Annals of Pharmacotherapy最新文献

{"title":"B-Cell Maturation Antigen-Directed Immunotherapies for the Treatment of Relapsed/Refractory Multiple Myeloma: A Review of the Literature and Implications for Clinical Practice.","authors":"Matthew R Peery, Hailey Hill, Amanda Sharps, Aarti Zaver, Donald C Moore","doi":"10.1177/10600280241282115","DOIUrl":"https://doi.org/10.1177/10600280241282115","url":null,"abstract":"<p><strong>Objective: </strong>To review the pharmacology, efficacy, safety, dosing and administration, and relevance to patient care and clinical practice of B-cell maturation antigen (BCMA) directed immunotherapies, including chimeric antigen receptor T-cell (CAR-T) therapy and bispecific antibodies (BsAb), for the management of relapsed/refractory multiple myeloma (RRMM).</p><p><strong>Data sources: </strong>A literature review of PubMed (1966 to July 2024) was conducted using the keywords <i>idecabtagene vicleucel</i>, <i>ciltacabtagene autoleucel, teclistamab, elranatamab</i>, and <i>multiple myeloma</i>. Data was also obtained from unpublished meeting abstracts and prescribing information.</p><p><strong>Study selection and data extraction: </strong>All relevant published articles, unpublished abstracts, and prescribing information on anti-BCMA immunotherapies for the treatment of RRMM were reviewed.</p><p><strong>Data synthesis: </strong>Idecabtagene vicleucel and ciltacabtagene autoleucel are BCMA-directed CAR-T cell therapies that have been compared to standard of care (SOC) regimens for MM in early relapse in the phase III trials KarMMa-3 and CARTITUDE-4, respectively. Both studies demonstrated a significantly improved in response rates, depth of response, and progression-free survival compared to SOC. BsAbs teclistamab and elranatamab have been evaluated in the phase II trials MajesTEC-1 and MagnetisMM-3, respectively. Overall response rates of 63 and 61% were observed with teclistamab and elranatamab, respectively, in a population of patients with heavily pretreated RRMM.</p><p><strong>Relevance to patient care and clinical practice in comparison with existing drugs: </strong>BCMA-directed immunotherapies have demonstrated efficacy in the treatment of RRMM. Safety issues with BCMA-directed immunotherapies include cytokine release syndrome, neurotoxicity, infections, and cytopenias. Operational challenges and issues with access to care exist with these therapies as they may be limited to institutions with the infrastructure to safely administer and monitor patients for toxicities.</p><p><strong>Conclusion: </strong>BCMA-directed immunotherapies represent an important advancement in the management of RRMM and have significantly added to the available treatment options for this disease.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":" ","pages":"10600280241282115"},"PeriodicalIF":2.3,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tolerability Assessment of Tyrosine Kinase Inhibitors in Patients With Solid Tumor Malignancies and Hypoalbuminemia.","authors":"Sarvnaz Sadrameli, Sydney Bringgold, Elizabeth Dow-Hillgartner","doi":"10.1177/10600280241284923","DOIUrl":"https://doi.org/10.1177/10600280241284923","url":null,"abstract":"<p><strong>Background: </strong>Hypoalbuminemia is common in patients with advanced solid tumor malignancies. However, despite the increased use of highly protein-bound tyrosine kinase inhibitors (TKIs) in cancer treatments, the tolerability of these agents in patients with hypoalbuminemia is not fully known.</p><p><strong>Objective: </strong>Our aim is to assess whether patients on oral TKIs with hypoalbuminemia are at higher risk for experiencing medication-related adverse events, therefore requiring careful considerations.</p><p><strong>Methods: </strong>This is a single-center, retrospective study including patients ≥18 years of age with a solid tumor malignancy who had taken at least one dose of oral TKIs with a protein binding of ≥90% between June 1, 2016, and June 1, 2021. The primary outcome was to compare time to TKI discontinuation due to adverse events between patients with and without hypoalbuminemia. Key secondary outcomes include TKI discontinuation and dose reduction rates, time to TKI dose reduction, and severity of adverse events.