Journal of comparative effectiveness research最新文献

{"title":"R WE ready for reimbursement? A round-up of developments in real-world evidence relating to health technology assessment: part 28.","authors":"Paul Arora, Kirk Geale, Sreeram V Ramagopalan","doi":"10.57264/cer-2026-0167","DOIUrl":"10.57264/cer-2026-0167","url":null,"abstract":"<p><p>In this update, we consider the role of real-world evidence in the European Union's new Joint Clinical Assessment (JCA) process and also review a systematic review and meta-analysis of the concordance between target trial emulations and their benchmarking randomized controlled trials.</p>","PeriodicalId":15539,"journal":{"name":"Journal of comparative effectiveness research","volume":" ","pages":"e260167"},"PeriodicalIF":2.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148793964","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":"Zanubrutinib versus fludarabine, cyclophosphamide and rituximab in fit, treatment-naïve patients with chronic lymphocytic leukemia: a matching-adjusted indirect comparison.","authors":"Talha Munir, Lianne Barnieh, Leyla Mohseninejad, Sheng Xu, Milica Jevdjevic, Walter Bouwmeester, Keri Yang","doi":"10.57264/cer-2025-0192","DOIUrl":"10.57264/cer-2025-0192","url":null,"abstract":"<p><p><b>Aim:</b> Fludarabine, cyclophosphamide and rituximab (FCR) is a first-line therapy for fit treatment-naive patients with chronic lymphocytic leukemia (CLL); however, its hematotoxicity and related infections necessitate more efficacious, safer treatments. Zanubrutinib is a highly potent and selective next-generation Bruton tyrosine kinase inhibitor approved for treatment-naive patients with CLL and small lymphocytic lymphoma. Given the absence of clinical trials providing head-to-head comparisons, the aim of this analysis was to conduct a matching-adjusted indirect comparison between zanubrutinib and FCR. <b>Materials & methods:</b> Patient-level data from SEQUOIA (zanubrutinib vs bendamustine + rituximab [BR]) was adjusted for interpopulation differences through propensity-score matching with aggregate data from the CLL10 trial (FCR vs BR). Progression-free survival (PFS) was compared among populations matched for immunoglobulin heavy-chain gene mutation, 11q deletion, β2-microglobulin, Binet stage and age. Sensitivity analyses incorporated geographic region, sex, creatinine clearance, the Cumulative Illness Rating Scale, Eastern Cooperative Oncology Group performance status and previous infections. <b>Results:</b> Zanubrutinib improved PFS compared with FCR, with a hazard ratio of 0.41 (95% CI: 0.20-0.81; effective sample size 174). Including geographic region, Eastern Cooperative Oncology Group performance status or previous infections as matching factors one by one in the propensity score model showed similar results. Incorporating Cumulative Illness Rating Scale or creatinine clearance showed numerically favorable PFS with zanubrutinib (hazard ratio [95% CI] 0.45 [0.16-1.24] and 0.52 [0.24-1.13], respectively), owing to the low effective sample size of the expanded model (64 and 123, respectively). <b>Conclusion:</b> Our findings suggest that zanubrutinib offers improved PFS over FCR in fit, treatment-naive patients with CLL, further supporting zanubrutinib as a first-line CLL treatment for multiple patient profiles.</p>","PeriodicalId":15539,"journal":{"name":"Journal of comparative effectiveness research","volume":" ","pages":"e250192"},"PeriodicalIF":2.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794013","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":"Matching-adjusted indirect comparison of fruquintinib versus ramucirumab in advanced gastric or gastroesophageal junction adenocarcinoma.","authors":"Nan An, Jiaying Chen, Jibin Li, Lin Shen, Weijian Guo, Tianshu Liu, Jin Li, Shukui Qin, Yuxian Bai, Zhendong Chen, Jufeng Wang, Yueyin Pan, Ruihua Xu, Feng Wang","doi":"10.57264/cer-2026-0072","DOIUrl":"10.57264/cer-2026-0072","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Aim:&lt;/b&gt; Fruquintinib (Fruq), a selective VEGFR 1/2/3 inhibitor, showed a significant progression-free survival (PFS) benefit in the Phase III FRUTIGA trial for advanced gastric/gastroesophageal junction (G/GEJ) adenocarcinoma. Ramucirumab (RAM), an anti-VEGFR2 antibody, demonstrated efficacy in the RAINBOW-Asia trial. This anchored matching-adjusted indirect comparison (MAIC) evaluated Fruq plus paclitaxel versus RAM plus