Clinical application of biological agents in rheumatoid arthritis

Transplant Immunology, Journal Year: 2025, Volume and Issue: unknown, P. 102187 - 102187

Published: Jan. 1, 2025

Language: Английский

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Neurological Adverse Events Associated with the Use of Janus Kinase Inhibitors: A Pharmacovigilance Study Based on Vigibase

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(3), P. 394 - 394

Published: March 11, 2025

Background: Janus kinase (JAK) inhibitors are a new class of targeted therapies that block cytokines and the signal transduction activators transcription (STAT) pathway. However, post-marketing surveillance studies have led to revised recommendations, highlighting potential serious heart-related events cancer risk JAK inhibitors. Here, we aimed determine neurological adverse (AEs) (tofacitinib, ruxolitinib, baricitinib) based on global real-world database. Methods: We analyzed individual case safety reports from Uppsala Monitoring Center January 1968 4 April 2022. A disproportionality analysis was performed using proportional reporting ratio (PRR), odds (ROR), information component (IC) detect signals. Signals were classified according hierarchy Medical Dictionary for Regulatory Activities (MedDRA). Additionally, stratified by age group sex major AEs. Results: total 30,051,159 all drugs in this study. Among 105,798 tofacitinib, 14.1% (14,863 reports) For ruxolitinib baricitinib, 14.5% (6317 10.2% (1216 AEs, respectively. Various AE signals detected tofacitinib with memory impairment exhibiting highest number positive group. Baricitinib did not reach detection threshold. Conclusions: This study suggests including impairment, associated use

Language: Английский

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The research progress of biologics in elderly-onset rheumatoid arthritis (EORA)

Frontiers in Aging, Journal Year: 2025, Volume and Issue: 5

Published: Jan. 23, 2025

Elderly-onset rheumatoid arthritis (EORA) is a distinct subtype of characterized by heightened treatment challenges due to immune aging and the complexity comorbidities. This review systematically summarizes definition, clinical features, epidemiological trends, therapeutic challenges, potential applications biologic agents in EORA . It primarily focuses on efficacy, safety, individualized strategies associated with various agents. Studies indicate that biologics, such as TNF- α inhibitors , IL-6 JAK can significantly reduce inflammation improve joint function patients. However, their long-term use closely linked increased risks infections, thrombosis, malignancies, underscoring importance personalized approaches dynamic monitoring. Moreover, advent novel agents, including IL-17 IL-23 well second-generation offers additional options for refractory patients demonstrates substantial optimizing both efficacy safety. With rapid progress precision medicine artificial intelligence (AI) technologies, gene profiling, biomarker analysis, AI-assisted decision-making are gradually steering towards more precise strategies. high cost limited accessibility these technologies remain significant barriers practice. Future research should focus validating safety therapies refining enhance patient outcomes quality life.

Language: Английский

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GM-CSF drives IL-6 production by macrophages in polymyalgia rheumatica

Annals of the Rheumatic Diseases, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Insight into the immunopathology of polymyalgia rheumatica (PMR) is scarce and mainly derived from peripheral blood studies. The limited data available point towards macrophages as potential key players in PMR. This study aimed to identify factors driving proinflammatory macrophage development their functions Monocyte phenotypes were investigated by flow cytometry (PMR, n = 22; healthy controls, 20) paired subacromial-subdeltoid (SASD) bursal fluid 9). Macrophages SASD bursa characterised immunohistochemistry immunofluorescence 12; controls undergoing shoulder replacement surgery, 10). cytokines expressed PMR-affected tissue examined using differentiation cultures 7; 7). Monocytes (CD14highCD16- CD14highCD16+) increased PMR patients activated fluid. dominated immune infiltrates tissue, expressing various cytokines. While interleukin (IL)-6 interferon-gamma (IFN-γ) expression was abundant both control granulocyte-macrophage colony-stimulating factor (GM-CSF) (M-CSF) significantly tissue. showed an elevated CD206/folate receptor β ratio, reflecting a GM-CSF skewed signature. A combination GM-CSF/M-CSF/IFN-γ boosted IL-6 production vitro, while observed without GM-CSF. monocyte compartment expanded produce such IL-6. network locally cytokines, including GM-CSF, M-CSF, IFN-γ, may drive these macrophages. Overall, constitute therapeutic targets for