</p><p><strong>Results: </strong>Out of 282 included patients, 134 (48%) patients had hypoalbuminemia and 148 (52%) had normal albumin levels. Compared with patients without hypoalbuminemia, patients with hypoalbuminemia had shorter median time on treatment at 2.8 months (95% CI = 2.3-4.5 months) versus 4.3 months (95% CI = 2.8-6.4 months; <i>P</i> = 0.003). In patients who had TKI discontinuation, dose reduction was associated with longer time on treatment in patients in the normal albumin group compared with patients in the hypoalbuminemia group or patients without dose reduction (<i>P</i> < 0.0001). Patients in the hypoalbuminemia group experienced significantly more grade 3/4 adverse events compared with those in the normal albumin group (73% vs 27%, <i>P</i> < 0.0001).</p><p><strong>Conclusion and relevance: </strong>Hypoalbuminemia is a risk factor for both shorter time on treatment and more severe adverse events in patients with solid tumor malignancies taking highly protein-bound oral TKIs. This study highlights the need for closer monitoring of this patient population by health care providers.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":" ","pages":"10600280241284923"},"PeriodicalIF":2.3,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Etrasimod: A Sphingosine-1-Phosphate Receptor Modulator for the Treatment of Ulcerative Colitis.","authors":"David Choi, Michelle Becker, Marina Ivanov, Shubha Bhat","doi":"10.1177/10600280231225770","DOIUrl":"10.1177/10600280231225770","url":null,"abstract":"<p><strong>Objective: </strong>To review the pharmacologic and clinical profile of etrasimod in the treatment of ulcerative colitis (UC).</p><p><strong>Data sources: </strong>A PubMed search was conducted from inception to November 2023 using the keywords <i>etrasimod</i>, <i>ulcerative colitis</i>, <i>and sphingosine-1-phosphate receptor modulator</i>. Information was also obtained from published abstracts and package insert.</p><p><strong>Study selection and data extraction: </strong>Phase 2 and 3 studies plus relevant literature on etrasimod pharmacologic and clinical profile were reviewed.</p><p><strong>Data synthesis: </strong>Per ELEVATE, 2 phase 3 studies, a higher proportion of patients with moderately to severely active UC achieved clinical remission in the induction and maintenance phase with etrasimod compared with placebo. In addition, a higher proportion of patients achieved secondary endpoints of clinical response, endoscopic improvement-histologic remission, corticosteroid-free remission, and endoscopic improvement with etrasimod vs placebo. Common adverse events include anemia and headache.</p><p><strong>Relevance to patient care and clinical practice in comparison with existing drugs: </strong>Etrasimod is now the second orally administered sphingosine-1-phosphate modulator approved for UC, providing patients with additional treatment options. Efficacy rates of this treatment are in line with other UC medication options. Similar to other sphingosine-1-phosphate receptor modulators, various assessments are required at baseline and during treatment to ensure safe and appropriate use.</p><p><strong>Conclusion: </strong>Etrasimod is another possibility in the armamentarium of UC treatment, providing patients with more oral medication options. Prior to treatment initiation, several assessments relating to safety, drug interactions, and pharmacogenomics factors are advised.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":" ","pages":"1054-1063"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139519245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of Glycemic Control on Sodium-Glucose Co-Transporter 2 Inhibitor-Associated Genitourinary Infections.","authors":"Anthony Gerber, Victoria Rupp, Natalia Ryabenkova, Nataliya Mikhelzon","doi":"10.1177/10600280241227973","DOIUrl":"10.1177/10600280241227973","url":null,"abstract":"<p><strong>Background: </strong>Patients with type 2 diabetes (T2D) are at an increased risk of genital urinary (GU) infections, with the risk increasing with higher A1Cs. Given the broad adoption of sodium-glucose co-transporter 2 inhibitors (SGLT2is) in patients with T2D, both providers and patients need to be aware of common adverse effects associated with these medications, specifically GU infections. However trials involving SGLT2is looked at patients with an average A1C of less than 9%, and thus, the incidence of GU infections may not truly reflect the general diabetic population.