paclitaxel as second-line therapy for G/GEJ adenocarcinoma in the absence of head-to-head trials. &lt;b&gt;Materials & methods:&lt;/b&gt; Data from individual patients in the FRUTIGA study (N = 703) and aggregated data from the RAINBOW-Asia study (N = 440) were analyzed. Baseline characteristics were balanced using entropy balancing. The placebo plus paclitaxel (PBO + PTX) groups served as the common comparators. The primary outcome was PFS; secondary outcomes included overall survival, objective response rate (ORR) and disease control rate (DCR). Rates of treatment-emergent adverse events (TEAEs) were also compared as an exploratory outcome using an adjusted indirect risk difference. Sensitivity analyses included restricted mean survival time and simulated treatment comparison. &lt;b&gt;Results:&lt;/b&gt; After weighting (effective sample size = 564), baseline covariates were balanced. The anchored MAIC demonstrated that Fruq + PTX significantly improved PFS compared with RAM + PTX (HR: 0.70; 95% CI: 0.51-0.96; p = 0.0280), corresponding to a 30% reduction in progression risk, with a significant restricted mean survival time benefit of 1.18 months at 20 months (95% CI: 0.08-2.27; p = 0.024). Fruq achieved significantly higher ORR (OR: 1.76, 95% CI: 1.16-2.68; p = 0.008) and DCR (OR: 1.94, 95% CI: 1.33-2.83; p &lt; 0.001). Overall survival was similar (0.97; 95% CI: 0.73-1.30; p = 0.8640). Subgroup analyses showed PFS benefits with Fruq in patients with ECOG PS 1, peritoneal metastases and two or fewer metastatic sites. In sensitivity analysis, the simulated treatment comparison also suggested a PFS benefit for Fruq + PTX (HR: 0.40, 95% CI: 0.32-0.50; p &lt; 0.0001). For any-grade TEAEs, the indirect comparison showed higher adjusted relative incidences of increased bilirubin with Fruq + PTX than with RAM + PTX (RD: 12.3%; 95% CI: 2.3-22.4%, p &lt; 0.05) and of hypokalemia (RD: 9.0%; 95% CI: 1.5-16.4%, p &lt; 0.05). For grade ≥3 TEAEs, the adjusted relative incidence of decreased body weight was higher with Fruq + PTX than with RAM + PTX (RD: 2.9%; 95% CI: 0.6-5.2%, p &lt; 0.05). The adjusted relative incidences of increased AST, ALT and hypocalcemia were numerically lower in the fruquintinib group than in the RAM group. &lt;b&gt;Conclusion:&lt;/b&gt; This MAIC indicates that Fruq + PTX may be more effective than RAM + PTX in second-line advanced G/GEJ adenocarcinoma, with potentially improved PFS, ORR and DCR, and similar overall survival. Safety analyses suggested generally comparable safety profiles across the two regimens. Fruq + PTX remains a valuable treatment op","PeriodicalId":15539,"journal":{"name":"Journal of comparative effectiveness research","volume":" ","pages":"e260072"},"PeriodicalIF":2.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148712624","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":"Validation of an all-source composite mortality endpoint in the US population.","authors":"Yanina Natanzon, Lukas Slipski, Mark S Walker","doi":"10.57264/cer-2025-0198","DOIUrl":"https://doi.org/10.57264/cer-2025-0198","url":null,"abstract":"<p><p><b>Aim:</b> To validate ConcertAI's All Source Composite Mortality Endpoint (ASCME), which combines information from electronic health records, obituary, government and administrative claims. To compare overall survival (OS) estimates using ASCME versus a National Death Index (NDI) dataset across clinical cohorts. <b>Materials & methods:</b> Retrospective study of oncology real-world data, reporting sensitivity, specificity, positive predictive value and negative predictive value compared with the NDI standard, plus 5, 7 and 15-day concordance on date of death. Additional comparisons included Kaplan-Meier OS measured by ASCME versus NDI. Data sources included ConcertAI's Patient360™ dataset, and a 2022 annual finalized NDI dataset. The sample included cancer patients prevalent from 1 April 2014 to 31 December 2022 in any of 10 of ConcertAI's solid tumor-specific datasets. <b>Results:</b> Of 32,358 study patients, 14,241 (44.0%) were deceased as defined by an NDI true match. Sensitivity was 95.0% overall (an incremental 5.2% due to claims) and ranged from 92.7% to 97.8% across clinical cohorts. Overall specificity was 96.5%, with positive predictive value and negative predictive value of 95.8% each. ASCME's 5-day concordance was 97.9%, with 7-day and 15-day concordance of 98.2% and 99.1%, respectively. ASCME and NDI-based median OS estimates differed by 12.2 days among non-metastatic cohorts, and 4.5 days among metastatic cohorts. <b>Conclusion:</b> Results show ConcertAI's ASCME death indicator to provide high completeness and accuracy, producing OS estimates largely indistinguishable from NDI-based estimates. Findings show the importance of including claims in composite mortality indicators and demonstrate the value of real-world data in assessing OS outcomes in metastatic and non-metastatic cancer patient populations.