Intrathecal treatment trial of rituximab in progressive MS

Abstract

ObjectivesTo perform a phase 1b assessment of the safety and feasibility of intrathecally delivered rituximab as a treatment for progressive multiple sclerosis (PMS) and to evaluate the effect of treatment on disability and CSF biomarkers during a 1-year follow-up period.MethodsThree doses of rituximab (25 mg with a 1-week interval) were administered in 23 patients with PMS via a ventricular catheter inserted into the right frontal horn and connected to a subcutaneous Ommaya reservoir. Follow-ups were performed at 1, 3, 6, 9, and 12 months.ResultsMild to moderate vertigo and nausea were common but temporary adverse events associated with intrathecal rituximab infusion, which was otherwise well tolerated. The only severe adverse event was a case of low-virulent bacterial meningitis that was treated effectively. Of 7 clinical assessments, only 1 showed statistically significant improvement 1 year after treatment. No treatment effect was observed during the follow-up period among 6 CSF biomarkers.ConclusionsIntrathecal administration of rituximab was well tolerated. However, it may involve a risk for injection-related infections. The lack of a control group precludes conclusions being drawn regarding treatment efficacy.ClinicalTrials.gov identifierNCT01719159.Classification of evidenceThis study provides Class IV evidence that intrathecal rituximab treatment is well tolerated and feasible in PMS but involves a risk of severe infections.

Ocrelizumab zur Behandlung der Multiplen Sklerose

“…Die Datenlage bezüglich intrathekaler Applikation von CD20-depletierenden monoklonalen Antikörpern ist gering [87]. Ferner ist hervorzuheben, dass es bei RMS-Patienten unter Ocrelizumab im Vergleich zu Interferon-β1a zu mehr Varizella-Zoster-Infektionen (17 vs. 8 [25]) und bei PPMS-Patienten unter Ocrelizumab im Vergleich zu Placebo zu mehr oralen Herpesinfektionen (2,3 % vs. 0,4 %; [26]) gekommen ist.…”

Intrathecal treatment trial of rituximab in progressive MS: results after a 2-year extension

“…Participants were recruited at the neurology departments of Norrland's University Hospital, Umeå and Uppsala Hospital, Sweden between 27th June 2009 and 11th May 2015. Inclusion-and exclusion criteria are described in detail elsewhere [1]. Baseline characteristics for both studies are shown in Table 1.…”

“…In the original ITT-PMS study, participants received an Ommaya reservoir as an access point for intraventricular injections [1].…”

“…Intrathecal (IT) administration of rituximab might, therefore, 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]. The short-term follow-up of that trial precluded the detection of any disease-modifying effect on disease progression.…”

<p>Rituximab Prevents the Development of Experimental Autoimmune Encephalomyelitis (EAE): Comparison with Prophylactic, Therapeutic or Combinational Regimens</p>

“…Rituximab also showed efficacy in ameliorating demyelinating disorders of the CNS. 12 Intrathecal administration of RTX in progressive MS was well tolerated, 13 demonstrating good tolerability and efficacy in cases of both relapsing and progressive forms of MS. 14 The risk of John Cunningham (JC) virus and progressive multifocal leukoencephalopathy (PML) in MS patients was lowest in RTX-treated MS patients as compared to natalizumab, fingolimod or other diseasemodifying therapy (DMT). 15,16 In this work, we systematically investigated the effects of RTX on ameliorating EAE disorder.…”