Biologics : Targets & Therapy最新文献

{"title":"Optimization of Recombinant Human Interferon-Gamma Expression and Purification in <i>E. coli</i>, and Developing an Immunization Protocol for the Production of Optimal Humoral Response.","authors":"Vanessa Uwituze, Claire M Mugasa, Monica Namayanja, David Paul Nalumenya, Jerome Ndayisenga, Kenneth Ssekatawa, Charles Drago Kato","doi":"10.2147/BTT.S584180","DOIUrl":"https://doi.org/10.2147/BTT.S584180","url":null,"abstract":"<p><strong>Background: </strong>Recombinant human interferon gamma (rhIFN-γ) and monoclonal antibodies are promising biomolecules for improving clinical medicines worldwide due to their biomedical applications. However, most African countries lack established production protocols. Although Freund's Complete Adjuvant (FCA) has been widely used to enhance antibody production, it has been reported to cause adverse effects. This study aimed to optimize the expression and purification of rhIFNγ and develop an immunization protocol for producing optimal humoral responses using alternative adjuvants such as RIBI Immunochem (RIBI) adjuvant and Freund's Incomplete Adjuvant (FIA), with FCA as the standard.</p><p><strong>Methodology: </strong>The human interferon gamma (NM000619.3) sequence was retrieved from NCBI and sent to GenScript for codon optimization and construct synthesis. The constructs were transformed into <i>E. coli</i> BL-21, and protein expression was induced with IPTG. The expression and purification conditions were optimized. To evaluate immunization regimens and alternative adjuvants to FCA, three groups of female BALB/c mice were immunized with varying concentrations of rhIFNγ (25, 50, and 100 µg) mixed with an equal volume of RIBI adjuvant, FIA, and FCA. An Enzyme-Linked Immunosorbent Assay was used to measure antibody levels from each group.</p><p><strong>Results: </strong>The study identified 0.6 mM of IPTG at 37°C and 250 rpm for 4 hours as the optimal conditions for rhIFNγ expression. Increasing imidazole concentration in wash and elution buffers enhanced rhIFNγ purity but reduced protein yield. Administration of 100 µg of rhIFNγ with RIBI adjuvant elicited a sufficient immune response, while higher concentrations of FCA and FIA increased side effects, indicating the need for lower adjuvant doses.</p><p><strong>Conclusion: </strong>Although FCA has been reported to produce high antibody titers with notable side effects, this study found no significant difference in antibody levels between mice immunized with 100 µg rhIFNγ mixed with FCA and the group immunized with 100 µg rhIFNγ plus RIBI adjuvant.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"20 ","pages":"584180"},"PeriodicalIF":3.4,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13097614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761406","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":"Enhancement of Gastric Mucosal Defense by Phytomedicine in the Context of <i>H. pylori</i>-Associated Ulcer Disease.","authors":"Raja Singh Paulraj, Parthasarathi Perumal, Arunkumar Ramachandran, Anbazhagan Sathiyaseelan","doi":"10.2147/BTT.S597797","DOIUrl":"https://doi.org/10.2147/BTT.S597797","url":null,"abstract":"<p><p>Gastric ulcer disease remains a significant global health concern, with <i>Helicobacter pylori</i> (<i>H. pylori</i>) infection being a primary etiological factor. Conventional therapies are increasingly limited by antibiotic resistance, treatment failure, and adverse effects. In this context, phytomedicine has emerged as a promising complementary and alternative therapeutic approach. This review systematically discusses the key mechanisms by which phytomedicines enhance gastric mucosal defense, including antioxidant activity, anti-inflammatory modulation, inhibition of urease and bacterial adhesion, suppression of virulence factors, and restoration of epithelial barrier integrity. Plant-derived bioactive compounds demonstrate multi-targeted gastroprotective effects through modulation of oxidative stress, cytokine signaling, prostaglandin synthesis, and tight junction preservation. While preclinical and limited clinical evidence support their therapeutic potential, further well-designed clinical trials and standardized phytochemical formulations are required to validate translational applicability.