Joakim Bergman1, Joachim Burman2, Jonathan D Gilthorpe2, Henrik Zetterberg2, Elena Jiltsova2, Tommy Bergenheim2, Anders Svenningsson2. 1. From the Department of Pharmacology and Clinical Neuroscience (J. Bergman, J.D.G., T.B., A.S.), Umeå University; Department of Neurosciences (J. Burman, E.J.), Uppsala University; Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square; UK Dementia Research Institute at UCL (H.Z.), London; and Department of Clinical Sciences (A.S.), Karolinska Institute Danderyd Hospital, Stockholm, Sweden. joakim.bergman@umu.se. 2. From the Department of Pharmacology and Clinical Neuroscience (J. Bergman, J.D.G., T.B., A.S.), Umeå University; Department of Neurosciences (J. Burman, E.J.), Uppsala University; Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square; UK Dementia Research Institute at UCL (H.Z.), London; and Department of Clinical Sciences (A.S.), Karolinska Institute Danderyd Hospital, Stockholm, Sweden.
Abstract
OBJECTIVES: To 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. METHODS: Three 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. RESULTS: Mild 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. CONCLUSIONS: Intrathecal 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. CLINICALTRIALSGOV IDENTIFIER: NCT01719159. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that intrathecal rituximab treatment is well tolerated and feasible in PMS but involves a risk of severe infections.
OBJECTIVES: To 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. METHODS: Three 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. RESULTS: Mild 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. CONCLUSIONS: Intrathecal 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. CLINICALTRIALSGOV IDENTIFIER: NCT01719159. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that intrathecal rituximab treatment is well tolerated and feasible in PMS but involves a risk of severe infections.
Authors: Pavan Bhargava; Cassie Wicken; Matthew D Smith; Roy E Strowd; Irene Cortese; Daniel S Reich; Peter A Calabresi; Ellen M Mowry Journal: Mult Scler Relat Disord Date: 2019-02-11 Impact factor: 4.339
Authors: Carmen Alcalá; Carlos Quintanilla-Bordás; Francisco Gascón; Ángel Perez Sempere; Laura Navarro; María Carcelén-Gadea; Lamberto Landete; Javier Mallada; Emmanuel Cañizares; Antonio Belenguer; Sara Carratalá; José Andrés Domínguez; Francisco Carlos Pérez-Miralles; Sara Gil-Perotín; Raquel Gasqué; Laura Cubas; Jéssica Castillo; Bonaventura Casanova Journal: J Neurol Date: 2022-02-02 Impact factor: 4.849
Authors: Giancarlo Comi; Amit Bar-Or; Hans Lassmann; Antonio Uccelli; Hans-Peter Hartung; Xavier Montalban; Per Solberg Sørensen; Reinhard Hohlfeld; Stephen L Hauser Journal: Ann Neurol Date: 2020-11-04 Impact factor: 10.422