Advances in Therapy最新文献

{"title":"Analysis of Real-World Progression and Insufficient Response Variables and Related Endpoints Among Patients with Non-Hodgkin Lymphoma","authors":"Madeline Richey,&nbsp;Christina Fullerton,&nbsp;Qianyi Zhang,&nbsp;Tori Williams,&nbsp;Douglas Donnelly,&nbsp;Hannah C. Wise,&nbsp;Aaron Dolor,&nbsp;Niquelle Wadé,&nbsp;Kelly Magee","doi":"10.1007/s12325-025-03143-5","DOIUrl":"10.1007/s12325-025-03143-5","url":null,"abstract":"<div><h3>Introduction</h3><p>Methods for assessing change in tumor burden differ between clinical trial and routine clinical care settings, presenting a unique opportunity to design novel methods to capture clinical outcomes from electronic health record (EHR) data. We adapted a previously established approach for solid tumors and modified it to capture real-world progression (rwP) and real-world insufficient response (rwIR) events in non-Hodgkin lymphoma (NHL).</p><h3>Methods</h3><p>This study used a nationwide EHR-derived deidentified database. The first phase assessed the rwP/rwIR approach in patients with follicular lymphoma (FL) and diffuse large B cell lymphoma (DLBCL). The second phase assessed the approach in a larger cohort of patients with mantle cell lymphoma (MCL). Performance was assessed through inter-abstractor agreement on event occurrence, date, and type, clinician assessment and source data completeness, downstream events after an rwP/rwIR event, and time-to-event analyses (real-world progression-free [rwPFS] and event-free [rwEFS] survival) and their correlation with real-world overall survival (rwOS).</p><h3>Results</h3><p>A total of 6162 patients with NHL were included in the study, comprising 672 patients with FL (median age, 64 years; female, 49%; male, 51%), 405 patients with DLBCL (median age, 70 years; female, 42%; male, 58%), and 5085 patients with MCL (median age, 69 years; female, 27%; male, 73%). Inter-abstractor agreement among all cohorts was 96–97% for event occurrence and 85–89% for event date within 30 days. The proportion of patients with an rwP/rwIR event was 26% in the FL cohort, 27% in the DLBCL cohort, and 42% in the MCL cohort. Clinically relevant downstream events were observed in 58% of the FL cohort, 63% of the DLBCL cohort, and 73% of the MCL cohort. In the MCL cohort, median rwPFS was 34.5 months, and median rwEFS was 32.2 months. Real-world OS correlated more strongly with rwPFS (85%) than with rwEFS (80%).</p><h3>Conclusions</h3><p>The NHL-specific rwP/rwIR approach is feasible, reliable, and scalable. Observed inter-abstractor agreement and rwP/rwIR event frequency show applicability across NHL cohorts. Endpoint analyses and correlations with rwOS in a real-world population demonstrate the clinical relevance of this approach.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 4","pages":"1979 - 1993"},"PeriodicalIF":3.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03143-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiovascular Risks and Survival with Abiraterone vs Enzalutamide in Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer in Germany: AVENGER Study","authors":"Axel S. Merseburger,&nbsp;Eugen Dornstauder,&nbsp;Carsten-Henning Ohlmann,&nbsp;Armen Aprikian,&nbsp;Sophia Junker,&nbsp;Philipp Hahn,&nbsp;Andrew Chilelli,&nbsp;Matthias Stoelzel,&nbsp;Alexis Serikoff,&nbsp;Stefan G. Spitzer","doi":"10.1007/s12325-025-03132-8","DOIUrl":"10.1007/s12325-025-03132-8","url":null,"abstract":"<div><h3>Introduction</h3><p>Recent real-world studies compared effectiveness and safety of enzalutamide (ENZA) and abiraterone acetate (AA) for metastatic castration-resistant prostate cancer (mCRPC). The growing evidence needs further substantiation with long-term data. This study, the first to use German data, investigated cardiovascular (CV) event risk and overall survival (OS) in patients initiating ENZA or AA. AA (2012) and ENZA (2014) are widely used for mCRPC in Germany.