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"20 ","pages":"597797"},"PeriodicalIF":3.4,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13092447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761431","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":"Rheumatoid Factor Beyond Rheumatoid Arthritis: A Potential Marker of Cardiometabolic and Hepatic Risk.","authors":"Simeon Ikechukwu Egba, Innocent Ogheneovo Orhonigbe, Ngozi Kalu Achi, Gavin Chibundu Ikechukwu, Charles Nnanna Chukwu, Chukwudi Humphrey Omeoga","doi":"10.2147/BTT.S603345","DOIUrl":"10.2147/BTT.S603345","url":null,"abstract":"<p><p>Rheumatoid factor (RF), which is an autoantibody that is predominantly targeted at the Fc region in IgG, has been a key point of diagnosis and prognostication of rheumatoid arthritis (RA). There is, however, an emergent body of evidence that RF positivity, including in persons with preexisting autoimmune disease as well as asymptomatic seropositive persons, can indicate more global immune dysregulation with consequences of cardiometabolic and hepatic health. RF is involved in the development of circulating immune complexes, which increases inflammation through complement activation, Fc receptor interaction and cytokine release. These routes are becoming well-known mechanistic causes of cardiometabolic diseases, such as atherosclerosis, insulin resistance, metabolic syndrome, and heart failure. Similarly, the immune-complex deposition and chronic inflammatory signaling also play a role in hepatic injury, metabolic dysfunction-associated fatty liver disease (MAFLD) and fibrosis. The present review summarizes the existing information about the role of RF as a predictor and a possible mediator of cardiometabolic and hepatic dysfunction in chronic diseases. We searched scientific databases for epidemiologic relationships, possible biological pathways, and clinical implications for risk stratification and integrated care. RF could serve as an accessible biomarker of systemic inflammatory risk, complementing its traditional role in rheumatology and, within the framework of precision medicine, helping to guide early detection and preventive strategies across diverse clinical populations.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"20 ","pages":"603345"},"PeriodicalIF":3.4,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13089473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721671","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":"Safety and Efficacy of Mesenchymal Stem Cell Therapy in Multiple System Atrophy: Systematic Review.","authors":"Noon Elimam, Shams Samih Albarari, Yara Shaalan, Shazaa Mahmoud Elsheikh, Ainaa A Alzamari, Nourhan Elmekkawi, Rahaf Mogahed, Razan H Alghuweiri","doi":"10.2147/BTT.S593367","DOIUrl":"https://doi.org/10.2147/BTT.S593367","url":null,"abstract":"<p><strong>Objective: </strong>To systematically evaluate the efficacy and safety of mesenchymal stem cell (MSC) therapy for patients with Multiple System Atrophy (MSA) by synthesising available clinical trial evidence and clarifying signals of disease modification.</p><p><strong>Background: </strong>MSA is a rapidly progressive and fatal neurodegenerative disorder for which no disease-modifying therapies exist. MSC therapy has emerged as a potential treatment, with mechanisms centered on neuroprotection and clinical benefit through anti-inflammatory and trophic effects rather than direct cell replacement.</p><p><strong>Methods: </strong>We systematically searched PubMed, Scopus, the Cochrane Library, and Web of Science for studies on mesenchymal stem cell (MSC) therapy in adults with probable or confirmed multiple system atrophy (MSA). Eligible studies included single-arm trials or comparisons with placebo or usual care. The primary outcome was safety and tolerability, assessed by the type and severity of adverse events. Secondary outcomes included the rate of disease progression measured by UMSARS total, Part I, and Part II scores.</p><p><strong>Results: </strong>A total of 123 participants from seven studies were included. MSCs were administered through multiple routes, and adverse events occurred in 65-70% of participants but were mostly mild and transient. No serious MSC-related toxicity was reported. Several studies suggested slower disease progression following MSC therapy. For example, in Singer et al (2019), patients receiving high-dose MSCs showed a markedly lower rate of UMSARS total score progression compared with a matched historical control group (0.40 ± 0.59 vs 1.44 ± 1.42 points/month, p = 0.004), suggesting a possible dose-dependent effect. However, treatment effects varied across studies depending on dose, administration route, and disease stage.</p><p><strong>Conclusion: </strong>MSC therapy shows potential for disease modification in MSA by slowing neurological deterioration. The treatment was well tolerated, supporting the need for larger, definitive trials with standardised protocols and longer follow-up to confirm clinical benefit.