Advances in Therapy最新文献

{"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}

{"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,&nbsp;Richard Keen,&nbsp;Shona Fang,&nbsp;Alexandros Zygouras,&nbsp;Muhammad K. Javaid,&nbsp;Tarekegn Geberhiwot,&nbsp;Kenneth E. S. Poole,&nbsp;Peter Selby,&nbsp;Jennifer S. Walsh,&nbsp;Judith S. Bubbear","doi":"10.1007/s12325-025-03168-w","DOIUrl":"10.1007/s12325-025-03168-w","url":null,"abstract":"<div><h3>Introduction</h3><p>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><h3>Methods</h3><p>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><h3>Results</h3><p>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; <i>n</i> = 24) at baseline and improved by 157.3 m (− 171.0, 479.5; <i>n</i> = 16) at month 6; results were sustained throughout follow-up. Median (min, max) Bleck score was 6.0 (2.0, 9.0; <i>n</i> = 24) at baseline and increased to 6.5 (5.0, 9.0; <i>n</i> = 10) at month 36. Median (min, max) aggregate Brief Pain Inventory Short Form severity score was 8.0 (4.3, 10.0; <i>n</i> = 24) at baseline and improved to 4.4 (1.0, 7.8; <i>n</i> = 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; <i>n</i> = 24) at baseline by 0.15 (− 0.36, 0.91; <i>n</i> = 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><h3>Conclusion</h3><p>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></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 5","pages":"2429 - 2444"},"PeriodicalIF":3.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03168-w.pdf","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":"OA","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,&nbsp;Joaquín Belzunegui,&nbsp;Blanca Hernández-Cruz,&nbsp;Itxaso Aguirregabiria,&nbsp;Sebastián Moyano,&nbsp;Amelia Cobo,&nbsp;Silvia Díaz-Cerezo","doi":"10.1007/s12325-025-03161-3","DOIUrl":"10.1007/s12325-025-03161-3","url":null,"abstract":"<div><h3>Introduction</h3><p>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><h3>Methods</h3><p>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><h3>Results</h3><p>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><h3>Conclusion</h3><p>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></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 5","pages":"2403 - 2428"},"PeriodicalIF":3.4,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03161-3.pdf","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":"OA","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,&nbsp;Yimin Mao,&nbsp;Nong Xu,&nbsp;Yuxian Bai,&nbsp;Dong Wang,&nbsp;Xiaojun Chen,&nbsp;Xianli Yin,&nbsp;Yanhong Deng,&nbsp;Jianwei Yang,&nbsp;Jieqing Zhang,&nbsp;Jie Tang,&nbsp;Yi Huang,&nbsp;Jiayi Li,&nbsp;Suxia Luo,&nbsp;Hong Zheng,&nbsp;Weidong Zhao,&nbsp;Miaomiao Xu,&nbsp;Nan Li,&nbsp;Yixiang Mao,&nbsp;Alexander Gozman,&nbsp;Jianming Xu","doi":"10.1007/s12325-025-03142-6","DOIUrl":"10.1007/s12325-025-03142-6","url":null,"abstract":"<div><h3>Introduction</h3><p>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><h3>Methods</h3><p>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><h3>Results</h3><p>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><h3>Conclusion</h3><p>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.</p><h3>Trial Registration Number</h3><p>NCT02628067.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 5","pages":"2480 - 2489"},"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}

{"title":"Point of Care Nucleic Acid Testing for Influenza-Like Illness: A Cost–Consequence Analysis for High-Risk Patients in Primary Care in Germany","authors":"Johannes Pöhlmann,&nbsp;Anika Joecker,&nbsp;Tanja Wittki,&nbsp;Tray Brown,&nbsp;Richard F. Pollock,&nbsp;Jordan Chase","doi":"10.1007/s12325-025-03156-0","DOIUrl":"10.1007/s12325-025-03156-0","url":null,"abstract":"<div><h3>Introduction</h3><p>Influenza A/B virus, severe acute respiratory coronavirus 2 (SARS-CoV-2), and respiratory syncytial virus (RSV) cause similar symptoms, often referred to as influenza-like illness, but require different treatments which must be administered within a short timeframe after symptom onset. This necessitates rapid detection and accurate differentiation by primary care providers, ideally at point of care (POC). POC nucleic acid tests such as the multiplex, real-time polymerase chain reaction (PCR) Xpert^® Xpress CoV-2/Flu/RSV <i>plus</i> (Xpert Xpress) offer a faster, more accurate alternative compared to antigen testing, clinical judgement alone, or send-out PCR. This cost–consequence analysis evaluated Xpert Xpress versus conventional testing methods, from a German statutory health insurance (SHI) perspective.