Advances in Therapy最新文献

{"title":"Baseline Characteristics and Treatment Patterns of Patients with Atopic Dermatitis Treated with Oral Systemic Therapies: An Interim Analysis of the AD-REAL Study","authors":"Matthias Augustin,&nbsp;Esther Serra-Baldrich,&nbsp;Julien Seneschal,&nbsp;Susanne Grond,&nbsp;Anastasia Lampropoulou,&nbsp;Mohamed Elrayes,&nbsp;Samuel Ogwu,&nbsp;Inmaculada de la Torre,&nbsp;Anthony Bewley,&nbsp;Andreas Pinter","doi":"10.1007/s12325-025-03137-3","DOIUrl":"10.1007/s12325-025-03137-3","url":null,"abstract":"<div><h3>Introduction</h3><p>AD-REAL is an ongoing 1-year multinational observational cohort study evaluating oral systemic therapies in the management of adults with atopic dermatitis (AD) in a real-world practice across four European countries. Herein, we provide insights on baseline disease characteristics and treatment patterns of patients treated with oral systemic therapies, including baricitinib.</p><h3>Methods</h3><p>AD-REAL included adults with moderate-to-severe AD for ≥ 6 months, who were initiated on an oral systemic treatment in clinical practice and enrolled either in the baricitinib or the other oral systemic (OOS) cohort. Here, we report baseline characteristics, including clinician-assessed outcomes (Eczema Area and Severity Index [EASI]) and patient-reported outcomes (PROs), and explore AD subgroups based on body surface area (BSA) ≤ 40% and Itch numerical rating scale (NRS) ≥ 7. Continuous outcomes were reported using mean and standard deviation (SD) and categorical variables using frequencies. Baseline continuous variables with missing data were imputed using the multiple imputation method.</p><h3>Results</h3><p>Baseline demographics were consistent across both baricitinib and OOS cohorts. Patients showed long disease duration (26.2 years), refractory to several systemic options, and a moderate EASI mean (SD) score of 17.5 (10.7). The majority (53.7%) presented with severe Validated Investigator Global Assessment (vIGA) and highly impacted Dermatology Life Quality Index (DLQI) score (14.0 [7.1]). At baseline, patients were predominantly female, with AD mainly affecting face/neck (89.4%) and upper extremities (90.3%). About 68.4% presented with BSA ≤ 40 and 33.8% with BSA ≤ 40 and Itch NRS ≥ 7. From those with BSA ≤ 40% and Itch NRS ≥ 7, 63.9% were treated with Janus kinase inhibitors (JAKi).</p><h3>Conclusion</h3><p>This analysis provides key information on baseline disease characteristics of patients treated with oral systemics, including baricitinib. Most patients treated with oral systemics in AD-REAL had long-lasting disease, refractory to systemic therapies, with moderate skin affectation but severe itch and impact on quality of life. AD-REAL is the first study to show many patients in real-world practice who are treated with oral systemics present with BSA ≤ 40 and Itch NRS ≥ 7, and most of these patients were treated with JAKi.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 6","pages":"2728 - 2738"},"PeriodicalIF":3.4,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03137-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794430","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":"Validation of an Administrative Claims-based Line of Therapy Algorithm for Women with Ovarian Cancer Using Medical Chart Review","authors":"Daniel Simmons,&nbsp;John White,&nbsp;Valery Walker,&nbsp;Stephanie V. Blank,&nbsp;Jiefen Munley,&nbsp;Kimmie McLaurin","doi":"10.1007/s12325-025-03174-y","DOIUrl":"10.1007/s12325-025-03174-y","url":null,"abstract":"<div><h3>Introduction</h3><p>New maintenance therapies to treat advanced ovarian cancer have added complexity to identifying lines of therapy (LOTs) for real-world evidence (RWE) studies. This study evaluated the performance of a claims-based algorithm that identifies LOTs among patients with ovarian cancer using medical chart review validation.</p><h3>Methods</h3><p>The algorithm was developed previously utilizing the Optum Research Database (ORD), a US database that contains administrative claims data. To validate the algorithm, LOT results generated using claims data vs chart data were compared at the patient level by calculating the percent agreement between total number of active and maintenance LOTs, type of therapy (neoadjuvant vs adjuvant classification), and type of regimen (individual drugs). Patients with a diagnosis of ovarian cancer who initiated chemotherapy between December 1, 2014, and September 15, 2017, were included in the study. We report descriptive statistics, the percentage correspondence between medical records and claims data, and kappa statistics to measure the magnitude of agreement.