</p><h3>Methods</h3><p>This retrospective study used data of chemotherapy-naïve patients with mCRPC on ENZA or AA (2012–2020) from two German claims databases (AOK PLUS and GWQ ServicePlus). The primary endpoint was time to first CV event (CV-related hospitalization) analyzed via a meta-analysis of Cox proportional hazard models of propensity score-matched (PSM) intention-to-treat cohorts. Other endpoints were baseline characteristics, CV event rate, number of CV events per patient, and OS.</p><h3>Results</h3><p>Of 2240 patients in the total study population (ENZA, 828; AA, 1412), 796 PSM patients were included in each group. ENZA patients were older and had a higher prevalence of some comorbidities, but without meaningful differences after PSM. Further, 386 patients had ≥ 1 CV event (ENZA, 172; AA, 214). ENZA was associated with a significantly lower risk of CV events (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.57–0.86, <i>p</i> = 0.001, <i>I</i>² = 0.0%), CV event rate (0.17 vs 0.23 per person-year; event rate ratio 0.75, 95% CI 0.61–0.92, <i>p</i> = 0.006; <i>I</i>² = 38.0%), fewer recurrent CV events (HR 0.77, 95% CI 0.61–0.96, <i>p</i> = 0.024; <i>I</i>² = 0.0%), and prolonged OS (HR 0.79, 95% CI 0.71–0.89, <i>p</i> &lt; 0.001) than AA.</p><h3>Conclusions</h3><p>The unmatched ENZA cohort had higher average age and more comorbidities than the AA cohort, but no meaningful differences were noted after PSM. ENZA was associated with a significantly lower risk of CV events and improved OS.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 4","pages":"1919 - 1934"},"PeriodicalIF":3.4,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03132-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First-Line Pembrolizumab Plus Chemotherapy for HER2-Negative Advanced Gastric Cancer: China Subgroup Analysis of the Randomized Phase 3 KEYNOTE-859 Study","authors":"Shukui Qin,&nbsp;Yuxian Bai,&nbsp;Jin Li,&nbsp;Hongming Pan,&nbsp;Suxia Luo,&nbsp;Yanli Qu,&nbsp;Feng Ye,&nbsp;Lin Yang,&nbsp;Tianshu Liu,&nbsp;Wei Li,&nbsp;Xi Chen,&nbsp;Jianwei Yang,&nbsp;Jieer Ying,&nbsp;Xiaoyan Lin,&nbsp;Lin Zhao,&nbsp;Xinjun Liang,&nbsp;Yixiang Mao,&nbsp;Run Guo,&nbsp;Yi Zuo,&nbsp;Sonal Bordia,&nbsp;Shouguo Li","doi":"10.1007/s12325-024-03069-4","DOIUrl":"10.1007/s12325-024-03069-4","url":null,"abstract":"<div><h3>Introduction</h3><p>Results of the global, randomized, phase 3 KEYNOTE-859 study (<i>N</i> = 1579) showed that first-line pembrolizumab plus chemotherapy produced a statistically significant and clinically meaningful improvement in overall survival (OS) with manageable toxicity versus placebo plus chemotherapy in patients with locally advanced or metastatic human epidermal growth factor receptor 2 (HER2)–negative gastric or gastroesophageal junction cancer. This subgroup analysis was conducted to investigate outcomes in patients enrolled in mainland China.</p><h3>Methods</h3><p>Adults with previously untreated advanced or metastatic HER2-negative gastric cancer or gastroesophageal junction adenocarcinoma were randomly assigned (1:1) to receive pembrolizumab or placebo with fluoropyrimidine- and platinum-containing chemotherapy. The primary outcome was OS. Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR), all assessed per RECIST v1.1 by blinded independent central review, and safety.</p><h3>Results</h3><p>Overall, 236 patients were enrolled in mainland China (126 pembrolizumab plus chemotherapy; 110 placebo plus chemotherapy). Median time from randomization to database cutoff (October 3, 2022) was 24.7 months (range 15.3–38.9). Median OS was 15.9 months (95% confidence interval [CI] 13.2–19.2) for pembrolizumab plus chemotherapy versus 12.2 months (95% CI 10.6–14.1) for placebo plus chemotherapy (hazard ratio [HR], 0.68; 95% CI 0.50–0.91). Median PFS was 8.1 months (95% CI 6.9–9.6) for pembrolizumab plus chemotherapy versus 5.7 months (95% CI 4.5–6.5) for placebo plus chemotherapy (HR, 0.65; 95% CI 0.48–0.88). ORR was 69.0% for pembrolizumab plus chemotherapy versus 45.5% for placebo plus chemotherapy; median DOR was 8.2 months (range 1.2+ to 34.6+) versus 5.5 months (range 1.3+ to 31.2+), respectively. Grade 3–5 treatment-related adverse events occurred in 82 patients (65.6%) treated with pembrolizumab plus chemotherapy and 54 patients (49.1%) treated with placebo plus chemotherapy.