Expert Opinion on Biological Therapy最新文献

{"title":"Trajectories of biologic drug use before, during and after pregnancy: an Italian cohort study from the VALORE project.","authors":"Sara Lopes, Michela Servadio, Andrea Spini, Luca L'Abbate, Ylenia Ingrasciotta, Sabrina Giometto, Ersilia Lucenteforte, Olivia Leoni, Martina Zanforlini, Domenica Ancona, Paolo Stella, Aurora Puccini, Ester Sapigni, Paola Rossi, Lucian Ejlli, Francesco Balducci, Antea Maria Pia Mangano, Stefano Ledda, Paolo Carta, Rita Francesca Scarpelli, Giovambattista De Sarro, Marco Massari, Stefania Spila Alegiani, Antonio Addis, Gianluca Trifirò, Valeria Belleudi","doi":"10.1080/14712598.2024.2442452","DOIUrl":"10.1080/14712598.2024.2442452","url":null,"abstract":"<p><strong>Background: </strong>Monitoring biologic drug therapy during pregnancy in women with immune-mediated inflammatory diseases (IMIDs) is crucial to ensure treatments align with evidence-based practices.</p><p><strong>Research design and methods: </strong>A retrospective cohort study based on healthcare claims data from eight Italian regions was conducted, analyzing deliveries between 2009 and 2021. The study included women receiving biologic drugs within nine months before their last menstruation. Exposures to biologics, conventional disease-modifying anti-rheumatic drugs (DMARDs) and symptom-relieving medications were assessed in the trimesters (T) before, during and after pregnancy. Factors influencing biologic treatment persistence during pregnancy were analyzed.</p><p><strong>Results: </strong>A cohort of 1,763 deliveries was considered. Biologic drugs were prescribed for rheumatic (33.6%), dermatological (32.6%), and gastrointestinal diseases (28.4%). Biologic use declined during pregnancy (TI = 37.3%; TII = 17.6%; TIII = 11.3%), increasing again postpartum. During pregnancy, there was increased use of symptom-relieving medications for rheumatic diseases and DMARDs for gastrointestinal diseases. Factors associated with continued biologic treatment included being older than 35 years and the region of delivery.</p><p><strong>Conclusions: </strong>This study found a decrease in biologics drug use during pregnancy and highlights the necessity for personalized therapeutic approaches. Geographic variations in biologic drug use emphasize the need for educational initiatives about the risk-benefit profiles of these therapies during pregnancy.</p>","PeriodicalId":12084,"journal":{"name":"Expert Opinion on Biological Therapy","volume":" ","pages":"119-131"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817113","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":"An up-to-date review of emerging biologic therapies for hypercholesterolemia.","authors":"Brian Tomlinson","doi":"10.1080/14712598.2024.2442455","DOIUrl":"10.1080/14712598.2024.2442455","url":null,"abstract":"<p><strong>Introduction: </strong>Hypercholesterolemia and other lipid disorders are major causes of atherosclerotic cardiovascular disease (ASCVD). Statins have been the mainstay of lipid-lowering therapy for many years, but they may not be adequate to achieve the target low-density lipoprotein (LDL) cholesterol levels and there are other residual lipid risk factors.</p><p><strong>Areas covered: </strong>This article reviews the biologic therapies in development for hypercholesterolemia identified by a PubMed search. Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) is a major focus, but the drugs targeting apolipoprotein C3 (apoC3) and angiopoietin-like 3 (ANGPTL3) that were originally developed to reduce the levels of triglyceride-rich lipoproteins are now being explored to reduce cardiovascular events in a wider range of patients. A brief overview of biologic therapies targeting lipoprotein(a) [Lp(a)] is also proved.</p><p><strong>Expert opinion: </strong>Inhibition of PCSK9 remains an attractive target. In addition to the currently available monoclonal antibodies (mAbs) and small interfering RNA (siRNA), new mAbs and the adenectin lerodalcibep are promising therapies. The antisense oligonucleotide (ASO) and siRNA inhibitors of apoC3 and ANGPTL3 are effective in severe hypertriglyceridemia and homozygous familial hypercholesterolemia, respectively, and may prove to have wider applications. ASO and siRNA inhibitors of Lp(a) are currently in cardiovascular outcome studies.</p>","PeriodicalId":12084,"journal":{"name":"Expert Opinion on Biological Therapy","volume":" ","pages":"69-78"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817192","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":"Advances in CD19-targeting CAR-T cell therapies for multiple myeloma.","authors":"Maximilian J Steinhardt, Hermann Einsele, Johannes M Waldschmidt","doi":"10.1080/14712598.2024.2443093","DOIUrl":"10.1080/14712598.2024.2443093","url":null,"abstract":"<p><strong>Introduction: </strong>Emerging evidence suggests that, while CD19 is primarily expressed on immature B-cell precursors, it is also present on drug-resistant plasma cells that have been postulated to function as multiple myeloma (MM) stem cells, driving the progression of relapsing disease. Targeting CD19 with chimeric antigen receptor (CAR) T cells offers a promising strategy for addressing this residual disease burden, potentially leading to more durable treatments and enhanced relapse prevention.