ArticleNeurology(R) neuroimmunology & neuroinflammation2022
CCR5 Blockade in Inflammatory PML and PML-IRIS Associated With Chronic Inflammatory Diseases' Treatments.
Article in Neurology(R) neuroimmunology & neuroinflammation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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10 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- Guidelines on the Use of Therapeutic Apheresis in Clinical Practice-Evidence-Based Approach From the Writing Committee of the American Society for Apheresis: The Tenth Special Issue.Journal of clinical apheresis · 2026Guideline
- Microglial Ccl4-Ccr5 signaling links systemic inflammation to synaptic loss and memory deficits in chronic kidney disease.Journal of neuroinflammation · 2026Article
- Successful treatment of HIV-related progressive multifocal leukoencephalopathy and immunological reconstitution inflammatory syndrome with intravenous human immunoglobulin: a case report.AIDS research and therapy · 2025Article
- Late-Onset Combined Immunodeficiency presenting with Progressive Multifocal Leukoencephalopathy and associated Immune Reconstitution Inflammatory Syndrome.Le infezioni in medicina · 2025Article
- Targeting cytokine networks in neuroinflammatory diseases.Nature reviews. Drug discovery · 2024Review
- Chemokine-mediated cell migration into the central nervous system in progressive multifocal leukoencephalopathy.Cell reports. Medicine · 2024Article
- Bridging the Gap: Immunotherapy in Progressive Multifocal Leukoencephalopathy: A New Hope?Neurology · 2023Article
- Progressive Multifocal Leukoencephalopathy Treated by Immune Checkpoint Inhibitors.Annals of neurology · 2023Article
- The CCR5 antagonist maraviroc exerts limited neuroprotection without improving neurofunctional outcome in experimental pneumococcal meningitis.Scientific reports · 2022Article
- Therapeutic advances in neuroinfectious diseases.Therapeutic advances in infectious diseaseReview
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Authors and funding
13 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesProgressive multifocal leukoencephalopathy (PML) is a disabling neurologic disorder resulting from the infection of the CNS by JC polyomavirus in immunocompromised individuals. For the last 2 decades, increasing use of immunotherapies leads to iatrogenic PML. Iatrogenic PML is often associated with signs of inflammation at onset (inflammatory PML) and/or after treatment withdrawal immune reconstitution inflammatory syndrome (PML-IRIS). Although immune reconstitution is a key element for viral clearance, it may also be harmful and induce clinical worsening. A C-C chemokine receptor type 5 (CCR5) antagonist (maraviroc) has been proposed to prevent and/or limit the deleterious immune responses underlying PML-IRIS. However, the data to support its use remain scarce and disputed.
methodsWe conducted a multicenter retrospective cohort study at 8 university hospitals in France and Switzerland by collecting clinical, biological, and radiologic data of patients who developed inflammatory PML (iPML) or PML-IRIS related to immunosuppressive therapies used for chronic inflammatory diseases between 2010 and 2020. We added to this cohort, a meta-analysis of individual case reports of patients with iPML/PML-IRIS treated with maraviroc published up to 2021.
resultsOverall, 27 cases were identified in the cohort and 9 from the literature. Among them, 27 met the inclusion criteria: 16 treated with maraviroc and 11 with standard of care (including corticosteroids use). Most cases were related to MS (92.6%) and natalizumab (88%). Inflammatory features (iPML) were present at onset in 12 patients (44.4%), and most patients (92.6%) received corticosteroids within the course of PML. Aggravation due to PML-IRIS was not prevented by maraviroc compared with patients who received only corticosteroids (adjusted odds ratio: 0.408, 95% CI: 0.06-2.63). Similarly, maraviroc did not influence time to clinical worsening due to PML-IRIS (adjusted hazard ratio = 0.529, 95% CI: 0.14-2.0) or disability at the last follow-up (adjusted odds ratio: 2, 95% CI: 0.23-17.3). DISCUSSION: The use of CCR5 blockade did not help to keep deleterious immune reconstitution in check even when associated with corticosteroids. Despite maraviroc's reassuring safety profile, this study does not support its use in iPML/PML-IRIS. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence showing that adding maraviroc to the management of iatrogenic iPML/PML-IRIS does not improve the outcome.
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