</p><h3>Results</h3><p>A total of 294 patients were included in the analysis; 164 received only chemotherapy and no maintenance, 77 received bevacizumab, and 53 patients received poly (ADP-ribose) polymerase inhibitors (PARPi). Mean age was 64.9 years, and 47.3% had stage III cancer. The algorithm demonstrated substantial agreement between claims and medical records for total number of lines of active and maintenance therapy (weighted kappa 0.65 and 0.62 <i>p</i> &lt; 0.0001). There was moderate-to-substantial agreement for neoadjuvant and adjuvant therapy (kappa 0.56 and 0.62 <i>p</i> &lt; 0.0001). The algorithm performed best at identifying early treatment with a regimen match of 82% and 88% agreement for first-line active and first-line maintenance, respectively.</p><h3>Conclusion</h3><p>We validated an administrative claims-based algorithm that demonstrates strong concordance with medical records for identifying LOT among patients with ovarian cancer. The algorithm can be applied in future studies to analyze treatment patterns and outcomes.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 6","pages":"2754 - 2766"},"PeriodicalIF":3.4,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03174-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794490","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":"Evinacumab for Homozygous Familial Hypercholesterolemia: The Italian Cohort of the ELIPSE HoFH Study","authors":"Gabriella Iannuzzo,&nbsp;Ilenia Calcaterra,&nbsp;Marco Gentile,&nbsp;Claudia Stanzione,&nbsp;Francesca De Ruberto,&nbsp;Maria Donata Di Taranto,&nbsp;Giuliana Fortunato,&nbsp;Matteo Di Minno","doi":"10.1007/s12325-025-03160-4","DOIUrl":"10.1007/s12325-025-03160-4","url":null,"abstract":"<div><h3>Introduction</h3><p>Homozygous familial hypercholesterolemia (HoFH) is a severe rare genetic disorder characterized by elevated plasma low-density lipoprotein (LDL) cholesterol levels. Here, we report data from the Italian cohort of the Evinacumab Lipid Studies in Patients with Homozygous Familial Hypercholesterolemia (ELIPSE HoFH) trial.</p><h3>Methods</h3><p>ELIPSE HoFH was conducted at 30 sites in 11 countries, with 2–10 patients enrolled per country. The study included patients aged ≥ 12 years with LDL cholesterol ≥ 70 mg/dl (1.8 mmol per liter) at screening despite stable maximally tolerated lipid-lowering therapy. Patients were randomly assigned evinacumab (15 mg/kg every 4 weeks) or matching placebo for 24 weeks, with an option for a 24-week open-label extension or follow-up period thereafter. The Italian cohort included seven patients assigned to evinacumab.</p><h3>Results</h3><p>Five patients (3 males and 2 females) received evinacumab and were included in this report. Substantial and consistent reductions in LDL cholesterol from baseline levels were observed in all patients at all follow-up time points. Overall, an 84.5% decrease in median (range) LDL cholesterol was observed, from 323 (203–587) mg/dl in 2016 to 50.0 (13–103) mg/dl (<i>P</i> = 0.043) in 2019, with LDL cholesterol levels stable through 2023. Total cholesterol, high-density lipoprotein (HDL) cholesterol, non-HDL cholesterol, and triglycerides decreased markedly over time. Evinacumab was well tolerated, with no treatment-related adverse events reported.</p><h3>Conclusion</h3><p>Evinacumab substantially lowered LDL cholesterol levels in patients with HoFH regardless of the degree of LDL receptor function, with low levels sustained over 5 years of follow-up.</p><h3>Trial Registration</h3><p>ClinicalTrials.gov identifier NCT03399786 registered 16 January 2018.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 5","pages":"2465 - 2479"},"PeriodicalIF":3.4,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03160-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762787","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":"The Composite Number Needed to Treat for Semaglutide in Populations with Overweight or Obesity and Established Cardiovascular Disease Without Diabetes","authors":"Christopher Lübker,&nbsp;Jigish Bhavsar,&nbsp;Ruben Duque do Vale,&nbsp;Scott S. Emerson,&nbsp;Emil Nørtoft,&nbsp;Jorge Plutzky,&nbsp;Geraint Roberts,&nbsp;Jens Magelund Tarp,&nbsp;A. Michael Lincoff","doi":"10.1007/s12325-025-03176-w","DOIUrl":"10.1007/s12325-025-03176-w","url":null,"abstract":"<div><h3>Introduction</h3><p>Number needed to treat (NNT), an outcome measure derived from the estimated risk results of clinical trials, is widely used to demonstrate value to stakeholders by identifying how many patients require treatment to avoid one event of interest. However, NNTs calculated for primary trial endpoints may underestimate a treatment’s value by not considering other outcomes. In this secondary analysis of data from the SELECT cardiovascular (CV) outcomes trial, we aimed to determine the NNT for semaglutide for major adverse cardiovascular events (MACE), in addition to NNTs when other clinically and payer-relevant outcomes are included.