Biologics : Targets & Therapy最新文献

{"title":"Treatment with Ixekizumab Following Secukinumab Failure in Patients with Psoriatic Arthritis: Real-Life Experience from a Resistant Population.","authors":"Julia Berman,&nbsp;Victoria Furer,&nbsp;Mark Berman,&nbsp;Ofer Isakov,&nbsp;Devy Zisman,&nbsp;Amir Haddad,&nbsp;Ori Elkayam","doi":"10.2147/BTT.S326792","DOIUrl":"https://doi.org/10.2147/BTT.S326792","url":null,"abstract":"<p><strong>Objective: </strong>To assess the clinical response to ixekizumab following secukinumab failure in patients with psoriatic arthritis.</p><p><strong>Methods: </strong>A retrospective multi-center observational study included psoriatic arthritis (PsA) patients with a history of treatment with secukinumab, further treated with ixekizumab. Primary endpoint was primary response to treatment (drug survival > 6 months); secondary endpoints were changes in disease activity indices from initiation of ixekizumab to 6 and 12 months later and overall drug survival.</p><p><strong>Results: </strong>Of 23 PsA patients, 86% (n = 20) received more than two TNF inhibitors (TNFi). Median secukinumab treatment time was 15 months (IQR 10-21.5 months). Subsequently, 19 patients (83%) had a primary response to ixekizumab. Overall treatment duration during follow-up period for primary responders was 14 months (IQR 10-20.5). Reasons for ixekizumab cessation were worsening psoriasis (27%), peripheral arthritis (27%), both (47%), worsening of axial disease (13%), and adverse events (6%). Articular disease indices including Disease Activity Index for Psoriatic Arthritis (DAPSA), tender joints count (TJC) and Simplified Disease Activity Index (SDAI) were significantly lower at 6 and 12 months (DAPSA 1.5-2 levels reduction; p = 0.018 and 1-1.5 levels reduction; p = 0.031, respectively; TJC -2.16 [-4.0, -0.3]; p = 0.025 and -1.69 [-3.09, -0.28]; p = 0.022, respectively; SDAI -10.13 [-16.4, -3.8], p = 0.003 and -12.2 [-17.1, -7.2], p = 0.0002, respectively). PASI75 at 6 and 12 months was achieved by 63% and 57%, respectively, and PASI100 at 6 and 12 months by 31% and 21%, respectively.</p><p><strong>Conclusion: </strong>Patients with resistant PsA, including inadequate response to secukinumab, demonstrated a good response to ixekizumab, albeit limited on time. Within class switch from secukinumab to ixekizumab may be a plausible therapeutic option in PsA patients following secukinumab failure.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":" ","pages":"463-470"},"PeriodicalIF":4.0,"publicationDate":"2021-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/98/d3/btt-15-463.PMC8608411.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39656135","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":"State-of-the-Art of Monoclonal Antibodies for the Treatment of Gastric Cancer.","authors":"Debora Basile,&nbsp;Francesca Simionato,&nbsp;Alessandro Cappetta,&nbsp;Silvio Ken Garattini,&nbsp;Giandomenico Roviello,&nbsp;Giuseppe Aprile","doi":"10.2147/BTT.S290323","DOIUrl":"https://doi.org/10.2147/BTT.S290323","url":null,"abstract":"<p><p>Gastric cancer (GC) is a complex and heterogeneous disease with poor prognosis and limited available treatment options. During recent years, several molecular stratifications have been proposed to optimize the overall treatment strategy for GC patients. Breakthroughs in cancer biology and in molecular profiling through DNA and RNA sequencing are now opening novel landscapes, leading to the personalization of molecular matched therapy. In particular, therapies against HER2, Claudine 18.2, Fibroblast Growth Factor Receptors (FGFR), and other molecular alterations could significantly improve survival outcomes in the advance phase of the disease. Furthermore, immunotherapy with checkpoint inhibitors also represents a promising option in a selected population. Hoping that precision oncology will enter soon in clinical practice, our review describes the state of the art of many novel pathways and the current evidence supporting the use of monoclonal antibodies implicated in GC treatment.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":" ","pages":"451-462"},"PeriodicalIF":4.0,"publicationDate":"2021-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/17/d2/btt-15-451.PMC8572727.