</p><h3>Conclusion</h3><p>Consistent with efficacy in the overall population from KEYNOTE-859, first-line pembrolizumab plus chemotherapy showed improved efficacy, versus placebo plus chemotherapy, and manageable safety in patients enrolled in mainland China.</p><h3>Trial Registration</h3><p>Clinicaltrials.gov: NCT03675737.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 4","pages":"1892 - 1906"},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-024-03069-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Experience with Luspatercept in Relapsed/Refractory Myelodysplastic Neoplasms: A Chinese Real-World Study","authors":"Zhuxin Zhang,&nbsp;Leyu Wang,&nbsp;Ziwei Liu,&nbsp;Chen Yang,&nbsp;Miao Chen,&nbsp;Bing Han","doi":"10.1007/s12325-025-03141-7","DOIUrl":"10.1007/s12325-025-03141-7","url":null,"abstract":"<div><h3>Introduction</h3><p>Luspatercept has been shown to be efficacious for patients with relapsed or refractory lower-risk myelodysplastic neoplasms (LR-MDS) in both clinical trials and real-world studies. Nevertheless, long-term follow-up data in real-world settings remain scarce, particularly in Asia.</p><h3>Methods</h3><p>Data from patients diagnosed with relapsed or refractory LR-MDS who had been treated with luspatercept at our center between June 2022 and May 2024 were retrospectively collected.</p><h3>Results</h3><p>In total, 60 patients were included in this study (63.4% males). The median duration of luspatercept exposure was 9 (range 3–25) months, and the median follow-up time was 15 (range 3–26) months. The hematologic improvement-erythroid (HI-E) rate was 46.7%, 51.0%, 48.6%, and 43.3% at the 3rd, 6th, and 12th months, and at the end of follow-up, respectively. Among patients who were transfusion-dependent prior to luspatercept, 48.3%, 38.7%, and 25.8% achieved transfusion independence for 8, 12, and 16 weeks or longer at the 6th month. Over time, patients treated with luspatercept had a significant increase in hemoglobin level compared with that of the baseline from the 1st month to the end of follow-up (all <i>P</i> &lt; 0.05). At the end of follow-up, 5 of 32 (15.6%) patients who had response had experienced a relapse, 1 patient (1.7%) had progressed to higher-risk myelodysplastic neoplasms (MDS), and 2 patients (3.3%) had progressed to acute myeloid leukemia. Three patients (5.0%) died of pulmonary infection. Serum erythropoietin (EPO) ≤ 500 IU/l at baseline was the only independent predictive factor for HI-E at the 3rd month (<i>P</i> = 0.007).</p><h3>Conclusion</h3><p>Luspatercept is proved efficacious and well tolerated in relapsed/refractory LR-MDS and appears to be beneficial in reducing disease progression and prolonging survival.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 4","pages":"1907 - 1918"},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient and Health Care Professional Perspectives on the Burden and Daily Life Impact of Ulcerative Colitis and Crohn’s Disease: Results from the Japanese CONFIDE Study","authors":"Toshifumi Hibi,&nbsp;Taku Kobayashi,&nbsp;Masaru Tanaka,&nbsp;Satoshi Osaga,&nbsp;Alison J. Potts Bleakman,&nbsp;Theresa Hunter Gibble,&nbsp;Marijana Nedeljkovic Protic,&nbsp;Isabel Redondo,&nbsp;Koji Matsuo,&nbsp;Tadakazu Hisamatsu","doi":"10.1007/s12325-024-03078-3","DOIUrl":"10.1007/s12325-024-03078-3","url":null,"abstract":"<div><h3>Introduction</h3><p>The global Communicating Needs and Features of Inflammatory Bowel Disease Experiences (CONFIDE) study aimed to evaluate the impact of ulcerative colitis (UC)- and Crohn’s disease (CD)-related symptoms on patients’ lives and elucidate communication gaps between patients and health care professionals (HCPs). We report the findings from the study in patients with UC or CD and HCPs in Japan.