New England Journal of Medicine最新文献

{"title":"First-Line Treatment of Pulmonary Sarcoidosis with Prednisone or Methotrexate.","authors":"Vivienne Kahlmann,Montse Janssen Bonás,Catharina C Moor,Jan C Grutters,Rémy L M Mostard,Henricus N A J van Rijswijk,Jan van der Maten,Emiel R Marges,Linda A A Moonen,Maria J Overbeek,Bart Koopman,Daan W Loth,Esther J Nossent,Michiel Wagenaar,Henk Kramer,Pascal L M L Wielders,Peter I Bonta,Stefan Walen,Brigitte A H A Bogaarts,Réne Kerstens,Mayka Overgaauw,Marcel Veltkamp,Marlies S Wijsenbeek","doi":"10.1056/nejmoa2501443","DOIUrl":"https://doi.org/10.1056/nejmoa2501443","url":null,"abstract":"BACKGROUNDPrednisone is currently recommended as the first-line treatment for pulmonary sarcoidosis but is associated with many side effects. Methotrexate, which is recommended as a second-line treatment, appears to have fewer side effects than prednisone but a slower onset of action. Data are needed on the efficacy and side-effect profile of methotrexate as compared with prednisone as first-line treatment for pulmonary sarcoidosis.METHODSIn this multicenter, open-label, noninferiority trial involving patients with pulmonary sarcoidosis who had not previously received treatment, we randomly assigned patients, in a 1:1 ratio, to receive prednisone or methotrexate according to a prespecified treatment schedule. The primary end point was the mean change from baseline to week 24 in the percentage of the predicted forced vital capacity (FVC), as estimated with the use of mixed models for repeated measures. The noninferiority margin for the primary end point was 5 percentage points.RESULTSOf the 138 patients who underwent randomization, 70 were assigned to receive prednisone and 68 to receive methotrexate. The unadjusted mean change from baseline to week 24 in the percentage of the predicted FVC was 6.75 percentage points (95% confidence interval [CI], 4.50 to 8.99) in the prednisone group and 6.11 percentage points (95% CI, 3.72 to 8.50) in the methotrexate group. Methotrexate was noninferior to prednisone with regard to the primary end point, with an adjusted between-group difference of -1.17 percentage points (95% CI, -4.27 to 1.93). Adverse events occurred in a similar percentage of patients in the two trial groups. Weight gain, insomnia, and increased appetite were the most common adverse events with prednisone, and nausea, fatigue, and any abnormal liver-function test were among the most common adverse events with methotrexate.CONCLUSIONSIn patients with pulmonary sarcoidosis, initial treatment with methotrexate was noninferior to that with prednisone with regard to the change from baseline to week 24 in the percentage of the predicted FVC. Differences in the side-effect profile between methotrexate and prednisone may inform shared decision making by providers and patients about the appropriate treatment approach. (Funded by the Dutch Lung Foundation; PREDMETH ClinicalTrials.gov number, NCT04314193.).","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"132 1","pages":""},"PeriodicalIF":158.5,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biopsy of Peripheral Lung Nodules - Inside Out or Outside In?","authors":"Michael K Gould","doi":"10.1056/nejme2504035","DOIUrl":"https://doi.org/10.1056/nejme2504035","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"30 1","pages":""},"PeriodicalIF":158.5,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Navigational Bronchoscopy or Transthoracic Needle Biopsy for Lung Nodules.","authors":"Robert J Lentz,Katherine Frederick-Dyer,Virginia B Planz,Tatsuki Koyama,Matthew C Aboudara,Sameer K Avasarala,Jonathan D Casey,George Z Cheng,Pierre-François D'Haese,Jennifer D Duke,Eric L Grogan,Todd C Hoopman,Joyce Johnson,James M Katsis,Jonathan S Kurman,See-Wei Low,Kamran