</p><h3>Methods</h3><p>This study is a secondary analysis of data from the randomized, double-blind SELECT trial (ClinicalTrials.gov NCT03574597) of once-weekly subcutaneous administration of semaglutide compared with placebo in 17,604 patients with overweight or obesity and with established cardiovascular disease (CVD) (39.8 months mean follow-up). The outcomes were NNT_3P-MACE (based upon the trial’s composite primary endpoint of death from cardiovascular causes, non-fatal myocardial infarction, non-fatal stroke), NNT_EXTENDED (inclusive of NNT_3P-MACE, hospitalization for any cause, coronary revascularization, and non-CV death), and NNT_CKM (inclusive of NNT_EXTENDED, glycated hemoglobin level [HbA_1c] ≥ 6.5%, and a 5-point nephropathy composite).</p><h3>Results</h3><p>The relative risk reductions observed for the events comprising the NNTs were 20% (NNT_3P-MACE), 20% (NNT_EXTENDED), and 41% (NNT_CKM). At 1 and 4 years post initiation of semaglutide, NNT_3P-MACE was 125 and 58, NNT_EXTENDED was 49 and 25, and NNT_CKM was 20 and 11, respectively.</p><h3>Conclusion</h3><p>When clinically and payer-relevant outcomes from the SELECT trial are included in calculations of NNT, semaglutide was associated with greater risk reductions and lower estimates of NNT than for the primary endpoint alone. Our findings suggest that including the broader effects of semaglutide beyond the primary trial endpoint recognizes additional value to stakeholders.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 5","pages":"2513 - 2525"},"PeriodicalIF":3.4,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03176-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741711","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":"Healthcare Utilization and Costs of Care in Patients With Irritable Bowel Syndrome With Constipation or Chronic Idiopathic Constipation After Initiating Oral Therapies: Real-World Analysis in the US Medicare Population","authors":"Eric Shah,&nbsp;Tsung-Ying Lee,&nbsp;Zachary Baldwin,&nbsp;Jens Kort,&nbsp;Masakazu Ando,&nbsp;Steven W. Champaloux,&nbsp;Mena Boules,&nbsp;Yuri Sanchez Gonzalez","doi":"10.1007/s12325-025-03163-1","DOIUrl":"10.1007/s12325-025-03163-1","url":null,"abstract":"<div><h3>Introduction</h3><p>Irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) are common functional intestinal disorders which impact all age groups, yet there is limited comparative evidence on the economic benefits of treatment of these conditions on the elderly. We assessed differences in healthcare resource utilization (HCRU) and total costs of care among Medicare-insured patients initiating linaclotide, lubiprostone, or plecanatide after 1 year.</p><h3>Methods</h3><p>Retrospective analysis from the Merative™ MarketScan^® Medicare Database (January 2017–September 2023), including adult patients who initiated a qualifying IBS-C/CIC medication (linaclotide, lubiprostone, plecanatide) (index date defined as date of initiation) and had at least 6 months of pre-index and 12 months of post-index continuous benefit coverage under fee-for-service Medicare plans. For HCRU and all-cause total cost (medical + pharmacy) outcomes, 12-month comparisons were characterized via count (for HCRU) or cost ratios between linaclotide and lubiprostone, and linaclotide and plecanatide. Generalized linear regression models adjusting for key baseline patient characteristics and 6-month pre-index HCRU and cost were used to estimate differences in outcomes at 12 months between treatment groups.