</p><h3>Methods</h3><p>Online, quantitative, cross-sectional surveys were conducted in Japan for patients with moderate-to-severe UC or CD and HCPs responsible for the care of patients with UC and/or CD. Subgroup analyses based on disease activity were conducted using the Manitoba Inflammatory Bowel Disease Index. Data were described using descriptive statistics.</p><h3>Results</h3><p>Surveys were completed by 124 patients with UC, 99 patients with CD, and 100 HCPs in Japan. Differences were noted in the most common patient-reported symptoms experienced in the month prior to survey completion between patients with UC and CD (diarrhea [45.2% UC, 68.7% CD], flatulence [34.7% UC, 32.3% CD], increased stool frequency [32.3% UC, 43.4% CD], bowel urgency [BU; 25.0% UC, 32.3% CD], and fatigue [36.4% CD]). More patients with active disease than inactive disease reported these symptoms. BU and BU-related accidents were among the symptoms ranked as most impactful by patients with UC and CD. HCP-perceived symptoms with the greatest impact on patients were diarrhea and blood in stool. Findings in the Japanese cohort of CONFIDE were generally consistent with those in the United States (US)/European cohorts. The percentage of patients reporting BU as the symptom with the greatest impact was higher in the US/European cohorts than in the Japanese cohort, potentially as a result of differences in baseline characteristics and social environments such as toilet facilities.</p><h3>Conclusion</h3><p>BU is an impactful symptom among Japanese patients with UC and CD and should be considered by HCPs during treatment of these conditions.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 4","pages":"1834 - 1859"},"PeriodicalIF":3.4,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-024-03078-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Southeast Asian, African, and Middle East Expert Consensus on Structured Physical Activity—Dance, Exercise, and Sports","authors":"Sarita Bajaj,&nbsp;Madhur Verma,&nbsp;Hanjabam Barun Sharma,&nbsp;Kaushik Ramaiya,&nbsp;Silver Bahendeka,&nbsp;Sanjay Kalra","doi":"10.1007/s12325-025-03148-0","DOIUrl":"10.1007/s12325-025-03148-0","url":null,"abstract":"<div><p>Physical inactivity (PIA) is a pressing public health issue globally, contributing significantly to the rise of non-communicable diseases (NCD), such as cardiovascular disease and type 2 diabetes. The World Health Organization emphasises the importance of regular physical activity (PA) for preventing and managing NCDs. Initiatives to promote active living have gained momentum, ranging from community programs to workplace wellness campaigns, all focused on reducing sedentary lifestyles in modern society. Structured Physical Activity—Dance, Exercise, and Sports (SPADES) has emerged as an innovative approach to addressing PIA and promoting holistic health. After thoroughly reviewing existing literature from PubMed and Google Scholar databases, a panel of experts developed consensus statements through in-depth discussions, and the strength of concurrence on these statements was voted on using a Likert scale. The panel reached a consensus on the best strategies for PA, dance, exercise, sports, and key factors to consider during PA. This consensus targets individuals with metabolic diseases, particularly in regions like South Asia, East Africa, the Gulf, and Latin America, where these conditions are highly prevalent. The SPADES guidelines emphasise overcoming the barriers people with metabolic disorders face in achieving adequate PA, providing tailored recommendations to improve health outcomes for this population.