Language: Английский

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Cancer Risk in IBD Patients Treated with JAK Inhibitors: Reassuring Evidence from Trials and Real-World Data

Cancers, Journal Year: 2025, Volume and Issue: 17(5), P. 735 - 735

Published: Feb. 21, 2025

The advent of Janus kinase (JAK) inhibitors, including tofacitinib, filgotinib, and upadacitinib, has significantly widened the therapeutic options for patients with inflammatory bowel disease (IBD). These agents offer advantage oral administration have demonstrated efficacy in inducing maintaining remission. However, concerns regarding their safety emerged, particularly concerning cardiovascular infectious complications, which appear more pronounced pre-existing risk factors such as older age, smoking, or comorbidities. While these risks are better understood, potential association between JAK inhibitors malignancies remains a subject ongoing investigation. Current data from randomised controlled trials, pooled integrated analyses, real-world studies provide conflicting evidence cancer risk. Notably, rheumatologic diseases treated contributed additional insights into long-term outcomes. Despite uncertainty surrounding malignancy risks, it is likely that predisposing factors, smoking history, long-standing IBD chronic inflammation, play substantial role development than inhibitor therapy alone. This paper reviews clinical meta-analyses, observational studies, focusing on IBD. We also review rheumatology highlighting need individualised assessment close monitoring to optimise profile medications practice.

Language: Английский

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Efficacy and safety of small molecule drugs in the treatment of pityriasis rubra pilaris—A systematic review

Frontiers in Medicine, Journal Year: 2025, Volume and Issue: 12

Published: Feb. 25, 2025

Background Pityriasis rubra pilaris is a chronic, scaly, keratotic skin disease, mainly manifested as scaly plaques and keratinized hair follicles. This condition significantly impacts the patient’s quality of life considered one intractable diseases in dermatology. Currently, no satisfactory clinical treatment options are available for this condition, presenting considerable challenge dermatologists. We conducted systematic evaluation to assess therapeutic potential existing small molecule drugs disease. Objectives To conduct review literature on use treating pityriasis evaluate their effectiveness safety. Methods all searched several databases until November 2024, including PubMed, Embase, Web Science, Cochrane Library. Results A total 16 patients with from 11 publications were included. The drugs, apremilast, upadacitinib, abrocitinib, tofacitinib, demonstrate good efficacy safety across ages, particularly who have failed systemic therapy poor response biological agents. However, conclusions limited by sample size need be further confirmed through large-scale randomized controlled trials. Conclusion Small favorable refractory pilaris, exhibiting relatively rapid onset high profile. findings may affected publication bias.

Language: Английский

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Challenges, opportunities and therapeutic potential of JAK inhibitors and their derived PROTACs (2022 – 2023)

Expert Opinion on Therapeutic Patents, Journal Year: 2025, Volume and Issue: unknown

Published: March 8, 2025

Introduction Since the approval of first JAK inhibitor, ruxolitinib, in 2011, development inhibitors has expanded significantly, with applications spanning autoimmune diseases, cancer, and inflammatory disorders. This review explores challenges therapeutic potential their evolution into proteolysis-targeting chimeras (PROTACs), which offer novel avenues for selective modulation.