</p><p><strong>Objective: </strong>The purpose of this study is to assess the association between GU infections in patients started on SGLT2is and A1C levels.</p><p><strong>Methods: </strong>A retrospective study was conducted on patients seen in an adult, primary care clinic, at New York City Health and Hospitals, South Brooklyn Health. Men and nonpregnant, nonlactating women >18 years old with a diagnosis of T2D who were initiated on an SGLT2i between January 2018 and January 2023 were included in the analysis. The primary endpoint is to compare the risk of GU infections in patients with T2D who were started on SGLT2is, regardless of dose, with hemoglobin A1C of >9% to those with hemoglobin A1C <9% at baseline.</p><p><strong>Results: </strong>Three hundred and twenty-eight patients were eligible based on specified inclusion and exclusion criteria. Overall, there was a statistically significant difference in the number of GU infections that occurred in patients with a baseline A1C >9% compared with those with an A1C <9% (95% confidence interval [CI] = 1.05-2.88; <i>P</i> = 0.041).</p><p><strong>Conclusions and relevance: </strong>Type 2 diabetes patients initiated on SGLT2is may experience an increased risk of GU infection, especially in those patients with an A1C of 9% or greater. Further research is necessary to validate and expand upon these findings.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":" ","pages":"1013-1019"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139696832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Response to Third-Line Angiotensin-II vs Epinephrine in Septic Shock: A Propensity-Matched Cohort Study.","authors":"Caitlyn R Blankenship, Kevin D Betthauser, Laura N Hencken, Julie A Maamari, Jenna Goetz, Bria D Giacomino, Gabrielle A Gibson","doi":"10.1177/10600280231226132","DOIUrl":"10.1177/10600280231226132","url":null,"abstract":"<p><strong>Background: </strong>The appropriate third-line vasopressor in septic shock patients receiving norepinephrine and vasopressin is unknown. Angiotensin-II (AT-II) offers a unique mechanism of action to traditionally used vasopressors in septic shock.</p><p><strong>Objective: </strong>The objective of this study was to compare the clinical efficacy and safety of third-line AT-II to epinephrine in patients with septic shock.</p><p><strong>Methods: </strong>A single-center, retrospective cohort study of critically ill patients was performed between April 1, 2019 and July 31, 2022. Propensity-matched (2:1) analysis compared adults with septic shock who received third-line AT-II to controls who received epinephrine following norepinephrine and vasopressin. The primary outcome was clinical response 24 hours after third-line vasopressor initiation. Additional efficacy and safety outcomes were investigated.</p><p><strong>Results: </strong>Twenty-three AT-II patients were compared with 46 epinephrine patients. 47.8% of AT-II patients observed a clinical response at hour 24 compared with 28.3% of epinephrine patients (<i>P</i> = 0.12). In-hospital mortality (65.2% vs 73.9%, <i>P</i> = 0.45), cardiac arrhythmias (26.1% vs 26.1%, <i>P</i> = 0.21), and thromboembolism (4.3% vs 2.2%, <i>P</i> = 0.61) were not observed to be statistically different between groups.</p><p><strong>Conclusions and relevance: </strong>Administration of AT-II as a third-line vasopressor agent in septic shock patients was not associated with significantly improved clinical response at hour 24 compared with epinephrine. Although underpowered to detect meaningful differences, the clinical observations of this study warrant consideration and further investigation of AT-II as a third-line vasopressor in septic shock.