Monoclonal antibodies directed against CD20 are increasingly employed as disease modifying therapies in multiple sclerosis (MS). Descriptions of iatrogenic neutropenia and neutropenic fever in this population are currently limited to small case series. Questions remain regarding this potentially severe complication, including its incidence, risk factors, and management.

This retrospective cohort study was completed in a 14-hospital health system. We systematically queried the electronic medical record to identify patients with MS on B-cell depleting therapies who developed neutropenia, severe neutropenia, or neutropenic fever between 10/15/2015 – 10/15/2024. For this study, neutropenia was defined as an absolute neutrophil count (ANC) < 1.5, severe neutropenia as an ANC < 0.5, and febrile neutropenia as an ANC < 0.5 with a documented fever of 38 degrees Celsius for at least an hour.

We identified 22 patients with neutropenia on ocrelizumab, with an average ANC nadir of 0.62. There were 12 patients who met severe neutropenia criteria on ocrelizumab, with an average ANC of 0.13. Five received granulocyte-macrophage colony-stimulating factor (GMCSF), all of whom had severe neutropenia. Nine patients developed febrile neutropenia on ocrelizumab, with an average ANC of 0.02, and four of them received GMCSF. Only two patients were identified with neutropenia on ofatumumab: one with an ANC of 0 who received GMCSF, and another with an ANC of 1.5 who did not. No patients on ofatumumab developed febrile neutropenia.

Neutropenia, severe neutropenia, and febrile neutropenia may be underrecognized complications of anti-CD20 medications in patients with MS. Many patients with neutropenia remain fever free and recover well, either with time alone or with GMCSF. In this cohort, GMCSF was well-tolerated and did not induce disease activity. Information regarding who develops neutropenia will be presented.