Currently, second-generation BTK inhibitors are under investigation for multiple autoimmune conditions, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), chronic spontaneous urticaria (CSU) and multiple sclerosis (MS).1,12 Incorporating learning from ongoing clinical trials, this review will evaluate the potential of second-generation BTK inhibitors, their improved selectivity and anticipated safety profile in the treatment of MS. This evidence concerns the gene BTK and rheumatoid arthritis.