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"20 ","pages":"593367"},"PeriodicalIF":3.4,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13050157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147621378","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":"Anifrolumab in Refractory Oral Manifestations in Systemic Lupus Erythematosus: A Case Report and Literature Review.","authors":"Olena Garmish, Svitlana Smiyan, Roman Komorovsky, Ivan Bilozetskyi","doi":"10.2147/BTT.S588071","DOIUrl":"https://doi.org/10.2147/BTT.S588071","url":null,"abstract":"<p><p>Oral manifestations are a frequent yet underrecognized feature of systemic lupus erythematosus (SLE), contributing substantially to patient morbidity and reduced quality of life. They are insufficiently represented in clinical outcome measures and therapeutic guidelines, despite their clinical relevance. We report the case of a 39-year-old woman with SLE who developed severe, refractory tongue ulcers and glossodynia persisting for three years, unresponsive to hydroxychloroquine (HCQ), azathioprine (AZA), colchicine, methotrexate (MTX), and glucocorticoids (GC). Belimumab was discontinued due to gastrointestinal intolerance and lack of efficacy on oral lesions. The patient was subsequently treated with anifrolumab 300 mg intravenously every four weeks. After the first infusion, oral ulcers resolved, arthritis improved, and corticosteroids were discontinued. Within three months, the tongue lesions had completely healed, enabling unrestricted oral intake and full resumption of professional activities. Clinical remission was maintained on anifrolumab and hydroxychloroquine alone at four months of follow-up. This case highlights the therapeutic challenge of refractory oral lesions in SLE, a manifestation not adequately addressed in current EULAR (2023 update) or ACR (2025) guidelines. While conventional immunosuppressants such as azathioprine, methotrexate, and mycophenolate mofetil remain options, their efficacy for isolated oral lesions is limited. Emerging evidence, including case reports and small series, suggests that anifrolumab may provide significant benefit for mucosal involvement. The key learning point is that refractory tongue involvement may represent a dominant and treatment-resistant manifestation of SLE, yet it can respond to targeted biologic therapy such as anifrolumab and our report adds to this growing body of evidence. Prospective comparative studies and registry analyses are required to define anifrolumab's effectiveness specifically for refractory oral manifestations and to compare outcomes with other biologics.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"20 ","pages":"588071"},"PeriodicalIF":3.4,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13004121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147497462","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":"Late-Onset Ocular Myasthenia Gravis-Like Symptoms During Erenumab Therapy for Chronic Migraine: A Case Report.","authors":"Arwa Qaqish, Arwa Al Anber, Ghada Abdelhafez","doi":"10.2147/BTT.S579731","DOIUrl":"https://doi.org/10.2147/BTT.S579731","url":null,"abstract":"<p><p>Chronic migraine (CM) is a disabling neurological disorder for which calcitonin gene-related peptide (CGRP)-targeted monoclonal antibodies, such as erenumab, provide effective prophylaxis. Although generally well tolerated, rare neuromuscular complications resembling ocular myasthenia gravis (MG) have been reported. A 46-year-old woman with CM achieved marked improvement with erenumab for over three years before developing diplopia and intermittent ptosis. Laboratory and imaging studies were unremarkable, but clinical suspicion for MG led to pyridostigmine therapy, resulting in rapid improvement. Brief episodes of dysarthria occurred but resolved within one month. Symptoms disappeared after discontinuation of erenumab and continued pyridostigmine. On re-initiation of erenumab, the patient maintained migraine control without recurrence of MG-like symptoms. This case illustrates a rare, late-onset, reversible MG-like complication of erenumab. Clinicians should remain alert to ocular manifestations even as delayed adverse effects of anti-CGRP therapy.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"20 ","pages":"579731"},"PeriodicalIF":3.4,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12969706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147430695","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":"First-Line Serplulimab versus Other Anti-PD-1/PD-L1 Antibodies Plus Chemotherapy for Esophageal Squamous Cell Carcinoma: A Systematic Review with Benefit-Risk Assessment via Matching-Adjusted Indirect Comparison.","authors":"Yi Zhu, Xiao Qi, Senmiao Ni, Wenting Qiu, Mengkai Chen","doi":"10.2147/BTT.S602654","DOIUrl":"https://doi.org/10.2147/BTT.S602654","url":null,"abstract":"<p><strong>Purpose: </strong>Blockade of the PD-L1/PD-1 pathway combined with chemotherapy has demonstrated significant survival benefits as first‑line therapy for esophageal squamous cell carcinoma (ESCC). However, comprehensive benefit-risk comparisons among approved agents remain limited. This study conducted an indirect comparison of serplulimab versus other anti-PD-1/PD-L1 antibodies plus chemotherapy in treatment-naïve ESCC patients.