Biologics : Targets & Therapy最新文献

{"title":"Remicade® (infliximab): 20 years of contributions to science and medicine","authors":"R. Melsheimer, A. Geldhof, I. Apaolaza, T. Schaible","doi":"10.2147/BTT.S207246","DOIUrl":"https://doi.org/10.2147/BTT.S207246","url":null,"abstract":"Abstract On August 24, 1998, Remicade® (infliximab), the first tumor necrosis factor-α (TNF) inhibitor, received its initial marketing approval from the US Food and Drug Administration for the treatment of Crohn’s disease. Subsequently, Remicade was approved in another five adult and two pediatric indications both in the USA and across the globe. In the 20 years since this first approval, Remicade has made several important contributions to the advancement of science and medicine: 1) clinical trials with Remicade established the proof of concept that targeted therapy can be effective in immune-mediated inflammatory diseases; 2) as the first monoclonal antibody approved for use in a chronic condition, Remicade helped in identifying methods of administering large, foreign proteins repeatedly while limiting the body’s immune response to them; 3) the need to establish Remicade’s safety profile required developing new methods and setting new standards for postmarketing safety studies, specifically in the real-world setting, in terms of approach, size, and duration of follow-up; 4) the study of Remicade has improved our understanding of TNF’s role in the immune system, as well as our understanding of the pathophysiology of a range of diseases characterized by chronic inflammation; and 5) Remicade and other TNF inhibitors have transformed treatment practices in these chronic inflammatory diseases: remission has become a realistic goal of therapy and long-term disability resulting from structural damage can be prevented. This paper reviews how, over the course of its development and 20 years of use in clinical practice, Remicade was able to make these contributions.","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"13 1","pages":"139 - 178"},"PeriodicalIF":4.0,"publicationDate":"2019-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/BTT.S207246","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41355401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical utility of ramucirumab in non-small-cell lung cancer.","authors":"Dipesh Uprety","doi":"10.2147/BTT.S175034","DOIUrl":"https://doi.org/10.2147/BTT.S175034","url":null,"abstract":"<p><p>Lung cancer is the leading cause of cancer-related mortality worldwide. Non-small-cell lung cancer (NSCLC) accounts for about 85% of all lung cancer cases and approximately 70% of patients with NSCLC have locally advanced or metastatic disease at presentation. In NSCLC patients with advanced or metastatic disease, second line treatment with chemotherapy is associated with a poor response rate. In this article, we have reviewed the role of ramucirumab in patients with NSCLC. Ramucirumab is not current standard of care in the first line setting in the treatment of advanced or metastatic NSCLC, based on phase II data which did not show any progression-free survival (PFS) and overall survival (OS) benefit when ramucirumab was compared with non-ramucirumab arm. The REVEL study was a phase III, placebo-controlled trial which included patients with stage IV NSCLC who had progressed during or after platinum-based chemotherapy, with or without bevacizumab. Median OS was 9.1 months vs 10.5 months (HR 0.86, 95% CI 0.75-0.98) in the placebo and ramucirumab group respectively. Seventy-nine percent of patients in ramucirumab arm and 71% of patients in non-ramucirumab arm had grade ≥3 treatment-related adverse events. The addition of ramucirumab to docetaxel can be considered in younger patients with good performance status as a second line treatment option. Additionally, combined blockage of the VEGFR and EGFR pathway has been utilized to overcome resistance to EGFR therapy. The RELAY trial was a phase III, placebo-controlled trial which included patients with sensitizing EGFR mutation positive stage IV NSCLC. Patients were randomized to either ramucirumab plus erlotinib or erlotinib. The trial showed that the combination therapy showed superior PFS benefit.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"13 ","pages":"133-137"},"PeriodicalIF":4.0,"publicationDate":"2019-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/BTT.S175034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41190497","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":"Therapeutic drug monitoring of biologics in psoriasis","authors":"M. M. Liau, H. Oon","doi":"10.2147/BTT.S188286","DOIUrl":"https://doi.org/10.2147/BTT.S188286","url":null,"abstract":"Biologics are an important component of the armamentarium of drugs in the treatment of moderate to severe psoriasis. There is increasing evidence that therapeutic drug monitoring (TDM) encompassing the measurement of trough concentrations and anti-drug antibodies (ADA), together with clinical response is emerging as a valuable tool for clinical decision