Biologics : Targets & Therapy最新文献

{"title":"Autologous Hematopoietic Stem Cell Transplantation (AHSCT): An Evolving Treatment Avenue in Multiple Sclerosis.","authors":"Reihane Mohammadi,&nbsp;Alisam Aryan,&nbsp;Mir Davood Omrani,&nbsp;Sayyed Mohammad Hossein Ghaderian,&nbsp;Zahra Fazeli","doi":"10.2147/BTT.S267277","DOIUrl":"https://doi.org/10.2147/BTT.S267277","url":null,"abstract":"<p><p>Autologous hematopoietic stem cell transplantation (AHSCT) is considered as the novel approach to improve multiple sclerosis (MS) patients with disease-modifying therapies (DMTs)-resistance. The results obtained from different studies indicate that AHSCT increases the life quality of MS patients. Several factors are known to be influenced on the successful rate of AHSCT in patients with MS. The individuals aged <40 years with a short duration of MS disease have been demonstrated to show a better response to AHSCT administration. Furthermore, this treatment approach was more effective in relapsing remitting MS (RRMS) patients than progressive MS (PMS). Different clinical trials revealed that AHSCT with a low density conditioning regimen could be suggested as a suitable candidate approach in the management of MS. Several molecular and cellular mechanisms are known to be involved in the resetting of the immune system following the AHSCT infusion in MS patients. These mechanisms play a role in the depletion of auto-reactive lymphocytes and immune system renewal. In the present review, we discuss different clinical and molecular aspects of AHSCT application in the alleviation of MS symptoms.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2021-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f4/c0/btt-15-53.PMC7936693.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25451038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biologic Treatments of Psoriasis: An Update for the Clinician.","authors":"Nicholas D Brownstone,&nbsp;Julie Hong,&nbsp;Megan Mosca,&nbsp;Edward Hadeler,&nbsp;Wilson Liao,&nbsp;Tina Bhutani,&nbsp;John Koo","doi":"10.2147/BTT.S252578","DOIUrl":"https://doi.org/10.2147/BTT.S252578","url":null,"abstract":"<p><p>The advent of biologic agents within the past two decades has dramatically improved the treatment of psoriasis and psoriatic arthritis. Given that there now exists 11 FDA approved biologic options available for psoriasis, with more in the pipeline, the therapeutic armamentarium has been greatly enhanced. However, the fact that there are so many available options has also caused confusion for providers. Therefore, this manuscript deliberately focuses on the most clinically useful facts (such as efficacy and safety data) about each and every FDA approved biologic agent (including pipeline agents) for psoriasis. Moreover, among the clinically relevant facts, this manuscript purposely emphasizes the unique merits and demerits of each agent to make it easier for the provider to select which one of these many options is the best for the particular patient on hand. The goal of this manuscript is to aid the busy practicing dermatologist in becoming more adept at using these agents with the ultimate aim of improving patient care.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2021-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8c/6d/btt-15-39.PMC7896737.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25398604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Convalescent Plasma for the Treatment of Severe COVID-19.","authors":"Massimo Franchini,&nbsp;Giancarlo Maria Liumbruno","doi":"10.2147/BTT.S272063","DOIUrl":"https://doi.org/10.2147/BTT.S272063","url":null,"abstract":"<p><p>The COVID-19 pandemic in 2020 is one of the worst catastrophic events in human history. Several non-specific antiviral drugs have been tried to defeat the SARS-CoV-2, with mixed results. Convalescent plasma from patients who have recovered from COVID-19 is one of the specific biologic therapies being considered to treat SARS-CoV-2 infection. Preliminary studies have shown that convalescent plasma, containing antibodies able to neutralize SARS-CoV-2, is promising in blocking viral replication and improving patients' clinical symptoms. The results of several ongoing randomized controlled trials are, however, keenly awaited to definitively elucidate the safety and efficacy of this blood component in COVID-19. In this narrative review, we summarize the current evidence from the literature on the treatment of severe COVID-19 with convalescent plasma. A concise overview of the hypothesized mechanisms of action is also presented.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2021-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5e/0b/btt-15-31.PMC7871873.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25359810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Switching and Discontinuation Patterns Among Patients Stable on Originator Infliximab Who Switched to an Infliximab Biosimilar or Remained on Originator Infliximab.","authors":"Timothy Fitzgerald, Richard Melsheimer, Marie-Hélène Lafeuille, Patrick Lefebvre, Laura Morrison, Kimberly Woodruff, Iris Lin, Bruno Emond","doi":"10.2147/BTT.S285610","DOIUrl":"10.2147/BTT.S285610","url":null,"abstract":"<p><strong>Objective: </strong>To compare switching and discontinuation patterns of patients stable on originator infliximab (IFX) who switched to an IFX biosimilar (switchers) or remained on originator IFX (continuers) in the United States.