Anti-CD20 Agents Provide New Therapeutic Approaches to Neurological Diseases

During the fourth congress of the European Academy of Neurology (EAN), held in Lisbon, Portugal, from June 16 to 19, researchers presented on the roles of both existing and investigational anti-CD20 drugs in treating neurological diseases.

Rituximab may have a role in treating immunoglobulin G4-related disease

Rituximab has been demonstrated to be useful in the treatment of neurological diseases such as multiple sclerosis (MS) and myasthenia gravis, but a case study presented during the EAN conference suggests that it may also have a role to play in treating diseases related to immunoglobulin G4 (IgG4).

Researchers from Portugal reported on the case of a 70-year old man who developed progressive right ptosis and vision loss that was associated with headache.¹ Magnetic resonance imaging (MRI) showed right frontal lobe hypersignal with homogeneous enhancement as well as meningeal thickening with dural enhancement. Computed tomography revealed ethmoidal and frontal bone erosion. A biopsy revealed a lymphoplasmacytic infiltrate, storiform fibrosis, and more than 10 IgG4-expressing plasma cells per field.

While corticosteroids were used with initial results, the patient experienced progressive deterioration of his vision as meningeal thickening increased. The patient then received 2 infusions of rituximab, after which he experienced improvement in his visual acuity (though MRI results remained unchanged).

According to the study’s authors, intravenous rituximab is a promising therapeutic strategy in treating IgG4-related disease in patients who do not have an adequate response to steroids, and intrathecal administration of rituximab may be a possibility in those who do not respond adequately to intravenous administration.

A novel anti-CD20 monoclonal antibody may allow for short infusion times in MS

While existing anti-CD20 drugs have demonstrated their utility in treating MS, lengthy infusion times may be burdensome for patients. In a phase 2 clinical trial, ublituximab, a novel anti-CD20 agent, was demonstrated to be safe and well tolerated when infused over time periods as low as 1 hour.²

The 52-week study included 24 patients with relapsing-remitting MS. Patients received 3 infusions of the investigational drug on days 1, 15, and week 24. All patients achieved 95% B-cell depletion within 4 weeks of treatment, and of the 11 patients who have so far completed 52 weeks of treatment, 87% remain relapse-free and 81% are free of disability progression.

The most commonly reported adverse events (AEs) were infusion site reactions, all of which were grade 1 or grade 2, which were reported in 17% of patients. No severe AEs were reported, and infusions times as low as 1 hour were not associated with an increase in AEs.

References

1. Soares C, Costa A, Pestana-Silva R, Faria O, Honavar M, Abreu P. A difficult case of immunoglobulin G4-hypertrophic pachymeningitis—rituximab as part of the solution. Presented at the European Academy of Neurology Congress, June 16-19, 2018; Lisbon, Portugal. Abstract EPR2143. https://ipp-ean18.netkey.at/index.php?p=recorddetail&rid=ed524a8c-f503-4bc5-9c97-ba95fa64edf7&t=browsepresentations.

2. Fox E, Lovett-Racke A, Inglese M, et al. Phase 2 multicenter study results of ublituximab, a novel glycoengineered antiCD20 monoclonal antibody (mAb), in patients with relapsing multiple sclerosis (RMS). Presented at the European Academy of Neurology Congress, June 16-19, 2018; Lisbon, Portugal. Abstract O331. https://ipp-ean18.netkey.at/index.php?p=recorddetail&rid=cf7552fb-319c-4ba5-a646-f130ca9def7c&t=browsepresentations.