{"title":"Regarding \"Effectiveness and Persistence of Anti-TNFα Treatment in Patients with Rheumatoid Arthritis - A 7 Years Real-World Cohort Study\" [Response to Letter].","authors":"Pedro Santos-Moreno","doi":"10.2147/BTT.S551546","DOIUrl":"10.2147/BTT.S551546","url":null,"abstract":"","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"19 ","pages":"423-424"},"PeriodicalIF":5.3,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12278969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681952","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":"Brodalumab for Moderate-to-Severe Psoriasis: A Comprehensive Review of Efficacy, Safety, and Clinical Positioning.","authors":"Nickoulet Babaei, Minka Gill, Mireya Cervantes, Dahyeon Kim, Seanna Yang, Jashin J Wu","doi":"10.2147/BTT.S532526","DOIUrl":"10.2147/BTT.S532526","url":null,"abstract":"<p><p>Brodalumab is a monoclonal antibody that targets interleukin-17 receptor A (IL-17RA), offering a novel approach to treating moderate-to-severe psoriasis. By blocking IL-17RA, brodalumab inhibits the activity of multiple pro-inflammatory IL-17 isoforms, including IL-17A, IL-17F, and IL-17C, which are critical in the pathogenesis of psoriasis. This review synthesizes data from Phase I-IV clinical trials and real-world studies to provide a comprehensive overview of brodalumab's efficacy, safety, and clinical role in the treatment of moderate-to-severe psoriasis. Clinical trial data consistently demonstrate its rapid onset of action, high rates of skin clearance, and durability of response. Real-world evidence supports its effectiveness in treatment-resistant cases and among patients with previous biologic failures. Safety considerations include the need for monitoring suicidality, although no causal relationship has been confirmed. Despite being one of the most effective biologic agents available for psoriasis, brodalumab remains underutilized, highlighting the need for improved awareness of its potential clinical advantages. Further research is warranted to better define its role in treatment algorithms and to assess long-term outcomes in broader patient populations.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"19 ","pages":"415-422"},"PeriodicalIF":5.3,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12275985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673901","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":"Effects of Dulaglutide in Doxorubicin Induced Renal Toxicity in Rats.","authors":"Hogr Jasim Hama Said, Zheen Aorahman Ahmed","doi":"10.2147/BTT.S523547","DOIUrl":"10.2147/BTT.S523547","url":null,"abstract":"<p><strong>Objective: </strong>The present study was designed to determine the anti-inflammatory and antioxidant effects of dulaglutide (DUL) on doxorubicin (DOX) -induced acute kidney injury (AKI).</p><p><strong>Methods: </strong>Twenty-eight male rats were randomly allocated into four groups: the negative control group (received Distilled water), the positive control group (received Distilled water and a single dose of DOX), DUL 0.2 mg/kg group (received DUL 0.2 mg/kg twice weekly and single dose of DOX), and DUL 0.6 mg/kg group (received DUL 0.2 mg/kg twice weekly and single dose of DOX). All DOX doses (20 mg/kg) were given at day 13th of the study and all treatments were administered intraperitoneally for 14 days. On day fifteenth, the rats were sacrificed, and blood was collected to measure the complete blood count (CBC), Neutrophile/Lymphocyte Ratio (NLR), Monocyte/Lymphocyte Ratio (MLR), And Platelet/Lymphocyte Ratio (PLR), C-reactive protein (CRP), blood urea nitrogen (BUN), and serum creatinine (SCr). The right kidney was used for histopathological examination, while the left kidney was homogenized to assess the renal tissue levels of malondialdehyde (MDA), total antioxidant capacity (TAOC), interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α), kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL).</p><p><strong>Results: </strong>DOX induces acute kidney injury was demonstrated by significant elevations in BUN, SCr, and CRP levels. DUL significantly lowered the levels of BUN, SCr, and CRP, and reduced the levels of blood inflammation markers, including NLR and MLR. Additionally, it resulted in a significant reduction in the renal tissue levels of MDA, IL-1β, and TNF-α, while the level of TAOC was significantly elevated. These findings were supported by histopathological assessments.