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39613261","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":"Adalimumab Therapy in a Patient with Psoriasis, Down Syndrome, and Concomitant Hepatitis B Virus Infection.","authors":"Abdulaziz Madani,&nbsp;Qais Almuhaideb","doi":"10.2147/BTT.S317888","DOIUrl":"https://doi.org/10.2147/BTT.S317888","url":null,"abstract":"Abstract Down syndrome is the most common chromosomal disorder and may present with a combination of dysmorphic features, congenital heart disease, and immunological deficiency. The association between Down syndrome and psoriasis is unclear. The prevalence of psoriasis in patients with Down syndrome ranges from 0.5% to 8%. The safety of biologics in the treatment of Down syndrome-related psoriasis is still debated. Down syndrome results in mild immunological abnormalities; consequently, the risk of infectious complications during immunosuppressive therapy might be higher in this group of patients. We report a case of a 33-year-old male, a case of chronic plaque psoriasis, Down syndrome (DS), asthma, and hepatitis B. The patient was started on Calcipotriene 0.005%-betamethasone 0.064% ointment, which failed to control the patient’s psoriasis; thus, adalimumab was started. His response to adalimumab was significant, where over 70% improvement of the psoriatic lesions was seen.","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":" ","pages":"375-378"},"PeriodicalIF":4.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/03/9f/btt-15-375.PMC8419868.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39408942","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":"Stem Cell Therapy for Burns: Story so Far.","authors":"Najath Abdul Kareem,&nbsp;Ayesha Aijaz,&nbsp;Marc G Jeschke","doi":"10.2147/BTT.S259124","DOIUrl":"https://doi.org/10.2147/BTT.S259124","url":null,"abstract":"<p><p>Burn injuries affect approximately 11 million people annually, with fatalities amounting up to 180,000. Burn injuries constitute a global health issue associated with high morbidity and mortality. Recent years have seen advancements in regenerative medicine for burn wound healing encompassing stem cells and stem cell-derived products such as exosomes and conditioned media with promising results compared to current treatment approaches. Sources of stem cells used for treatment vary ranging from hair follicle stem cells, embryonic stem cells, umbilical cord stem cells, to mesenchymal stem cells, such as adipose-derived mesenchymal stem cells, bone marrow-derived mesenchymal stem cells, and even stem cells harvested from discarded burn tissue. Stem cells utilize various pathways for wound healing, such as PI3/AKT pathway, WNT-β catenin pathway, TGF-β pathway, Notch and Hedgehog signaling pathway. Due to the paracrine signaling mechanism of stem cells, exosomes and conditioned media derived from stem cells have also been utilized in burn wound therapy. As exosomes and conditioned media are cell-free therapy and contain various biomolecules that facilitate wound healing, they are gaining popularity as an alternative treatment strategy with significant improvement in outcomes. The treatment is provided either as direct injections or embedded in a natural/artificial scaffold. This paper reviews in detail the different sources of stem cells, stem cell-derived products, their efficacy in burn wound repair, associated signaling pathways and modes of delivery for wound healing.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":" ","pages":"379-397"},"PeriodicalIF":4.0,"publicationDate":"2021-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/97/41/btt-15-379.PMC8418374.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39408943","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":"An Overview of the Safety and Efficacy of Monoclonal Antibodies for the Chronic Obstructive Pulmonary Disease.","authors":"Mario Cazzola,&nbsp;Josuel Ora,&nbsp;Francesco Cavalli,&nbsp;Paola Rogliani,&nbsp;Maria Gabriella Matera","doi":"10.2147/BTT.S295409","DOIUrl":"https://doi.org/10.2147/BTT.S295409","url":null,"abstract":"<p><p>Several mAbs have been tested or are currently under clinical evaluation for the treatment of COPD. They can be subdivided into those that aim to block specific pro-inflammatory and pro-neutrophilic cytokines and chemokines, such as TNF-α, IL-1β, CXCL8 and IL-1β, and those that act on T2-mediated inflammation, respectively, by blocking IL-5 and/or its receptor, preventing IL-4 and IL-13 signaling, affecting IL-33 pathway and blocking TSLP. None of these approaches has proved to be effective, probably because in COPD there is no dominant cytokine or chemokine and, therefore, a single mAb cannot be effective on all pathways. With a more in-depth understanding of the numerous pheno/endotypic pathways that play a role in COPD, it may eventually be possible to identify those specific patients in whom some of these cytokines or chemokines might predominate. In this case, it will be possible to implement a personalized treatment, but the use of each mAb will only be reserved for a very limited number of subjects.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":" ","pages":"363-374"},"PeriodicalIF":4.0,"publicationDate":"2021-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/70/34/btt-15-363.PMC8407524.