Pulmonary Therapy最新文献

{"title":"The Role of Surgery in Pleural Mesothelioma: A Journey through the Evidence, MARS 2 and Beyond.","authors":"Avinash Aujayeb, Philippe Astoul, Francesco Londero, Andrea Zuin","doi":"10.1007/s41030-025-00295-1","DOIUrl":"https://doi.org/10.1007/s41030-025-00295-1","url":null,"abstract":"<p><p>Pleural mesothelioma (PM) is a rare incurable disease, predominantly linked to asbestos exposure. Not only is diagnosis difficult, but treatment choices are often limited to systemic anti-cancer treatment with chemotherapy or immunotherapy. Surgery has been employed for decades, but its application has been fiercely debated despite some randomized controlled trials such as the recent Mesothelioma and Radical Surgery 2 (MARS 2) study. We provide a commentary on this controversial topic.</p>","PeriodicalId":20919,"journal":{"name":"Pulmonary Therapy","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143773121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Phase 2a, Randomized, Placebo-Controlled Human Challenge Trial to Evaluate the Efficacy and Safety of Molnupiravir in Healthy Participants Inoculated with Respiratory Syncytial Virus.","authors":"Mickie H Cheng, Alex J Mann, Brian M Maas, Tian Zhao, Melissa Bevan, Andrea K Schaeffer, Laura E Liao, Andrew P Catchpole, David W Hilbert, S Aubrey Stoch, Carisa S De Anda","doi":"10.1007/s41030-025-00289-z","DOIUrl":"https://doi.org/10.1007/s41030-025-00289-z","url":null,"abstract":"<p><strong>Introduction: </strong>Human respiratory syncytial virus (RSV) infections can result in hospitalization and/or death among vulnerable populations. Molnupiravir is a prodrug of ß-D-N4-hydroxycytidine, which has broad-spectrum preclinical activity against RNA viruses. We conducted a pilot trial evaluating molnupiravir for RSV infection.</p><p><strong>Methods: </strong>Double-blind, placebo-controlled, phase 2a human challenge study in healthy adults (≥ 18 to ≤ 55 years old). Eligible participants were randomized 1:1:1 to molnupiravir prophylaxis (5 days, 800 mg twice daily; followed by placebo), molnupiravir treatment (5 days, 800 mg twice daily; started on day 5, unless triggered earlier by positive PCR test; preceded and followed by placebo), or placebo. Study intervention was administered for 11 days, from day -1 (evening), prior to inoculation with RSV on day 0 (morning). For 10 days, quarantined participants reported symptoms thrice daily and underwent nasal wash sample collection twice daily. Primary efficacy endpoints (assessed by quantitative viral culture on plaque assay) were peak viral load (PVL) in all participants (for prophylaxis) and area under the viral-load time curve (VL-AUC) in participants with confirmed infection (for treatment). Adverse events were assessed from day 0 to day 28.</p><p><strong>Results: </strong>Forty participants each were randomized to prophylaxis and placebo and 36 to treatment. Molnupiravir was not statistically significant from placebo in either primary endpoint: with prophylaxis, the difference in mean log₁₀ PVL was - 0.29 plaque-forming units (PFU)/ml (90% CI - 1.16, 0.58; p = 0.578), and with treatment, the difference in mean log₁₀ VL-AUC was - 2.69 day*PFU/ml (90% CI - 6.17, 0.79; p = 0.201). Molnupiravir treatment resulted in significantly faster symptom resolution: 6.0 days versus 8.5 days with placebo (hazard ratio: 2.24 [95% CI: 0.99, 5.07]; p = 0.0459). Adverse event rates were comparable between arms.</p><p><strong>Conclusions: </strong>Although the primary endpoints were not met, modest, non-significant benefits with molnupiravir treatment were seen across virologic endpoints, along with significantly faster symptom resolution.</p><p><strong>Clinical trail registration: </strong>ClinicalTrials.gov NCT0555005.</p>","PeriodicalId":20919,"journal":{"name":"Pulmonary Therapy","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143773117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monoclonal Antibodies for the Treatment of Chronic Obstructive Pulmonary Disease.","authors":"Dimitrios Toumpanakis, Konstantinos Bartziokas, Agamemnon Bakakos, Evangelia Fouka, Petros Bakakos, Stelios Loukides, Paschalis Steiropoulos, Andriana I Papaioannou","doi":"10.1007/s41030-025-00291-5","DOIUrl":"https://doi.org/10.1007/s41030-025-00291-5","url":null,"abstract":"<p><p>Chronic obstructive pulmonary disease (COPD) is a common and complex disease characterized by persistent airflow limitation and the presence of exacerbations, resulting in significant morbidity and mortality. Although the pathogenesis of COPD is multifactorial, airway inflammation plays a significant role in disease progression. Despite the advantages of non-pharmaceutical and pharmaceutical interventions that