Safety of different small molecules / protein kinase inhibitors

Salgado and colleagues looked at the safety profiles of 18 protein kinase inhibitors (AMG-548, ARRY-371797, BMS-582949, dilmapimod, doramapimod, pamapimod, PH-797804, SCIO-323, talmapimod, VX-702, VX-745, LY3009104, tofacitinib, ruxolitinib, fostamatinib disodium, imatinib mesylate, masitinib and ARRY-438162) in clinical trials in rheumatoid arthritis. Most interesting for the being are tofacitinib and fostamatinib, of course. Tofacitinib is closer to being launched than fostamatinib. Tofacitinib shows higher rates of adverse events concerning cholesterol, headaches, and renal impairment. LY3009104, another Jak inhibitor also has higher rates of adverse events for cholesterol and headaches. Fostmatinib showed higher rates af adverse events for mild increase of transaminases, hypertension, and diarrhea. I’ll come back to this excellent review, when other small molecules mentioned here surface with relevant studies in rheumatoid arthritis.

[THU0097] SYSTEMATIC REVIEW OF THE SAFETY OF PROTEIN KINASE INHIBITORS IN CLINICAL TRIALS IN RHEUMATOID ARTHRITIS - POSTER TOURS
E. Salgado1, J.R. Maneiro1, L. Carmona1,2, J.J. Gomez-Reino1,3. 1Hospital Clinico Universitario De Santiago, Santiago de Compostela; 2Universidad Camilo José Cela, Madrid; 3Universidad de Santiago de Compostela, Santiago de Compostela, Spain
Conclusions: In RA, a unique safety profile seems related to the different PK inhibitors. Dizziness, rash and neutrophilia are related with p38 inhibition; cholesterol increase with JAK inhibition; mild transaminases increase, hypertension and diarrhea with Syk inhibition; and headache, rash, peripheral edema, nausea, vomiting and diarrhea with cKit inhibition.