Progressive multifocal leukoencephalopathy in anti-CD20 and other monoclonal antibody (mAb) therapies used in multiple sclerosis: A review

Sharma, K Aparna; Tolaymat, Sarah; Yu, Hongxuyang; Elkhooly, Mahmoud; Jaiswal, Shruti; Jena, Anek; Kakara, Mihir; Sriwastava, Shitiz

doi:10.1016/j.jns.2022.120459

Cited by 13 publications

(6 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Three cases of PML in patients with MS have been reported in the setting of ocrelizumab use without preceding fingolimod or natalizumab exposure; no cases have been reported with ofatumumab or ublituximab. 9 How to extrapolate this to risk for recurrence after natalizumab-associated PML is uncertain. Anti-CD20 DMTs cause sustained depletion of peripheral B-cells and potential development of hypogammaglobulinemia.…”

Section: Discussionmentioning

confidence: 99%

“…Natalizumab is the most common cause of DMT-associated PML, with risk associated with longer duration of treatment (especially >24 months), higher JC virus antibody titer (index >0.9 on STRATIFY), and previous use of immunosuppressive therapies. 8,9 Natalizumab-associated PML results in death in ∼25% of patients. 10 For patients who survive natalizumab-associated PML, there is limited experience on how to retreat with DMT.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Escalation to Anti-CD20 Treatment for Multiple Sclerosis Following Natalizumab-Associated Progressive Multifocal Leukoencephalopathy

Wolf,

Corboy

2024

Neur Clin Pract

View full text Add to dashboard Cite

ObjectivesDisease-modifying therapy (DMT) for multiple sclerosis (MS) after natalizumabassociated progressive multifocal leukoencephalopathy (PML) is controversial due to concern for recurrent PML. We describe DMT utilization for over a decade in a patient with MS who survived PML. Methods Case report. ResultsA 36-year-old woman was diagnosed with MS in 2002 and treated with interferon beta-1a until 2006, when she transitioned to natalizumab due to relapses. She presented in 2012 with 2 months of progressive cognitive and gait concerns and was diagnosed with PML by positive CSF JC virus testing with concordant clinical and MRI findings. She was treated with plasma exchange and then corticosteroids for PML immune reconstitution inflammatory syndrome before starting glatiramer acetate for DMT. She transitioned to dimethyl fumarate in 2013 after MS activity on MRI with negative CSF JC virus testing. Owing to worsening footdrop consistent with progression, she transitioned to ocrelizumab in 2017 and then to ofatumumab in 2020 due to logistics of medication administration. There has been no clinicoradiographic or CSF evidence of recurrent PML. DiscussionDMT selection is challenging for patients with MS who survive PML. We used an escalation approach extending to ocrelizumab and ofatumumab due to MS progression. Anti-CD20 DMTs are a high-efficacy option post-PML. Classification of EvidenceThis provides Class IV evidence. It is a single observational study without controls.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Escalation to Anti-CD20 Treatment for Multiple Sclerosis Following Natalizumab-Associated Progressive Multifocal Leukoencephalopathy

Wolf,

Corboy

2024

Neur Clin Pract

View full text Add to dashboard Cite

show abstract

“…Currently, there are no therapeutic modalities to reverse demyelination or neurodegeneration, even to a modest degree. Their safety profile might be concerning, and the possibility of serious side effects may lead to non-compliance or even treatment discontinuation [126][127][128][129]. Subsequently, there is an unmet need to improve outcomes in MS, especially in the progressive forms.…”

Section: Discussionmentioning

confidence: 99%

From Animal Models to Clinical Trials: The Potential of Antimicrobials in Multiple Sclerosis Treatment