</p><p><strong>Patients and methods: </strong>A systematic review with matching-adjusted indirect comparisons (MAICs) was conducted using individual patient data (IPD) from ASTRUM-007 and aggregate data (AgD) from seven comparator trials, including CheckMate 648, ESCORT-1st, GEMSTONE-304, JUPITER-06, KEYNOTE-590, ORIENT-15, and RATIONALE-306. IPD were reweighted to match key baseline characteristics. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were estimated using the Bucher method. Subgroup analyses were further explored using Bayesian network meta-analysis.</p><p><strong>Results: </strong>Eight Phase 3 randomized controlled trials comprising 4,702 patients were included. After adjusting for baseline imbalances, serplulimab demonstrated comparable efficacy to other PD-1/PD-L1 inhibitors. The pooled adjusted OS HR was 0.98 (95% CI, 0.87-1.11), with numerically favorable OS versus nivolumab (HR, 0.76; 95% CI 0.47-1.24) and comparable OS versus pembrolizumab (HR, 0.93; 95% CI, 0.71-1.22) and camrelizumab (HR, 0.93; 95% CI, 0.70-1.24). The pooled adjusted PFS HR was 0.91 (95% CI, 0.81-1.02), significantly favoring serplulimab over nivolumab (HR, 0.56; 95% CI, 0.33-0.96), with favorable trends versus pembrolizumab (HR, 0.83; 95% CI, 0.63-1.10) and sugemalimab (HR, 0.86; 95% CI, 0.63-1.16). Subgroup analyses suggested greater relative benefit in women and patients with locally advanced disease. Grade 3-5 treatment-related adverse events occurred in 52.9% of serplulimab-treated patients, comparable to other PD-1/PD-L1 inhibitors (range, 47.4%-71.9%).</p><p><strong>Conclusion: </strong>This indirect comparison provides comparative benefit-risk evidence to inform first‑line treatment selection for locally advanced or metastatic ESCC. Serplulimab plus chemotherapy demonstrated a clinically meaningful PFS benefit, comparable OS after matching, and a manageable safety profile consistent with the PD-1/PD-L1 inhibitor class.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"20 ","pages":"602654"},"PeriodicalIF":3.4,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12958973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147364204","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":"Network Pharmacology-Based Exploration: Non-Targeted Metabolites of <i>Lactobacillus</i>-Fermented <i>Chaenomeles speciosa (Sweet) Nakai, Smilax glabra Roxb</i>. and <i>Pueraria montana var. Lobata</i> in Uric Acid Metabolism Intervention.","authors":"Wei Tan, Zongjun Li","doi":"10.2147/BTT.S578004","DOIUrl":"https://doi.org/10.2147/BTT.S578004","url":null,"abstract":"<p><strong>Background: </strong>Previous studies have demonstrated that numerous medicine and food homology (MFH) possess the potential to regulate purine metabolism disorders, promote uric acid excretion, and alleviate hyperuricemia symptoms. Examples include CS (<i>Chaenomeles speciosa (Sweet) Nakai</i>), SR (<i>Smilax glabra Roxb.</i>) and PL (<i>Pueraria montana var. lobata</i>).</p><p><strong>Methods: </strong>Metabolomics was employed to analyze the compositional changes in medicinal and edible extracts before and after fermentation. Network pharmacology and molecular docking studies were further utilized to elucidate the interactions between these differential metabolites and the core targets of hyperuricemia. In vitro enzyme activity assays were conducted to confirm the therapeutic effects.</p><p><strong>Results: </strong>A total of 283, 248, and 18 differential metabolites were identified in CS,SR and PL samples, respectively. Among these, 54 significantly upregulated differential metabolites were selected for screening. Based on these metabolites, 53 HUA-related targets were identified for CS, SR and PL. Functional enrichment analysis revealed their roles in inflammatory stress and uric acid production pathways, particularly the MAPK signaling pathway and purine metabolism regulated by XDH. Additionally, other targets in the purine metabolism pathway, such as ADA, PNP, AMPD3, and IMPDH2, were co-regulated. Enzyme activity assays indicate that fermented MFH more effectively inhibits XOD, thereby regulating the conversion of xanthine and hypoxanthine into uric acid. Molecular docking revealed two significantly upregulated compounds in <i>CS</i>; and five in PL; and four in SR. exhibit strong binding to XOD.</p><p><strong>Conclusion: </strong>These findings provide theoretical support for FMFH as a potential effective component in preventing and treating hyperuricemia. Our research demonstrates that FMFH targets multiple pathways associated with hyperuricemia, offering a promising approach for preventing this condition.