Advances in Therapy最新文献

{"title":"Comparative Efficacy and Safety of Electrical Stimulation Therapies for Diabetic Ulcers: A Network Meta-analysis of Randomized Controlled Trials.","authors":"Jiaxin Zhong, Yi Lan, Zixin Cai","doi":"10.1007/s12325-025-03380-8","DOIUrl":"https://doi.org/10.1007/s12325-025-03380-8","url":null,"abstract":"<p><strong>Introduction: </strong>Diabetic ulcers (DUs) are a common complication of diabetes, significantly impairing quality of life and placing a burden on healthcare systems. Electrical stimulation (ES) therapy is a non-invasive technique that promotes wound healing using various current types, including direct current (DC), pulsed current (PC), and alternating current (AC). However, the comparative efficacy and safety of these ES modalities for DUs remain unclear.</p><p><strong>Methods: </strong>This study presents a network meta-analysis (NMA) of randomized controlled trials (RCTs) comparing the efficacy and safety of various ES therapies for DU treatment. A comprehensive literature search was conducted to identify studies evaluating ulcer healing rates, the number of healed ulcers, and adverse events. The treatments analyzed included symmetry biphasic square-wave pulse, asymmetric biphasic square-wave pulse, very low levels of stimulation current, twin-peak monophasic pulse, cathodal direct current (CDC), high-voltage pulsed current (HVPC), and low-intensity biphasic pulse current. The SUCRA (surface under the cumulative ranking curve) and mean rank values were used to assess the relative effectiveness of each modality.</p><p><strong>Results: </strong>The analysis included data from 11 RCTs. Treatment effects were compared using SUCRA and mean ranking values. HVPC, CDC, and asymmetric biphasic square-wave pulse were ranked highest for ulcer healing rates and the number of healed ulcers, with asymmetric biphasic square-wave pulse demonstrating the most consistent efficacy across these outcomes.</p><p><strong>Conclusion: </strong>This network meta-analysis suggests that HVPC, CDC, and asymmetric biphasic square-wave pulse are the most effective ES therapies for promoting DU healing.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172195","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":"The IMPACT Survey: The Humanistic Impact of Caring for an Individual with Osteogenesis Imperfecta.","authors":"Ingunn Westerheim, Frank Rauch, Tracy Hart, Lena Lande Wekre, Taco van Welzenis, Cathleen Raggio, Heather Mulhall, Alysia Battersby, Samantha Prince, Oliver Semler","doi":"10.1007/s12325-025-03372-8","DOIUrl":"https://doi.org/10.1007/s12325-025-03372-8","url":null,"abstract":"<p><strong>Introduction: </strong>The IMPACT Survey (\"IMPACT\") investigated the humanistic, clinical, and economic impact of osteogenesis imperfecta (OI) on affected individuals, caregivers, and the broader community. Prior publications reported the methodology, initial findings, and economic and humanistic impacts on adults with OI. Here, data is presented on the humanistic impact of OI on caregivers to explore how caring for an individual with OI impacts their quality of life (QoL), and any drivers of impact. We hypothesise that caring for an individual with OI will impact the QoL of caregivers.</p><p><strong>Methods: </strong>IMPACT, fielded July through September 2021 in eight languages, targeted adults and adolescents with OI, close relatives, and caregivers with or without OI. The survey covered demographics, socioeconomic factors, clinical characteristics, treatment patterns, QoL, and health economics. The impact of caring for an individual with OI was measured across QoL and worry domains. We performed descriptive analyses of the QoL of caregivers without OI and exploratory regression analyses to identify independent associations between caregiver and care recipient characteristics (\"predictors\"), and their QoL impact on caregivers.</p><p><strong>Results: </strong>Of 528 caregivers without OI with one care recipient, across 10 areas and three domains (career and finances, social and relationships, and mental and physical well-being), 58-83% reported that caring for an individual with OI negatively impacted their QoL; 80% and 83% reported impacted mental health and time for leisure activities, respectively. Predictors of QoL impact included caregiver age, care recipient OI severity, age, and clinical signs, symptoms and events (SSEs). Additionally, 36-96% worried about their care recipients' future lives, medication access, and transition to adult care.