</p><h3>Methods</h3><p>A 1-year decision tree was developed to compare Xpert Xpress with antigen testing, send-out PCR, and empiric diagnosis, for influenza A/B virus, SARS-CoV-2, and RSV. The model accounted for diagnostic accuracy and projected the share of patients receiving results within guideline-recommended treatment windows. Data on test accuracy, treatment effects, and costs were sourced from literature and German databases. The main outcome was total cost to the SHI for the 2023/24 respiratory illness season.</p><h3>Results</h3><p>Xpert Xpress was associated with the highest number of net correct treatment courses (<i>n</i> = 443,600) versus empiric diagnosis (<i>n</i> = 239,250), antigen testing (<i>n</i> = 347,218), and send-out PCR (<i>n</i> = 280,527). Acquisition costs were highest for Xpert Xpress (EUR 38.4 million versus EUR 27.4 million for antigen testing and EUR 33.5 million for send-out PCR) but were offset by reduced hospitalization and intensive care costs. Overall, Xpert Xpress was associated with cost savings of EUR 1.97 million versus empiric diagnosis, EUR 10.1 million versus antigen testing, and EUR 20.8 million versus send-out PCR.</p><h3>Conclusions</h3><p>Using Xpert Xpress at POC combined fast turnaround with high diagnostic accuracy, thereby increasing correct treatment courses while reducing total costs for influenza, COVID-19, and RSV, offering substantial savings to the German SHI.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 5","pages":"2385 - 2402"},"PeriodicalIF":3.4,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03156-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690728","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":"Pharmacokinetic Comparability and Safety Between Original and Citrate-Free Mirikizumab Formulations for Subcutaneous Injections: Results from Three Clinical Trials","authors":"Yuki Otani,&nbsp;Brian G. Feagan,&nbsp;Geert R. D’Haens,&nbsp;Rodrigo Escobar,&nbsp;Nathan J. Morris,&nbsp;Christopher D. Payne,&nbsp;Michelle Ugolini Lopes,&nbsp;Xin Zhang","doi":"10.1007/s12325-025-03158-y","DOIUrl":"10.1007/s12325-025-03158-y","url":null,"abstract":"<div><h3>Introduction</h3><p>Mirikizumab, a p19-directed antibody against interleukin-23 (IL-23), is administered by subcutaneous (SC) injection. Injection site pain (ISP) associated with citrate buffers may negatively affect patient adherence to SC-administered treatments. We assessed the bioequivalence and safety of the citrate-free (CF) and original formulations of mirikizumab.</p><h3>Methods</h3><p>The formulations were assessed in three phase 1, two-arm, randomized, single-dose, parallel design studies in healthy participants: study A (NCT04548219), study B (NCT05515601), and study C (NCT05644353). Participants were randomized 1:1 to either formulation, then further randomized to injection site locations of abdomen, arm, or thigh. The relative bioavailability (RBA) study A had a primary objective of assessing the RBA of a single 200 mg dose. Bioequivalence (BE) studies B and C had the primary objective of assessing the BE of a 200 and 300 mg dose, respectively. In all studies, the primary endpoints were <i>C</i>_max, AUC(0–∞), and AUC(0–<i>t</i>_last). The secondary objective was to assess safety and tolerability by treatment-emergent adverse events and serious adverse events. In study A, ISP was quantified prospectively using the 100-mm validated visual analogue scale (VAS) assessment form.