</p><p><strong>Areas covered: </strong>This review examines the molecular basis of CD19-targeted CAR-T therapy in MM, highlighting its potential, key challenges, and efficacy and safety in early clinical trials for relapsed/refractory and newly diagnosed MM.</p><p><strong>Expert opinion: </strong>CD19 expression in MM correlates with poor prognosis and may be significantly underestimated, particularly following debulking therapy, as demonstrated by advanced visualization technologies like single molecule-sensitive direct stochastic optical reconstruction microscopy (dSTORM). Early-phase trials using CD19-directed CAR-T as post-transplant consolidation show promise in prolonging progression-free survival. Multi-target approaches, e.g. the bispecific BCMA×CD19 CAR-T product GC012F, are advancing through clinical development with encouraging safety and efficacy data. However, randomized controlled trials will be necessary to confirm the role and positioning of CD19-directed CAR-T cells within the current MM treatment landscape.</p>","PeriodicalId":12084,"journal":{"name":"Expert Opinion on Biological Therapy","volume":" ","pages":"21-25"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817601","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":"Pooled safety analysis from the VOLTAIRE clinical trials of adalimumab-adbm and adalimumab reference product in patients with rheumatoid arthritis, Crohn's disease, and chronic plaque psoriasis.","authors":"Stanley Cohen, Shaun Bender, Amy Shaberman, Richard Vinisko, Dottie McCabe","doi":"10.1080/14712598.2024.2426637","DOIUrl":"10.1080/14712598.2024.2426637","url":null,"abstract":"<p><strong>Objectives: </strong>This analysis reported the incidence of safety endpoints across five phase 3 randomized controlled clinical trials in patients with rheumatoid arthritis (RA), Crohn's disease (CD), and chronic plaque psoriasis (PsO) who received ≥ 1 dose of adalimumab-adbm or adalimumab reference product (RP).</p><p><strong>Methods: </strong>Exposure-adjusted incidence rates for safety endpoints were calculated per 100 patient-years and reported by disease indication and treatment arm. Subgroup analyses by patient age and sex were also conducted.</p><p><strong>Results: </strong>The mean length of follow-up was 62 weeks, 48 weeks, and 32 weeks for patients with RA, CD, and PsO, respectively. Rates of serious adverse events (SAEs) and discontinuations due to adverse events (AEs) were similar among patients with RA and PsO, but slightly higher among those with CD. Incidence rates of all safety endpoints were consistent between the adalimumab-adbm and adalimumab RP treatment arms within each indication Subgroup analyses of patients with RA, CD, and PsO showed no between-group differences by age and sex.</p><p><strong>Conclusions: </strong>In patients with RA, CD, and PsO, there were no differences between biosimilar adalimumab-adbm or the adalimumab RP regarding the rate of AEs, SAEs, discontinuations due to AEs, deaths, or any AEs of special interest.</p>","PeriodicalId":12084,"journal":{"name":"Expert Opinion on Biological Therapy","volume":" ","pages":"133-138"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582644","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":"Integrating gene therapy into the treatment paradigm for non-muscle invasive bladder cancer.","authors":"Alexis R Steinmetz, Behzad Jazayeri, Morgan Pierce, Sharada Mokkapati, David McConkey, Roger Li, Colin P Dinney","doi":"10.1080/14712598.2024.2445674","DOIUrl":"10.1080/14712598.2024.2445674","url":null,"abstract":"<p><strong>Introduction: </strong>Approximately 75% of bladder cancer cases are non-muscle invasive at diagnosis. Drug development for non-muscle invasive bladder cancer (NMIBC) has historically lagged behind that of other malignancies. No treatment has demonstrated the ability to overcome drug resistance that ultimately leads to recurrence and progression. Gene therapy is emerging as a promising option for patients with NMIBC.</p><p><strong>Areas covered: </strong>This review summarizes the clinical application of gene therapy in NMIBC management and discusses recent clinical trials involving the adenoviral vector-based treatment nadofaragene firadenovec, and the oncolytic serotype 5 adenovirus, cretostimogene grenadenorepvec. Nadofaragene received approval by the Food and Drug Administration in December 2022, and cretostimogene has been granted Fast Track Designation and Breakthrough Therapy Designation. Ongoing trials are investigating strategies to augment efficacy and durability of these therapies.</p><p><strong>Expert opinion: </strong>Gene therapy may overcome resistance mechanisms of other NMIBC treatments, and data suggest a role for combination therapy with additive or synergistic agents. Significant differences in trial design limit comparability of agents across trials, highlighting the need for critical assessment of published findings. While initial investigations were in high-risk patients who recur despite frontline therapy with Bacillus Calmette-Guerin (BCG), there is growing interest in BCG-naïve and intermediate-risk populations.