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":" ","pages":"1003-1012"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139671136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monoclonal Antibody Infusions for Outpatient Management of Mild-Moderate COVID-19.","authors":"Hannah B Knox, Lisa A Dykes, Lancer A Scott, Bradley C Presley, Lara C Lambert","doi":"10.1177/10600280231222465","DOIUrl":"10.1177/10600280231222465","url":null,"abstract":"<p><strong>Background: </strong>The COVID-19 pandemic has led to a rapid, exponential increase in hospitalizations and morbidity/mortality. In November 2020, the Food and Drug Administration (FDA) issued Emergency Use Authorizations (EUAs) permitting administration of the first monoclonal antibodies (mAb) for outpatient treatment of COVID-19. Early data showed a reduction in COVID-19-related hospitalizations with few adverse events. However, since these treatments are only authorized under an EUA, real-world data are minimal.</p><p><strong>Objective: </strong>To assess efficacy and safety of mAbs in a veteran population.</p><p><strong>Methods: </strong>This retrospective study analyzed veterans at the Ralph H. Johnson Veterans Affairs Health Care System with mild-moderate COVID-19 and screened for mAb eligibility between December 1, 2020, and October 31, 2021. The primary outcome was hospitalizations and/or emergency department (ED) visits within 30 days. Secondary outcomes included 30-day mortality and post-COVID-19 conditions. Adverse events were also evaluated. Outcomes were compared between mAb-treated patients and eligible veterans who were not treated.</p><p><strong>Results: </strong>There were 296 and 275 veterans in the mAb and control groups, respectively. No statistically significant difference was found for the primary outcome overall (25.7% vs 25.1%; <i>P</i> = 0.87), nor for COVID-19-related return visits or hospitalizations (13.9% v. 16%; <i>P</i> = 0.4). However, the mAb group had more return ED visits (<i>P</i> = 0.35), and the control group had significantly more hospitalizations (<i>P</i> = 0.02). Vaccinated veterans who received an mAb had fewer return visits and hospitalizations (<i>P</i> = 0.01). More mAb-treated veterans experienced post-COVID-19 conditions. No difference in mortality was found. Four nonsevere adverse events occurred after the mAb therapy.</p><p><strong>Conclusion and relevance: </strong>Overall, the mAbs appeared safe and effective. Sicker, higher-risk mAb-treated veterans faired similarly to less-sick, high-risk veterans not treated. Those who were vaccinated seemed to benefit the most from mAb therapy. Future prospective studies with more matched groups are needed to assess full benefits and risks of mAbs shown to neutralize the predominant variants.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":" ","pages":"985-993"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139574998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidemiology of Vancomycin in Combination With Piperacillin/Tazobactam-Associated Acute Kidney Injury in Children: A Systematic Review and Meta-analysis.","authors":"Miao Zhang, Liang Huang, Yu Zhu, Linan Zeng, Zhi-Jun Jia, Guo Cheng, Hailong Li, Lingli Zhang","doi":"10.1177/10600280231220379","DOIUrl":"10.1177/10600280231220379","url":null,"abstract":"<p><strong>Background: </strong>Several studies have shown that vancomycin combined with piperacillin/tazobactam (VPT) increased the risk of acute kidney injury (AKI) compared with other antibiotics in children. However, the epidemiology of VPT-associated AKI in children is unknown.</p><p><strong>Objective: </strong>To evaluate the incidence and risk factors of VPT-associated AKI in children.</p><p><strong>Data sources: </strong>Literature databases of PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, WanFang Database, and China Biology Medicine Disc were searched from inception to November 2023. References of included studies were also manually checked.</p><p><strong>Study selection and data extraction: </strong>Two independent reviewers selected studies, extracted data, and quality assessment. Meta-analyses were performed to quantify the incidence and risk factors of VPT-associated AKI in children.</p><p><strong>Data synthesis: </strong>Sixteen cohort studies were identified. Overall, the incidence of VPT-associated AKI in children was 24.3% (95% CI: 17.9%-30.6%). The incidence of VPT-associated AKI in critically ill children (26.6%) was higher than that in noncritically ill children (10.9%). Moreover, higher serum vancomycin trough concentration (>15 mg/L), use of vasopressors, combination of nephrotoxins and intensive care unit admission were risk factors for VPT-associated AKI in children (<i>P</i> < 0.05).