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 4","pages":"1692 - 1715"},"PeriodicalIF":3.4,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of a Value Framework to Determine the Value of Prophylaxis Versus On-Demand Treatment in Adults with Hemophilia A in China","authors":"Baoying Tan,&nbsp;Ailing Lin,&nbsp;Rong Han,&nbsp;Lu Bai,&nbsp;Jing Sun,&nbsp;Shanlian Hu,&nbsp;Jianwei Xuan","doi":"10.1007/s12325-025-03131-9","DOIUrl":"10.1007/s12325-025-03131-9","url":null,"abstract":"<div><h3>Introduction</h3><p>This study aimed to establish and apply a multicriteria value framework to determine the value of prophylaxis versus on‑demand treatment in adult patients with hemophilia A in China, which could enhance evidence-based care decisions.</p><h3>Methods</h3><p>The framework was developed using key literature to identify dimensions and indicators for assessing the value of hemophilia A. We interviewed 21 stakeholders—including clinical experts, medical insurance experts, health economics and outcomes research (HEOR) experts, charity organization representatives, and patient advocacy organization representatives—to evaluate the relative importance of indicators. The interviewees also assessed the value of prophylaxis and on-demand treatments for adults, providing justification for their ratings. The analytic hierarchy process (AHP) was employed to calculate the weight of each indicator based on stakeholder ratings. A linear additive value function was used to calculate total value scores. The main outcomes of the study include the weighted indicators of the value framework and the comprehensive value scores for different hemophilia A care strategies.</p><h3>Results</h3><p>The primary indicators in the value framework were clinical value, economic value, patient value, and social value. These were further broken down into nine secondary indicators. Overall, interviewees rated patient value highest (32.88%), followed by clinical value (30.08%), social value (22.25%), and economic value (14.79%). The adult prophylaxis strategy scored higher than on-demand treatment in all four primary value categories, with the largest difference observed in patient value. The total value score for adult prophylaxis (8.42) was higher than that for on-demand treatment (5.90), with an absolute difference of 2.52 (95% confidence interval [CI] 1.68–3.36).</p><h3>Conclusion</h3><p>The hemophilia value framework affirmed value of prophylaxis for adult patients with hemophilia A versus on-demand treatment, with benefit in terms of clinical value, economic value, patient value, and social value. The study also demonstrates that the value framework is an excellent tool for assisting stakeholders in decision-making that is grounded in patient-centered value in China.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 4","pages":"1881 - 1891"},"PeriodicalIF":3.4,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population Pharmacokinetics of Niraparib/Abiraterone Acetate Administered as Single-Agent Combination and Dual-Acting Tablets Plus Prednisone for Metastatic Castration-Resistant Prostate Cancer","authors":"Alberto Russu,&nbsp;Anasuya Hazra,&nbsp;Hui Tian,&nbsp;Nahor Haddish-Berhane,&nbsp;Juan Jose Perez Ruixo,&nbsp;Muriel Boulton","doi":"10.1007/s12325-025-03104-y","DOIUrl":"10.1007/s12325-025-03104-y","url":null,"abstract":"<div><h3>Introduction</h3><p>Use of niraparib and abiraterone acetate (AA; abiraterone prodrug) in patients with metastatic castration-resistant prostate cancer (mCRPC) targets two oncogenic drivers: homologous recombination repair (HRR) gene alterations and the androgen-receptor axis. Fixed-dose niraparib/AA combination is available as regular-strength dual-action tablets (RS-DAT; 200 mg/1000 mg) and low-strength DAT (LS-DAT; 100 mg/1000 mg, enabling niraparib dose reduction). We characterized the population pharmacokinetics (PPK) of niraparib and abiraterone, administered alone or in combination, in patients with mCRPC.