</p><h3>Results</h3><p>A total of 7916 Medicare patients were included in the analysis, of whom 5773 initiated linaclotide, 1856 initiated lubiprostone, and 287 initiated plecanatide. After adjusting for key patient characteristics and pre-index HCRU, count ratios &gt; 1 demonstrated that patients who received lubiprostone versus linaclotide had significantly greater HCRU (<i>P</i> &lt; 0.05) at 12 months. After 12 months follow-up, adjusted all-cause total costs of care were significantly lower among patients who received linaclotide versus lubiprostone or plecanatide, largely driven by lower all-cause medical costs observed in patients who received linaclotide (<i>P</i> &lt; 0.05).</p><h3>Conclusion</h3><p>These findings suggest that linaclotide treatment may be associated with lower total healthcare costs compared to lubiprostone and plecanatide for patients initiating IBS-C/CIC-related drugs in Medicare populations.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 5","pages":"2500 - 2512"},"PeriodicalIF":3.4,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03163-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735535","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":"Loncastuximab Tesirine Versus Polatuzumab Vedotin Plus Bendamustine and Rituximab in Relapsed/Refractory DLBCL After ≥ 2 Lines of Therapy: Matching-Adjusted Indirect Comparison","authors":"Koo Wilson,&nbsp;Francesca Chiodi,&nbsp;Abby Paine,&nbsp;Zalmai Hakimi,&nbsp;Victoria Ward,&nbsp;Tom Macmillan,&nbsp;Daniel Eriksson,&nbsp;Silvia Mappa","doi":"10.1007/s12325-025-03169-9","DOIUrl":"10.1007/s12325-025-03169-9","url":null,"abstract":"<div><h3>Introduction</h3><p>Despite recent approvals of new treatments, relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) remains challenging to treat, with limited durable responses and a high proportion of patients relapsing after two or more lines of therapy. Loncastuximab tesirine (Lonca) is a highly potent CD19-targeted antibody drug conjugate with convenient dosing for patients with third-line R/R DLBCL.</p><h3>Methods</h3><p>In the absence of head-to-head trials, unanchored matching-adjusted indirect comparisons (MAICs) were conducted to compare the relative efficacy and safety of Lonca with polatuzumab vedotin + bendamustine and rituximab (Pola + BR).</p><h3>Results</h3><p>Four studies included in the MAICs were identified via systematic review and hand-searching. Lonca (LOTIS-2) was compared with three comparator studies for Pola + BR (GO29365 extension study, COTA database, Dal et al. 2023). Overall, there was no evidence of a difference in overall response and complete response (CR) rates. Despite Pola + BR demonstrating a higher CR rate in the GO29365 extension study, this did not translate into significant improvements in progression-free or overall survival. Survival analyses indicated similar efficacy between treatments across studies, with most comparisons/meta-analyses showing no statistically significant differences. Lonca had significantly lower odds of Grade 3–4 infections, any serious adverse event (SAE), and specific SAEs including febrile neutropenia, pneumonia and pyrexia. Of the safety endpoints analyzed, none indicated significant differences in favor of Pola + BR.</p><h3>Conclusion</h3><p>These results suggest no evidence of a difference in efficacy between the two treatments and potentially more favorable safety profile for Lonca compared with Pola + BR in patients with R/R DLBCL after two or more lines of treatment.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 5","pages":"2445 - 2464"},"PeriodicalIF":3.4,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03169-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735536","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":"Management of Atherosclerotic Cardiovascular Risk in Inflammatory Bowel Disease: Current Perspectives","authors":"Walter Masson,&nbsp;Gonzalo Fernández-Villar,&nbsp;Solange Martinez-Elhelou","doi":"10.1007/s12325-025-03154-2","DOIUrl":"10.1007/s12325-025-03154-2","url":null,"abstract":"<div><p>Inflammatory bowel disease (IBD) is a complex condition characterized by inflammation of the gastrointestinal system, encompassing Crohn’s disease and ulcerative colitis. Patients diagnosed with IBD have an increased risk of atherosclerotic cardiovascular disease. This heightened risk can be attributed to a combination of mechanisms, including traditional risk factors, chronic inflammation, intestinal dysbiosis, increased risk of thrombosis, and the use of certain medications such as corticosteroids. There are significant gaps in current knowledge, particularly regarding the management of risk factors and the use of medications for cardiovascular disease prevention. Similarly, the cardiovascular effects of specific