</p><p><strong>Conclusion: </strong>The present study indicates that DUL mitigates doxorubicin-induced kidney damage by reducing oxidative stress and inflammation.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"19 ","pages":"399-412"},"PeriodicalIF":5.3,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12235444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590411","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":"IRAK4 Targeting: A Breakthrough Approach to Combat Hidradenitis Suppurativa.","authors":"Hui Zhang, Zhi Liu, Bozhao Qin, Dapeng Cheng, Peisheng Chen, Xinling Bi","doi":"10.2147/BTT.S525106","DOIUrl":"10.2147/BTT.S525106","url":null,"abstract":"<p><p>Hidradenitis suppurativa (HS), a chronic inflammatory condition, features recurrent, painful lesions in the perineal area, severely impairing patients' quality of life. Despite its clinical significance, HS pathogenesis remains incompletely understood, and effective treatments are scarce. Interleukin-1 receptor-associated kinase 4 (IRAK4) is located downstream of IL-1R/TLR in the IL-1R/TLR signaling pathway, which is upstream of the end products of the pathway. IRAK4-targeted drugs can potentially block this pathway, reducing cytokine secretion and alleviating HS symptoms. This paper comprehensively reviews IRAK4 and its family members' physiological functions, systematically examines the IRAK family's roles in the IL-1R/TLR pathway, with a focus on IRAK4, analyzes IRAK4's specific role in HS, strengthening the theoretical basis for using IRAK4-targeted drugs. The text also covers representative drugs of the major biologics currently used in the treatment of HS and describes the IRAK4 inhibitor Zimlovisertib and the IRAK4 degrader KT-474, along with a discussion of the current status of drugs that inhibit IRAK4 in the treatment of HS and the challenges they face.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"19 ","pages":"387-397"},"PeriodicalIF":5.3,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12226999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574788","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":"Marstacimab for the Treatment of Hemophilia A or B.","authors":"Johnny Mahlangu","doi":"10.2147/BTT.S500480","DOIUrl":"10.2147/BTT.S500480","url":null,"abstract":"<p><p>Hemophilia A and B, caused by deficiencies of coagulation factors VIII or IX, result in impaired thrombin generation with consequent spontaneous or trauma-related bleeding, particularly hemarthroses. Although prophylactic factor replacement therapy remains the global standard of care for hemophilia, it has significant limitations, including intravenous administration, breakthrough bleeding, inhibitor development, and deteriorating arthropathy despite prophylaxis. Marstacimab, an IgG1 monoclonal antibody targeting tissue factor pathway inhibitor (TFPI), represents a novel non-factor approach. Marstacimab restores thrombin generation via the extrinsic pathway, bypassing intrinsic pathway deficiencies and offering prophylactic benefit independent of inhibitor status. Clinical evaluation across Phase 1b/2 and Phase 3 (BASIS) trials and ongoing extension studies has demonstrated robust efficacy. In Phase 3, marstacimab reduced annualized bleed rates by 91.6% compared with episodic treatment and was non-inferior to factor prophylaxis. Bleed control was sustained though zero-bleed outcomes were not uniformly achieved. Pharmacokinetic data support once-weekly fixed dosing independent of body weight, simplifying administration and potentially improving adherence. Across all studies, marstacimab demonstrated a favorable safety profile. Injection site reactions were the most common adverse events, while anti-drug antibodies, including neutralizing types, were transient and without clinical impact. Marstacimab, the first FDA-approved anti-TFPI antibody for prophylaxis in hemophilia A and B without inhibitors, addresses key unmet needs, particularly for hemophilia B patients lacking subcutaneous (SC) prophylaxis options. Its novel mechanism, ease of administration, and sustained efficacy position it as a significant therapeutic advance. Marstacimab's exact role in the hemophilia treatment armamentarium is yet to be established with the availability of coming real-world experience data. The long-term studies remain essential to fully demonstrate its role, especially in populations with inhibitors and in the context of evolving non-factor therapies. This review summarises currently available clinical data and contextualises these in light of other treatments in hemophilia.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"19 ","pages":"379-386"},"PeriodicalIF":5.3,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12205756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526425","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}
