Abstract
ObjectivesTo evaluate the effect of intrathecally (IT) delivered rituximab as a therapeutic intervention for progressive multiple sclerosis (PMS) during a 3-year follow-up period.MethodsParticipants of a 1-year open-label phase 1b study of IT delivered rituximab to patients with PMS were offered extended treatment with follow-up for an additional 2 years. During the extension phase, treatment with 25 mg rituximab was administered every 6 months via a subcutaneous Ommaya reservoir connected to the right frontal horn with a ventricular catheter.ResultsMild to moderate vertigo and nausea occurred in 4 out of 14 participants as temporary adverse events associated with IT rituximab infusion. During the entire 3-year period, two cases of low-virulent bacterial meningitis occurred, which were successfully treated. Walking speed deteriorated significantly during the study.ConclusionsIT administration of rituximab via a ventricular catheter was well tolerated. Considering the meningitis cases, the risk of infection was not negligible. The continued loss of walking speed indicates that IT rituximab was not able to stop disease progression.Classification of evidenceThis study provides class IV evidence that intraventricularly administered rituximab in progressive MS is associated with a risk for bacterial meningitis and does not halt disease progression.EU Clinical Trial RegisterEudraCT; 2008-002626-11 and 2012-000721-53
Highlights
B-cells located within the CNS constitute a potential target for treatment in progressive MS (PMS) [7]
Two cases of low-virulent bacterial meningitis caused by Propionibacterium were recorded, one in the ITT-PMS and one in the extension trial
One important feature of PMS is the deterioration in walking ability
Summary
B-cells located within the CNS constitute a potential target for treatment in progressive MS (PMS) [7]. Administration of B cell depleting antibodies are highly efficacious in the relapsing phase but results in progressive MS (PMS) have been less convincing [5, 6, 8]. Low penetrance to the CNS compartment may explain the limited treatment effect in PMS [6, 8]. Intrathecal (IT) administration of rituximab might, be beneficial for PMS. We conducted a 1-year phase 1b Intrathecal Treatment Trial in Progressive Multiple Sclerosis (ITT-PMS) study on a group of PMS patients either failing, or not benefitting from, existing immunomodulatory treatments confirming the feasibility and tolerability of that treatment approach [1]. After an additional 2-year extension study, we have here evaluated the potential clinical benefit of rituximab over the total 3-year period
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