Bruton's tyrosine kinase (BTK) inhibitors are an emerging class of therapeutics in multiple sclerosis (MS). BTK is expressed in B-cells and myeloid cells, key progenitors of which include dendritic cells, microglia and macrophages, integral effectors of MS pathogenesis, along with mast cells, establishing the relevance of BTK inhibitors to diverse autoimmune conditions. First-generation BTK inhibitors are currently utilized in the treatment of B-cell malignancies and show efficacy in B-cell modulation. B-cell depleting therapies have shown success as disease-modifying treatments (DMTs) in MS, highlighting the potential of BTK inhibitors for this indication; however, first-generation BTK inhibitors exhibit a challenging safety profile that is unsuitable for chronic use, as required for MS DMTs. A second generation of highly selective BTK inhibitors has shown efficacy in modulating MS-relevant mechanisms of pathogenesis in preclinical as well as clinical studies. Six of these BTK inhibitors are undergoing clinical development for MS, three of which are also under investigation for chronic spontaneous urticaria (CSU), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Phase II trials of selected BTK inhibitors for MS showed reductions in new gadolinium-enhancing lesions on magnetic resonance imaging scans; however, the safety profile is yet to be ascertained in chronic use. Understanding of the safety profile is developing by combining safety insights from the ongoing phase II and III trials of second-generation BTK inhibitors for MS, CSU, RA and SLE. This narrative review investigates the potential of BTK inhibitors as an MS DMT, the improved selectivity of second-generation inhibitors, comparative safety insights established thus far through clinical development programmes and proposed implications in female reproductive health and in long-term administration.
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http://dx.doi.org/10.1177/17562864241233041 | DOI Listing |
Bull Cancer
December 2024
Service d'hématologie, CHU de Poitiers, CIC 1402 Inserm université, 86000 Poitiers, France.
Hairy cell proliferations represent very different entities. They include hairy cell leukemia in its classic form (HCL), a well-defined entity, but also the variant form of HCL (LT-V ou HCL-V), whose presentation is far from HCL and whose prognosis is poorer. Other hairy cell proliferations include splenic red pulp lymphoma (SDRPL) and splenic marginal zone lymphomas (SMZL) with circulating villous cells.
View Article and Find Full Text PDFAnal Bioanal Chem
December 2024
Department of Pharmacy, Peking University Third Hospital, Beijing, 100191, China.
Bruton's tyrosine kinase inhibitors (BTKis) exhibit significant interindividual pharmacokinetics, making therapeutic drug monitoring (TDM) a promising approach for personalized therapy. However, simultaneous quantification of multiple BTKis poses technical challenges. A unified protocol for BTKis detection would be clinically desirable.
View Article and Find Full Text PDFAnn Hematol
December 2024
Department of Neuro-Oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, No.119 West Nansihuan Road, Beijing, 100070, China.
To investigate the prognostic significance of clinicopathological factors in patients with primary central nervous system lymphoma (PCNSL) in a single center. Patients newly diagnosed with PCNSL at our center were recruited between January 2019 and March 2023. Baseline demographic and clinicopathological data were collected retrospectively.
View Article and Find Full Text PDFCrit Rev Oncol Hematol
December 2024
Hamad Medical Corporation, Doha, Qatar. Electronic address:
Background: Primary central nervous system lymphoma (CNSL) is a rare, aggressive non-Hodgkin lymphoma confined to the CNS. Although radiation and chemotherapy, particularly high-dose methotrexate (HD-MTX), are effective treatments, the relapse rates remain high, prompting the exploration of novel therapeutic options. Ibrutinib, an irreversible Bruton tyrosine kinase (BTK) inhibitor, has shown promise in various B-cell malignancies, including CNSL.
View Article and Find Full Text PDFFront Pharmacol
December 2024
Department of Clinical Pharmacology and Pharmacy, Okayama University, Okayama, Japan.
Introduction: Advances in the early detection and treatment of cancer have significantly improved the prognosis of patients with cancer. Tyrosine kinase inhibitors (TKIs) are effective targeted treatments for various malignancies that act by inhibiting kinase activity. Although these drugs share a common mechanism of action, they differ in their targeted kinases, pharmacokinetics, and side effects.
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