Huiwen Yang, Linlin Yang, Yingxin Liu, Linlin Wang
{"title":"Adebrelimab in Small Cell Lung Cancer: From Current Advances to Emerging Combination Strategy and Challenge.","authors":"Huiwen Yang, Linlin Yang, Yingxin Liu, Linlin Wang","doi":"10.2147/BTT.S500470","DOIUrl":"10.2147/BTT.S500470","url":null,"abstract":"<p><p>Adebrelimab is a fully humanized monoclonal antibody against programmed cell death-ligand 1 (PD-L1) that has been approved in combination with chemotherapy as the first-line treatment for extensive-stage small cell lung cancer (ES-SCLC). This approval was driven by the landmark CAPSTONE-1 trial, where adebrelimab demonstrated superior survival outcomes: median overall survival (mOS) improved from 12.8 to 15.3 months (HR=0.72, p=0.0017) and 3-year survival rates doubled (21.1% vs 10.5%) compared to chemotherapy alone. Based on this systemic treatment, addition of sequential thoracic radiotherapy achieved unprecedented mOS of 22.9 months in a Phase II trial. In limited-stage small cell lung cancer (LS-SCLC), the initial results of adebrelimab combined with concurrent chemoradiotherapy are promising. Whether in first-line or later-line treatment, there are numerous ongoing clinical trials to explore the potential of the novel adebrelimab-based regimen, and the results are highly anticipated. Despite ongoing efforts to identify biomarkers that may guide treatment decisions, no validated prognostic or predictive biomarkers are currently available for SCLC. This review summarizes the present role of adebrelimab in SCLC and outlines novel strategies aimed to further improve survival outcome.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"19 ","pages":"365-377"},"PeriodicalIF":5.3,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12138384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233104","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}
Ferdinando D'Amico, Sarah Bencardino, Fernando Magro, Axel Dignass, Ana Gutiérrez Casbas, Bram Verstockt, Ailsa Hart, Alessandro Armuzzi, Laurent Peyrin-Biroulet, Silvio Danese
{"title":"Positioning Guselkumab in The Treatment Algorithm of Patients with Crohn's Disease.","authors":"Ferdinando D'Amico, Sarah Bencardino, Fernando Magro, Axel Dignass, Ana Gutiérrez Casbas, Bram Verstockt, Ailsa Hart, Alessandro Armuzzi, Laurent Peyrin-Biroulet, Silvio Danese","doi":"10.2147/BTT.S530354","DOIUrl":"10.2147/BTT.S530354","url":null,"abstract":"<p><p>Guselkumab, a selective interleukin-23 (IL-23) inhibitor, has emerged as a promising biologic therapy for the management of patients with moderate-to-severe Crohn's disease (CD) and has been recently approved for its treatment. Unlike conventional therapies, guselkumab offers a different mechanism of action by selectively inhibiting IL-23, a key cytokine implicated in the pathogenesis of CD. IL-23 drives intestinal inflammation through activation of the Th17 cell pathway and other immune processes, positioning IL-23 inhibition as a critical therapeutic approach. In randomized Phase III clinical trials, guselkumab proved to be effective in inducing clinical and endoscopic remission both in patients naive to biologics and in patients already exposed to advanced therapies. Furthermore, no safety issues were found, supporting the well-characterized safety in other indications and its use in clinical practice also in IBD. Moreover, guselkumab has been approved for other immunomediated inflammatory disease moderate to severe plaque psoriasis, psoriatic arthritis and ulcerative colitis. This review summarizes the available evidence on efficacy and safety of guselkumab in patients with moderate to severe CD, focusing on its positioning in the treatment algorithm.