</p><p><strong>Conclusion: </strong>Our results suggest that caring for individuals with OI might have considerable impacts on QoL and worries. The level of impact may be predicted by caregiver age and care recipient OI severity, age, and clinical SSEs.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147494","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":"Correction to: The Association Between Short-Acting β₂-Agonist Over-Prescription, and Patient-Reported Acquisition and Use on Asthma Control and Exacerbations: Data from Australia.","authors":"David Price, Christine Jenkins, Kerry Hancock, Rebecca Vella, Florian Heraud, Porsche Le Cheng, Ruth Murray, Maarten Beekman, Sinthia Bosnic-Anticevich, Fabio Botini, Victoria Carter, Angelina Catanzariti, Joe Doan, Kirsty Fletton, Ata Kichkin, Thao Le, Chantal Le Lievre, Chi Ming Lau, Dominique Novic, John Pakos, Kanchanamala Ranasinghe, Alexander Roussos, Josephine Samuel-King, Anita Sharma, Deb Stewart, Bruce Willet, Eric Bateman","doi":"10.1007/s12325-025-03371-9","DOIUrl":"https://doi.org/10.1007/s12325-025-03371-9","url":null,"abstract":"","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147527","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":"Meta-analysis to Investigate the Correlation Between Event-Free Survival and Overall Survival in Patients with Resectable Locally Advanced Head and Neck Squamous Cell Carcinoma.","authors":"Dandan Zheng, Ali Mojebi, Yuexin Tang, Braden Hale, Sanjay Merchant, Sichen Liu, Sam Keeping","doi":"10.1007/s12325-025-03351-z","DOIUrl":"https://doi.org/10.1007/s12325-025-03351-z","url":null,"abstract":"<p><strong>Introduction: </strong>While overall survival (OS) is a widely accepted trial endpoint in oncology, survival data are often immature in early-stage populations. Alternative time-to-event outcomes have been considered by regulatory and reimbursement agencies to allow for early patient access. Event-free survival (EFS) has shown strong correlations with OS in patients with locally advanced (LA) head and neck squamous cell carcinoma (HNSCC) and within the subgroup with unresectable tumors. With novel neoadjuvant and adjuvant immunotherapies being investigated in resectable LA-HNSCC, this study aimed to assess the trial-level correlation of EFS and OS in patients with resectable LA-HNSCC.</p><p><strong>Methods: </strong>A systematic review (October 29, 2024) identified randomized controlled trials evaluating surgery with adjuvant therapy, neoadjuvant therapy, or both in patients with resectable LA-HNSCC. Trials reporting hazard ratios (HRs) or Kaplan-Meier curves for OS (time from randomization to death) and EFS (time from randomization to disease progression/recurrence or death) were eligible for the analysis. Base case included trials comparing neoadjuvant therapy + surgery + adjuvant therapy versus surgery + adjuvant therapy. Sensitivity analyses included models with trials comparing broader regimens (e.g., adjuvant therapy versus adjuvant therapy), excluding an outlier trial and restricting to publications after 2004. Correlations were measured between log(EFS HR) and log(OS HR) using regression models, with their strength measured using Pearson's correlation coefficient (R).</p><p><strong>Results: </strong>The review included 45 trials, with 20 trials qualifying for correlation analysis. R (95% confidence interval) was 0.91 (0.36, 0.99) in the base case (n = 5 trials) and 0.41 (-0.01, 0.71; n = 20), 0.78 (0.52, 0.91; n = 19), and 0.76 (0.41, 0.92; n = 13) in the three sensitivity analyses, respectively.</p><p><strong>Conclusion: </strong>Strong trial-level correlations were observed between EFS and OS, suggesting EFS is a valid surrogate for OS in patients with resectable LA-HNSCC, particularly in trials investigating neoadjuvant therapy + surgery + adjuvant therapy.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136255","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 Comparative Effectiveness Study in Patients with Asthma Initiating Fluticasone Furoate/Vilanterol or Beclometasone Dipropionate/Formoterol Fumarate in General Practice in England.","authors":"Ashley Woodcock, John Blakey, Arnaud Bourdin, Giorgio Walter Canonica, Christian Domingo, Alexander Ford, Rosie Hulme, Theo Tritton, Ines Palomares, Sanchayita Sadhu, Arunangshu Biswas, Manish Verma","doi":"10.1007/s12325-025-03349-7","DOIUrl":"https://doi.org/10.1007/s12325-025-03349-7","url":null,"abstract":"<p><strong>Introduction: </strong>We compared the real-world effectiveness of initiating beclometasone dipropionate/formoterol fumarate (BDP/FOR) versus fluticasone furoate/vilanterol (FF/VI) in a general practice (GP) asthma cohort in England.