Bruton's Tyrosine Kinase (BTK) Inhibitors and Autoimmune Diseases: Making Sense of BTK Inhibitor Specificity Profiles and Recent Clinical Trial Successes and Failures
Source : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8595937/
Research into the treatment of autoimmune diseases has made great strides toward improving our understanding of disease mechanisms driving pathology. This has led to the development of therapies that go beyond symptomatic treatment and allow for therapeutic interventions that delay or halt disease progression.
Conclusion/Relevance: Based on the data collected in this study, we propose that current compound characteristics of BTK inhibitor drug candidates for the treatment of autoimmune diseases have achieved the selectivity, safety, and coverage requirements necessary to deliver therapeutic benefit.
• Source: Frontiers in Immunology
• Conclusion/Relevance: “Collectively, the new class of BTK inhibitors show promise in bringing new treatment paradigms to treating autoimmune disease disorders. Enhancement of selectivity, unique enzyme coverage characteristics, and pharmacokinetic profiles has improved safety margins for most members in this BTK group of clinical drug candidates. Recent success in clinical trials treating antibody mediated diseases such as MS, PV and potentially RA appear to be most promising, while broader less causally understood disease like SLE and SJ appear not to be of therapeutic benefit.”
• According to the review, indication selection with regard to BTK inhibitors has gravitated towards the rheumatic diseases RA and SLE, with less concentration on MS, PV, SJ, CSU, IP, GVHD, and asthma.
• “We also found advancements in drug selectivity and the inclusion of covalent bond formation have led to improvements in effective BTK inhibition coverage and clinical safety parameters in subjects treated with this new generation of BTK inhibitors,” wrote the authors.
• The authors stated that it remains to be elucidated what level of BTK inhibition is needed for clinical efficacy with regard to the treatment autoimmune diseases, with twice-daily dosing regimens seeming to attain near complete inhibition of BTK activity