</p><p><strong>Relevance to patient care and clinical practice: </strong>Identifying high-risk groups and determining safer treatments is critical to reducing the incidence of VPT-associated AKI in children.</p><p><strong>Conclusions: </strong>The incidence of VPT-associated AKI in children is high, especially in critically ill children. Medication regimens should be personalized based on the presence of individual risk factors. Moreover, renal function was regularly assessed throughout treatment with VPT.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":" ","pages":"1034-1044"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139568914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Documentation of the Patient Characteristics Morbid Obesity and Bariatric Surgery in the Hospital Information System and the Influence on the Number of Medication-Related Problems.","authors":"Jurjen S Kingma, Iris A M Brenkman, Marcel P H van den Broek, Patricia M L A van den Bemt, Karin Janssen, Catherijne A J Knibbe, Desirée M T Burgers","doi":"10.1177/10600280231226243","DOIUrl":"10.1177/10600280231226243","url":null,"abstract":"<p><strong>Background: </strong>As a result of pharmacokinetic changes, individuals with morbid obesity and/or with bariatric surgery may require dose adjustments, additional monitoring or medication should be avoided. Clinical decision support (CDS) may provide automated alerts enabling correct prescribing but requires documentation of these patient characteristics in the Hospital Information System (HIS) to prevent medication-related problems (MRPs).</p><p><strong>Objective: </strong>The primary objective is to determine the proportion of patients with documentation of the patient characteristics morbid obesity and bariatric surgery in the HIS. The secondary objective is to compare the proportion of patients with an MRP in the group with <i>versus</i> without documentation. Also, the type and severity of MRPs and the medication involved are determined.</p><p><strong>Methods: </strong>A prospective cohort study was performed. Patients admitted to the hospital were identified as morbidly obese and/or with bariatric surgery. In the identified patients, the proportion of patients with documentation of the patient characteristics in the HIS was evaluated as primary outcome. Subsequently, patient records were reviewed for MRPs, which were categorized and associated medication was registered. For the primary objective, descriptive statistics was used. For the secondary outcome, the Fisher's exact test was used.</p><p><strong>Results: </strong>In 43 (21.4%, 95% confidence interval [CI]: 15.7%-27.1%) of 201 included patient (113 morbid obesity, 70 bariatric surgery and 18 both), the patient characteristics were documented. An MRP occurred in 2.3% <i>versus</i> 13.9% (<i>P</i> = 0.032) of patients with and without documentation, respectively. The most common MRP was underdosing in morbid obesity, while in patients with bariatric surgery it was prescription of contra-indicated medication.</p><p><strong>Conclusion and relevance: </strong>The proportion of patients with documentation of the patient characteristics bariatric surgery and/or morbid obesity in the HIS is low, which appears to be associated with more MRPs. To improve medication safety, it is important to document these patient characteristics.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":" ","pages":"1020-1026"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139545385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lecanemab: A Humanized Monoclonal Antibody for the Treatment of Early Alzheimer Disease.","authors":"Juliane Park, Carson Simpson, Katie Patel","doi":"10.1177/10600280231218253","DOIUrl":"10.1177/10600280231218253","url":null,"abstract":"<p><strong>Objective: </strong>To review current pharmacology, pharmacokinetics/pharmacodynamics, safety, and efficacy of lecanemab in patients with Alzheimer disease.</p><p><strong>Data sources: </strong>A literature search of PubMed (April 1, 2016-November 15, 2023) and ClinicalTrials.gov search were conducted using the following search terms: lecanemab and BAN2401. Additional articles were identified by hand from references.