</p><p><strong>Methods: </strong>Patients newly initiating BDP/FOR or FF/VI between 1 December 2015 and 28 February 2019 (index), were selected from anonymised Clinical Practice Research Datalink data. Baseline was < 12 months pre-index with ≤ 12 months follow-up post-index. Eligible patients were aged ≥ 18 years at index, had diagnosed asthma, ≥ 1 FF/VI or BDP/FOR prescription, medical records eligible for linkage to secondary care data and continuous GP-registration ≥ 12 months pre-index. Patients with chronic obstructive pulmonary disease, ≥ 1 fixed-dose inhaled corticosteroid/long-acting β₂-agonist, single-inhaler triple or biologic therapy at index were excluded. The primary study outcome was asthma exacerbation rate. Secondary outcomes included medication persistence and oral corticosteroid (OCS) use. Propensity scores were generated for each treatment comparison; inverse probability of treatment weighting adjusted for confounding in baseline characteristics between groups, applied to each outcome separately. Analyses considered intercurrent events (ICEs; treatment switching, discontinuation, loss to follow-up, death, rescue medication use).</p><p><strong>Results: </strong>Weighted group standard mean differences showed adequate balance for most covariates. Patients initiating BDP/FOR (n = 46,809) and FF/VI (n = 3773) had numerically similar exacerbation rates per person per year (PPPY) while-on index treatment [measuring outcome until ICE; BDP/FOR, 0.1479 (n = 31,715); FF/VI, 0.1338 (n = 2547); rate ratio 0.9048, p = 0.2841]. Patients continuing uninterrupted index treatment for 12 months had a lower exacerbation rate PPPY for FF/VI [0.0681 (n = 384)] than BDP/FOR [0.1104 (n = 3342); rate ratio, 0.6162 (p = 0.0293)]. For patients initiating FF/VI versus BDP/FOR, treatment persistence was greater [hazard ratio, 0.76 (p < 0.0001)].</p><p><strong>Conclusion: </strong>Overall, patients initiating FF/VI and BDP/FOR had numerically similar exacerbation rates; of the patients continuing 12 months' uninterrupted treatment, the FF/VI group had a lower exacerbation rate versus BDP/FOR. Patients initiating FF/VI were less likely to discontinue treatment than those initiating BDP/FOR.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145135944","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":"Estimated Long-Term Durability of Valoctocogene Roxaparvovec Treatment in Male patients with Severe Hemophilia A: An Extrapolation of Clinical Data.","authors":"Sandra Santos, Tara M Robinson, David Trueman","doi":"10.1007/s12325-025-03368-4","DOIUrl":"https://doi.org/10.1007/s12325-025-03368-4","url":null,"abstract":"<p><strong>Introduction: </strong>Valoctocogene roxaparvovec is a single administration gene therapy treatment that enables endogenous factor VIII (FVIII) production to prevent bleeding in people with severe hemophilia A. Valoctocogene roxaparvovec is associated with a higher probability of being bleed-free, improvements in annualized bleed rates, and improvements in health-related quality of life compared with FVIII prophylaxis. The economic value of valoctocogene roxaparvovec will be determined, in part, by the duration of time over which the treatment effect is maintained, and the consequences associated with loss of response. Therefore, this analysis aimed to estimate the long-term durability of valoctocogene roxaparvovec treatment effect by extrapolating pivotal and longer-term trial data (Phase 3 GENEr8-1 4- to 5-year and a Phase 1/2 study 7-year data) to inform decision-making.</p><p><strong>Methods: </strong>Using data from the pivotal Phase 3 study GENEr8-1 and longer-term data from the 6E13 vg/kg cohort of Phase 1/2 Study 270-201, time to loss of response was analyzed within a time-to-event analysis framework. Loss of response was defined as a combination of: FVIII level decline < 5% and return to continuous prophylactic treatment and experiencing ≥ 2 treated bleed events in the previous 6 months at the time of return to prophylactic treatment.</p><p><strong>Results: </strong>Data were available for 134 participants from GENEr8-1, and 7 participants from Study 270-201. The main analysis results for predicted median durability ranged from 11.0 to 17.0 years considering the three statistically best-fitting parametric distributions; considering five plausible distributions, results ranged from 8.1 to 25.6 years. In scenario analyses using different definitions of loss of response, the results were broadly similar, with median durability ranging from 7.2 to 31.8 years.