2023 American Academy of Neurology Abstract Website

Kanika Sharma¹, Samiksha Srivastava², Anek Jena³, Mihir Kakara⁴, Shitiz Sriwastava⁵, Maha Daimee⁶, Jian Xu⁷
¹Neurology, Department of Neurology, Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV, ²Neurology, Sinai Grace Hospital-DMC, ³Neurology, Calcutta Medical College, Calcutta, India, ⁴Neurology, Department of Neurology, Perelman School of Medicine, University of Pennsylvania, PA, ⁵Neurology, West Virginia Clinical and Translational Science Institute, Morgantown, WV;, ⁶Neurology, Beaumont Hospital, ⁷Neurology, Henry Ford Hospital

Objective:

To review the incidence of progressive multifocal leukoencephalopathy (PML) associated with monoclonal antibody (mAb) therapies, specifically anti-CD20 medications used in multiple sclerosis (MS).

Background:

PML is an opportunistic and fatal inflammatory disease of the central nervous system, which occurs almost exclusively in immunocompromised hosts; therefore, patients receiving mAb immunotherapy become an at-risk population. B cell-depleting mAbs targeting CD20+ cells have become widely used in MS. Although their efficacy is well-known, their associated risk of PML, especially among those without previous disease-modifying therapy (DMT) exposure, has been insufficiently studied.

Design/Methods:

A systematic literature review of PubMed, Google Scholar, EMBASE, and Scopus was conducted by two independent researchers from June 1, 1997, to July 10, 2022. Further data was obtained from the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database and individual pharmaceutical companies (Genentech, Novartis, and TG Therapeutics). Carry-over cases from prior exposure to other immunosuppressants were excluded.

Results:

Between 2015 and 2017, 10 cases of PML were reported in the FAERS database among 334 MS patients taking rituximab; two had previously received natalizumab, leaving eight cases in total. Rituximab-associated PML was also seen in lymphoproliferative disorders (n=52), rheumatoid arthritis (n=9), and granulomatosis with polyangiitis (n=2). Two fatal PML cases were found in MS patients taking ocrelizumab. No cases of PML were reported with ofatumumab in MS; however, 5 cases were reported in chronic lymphocytic leukemia. PML has not been observed with ublituximab, which is currently under FDA review. Among other DMTs, PML was frequently reported with natalizumab (n=884), fingolimod (n=30), dimethyl fumarate (n=12), and alemtuzumab (n=1).

Conclusions:

Anti-CD20 therapies are a safe class of medications with a low infectious risk for PML, especially compared to other mAbs used in MS, such as natalizumab. Nonetheless, risk stratification in susceptible individuals, as done with natalizumab, could prove beneficial with all mAb treatments.