</p><p><strong>Study selection and data extraction: </strong>We included English-language clinical trials, randomized controlled trials, reviews, and systematic reviews evaluating lecanemab pharmacology, efficacy, or safety in humans for the management of Alzheimer disease.</p><p><strong>Data synthesis: </strong>In the Clarity AD phase III trial, lecanemab led to a decrease in brain amyloid levels and showed moderate improvement in clinical measures of cognition and function. At 18 months, lecanemab 10 mg/kg biweekly exhibited a lower least squares mean change from baseline (1.21) compared to placebo (1.66) of Clinical Dementia Rating-Sum of Boxes score, signifying a significant difference of -0.45 (95% CI, -0.67 to -0.23; <i>P</i> < 0.001). In a subset of 698 participants, lecanemab reduced brain amyloid burden by -59.1 Centiloids (95% CI, -62.6 to -55.6). Lecanemab demonstrated favorable differences in Alzheimer Disease Assessment Scale-cognitive subscale 14, Alzheimer Disease Composite Score, and Alzheimer Disease Cooperative Study-Mild Cognitive Impairment-Activities of Daily Living scores. Adverse events included infusion-related reactions (26.4%) and amyloid-related imaging abnormalities (12.6%).</p><p><strong>Relevance to patient care and clinical practice: </strong>Lecanemab reduces cognitive decline but raises concerns about intravenous administration, cost, and magnetic resonance imaging needs. Ongoing trials exploring subcutaneous dosing and positron emission tomography scans may offer solutions.</p><p><strong>Conclusion: </strong>Lecanemab is a humanized monoclonal antibody that is selective for soluble amyloid-beta (Aβ) aggregates. Lecanemab has exhibited a decrease in brain Aβ plaques and moderately less decline on clinical measures of cognitive function.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":" ","pages":"1045-1053"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138795652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pirtobrutinib: A New and Distinctive Treatment Option for B-Cell Malignancies.","authors":"Madeline D Schultze, David J Reeves","doi":"10.1177/10600280231223737","DOIUrl":"10.1177/10600280231223737","url":null,"abstract":"<p><strong>Objective: </strong>The objective was to evaluate the efficacy/safety of pirtobrutinib in the treatment of B-cell malignancies and distinguish it from other available Bruton's tyrosine kinase (BTK) inhibitors.</p><p><strong>Data sources: </strong>A literature search of PubMed (January 2021 through November 2023) and Clinicaltrials.gov was conducted using terms <i>pirtobrutinib, Jaypirca</i>, and <i>LOXO 305.</i> Licensing trials of available BTK inhibitors were also reviewed.</p><p><strong>Study selection and data extraction: </strong>Relevant English-language clinical trials were evaluated.</p><p><strong>Data synthesis: </strong>Pirtobrutinib was approved by the US Food and Drug Administration for the treatment of relapsed/refractory mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL) based largely on a phase 1/2 study in B-cell malignancies. Pirtobrutinib demonstrated a 73% overall response rate (ORR) in the CLL population and 58% in MCL. Pirtobrutinib has activity in patients resistant to earlier-generation, covalent BTK inhibitors. In fact, the ORRs were similar in BTK-pretreated and naïve patients. Adverse effects include fatigue, diarrhea, bleeding, and infection. Atrial fibrillation, a class effect of BTK inhibitors, may be less common with pirtobrutinib.</p><p><strong>Relevance to patient care and clinical practice in comparison with existing drugs: </strong>Compared with earlier-generation BTK inhibitors, pirtobrutinib is more selective for BTK and binds noncovalently to the receptor. Ongoing studies are evaluating pirtobrutinib's use in multiple B-cell malignancies and comparing it with other BTK inhibitors.</p><p><strong>Conclusion: </strong>The characteristics of pirtobrutinib render it useful in the treatment of B-cell malignancies no longer responding to a previous BTK inhibitor, and results from ongoing clinical trials may support future expanded use.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":" ","pages":"1064-1073"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139484630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}