Advances in Therapy最新文献

{"title":"The Composite Number Needed to Treat for Semaglutide in Populations with Overweight or Obesity and Established Cardiovascular Disease Without Diabetes.","authors":"Christopher Lübker, Jigish Bhavsar, Ruben Duque do Vale, Scott S Emerson, Emil Nørtoft, Jorge Plutzky, Geraint Roberts, Jens Magelund Tarp, A Michael Lincoff","doi":"10.1007/s12325-025-03176-w","DOIUrl":"https://doi.org/10.1007/s12325-025-03176-w","url":null,"abstract":"<p><strong>Introduction: </strong>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><p><strong>Methods: </strong>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><p><strong>Results: </strong>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><p><strong>Conclusion: </strong>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>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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, Tsung-Ying Lee, Zachary Baldwin, Jens Kort, Masakazu Ando, Steven W Champaloux, Mena Boules, Yuri Sanchez Gonzalez","doi":"10.1007/s12325-025-03163-1","DOIUrl":"https://doi.org/10.1007/s12325-025-03163-1","url":null,"abstract":"<p><strong>Introduction: </strong>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><p><strong>Methods: </strong>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><p><strong>Results: </strong>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 > 1 demonstrated that patients who received lubiprostone versus linaclotide had significantly greater HCRU (P < 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 (P < 0.05).</p><p><strong>Conclusion: </strong>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>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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, Francesca Chiodi, Abby Paine, Zalmai Hakimi, Victoria Ward, Tom Macmillan, Daniel Eriksson, Silvia Mappa","doi":"10.1007/s12325-025-03169-9","DOIUrl":"https://doi.org/10.1007/s12325-025-03169-9","url":null,"abstract":"<p><strong>Introduction: </strong>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><p><strong>Methods: </strong>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><p><strong>Results: </strong>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><p><strong>Conclusion: </strong>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>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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, Gonzalo Fernández-Villar, Solange Martinez-Elhelou","doi":"10.1007/s12325-025-03154-2","DOIUrl":"https://doi.org/10.1007/s12325-025-03154-2","url":null,"abstract":"<p><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>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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, Vivek Charu, Richard J Glassock","doi":"10.1007/s12325-025-03167-x","DOIUrl":"https://doi.org/10.1007/s12325-025-03167-x","url":null,"abstract":"<p><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>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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, Franco Locatelli, Michael J Eckrich, Suzan Imren, Nanxin Li, Fengjuan Xuan, Stephan A Grupp","doi":"10.1007/s12325-025-03162-2","DOIUrl":"https://doi.org/10.1007/s12325-025-03162-2","url":null,"abstract":"<p><strong>Introduction: </strong>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><p><strong>Methods: </strong>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, L-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><p><strong>Results: </strong>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 L-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 > 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><p><strong>Conclusion: </strong>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 L-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>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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, Marcus Erdler, Margaret R Frey, Michael A Lopez","doi":"10.1007/s12325-025-03171-1","DOIUrl":"https://doi.org/10.1007/s12325-025-03171-1","url":null,"abstract":"<p><strong>Introduction: </strong>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><p><strong>Methods: </strong>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><p><strong>Results: </strong>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><p><strong>Conclusions: </strong>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. Graphical abstract available for this article.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mobility and Quality of Life in Adults with Paediatric-Onset Hypophosphatasia Treated with Asfotase Alfa: Results from UK Managed Access Agreement.","authors":"Katie E Moss, Richard Keen, Shona Fang, Alexandros Zygouras, Muhammad K Javaid, Tarekegn Geberhiwot, Kenneth E S Poole, Peter Selby, Jennifer S Walsh, Judith S Bubbear","doi":"10.1007/s12325-025-03168-w","DOIUrl":"https://doi.org/10.1007/s12325-025-03168-w","url":null,"abstract":"<p><strong>Introduction: </strong>Hypophosphatasia (HPP) is a rare disease caused by deficient tissue-non-specific alkaline phosphatase (ALP) activity. Asfotase alfa is a tissue-non-specific ALP enzyme-replacement therapy which was reimbursed in the UK under a Managed Access Agreement (MAA). This analysis assessed safety and effectiveness of asfotase alfa in adults with HPP.</p><p><strong>Methods: </strong>This prospective, observational data collection included adults with paediatric-onset HPP enroled in the MAA and treated with asfotase alfa for ≥ 6 months to 5 years. Assessments included mobility, pain, and health-related quality of life (HRQoL), each reported at regular intervals through year 3. Analgesic use, fractures, and events of interest (EOIs) were each reported continuously throughout follow-up.