</p>","PeriodicalId":12084,"journal":{"name":"Expert Opinion on Biological Therapy","volume":" ","pages":"149-159"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946835","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":"Clinical updates in mesenchymal stromal cell therapy for osteoarthritis treatment.","authors":"Gun-Il Im","doi":"10.1080/14712598.2024.2446612","DOIUrl":"10.1080/14712598.2024.2446612","url":null,"abstract":"<p><strong>Introduction: </strong>Osteoarthritis (OA) is a common chronic musculoskeletal disease with heterogeneous clinical manifestations and variable responses to different treatments. Unfortunately, there is no effective disease modifying therapy at present that can alter the natural course of the disease. Cell therapy based on mesenchymal stromal cells (MSCs) may offer an attractive therapeutic option for OA with their multiple modes of action, particularly immune-regulatory and regenerative capacities.</p><p><strong>Areas covered: </strong>In this narrative review, updates on mode of action based on patient's data, factors that can influence the efficacy of MSC treatment, current status in clinical application of MSCs as seen from randomized, controlled OA trials are introduced as well as the author's perspectives in the future of MSCs as OA therapeutics.</p><p><strong>Expert opinion: </strong>Symptomatic relief is not sufficient to justify the high cost associated with culture-expanded stem cells. Its advantages and efficacy over simple and low risk/cost modalities should be seriously reevaluated. Also, as the short-term strategy, efforts should be made to lower the cost of MSC therapy. In the future, multiomics technology may help to predict that subgroup of patients who will favorably respond to stem cell treatment, which would enhance the cost effectiveness and therapeutic benefit of MSC therapy.</p>","PeriodicalId":12084,"journal":{"name":"Expert Opinion on Biological Therapy","volume":" ","pages":"187-195"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876690","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":"Biosimilars in pediatric rheumatology: innovations, challenges, and opportunities.","authors":"Ali Öksel, Hafize Emine Sönmez, Nihal Şahin","doi":"10.1080/14712598.2025.2453516","DOIUrl":"10.1080/14712598.2025.2453516","url":null,"abstract":"<p><strong>Introduction: </strong>Biosimilars are biologic medications designed to closely replicate the properties of previously approved biologic disease-modifying anti-rheumatic drugs (bDMARDs). They offer a cost-effective alternative once the original product's patent has expired.</p><p><strong>Areas covered: </strong>In pediatric rheumatology, the use of biosimilars began in 2013 with the launch of the infliximab biosimilar. Since then, more biosimilars, including etanercept, rituximab, and adalimumab, have been introduced, providing additional treatment options for children with rheumatic diseases. This article explores the role of biosimilars in pediatric rheumatology, particularly in juvenile idiopathic arthritis, focusing on their development, safety, and efficacy, as well as the challenges associated with their clinical adoption. It also addresses the importance of education in improving understanding of biosimilars.</p><p><strong>Expert opinion: </strong>The article provides insights into their safety, effectiveness, and economic impact by reviewing current literature to help healthcare professionals make informed decisions for treating pediatric rheumatic diseases. Education for both patients and healthcare providers, effective communication, and expectation management play a critical role in ensuring appropriate treatment continuity.</p>","PeriodicalId":12084,"journal":{"name":"Expert Opinion on Biological Therapy","volume":" ","pages":"197-204"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970074","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":"Strategies for extending the half-life of biotherapeutics: successes and complications.","authors":"Uli Binder, Arne Skerra","doi":"10.1080/14712598.2024.2436094","DOIUrl":"10.1080/14712598.2024.2436094","url":null,"abstract":"<p><strong>Introduction: </strong>Engineering of the drug half-life in vivo has become an integral part of modern biopharmaceutical development due to the fact that many proteins/peptides with therapeutic potential are quickly cleared by kidney filtration after injection and, thus, circulate only a few hours in humans (or just minutes in mice).</p><p><strong>Areas covered: </strong>Looking at the growing list of clinically approved biologics that have been modified for prolonged activity, and also the plethora of such drugs under preclinical and clinical development, it is evident that not one solution fits all needs, owing to the vastly different structural features and functional properties of the pharmacologically active entities. This article provides an overview of established half-life extension strategies, as well as of emerging novel concepts for extending the in vivo stability of biologicals, and their pros and cons.