The University of Pennsylvania has received a USD 1.34 million NIH U01 award to conduct a randomized, placebo-controlled trial testing whether ocrelizumab (Ocrevus; Roche/Genentech) can be safely discontinued in patients with relapsing multiple sclerosis — a question with direct implications for long-term treatment strategy in a disease affecting nearly 1 million people in the US.
Anti-CD20 therapies such as ocrelizumab are among the most effective agents for relapsing MS, but indefinite use carries accumulating risks including hypogammaglobulinemia and increased infection susceptibility. Most patients currently remain on anti-CD20 therapy indefinitely because clinicians lack evidence to identify who can safely stop treatment. The AMS05 trial, led by Amit Bar-Or in Penn's neurology department, will enroll patients with early active MS, treat them with open-label ocrelizumab for 24 months, then randomize them to placebo or continued therapy. The central hypothesis is that B cell depletion during early disease may reset aberrant immune profiles sufficiently to permit durable remission after drug withdrawal — an approach analogous to inducing immune tolerance rather than requiring lifelong suppression.
Mechanistic and biomarker substudies will use serial MRI and biosampling, including single-cell RNA sequencing, to characterize immune cell phenotypes associated with sustained remission versus disease breakthrough, and to develop predictive models incorporating immune, demographic, and clinical variables.