ArticleAnnals of clinical and translational neurology2016
Insufficient disease inhibition by intrathecal rituximab in progressive multiple sclerosis.
Article in Annals of clinical and translational neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 84 papers, 8 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Double Blind Combination of Rituximab by Intravenous and Intrathecal Injection Versus Placebo in Patients With Low-Inflammatory Secondary Progressive Multiple Sclerosis (RIVITaLISe)
Cerebrospinal Fluid-biomarkers-based Diagnostic and Prognostic Models for Multiple Sclerosis
Who cites it
84 citing papers in PubMed, 8 syntheses or guidelines pooled it, 150 citations in OpenAlex.
- Rituximab for people with multiple sclerosis.The Cochrane database of systematic reviews · 2025Pooled it
- Immunomodulators and immunosuppressants for progressive multiple sclerosis: a network meta-analysis.The Cochrane database of systematic reviews · 2024Pooled it
- Disease-modifying therapy in progressive multiple sclerosis: a systematic review and network meta-analysis of randomized controlled trials.Frontiers in neurology · 2024Pooled it
- Efficacy and safety of rituximab in multiple sclerosis: a systematic review and meta-analysis.Acta neurologica Belgica · 2023Pooled it
- Adverse effects of immunotherapies for multiple sclerosis: a network meta-analysis.The Cochrane database of systematic reviews · 2023Pooled it
- The Efficacy and Safety of Anti-CD20 Antibody Treatments in Relapsing Multiple Sclerosis: A Systematic Review and Network Meta-analysis.CNS drugs · 2022Pooled it
- Rituximab for people with multiple sclerosis.The Cochrane database of systematic reviews · 2021Pooled it
- Systematic Review of Safety and Efficacy of Rituximab in Treating Immune-Mediated Disorders.Frontiers in immunology · 2019Pooled it
- Clemastine fumarate accelerates accumulation of disability in progressive multiple sclerosis by enhancing pyroptosis.The Journal of clinical investigation · 2025Trial
- Idebenone does not inhibit disability progression in primary progressive MS.Multiple sclerosis and related disorders · 2020Trial
- CSF inflammatory biomarkers responsive to treatment in progressive multiple sclerosis capture residual inflammation associated with axonal damage.Multiple sclerosis (Houndmills, Basingstoke, England) · 2019Trial
- Early Combined B-Cell Depletion and BTK Inhibition Reduced TLS-like Structures and Relapse in PLPInternational journal of molecular sciences · 2026Article
- Extensive peripheral immunoglobulin repertoire analyses in people with multiple sclerosis reveal disease-specific signatures and distinct treatment effects of disease modifying drugs.Journal of neuroinflammation · 2026Article
- Preclinical B cell depletion and safety profile of a brain-shuttled crystallizable fragment-silenced CD20 antibody.Clinical and translational medicine · 2025Article
- Effects of cladribine on intrathecal and peripheral B and plasma cells.Clinical and experimental immunology · 2025Article
- B cell depletion attenuates CD27 signaling of T helper cells in multiple sclerosis.Cell reports. Medicine · 2024Article
- New views on the complex interplay between degeneration and autoimmunity in multiple sclerosis.Frontiers in cellular neuroscience · 2024Article
- Bruton tyrosine kinase inhibitors for multiple sclerosis.Nature reviews. Neurology · 2023Review
- Multiple sclerosis plasma IgG aggregates induce complement-dependent neuronal apoptosis.Cell death & disease · 2023Article
- Cladribine treatment specifically affects peripheral blood memory B cell clones and clonal expansion in multiple sclerosis patients.Frontiers in immunology · 2023Article
24 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveInaccessibility of the inflammation compartmentalized to the central nervous system (CNS) may underlie the lack of efficacy of immunomodulatory treatments in progressive multiple sclerosis (MS). The double blind combination of Rituximab by IntraVenous and IntraThecAl injection versus placebo in patients with Low-Inflammatory SEcondary progressive MS (RIVITALISE; NCT01212094) trial was designed to answer: (1) Whether an induction dose of intravenous and intrathecal rituximab efficiently depletes CNS B cells? and (2) If so, whether this leads to global inhibition of CNS inflammation and slowing of CNS tissue destruction?
methodsPatients aged 18-65 years were randomly assigned to rituximab or placebo. Protocol-stipulated interim analysis quantified the efficacy of B-cell depletion.
resultsThe efficacy on cerebrospinal fluid (CSF) biomarkers failed to reach criteria for continuation of the trial. B-cell-related CSF biomarkers (sCD21 and B-cell activating factor) changed only in the active-treatment arm. While CSF B cells were killed robustly (median -79.71%, P = 0.0176), B cells in CNS tissue were depleted inadequately (~-10-20%, P < 0.0001). Consequently, the T-cell-specific CSF biomarker sCD27 decreased slightly (-10.97%, P = 0.0005), while axonal damage marker, neurofilament light chain did not change. Insufficient saturation of CD20, lack of lytic complement, and paucity of cytotoxic CD56(dim) NK cells contribute to decreased efficacy of rituximab in the CNS.
interpretationBiomarker studies reliably quantified complementary pharmacodynamic effects of rituximab in the CNS, exposed causes for poor efficacy and determined that RIVITALISE trial would be underpowered to measure efficacy on clinical outcomes. Identified mechanisms for poor efficacy are applicable to all CNS-inflammation targeting monoclonal antibodies.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.