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Drug News Abstracts - October 2024

Ziresovir for Respiratory Syncytial Virus in Young Children

Respiratory syncytial virus (RSV) poses a serious health threat, particularly to young children, leading to millions of hospitalizations and significant mortality each year. Although some vaccines exist for adults and pregnant women, there is currently no approved vaccine for children.

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Liraglutide Effective for Weight Loss in Children with Obesity

Many children with severe obesity struggle to achieve weight loss through standard lifestyle therapies alone, creating a need for more effective treatments. The SCALE Kids trial evaluated liraglutide for weight loss in children with obesity and found it an encouraging treatment option when paired with lifestyle changes. As there are currently no approved medications for obesity treatment in children under age 12, this trial is a potential breakthrough for addressing pediatric obesity.

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Erenumab Provides Relief for Medication-Overuse Headache in Chronic Migraine

Medication-overuse headache (MOH) is a concern for patients with chronic migraine, often resulting from the excessive use of headache medications, such as analgesics, triptans, and opioids. MOH is linked to increased health care utilization, psychiatric comorbidities, and a decline in quality of life, making effective management crucial.

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Cabozantinib for Advanced Neuroendocrine Tumors

Neuroendocrine tumors (NETs) are diverse malignancies primarily found in the GI tract, lungs, and pancreas. Treatment for advanced NETs depends on multiple factors, such as tumor location, differentiation grade, symptoms, and somatostatin-receptor expression. Options, including somatostatin analogues, everolimus, and sunitinib are available; however, most patients experience disease progression despite these treatments.

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Drug News Abstracts Archive

Drug News Abstracts - October 2024
Ziresovir for Respiratory Syncytial Virus in Young ChildrenRespiratory syncytial virus (RSV) poses a serious health threat, particularly to young children, leading to millions of hospitalizations and significant mortality each year. Although some vaccines exist for adults and pregnant women, there is currently no approved vaccine for children.READ MORE...AIRFLO, a phase 3 trial, assessed the selective oral RSV F protein inhibitor, ziresovir, for its effictiveness and safety in children ages 1 to 24 months hospitalized with RSV. The study ran from September 2020 to January 2022 and was conducted across multiple centers in China. Participants, most age 6 months or younger, were randomly assigned to receive either ziresovir or placebo, focusing on clinically relevant cases of RSV infection.The trial comprised two parts: the first assessed safety and pharmacokinetics, while the second evaluated efficacy. Participants received doses of ziresovir every 12 hours for 5 days, tailored to their body weight. The primary efficacy endpoint was the Wang bronchiolitis clinical score, which measures the severity of respiratory symptoms, while secondary endpoints included viral load reductions and symptom-based assessments.Results showed that ziresovir improved clinical scores compared to placebo. Specifically, ziresovir produced notable reductions in the Wang score (−3.4 points versus −2.7 points for placebo), with reductions observed as early as 48 hours after treatment initiation. Furthermore, ziresovir achieved a decrease in RSV viral load, affirming its antiviral effectiveness. Improvements were consistent across various patient subgroups, including those at higher risk for severe outcomes.In terms of safety, adverse events were similar between the ziresovir and placebo groups and were predominantly mild to moderate in severity. Overall, the trial's encouraging clinical and virological results highlight the need for further international trials to explore ziresovir's potential as a treatment for RSV in young children worldwide. (Zhao, S., et al. (2024). Ziresovir in hospitalized infants with respiratory syncytial virus infection. NEJM, 391, 1096–1107. Retrieved September 2024 from https://www.nejm.org/doi/full/10.1056/NEJMoa2313551)Released: October 2024Nursing Drug Handbook© 2024 Wolters KluwerLiraglutide Effective for Weight Loss in Children with ObesityMany children with severe obesity struggle to achieve weight loss through standard lifestyle therapies alone, creating a need for more effective treatments. The SCALE Kids trial evaluated liraglutide for weight loss in children with obesity and found it an encouraging treatment option when paired with lifestyle changes. As there are currently no approved medications for obesity treatment in children under age 12, this trial is a potential breakthrough for addressing pediatric obesity.READ MORE...SCALE Kids, a phase 3 trial, involved 82 participants ages 6 to less than 12 with a BMI of 95% or higher, randomized to receive liraglutide or placebo, alongside lifestyle interventions. Results showed a major reduction in BMI and body weight for the liraglutide group. After 56 weeks, the liraglutide group had a BMI reduction of −5.8% compared to +1.6% in the placebo group, marking a substantial difference of −7.4% favoring liraglutide.Secondary endpoints, including blood pressure and glycated hemoglobin levels, also supported liraglutide. However, waist circumference changes were not significantly different between groups, and GI side effects were more common with the treatment. In addition, the study doesn't discuss how body composition changes with treatment and whether the weight loss comes from fat mass or lean mass.Although liraglutide shows promise for treating severe obesity in children who don't respond to lifestyle changes, it's important to consider a careful, individualized approach. The goal should not be to prescribe medication broadly for all children with elevated BMI but rather to identify those who truly need additional help because of severe obesity and related health complications. (Neale, T. (2024). Liraglutide helps shed weight in young children with obesity. TCTMD. Retrieved September 2024 from https://www.tctmd.com/news/liraglutide-helps-shed-weight-young-children-obesity; Fox, C. K., et al. (2024). Liraglutide for children 6 to < 12 years of age with obesity — a randomized trial. NEJM. Advance online publication. Retrieved September 2024 from https://www.nejm.org/doi/full/10.1056/NEJMoa2407379)Released: October 2024Nursing Drug Handbook© 2024 Wolters KluwerErenumab Provides Relief for Medication-Overuse Headache in Chronic MigraineMedication-overuse headache (MOH) is a concern for patients with chronic migraine, often resulting from the excessive use of headache medications, such as analgesics, triptans, and opioids. MOH is linked to increased health care utilization, psychiatric comorbidities, and a decline in quality of life, making effective management crucial.READ MORE...Management strategies emphasize the withdrawal of overused medications; however, this withdrawal process can lead to high relapse rates. Recent studies have focused instead on targeting the calcitonin gene-related peptide (CGRP) pathway, which is implicated in migraine pathogenesis. Erenumab, a monoclonal antibody that inhibits CGRP receptors, is a promising candidate for helping patients with MOH revert to nonmedication overuse status.A recent study investigated the efficacy and safety of erenumab in adults diagnosed with chronic migraine