</p>","PeriodicalId":15539,"journal":{"name":"Journal of comparative effectiveness research","volume":" ","pages":"e250198"},"PeriodicalIF":2.8,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148864972","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":"Access in all areas? A round-up of developments in market access and health technology assessment: part 16.","authors":"Sreeram V Ramagopalan, Annie Jullien Pannelay","doi":"10.57264/cer-2026-0153","DOIUrl":"https://doi.org/10.57264/cer-2026-0153","url":null,"abstract":"<p><p>In this update we review new evidence on the rising prevalence of prior authorization rejections, delays and denials affecting US patients seeking access to branded prescription medications. We also examine a comparative study of cost-effectiveness thresholds cited in the USA and in countries designated as comparators under the Most-Favored-Nations Executive Order.</p>","PeriodicalId":15539,"journal":{"name":"Journal of comparative effectiveness research","volume":" ","pages":"e260153"},"PeriodicalIF":2.8,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148829076","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":"Indirect treatment comparisons find enhanced effectiveness of pegcetacoplan versus crovalimab in both complement inhibitor-naïve and -experienced patients with paroxysmal nocturnal hemoglobinuria.","authors":"Raymond Siu Ming Wong, Koo Wilson, Zalmai Hakimi, Mikolaj Parkitny, Piotr Wojciechowski, Catherine Flynn, Francis Fatoye","doi":"10.57264/cer-2026-0015","DOIUrl":"https://doi.org/10.57264/cer-2026-0015","url":null,"abstract":"<p><p><b>Aim:</b> Paroxysmal nocturnal hemoglobinuria (PNH) is an ultra-rare hematological condition, which if undertreated, is associated with significant morbidity and early mortality. This indirect treatment comparison (ITC) evaluated the effectiveness of pegcetacoplan (the first approved proximal inhibitor) versus crovalimab, a new C5i inhibitor (C5i), for treatment of PNH in C5i-naive and C5i-experienced patients. <b>Materials & methods:</b> In the C5i-naive, an unanchored matching-adjusted indirect comparison (MAIC) was conducted with patient-level data for pegcetacoplan-versus-best-supportive-care from PRINCE (NCT0408560) and published data for crovalimab-versus-eculizumab from COMMODORE 2 (NCT04434092)/COMMODORE 3 (NCT04654468). In the C5i-experienced ITC (Bucher's method), patient-level data were from PEGASUS (NCT03500549; pegcetacoplan vs eculizumab) and aggregated data from COMMODORE 1 (NCT04432584; crovalimab-vs-eculizumab). Evaluated outcomes in both settings included red-blood-cell transfusion-avoidance; hemoglobin (Hb) stabilization; hemolysis control; mean change-from-baseline on Functional Assessment of Chronic Illness Therapy-Fatigue total scores; additionally, the C5i-experienced ITC evaluated, mean change-from-baseline to week-25 for red blood cell units and domain scores on the European Organization for Research and Treatment of Cancer instrument. <b>Results:</b> Pegcetacoplan versus crovalimab in the C5i-naive was associated with significantly (p < 0.05) higher probabilities of transfusion-avoidance and Hb stabilization, and greater odds of hemolysis control. In the C5i-experienced, all outcomes significantly (p < 0.05) favored pegcetacoplan. <b>Conclusion:</b> Pegcetacoplan provides high clinical advantages across the full PNH treatment pathway.