have significantly improved the symptom burden and exacerbation frequency in COPD, there is a lack of disease-modifying therapies that target the underlying disease mechanisms. Monoclonal antibodies (mAbs), a drug class that has improved treatment in severe asthma by blocking mediators of the type 2 (Th2) and allergic inflammatory cascades, are currently under investigation for their efficacy in COPD. Our review summarizes the evidence for the use of monoclonal antibodies in COPD and discusses current limitations and promising advances. Although targeting Th1 inflammation has failed to improve COPD outcomes, recent clinical trials have shown beneficial effects of monoclonal antibodies targeting Th2 inflammation, providing evidence for a personalized approach in COPD treatment.</p>","PeriodicalId":20919,"journal":{"name":"Pulmonary Therapy","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143693140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physical Activity in Adults with Severe Asthma On-Treatment with Biological Therapies: A 1-Year Retrospective Analysis of Real-World Data.","authors":"Caroline Reilly, Antonios Stavropoulos-Kalinoglou, Daniel Peckham, Ian J Clifton, Oliver J Price","doi":"10.1007/s41030-025-00292-4","DOIUrl":"https://doi.org/10.1007/s41030-025-00292-4","url":null,"abstract":"<p><strong>Introduction: </strong>Asthma is a complex airways disease that affects over 350-million people worldwide. It is estimated that up to 10% of adults and 2.5% of children with asthma have severe disease, which is associated with reduced physical activity. The introduction of biological therapies has revolutionised the management of severe asthma; however, it remains to be determined whether this translates into improvements in physical activity status.</p><p><strong>Method: </strong>This 1-year retrospective study evaluated step-based physical activity (via a smartphone pedometer) in adults with severe asthma (n = 20) and two matched sub-groups (n = 20 mild asthma and n = 20 healthy controls).</p><p><strong>Results: </strong>The annual daily step count was significantly less in adults with severe asthma (4698 ± 1927) versus mild asthma (7239 ± 1815) (P = 0.009) and healthy controls (8252 ± 2115) (P = 0.001). No difference in physical activity was observed between those with mild asthma and healthy controls (P > 0.05).</p><p><strong>Conclusion: </strong>Despite long-term treatment with biological therapies, physical activity remains significantly lower in adults with severe asthma. The development of personalised evidence-based interventions to promote physical activity in people with severe asthma remains a priority.</p>","PeriodicalId":20919,"journal":{"name":"Pulmonary Therapy","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic Delays and Quality of Life in Japanese Patients with Pulmonary Hypertension: A Nationwide Survey.","authors":"Noriko Murakami, Daiki Asano, Natsuko Tokushige, Junichi Omura, Megumi Watanabe, Seitaro Nomura, Hiroaki Kitaoka, Yuichi Tamura","doi":"10.1007/s41030-025-00290-6","DOIUrl":"https://doi.org/10.1007/s41030-025-00290-6","url":null,"abstract":"<p><strong>Introduction: </strong>Pulmonary hypertension (PH) is a rare and severe disorder that significantly affects patients' lives. However, a comprehensive picture of the diagnosis and treatment of this condition in Japan remains unclear. This study aimed to elucidate these aspects by conducting a nationwide survey targeting patients with PH and treating physicians.</p><p><strong>Methods: </strong>A cross-sectional survey was conducted among 160 patients with PH (119 with pulmonary arterial hypertension [PAH] and 41 with chronic thromboembolic pulmonary hypertension [CTEPH]), of whom 121 were female (75.6%), and 211 physicians across Japan. The questionnaires assessed patients' diagnostic journey, employment status, communication with physicians regarding treatment goals, health-related quality of life (HRQoL), and medication adherence.</p><p><strong>Results: </strong>Patients visited a mean of 2.3 medical facilities before receiving a PH diagnosis (PAH patients: 2.2 visits; CTEPH patients: 2.3 visits), with a mean time from symptom onset to diagnosis of 18.0 months (PAH: 20.2 months; CTEPH: 12.2 months). Employment and school attendance rates declined from 68.8% before diagnosis to 44.4% immediately after diagnosis, and further to 36.9% at the time of the survey. Discrepancies in communication about treatment goals were observed between patients and physicians, particularly in patients with CTEPH (82.9% of patients reported such discussions vs. 41.2% of treating physicians). Median HRQoL scores, as assessed by the emPHasis-10 questionnaire, indicated impairment (PAH: 21.5; CTEPH: 18.0), which worsened with increasing disease severity.