and concomitant MOH. The phase 4, randomized, controlled trial, which ran from October 2019 to November 2022, enrolled 584 participants who had a history of preventive treatment failure. Participants received either erenumab (140 mg or 70 mg) or placebo for 24 weeks, with a primary endpoint focused on the absence of MOH by month 6.Results indicated that a significant proportion of participants receiving erenumab achieved MOH remission (69.1% with 140-mg dose; 60.3% with 70-mg dose) compared to those on placebo (52.6%), with improvements in acute medication use and overall functionality. Additionally, participants reported a reduction in average monthly headache days and improvements in physical impairment and quality-of-life metrics, reinforcing the benefits of effective preventive therapies for managing MOH.These findings support the use of erenumab as an effective treatment option for patients suffering from MOH due to chronic migraine. The study's outcomes support the importance of preventive treatment strategies that not only alleviate headache frequency but also enhance the overall quality of life for these patients. (Tepper, S. J., et al. (2024). Efficacy and safety of erenumab for nonopioid medication overuse headache in chronic migraine: A phase 4, randomized, placebo-controlled trial. JAMA Neurology. Advance online publication. Retrieved September 2024 from https://jamanetwork.com/journals/jamaneurology/fullarticle/2823594)Released: October 2024Nursing Drug Handbook© 2024 Wolters KluwerCabozantinib for Advanced Neuroendocrine TumorsNeuroendocrine tumors (NETs) are diverse malignancies primarily found in the GI tract, lungs, and pancreas. Treatment for advanced NETs depends on multiple factors, such as tumor location, differentiation grade, symptoms, and somatostatin-receptor expression. Options, including somatostatin analogues, everolimus, and sunitinib are available; however, most patients experience disease progression despite these treatments.READ MORE...In a phase 2 trial, cabozantinib, a tyrosine kinase inhibitor, showed potential in treating advanced NETs. This prompted the CABINET trial: a phase 3, double-blind, randomized, controlled study, designed to assess cabozantinib's efficacy in patients with previously treated, progressive extrapancreatic or pancreatic NETs. This trial was critical for evaluating new treatment avenues after standard therapies.The CABINET trial ran from October 2018 to August 2023 and enrolled 203 adults with extrapancreatic NETs and 95 with pancreatic NETs across multiple U.S. sites. It included patients with well- or moderately- differentiated NETs of grades 1 to 3. The study randomly assigned patients to receive either cabozantinib (60 mg) or a placebo. The primary endpoint was progression-free survival, defined as the time from randomization to disease progression or death.The results indicated a significant advantage for cabozantinib in delaying disease progression. In the extrapancreatic cohort, those receiving cabozantinib experienced a median progression-free survival of 8.4 months, compared to 3.9 months for placebo. Similarly, in the pancreatic cohort, cabozantinib led to a median progression-free survival of 13.8 months versus 4.4 months for placebo, demonstrating its potential as an effective treatment option.Although cabozantinib showed improved progression-free survival rates, overall survival results were not statistically significant, likely due to subsequent therapies received by patients. The trial did report adverse events consistent with the known safety profile of cabozantinib, with many patients requiring dose adjustments. Despite this, the CABINET trial supports cabozantinib as a promising therapy for advanced NETs. (Chan, J. A., et al. (2024). Phase 3 trial of cabozantinib to treat advanced neuroendocrine tumors. NEJM. Advance online publication. Retrieved September 2024 from https://www.nejm.org/doi/full/10.1056/NEJMoa2403991)Released: October 2024Nursing Drug Handbook© 2024 Wolters Kluwer
Drug News Abstracts - September 2024
New RSV Vaccination Recommendations for Older AdultsRespiratory syncytial virus (RSV) poses a major risk to older adults, especially during the fall and winter months. In response, the Advisory Committee on Immunization Practices (ACIP) initially recommended RSV vaccination for U.S. adults age 60 and older in June 2023. However, due to new evidence and postlicensure data, the ACIP updated its guidance on June 26, 2024. The revised recommendation advises a single dose of any FDA-approved RSV vaccine for all adults age 75 and older and for those ages 60 to 74 who are at higher risk for severe RSV disease. This update aims to improve vaccination coverage and target those who would benefit most.READ MORE...As of spring 2024, RSV vaccination uptake among adults 60 and older was about 20% to 25%. The updated recommendations were informed by new clinical trial data and postlicensure studies, including those for Moderna's mResvia, which showed an efficacy of about 78.7% initially, though it waned over time. Safety data indicated more severe reactions compared to placebo but didn't show a significant increase in serious adverse events. For other vaccines like GlaxoSmithKline's Arexvy and Pfizer's Abrysvo, effectiveness ranged from 75% to 82% in preventing RSV-related hospitalizations, with some safety concerns about Guillain-Barré syndrome, though not conclusively linked to the vaccines.The ACIP's updated recommendations aim to simplify vaccination guidelines based on age and risk. The committee will continue to assess and update recommendations as new evidence emerges and will consider the need for additional doses in the future. (Britton, A., et al. (2024). Use of respiratory syncytial virus vaccines in adults aged ≥60 years: Updated recommendations of the Advisory Committee on Immunization Practices: United States, 2024. MMWR Weekly, 73(32), 696–702. Retrieved August 2024 from https://www.cdc.gov/mmwr/volumes/73/wr/mm7332e1.htm?s_cid=mm7332e1_w)Released: September 2024Nursing Drug Handbook© 2024 Wolters KluwerOsimertinib Improves Progression-Free Survival in EGFR-Mutated NSCLCPatients with epidermal growth factor receptor (EGFR) mutations tend to experience shorter progression-free survival and higher incidence of distant metastases compared to those without mutations. For patients with unresectable stage III non-small-cell lung cancer (NSCLC) with EGFR mutations, the current standard treatment involves concurrent chemoradiotherapy followed by consolidation with durvalumab. However, targeted treatments are lacking, and previous studies suggest poorer outcomes for these patients.READ MORE...LAURA, an international, phase 3, double-blind, placebo-controlled trial, evaluated the efficacy and safety of osimertinib, an EGFR tyrosine-kinase inhibitor, in EGFR-mutated unresectable stage III NSCLC. The study ran from August 2018 through July 2022 and enrolled 216 patients. Eligible participants had completed chemoradiotherapy and showed no progression. They were randomized to receive either osimertinib (80 mg once per day) or placebo. The primary endpoint was progression-free survival.Results showed that osimertinib significantly improved progression-free survival compared to placebo, with a median of 39.1 months versus 5.6 months, respectively, and demonstrated a substantial reduction in the risk of disease progression or death (hazard ratio, 0.16). The treatment also showed lower rates of local progression, distant metastases, and new lesions, particularly brain lesions, compared to placebo.Adverse events with osimertinib included radiation pneumonitis and diarrhea. Although the incidence of interstitial lung disease was higher with osimertinib compared to placebo, most cases were mild. Despite the higher incidence of some adverse effects, osimertinib's overall safety profile was manageable.The results of the LAURA trial indicate that osimertinib may be a promising postchemoradiotherapy option for patients with unresectable stage III EGFR-mutated NSCLC compared to placebo, suggesting a shift in treatment strategies for this specific patient group. (Lu, S., et al. (2024). Osimertinib after chemoradiotherapy in stage III EGFR-mutated NSCLC. NEJM, 391, 585–597. Retrieved August 2024 from https://www.nejm.org/doi/10.1056/NEJMoa2402614?