</p><p><strong>Conclusion: </strong>This analysis demonstrates the potential therapeutic benefit of valoctocogene roxaparvovec may be sustained beyond the follow-up period in existing clinical trials and across all parametric extrapolations and definitions analyzed, indicating that gene therapy may offer long-term benefits beyond what has been previously reported (i.e., 7 years).</p><p><strong>Trial registration number: </strong>GENEr8-1: ClinicalTrials.gov identifier, NCT03370913. Study 270-201: ClinicalTrials.gov identifier NCT02576795.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145123890","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":"Lateral Femoral Cutaneous Nerve Radiofrequency Ablation for Meralgia Paresthetica: A Description of a Novel Technique.","authors":"Alaa Abd-Elsayed, Muhammed Zahid Sahin, Barnabas T Shiferaw","doi":"10.1007/s12325-025-03360-y","DOIUrl":"https://doi.org/10.1007/s12325-025-03360-y","url":null,"abstract":"<p><p>Meralgia paresthetica (MP) is neuropathic pain in the anterolateral thigh, most often caused by compression or injury to the lateral femoral cutaneous nerve (LFCN). Conservative treatments include weight loss, avoidance of compressive clothing, medical management with anti-inflammatory and neuropathic agents, and corticosteroid injections. For patients with MP refractory to these measures, radiofrequency ablation (RFA) is a minimally invasive option that may provide pain relief. This article introduces a novel ultrasound-guided continuous RFA technique designed to create a controlled thermal lesion of the LFCN, along with preliminary clinical outcomes. Pronounced anatomic variation of the LFCN at the anterior superior iliac spine makes real-time imaging essential for procedural accuracy, with ultrasound offering consistent nerve visualization and precise needle placement. Continuous RFA has demonstrated substantial and durable reductions in VAS scores, whereas pulsed RFA provides shorter-term relief with a favorable safety profile, and cooled RFA produces broader lesions that may help address anatomical variability, although supporting evidence is limited. Overall, RFA can be an effective treatment for MP refractory to conservative therapy, with optimal results dependent on detailed anatomical knowledge and accurate image guidance, particularly when using the novel continuous RFA approach described in this study.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145123939","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":"A Strategic Roadmap to Support Communication on and Acceptance of Surrogate Endpoints: The REnal Surrogacy accEpTance in Chronic Kidney Disease (RESET CKD) Collaboration.","authors":"Juan José Garcia Sanchez, Marta Trapero-Bertran, Oriana Ciani, Bruno Detournay, Loreto Gesualdo, Hiddo J L Heerspink, Lesley A Inker, Smeeta Sinha, Christoph Wanner, Dustin J Little, Marvin Sinsakul, You-Seon Nam, Rod S Taylor","doi":"10.1007/s12325-025-03370-w","DOIUrl":"https://doi.org/10.1007/s12325-025-03370-w","url":null,"abstract":"<p><strong>Introduction: </strong>Developing effective treatments in chronic, progressive diseases like chronic kidney disease (CKD) is challenging because patients may only experience relevant outcomes such as kidney failure after long periods of disease progression. Surrogate endpoints provide a valuable alternative to definitive final patient-relevant outcomes, which may accelerate clinical development processes. However, optimal utilization of surrogate endpoints for reimbursement decisions requires alignment across multiple stakeholders, including health technology assessment (HTA) bodies and reimbursement agencies, who are generally more cautious than regulatory bodies in their acceptance of surrogate endpoint evidence. The aim of this paper is to propose a strategic roadmap to facilitate cross-stakeholder collaboration and support the consideration of surrogate endpoints in regulatory and reimbursement decisions.</p><p><strong>Methods: </strong>An international group of experts in surrogate endpoints, reimbursement decisions, and kidney disease formed The REnal Surrogacy accEpTance in Chronic Kidney Disease (RESET CKD) Collaboration. This scientific steering committee held several meetings to develop a roadmap of activities with the aim of enabling the appropriate consideration of surrogate endpoints through structured multi-stakeholder engagement involving regulators, clinicians, HTA bodies, payers, industry, and patients.