</p><p><strong>Methods: </strong>Symphony Health Solutions' Patient Transactional Datasets (10/2012-03/2019) were used to identify adults with ≥2 claims for either rheumatoid arthritis (RA), psoriatic arthritis, plaque psoriasis, ankylosing spondylitis, or inflammatory bowel disease (IBD); and ≥1 claim for originator or biosimilar IFX. The index date was the first IFX biosimilar claim for switchers or a random originator IFX claim for continuers. All patients were required to have ≥5 originator IFX claims during the 12 months pre-index (prevalent population). The subset of patients with ≥12 months of observation prior to the first originator IFX claim was also analyzed (incident population). Switchers were matched 1:3 to continuers. Discontinuation was defined as having ≥120 days between 2 consecutive index treatment claims.</p><p><strong>Results: </strong>Prevalent switchers (N=1109) were 3.57-times more likely than continuers (N=3327) to switch to another originator biologic (hazard ratio [HR]=3.57, p<0.001). Of 249 prevalent switchers who switched to another originator biologic, 200 (80.3%) switched back to originator IFX. Incident switchers (N=571) were 2.55-times more likely than continuers (N=1713) to switch to another originator biologic (HR=2.55, p<0.001). Of 118 incident switchers who switched to another originator biologic, 90 (76.3%) switched back to originator IFX. Prevalent switchers were 1.25-times more likely than continuers to discontinue index therapy (HR=1.25, p<0.001). Similar results were observed in RA (prevalent population; switching: HR=3.49, p<0.001; discontinuation: HR=1.23, p=0.009) and IBD (prevalent population; switching: HR=3.82, p<0.001; discontinuation: HR=1.29, p=0.003) subgroups.</p><p><strong>Conclusion: </strong>Patients switching from originator to biosimilar IFX were more likely to switch to another originator biologic (notably back to originator IFX) and discontinue index treatment than those remaining on originator IFX; however, reasons for switching are unknown.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2021-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/47/f3/btt-15-1.PMC7797299.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10343101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biologic Therapies for Giant Cell Arteritis.","authors":"Robert Harrington,&nbsp;Shamma Ahmad Al Nokhatha,&nbsp;Richard Conway","doi":"10.2147/BTT.S229662","DOIUrl":"https://doi.org/10.2147/BTT.S229662","url":null,"abstract":"<p><p>Glucocorticoids have been the mainstay of treatment in giant cell arteritis (GCA) for the past 70 years. Conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) have largely failed to show significant clinical efficacy or reduction of the glucocorticoid burden in GCA. Tocilizumab is the first biologic to make a substantial impact in GCA treatment. With the current understanding of GCA pathogenesis implicating multiple cytokines, notably interleukin (IL) 6, IL-12, IL-23, IL-1β, and the role of janus kinases (JAKs) and the signal transducer and activator of transcription (STAT) pathway in these cytokines, many biologics are currently being investigated in GCA. This review article looks at the existing evidence for biologic agents in GCA. In addition to tocilizumab, the potential role of ustekinumab, abatacept, JAK inhibitors and other promising biologics in GCA are discussed in detail. A treatment algorithm based on the best evidence to date is also presented.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2021-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4f/a7/btt-15-17.PMC7797292.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38817977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How Can We Engineer CAR T Cells to Overcome Resistance?","authors":"Maya Glover,&nbsp;Stephanie Avraamides,&nbsp;John Maher","doi":"10.2147/BTT.S252568","DOIUrl":"https://doi.org/10.2147/BTT.S252568","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR) T cell therapy has achieved unrivalled success in the treatment of B cell and plasma cell malignancies, with five CAR T cell products now approved by the US Food and Drug Administration (FDA). However, CAR T cell therapies for solid tumours have not been nearly as successful, owing to several additional challenges. Here, we discuss mechanisms of tumour resistance in CAR T cell therapy and the emerging strategies that are under development to engineer CAR T cells to overcome resistance.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/52/56/btt-15-175.PMC8141613.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9578933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fetal Acrania (Exencephaly) in the Context of a Pregnant Female Taking Adalimumab for Psoriasis: A Case Report.","authors":"Nujud Daham,&nbsp;Abdullah AlMuqrin,&nbsp;Abdulaziz Madani,&nbsp;Fahad AlSaif","doi":"10.2147/BTT.S273762","DOIUrl":"https://doi.org/10.2147/BTT.S273762","url":null,"abstract":"<p><p>Adalimumab is a fully human, recombinant, IgG1 monoclonal antibody that targets tumor necrosis factor-alpha (TNF-alpha). It has been established that adalimumab can cross the placenta and can be detected in the fetal circulation for up to 6 months postpartum. However, clinical studies have failed to show any consistent or specific adverse fetal outcomes from maternal exposure to adalimumab during pregnancy. In our report, we present a case of fetal acrania (exencephaly) in the setting of a pregnant female taking adalimumab prior to and during pregnancy. Exencephaly is a neural tube defect (NTD) that results from failure of closure of the neural fold. It is true that there were other risk factors that might have contributed to our patient's unfortunate outcome. For example, she did not take folic acid supplementation prior to or during her pregnancy. Nonetheless, studies have shown that folic acid deficiency alone is not sufficient to lead to the development of NTDs. Our patient's exposure to adalimumab during her pregnancy might have added to the risk in her situation. Our report aims to inform clinicians of that possible risk and to stimulate them to report any similar outcomes.