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed)Released: September 2024Nursing Drug Handbook© 2024 Wolters KluwerOlanzapine for Nausea and Vomiting in Moderately Emetogenic ChemotherapyChemotherapy-induced nausea and vomiting (CINV) remain significant challenges for cancer patients undergoing treatment, impacting their quality of life (QOL). Guidelines for antiemetic prophylaxis (AEP) have evolved to address these issues, but clinical studies indicate that breakthrough CINV remains a problem, prompting further research.READ MORE...Olanzapine, an atypical antipsychotic, has shown promise in controlling nausea and vomiting in highly emetogenic chemotherapy regimens. A recent phase 3 trial aimed to determine if incorporating olanzapine into standard AEP protocols could enhance complete response (CR) rates in patients receiving moderately emetogenic chemotherapy (MEC) regimens, including oxaliplatin, carboplatin, or irinotecan, and to assess its impact on patient-reported outcomes.Conducted from March 2019 to August 2023, this multicenter trial involved 560 chemotherapy-naïve patients receiving MEC regimens. Participants were randomized to receive either standard AEP or the same regimen with the addition of olanzapine. The study included randomization and blinding of medical professionals and statisticians to ensure accurate results. Patients recorded their symptoms and treatment responses, and QOL was measured using the Functional Living Index - Emesis questionnaire.The trial found that adding olanzapine significantly improved CR rates compared to standard AEP alone, with a notable benefit in the delayed phase of CINV. Specifically, 91% of patients in the olanzapine group achieved CR compared to 82% in the observation group, and this improvement was maintained during the later assessment period. The olanzapine group also experienced better nausea and CINV control and used fewer rescue medications.QOL assessments confirmed these results, with fewer patients in the olanzapine group experiencing deterioration in QOL related to CINV. Although the addition of olanzapine didn't significantly change nausea control compared to the observation group, it did improve overall control of nausea and vomiting combined.Study limitations include the absence of a placebo control and the lack of evaluation for lower doses of olanzapine. Also, the predominance of GI cancer patients receiving oxaliplatin could influence the findings. Nonetheless, the trial supports the incorporation of olanzapine into AEP protocols for MEC regimens, suggesting that it could become a standard part of antiemetic therapy. (Ostwal, V., et al. (2024). Olanzapine as antiemetic prophylaxis in moderately emetogenic chemotherapy: A phase 3 randomized clinical trial. JAMA Network Open, 7(8), Article e2426076. Retrieved August 2024 from https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2822027)Released: September 2024Nursing Drug Handbook© 2024 Wolters KluwerEnfortumab Vedotin Plus Pembrolizumab for Urothelial CancerEnfortumab vedotin, an antibody-drug conjugate targeting nectin-4, combined with pembrolizumab, a programmed death-1 inhibitor, has shown promise in treating advanced urothelial carcinoma. Based on positive phase 1b/2 trial results showing high response rates and durable outcomes, the FDA granted accelerated approval for this combination for patients who are ineligible for cisplatin-based chemotherapy.READ MORE...The EV-302 trial, a global phase 3 study, aimed to compare the effectiveness and safety of enfortumab vedotin plus pembrolizumab versus platinum-based chemotherapy in patients with previously untreated advanced urothelial carcinoma. The trial included 886 patients, median age 69 years, with a range of histologic types. Patients were randomly assigned to either the combination therapy or the chemotherapy group and treated accordingly.Results from the trial showed that enfortumab vedotin and pembrolizumab significantly improved progression-free survival compared to chemotherapy, with a median of 12.5 months versus 6.3 months, respectively. Overall survival was longer in the combination group as well, with a median of 31.5 months compared to 16.1 months in the chemotherapy group.Adverse events associated with enfortumab vedotin and pembrolizumab, such as skin reactions and peripheral neuropathy, were still present, but manageable. The combination therapy also resulted in fewer severe adverse events compared to chemotherapy, despite the longer duration of treatment.The EV-302 trial demonstrated that enfortumab vedotin and pembrolizumab offer significant benefits over platinum-based chemotherapy for untreated advanced or metastatic urothelial carcinoma. The improved survival and response rates make this combination a compelling alternative, potentially changing the standard treatment paradigm for this challenging cancer. (Levitan, D. (2024). Enfortumab vedotin plus pembrolizumab offer improved survival without detriment to quality of life. American Society of Clinical Oncology, Daily News. Retrieved August 2024 from https://dailynews.ascopubs.org/do/enfortumab-vedotin-plus-pembrolizumab-offer-improved-survival-without-detriment-quality; Powles, T., et al. (2024). Enfortumab vedotin and pembrolizumab in untreated advanced urothelial cancer. NEJM, 390, 875–888. Retrieved August 2024 from https://www.nejm.org/doi/full/10.1056/NEJMoa2312117)Released: September 2024Nursing Drug Handbook© 2024 Wolters Kluwer
Drug News Abstracts - August 2024
Comparing Safety and Efficacy of Chemotherapy Regimens for Hodgkin LymphomaSurvival outcomes for advanced-stage classical Hodgkin lymphoma were poor before the advent of modern chemotherapy. The high-intensity regimen, eBEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone), has been standard but is associated with serious toxicities. BrECADD, which incorporates the antibody-drug conjugate brentuximab vedotin, was developed to potentially offer comparable effectiveness with fewer toxic side effects. A study comparing the two chemotherapy regimens aimed to balance treatment efficacy with reduced toxicity, particularly focusing on long-term health impacts like organ dysfunction and infertility in young adults with Hodgkin lymphoma.READ MORE...The phase 3 randomized, multicenter, parallel, intergroup clinical trial was conducted between July 2016 and August 2020, and enrolled 1,500 patients (age 60 and younger) across multiple countries. Patients received cycles of either eBEACOPP or BrECADD (both initiated at full-dose level 4) administered in 21-day intervals. Positron emission tomography (PET) guided treatment adaptation to tailor therapy based on early response assessment.Researchers sought to compare treatment-related morbidity and progression-free survival between the two regimens. BrECADD demonstrated significantly lower treatment-related morbidity rates, with 42% of patients experiencing at least one treatment-morbidity event compared to 59% of patients receiving eBEACOPP. Both groups achieved similar rates of complete remission