Mahmood,Otis B Rickman,Lance Roller,Cristina Salmon,Samira Shojaee,Briana Swanner,Momen M Wahidi,Charla Walston,Gerard A Silvestri,Lonny Yarmus,Najib M Rahman,Fabien Maldonado,","doi":"10.1056/nejmoa2414059","DOIUrl":"https://doi.org/10.1056/nejmoa2414059","url":null,"abstract":"BACKGROUNDEach year, millions of pulmonary nodules are identified incidentally or through lung cancer screening, and many involve biopsy to distinguish cancer from benign processes. Both navigational bronchoscopy and computed tomography-guided transthoracic needle biopsy are commonly used in patients undergoing biopsies of peripheral pulmonary nodules, but the relative diagnostic accuracy of these two approaches is unclear.METHODSIn this multicenter, randomized, parallel-group, noninferiority trial, we assigned patients with an intermediate-risk or high-risk peripheral pulmonary nodule measuring 10 to 30 mm in diameter to undergo navigational bronchoscopy or transthoracic needle biopsy at seven centers across the United States. The primary outcome was diagnostic accuracy, which was defined as the percentage of patients with biopsies that showed a specific diagnosis (cancer or a specific benign condition) that was confirmed to be accurate through 12 months of clinical follow-up (nonferiority margin, 10 percentage points). Secondary outcomes included procedural complications such as the occurrence of pneumothorax.RESULTSAmong the 234 patients included in the primary-outcome analysis (5 of whom were lost to follow-up), biopsy resulted in a specific diagnosis that was confirmed to be accurate through month 12 in 94 of 119 patients (79.0%) in the navigational bronchoscopy group and in 81 of 110 patients (73.6%) in the transthoracic needle biopsy group (absolute difference, 5.4 percentage points; 95% confidence interval, -6.5 to 17.2; P = 0.003 for noninferiority; P = 0.17 for superiority). Pneumothorax occurred in 4 of 121 patients (3.3%) in the navigational bronchoscopy group and in 32 of 113 patients (28.3%) in the transthoracic needle biopsy group and led to the placement of a chest tube, hospital admission, or both in 1 patient (0.8%) and 13 patients (11.5%), respectively.CONCLUSIONSThe diagnostic accuracy of navigational bronchoscopy was noninferior to that of transthoracic needle biopsy among patients with peripheral pulmonary nodules measuring 10 to 30 mm. (Funded by Medtronic and others; VERITAS ClinicalTrials.gov number, NCT04250194.).","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"8 1","pages":""},"PeriodicalIF":158.5,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nerandomilast in Patients with Idiopathic Pulmonary Fibrosis.","authors":"Luca Richeldi,Arata Azuma,Vincent Cottin,Michael Kreuter,Toby M Maher,Fernando J Martinez,Justin M Oldham,Claudia Valenzuela,Emmanuelle Clerisme-Beaty,Maud Gordat,Daniel Wachtlin,Yi Liu,Christina Schlecker,Susanne Stowasser,Donald F Zoz,Marlies S Wijsenbeek,","doi":"10.1056/nejmoa2414108","DOIUrl":"https://doi.org/10.1056/nejmoa2414108","url":null,"abstract":"BACKGROUNDNerandomilast (BI 1015550) is an orally administered preferential inhibitor of phosphodiesterase 4B with antifibrotic and immunomodulatory effects. In a phase 2 trial involving patients with idiopathic pulmonary fibrosis, treatment with nerandomilast stabilized lung function over a period of 12 weeks.METHODSIn this phase 3, double-blind trial, we randomly assigned patients with idiopathic pulmonary fibrosis in a 1:1:1 ratio to receive nerandomilast at a dose of 18 mg twice daily, nerandomilast at a dose of 9 mg twice daily, or placebo, with stratification according to background antifibrotic therapy (nintedanib or pirfenidone vs. none). The primary end point was the absolute change from baseline in forced vital capacity (FVC), measured in milliliters, at