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"19 ","pages":"351-363"},"PeriodicalIF":5.3,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12136076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224201","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":"Targeting CREBRF in Cancer: Mechanistic Insights and Future Directions.","authors":"Baixue Lv, Dongdong Zhang","doi":"10.2147/BTT.S522325","DOIUrl":"10.2147/BTT.S522325","url":null,"abstract":"<p><p>Luman/CREB3 recruitment factor (LRF), also known as CREBRF, was initially identified as a cellular binding protein of Luman through yeast two-hybrid screening of a human brain cDNA library. CREBRF plays a critical role in various biological processes, with its functions garnering significant attention in the field of oncology. Notably, CREBRF is involved in endoplasmic reticulum (ER) stress and regulates the unfolded protein response (UPR), leading to an accumulation of misfolded proteins. This can ultimately result in cellular dysfunction, apoptosis, and even tumorigenesis. In solid tumors, hypoxia is a common condition, and CREBRF has been implicated in hypoxia-induced autophagy, which promotes tumor cell proliferation. Depending on the tumor type and microenvironment, CREBRF exerts diverse effects by modulating distinct signaling pathways. This review summarizes CREBRF's involvement in ER stress, cell cycle regulation, autophagy, and the mechanisms through which it influences tumor initiation and progression across various cancer types. Furthermore, the potential of CREBRF as a therapeutic target in cancer treatment is discussed, providing insights into future research and clinical applications.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"19 ","pages":"341-350"},"PeriodicalIF":5.3,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12132502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214835","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}
Naim Ata, Hasan Satış, Orhan Küçükşahin, Erdem Karabulut, Gizem Ayan, Abdulsamet Erden, Emre Bilgin, Berkan Armağan, Duygu Tecer, Hakan Babaoğlu, Alper Sarı, Levent Kılıç, Mustafa Mahir Ülgü, Mustafa Okan Ayvalı, Şuayip Birinci, Umut Kalyoncu
{"title":"From Conventional to Advanced Therapies: A National Health Registry Report (2016-2022) on DMARDs in Rheumatoid Arthritis Treatment in Turkey.","authors":"Naim Ata, Hasan Satış, Orhan Küçükşahin, Erdem Karabulut, Gizem Ayan, Abdulsamet Erden, Emre Bilgin, Berkan Armağan, Duygu Tecer, Hakan Babaoğlu, Alper Sarı, Levent Kılıç, Mustafa Mahir Ülgü, Mustafa Okan Ayvalı, Şuayip Birinci, Umut Kalyoncu","doi":"10.2147/BTT.S507132","DOIUrl":"10.2147/BTT.S507132","url":null,"abstract":"<p><strong>Objective: </strong>There are national and international guidelines on the optimal use of disease-modifying anti-rheumatic drugs. In this study, we aimed to provide critical insights into the real-world efficacy and adherence of these DMARDs, providing a data-driven basis for optimizing treatment paradigms for RA within the national healthcare framework.</p><p><strong>Methods: </strong>This nationwide cohort study utilized data from the Turkish Ministry of Health National Electronic Database, known as E-Pulse between January 2016 and December 2022. In this analysis, cases of RA were identified using ICD-10 codes two times at least 30 days apart Treatment prescriptions were recorded based on their prescription at baseline and follow-up.</p><p><strong>Results: </strong>There were a total of 347,902 RA (79.5% female) patients in the E-Pulse system. The mean (SD) age of RA patients was 59.1 (14.8) years Methotrexate and sulfasalazine (35.1% vs 30.5%, OR 95% CI 0.81 usage was more common in men and hydroxychloroquine was more common in women 46.764 (13.4%) patients were prescribed bDMARD and/or tsDMARD 494.499 times. AntiTNF drugs are the most commonly prescribed drugs. This is followed by B-cell blockers, JAK inhibitors, anti-IL6 and T-cell blockers.</p><p><strong>Conclusion: </strong>Turkish national health database highlights the widespread use of synthetic DMARDs in treating rheumatoid arthritis (RA). While traditional DMARDs like methotrexate and hydroxychloroquine are favored the cautious use of advanced therapies, particularly anti-TNFs, suggests a potential for optimizing treatment protocols.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"19 ","pages":"331-339"},"PeriodicalIF":5.3,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12124983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198250","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}