IBD therapies, particularly the newer ones, are not yet fully understood. This review focuses on the epidemiological evidence linking IBD with cardiovascular risk factors and cardiovascular disease. It describes the potential pathophysiological mechanisms underlying this association and examines the challenges involved in accurately assessing cardiovascular risk in these patients, including the utility of complementary tools such as subclinical atherosclerosis detection. Additionally, we consider the potential therapeutic implications for managing these patients. Finally, this review also underscores the importance of multidisciplinary collaboration. Effective teamwork among gastroenterologists, cardiologists, and general practitioners is essential for providing comprehensive care to patients with IBD.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 5","pages":"2118 - 2134"},"PeriodicalIF":3.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03154-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717812","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":"Expert Discussion on Immune Complex-Mediated Membranoproliferative Glomerulonephritis: Challenges and Considerations","authors":"Richard A. Lafayette,&nbsp;Vivek Charu,&nbsp;Richard J. Glassock","doi":"10.1007/s12325-025-03167-x","DOIUrl":"10.1007/s12325-025-03167-x","url":null,"abstract":"<div><p>Immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) is a rare pattern of kidney injury and a progressive nephropathy characterized by the glomerular deposition of immune complexes and complement proteins. The IC-MPGN pattern of injury exhibits a membranoproliferative glomerulonephritis appearance by light microscopy and occurs secondary to various conditions or, more rarely, idiopathically, when no underlying etiology can be determined. Kidney biopsy is the only method for identifying IC-MPGN, distinguishing between IC-MPGN and complement 3 glomerulopathy (C3G), and for providing critical pathologic insights that guide further clinical evaluation for underlying etiologies and inform patient management. Given the progressive nature of IC-MPGN, it is crucial to identify patients early and to define the underlying pathophysiology for timely and appropriate treatment. However, several challenges remain in the accurate interpretation of kidney biopsy specimens and the effective treatment of idiopathic disease. In this commentary, two nephrologists and a nephropathologist review best practices in the clinical and histopathologic evaluation of IC-MPGN and discuss the central role of kidney biopsy in the differentiation of IC-MPGN and C3G. The challenges and considerations discussed are explored through an illustrative case of idiopathic disease, drawn from the authors' clinical experiences. Finally, remaining unmet needs are highlighted, and future perspectives on targeted treatments under investigation for patients with idiopathic IC-MPGN are provided.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 5","pages":"2003 - 2014"},"PeriodicalIF":3.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03167-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717786","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":"Impact of Different Definitions of Vaso-Occlusion on Efficacy Assessments in Sickle Cell Disease Clinical Trials","authors":"Haydar Frangoul,&nbsp;Franco Locatelli,&nbsp;Michael J. Eckrich,&nbsp;Suzan Imren,&nbsp;Nanxin Li,&nbsp;Fengjuan Xuan,&nbsp;Stephan A. Grupp","doi":"10.1007/s12325-025-03162-2","DOIUrl":"10.1007/s12325-025-03162-2","url":null,"abstract":"<div><h3>Introduction</h3><p>Patients with sickle cell disease (SCD) experience recurrent, severe pain events due to vaso-occlusion. Eliminating these acute pain events is a key outcome in SCD clinical trials; however, the definition of a vaso-occlusive crisis (VOC) or a vaso-occlusive event (VOE) has not been consistently applied, hampering comparisons of treatment efficacy between different therapeutic approaches. We have examined the degree to which differing definitions of vaso-occlusion in clinical trial endpoints impact efficacy outcomes.</p><h3>Methods</h3><p>Descriptions of clinical endpoints related to vaso-occlusion and pain events were reviewed from trials of exagamglogene autotemcel (exa-cel), lovotibeglogene autotemcel (lovo-cel), renizgamglogene autogedtemcel (reni-cel), hydroxyurea, <span>l</span>-glutamine, voxelotor, and crizanlizumab. Patient-level data from the published exa-cel Phase 3 pivotal trial (CLIMB SCD-121; data cut 14 Jun 2023) was used to evaluate efficacy outcomes based on differing endpoint definitions of vaso-occlusion.