making. It aids in targeted dose adjustments in patients with low drug concentrations, monitoring of adherence and assessment of patients who lose response to biologics or do not respond at all. The high prevalence of psoriasis, its impact on patients’ lives and costs spent on therapy motivate an evidence-based and cost-effective utility of biologics. We performed a literature review on the TDM of TNF alpha antagonists (adalimumab, infliximab, etanercept), IL12/23 antagonists (ustekinumab, guselkumab, tildrakizumab), IL17A inhibitors (secukinumab, ixekizumab) and biosimilars used in the treatment of psoriasis. Although establishing target therapeutic ranges for biologics is ideal, this has only been explored in adalimumab. We also propose a treatment algorithm for the practical application of TDM depending on drug trough concentrations, presence/absence of anti-drug antibodies and clinical response of patients. The practice of TDM is recommended in routine clinical practice where possible.","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"13 1","pages":"127 - 132"},"PeriodicalIF":4.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/BTT.S188286","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45305554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antitumor and antibacterial properties of virally encoded cationic sequences","authors":"J. Colle, B. Périchon, Alphonse Garcia","doi":"10.2147/BTT.S201287","DOIUrl":"https://doi.org/10.2147/BTT.S201287","url":null,"abstract":"Objective: The objective of this study was to test our Viral Quinta Columna Strategy (VQCS), a new biological hypothesis predicting that specific multifunctional virally encoded cationic domains may have the capacity to penetrate human cells and interact with PP2A proteins to deregulate important human intracellular pathways, and may display LL37 cathelicidin-like antagonistic effects against multiple pathogens such as bacteria or viruses. Methods: We comparatively analyzed the host defense properties of adenodiaphorins and of some specific cationic sequences encoded by different viruses using two distinct biological models: U87G, a well-characterized cell tumor model; and a group B Streptococcus agalactiae NEM316 ΔdltA, highly sensitive to LL37 cathelicidin. Results: We found that the adenovirus type 2 E4orf4 is a cell-permeable protein containing a new E4orf464–95 protein transduction domain, named large adenodiaphorin or LadD64–95. Interestingly, the host defense LL37 peptide is the unique cathelicidin in humans. In this context, we also demonstrated that similarly to LL37 LadD64–95, several virally encoded cationic sequences including the C-terminus HIV-1 89.6 Vpr77–92, shorter adenodiaphorins AdD67–84/AdD/69–84/AdD69–83, as well as HIV-2 Tat67–90 and JC polyomavirus small t115–134, displayed similar toxicity against Gram-positive S. agalactiae NEM316 ΔdltA strain. Finally, LadD64–95, adenodiaphorin AdD67–84, AdD69–84, and LL37 and LL17–32 cathelicidin peptides also inhibited the survival of human U87G glioblastoma cells. Conclusion: In this study, we demonstrated that specific cationic sequences encoded by four different viruses displayed antibacterial activities against S. agalactiae NEM316 ΔdltA strain. In addition, HIV-1 Vpr71–92 and adenovirus 2 E4orf464–95, two cationic penetrating sequences that bind PP2A, inhibited the survival of U87G glioblastoma cells. These results illustrate the host defense properties of virally encoded sequences and could represent an initial step for future complete validation of the VQCS hypothesis.","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"13 1","pages":"117 - 126"},"PeriodicalIF":4.0,"publicationDate":"2019-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/BTT.S201287","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44517857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recurrent ruptured abdominal aneurysms in polyarteritis nodosa successfully treated with infliximab","authors":"Butsabong Lerkvaleekul, S. Treepongkaruna, Nichanan Ruangwattanapaisarn, T. Treesit, S. Vilaiyuk","doi":"10.2147/BTT.S204726","DOIUrl":"https://doi.org/10.2147/BTT.S204726","url":null,"abstract":"Abstract Systemic polyarteritis nodosa (PAN) is a rare form of necrotizing vasculitis in children. Recurrent episodes of abdominal aneurysm ruptures are uncommon and life-threatening condition in children. Failures of response to immunosuppressive medications and radiological intervention also lead to high mortality. Some reports suggested that tumor necrosis factor (TNF) might have role in the inflammation of this disease. After an English-language literature review, this is the first case report in children of recurrent abdominal-ruptured aneurysms with a failure of conventional therapy but successfully treated with anti-TNF-α monoclonal antibody. We herein describe a 9-year-old girl who presented with chronic abdominal pain, hypertension, and massive lower gastrointestinal bleeding. The disease was refractory to conventional treatment, including administration