week 52.RESULTSA total of 1177 patients underwent randomization, of whom 77.7% were taking nintedanib or pirfenidone at enrollment. Adjusted mean changes in FVC at week 52 were -114.7 ml (95% confidence interval [CI], -141.8 to -87.5) in the nerandomilast 18-mg group, -138.6 ml (95% CI, -165.6 to -111.6) in the nerandomilast 9-mg group, and -183.5 ml (95% CI, -210.9 to -156.1) in the placebo group. The adjusted difference between the nerandomilast 18-mg group and the placebo group was 68.8 ml (95% CI, 30.3 to 107.4; P<0.001), and the adjusted difference between the nerandomilast 9-mg group and the placebo group was 44.9 ml (95% CI, 6.4 to 83.3; P = 0.02). The most frequent adverse event in the nerandomilast groups was diarrhea, reported in 41.3% of the 18-mg group and 31.1% of the 9-mg group, as compared with 16.0% in the placebo group. Serious adverse events were balanced across trial groups.CONCLUSIONSIn patients with idiopathic pulmonary fibrosis, treatment with nerandomilast resulted in a smaller decline in the FVC than placebo over a period of 52 weeks. (Funded by Boehringer Ingelheim; FIBRONEER-IPF ClinicalTrials.gov number, NCT05321069.).","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"21 1","pages":""},"PeriodicalIF":158.5,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methotrexate as Initial Therapy for Symptomatic Pulmonary Sarcoidosis?","authors":"Robert P Baughman,Elyse E Lower","doi":"10.1056/nejme2504736","DOIUrl":"https://doi.org/10.1056/nejme2504736","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"128 1","pages":""},"PeriodicalIF":158.5,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Xenotransplantation of a Porcine Kidney for End-Stage Kidney Disease.","authors":"Tatsuo Kawai, Winfred W Williams, Nahel Elias, Jay A Fishman, Kerry Crisalli, Alban Longchamp, Ivy A Rosales, Michael Duggan, Shoko Kimura, Leela Morena, Thiago J Borges, Toshihide Tomosugi, Ahmad Karadagi, Tsukasa Nakamura, Kassem Safa, Alessia Giarraputo, Claire T Avillach, Eva D Patalas, R Neal Smith, David H Sachs, A Benedict Cosimi, Joren C Madsen, David K C Cooper, Richard Pierson, Steve Perrin, Ranjith P Anand, Sagar Chhangawala, Matthew Coscarella, Alexandre Daigneault, Feng Li, Owen Pearce, Wenning Qin, William T Serkin, Vincent Yeung, Kristen Getchell, Susan C Low, Michael Curtis, Robert B Colvin, Leonardo V Riella","doi":"10.1056/NEJMoa2412747","DOIUrl":"10.1056/NEJMoa2412747","url":null,"abstract":"<p><p>Xenotransplantation offers a potential solution to the organ shortage crisis. A 62-year-old hemodialysis-dependent man with long-standing diabetes, advanced vasculopathy, and marked dialysis-access challenges received a gene-edited porcine kidney with 69 genomic edits, including deletion of three glycan antigens, inactivation of porcine endogenous retroviruses, and insertion of seven human transgenes. The xenograft functioned immediately. The patient's creatinine levels decreased promptly and progressively, and dialysis was no longer needed. After a T-cell-mediated rejection episode on day 8, intensified immunosuppression reversed rejection. Despite sustained kidney function, the patient died from unexpected, sudden cardiac causes on day 52; autopsy revealed severe coronary artery disease and ventricular scarring without evident xenograft rejection. (Funded by Massachusetts General Hospital and eGenesis.).</p>","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":"1933-1940"},"PeriodicalIF":96.