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High-efficacy MS drugs aren't enough. At a NeurologyLive forum in New York, MS specialists agreed that while anti-CD20 therapies have transformed relapse control, patients still accumulate disability through a process called PIRA — and the next wave of treatments, from BTK inhibitors to CAR-T therapy, may be needed to address the deeper biology driving decline. Physicians also acknowledged a striking gap between what they and their patients prioritize in care.
At a NeurologyLive Clinical Forum in New York, a group of MS specialists gathered to wrestle with a hard truth: even the best current therapies aren't fully controlling the disease. Anti-CD20 agents have dramatically reduced relapses, but patients can still accumulate disability independent of relapse activity — a phenomenon known as PIRA (progression independent of relapse activity). "That is the natural course of the disease that we're failing to control, even with high-efficacy therapies," one attendee noted.
The conversation quickly turned to what comes next. BTK inhibitors, CAR-T therapy targeting CD19, anti-CD40 blockade, and a more selective DHODH inhibitor all emerged as promising candidates for reaching the compartmentalized, innate inflammation that current antibody therapies largely miss. A majority (57%) of attendees favored CAR-T as the most promising approach — though safety concerns, including deaths reported in a BTK inhibitor trial, tempered enthusiasm.
Key Takeaways:
Why it matters: The forum highlighted a dual gap in MS care — one biological (current therapies missing key drivers of disability) and one relational (physicians underestimating what patients actually struggle with most). Closing both gaps will be essential as the field moves toward the next generation of treatments.