post-chemotherapy, with a substantial proportion of patients benefiting from PET-guided treatment adjustments.Regarding efficacy, BrECADD showed noninferiority and, in a subsequent analysis, superiority in progression-free survival compared to eBEACOPP (4-year progression-free survival for BrECADD was 94.3% versus 90.9% for eBEACOPP). Safety assessments included resolution of toxicities within a year posttreatment, showing generally manageable long-term impacts on patients' health. Additionally, BrECADD was associated with better preservation of gonadal function and fewer second primary malignancies compared to eBEACOPP.Overall, the study supports BrECADD as a promising alternative to eBEACOPP for treating advanced-stage Hodgkin lymphoma, offering comparable efficacy with significantly reduced treatment-related toxicity. These findings are likely to influence future treatment guidelines and improve outcomes for young adults facing this challenging cancer diagnosis. (Borchmann, P., et al. (2024). Assessing the efficacy and tolerability of PET-guided BrECADD versus eBEACOPP in advanced-stage, classical Hodgkin lymphoma (HD21): A randomised, multicentre, parallel, open-label, phase 3 trial. The Lancet. Advance online publication. Retrieved July 2024 from https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)01315-1/fulltext)Released: August 2024Nursing Drug Handbook© 2024 Wolters KluwerCendakimab Improves Skin Symptoms in Severe Atopic DermatitisAtopic dermatitis, a chronic inflammatory skin condition, causes substantial patient burden including severe itching, sleep disturbances, and impacts on daily activities. When topical treatments are inadequate for moderate to severe atopic dermatitis, systemic therapies like biologics become necessary. Biologics approved for atopic dermatitis target interleukin (IL)-4 or IL-13 pathways due to their involvement in atopic dermatitis pathogenesis.READ MORE...Cendakimab, a monoclonal antibody targeting IL-13, was evaluated in a phase 2 randomized, double-blind, placebo-controlled clinical trial for its efficacy and safety in adults with moderate to severe atopic dermatitis. The study, which ran from May 2021 to November 2022, randomized 221 patients to receive varying doses of cendakimab (720 mg, once weekly; 720 mg, every 2 weeks; or 360 mg, every 2 weeks) or placebo for 16 weeks. Primary endpoints included improvement in Eczema Area and Severity Index (EASI) scores, with secondary endpoints focusing on skin clearance and pruritus reduction.Overall, a larger proportion of cendakimab patients achieved a 75% or greater reduction in EASI (720 mg, once weekly: 50.0%; 720 mg, every 2 weeks: 48.2%; 360 mg, every 2 weeks: 52.7%) compared to placebo (26.3%). There was also a noticeable improvement in skin clearance in patients receiving 720-mg weekly cendakimab, with 33.3% of patients achieving a score of 0 (clear) or 1 (almost clear) than with placebo (9.4%). Safety assessments indicated manageable adverse events, with conjunctivitis being the most notable, consistent with other IL-13 inhibitors.This study supports cendakimab as a potential therapeutic option for treating moderate to severe atopic dermatitis, particularly in reducing inflammation and improving skin symptoms. Further research could explore its long-term efficacy and broader applicability in diverse patient populations. (Blauvelt, A., et al. (2024). Cendakimab in patients with moderate to severe atopic dermatitis: A randomized clinical trial. JAMA Dermatology. Published online. Retrieved July 2024 from https://jamanetwork.com/journals/jamadermatology/fullarticle/2821285)Released: August 2024Nursing Drug Handbook© 2024 Wolters KluwerEfanesoctocog Alfa Manages Bleeding in Children with Severe Hemophilia AHemophilia A is characterized by deficiency in factor VIII, leading to recurrent bleeding episodes, particularly into joints, despite current therapies. Standard treatments require frequent injections due to their limited duration of action, which poses challenges for adherence, especially in children. XTEND-Kids, a phase 3 open-label, international, single-group study, evaluated efanesoctocog alfa, a new factor VIII replacement therapy, in previously treated children with severe hemophilia A. Efanesoctocog alfa is designed to extend factor VIII half-life, which allows for weekly dosing, potentially improving treatment adherence.READ MORE...The study enrolled 74 patients (younger than age 12) who received prophylactic intravenous efanesoctocog alfa (50 IU/kg) once per week for 52 weeks. For bleeding episodes, one dose of efanesoctocog alfa (50 IU/kg) was given, with additional 30 or 50 IU/kg doses every 2 or 3 days, as needed. The primary endpoint was the development of inhibitors to factor VIII, which did not occur in any patient. Adverse events were mostly nonserious, and no treatment discontinuations due to adverse effects were reported.Efanesoctocog provided effective bleeding prevention, with a median annualized bleeding rate of 0.00 and a mean rate of 0.89. Bleeding episodes were likewise managed efficiently, with most resolved using a single injection. Joint health showed overall improvement, indicating potential long-term benefits in joint preservation. In addition, sustained factor VIII levels above therapeutic thresholds were observed for up to 7 days, supporting the weekly prophylactic dosing.Demonstrating promising safety and efficacy profiles in children with severe hemophilia A, efanesoctocog alpha offers a convenient weekly prophylactic option that may enhance treatment outcomes and patient quality of life compared to current therapies. Future studies will further explore its long-term safety and efficacy, including for previously untreated patients and different age groups. (Malec, L., et al. (2024). Efanesoctocog alfa prophylaxis for children with severe hemophilia A. N Engl J Med, 391, 235—246. Retrieved July 2024 from https://www.nejm.org/doi/abs/10.1056/NEJMoa2312611)Released: August 2024Nursing Drug Handbook© 2024 Wolters Kluwer Lowering LDL Cholesterol with Lerodalcibep in Patients with or at Risk for Cardiovascular DiseaseRecent updates to lipid guidelines suggest more aggressive treatment for lowering LDL cholesterol to prevent cardiovascular (CV) events, advocating for additional medications and stricter targets if statins alone are insufficient. However, lerodalcibep, a third-generation PCSK9 inhibitor, appears effective in achieving these lower targets.READ MORE...Lerodalcibep works by blocking proprotein convertase subtilisin/kexin type 9 (PCSK9) from binding to LDL cholesterol, thereby enhancing cholesterol clearance without significant safety concerns. The drug combines adnectin, an anti-PCSK9 binding protein, with human serum albumin, allowing for a smaller injection volume compared to existing monoclonal antibodies.The phase 3 LIBerate-HR study aimed to evaluate the effectiveness of lerodalcibep in lowering LDL cholesterol in patients at risk for CV disease. The study included 922 patients, with or at high risk for CV disease, randomized to receive monthly subcutaneous injections of lerodalcibep (300 mg) or placebo for 52 weeks. Results showed that lerodalcibep achieved a profound reduction in LDL cholesterol, with 94% of treated patients achieving at least a 50% reduction compared to placebo (19%). The drug also lowered non-HDL cholesterol (−47.3%), apolipoprotein B (−43%), lipoprotein(a) (−33.4%), and triglycerides (−16.5%) while increasing HDL cholesterol by 6.5%. Safety profiles were similar to placebo, with manageable injection-site reactions and no immunogenicity issues reported.Lerodalcibep may be a versatile option for patients needing PCSK9 inhibitors, with the advantage of monthly injections over bi-weekly injections required by current monoclonal antibodies. However, concerns remain regarding long-term safety and immunogenicity, given past issues with other PCSK9 inhibitors like bococizumab.Results of this study show lerodalcibep to be an effective and well-tolerated PCSK9 inhibitor, potentially enhancing treatment options for patients with or at high risk for CV disease, pending further regulatory and safety evaluations. (Maxwell, Y. L. (2024). LIBerate-HR: Lerodalcibep lowers LDL more sharply than placebo over 1 year. TCTMD. Retrieved July 2024 from https://www.tctmd.com/news/now-published-liberate-hr-lerodalcibep-lowers-ldl-more-sharply-placebo-over-1-year; Klug, E. Q., et al. (2024). Efficacy and safety of lerodalcibep in patients with or at high risk of cardiovascular disease: A randomized clinical trial. JAMA Cardiol. Advance online publication. Retrieved July 2024 from https://jamanetwork.com/journals/jamacardiology/article-abstract/2820248)Released: August 2024Nursing Drug Handbook© 2024 Wolters Kluwer