</p><p><strong>Expert opinion: </strong>Beyond the classical and still dominating technologies for improving drug pharmacokinetics and bioavailability, Fc fusion and PEGylation, various innovative approaches that offer advantages in different respects have entered the clinical stage. While the Fc fusion partner may be gradually superseded by engineered albumin-binding domains, chemical PEGylation may be replaced by biodegradable recombinant amino-acid polymers like PASylation, thus also offering a purely biotechnological manufacturing route.</p>","PeriodicalId":12084,"journal":{"name":"Expert Opinion on Biological Therapy","volume":" ","pages":"93-118"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812307","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":"An evaluation of pozelimab for the treatment of CHAPLE disease.","authors":"Salim Can, Melek Yorgun Altunbas, Ahmet Ozen","doi":"10.1080/14712598.2024.2438740","DOIUrl":"10.1080/14712598.2024.2438740","url":null,"abstract":"<p><strong>Introduction: </strong>CHAPLE disease is a severe, ultra-rare disorder caused by CD55 gene mutations, leading to uncontrolled complement hyperactivation, protein-losing enteropathy, and systemic thrombosis. Recent advances in targeted therapies, particularly the C5 inhibitor pozelimab (Veopoz), offer new treatment options by addressing complement dysregulation, marking a shift from symptomatic to precision therapy.</p><p><strong>Areas covered: </strong>This review explores the pathophysiology, clinical manifestations, and current treatments for CHAPLE disease. It examines pozelimab's pharmacological development, its mechanism as a C5 inhibitor, and results from Phase 1 to Phase 3 studies. Additionally, potential use of other anti-C5 therapies and emerging agents targeting proximal complement components are discussed. A systematic literature search using PubMed, Google Scholar, and ClinicalTrials.gov focused on studies from 2017 onwards to provide a comprehensive overview.</p><p><strong>Expert opinion: </strong>Managing CHAPLE disease requires a combination of targeted anti-complement therapies like pozelimab and supportive measures, including nutritional support and thrombosis management. While pozelimab shows promise in reversing core symptoms, risks like serious infections necessitate preventive measures, such as vaccination and antibiotic prophylaxis. Future research should focus on optimizing dosing, evaluating long-term safety, and assessing the need for lifelong therapy. Expanding our understanding of the disease's pathophysiology will refine treatment strategies and improve outcomes.</p>","PeriodicalId":12084,"journal":{"name":"Expert Opinion on Biological Therapy","volume":" ","pages":"1-7"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827770","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":"Idecabtagene vicleucel (ide-cel) for the treatment of triple-class exposed relapsed and refractory multiple myeloma.","authors":"Katia Mancuso, Simona Barbato, Marco Talarico, Paola Tacchetti, Elena Zamagni, Michele Cavo","doi":"10.1080/14712598.2024.2433518","DOIUrl":"10.1080/14712598.2024.2433518","url":null,"abstract":"<p><strong>Introduction: </strong>Modern anti-myeloma therapies have broken new ground in the treatment of the disease, and the incorporation of ide-cel in the treatment landscape represents one of the major scientific and clinical advances.</p><p><strong>Areas covered: </strong>Ide-cel was the first cell-based gene therapy approved for the treatment of triple-class exposed relapsed/refractory myeloma patients, showing impressive results, and demonstrating superiority over standard regimens in terms of efficacy, potential treatment-free intervals, and improved quality of life in heavily pretreated patients and in high-risk disease. This review summarizes the state-of-the-art of the most recent updates deriving from the use of ide-cel within ongoing, or upcoming, clinical trials, and from real-life experiences.</p><p><strong>Expert opinion: </strong>As the use of chimeric antigen receptor (CAR)-T therapy is likely to progressively increase over time and current indications expand to earlier treatment lines, efforts should be directed toward ameliorating overall management to facilitate proactive planning for treatment sequencing and provide adequate time for logistical planning. Importantly, the potential limited availability of CAR-T therapy highlights the importance of careful patient selection and coordination among centers. Meanwhile, attempts are underway to improve tolerance and reduce toxicity while enhancing anti-myeloma activity.</p>","PeriodicalId":12084,"journal":{"name":"Expert Opinion on Biological Therapy","volume":" ","pages":"27-46"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800014","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}