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"20 ","pages":"578004"},"PeriodicalIF":3.4,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12949976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147343485","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":"Net Present Value Impact of FDA's Phase 3 Waivers on Monoclonal Antibody Biosimilar Development.","authors":"Ranjit Ranbhor, Priyanka Kulkarni","doi":"10.2147/BTT.S581013","DOIUrl":"https://doi.org/10.2147/BTT.S581013","url":null,"abstract":"<p><strong>Background: </strong>The FDA's October 2025 guidance proposes waiving Phase 3 comparative efficacy studies for biosimilars when analytical and pharmacokinetic similarity are demonstrated.</p><p><strong>Methods: </strong>We conducted a net present value (NPV) analysis comparing traditional biosimilar development pathways (with Phase 3 comparative efficacy studies) to streamlined pathways utilizing FDA's Phase 3 waiver framework. The model incorporates industry-benchmarked cost data (Phase 3 studies: $20-28M), development timelines (Phase 3 duration: 1-3 years). Economic outcomes were evaluated across three monoclonal antibody biosimilar programs representing high-, moderate-, and lower-complexity scenarios. Sensitivity analysis evaluated parameter variation across realistic ranges.</p><p><strong>Results: </strong>Waiving Phase 3 studies reduces development costs by $25 million per program (18% reduction) and shortens timelines by 1.5 years (21% reduction). Risk-adjusted NPV improves by $25 million (29%), and minimum viable peak sales threshold decreases from $300 million to $250 million.</p><p><strong>Conclusion: </strong>Phase 3 waivers can substantially reduce development costs (~$25M average), accelerate timelines (~1.5 years), and improve NPV (~25-29%) for well-characterized monoclonal antibody biosimilars meeting FDA's analytical similarity and pharmacokinetic equivalence criteria. Economic benefits are conditional on robust analytical data, regulatory approval of waiver requests, and appropriate product selection (Tier 1/2/3 classification). Real-world realization requires post-implementation surveillance of FDA approval patterns, achieved cost reductions, and timeline compression beginning 2026-2027.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"20 ","pages":"581013"},"PeriodicalIF":3.4,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12912049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146218494","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":"Successful and Risk-Minimizing Treatment of Ulcerative Colitis by Positive Switch from JAK Inhibitors to Ustekinumab.","authors":"Haruka Otake, Satohiro Matsumoto, Hirosato Mashima","doi":"10.2147/BTT.S561965","DOIUrl":"https://doi.org/10.2147/BTT.S561965","url":null,"abstract":"<p><strong>Background: </strong>Janus kinase (JAK) inhibitors are highly effective at inducing remission in moderate-to-severe ulcerative colitis (UC). Because JAK inhibitors are small molecules, they can be administered orally, are rapidly absorbed, and have a rapid onset of action. However, potential adverse events, such as serious infections, opportunistic infections, herpes zoster infections, venous thrombosis, and cardiovascular events have been identified. To avoid the side effects associated with the long-term administration of JAK inhibitors, switching to biologics may be considered, even if remission is maintained with JAK inhibitors (positive switch).</p><p><strong>Case report: </strong>Case 1: A 53-year-old man with steroid-dependent UC achieved rapid symptomatic improvement and complete mucosal healing on upadacitinib. Due to recurrent common colds and concerns regarding long-term adverse events, he underwent a positive switch to ustekinumab. Clinical and endoscopic remission have been maintained for one year. Case 2: A 36-year-old woman with refractory UC achieved clinical remission and mucosal healing with filgotinib following inadequate response to vedolizumab and corticosteroids. Given her desire for pregnancy and the potential risks of long-term JAK inhibitor use, she was switched to ustekinumab, which is considered safe during pregnancy. Remission has been maintained for one year.</p><p><strong>Conclusion: </strong>In two UC patients who achieved mucosal healing with a JAK inhibitor, remission was successfully maintained after switching to ustekinumab. These cases suggest that a positive switch may be a reasonable option for patients who respond to JAK inhibitors but have concerns about long-term safety. Additional cases are required to better define the clinical role of this strategy.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"20 ","pages":"561965"},"PeriodicalIF":3.4,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13003793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147497546","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}