</p>","PeriodicalId":15539,"journal":{"name":"Journal of comparative effectiveness research","volume":" ","pages":"e260015"},"PeriodicalIF":2.8,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148812827","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":"Progressive familial intrahepatic cholestasis disease burden and clinical approaches: a systematic review.","authors":"Simon P Horslen, Georg Vogel, Jolan Terner-Rosenthal, Nadav Zadok, Lorenzo D'Antiga","doi":"10.57264/cer-2026-0047","DOIUrl":"https://doi.org/10.57264/cer-2026-0047","url":null,"abstract":"<p><p><b>Aim:</b> Progressive familial intrahepatic cholestasis (PFIC) comprises a group of rare, heterogeneous genetic liver disorders characterized by impaired bile formation and cholestasis. Historically, treatment focused on supportive management and symptomatic relief, but disease-specific therapies, including ileal bile acid transporter inhibitors, have recently become available. This systematic review updates previous evidence on the epidemiology, natural history, psychosocial and economic burden of PFIC, and summarizes evidence on the efficacy, safety and cost-effectiveness of therapies used primarily in patients with PFIC type 2 (bile salt export pump [BSEP] deficiency). <b>Materials & m</b> <b>ethods:</b> Twenty-seven databases and supplementary literature sources were searched in February 2021 and updated in January 2025. Studies were selected to address five review questions. Due to substantial heterogeneity in study populations, PFIC subtypes, outcome definitions and study designs, findings were synthesized narratively. <b>Results:</b> A total of 114 publications were included. Findings relating to epidemiology, natural history, psychosocial burden and economic burden were broadly consistent with previous reviews and highlighted the substantial impact of PFIC on children and their caregivers. Many patients treated with maralixibat and odevixibat demonstrated improvements in pruritus, serum bile acid concentrations, quality of life and markers of liver health, particularly those with PFIC2/BSEP deficiency. However, treatment responses varied across studies and genotypes, and long-term data remain limited. Only a small amount of economic evidence was identified. <b>Conclusion:</b> PFIC is associated with significant clinical and psychosocial burden. Ileal bile acid transporter inhibitors provide a novel, targeted, nonsurgical treatment option for many patients: current evidence supports improvements in pruritus and serum bile acid control, particularly in PFIC2/BSEP deficiency; however, treatment responses are heterogeneous and additional long-term clinical and economic evidence is needed.</p>","PeriodicalId":15539,"journal":{"name":"Journal of comparative effectiveness research","volume":" ","pages":"e260047"},"PeriodicalIF":2.8,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148793975","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":"Access in all areas? A round-up of developments in market access and health technology assessment: part 15.","authors":"Sreeram V Ramagopalan, Annie Jullien Pannelay","doi":"10.57264/cer-2026-0111","DOIUrl":"10.57264/cer-2026-0111","url":null,"abstract":"<p><p>In this update we examine the inaugural report of the Health Economics Methods Advisory group on defining appropriate benefits for economic evaluation and the responses it has generated. We also review recent research on the timeliness of commercial health plan coverage policy updates following US FDA label revisions, which reveals substantial delays and wide variation across plans that may limit patient access to specialty therapies.</p>","PeriodicalId":15539,"journal":{"name":"Journal of comparative effectiveness research","volume":" ","pages":"e260111"},"PeriodicalIF":2.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13436051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148360520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding the economic and healthcare burden of metabolic dysfunction-associated steatohepatitis: a real-world claims data analysis from Germany.","authors":"Frank Tacke, Yestle Kim, Jennifer S Haas, Melinda J Daumont, Christopher Maas, John O'Donnell, Jörn M Schattenberg","doi":"10.57264/cer-2026-0092","DOIUrl":"10.57264/cer-2026-0092","url":null,"abstract":"<p><p><b>Aim:</b> Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive form of metabolic dysfunction-associated steatotic liver disease, linked to hepatic and extra-hepatic complications and substantial healthcare costs. Despite its clinical and economic impact, real-world evidence on disease progression and costs in Germany is limited. <b>Materials & methods:</b> We conducted a retrospective cohort study using statutory health insurance claims from the InGef database (2016-2023), covering 4.7% of the German population. Patients with MASH were identified using ICD-10-GM code K75.8, in absence of the more specific code in the German coding