Language: Английский

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Pharmacotherapeutic strategies to promote regulatory T cell function in autoimmunity

Current Opinion in Immunology, Journal Year: 2025, Volume and Issue: 94, P. 102554 - 102554

Published: April 6, 2025

Autoimmune diseases arise when self-antigen-specific T and B cells escape central peripheral mechanisms of tolerance. One such mechanism is control autoreactivity by regulatory (Tregs), which have an essential role in suppressing autoimmunity. Consequently, there significant interest developing ways to boost or restore the function Tregs order prevent treat autoimmunity, induce tolerance, thus reduce reliance on broadly immunosuppressive agents. Strategies include enhancing numbers and/or directly vivo via adoptive cell therapy. Here, we review recent advances our understanding how pharmacologic approaches can be applied enhance Treg through repurposing established drug therapies application new therapies. Specifically, discuss potential Treg-promoting drugs, including interleukin-2 its derivatives, tumor necrosis factor receptor 2 agonists, as well Treg-preserving tyrosine kinase inhibitors. We co-stimulatory blockade with CTLA-4 immunoglobulin affects tolerogenic environments consider whether lymphodepleting therapies, antithymocyte globulin teplizumab, might needed condition environment for better effects. focus drugs type 1 diabetes draw evidence from transplantation. With multiple pharmacotherapeutic strategies optimize vivo, promise effectively durably autoimmune disease remission.

Language: Английский

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A Case Series and Review of Febrile-Infection Related Epilepsy Syndrome (FIRES)

Children, Journal Year: 2025, Volume and Issue: 12(4), P. 485 - 485

Published: April 10, 2025

FIRES is a rare and catastrophic presentation of de novo refractory status epilepticus (RSE) in healthy individuals following mild febrile illness. It carries high burden morbidity an estimated mortality 12% children. In over half patients, underlying cause not discovered (cryptogenic FIRES). The theory that post-infectious inflammation promotes aberrant neuronal excitation has led to the use immunomodulatory therapies as treatment for FIRES. High-dose glucocorticoids intravenous immunoglobulin (IVIG) are used first-line but ineffective most cases. A comprehensive initial evaluation critical directing second-line therapies; however, autoimmune inflammatory workup seldom completed prior treatment. Despite recent trends toward using cytokine-directed therapies, outcomes remain poor. This single-institution retrospective case series describes three cases similarly aged Each patient experienced super-refractory (SRSE) resistant systemic immunotherapy (SIT). novel baricitinib, non-selective JAK inhibitor, proved effective one patient, while IL-1 IL-6 inhibition were other two. All patients suffered moderate-to-severe neurologic cognitive impairment at time discharge. poorly understood requiring multimodal approach Cytokine profiling can be helpful identifying cryptogenic from those with if conducted early clinical course. may aid decreasing neuroinflammation improve outcomes.

Language: Английский

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Integration of transcriptome and immunophenotyping data highlights differences in the pathogenetic kinetics of B cells across immune-mediated disease

RMD Open, Journal Year: 2025, Volume and Issue: 11(2), P. e005310 - e005310

Published: April 1, 2025

Objective To elucidate crucial immune cell subsets and associated immunological pathways by stratifying patients with immune-mediated diseases (IMDs) using immunophenotyping transcriptomic approaches. Methods We conducted flow cytometric analyses in 23 derived from 235 six IMDs, our database, utilizing ImmuNexUT. Patients were stratified based on data. Subsequently, we examined clinical differences among these clusters. Results IMDs into two clusters their immunophenotypes. Cluster 1 was enriched differentiated B cells, including unswitched memory cells (USM B), switched double-negative plasmablasts, while cluster 2 naïve cells. Higher disease activity rheumatoid arthritis decreased respiratory functions systemic sclerosis observed 1, whereas the of lupus erythematosus higher 2. Numerous differentially expressed genes detected USM B. glycosylation processes elevated cell-activating factor signalling myeloid exhibited B-cell receptor 2, which had an age-associated signature, more frequent flares, suggesting that increased proportion this signature is poor prognosis. Conclusion Immunophenotyping-based transcriptome-based states revealed quantitative qualitative predict IMD prognosis, assessing both quantity quality may be crucial.

Language: Английский

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