Publications by authors named "Jan Guse"
Article Synopsis
- The study investigates how immunomodulator comedication can help reverse loss of therapeutic response (LOR) to TNF inhibitors in patients with inflammatory bowel disease (IBD) who have developed anti-drug antibodies (ADA).
- Out of 123 IBD patients analyzed, those who received immunomodulator comedication showed significantly better outcomes in regaining clinical remission and clearing ADA compared to those who only had their TNF inhibitor doses increased.
- The findings suggest that adding immunomodulators like azathioprine or methotrexate significantly improves the chances of maintaining effective treatment in IBD patients experiencing LOR due to ADA.
Modulation of Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling is a promising method of treating autoimmune diseases, and the profound potency of clinical compounds makes this mode of action particularly attractive. Other questions that remain unanswered also include: What is the ideal selectivity between JAK1 and JAK3? Which cells are most relevant to JAK blockade? And what is the ideal tissue distribution pattern for addressing specific autoimmune conditions? We hypothesized that JAK3 selectivity is most relevant to low-dose clinical effects and interleukin-10 (IL-10) stimulation in particular, that immune cells are the most important compartment, and that distribution to inflamed tissue is the most important pharmacokinetic characteristic for disease modification. To test these hypotheses, we prepared modified derivatives of JAK3 specific inhibitors that target C909 near the ATP binding site based on FM-381, first reported in 2016; a compound class that was hitherto limited in uptake and exposure .
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