</p><h3>Results</h3><p>In the seven clinical trials reviewed, definitions of vaso-occlusion and/or pain events varied by care setting, duration of care, treatments used, and associated complications, with the frequency and duration of medical facility visits for acute pain events being most dissimilar between trials. Definitions of severe VOCs (exa-cel), VOC (voxelotor), and sickle cell-related pain crises (SCPCs; crizanlizumab and <span>l</span>-glutamine) included pain events requiring a medical facility visit of any duration, whereas the definition of painful crises (hydroxyurea) required a medical facility visit of &gt; 4 h and the definition of severe vaso-occlusive events (VOEs; lovo-cel and reni-cel) required a hospital or emergency room (ER) observation unit visit lasting ≥ 24 h or ≥ 2 visits to a day unit or ER over a 72-h period. Based on the definition of severe VOCs, 29/30 patients [96.7%; 95% confidence interval (CI): 82.8, 99.9] in the CLIMB SCD-121 trial were considered free from severe VOCs for ≥ 12 consecutive months, whereas when the severe VOEs definition was applied to the same data, all patients (30/30; 100.0%; 95% CI: 88.4, 100.0) were considered free from severe VOEs for ≥ 12 consecutive months.</p><h3>Conclusion</h3><p>Differences exist in definitions of vaso-occlusion and pain events used in SCD clinical trials. Severe VOCs (exa-cel), VOC (voxelotor), and SCPCs (crizanlizumab and <span>l</span>-glutamine) were more broadly inclusive than severe VOEs (lovo-cel and reni-cel) or painful crisis (hydroxyurea). Clinically, these differences resulted in differing numbers of patients being considered free from vaso-occlusion pain events, underscoring the challenge in comparing frequencies of pain events across SCD clinical trials.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 5","pages":"2490 - 2499"},"PeriodicalIF":3.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03162-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717810","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":"Fertility Outcomes in Risdiplam-Treated Male Patients with Spinal Muscular Atrophy: A Multicenter Case Series","authors":"Shelley Coskery,&nbsp;Marcus Erdler,&nbsp;Margaret R. Frey,&nbsp;Michael A. Lopez","doi":"10.1007/s12325-025-03171-1","DOIUrl":"10.1007/s12325-025-03171-1","url":null,"abstract":"<div><h3>Introduction</h3><p>Spinal muscular atrophy (SMA) is a genetic, progressive neuromuscular disease caused by pathogenic variants in the survival of motor neuron survival of motor neuron (SMN) 1 gene leading to a deficiency in SMN protein. Three disease-modifying therapies are available for the treatment of SMA, affording many with the opportunity for family planning. Fertility outcomes in patients with SMA treated with risdiplam have not been previously reported.</p><h3>Methods</h3><p>This study was a multicenter, non-interventional retrospective case review that included three adult male patients with SMA from three sites in Austria and the USA. The primary objective was to characterize the reproductive history and fertility journey of men with SMA who were exposed to risdiplam and whose partner had conceived.</p><h3>Results</h3><p>Three male patients aged 21–34 years with late-onset SMA were taking risdiplam during the window of conception. Of the three resultant pregnancies, two were full term and resulted in healthy babies and one was voluntarily terminated. The babies were healthy and developing normally.</p><h3>Conclusions</h3><p>This series presents three cases of successful conception while a male patient was receiving risdiplam, a US Food and Drug Administration–approved treatment for SMA. Although there were reproductive concerns due to impairment in spermatogenesis that arose during nonclinical studies, this case series demonstrates that there was sufficient sperm production while on risdiplam to result in pregnancy. More research is needed to provide a complete understanding of the effects of risdiplam on male fertility in humans.</p><p>Graphical abstract available for this article.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 5","pages":"2526 - 2536"},"PeriodicalIF":3.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03171-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717787","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}