To investigate neutropenia in people with demyelinating diseases undergoing B-cell depleting therapies. 

Transient asymptomatic neutropenia is a rare complication of monoclonal antibody medications. There are limited studies on this complication in real-world populations. 

Patients seen by a neuroimmunologist at our tertiary referral center from 2008-2025 who had an international classification of disease (ICD) code for neutropenia were screened. Cases with confirmed concomitant anti-CD20 use were retained. The period prevalence of anti-CD20 use was estimated from ICD codes for demyelinating diseases and any anti-CD20 medication within their medication list. 

Among all 2912 patients treated with anti-CD20s at our center from 2008-2025, neutropenia was observed in 35 individuals (1.2%). Episodes of neutropenia occurred with ocrelizumab (n=24), rituximab (n=8), ofatumumab (n=9) and ublituximab (n=1). The average age at neutropenia onset was 41.1±10.7 years and 91% had multiple sclerosis. 12 patients presented with fever, sepsis and/or mucous membrane sores and 11 required hospitalization. 13 cases had absolute neutrophil counts <500 cell/µL; 6 required treatment with granulocyte colony stimulating factor. The neutropenia was deemed a drug related adverse event in 7, infectious sequelae in 2, “benign”/genetic or cyclic in 18, autoimmune in 2 and of unclear etiology in 6. Disease modifying therapy was changed in 12 patients; 4 stopped all therapies, 3 were switched to a fumarate, 2 moved to extended interval dosing, and 3 switched to other B cell depleting therapies. However, within this latter group, 2 subsequently developed recurrent neutropenia. 

In our experience, patients who had asymptomatic cyclic or presumed “benign” neutropenia tolerated B-cell depletion well, whereas neutropenia as an adverse drug effect, associated with sepsis/fever, prompted medication switches. Neutropenia did not always spontaneously reverse and in some people, neutropenia appeared to be a class effect of B-cell depleting therapies, possibly reflecting presence of an inherent susceptibility.