Drug News Abstracts - July 2024
Neoadjuvant Immunotherapy for Mismatch Repair Deficient Colon Cancer: Redefining TreatmentLocally advanced DNA mismatch repair-deficient (dMMR) colon cancer accounts for up to 15% of nonmetastatic colon cancers. These tumors are typically managed similarly to mismatch repair-proficient tumors, with surgery followed by adjuvant chemotherapy. However, recent studies, including the NICHE-2 trial, suggest potential benefits of immunotherapy over chemotherapy in this patient population.READ MORE...The NICHE-2, a phase 2, multicenter, single-group study, conducted by the Netherlands Cancer Institute, aimed to evaluate the safety and efficacy of neoadjuvant therapy using a combination of nivolumab (a programmed cell death 1 [PD-1] inhibitor) and ipilimumab (a cytotoxic T-lymphocyte antigen 4 [CTLA-4] inhibitor) in patients with unresected, locally advanced dMMR colon cancer. The study, which ran from July 2017 to July 2022, enrolled 115 patients (median age, 60 years; 58% women) with stage II or III disease, confirmed as resectable with no distant metastases. Patients received 4-weeks of neoadjuvant treatment (2-week cycles, with treatment at the start of each cycle) prior to surgery. Primary end points of the study were timely surgery (delay of no more than 2 weeks) and 3-year disease-free survival.Key findings from NICHE-2 included a high pathologic response rate: 98% of patients showed some degree of pathologic response to the immunotherapy regimen, affording them a timely surgery, with 68% achieving a pathologic complete response (no residual viable tumor in the tumor bed or lymph nodes). Importantly, no disease recurrences were observed during the study's follow-up period (median, 26.2 months), suggesting promising long-term disease control outcomes. This contrasts with historic recurrence rates seen in dMMR colon cancer despite adjuvant chemotherapy.The safety profile of the regimen was also assessed, with most adverse events being manageable grade 1 or 2 immune-related adverse events. Grade 3 or 4 adverse events occurred in a small percentage of patients and were generally reversible.The NICHE-2 trial contributes significant evidence supporting the use of neoadjuvant PD-1 and CTLA-4 inhibitors in locally advanced dMMR colon cancer, potentially redefining standard treatment for this subset of patients. (Chalabi, M., et al. (2024). Neoadjuvant immunotherapy in locally advanced mismatch repair-deficient colon cancer. N Engl J Med, 390, 1949-1958. Retrieved June 2024 from https://www.nejm.org/doi/full/10.1056/NEJMoa2400634)Released: July 2024Nursing Drug Handbook© 2024 Wolters KluwerPeceleganan Spray for Skin Wound InfectionsSkin wound infections are typically treated with antibiotics, but frequent use of these drugs can cause antibiotic resistance. As a result, antimicrobial peptides (AMPs), like peceleganan (PL-5), have been considered as an alternative treatment option for skin wound infections. AMPs work via nonspecific mechanisms of disrupting bacterial cells, which reduces the likelihood of antibiotic resistance.READ MORE...In a phase 3 clinical trial conducted across 37 hospitals in China, PL-5 spray was evaluated for its efficacy and safety in treating skin wound infections compared to silver sulfadiazine (SSD) cream, a conventional topical antibiotic. The trial enrolled 570 patients, ages 18 to 75, with secondary open wound infections randomized to receive either 2% peceleganan spray (n = 381) or 1% SSD cream (n = 189). The primary endpoint, clinical efficacy rate on day 8, showed that 90.4% of patients treated with PL-5 achieved clinical efficacy compared to 78.7% in the SSD group, a statistically significant difference. Although SSD showed higher rates of bacterial clearance (46.0%) compared to PL-5 (24.0%), PL-5 still exhibited substantial effectiveness against common wound pathogens like Staphylococcus aureus and Pseudomonas aeruginosa.Safety evaluations indicated that PL-5 spray had a comparable incidence of adverse events to SSD cream, with no unexpected safety issues reported. Both treatments were well-tolerated among the study population, which included diverse wound types, such as burns, physical injuries, and diabetic foot ulcers.Overall, PL-5 spray demonstrated promising clinical efficacy and safety in treating skin wound infections, likely due to its unique antimicrobial action against a broad spectrum of bacteria, including drug-resistant strains. Further research is recommended to explore its mechanism of action and optimize its clinical applications, possibly expanding its role in wound care management. (Wei, Y., et al. (2024). Peceleganan spray for the treatment of skin wound infections: A randomized clinical trial. JAMA Netw Open, 7(6), Article e2415310. Retrieved June 2024 from https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2819836) Released: July 2024Nursing Drug Handbook© 2024 Wolters KluwerLinvoseltamab: A Different Approach to Treating Relapsed and Refractory Multiple MyelomaMultiple myeloma remains incurable despite advances in therapies, and there is a need for treatments that produce deep and long-lasting remissions, especially in patients who are resistant to current standard therapies. Linvoseltamab, a B-cell maturation antigen (BCMA)xCD3 bispecific antibody, which has shown antitumor activity in previous studies, has been suggested as a possible treatment option for relapsed and refractory multiple myeloma (RRMM).READ MORE...LINKER-MM1, an open-label, phase 1/2 clinical trial, sought to evaluate the efficacy of linvoseltamab in treating RRMM. The trial was conducted at 23 centers in multiple countries between January 2019 and October 2022 and included 282 patients (median age, 70) with triple-class refractory multiple myeloma. Phase 1 and 2 of the trial treated patients with varying doses of linvoseltamab (ranging from 3 mg to 800 mg) for a minimum of 24 weeks, and evaluated overall response rate, duration of response, and progression-free survival.Results showed that the optimal dose of linvoseltamab was 200 mg, which provided an overall response rate of 70.9%, with 63.2% of patients achieving very good partial response or better, and 49.6% achieving complete response. Responses were rapid and long-lasting, with a median time of response of 29.4 months and a progression-free survival not reached at the data cutoff. Safety profiles indicated mild to moderate adverse events. Infections were common but decreased over time, especially among patients achieving deep responses.The outcomes of this study support linvoseltamab as a valuable addition to the