No Early Effect of Intrathecal Rituximab in Progressive Multiple Sclerosis (EFFRITE Clinical Trial)

Mickael Bonnan; Sylvie Ferrari; Henri Courtade; Paul Money; Pauline Desblache; Bruno Barroso; Stéphane Debeugny

doi:10.1155/2021/8813498

No Early Effect of Intrathecal Rituximab in Progressive Multiple Sclerosis (EFFRITE Clinical Trial)

Mult Scler Int. 2021 Mar 8:2021:8813498. doi: 10.1155/2021/8813498. eCollection 2021.

Authors

Mickael Bonnan¹, Sylvie Ferrari², Henri Courtade³, Paul Money⁴, Pauline Desblache⁴, Bruno Barroso¹, Stéphane Debeugny⁵

Affiliations

¹ Service de Neurologie, Hôpital F. Mitterrand, 4 bd Hauterive, 64046 Pau, France.
² Pharmacie, Hôpital F. Mitterrand, 4 bd Hauterive, 64046 Pau, France.
³ Biologie Médicale, Hôpital F. Mitterrand, 4 bd Hauterive, 64046 Pau, France.
⁴ Service de Radiologie, Hôpital F. Mitterrand, 4 bd Hauterive, 64046 Pau, France.
⁵ Département de Recherche Clinique, Hôpital F. Mitterrand, 4 bd Hauterive, 64046 Pau, France.

Abstract

Background: The progressive phase of multiple sclerosis (MS) is characterized by an intrathecal (IT) compartmentalization of inflammation, involving B-cells within meningeal follicles, and resisting all the available immunosuppressive treatments. A new therapeutic paradigm may be to target this inflammation by injecting immunosuppressive drugs inside the central nervous system compartment.

Methods: We designed a single-center, open-label, randomized, controlled, phase II study designed to evaluate the safety and efficacy of IT rituximab in progressive MS (EFFRITE trial; ClinicalTrial Registration NCT02545959). Patients were randomized into three arms (1 : 1 : 1): control group, IT rituximab (20 mg, IT) group, and intravenous+IT (IV+IT) group. The main outcome was a change in levels of CSF biomarkers of inflammation (osteopontin). Secondary outcomes were changes in levels of CSF biomarkers of axonal loss (neurofilament light chain) and clinical and MRI changes.

Results: Ten patients were included (2 : 4 : 4). No adverse event occurred. OPN level remained stable in CSF at each time point, whereas NFL had slightly decreased (-8.7%) at day 21 (p = 0.02). Clinical parameters remained stable and leptomeningeal enhancements remained unchanged.

Conclusion: Clinical outcome and biomarkers of inflammation were not dramatically modified after IT injection of rituximab, probably due to its limited efficiency in CSF. Drug issues for future studies are discussed.