</p><h3>Methods</h3><p>PPK modeling and covariate analysis using a non-linear mixed-effect modeling approach were conducted using pooled PK data from patients with mCRPC enrolled in the BEDIVERE (NCT02924766), GALAHAD (NCT02854436), QUEST (NCT03431350), and MAGNITUDE (NCT03748641) studies and in a study of relative bioavailability for LS-DAT and bioequivalence for RS-DAT. In all but GALAHAD (niraparib monotherapy), AA + prednisone was given alone or with niraparib. Overall, 9935 and 6289 niraparib and abiraterone plasma PK samples from 916 and 954 patients, respectively, were available.</p><h3>Results</h3><p>Niraparib and abiraterone PK were adequately described by an open two-compartment disposition model with linear elimination, with a zero-order rate of drug release into the depot compartment followed by first-order absorption (via two transit compartments for abiraterone) into the central compartment. For niraparib, identified covariates were creatinine clearance on apparent oral clearance; LS-DAT on zero-order drug-release duration and apparent oral bioavailability; HRR status on apparent oral clearance; race on first-order absorption-rate constant, intercompartmental clearance, and peripheral compartment volume of distribution. Covariate effects had no clinically relevant impact on niraparib exposure, warranting no dose adjustments. For abiraterone, RS-DAT was the only newly identified covariate on apparent oral bioavailability, first-order absorption-rate constant, and zero-order drug-release duration; however, effect magnitude was deemed not clinically relevant.</p><h3>Conclusion</h3><p>PPK analyses support the selected clinical dosage of RS-DAT (200-mg niraparib/1000-mg AA) plus 10-mg prednisone daily for treating patients with mCRPC and HRR gene alterations.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 4","pages":"1860 - 1880"},"PeriodicalIF":3.4,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparability of Randomized Controlled Trials Evaluating Pharmacological Interventions for Pemphigus Vulgaris and Pemphigus Foliaceus: A Systematic Mapping Review","authors":"Corinne Le Reun,&nbsp;Najeeda Yasmeen,&nbsp;Alexis E. Cullen,&nbsp;Laura Sawyer,&nbsp;Olga Ostrovskaya,&nbsp;Francesca Barion","doi":"10.1007/s12325-025-03118-6","DOIUrl":"10.1007/s12325-025-03118-6","url":null,"abstract":"<div><h3>Introduction</h3><p>Pemphigus diseases are a family of chronic, autoimmune, blistering skin conditions. Despite advances in treatment approaches, more effective and safer therapies for pemphigus are urgently needed. Trials investigating novel therapeutics must be designed to yield evidence that can be compared to existing data, necessitating a comprehensive understanding of the clinical trial landscape. We aimed to perform a mapping review to assess the comparability of randomized controlled trials (RCTs) evaluating existing treatments for pemphigus vulgaris (PV) and pemphigus foliaceous (PF).</p><h3>Methods</h3><p>Embase, MEDLINE, and Cochrane Library were systematically searched from inception to July 2023, supplemented with conference abstracts, clinical trial registries, and grey literature searches, for RCTs evaluating pharmacotherapies in adults with moderate-to-severe PV or PF. Comparability of study populations (demographic and clinical characteristics), interventions and comparators (dose, administration route, regimen), and outcomes (definition, time point, measure) across trials was assessed.</p><h3>Results</h3><p>Fifteen RCTs were eligible for inclusion. Substantial heterogeneity was observed in participant age, sex, and disease duration at baseline, and none of the studies used the same criteria to assess illness severity. Doses and regimens differed across trials assessing the same interventions. Across 16 outcome measures extracted, clinical remission outcomes had limited comparability across studies and were often not defined according to published guidelines. Cumulative corticosteroid dose during the study period had the highest comparability. Health-related quality of life data and serious adverse events were infrequently reported.