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143384127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tolebrutinib versus Teriflunomide in Relapsing Multiple Sclerosis.","authors":"Jiwon Oh, Douglas L Arnold, Bruce A C Cree, Carolina Ionete, Ho Jin Kim, Maria Pia Sormani, Sana Syed, Yixin Chen, Christina R Maxwell, Patrick Benoit, Timothy J Turner, Erik Wallstroem, Heinz Wiendl","doi":"10.1056/NEJMoa2415985","DOIUrl":"10.1056/NEJMoa2415985","url":null,"abstract":"<p><strong>Background: </strong>Tolebrutinib is an oral, brain-penetrant, and bioactive Bruton's tyrosine kinase inhibitor that modulates peripheral inflammation and persistent immune activation within the central nervous system, including disease-associated microglia and B cells. More data are needed on its efficacy and safety in treating relapsing multiple sclerosis.</p><p><strong>Methods: </strong>In two phase 3, double-blind, double-dummy, event-driven trials (GEMINI 1 and GEMINI 2), participants with relapsing multiple sclerosis were randomly assigned in a 1:1 ratio to receive tolebrutinib (60 mg once daily) or teriflunomide (14 mg once daily), each with matching placebo. The primary end point was the annualized relapse rate. The key secondary end point was confirmed worsening of disability that was sustained for at least 6 months, which was assessed in a time-to-event analysis that was pooled across trials.</p><p><strong>Results: </strong>A total of 974 participants were enrolled in GEMINI 1, and 899 were enrolled in GEMINI 2. The median follow-up was 139 weeks. The annualized relapse rate in the tolebrutinib and teriflunomide groups was 0.13 and 0.12, respectively, in GEMINI 1 (rate ratio, 1.06; 95% confidence interval [CI], 0.81 to 1.39; P = 0.67) and 0.11 and 0.11, respectively, in GEMINI 2 (rate ratio, 1.00; 95% CI, 0.75 to 1.32; P = 0.98). The pooled percentage of participants with confirmed disability worsening sustained for at least 6 months was 8.3% with tolebrutinib and 11.3% with teriflunomide (hazard ratio, 0.71; 95% CI, 0.53 to 0.95; no formal hypothesis testing was conducted owing to the prespecified hierarchical testing plan, and the width of the confidence interval is not adjusted for multiple testing). The percentage of participants who had adverse events was similar in the two treatment groups, although the percentage with minor bleeding was higher in the tolebrutinib group than in the teriflunomide group (petechiae occurred in 4.5% vs. 0.3%, and heavy menses in 2.6% vs. 1.0%).</p><p><strong>Conclusions: </strong>Tolebrutinib was not superior to teriflunomide in decreasing annualized relapse rates among participants with relapsing multiple sclerosis. (Funded by Sanofi; GEMINI 1 and GEMINI 2 ClinicalTrials.gov numbers, NCT04410978 and NCT04410991, respectively.).</p>","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":"1893-1904"},"PeriodicalIF":96.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paget's Disease of Bone.","authors":"Masashi Hasebe, Akihiro Hamasaki","doi":"10.1056/NEJMicm2414362","DOIUrl":"10.1056/NEJMicm2414362","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":"1953"},"PeriodicalIF":96.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144052959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient-Specific In Vivo Gene Editing to Treat a Rare Genetic Disease.","authors":"Kiran Musunuru,Sarah A Grandinette,Xiao Wang,Taylor R Hudson,Kevin Briseno,Anne Marie Berry,Julia L Hacker,Alvin Hsu,Rachel A Silverstein,Logan T Hille,Aysel N Ogul,Nancy A Robinson-Garvin,Juliana C Small,Sarah McCague,Samantha M Burke,Christina M Wright,Sarah Bick,Venkata Indurthi,Shweta Sharma,Michael Jepperson,Christopher A Vakulskas,Michael Collingwood,Katie Keogh,Ashley Jacobi,Morgan Sturgeon,Christian Brommel,Ellen Schmaljohn,Gavin Kurgan,Thomas Osborne,He Zhang,Kyle Kinney,Garrett Rettig,Christopher J Barbosa,Sean C Semple,Ying K Tam,Cathleen Lutz,Lindsey A George,Benjamin P Kleinstiver,David R Liu,Kim Ng,Sadik H Kassim,Petros Giannikopoulos,Mohamad-Gabriel Alameh,Fyodor D Urnov,Rebecca C Ahrens-Nicklas","doi":"10.1056/nejmoa2504747","DOIUrl":"https://doi.org/10.1056/nejmoa2504747","url":null,"abstract":"Base