Raghib,

Bernitsas

2023

Biomedicines

View full text Add to dashboard Cite

Multiple sclerosis (MS) is a chronic, autoimmune, demyelinating disease of the central nervous system (CNS). Microbes, including bacteria and certain viruses, particularly Epstein–Barr virus (EBV), have been linked to the pathogenesis of MS. While there is currently no cure for MS, antibiotics and antivirals have been studied as potential treatment options due to their immunomodulatory ability that results in the regulation of the immune process. The current issue addressed in this systematic review is the effect of antimicrobials, including antibiotics, antivirals, and antiparasitic agents in animals and humans. We performed a comprehensive search of PubMed, Google Scholar, and Scopus for articles on antimicrobials in experimental autoimmune encephalomyelitis animal models of MS, as well as in people with MS (pwMS). In animal models, antibiotics tested included beta-lactams, minocycline, rapamycin, macrolides, and doxycycline. Antivirals included acyclovir, valacyclovir, and ganciclovir. Hydroxychloroquine was the only antiparasitic that was tested. In pwMS, we identified a total of 24 studies, 17 of them relevant to antibiotics, 6 to antivirals, and 1 relevant to antiparasitic hydroxychloroquine. While the effect of antimicrobials in animal models was promising, only minocycline and hydroxychloroquine improved outcome measures in pwMS. No favorable effect of the antivirals in humans has been observed yet. The number and size of clinical trials testing antimicrobials have been limited. Large, multicenter, well-designed studies are needed to further evaluate the effect of antimicrobials in MS.

show abstract

“…Progressive multifocal leukoencephalopathy is a potential serious complication of immunotherapy. Based on cases collectively reported from the Genentech, Novartis, and other drug registry data in patients with MS, ten on rituximab (two carry-over cases with prior natalizumab exposure) [16,49], nine on ocrelizumab (seven carry-over cases with prior exposure to natalizumab (6) or fingolimod ( 1)) [18,50,51], and none on ofatumumab or ublituximab have been reported to have developed treatment-related progressive multifocal leukoencephalopathy through October 2022 [52].…”

Section: Progressive Multifocal Leukoencephalopathymentioning

confidence: 99%

Drugs Targeting CD20 in Multiple Sclerosis: Pharmacology, Efficacy, Safety, and Tolerability

Carlson,

Amin,

Cohen

2024

Drugs

View full text Add to dashboard Cite

Currently, there are four monoclonal antibodies (mAbs) that target the cluster of differentiation (CD) 20 receptor available to treat multiple sclerosis (MS): rituximab, ocrelizumab, ofatumumab, and ublituximab. B-cell depletion therapy has changed the therapeutic landscape of MS through robust efficacy on clinical manifestations and MRI lesion activity, and the currently available anti-CD20 mAb therapies for use in MS are a cornerstone of highly effective disease-modifying treatment. Ocrelizumab is currently the only therapy with regulatory approval for primary progressive MS. There are currently few data regarding the relative efficacy of these therapies, though several clinical trials are ongoing. Safety concerns applicable to this class of therapeutics relate primarily to immunogenicity and mechanism of action, and include infusion-related or injection-related reactions, development of hypogammaglobulinemia (leading to increased infection and malignancy risk), and decreased vaccine response. Exploration of alternative dose/dosing schedules might be an effective strategy for mitigating these risks. Future development of biosimilar medications might make these therapies more readily available. Although anti-CD20 mAb therapies have led to significant improvements in disease outcomes, CNS-penetrant therapies are still needed to more effectively address the compartmentalized inflammation thought to play an important role in disability progression.

show abstract

Progressive multifocal leukoencephalopathy in anti-CD20 and other monoclonal antibody (mAb) therapies used in multiple sclerosis: A review

Cited by 13 publications

References 28 publications

Escalation to Anti-CD20 Treatment for Multiple Sclerosis Following Natalizumab-Associated Progressive Multifocal Leukoencephalopathy

Escalation to Anti-CD20 Treatment for Multiple Sclerosis Following Natalizumab-Associated Progressive Multifocal Leukoencephalopathy

From Animal Models to Clinical Trials: The Potential of Antimicrobials in Multiple Sclerosis Treatment

Drugs Targeting CD20 in Multiple Sclerosis: Pharmacology, Efficacy, Safety, and Tolerability

Contact Info

Product

Resources

About