</p><h3>Results</h3><p>The primary objective was met in all studies. The RBA study found no significant difference in exposure between the formulations. BE was demonstrated between CF and original mirikizumab in both BE studies, with the 90% confidence intervals of the ratios of geometric least squares means within the pre-specified equivalence limits of 0.80 and 1.25. The frequency of ISP and injection site reactions (ISRs) was lower for CF than original mirikizumab in all studies. Furthermore, a significant difference in mean VAS score was observed in study A.</p><h3>Conclusion</h3><p>Mirikizumab CF and original formulations were bioequivalent. The CF formulation was associated with less pain and fewer ISRs, with no other notable differences in safety profiles.</p><h3>Trial Registration</h3><p>ClinicalTrials.gov identifier NCT04548219, NCT05515601, NCT05644353.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 5","pages":"2369 - 2384"},"PeriodicalIF":3.4,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03158-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143672893","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":"An Up-to-Date Description of the Use of Non-steroidal Anti-inflammatory Drugs (NSAIDs) in Italy: Evidence from Real Clinical Practice","authors":"Valentina Perrone,&nbsp;Chiara Veronesi,&nbsp;Maria Ciappetta,&nbsp;Domenico Lucatelli,&nbsp;Andrea Cinti Luciani,&nbsp;Luca Degli Esposti","doi":"10.1007/s12325-025-03153-3","DOIUrl":"10.1007/s12325-025-03153-3","url":null,"abstract":"<div><h3>Introduction</h3><p>The prescription of non-steroidal anti-inflammatory drugs (NSAIDs) covered by the Italian National Health Service is limited to certain pathologies defined in the 2018 update of Note 66 of the Italian Medicines Agency (AIFA), meant to ensure appropriate use of NSAIDs. This analysis was conducted in real clinical practice to describe NSAID utilization from 2019 to 2022 with respect to Note 66 update.</p><h3>Methods</h3><p>For this real-world analysis, data were extracted from the administrative databases of healthcare institutions covering ~ 9.1 million citizens. From 2019 to 2022, all subjects with ≥ 1 NSAID prescription were identified. Demographic and clinical characteristics, the proportion of NSAID-treated patients over time, the most prescribed molecules, and drug consumption defined as daily dose (DDD) per 1000 inhabitants/day were recorded.</p><h3>Results</h3><p>The percentage NSAID-treated patients showed a slight increase over time (1.9–3.0%). The most prescribed active ingredients were diclofenac, ketoprofen, nimesulide, etoricoxib, and ibuprofen. NSAID consumption increased from 15.5 to 16.8 DDD/1000 inhabitants/day over 2020–2022, especially in older patients (65–74 years group: 36.2–39.3 DDD/1000 inhabitants/day). From 2019 to 2022, 2,811,910 patients with NSAID prescription(s) in Note 66 were identified, whose average age was 59.7 years. Among them, 0.1–1.0% received NSAIDs for rheumatic diseases and 11.9% in the oncological setting. While diclofenac, etoricoxib, and ketoprofen were commonly prescribed at medium–low dosage as recommended, ibuprofen was used at high dosage (600 mg) in 80% of cases.</p><h3>Conclusion</h3><p>The analysis showed that patients prescribed with NSAIDs were relatively young (~ 60 years), in contrast with the pathologies covered by Note 66, which typically affect elderly people. Moreover, rheumatic and oncological diseases were poorly represented, thus it is possible that NSAIDs might have been prescribed for indications outside the note. These findings suggest that the use of NSAIDs for pain management in Italy should be optimized, properly weighting their risks and benefits.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 5","pages":"2354 - 2368"},"PeriodicalIF":3.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03153-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661962","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}