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2020-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/BTT.S273762","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38614227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Therapeutic Drug Monitoring in the Clinical Management of Patients with Rheumatic Diseases: Data from a Retrospective Single-Center Cohort Study.","authors":"Lise Pedersen,&nbsp;Pal Bela Szecsi,&nbsp;Per Birger Johansen,&nbsp;Poul Jannik Bjerrum","doi":"10.2147/BTT.S262511","DOIUrl":"https://doi.org/10.2147/BTT.S262511","url":null,"abstract":"<p><strong>Purpose: </strong>Treatment of rheumatic diseases with tumor necrosis factor inhibitors leads to improved clinical outcomes. Therapeutic drug monitoring (TDM) may assist in guiding clinical decisions. This study investigates the impact of TDM on clinical outcome, decision-making and biologics cost expenditure.</p><p><strong>Patients and methods: </strong>In a retrospective observational study of 306 patients with rheumatic diseases treated with four different tumor necrosis factor inhibitors, drug levels and antidrug antibodies were measured over a period of one year. Primary outcomes were the clinicians' response to each TDM result and the clinical outcome two years after TDM initiation. Outcomes were compared between the 111 TDM-guided patients and the 195 empirically guided patients.</p><p><strong>Results: </strong>Treatment change occurred in 55% of the patients in the TDM group, but in only 38% in the empirically guided group. In the TDM group, 89 (79.5%) patients were in remission or had low disease activity after two years follow-up compared to 128 (65.6%) patients in the empirical group. The average cost of biologics per patient per year was lower in the TDM group than in the empirical group for patients receiving infliximab, adalimumab or etanercept at baseline but not for golimumab.</p><p><strong>Conclusion: </strong>TDM-guided decision-making is useful in rheumatic patients receiving TNFi and may optimize therapeutic decisions, leading to a better control of disease activity. Proactive TDM may support decisions on dose tapering, resulting in lower drug consumption and biologics cost expenditure.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2020-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/BTT.S262511","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38578685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nucleic Acid Therapy for β-Thalassemia.","authors":"Annette d'Arqom","doi":"10.2147/BTT.S265767","DOIUrl":"https://doi.org/10.2147/BTT.S265767","url":null,"abstract":"<p><p>β-thalassemia is caused by mutations in the β-globin gene which diminishes or abolishes β-globin chain production. This reduction causes an imbalance of the α/β-globin chain ratio and contributes to the pathogenesis of the disease. Several approaches to reduce the imbalance of the α/β ratio using several nucleic acid-based technologies such as RNAi, lentiviral mediated gene therapy, splice switching oligonucleotides (SSOs) and gene editing technology have been investigated extensively. These approaches aim to reduce excess free α-globin, either by reducing the α-globin chain, restoring β-globin expression and reactivating γ-globin expression, leading a reduced disease severity, treatment necessity, treatment interval, and disease complications, thus, increasing the life quality of the patients and alleviating economic burden. Therefore, nucleic acid-based therapy might become a potential targeted therapy for β-thalassemia.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2020-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/BTT.S265767","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38424125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene, Cell and Antibody-Based Therapies for the Treatment of Age-Related Macular Degeneration.","authors":"Engin Akyol, Andrew Lotery","doi":"10.2147/BTT.S252581","DOIUrl":"10.2147/BTT.S252581","url":null,"abstract":"<p><p>Here we discuss antibody, cell and gene-based therapies that are currently available and under investigation for both wet and dry age-related macular degeneration (AMD). We initially discuss ocular anatomy, AMD modelling as well as the underlying pathophysiology of AMD. The antibody-based trials which have revolutionised the management of wet AMD are reviewed. The latest concepts in antibody therapy for wet AMD such as the port delivery systems, bispecific antibodies, designed ankyrin repeat protein (DARPINs) and brolucizumab are explored. Furthermore, the antibody-based trials targeting the complement pathway to reduce progression of geographic atrophy (GA) in dry AMD are discussed. Stem cell therapy and gene therapy are novel treatment modalities with no established clinical use in wet or dry AMD. Here, we discuss their efficacy so far in clinical trials. Their benefits and risk in the treatment of both wet and dry AMD are evaluated.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2020-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/40/8e/btt-14-83.PMC7494004.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38424124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}