</p><h3>Conclusions</h3><p>The lack of comparability across studies has major implications for developers of new treatments for PV and PF and for decision-makers who must evaluate the efficacy, safety, and cost-effectiveness of these treatments relative to existing therapeutics.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 4","pages":"1642 - 1691"},"PeriodicalIF":3.4,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astaxanthin (AstaReal®) Improved Acute and Chronic Digital Eye Strain in Children: A Randomized Double-Blind Placebo-Controlled Trial","authors":"Karen A. Hecht,&nbsp;Megha Marwah,&nbsp;Vincent Wood,&nbsp;Yasuhiro Nishida,&nbsp;Austin E. Bach,&nbsp;Jeffry Gerson,&nbsp;Milton M. Hom,&nbsp;Joerg Schnackenberg,&nbsp;Sonal Raote,&nbsp;Shalini Srivastava,&nbsp;Pankaj Negi,&nbsp;Eric Caston","doi":"10.1007/s12325-025-03125-7","DOIUrl":"10.1007/s12325-025-03125-7","url":null,"abstract":"<div><h3>Introduction</h3><p>This study assessed the effects of astaxanthin supplementation on chronic and acute digital eye strain in school-aged children (10–14 years) and evaluated its safety. While previous studies focused on adults, this study examined astaxanthin’s effects on developing eyes.</p><h3>Methods</h3><p>A randomized, double-blind, placebo-controlled trial was conducted over 84 days involving 64 children engaged in ≥ 4 h of screen time daily and experiencing mild to moderate computer vision syndrome (CVS) symptoms as indicated by a CVS-Questionnaire (CVS-Q) score ≥ 8 and &lt; 19. Participants received a daily 4-mg astaxanthin soft capsule for 84 days. Primary outcomes were measured using CVS-Q, while secondary outcomes included visual fatigue Likert scale (VFLS), visual acuity, spherical equivalence, near point of accommodation, near exophoria, dry eye intensity, pupil size, stereopsis, blinking frequency, immunity, and safety variables.</p><h3>Results</h3><p>Of the 64 participants (mean age 11.5–11.7 years), 35 were male and 29 were female. Astaxanthin supplementation significantly improved CVS-Q scores after 84 days (− 4.00 ± 4.05 arbitrary units (A.U.) from baseline, <i>p</i> &lt; 0.0001) compared to placebo (− 1.72 ± 3.61 A.U., <i>p</i> &lt; 0.05), a 20% between group difference. The mean VFLS scores were significantly lower in the astaxanthin group (11.55 ± 5.78 A.U.) compared to placebo (15.78 ± 7.12 A.U., <i>p</i> = 0.01), showing a 27% improvement after 84 days. Stereopsis improved significantly after acute visual load at 28 and 84 days (<i>p</i> &lt; 0.05, <i>p</i> &lt; 0.0001 vs. placebo, respectively), and pupillary light reflex improved after 84 days (<i>p</i> &lt; 0.05 vs. placebo). Tear production increased after 14, 56, and 84 days (<i>p</i> &lt; 0.05, <i>p</i> &lt; 0.001, and <i>p</i> &lt; 0.001 vs. baseline, respectively) in the astaxanthin group, with no significant intergroup difference in the Schirmer I test, visual acuity, spherical equivalence, near point of accommodation, near exphoria, immune markers, or safety variables.</p><h3>Conclusion</h3><p>Astaxanthin supplementation effectively reduced chronic and acute digital eye strain, while enhancing objective measures of visual performance in school-aged children, underscoring the benefits of astaxanthin in pediatric visual health and performance.</p><h3>Trial Registration</h3><p>NIH ClinicalTrials.gov (Identifier: NCT05602402); Clinical Trials Registry India (Registration Number: CTRI/2022/10/046606).</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 4","pages":"1811 - 1833"},"PeriodicalIF":3.4,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}