system. Baseline characteristics and comorbidities were assessed over 2 years prior to index diagnosis. Progression was defined by transitions through end-stage liver disease (ESLD) stages: compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma and liver transplantation. Healthcare costs were analyzed descriptively and via regression models. <b>Results:</b> Among 4710 patients with MASH (prevalence: 0.15%), 39.4% had documented ESLD during follow-up (mean follow-up in days 1530). Disease progression to ESLD occurred in 26.0% of patients without baseline ESLD (n = 922/3490), whereas 4.0% of patients with baseline ESLD (n = 48/1188) progressed to a more severe ESLD stage during follow-up, with a mean time to first progression of approximately 25.3 months. Patients with ESLD incurred annual costs of €12,737 versus €4928 for those without ESLD. Progression to hepatocellular carcinoma and liver transplantation resulted in predicted costs of €12,948 and €75,719 per patient-year, respectively. Mortality was significantly higher among patients with ESLD (incidence rate ratio: 4.65; 95% CI: 3.76-5.79). <b>Discussion:</b> Over a quarter of identified patients with MASH already had advanced liver disease at baseline, suggesting potential underdiagnosis or late recognition in routine clinical practice. Early detection, proactive management and targeted therapies are essential to reduce progression and economic burden.</p>","PeriodicalId":15539,"journal":{"name":"Journal of comparative effectiveness research","volume":" ","pages":"e260092"},"PeriodicalIF":2.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13435893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematic review and network meta-analysis of the efficacy, safety and tolerability of xanomeline plus trospium chloride compared with eight oral antipsychotics for the acute treatment of schizophrenia.","authors":"Conor Hickey, Matthew F Sidovar, Andrea Garcia, Ken Kramer, Jen-Yu Amy Chang, Katrin Kupas, Vyshnavi Telukuntla, Jake Horgan, Haris Jameel, Tracy Westley, Kristin K Gillard, Andrew J Cutler","doi":"10.57264/cer-2026-0045","DOIUrl":"10.57264/cer-2026-0045","url":null,"abstract":"<p><p><b>Aim:</b> The recently approved first-in-class combination therapy xanomeline/trospium chloride (KarXT) demonstrated superiority over placebo in three randomized controlled trials (RCTs) of adults with schizophrenia. This analysis investigates its relative efficacy, safety and tolerability compared with eight second-generation antipsychotics for the acute treatment of schizophrenia via network meta-analyses (NMAs). <b>Materials & methods:</b> A 2019 systematic literature review was adapted and updated to identify RCTs of eight antipsychotics in adults with schizophrenia. NMAs were conducted to compare KarXT against these antipsychotics for 11 endpoints of interest, measured at 4-6 weeks, covering efficacy (Positive and Negative Syndrome Scale [PANSS]; Clinical Global Impressions - Severity [CGI-S]), safety (weight change, sedation and somnolence) and tolerability (discontinuation; all-cause and due to adverse events). <b>Results:</b> A network of 49 RCTs including 14,680 patients was formed. KarXT was associated with greater odds of clinical response (≥30% improvement in PANSS total score) than aripiprazole (odds ratio [OR]: 1.85; 95% credible interval [CrI]: 1.11, 3.11), brexpiprazole (OR: 2.23; 95% CrI: 1.34, 3.83) and cariprazine (OR: 2.05; 95% CrI: 1.19, 3.57); improved change from baseline (CFB) PANSS positive symptoms score versus brexpiprazole; improved CFB CGI-S score against aripiprazole, brexpiprazole, cariprazine and olanzapine; reduced odds of clinically significant (≥7%) weight gain over all comparators except clozapine (no data); improved CFB weight against brexpiprazole, clozapine, olanzapine, quetiapine and risperidone; and greater odds of all-cause discontinuation than aripiprazole, brexpiprazole, clozapine, lumateperone, olanzapine, quetiapine and risperidone. <b>Conclusion:</b> In this NMA, for patients receiving acute treatment for schizophrenia, KarXT compared favorably with second-generation antipsychotics on key efficacy endpoints and in terms of unwanted weight gain.</p>","PeriodicalId":15539,"journal":{"name":"Journal of comparative effectiveness research","volume":" ","pages":"e260045"},"PeriodicalIF":2.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13435969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}