treatment landscape for multiple myeloma, offering deep and durable responses with a manageable safety profile compared to other BCMA-targeted therapies. (Bumma, N., et al. (2024). Linvoseltamab for treatment of relapsed/refractory multiple myeloma. Journal of Clinical Oncology. Advanced online publication. Retrieved June 2024 from https://ascopubs.org/doi/10.1200/JCO.24.01008)Released: July 2024Nursing Drug Handbook© 2024 Wolters KluwerTirzepatide Shows Promise in Managing Obstructive Sleep ApneaObstructive sleep apnea (OSA), characterized by disrupted breathing during sleep, is linked to cardiovascular complications, often exacerbated by excess weight. Traditional treatments, like positive airway pressure (PAP), have limitations in adherence and long-term effectiveness, prompting exploration of pharmaceutical interventions, like the GLP-1 receptor agonist, tirzepatide.READ MORE...SURMOUNT-OSA, comprised of two 52-week, phase 3 clinical trials, was conducted from June 2022 to March 2024 at 60 sites in multiple countries to assess tirzepatide as a treatment option for moderate-to-severe sleep apnea in those who are obese. The trials enrolled 469 participants either not using PAP (trial 1, 234 participants) or currently using PAP (trial 2, 235 participants) and randomized them to receive either tirzepatide (2.5 mg once weekly, then 2.5-mg dose increase every 4 weeks until week 20) or placebo for 52 weeks. The primary endpoint was the change in apnea-hypopnea index (AHI), with secondary endpoints including changes in body weight, hypoxic burden, inflammatory markers, and blood pressure. Baseline characteristics showed high AHI levels (average 51.5 to 49.5 events per hour) and severe obesity (average BMI 39.1 to 38.7).Results demonstrated significant reductions in AHI with tirzepatide compared to placebo in both trials: −20.0 to −23.8 events per hour. Secondary endpoints, such as body weight, high-sensitivity C-reactive protein concentration, and systolic blood pressure also showed improvements with tirzepatide. Adverse events, predominantly gastrointestinal, were mostly mild to moderate and occurred more frequently during dose escalation.These findings support further research of GLP-1 receptor agonists, such as tirzepatide, as a treatment option for OSA in individuals with obesity, addressing both sleep-related and cardiovascular risks associated with the condition. (Malhotra, A., et al. (2024). Tirzepatide for the treatment of obstructive sleep apnea and obesity. NEJM. Advanced online publication. Retrieved June 2024 from https://www.nejm.org/doi/full/10.1056/NEJMoa2404881)Released: July 2024Nursing Drug Handbook© 2024 Wolters Kluwer
Drug News Abstracts - June 2024
Analysis of Self-Administered Aspirin Post-Chest Pain to Prevent Cardiovascular MortalityAccording to the American Heart Association, someone experiences an acute myocardial infarction (AMI) in the United States every 40 seconds, making it a leading cause of mortality. However, a significant number of AMI deaths occur outside the hospital, with delayed access to medical care being a contributing factor. The International Study of Infarct Survival sought to analyze the potential benefits and risks of self-administering aspirin within 4 hours of experiencing severe chest pain to reduce mortality post-AMI.READ MORE...The analysis used a population simulation model with data pooled from the 2019 U.S. Census. It included adults age 40 and older who self-administered 325 mg of aspirin within 4 hours after chest-pain onset (with or without AMI) and continued aspirin treatment for 28 days after AMI diagnosis (standard care). This data was compared to the results of patients who received aspirin therapy more than 4 hours after symptoms began. The primary outcome was estimating the potential number of deaths delayed post-AMI and the increased risk of bleeding associated with aspirin use.The study found that self-administration of aspirin within 4 hours of chest pain onset resulted in 13,016 deaths delayed in the United States in 2019 among adults age 40 and older. The bleeding deaths due to aspirin use in the same population was 963. Despite the bleeding risk, the researchers suggest that the benefits of aspirin self-administration should be promoted as a simple and cost-effective intervention for reducing AMI mortality.The findings highlight the need for further research and efforts to scale up aspirin self-administration initiatives to reach more individuals at risk for AMI. (Russo, R. G., et al. (2024). Self‐administration of aspirin after chest pain for the prevention of premature cardiovascular mortality in the United States: A population‐based analysis. Journal of the American Heart Association. Advance online publication. Retrieved May 2024 from https://www.ahajournals.org/doi/10.1161/JAHA.123.032778)Released: June 2024Nursing Drug Handbook© 2024 Wolters KluwerDequalinium as Potential Treatment for Bacterial VaginosisBacterial vaginosis (BV), a common and recurrent vaginal infection in females of reproductive age, is typically treated with antibiotics, like metronidazole and clindamycin. However, their adverse effects and risk of antibiotic resistance necessitate alternative treatments. A recent study evaluated the efficacy of dequalinium chloride, an antiseptic with broad-spectrum activity against various microorganisms, as a potential nonantibiotic treatment for BV.READ MORE...The phase 4, multicenter, triple-blind, parallel clinical trial aimed to compare the safety and efficacy of dequalinium to oral metronidazole, as first-line treatment for BV. The study, which ran from July 2021 to August 2022, recruited 151 premenopausal females (age 18 and older) with BV from Poland, the Czech Republic, and Slovakia. The participants were randomized into two groups receiving either dequalinium or placebo (10-mg intravaginal tablets used once a day for 6 days), or metronidazole or placebo (500-mg oral tablets taken twice a day for 7 days). Patients were asked to keep track of symptoms, tolerability, efficacy, and adverse events in an electronic diary. Two follow-up visits occurred after the start of treatment (on days 7 to 11 and days 20 to 40) for clinical evaluation.Various measures, including clinical and bacteriologic cure rates, safety profiles, and rate of recurrence, were evaluated over the course of the study. Results showed that dequalinium had similar results to metronidazole in terms of clinical cure rates, with over 90% of patients in both groups showing resolution of symptoms at the first visit (93.1% dequalinium versus 90.6% metronidazole). Furthermore, dequalinium demonstrated better tolerability (60.0% rated dequalinium "very good" versus 38.9% for metronidazole) and fewer adverse events compared to metronidazole (7 versus 11). The rate of BV recurrence, which tends to be high (30% to 70% within 6 months), was the same between the groups.The study's findings suggest that dequalinium chloride could be considered as first-line treatment for BV due to its comparable efficacy to antibiotics, broader spectrum of activity, better tolerability, and lower likelihood of resistance development. However, the high BV recurrence rate was similar to antibiotics, indicating the need for further research into strategies to prevent recurrence, such as probiotic use. (Raba, G., et al. (2024). Efficacy of dequalinium chloride vs metronidazole for the treatment of bacterial vaginosis: A randomized clinical trial. JAMA Network Open, 7(5), Article e248661. Retrieved May 2024 from https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2818221)Released: June 2024Nursing Drug Handbook© 2024 Wolters Kluwer Progestogen Versus Combined Oral