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39378861","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":"HHLA2 Expression is Associated with Poor Survival in Patients with Hepatocellular Carcinoma.","authors":"Yituo Xu,&nbsp;Zhijie Huang,&nbsp;Xingjuan Yu,&nbsp;Zhixiong Li,&nbsp;Limin Zheng,&nbsp;Jing Xu","doi":"10.2147/BTT.S325019","DOIUrl":"https://doi.org/10.2147/BTT.S325019","url":null,"abstract":"<p><strong>Background: </strong>Human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2) is a member of the B7 family; however, little is known regarding its expression and clinical relevance in hepatocellular carcinoma (HCC).</p><p><strong>Methods: </strong>To better characterize HHLA2 expression in HCC, we analyzed its expression by in situ staining and further investigated its correlation with immune infiltration and patient prognosis.</p><p><strong>Results: </strong>HHLA2 was primarily expressed in the peri-tumor region of HCC tissues and co-localized with CD68⁺ monocytes/macrophages. In vitro analysis and multi-immunofluorescence staining showed up-regulated HHLA2 expression in tumor-activated monocytes/macrophages, and HHLA2⁺ monocytes/macrophages expressed high levels of HLA-DR in HCC tissue. A correlation analysis showed that samples displaying high HHLA2 expression in the peri-tumor region had significant tumor infiltration of CD204⁺ and CD11b⁺ cells, and low expression of genes associated with an anti-tumor immune response. The high level of peri-tumoral HHLA2 expression was associated with a poor patient overall survival (OS; <i>P</i> = 0.008). A multivariate analysis revealed that HHLA2 expression in the peri-tumor region was an independent prognostic factor for OS (hazard ratio = 1.872, <i>p</i> = 0.003). Moreover, the expression of HHLA2 was negatively correlated with PD-L1, and patients exhibiting HHLA2 and programmed cell death-ligand 1(PD-L1) co-expression had the shortest survival time.</p><p><strong>Conclusion: </strong>HHLA2 expression represented an immunosuppressive microenvironment in HCC, and may serve as a potential target for immunotherapy.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":" ","pages":"329-341"},"PeriodicalIF":4.0,"publicationDate":"2021-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/dd/95/btt-15-329.PMC8370585.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39327876","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":"Biological Therapies for Rheumatoid Arthritis: An Overview for the Clinician.","authors":"Kate E Findeisen,&nbsp;Julia Sewell,&nbsp;Andrew J K Ostor","doi":"10.2147/BTT.S252575","DOIUrl":"https://doi.org/10.2147/BTT.S252575","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a disease characterised by inflammation of synovial joints and poses a substantial healthcare burden on both the individual and society. One of the most significant shifts in the RA therapeutic landscape has occurred with the introduction of biological disease modifying anti-rheumatic drugs (bDMARDs). There are five classes of bDMARDs currently available, each with a different molecular target and subtle differences in their efficacy and safety profile. This review also describes the \"real-world\" use of bDMARDs and how they fit into the overall RA treatment guidelines.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":" ","pages":"343-352"},"PeriodicalIF":4.0,"publicationDate":"2021-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/60/59/btt-15-343.PMC8370108.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39327877","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":"Infliximab in Combination with Low-Dose Acitretin in Generalized Pustular Psoriasis: A Report of Two Cases and Review of the Literature.","authors":"Marta Kołt-Kamińska,&nbsp;Magdalena Żychowska,&nbsp;Adam Reich","doi":"10.2147/BTT.S323239","DOIUrl":"https://doi.org/10.2147/BTT.S323239","url":null,"abstract":"<p><p>Generalized pustular psoriasis (GPP) is a severe, life-threatening disease that represents a major therapeutic challenge. There is a lack of randomized controlled trials assessing the efficacy of various treatment options for GPP. TNFα inhibitors have proven to be effective and are increasingly used in this indication. In the current paper, we present two patients with GPP treated with infliximab (Ifx) and a literature review appraising currently available data on the use of Ifx in GPP. Case 1 was a 73-year-old woman with GPP who exhibited lack of treatment response or primary intolerance to standard therapeutic options (high-dose acitretin, methotrexate, cyclosporine A, and methylprednisolone). However, Ifx therapy combined with low-dose acitretin resulted in rapid and sustained resolution of skin lesions. Case 2 was a 60-year-old man with GPP and numerous comorbidities who was initially treated with Ifx in combination with methotrexate, with good treatment response for 9 months. Following an infection-induced flare of GPP at week 38, methotrexate was discontinued in favor of low-dose acitretin and Ifx continued. This regimen again resulted in rapid resolution of pustules. We present these cases to highlight the advantage of long-term Ifx therapy with low-dose acitretin in GPP.