editors can correct disease-causing genetic variants. After a neonate had received a diagnosis of severe carbamoyl-phosphate synthetase 1 deficiency, a disease with an estimated 50% mortality in early infancy, we immediately began to develop a customized lipid nanoparticle-delivered base-editing therapy. After regulatory approval had been obtained for the therapy, the patient received two infusions at approximately 7 and 8 months of age. In the 7 weeks after the initial infusion, the patient was able to receive an increased amount of dietary protein and a reduced dose of a nitrogen-scavenger medication to half the starting dose, without unacceptable adverse events and despite viral illnesses. No serious adverse events occurred. Longer follow-up is warranted to assess safety and efficacy. (Funded by the National Institutes of Health and others.).","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"57 1","pages":""},"PeriodicalIF":158.5,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oveporexton, an Oral Orexin Receptor 2-Selective Agonist, in Narcolepsy Type 1.","authors":"Yves Dauvilliers,Giuseppe Plazzi,Emmanuel Mignot,Gert Jan Lammers,Rafael Del Río Villegas,Ramin Khatami,Mitsutaka Taniguchi,Anson Abraham,Yaming Hang,Harisha Kadali,Marta Lamberton,Sarah Sheikh,Ellie Stukalin,Rachel Neuwirth,Todd J Swick,Shinichiro Tanaka,Christian von Hehn,Philipp von Rosenstiel,Hao Wang,Alice Cai,Melissa Naylor,Tina Olsson","doi":"10.1056/nejmoa2405847","DOIUrl":"https://doi.org/10.1056/nejmoa2405847","url":null,"abstract":"BACKGROUNDNarcolepsy type 1 is a disorder of hypersomnolence caused by a loss of orexin neurons, which results in low orexin levels in the brain.METHODSIn this phase 2, randomized, placebo-controlled trial, participants with narcolepsy type 1 received once- or twice-daily oveporexton (TAK-861), an oral orexin receptor 2-selective agonist, or placebo. The primary end point was the mean change from baseline to week 8 in average sleep latency (the time it takes to fall asleep) on the Maintenance of Wakefulness Test (MWT) (range, 0 to 40 minutes; normal, ≥20). Secondary end points included the change from baseline to week 8 in the Epworth Sleepiness Scale (ESS) total score (range, 0 to 24; normal, ≤10), the weekly cataplexy rate at week 8, and the occurrence of adverse events.RESULTSA total of 90 participants received oveporexton (0.5 mg twice daily, 23 participants; 2 mg twice daily, 21 participants; 2 mg followed by 5 mg daily, 23 participants; and 7 mg once daily, 23 participants), and 22 received placebo. The mean changes from baseline to week 8 in average sleep latency on the MWT were 12.5, 23.5, 25.4, 15.0, and -1.2 minutes, respectively (adjusted P≤0.001 for all comparisons vs. placebo). The mean changes in the ESS total score at week 8 were -8.9, -13.8, -12.8, -11.3, and -2.5, respectively (adjusted P≤0.004 for all comparisons vs. placebo). The weekly incidence of cataplexy at week 8 was 4.24, 3.14, 2.48, 5.89, and 8.76, respectively (adjusted P<0.05 for 2 mg twice daily and 2 mg followed by 5 mg daily vs. placebo). The most common adverse events associated with oveporexton were insomnia (in 48% of the participants; most cases resolved within 1 week), urinary urgency (in 33%), and urinary frequency (in 32%), without any hepatotoxic effects.CONCLUSIONSIn this phase 2 trial involving participants with narcolepsy type 1, oveporexton significantly improved measures of wakefulness, sleepiness, and cataplexy over a period of 8 weeks. (Funded by Takeda Development Center Americas; TAK-861-2001 ClinicalTrials.gov number, NCT05687903.).","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"74 1","pages":"1905-1916"},"PeriodicalIF":158.5,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}