</p><p><strong>Conclusion: </strong>This nationwide study provides a comprehensive overview of the challenges faced by patients with PH in Japan. The findings suggest the essential need for earlier diagnosis, support for employment and education among patients, and improved patient-physician communication to reduce the burden of PH and enhance patient outcomes. Graphical abstract avaliable for this article.</p>","PeriodicalId":20919,"journal":{"name":"Pulmonary Therapy","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Brief Report on a Systematic Review of Real-World Effectiveness Studies of ICS/LAMA/LABA for Treatment of Adults with Asthma in the US.","authors":"Stephen G Noorduyn, Kejsi Begaj, Amber Martin, Sergio Forero-Schwanhaeuser, Kassandra Schaible, Alison Moore, Rosirene Paczkowski","doi":"10.1007/s41030-025-00288-0","DOIUrl":"https://doi.org/10.1007/s41030-025-00288-0","url":null,"abstract":"<p><strong>Introduction: </strong>Long-acting muscarinic antagonist (LAMA) addition to inhaled corticosteroid/long-acting β₂-agonist (ICS/LABA) dual therapy is recommended for severe asthma, but its real-world effectiveness is not well established.</p><p><strong>Methods: </strong>A systematic literature review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) to investigate clinical outcomes in US adults with asthma receiving ICS + LABA + LAMA as multiple-/single-inhaler triple therapy (MITT/SITT). Real-world/observational studies published in English in Embase/MEDLINE databases (2014-2024) and conference abstracts presented 2022-2024 were eligible for inclusion.</p><p><strong>Results: </strong>From 588 identified records, only 8 articles reporting 6 unique studies were included; 2 assessed SITT and 4 assessed MITT, and 4 treatments were investigated. Exacerbation rates reported in two studies were significantly reduced with tiotropium (TIO) + ICS + LABA MITT versus high-dose ICS + LABA within 6 (64% lower) and 12 months (73%), and fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 mcg SITT versus pre-treatment after 12 months (41%). Oral corticosteroid (OCS) use was reported in two studies. The proportion of patients with ≥ 1 rescue OCS dispensing decreased with TIO 1.25 mcg + ICS + LABA MITT, with greatest reductions for MITT ± leukotriene receptor antagonist (pre-treatment: 68.4%, post treatment: 54.2%). Mean number of OCS dispensings/patient/year significantly decreased (29%, p < 0.001) following FF/UMEC/VI 100/62.5/25 mcg SITT initiation. Treatment adherence/persistence was reported in three studies. Mean (standard deviation) proportion of days covered was significantly higher (p < 0.001) for FF/UMEC/VI SITT versus MITT after 6 (0.56 [0.31] versus 0.46 [0.31]) and 12 months (0.46 [0.33] versus 0.35 [0.30]). Persistence at 12 months was 25.9% and 12.0%, respectively. Lung function, clinical remission, quality of life, and safety outcomes were not reported in any study.</p><p><strong>Conclusions: </strong>This brief communication reports a systematic review that identified few sources of SITT or MITT in US patients with asthma. Although inclusion of observational studies can result in reporting/selection bias, we identified greater clinical benefits with triple therapies versus dual therapies.</p>","PeriodicalId":20919,"journal":{"name":"Pulmonary Therapy","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Εosinophilic Chronic Obstructive Pulmonary Disease. What Do We Know So Far?","authors":"Konstantinos Bartziokas, Andriana I Papaioannou, Nikoletta Rovina, Georgia Papaiakovou, Stelios Loukides, Paschalis Steiropoulos","doi":"10.1007/s41030-024-00280-0","DOIUrl":"10.1007/s41030-024-00280-0","url":null,"abstract":"<p><p>The latest advances in asthma treatment have highlighted the significance of eosinophilia and the possible role of some pro-eosinophilic mediators, like interleukins (IL) IL-5, IL-4/IL-13, and IL-33 in the disease's pathogenesis. Considering that a subgroup of patients with chronic obstructive pulmonary disease (COPD) may have blood eosinophilia akin to that seen in asthma, numerous studies in the last decade have suggested that eosinophilic COPD is a separate entity. While the exact role of blood eosinophils in the pathophysiology of COPD remains unclear, eosinophilia seems to increase the effectiveness of corticosteroid therapy. Currently, monoclonal antibodies targeting the interleukins (IL-5, IL-4, IL-13, and IL-33) or their receptors are being investigated in patients with COPD belonging in T2-high endotype. This review focuses on the mechanisms of eosinophilia in COPD, the effects of eosinophilia on disease outcome, and examines the most recent data on the use of peripheral blood eosinophilia in treating patients with COPD. Finally, we emphasize the current implication of monoclonal antibodies in COPD in the context of eosinophilic airway inflammation.