., et al. (2024). Oral simnotrelvir for adult patients with mild-to-moderate Covid-19. New Engl J Med, 390, 230–241. Retrieved February 2024 from https://www.nejm.org/doi/full/10.1056/NEJMoa2301425?query=featured_home)Released: February 2024Nursing Drug Handbook© 2024 Wolters KluwerTestosterone Therapy in Older Males and Fracture RiskAmong middle-aged and older males with hypogonadism, testosterone treatment did not result in a lower incidence of clinical fracture than placebo; the fracture incidence was numerically higher among males who received testosterone than among those who received placebo. This finding was reported in an issue of the New England Journal of Medicine, in a paper detailing the results of a subtrial of the TRAVERSE trial (Testosterone Replacement Therapy for Assessment of Long-term Vascular Events and Efficacy Response in Hypogonadal Men). TRAVERSE was a double-blind, randomized, placebo-controlled trial conducted at 316 sites in the United States that assessed the cardiovascular safety of testosterone treatment in older males with hypogonadism.READ MORE...Testosterone is required for a healthy skeletal system in males; males need sufficient exposure to achieve peak bone mass and strength during early adulthood and to prevent accelerated bone resorption during aging. It has been shown to increase bone mineral density on dual-energy X-ray absorptiometry, leading to improved bone strength and microarchitecture, so it would seem to follow that its use would reduce fracture risk in older males with hypogonadism. But this study did not demonstrate that.The study randomized 5,204 males with preexisting cardiovascular disease or at high risk of CV disease, symptoms of hypogonadism, and two morning serum testosterone concentrations lower than 300 mg/dL (10.4 nmol/L) to low-dose testosterone or placebo for up to 4 years. Median age of participants was 64; 80% were White, with mean body mass index of 35; about 70% had diabetes. Importantly, less than 1% took osteoporosis medications. The fracture subtrial was designed separately from the CV trial. Participants were assigned to a transdermal 1.62% testosterone gel, dosage adjusted to maintain a serum testosterone concentration of 350 to 750 mg/dL, or to placebo. At every visit, participants were asked if they had experienced a fracture since the previous visit. If so, medical records were obtained and examined by an independent judge. The main fracture endpoint was the time to the first clinical fracture; other endpoints included time to first non-high-impact fracture, time to clinical fracture in patients not taking osteoporosis medications, and fracture-free survival.Testosterone treatment in this trial did NOT result in a lower incidence of clinical fracture; rather, a numerically higher fracture incidence was seen in participants using testosterone than among those using placebo. Clinical fractures occurred in 91/2,601 participants (3.50%) in the testosterone group and in 64/2,603 participants (2.46%) in the placebo group after a median follow-up of 3.19 years. The most common sites of fractures were ribs, wrist, and ankle.This trial had limitations. The incidence of fracture was lower than estimated for statistical power; in addition, it's possible that participants, most of whom had obesity or diabetes, conditions that suppress sex hormone-binding globulin, did not have hypogonadism but pseudohypogonadism (that is, low serum testosterone but normal free testosterone). In decision making about testosterone treatment for males with low serum testosterone levels because of aging or obesity, the potential increase in future risk should be taken into consideration. Males at high risk for fracture because of bone fragility should receive osteoporosis treatment independent of testosterone treatment. Further trials need to have enough power to further characterize the fracture risk in this population. (Grossmann, M., & Anawalt, B. D. (2024). Breaking news — Testosterone treatment and fractures in older men. New Engl J Med, 390, 267–268 Retrieved February 2024 from https://www.nejm.org/doi/full/10.1056/NEJMe2313787; Snyder, P. J., et al. (2024). Testosterone treatment and fractures in men with hypogonadism. New Engl J Med, 390, 203–211. Retrieved February 2024 from https://www.nejm.org/doi/full/10.1056/NEJMoa2308836.)Released: February 2024Nursing Drug Handbook© 2024 Wolters Kluwer
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
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