Contraceptive for Endometriosis PainEndometriosis, affecting up to 1-in-10 women of reproductive age, involves the growth of endometrial-like tissue outside the uterus, leading to severe pelvic pain and infertility. Surgical treatment is common, but recurrence rates are high, with many women undergoing multiple operations. Hormonal treatments, like the combined oral contraceptive pill (COCP) and progestogens, are recommended postsurgery, but it's uncertain which is more effective in preventing pain recurrence.READ MORE...PRE-EMPT (Preventing Recurrence of Endometriosis), a multicenter, parallel group, randomized controlled trial, aimed to compare long-acting progestogens (LAPs) with COCP in preventing pain recurrence postsurgery for endometriosis. The study spanned from November 2015 to March 2019 and recruited 405 women ages 16 to 45. Participants underwent laparoscopy for endometriosis, and then were randomized to receive LAP (depot medroxyprogesterone acetate 150 mg IM every 3 months or levonorgestrel-releasing intrauterine system delivering 20 mcg daily for 5 years) or COCP (30-mcg ethinylestradiol and 150-mcg levonorgestrel taken continuously or cyclically each month). The primary outcome was pain recurrence measured via the Endometriosis Health Profile-30 pain domain after 3 years postrandomization.After 3 years, both LAP and COCP groups showed around a 40% reduction in pain scores from preoperative levels. Both treatments also demonstrated improvements in other quality of life measures, and adverse events were similar between groups and not directly related to trial treatments. However, the study showed that LAPs had an 11% lower rate of treatment failure, and fewer women required further interventions with LAPs compared to COCP (73 versus 97).Based on these results, providers can assure patients that either class of hormonal drug can help with pain reduction over the next 3 years after endometriosis surgery, but LAPs may reduce the risk of needing additional treatments and surgeries. Future research should explore newer hormonal treatments and focus on early, noninvasive diagnosis to improve long-term pain management and quality of life for endometriosis patients. (Cooper, K. G., et al. (2024). Long acting progestogens versus combined oral contraceptive pill for preventing recurrence of endometriosis related pain: The PRE-EMPT pragmatic, parallel group, open label, randomised controlled trial. BMJ, 385, Article e079006. Retrieved May 2024 from https://www.bmj.com/content/385/bmj-2023-079006)Released: June 2024Nursing Drug Handbook© 2024 Wolters KluwerPerioperative Nivolumab for Non-Small-Cell Lung CancerNivolumab, an antibody targeting programmed death-1, in combination with chemotherapy is standard neoadjuvant treatment for patients with resectable non-small-cell lung cancer (NSCLC). Studies, including the landmark CheckMate 816 trial, showed significant improvements in event-free survival and pathologic complete response with this combination compared to chemotherapy alone. Based on these results, researchers questioned whether a perioperative approach, combining neoadjuvant therapy with nivolumab, followed by surgery and adjuvant therapy, could reduce disease relapse rates, and enhance clinical outcomes by bolstering antitumor immunity.READ MORE...The CheckMate 77T trial, a phase 3, randomized, double-blind study, compared perioperative nivolumab to chemotherapy alone in resectable NSCLC patients. The trial, between November 2019 and April 2022, randomized 461 patients to nivolumab or chemotherapy. The first group received four cycles of neoadjuvant nivolumab and chemotherapy, followed by definitive surgery, and then 1 year of adjuvant treatment with nivolumab. The second group had four cycles of a placebo and chemotherapy, plus definitive surgery, and adjuvant treatment with a placebo for 1 year.Results showed significantly longer event-free survival at 18 months with perioperative nivolumab (70.2%) compared to chemotherapy alone (50.0%), alongside higher rates of pathologic complete response (25.3% nivolumab versus 4.7% chemotherapy) and major pathologic response (35.4% nivolumab versus 12.1% chemotherapy). Safety profiles were comparable between groups, with no new safety signals observed with perioperative nivolumab. Adverse events, including immune-related ones, were manageable, and surgical outcomes were similar between treatment arms.This trial points to the efficacy of perioperative nivolumab in improving event-free survival, pathologic response, and disease-related symptoms compared to chemotherapy alone in resectable NSCLC patients. These findings support the role of immunotherapy in perioperative treatment strategies for NSCLC, potentially offering long-term clinical benefits as data continue to mature. (Cascone, T., et al. (2024). Perioperative nivolumab in resectable lung cancer. NEJM, 390(19), 1756–769. Retrieved May 2024 from https://www.nejm.org/doi/full/10.1056/NEJMoa2311926)Released: June 2024Nursing Drug Handbook© 2024 Wolters Kluwer
Drug News Abstracts - May 2024
Trastuzumab Deruxtecan for HER2-positive Metastatic Breast CancerHER2-positive breast cancer, known for its aggressive behavior and poor prognosis in advanced metastatic stages, presents a considerable challenge in treatment. Despite efforts, alternatives to trastuzumab emtansine show limited efficacy, underscoring the urgent requirement for more effective therapies in this patient cohort.READ MORE...DESTINY-Breast02, a randomized, open-label, phase 3 study, aimed to compare the efficacy and safety of trastuzumab deruxtecan with the provider's choice of treatment (either capecitabine plus trastuzumab or capecitabine plus lapatinib) in patients with HER2-positive metastatic breast cancer who had previously failed trastuzumab emtansine.The study enrolled 608 patients (603 female and 5 male) and randomly assigned them to receive either trastuzumab deruxtecan (5.4 mg/kg IV once every 21 days) or capecitabine (1,250 mg/m2 orally b.i.d. on days 1 to 14) plus trastuzumab (8 mg/kg IV on day 1, then 6 mg/kg once per day); or capecitabine (1,000 mg/m2) plus lapatinib (1,250 mg orally once per day on days 1 to 21). Tumor assessments were conducted regularly, and treatment continued until disease progression or unacceptable toxicity occurred. The primary endpoint was progression-free survival, and secondary endpoints included patient-reported outcomes and hospitalization data.Results showed that patients on trastuzumab deruxtecan had longer time to definitive deterioration over provider's choice (14.1 months versus 5.9 months), as well as better results in global health status, physical functioning, pain symptoms, breast symptoms, and overall self-rated health compared to provider's choice treatment. Although both treatments had similar hospitalization rates, trastuzumab deruxtecan delayed the time to first hospitalization (133 days versus 83 days).Overall, trastuzumab deruxtecan improved progression-free survival, maintained quality of life, and delayed symptom deterioration compared to provider's choice treatment in patients with HER2-positive metastatic breast cancer who had previously failed trastuzumab emtansine. The study highlights the importance of patient-reported outcomes in evaluating treatment benefits as well as the need for continuous data collection and patient engagement in future studies. (Fehm, T., et al. (2024). Trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): Patient-reported outcomes from a randomised, open-label, multicentre, phase 3 trial. The Lancet, Oncology. 