of a corticosteroid, cyclophosphamide, and intravenous immunoglobulin, and recurrent-ruptured aneurysms developed in the gastrointestinal tract. Arterial embolization during angiography resulted in temporary improvement of the gastrointestinal bleeding. Infliximab, a chimeric anti-tumor necrosis factor-α monoclonal antibody, was initiated and resulted in disease remission with resolution of the gastrointestinal bleeding and abdominal pain. Anti-TNF therapy might be another treatment option for refractory disease to prevent ongoing inflammation that could lead to aneurysmal dilatation or even rupture. However, early recognition of refractory disease and aggressive treatment in the early course of the disease are crucial to reduce morbidity and mortality.","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"13 1","pages":"111 - 116"},"PeriodicalIF":4.0,"publicationDate":"2019-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/BTT.S204726","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41844691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRIP6 functions as a potential oncogene and facilitated proliferation and metastasis of gastric cancer","authors":"Lirong Zhu, Xiaodong Xu, Yijie Tang, Xiaochao Zhu","doi":"10.2147/BTT.S191863","DOIUrl":"https://doi.org/10.2147/BTT.S191863","url":null,"abstract":"Background: Increasing evidence suggests that TRIP6 has been considered to be aberrantly regulated in several malignancies and involved in tumor growth and metastasis. However, the biological role and prognostic significance of TRIP6 in gastric cancer (GC) still remains unclear. Materials and methods: TRIP6 expression was determined in matched GC tissues and adjacent normal tissues by western blot and real-time PCR. Then, immunohistochemistry was used to detect the expression of TRIP6 in GC patients. Statistical analysis was performed to evaluate the correlation between TRIP6 expression and clinicopathological characteristics and prognosis. Moreover, the effects of TRIP6 on GC cell proliferation and migration were also investigated by using MTT, colony formation and transwell assays. Results: We observed that the expression of TRIP6 was significantly up-regulated in GC tissues and cell ines. Our data indicated that high TRIP6 expression exhibited a significant correlation with poor prognosis for GC patients. Multivariate analysis showed that TRIP6 expression was an independent prognostic factor of the overall survival of GC patients. Furthermore, ectopic expression of TRIP6 promotes cell proliferation and migration in BGC823 cells, whereas knockdown of TRIP6 suppresses cell proliferation and migration in MKN45 cells. Conclusion: These findings demonstrate that TRIP6 exerts an important role in cancer development, which represents a potential prognostic indicator in GC.","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"13 1","pages":"101 - 110"},"PeriodicalIF":4.0,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/BTT.S191863","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47849512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Infliximab in treatment of idiopathic refractory childhood pyoderma gangrenosum (PG).","authors":"Farhad Salehzadeh,&nbsp;Yusef Mohammadikebar,&nbsp;Afsaneh Enteshary,&nbsp;Omid Ghanbarpour,&nbsp;Mehrdad Mirzarahimi","doi":"10.2147/BTT.S203753","DOIUrl":"https://doi.org/10.2147/BTT.S203753","url":null,"abstract":"<p><p>We report a case of refractory idiopathic childhood pyoderma gangrenosum in a young boy who had suffered from this disease since 3 years of age. He had unfavorable responses and intermittent relapses under different combinations of cytotoxic and steroid therapies. Although there was not much information available about infliximab use for biologic and childhood pyoderma gangrenosum, eventually we decided to use infliximab in this patient. Infliximab showed a dramatic response and resulted in full recovery during 2 years' follow-up.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"13 ","pages":"97-99"},"PeriodicalIF":4.0,"publicationDate":"2019-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/BTT.S203753","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37367590","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":"New horizons for the treatment of severe, eosinophilic asthma: benralizumab, a novel precision biologic.","authors":"Marco Caminati,&nbsp;Diego Bagnasco,&nbsp;Rachele Vaia,&nbsp;Gianenrico Senna","doi":"10.2147/BTT.S157183","DOIUrl":"https://doi.org/10.2147/BTT.S157183","url":null,"abstract":"<p><p>In the last decades, the increasing evidence concerning inflammation mechanisms underlying severe eosinophilic asthma has highlighted new potential therapeutic targets and has paved the way to new selective biologic drugs. Understanding the mechanism of action and the clinical outcomes of a particular drug along with the clinical and biological characteristics of the patient population for which that drug was intended may ensure appropriate selection of patients that will respond to that drug. Under