</p>","PeriodicalId":20919,"journal":{"name":"Pulmonary Therapy","volume":" ","pages":"7-24"},"PeriodicalIF":2.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11861475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Retrospective Study Evaluating Asthma Control in Patients on Fluticasone Propionate/Salmeterol Proactive Regular Dosing with a History of Uncontrolled Asthma.","authors":"Ahmad Izuanuddin Ismail, Irfhan Ali Hyder Ali, Chee Kuan Wong, Andrea Yu-Lin Ban, Fatimah Mz Zahrah, Li Khen Lem, Zamzurina Abu Bakar, Arvindran Alaga, Azza Omar, Azlina Samsudin, Siew Li Lai, Alap Gandhi","doi":"10.1007/s41030-024-00278-8","DOIUrl":"10.1007/s41030-024-00278-8","url":null,"abstract":"<p><strong>Introduction: </strong>The MERIT study in Malaysia is a real-world retrospective, observational, multicenter study that evaluated asthma control in patients with uncontrolled asthma who were switched from as-needed (pro re nata [PRN]) budesonide/formoterol or inhaled corticosteroid (ICS) whenever a short-acting beta-agonist (SABA) was taken, to proactive regular dosing of fluticasone propionate/salmeterol (FP/SAL PRD).</p><p><strong>Methods: </strong>Data from the medical records of patients who were stepped up to FP/SAL PRD were extracted retrospectively at baseline and follow-up (between 3 and 6 months after stepping up to FP/SAL PRD). The primary endpoint was the percentage of patients with improvement in asthma control assessed via the Asthma Control Test (ACT). Secondary endpoints included safety and the percentage of patients with moderate and severe exacerbations. Additionally, patient-reported use of reliever medication, systemic corticosteroids, emergency department visits, or hospitalization was also analyzed.</p><p><strong>Results: </strong>One hundred twenty patients with uncontrolled asthma who were stepped up to FP/SAL PRD were enrolled in the study. Of these, 76 (63.3%) patients were on prior budesonide/formoterol PRN, and 44 (36.7%) were on prior ICS with SABA PRN treatment. After stepping up to FP/SAL PRD with a mean follow-up of 5.8 months, 110 (91.7%) patients achieved asthma control at the follow-up visit (p < 0.001). Similar improvements were observed regardless of prior PRN regimen. A statistically significant improvement was observed in the mean ACT score at the follow-up visit (p < 0.0001). The proportion of patients with moderate and severe exacerbations was also reduced after stepping up to FP/SAL PRD, with no adverse events reported. Over 80% of patients reported a decrease in the use of systemic corticosteroids, visits to the emergency department, or hospitalization.</p><p><strong>Conclusion: </strong>This study highlights the effectiveness of the FP/SAL PRD treatment approach in patients with uncontrolled asthma on a PRN treatment regimen.</p>","PeriodicalId":20919,"journal":{"name":"Pulmonary Therapy","volume":" ","pages":"25-40"},"PeriodicalIF":2.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11861446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142626891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retrospective Cohort Study of Elderly Users of Single- or Multiple-Inhaler Triple Therapy for the Treatment of Asthma in the USA.","authors":"Russell A Settipane, Guillaume Germain, Francois Laliberté, Malena Mahendran, Annalise Hilts, Mei Sheng Duh, Rosirene Paczkowski, Emmeline Burrows","doi":"10.1007/s41030-024-00285-9","DOIUrl":"10.1007/s41030-024-00285-9","url":null,"abstract":"<p><strong>Introduction: </strong>Escalation to single- or multiple-inhaler triple therapy (SITT; MITT) is a recommended option for patients with asthma who remain uncontrolled by medium-dose inhaled corticosteroid/long-acting β₂-agonist; however, characterization of elderly users of triple therapy is limited. This real-world cohort study describes demographics and clinical characteristics of elderly patients with asthma with and without comorbid chronic obstructive pulmonary disease (COPD) who are new users of triple therapy, and asthma treatment patterns preceding triple therapy initiation.</p><p><strong>Methods: </strong>This retrospective cohort study used administrative claims data from the Optum Clinformatics Data Mart database. Eligible patients were ≥ 65 years of age with asthma or with asthma and comorbid COPD who initiated either triple therapy with single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI; 100/62.5/25 μg) or MITT between September 18, 2017 and September 30, 2020. Demographics, clinical characteristics, healthcare resource utilization, healthcare costs, and asthma treatment patterns were described in the 12-month period before triple therapy initiation (baseline period).