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":" ","pages":"317-327"},"PeriodicalIF":4.0,"publicationDate":"2021-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/08/84/btt-15-317.PMC8357619.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39311856","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":"View Point: Disease Modification and Cell Secretome Based Approaches in Parkinson's Disease: Are We on the Right Track?","authors":"Thomas Müller","doi":"10.2147/BTT.S267281","DOIUrl":"https://doi.org/10.2147/BTT.S267281","url":null,"abstract":"<p><p>The term idiopathic Parkinson's disease describes an entity of various not well-characterized disorders resembling each other. They are characterized by chronic neuronal dying originating from various disease mechanisms. They result in the onset of motor and related non-motor features, both of which respond to administration of personalized drug combinations and surgical therapies. The unmet need is beneficial disease course modification with repair and neurogenesis. Objectives are to discuss the value of cell secretome based treatments including neuronal graft transplantation and to suggest as an alternative the stimulation of an endogenous available approach for neuronal repair. Chronic neurodegenerative processes result from different heterogeneous, but complementing metabolic, pathological cascade sequences. Accumulated evidence from experimental research suggested neuron transplantation, stem cell application and cell secretome-based therapies as a promising future treatment with cure as an ultimate goal. To date, clinical testing of disease-modifying treatments has focused on substitution or repair of the remaining dopamine synthesizing neurons following diagnosis. At diagnosis, many of the still surviving and functioning, but already affected neurons have lost most of their axons and are primed for cell death. A more promising therapeutic concept may be the stimulation of an existing, endogenous repair system in the peripheral and central nervous systems. The abundant protein repulsive guidance molecule A blocks restoration and neurogenesis, both of which are mediated via the neogenin receptor. Inhibition of the physiological effects of repulsive guidance molecule A is an endogenous available repair pathway in chronic neurodegeneration. Antagonism of this protein with antibodies or stimulation of the neogenin receptor should be considered as an initial repair step. It is an alternative to cell replacement, stem cell or associated cell secretome concepts.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":" ","pages":"307-316"},"PeriodicalIF":4.0,"publicationDate":"2021-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1a/a2/btt-15-307.PMC8328382.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39278051","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":"Stem Cell Therapy for Retinal Degeneration: The Evidence to Date.","authors":"Amit Sharma,&nbsp;Bithiah Grace Jaganathan","doi":"10.2147/BTT.S290331","DOIUrl":"https://doi.org/10.2147/BTT.S290331","url":null,"abstract":"<p><p>There is a rise in the number of people who have vision loss due to retinal diseases, and conventional therapies for treating retinal degeneration fail to repair and regenerate the damaged retina. Several studies in animal models and human trials have explored the use of stem cells to repair the retinal tissue to improve visual acuity. In addition to the treatment of age-related macular degeneration (AMD) and diabetic retinopathy (DR), stem cell therapies were used to treat genetic diseases such as retinitis pigmentosa (RP) and Stargardt's disease, characterized by gradual loss of photoreceptor cells in the retina. Transplantation of retinal pigment epithelial (RPE) cells derived from embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have shown promising results in improving retinal function in various preclinical models of retinal degeneration and clinical studies without any severe side effects. Mesenchymal stem cells (MSCs) were utilized to treat optic neuropathy, RP, DR, and glaucoma with positive clinical outcomes. This review summarizes the preclinical and clinical evidence of stem cell therapy and current limitations in utilizing stem cells for retinal degeneration.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":" ","pages":"299-306"},"PeriodicalIF":4.0,"publicationDate":"2021-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d1/08/btt-15-299.PMC8327474.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39276633","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}