this perspective, the present review will focus on the mechanisms of action and clinical evidence of benralizumab as a treatment option for severe eosinophilic asthma, in order to provide a concise overview and a reference for clinical practice. Benralizumab is a fully humanized afucosylated IgG1κ mAb that binds to an epitope on IL-5 Rα, and inhibits IL-5 signaling. Benralizumab also sustains antibody-directed cell-mediated cytotoxicity (ADCC) of eosinophils and basophils and consequently depletes IL-5Rα-expressing cells. As a result, it is responsible for a substantial depletion of blood, tissue, and bone marrow eosinophilia. This unique mechanism of action may account for a more complete and rapid action profile. Randomized clinical trials have demonstrated that benralizumab provides an optimal safety profile, and is able to significantly reduce asthma exacerbations, oral steroid intake, and to improve lung function. Some clinical predictors of enhanced clinical response to benralizumab have also been identified, including: a level of blood eosinophils ≥300 μL^-1, oral steroids use, the presence of nasal polyposis, FVC <65% of predicted, and a history of three or more exacerbations per year at baseline. These results can be helpful in identifying the best responder patients to benralizumab. As a step forward, the definition of the responder profile for each of the available biological treatment options will potentially support even more the pathway to precision medicine and the critical matching of the right drug with the right patient.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"13 ","pages":"89-95"},"PeriodicalIF":4.0,"publicationDate":"2019-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/BTT.S157183","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37324019","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":"Outcomes of various types of therapy in patients with treatment-resistant acrodermatitis continua of Hallopeau.","authors":"L M Smirnova,&nbsp;E Yu Vertieva,&nbsp;O Yu Olisova,&nbsp;E M Anpilogova","doi":"10.2147/BTT.S199100","DOIUrl":"https://doi.org/10.2147/BTT.S199100","url":null,"abstract":"<p><p><b>Background:</b> Chronic acrodermatitis continua of Hallopeau (ACH) is a rare form of pustular psoriasis predominantly affecting the distal phalanges of the fingers and toes. The disease manifests by pustular rash with marked infiltration, fissures, and often results into severe dystrophy of nail plates. ACH is refractory to most of psoriasis standard of care (SOC) therapies. <b>Objective:</b> The objective of this study is to assess the prospects of secukinumab therapy of ACH based on current clinical observation. <b>Methods:</b> We observed a female patient with ACH. Number of SOC treatments were applied in that case including local PUVA therapy, systemic retinoids, methotrexate, and biologic agents. <b>Result:</b> Secukinumab, a IL-17 inhibitor, demonstrated pronounced clinical effect in the case of ACH refractory to other SOC therapies. <b>Conclusion:</b> IL-17 inhibition provided by secukinumab was linked to clinically meaningful improvement in the heavily pretreated ACH. Further exploration and clinical studies may be important to provide more data on secukinumab effects in ACH.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"13 ","pages":"83-87"},"PeriodicalIF":4.0,"publicationDate":"2019-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/BTT.S199100","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37324018","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":"Dupilumab side effect in a patient with atopic dermatitis: a case report study.","authors":"Sakhar S Albader,&nbsp;Abdulmajeed A Alharbi,&nbsp;Rakan F Alenezi,&nbsp;Fahad M Alsaif","doi":"10.2147/BTT.S195512","DOIUrl":"https://doi.org/10.2147/BTT.S195512","url":null,"abstract":"<p><p>Atopic dermatitis (eczema) is a common chronic disease that is described as severe itching associated with recurrent eczematous lesions. In 2017 the US Food and Drug Administration approved dupilumab for treatment of adults with moderate to severe atopic dermatitis not well controlled with topical therapies or when other therapies are inadvisable. Dupilumab is a monoclonal antibody that inhibits interleukin-4 (IL-4) and IL-13 signaling by specifically binding to the IL-4R-alpha subunit shared by the IL-4 and IL-13 receptor complexes. There are many adverse effects reported after dupilumab therapy; commonly reported adverse effects include local injection site reactions, conjunctivitis, headache, and nasopharyngitis. Some adverse effects are rare, eg, alopecia areata and cicatricial extropion. We report a new case of a 28-year-old female who experienced face and neck rash after dupilumab injection.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"13 ","pages":"79-82"},"PeriodicalIF":4.0,"publicationDate":"2019-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/BTT.S195512","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37324016","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}