An Open Labeled Observational Study of Rituximab and Plasma Exchange (PLEX) in Progressive Multiple Sclerosis (MS) (P3.264)

Objective: The purpose of our open label observational trial was to determine tolerability, safety, disease modifying effects (including functional capabilities and symptoms) of PLEX/Rituximab or PLEX alone in patients with progressive MS Background: Insights into pathophysiology of progressive MS have elucidated a role for B cell follicles and meningeal inflammation.1 Rituximab, a monoclonal antibody against CD-20 protein on B cells, may be effective in mitigating ongoing disease activity (and potentially disease progression) in MS patients. PLEX in conjunction with immunosuppressive agents, has been shown to be effective in progressive patients when other therapies have failed.2 Design/Methods: This is an observational study of progressive MS patients (n=28, 79[percnt] secondary progressive) with recalcitrant disease who underwent PLEX or PLEX/rituximab. PLEX involved five full volume exchanges; generally requiring 8-10 days. Data ascertainment was done through follow up visits and phone interviews along with chart review. Results: One patient reported recovery of profound loss in hand strength and dexterity over a period of six months to a year after initial PLEX/Rituximab therapy. Two other patients noted significant improvements in gait lasting 6-12 weeks; both have transitioned to receive monthly maintenance PLEX. Of these, one has reported durable gains from maintenance PLEX. Eight patients reported some improvement initially; follow up is ongoing. No life threatening adverse effects were reported. Adverse effects included infections in a few patients, bleeding from mediport in one patient, and a hypersensitivity reaction to Rituximab, despite pre-treatment with steroids. Conclusions: PLEX and Rituximab in progressive MS patients appear to be well tolerated without any serious adverse events. A subset of patients exhibited conspicuous improvements in functional capabilities and disease symptoms, albeit of limited duration. Long term follow up in larger cohorts will indicate if maintenance PLEX (with or without Rituximab) is associated with durable and functionally relevant gains in neurologic capabilities. Disclosure: Dr. Qureshi has nothing to disclose. Dr. Abraham has nothing to disclose. Dr. Logan has nothing to disclose. Dr. Frohman has received personal compensation for activities with Biogen Idec, Novartis, Acorda Therapeutics, and Questcor. Dr. Frohman has participated in the speakers9 bureau for Teva Neurosciences, Acorda, and Novartis and has received consulting fees from TEVA Neurosciences, and Acorda.,