b"Medicine & ResearchDoctors NotesThe MS News column includes analysis from Ben Thrower, M.D., MS Focus senior medical advisor. He draws from the top news stories of the quarter and explains what the news means to you, the person with MS. Christine Willis, MLIS, AHIP, is the Clinical Information Librarian at Children's Healthcare of Atlanta, Egleston Hospital.BTK inhibitor therapy trials stoppedtherapeutic possibility? There are several reasons. Two recent clinical trials of evobrutinib,Research is pointing towards smoldering or an investigational Brutons tyrosine kinaselow-level inflammation in the CNS as a inhibitor in development for patients withpotentialexplanationforprogressionof multiple sclerosis, have stopped after theydisability, in the absence of relapses or new did not produce a more superior reduction inMRI lesions. This clinical situation has been annualized relapse rates than teriunomide, atermed progression independent of relapse previously approved disease-modifying agent.activity. In the clinic, we frequently see The trials, evolutionRMS 1 and evolutionRMSindividuals who have not had recent relapses 2, were in a Phase III, multicenter, randomized,or new lesions on MRI but are still seeing a parallel group, double-blind with more thanslow progression in disability. Smoldering 2,200 participants anticipated. Merck plans toinammation driven by microglial cells in the review the collected study data for presentationCNS may be one explanation for PIRA. It was and publication of the results. hoped that BTK inhibitors might address this type of inammation and slow PIRA in patients. Thrower -As we look toward future MSIf BTK inhibitors can slow this type of disability therapeutic options, the class of drugs knownprogression, they may be effective in both as BTK inhibitors has generated great interest.primary progressive MS and secondary These oral medications work through B-cellprogressive MS.pathways in a different way than our currentAncient pastoralists B-cell therapies (Ocrevus, Kesimpta, Briumvi,possible source of MS genesand rituximab). While there are several BTKResearchers from across Europe joined inhibitors in testing for MS, evobrutinib appearedtogether to examine gene variability from a to be the closest to potential FDA-approval.large, ancient DNA dataset. Tooth or bone The results from a phase 3 study of evobrutinibsamplesof86ancientindividualsfrom versus teriunomide in relapsing forms of MSmedievalandpostmedievalperiodsfrom were not successful. Evobrutinib was not shownDenmark were used to create the genomic data to be superior to teriunomide in reducingin this study. Using this DNA data, researchers the annualized relapse rate.were able to show the genetic risk for MS rising Further analysis of this study is expectedamong pastoralists from the Pontic steppe and to be done and other BTK inhibitors are stillbeing brought into Europe by the Yamnaya-in testing. So, why the excitement about thisrelated migration approximately 5,000 years msfocusmagazine.org 44"