</p><p><strong>Results: </strong>In total, 15,557 patients were included. Among FF/UMEC/VI initiators with asthma (N = 635) mean age was 73.3 years and 66.6% were female. During the baseline period, > 75% of patients used controller therapy, > 92% used rescue medications, 27.9% experienced ≥ 1 asthma-related exacerbation, with mean annual exacerbation rate of 0.42, and mean all-cause healthcare costs were $23,407. Patients with asthma initiating MITT and patients with asthma and comorbid COPD initiating FF/UMEC/VI or MITT had similar characteristics, healthcare resource utilization, healthcare costs, and asthma treatment patterns to FF/UMEC/VI initiators with asthma.</p><p><strong>Conclusions: </strong>Triple therapy is often initiated following use of other asthma controller medications in real-world practice. Substantial rescue medication use and high disease and economic burden among this elderly patient population suggest that their asthma was not adequately controlled prior to triple therapy initiation. This retrospective study provides an early profile of elderly patients with asthma in the USA.</p>","PeriodicalId":20919,"journal":{"name":"Pulmonary Therapy","volume":" ","pages":"81-100"},"PeriodicalIF":2.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11861473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Safety and Efficacy of Macitentan in Inoperable Chronic Thromboembolic Pulmonary Hypertension: Results from MERIT and its Open-Label Extension.","authors":"Nick H Kim, Andrea M D'Armini, Luke S Howard, David P Jenkins, Zhi-Cheng Jing, Eckhard Mayer, Liliya Chamitava, Gabriela Lack, Hany Rofael, Maria Solonets, Hossein-Ardeschir Ghofrani","doi":"10.1007/s41030-024-00276-w","DOIUrl":"10.1007/s41030-024-00276-w","url":null,"abstract":"<p><strong>Introduction: </strong>Evidence for use of pulmonary arterial hypertension targeted-therapies in patients with chronic thromboembolic pulmonary hypertension (CTEPH) is limited. In MERIT-1, the endothelin receptor antagonist macitentan improved hemodynamic and functional parameters versus placebo in patients with inoperable CTEPH over a 24-week double-blind (DB) period. Its open-label (OL) extension study (MERIT-2) provides long-term safety/efficacy data.</p><p><strong>Methods: </strong>MERIT-2 (NCT02060721) was a multicenter, single-arm, OL, phase 2 extension study of MERIT-1. Patients completing MERIT-1 were eligible to receive 10 mg macitentan once-daily in MERIT-2. Safety and efficacy (6-min walk distance [6MWD] and change in World Health Organization functional class [WHO FC]) were assessed in all patients in MERIT-2 regardless of treatment received in DB (All patients MERIT-2 OL macitentan 10 mg group) and the subgroup of patients receiving DB macitentan in MERIT-1 (Long-term [DB/OL] macitentan 10 mg subgroup).</p><p><strong>Results: </strong>Of the 80 patients randomized in MERIT-1, 76 entered MERIT-2 (All patients MERIT-2 OL macitentan 10 mg group): 40 who received DB macitentan (DB-macitentan patients) and 36 DB placebo (DB-placebo patients). Median (interquartile range) macitentan exposure in the All patients MERIT-2 OL macitentan 10 mg group was 45.5 (26.0, 66.1) months. During the OL period, treatment-emergent adverse events (AE) were reported in 72 (94.7%) patients; most frequent were worsening of pulmonary hypertension (19.7%), decreased hemoglobin (18.4%) and upper respiratory tract infection (15.8%). Fourteen (18.4%) patients died; none were assessed as macitentan-related. At Month 6 post-OL baseline, mean (standard deviation) change in 6MWD was - 0.4 m (43.62) for DB-macitentan patients and 10.7 m (45.63) for DB-placebo patients; the majority had unchanged (83.3%) or improved (12.5%) WHO FC. Safety/efficacy analyses were consistent in the Long-term (DB/OL) macitentan 10 mg subgroup.</p><p><strong>Conclusion: </strong>These analyses provide long-term safety/efficacy data in patients with inoperable CTEPH treated with macitentan. No unexpected safety findings occurred; reported AEs were consistent with the known safety profile of macitentan. At 6 months post-OL baseline, DB-placebo patients modestly improved 6MWD; DB-macitentan patients maintained improvements observed in MERIT-1. WHO FC was largely unchanged.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifiers: NCT02021292; NCT02060721.</p>","PeriodicalId":20919,"journal":{"name":"Pulmonary Therapy","volume":" ","pages":"101-116"},"PeriodicalIF":2.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11861443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142626902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}