25(5), 614–625. Retrieved April 2024 from https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(24)00128-1/fulltext?rss=yes)Released: May 2024Nursing Drug Handbook© 2024 Wolters KluwerAssessing Antihypertensive Use and Dementia Risk in Older AdultsA recent Italian study published in the Journal of the American College of Cardiology emphasizes the potential benefits of antihypertensive medication in reducing dementia risk among older adults, including those in their 80s.READ MORE...Led by researchers from the University of Milano-Bicocca, the nested case-control study analyzed data from 215,547 patients age 65 and older who initiated antihypertensive treatment between 2009 and 2012. Of these individuals, 13,812 developed dementia or Alzheimer disease over the follow-up period of 7.3 years. Approximately 80% of those patients were treated with a renin-angiotensin-system blocker as monotherapy, and if a second drug was prescribed, it was commonly a diuretic.Findings revealed a significant association between higher exposure to antihypertensive drugs and progressively lower risk of dementia (low, intermediate, and high exposure exhibited a 2%, 12%, and 24% risk reduction, respectively), even in patients age 85 and older and those considered frail. The researchers explain that, although there may be differences among antihypertensive agents, the real benefit is in overall reduction in blood pressure, regardless of the drug used. This observational evidence contributes to the growing body of research supporting the link between lower blood pressure and reduced dementia risk, although the exact mechanisms underlying this relationship remain unclear.Researchers acknowledge that different types of cognitive impairment, such as Alzheimer disease, may have distinct processes, necessitating further investigation into these complexities. Additionally, questions remain regarding the impact of variations in blood pressure readings and medication adherence rates, particularly in older adults who may experience age-related changes affecting blood pressure regulation.Despite these uncertainties, the study reinforces the potential importance of antihypertensive treatment in mitigating dementia risk among older adults and offering valuable insights for clinical practice and further investigation. Future research should focus on identifying optimal blood pressure targets for reducing dementia risk and clarifying the relationship between antihypertensive medication and cognitive outcomes. (Rea, F., et al. (2024). Risk of dementia during antihypertensive drug therapy in the elderly. J Am Coll Cardiol, 83(13), 1194–1203. Retrieved April 2024 from https://www.sciencedirect.com/science/article/abs/pii/S0735109724002584?via%3Dihub; Cox, C. E. (2024). Antihypertensives linked to lower long-term dementia risk. TCTMD. Retrieved April 2024 from https://www.tctmd.com/news/antihypertensives-linked-lower-long-term-dementia-riskReleased: May 2024Nursing Drug Handbook© 2024 Wolters KluwerEsketamine after Childbirth for Mothers with Prenatal DepressionPrenatal depression is identified as a significant predictor of postpartum depression, stressing the importance of early intervention. Mothers with perinatal depression can experience feelings of anxiety and poor mother-infant attachment. Traditional antidepressants are sometimes necessary but can have limitations, leading to the exploration of alternative treatments, like ketamine and esketamine.READ MORE...A randomized, double-blind, placebo-controlled trial was conducted across multiple hospitals in China to investigate the efficacy of a single low dose of esketamine in reducing depression among mothers with prenatal depression. A total of 364 participants were assessed using validated scales, including depression, anxiety, and social support. Patients were randomly assigned to receive either esketamine (0.2 mg/kg) or placebo (20 mL normal saline) via IV infusion over 40 minutes after childbirth.The primary endpoint of the trial was the prevalence of major depressive episodes at 42 days postpartum. The results showed a significant reduction in major depressive episodes among mothers who received esketamine compared to those who received a placebo (major depressive episode occurred in 6.7% of esketamine group versus 25.4% of placebo). Secondary endpoints, including pain intensity, also favored the esketamine group (persistent pain at 42 days: 35.2% with esketamine versus 47.5% with placebo). Exploratory analyses supported the antidepressant effects of esketamine as well, with higher rates of improvement in depression scores among the esketamine group.Safety assessments revealed transient neuropsychiatric symptoms among esketamine recipients, but these were generally well-tolerated and didn't require treatment. Overall, esketamine was found to be an effective intervention for reducing perinatal depression in mothers with prenatal depression. These results should prompt further research on esketamine's effectiveness in more severe cases of depression. (Wang, S., et al. (2024). Efficacy of a single low dose of esketamine after childbirth for mothers with symptoms of prenatal depression: Randomised clinical trial. BMJ, 385, Article e078218. Retrieved April 2024 from https://www.bmj.com/content/385/bmj-2023-078218)Released: May 2024Nursing Drug Handbook© 2024 Wolters KluwerStatin Use Associated with Better Outcomes in Non-Hodgkin LymphomaRegular statin use in patients with non-Hodgkin lymphoma may reduce the risk of heart failure and improve overall survival, according to a study published in the Journal of the American College of Cardiology: CardioOncology.READ MORE...This retrospective cohort study investigated the impact of statin use on clinical outcomes in non-Hodgkin lymphoma using data from the Taiwan National Health Insurance Research Database and the National Cancer Registry. After analyzing 15,466 patients diagnosed with non-Hodgkin lymphoma between 2012 and 2019, statin users (those who received statins within 6 months before lymphoma diagnosis and continued for more than 90% of the subsequent 30-day period) were compared with non-statin users. Of the patients in the study, 55.0% were male, with an average age of 62.7 years, and 14.6% were statin users. The main outcomes assessed were heart failure (HF) events, major arterial or venous events, and overall survival.The study found that statin users had a 19% lower risk of HF events compared to nonstatin users (0.6% versus 0.9%, respectively). Statin use was also associated with improved overall survival (cumulative incidence of death: 45.6% for statin users versus 50.3% for nonstatin users) and a lower risk of cancer-related deaths (29.8% for statin users versus 35.0% for nonstatin users). There were no significant differences in the risk of arterial or venous events between statin groups.Although the results of this study are promising, the relationship between statins and cancer is still unclear. Further randomized trials are needed to confirm these findings and clarify the potential benefits of statins in this patient population. (Chen, C.-Y., et al. (2024). Statin use is associated with reduced heart failure and risk of death in non-Hodgkin lymphoma. JACC: CardioOncology, 6(1), 133–>135. Retrieved April 2024 from https://www.sciencedirect.com/science/article/pii/S2666087324000048?via%3Dihub; Azvolinksy, A. (2024). Statin use linked to reduced heart failure, risk of death among patients with non-Hodgkin lymphoma. ASH Clinical News. Retrieved April 2024 from https://ashpublications.org/ashclinicalnews/news/7800/Statin-Use-Linked-to-Reduced-Heart-Failure-Risk-of)Released: May 2024Nursing Drug Handbook© 2024 Wolters Kluwer
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
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