</p><p><strong>Results: </strong>Of 28 enroled treated adults, 24 were assessed for effectiveness. Distance walked in the 6-Minute Walk Test was median (min, max) 172.5 m (0.0, 380.0; n = 24) at baseline and improved by 157.3 m (- 171.0, 479.5; n = 16) at month 6; results were sustained throughout follow-up. Median (min, max) Bleck score was 6.0 (2.0, 9.0; n = 24) at baseline and increased to 6.5 (5.0, 9.0; n = 10) at month 36. Median (min, max) aggregate Brief Pain Inventory Short Form severity score was 8.0 (4.3, 10.0; n = 24) at baseline and improved to 4.4 (1.0, 7.8; n = 10) at month 36. During follow-up, 8 participants (33.3%) decreased or discontinued opioid use throughout follow-up and 4 (16.7%) reported fractures. Median (min, max) EQ-5D-3L utility scores improved from 0.21 (- 0.26, 0.60; n = 24) at baseline by 0.15 (- 0.36, 0.91; n = 24) at month 6 and were similar throughout follow-up. Injection site reactions were the most common treatment-related EOI, reported in 17 participants (60.7%). Three participants reported treatment-related serious adverse events.</p><p><strong>Conclusion: </strong>Asfotase alfa treatment improved mobility, physical function, pain, and HRQoL and was well tolerated. These data show the benefit of asfotase alfa in adults with paediatric-onset HPP.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727379","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":"Real-World Evidence for Baricitinib in the Treatment of Rheumatoid Arthritis in Spain: A Systematic Literature Review.","authors":"José Rosas, Joaquín Belzunegui, Blanca Hernández-Cruz, Itxaso Aguirregabiria, Sebastián Moyano, Amelia Cobo, Silvia Díaz-Cerezo","doi":"10.1007/s12325-025-03161-3","DOIUrl":"https://doi.org/10.1007/s12325-025-03161-3","url":null,"abstract":"<p><strong>Introduction: </strong>Baricitinib is a Janus kinase inhibitor approved for the treatment of moderate-to-severe rheumatoid arthritis (RA) in adults who have responded inadequately, or are intolerant, to disease-modifying antirheumatic drugs (DMARDs). This systematic literature review was conducted to understand the use of baricitinib in RA in the real-world setting in Spain.</p><p><strong>Methods: </strong>Embase and MEDLINE databases were systematically searched for publications (in English or Spanish) published between March 2017 and June 2023; Spanish data presented at national rheumatology congresses were also obtained, with a date limitation of 2021-2023.</p><p><strong>Results: </strong>Nineteen eligible publications were identified (5 full papers, 14 conference abstracts), including more than 1000 patients who received baricitinib for RA in Spain. Most patients were older and female with long disease duration, and moderate-to-severe active disease. Studies included both biologic DMARD-experienced and DMARD-naïve patients, and most patients received baricitinib 4 mg/day. Baricitinib persistence ranged from 6 to 48 months, with ineffectiveness (primary or secondary) being the most frequently reported reason for discontinuation. Baricitinib was consistently shown to decrease disease activity, across all outcome measures (Disease Activity Score-28 for RA, the Simplified and Clinical Disease Activity Indexes, swollen and tender joint counts and patient-reported outcomes). Thirteen studies reported safety outcomes, with discontinuation rates due to adverse events ranging from 9.5 to 20%. Across these studies, adverse events of interest included eleven cases of herpes zoster, six serious infections, two major adverse cardiovascular events, and three malignant neoplasms.</p><p><strong>Conclusion: </strong>These results suggest baricitinib is effective in the real-world setting in Spain, with a consistent safety profile, similar to findings reported in clinical studies and in real-world studies conducted in other countries.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690677","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":"Pembrolizumab in Patients of Chinese Descent with Microsatellite Instability-high/Mismatch Repair Deficient Advanced Solid Tumors: KEYNOTE-158 Final Analysis.","authors":"Xiaohua Wu, Yimin Mao, Nong Xu, Yuxian Bai, Dong Wang, Xiaojun Chen, Xianli Yin, Yanhong Deng, Jianwei Yang, Jieqing Zhang, Jie Tang, Yi Huang, Jiayi Li, Suxia Luo, Hong Zheng, Weidong Zhao, Miaomiao Xu, Nan Li, Yixiang Mao, Alexander Gozman, Jianming Xu","doi":"10.1007/s12325-025-03142-6","DOIUrl":"https://doi.org/10.1007/s12325-025-03142-6","url":null,"abstract":"<p><strong>Introduction: </strong>KEYNOTE-158 (NCT02628067) supported the US Food and Drug Administration approval of pembrolizumab for microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) advanced solid tumors. Incidence of MSI-H/dMMR tumors in patients of Chinese descent is similar to that of Western populations. Cohort L of KEYNOTE-158 evaluated pembrolizumab in patients of Chinese descent with previously treated MSI-H/dMMR tumors. We previously reported an objective response rate (ORR) of 70% in 20 patients from cohort L which supported the approval in China of pembrolizumab in patients with MSI-H/dMMR solid tumors. Here we present results of the final analysis for 30 patients with median follow-up of 18 months.</p><p><strong>Methods: </strong>Eligible patients who had confirmed unresectable or metastatic MSI-H/dMMR tumors, and one or more prior lines of therapy, received 200 mg pembrolizumab Q3W (up to 35 cycles) until progression, toxicity, or withdrawal. Primary endpoint was ORR per RECIST 1.1 by central review. Secondary endpoints were duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.</p><p><strong>Results: </strong>Thirty patients were enrolled; 7 (23%) were aged ≥ 65 years, and 20 (67%) were female. With median follow-up of 18 months, ORR was 66.7%. Median DOR was not reached (NR), with 12-month DOR rate of 85.9%. Median PFS was NR, with 18-month PFS rate of 63.0%. Median OS was NR, with 18-month OS rate of 78.8%. Treatment-related adverse events (AE) were reported in 22 (73%) patients. Grade 3-4 treatment-related AEs occurred in 7 (23%) patients. Immune-mediated AEs occurred in 11 (37%) patients of which 2 (7%) had grade 3 AEs. No grade ≥ 4 immune-mediated AEs occurred.</p><p><strong>Conclusion: </strong>Pembrolizumab continues to provide clinically meaningful antitumor activity and durable responses with a manageable safety profile in patients of Chinese descent with MSI-H/dMMR advanced solid tumors. These results are consistent with those reported for patients in the global population and further support the use of pembrolizumab in patients of Chinese descent with MSI-H/dMMR tumors. TRIAL REGISTRATION NUMBER: NCT02628067.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690721","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}