</p><p><strong>Results: </strong>The strategic roadmap focuses on four areas: identifying the need for evidence; engaging stakeholders; collaborating in regulatory and reimbursement processes; and disseminating evidence. The RESET CKD collaboration is currently implementing the roadmap in the field of CKD through collating relevant evidence for a CKD-relevant surrogate endpoint in a scientific playbook, conducting economic evaluations, developing a position paper, and engaging patient groups.</p><p><strong>Conclusions: </strong>Disparities between regulatory and reimbursement processes and decisions underscore the need for a structured approach to enhancing transparency, consistency, and timeliness in the use of surrogate endpoint evidence in healthcare decision-making. The roadmap developed through the RESET CKD Collaboration addresses this need and is already demonstrating practical value in its implementation. Although initially focused on CKD, the framework is designed to be transferable to other therapeutic areas. Key challenges remain, including the integration of surrogate endpoints into adaptive pricing models and performance-based agreements.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145123916","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":"Podcast Synopsis of Updates to the European Renal Best Practice and UK Kidney Association Guidelines for Treatment of Anaemia in Chronic Kidney Disease.","authors":"Mario Cozzolino, Sokratis Stoumpos, Sunil Bhandari","doi":"10.1007/s12325-025-03366-6","DOIUrl":"https://doi.org/10.1007/s12325-025-03366-6","url":null,"abstract":"<p><p>Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) were developed as an alternative to erythropoiesis-stimulating agents (ESAs) for the treatment of anaemia of chronic kidney disease (CKD). In 2024, the European Renal Best Practice Board (ERBP) of the European Renal Association published a clinical practice document for the use of HIF-PHIs; in 2025, the UK Kidney Association (UKKA) updated its treatment guidelines for anaemia of CKD, including HIF-PHIs as a recommended additional therapy. This podcast provides an overview of HIF-PHIs compared to ESAs, followed by a summary of general recommendations for the treatment of anaemia of CKD, with reference to both ERBP and UKKA guidelines. Considerations for prescribing ESAs and HIF-PHIs to specific patient groups, including those with inflammation, a history of cancer or cardiovascular events, kidney transplant recipients, and hospitalised patients, are then discussed. Podcast Audio (MP4 169314 KB).</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145123897","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":"IL-17C as a Driver of Inflammation in Psoriasis.","authors":"George Han, April Armstrong, James G Krueger, Abby Jacobson","doi":"10.1007/s12325-025-03363-9","DOIUrl":"https://doi.org/10.1007/s12325-025-03363-9","url":null,"abstract":"<p><p>In psoriatic lesions, interleukin (IL)-17C protein expression has been reported as high as 125 times that of IL-17A; as such, it is crucial to understand the role that IL-17C plays in psoriasis, inflammation, and treatment response. Overexpression or injection of IL-17C in mice results in increased epidermal thickening and inflammation, whereas psoriatic mice with IL-17C knockout have decreased disease severity compared with control littermates. In psoriasis, IL-17C likely acts as a critical inflammatory amplifier via a feed-forward mechanism, wherein IL-17-producing CD4⁺ helper T (T_H17) cells and IL-17-producing CD8⁺ cytotoxic T (T_C17) cells stimulate IL-17C expression in keratinocytes. Then, keratinocyte-derived IL-17C induces IL-17A expression in T_H17 and T_C17 cells. Additionally, keratinocyte-derived IL-17C propagates its own signaling in an autocrine manner. Furthermore, studies suggest that IL-17C acts as an early mediator of psoriasis. No approved therapies directly target IL-17C. Brodalumab is an IL-17 receptor (IL-17R) A antagonist that inhibits IL-17A, F, C, and E signaling and has a unique mechanism of action among biologic therapies for psoriasis. By way of IL-17RA blockade, brodalumab is the only approved therapy for psoriasis that inhibits IL-17C signaling. This unique mechanism of action is hypothesized to correlate with efficacy in patients with prior failures to anti-IL-17A therapies and relatively higher rates of early skin clearance compared with those of other biologic therapies. Clinical studies are needed to confirm these correlations. In summary, IL-17C is an inflammatory amplifier and early psoriatic mediator, and inhibition of IL-17C may be beneficial in psoriasis management.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145123887","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}