To highlight idiosyncratic drug-induced neutropenia (IDIN) as a complication of ofatumumab exposure in multiple sclerosis (MS).

MS is a chronic demyelinating disorder of the central nervous system. B-cell depleting therapies, which target the cluster of differentiation 20 (CD20) receptor using monoclonal antibodies (mAbs), have shown high efficacy and relative safety in altering the course of MS. Three anti-CD20 mAbs (ocrelizumab, ofatumumab, and ublituximab) are currently approved by the Food and Drug Administration (FDA) for MS treatment. Despite the selectivity of anti-CD20 mAbs, the potentially fatal complication of IDIN (neutrophils <1.5 × 10⁹/L) can occur. Existing FDA prescribing information describes neutropenia risk for ocrelizumab and ublituximab, but not ofatumumab.

Case report and FDA Adverse Event Reporting System (FAERS) review for “neutropenia”, “neutrophil count decreased”, “febrile neutropenia”, “neutropenic sepsis”, and “agranulocytosis” with ofatumumab for MS from FDA approval through June 30, 2024. 

A woman in her 20s with MS developed gingival pain and oral lesions after being on ofatumumab for three months. Complete blood count revealed agranulocytosis (<0.5 × 10⁹ neutrophils/L) with 0 neutrophils prompting ofatumumab discontinuation and intravenous antimicrobials. Neutrophil count normalized after seven days, but one month later symptoms recurred with agranulocytosis. She was admitted and restarted on antimicrobials with resolution of agranulocytosis after ten days. 

Analysis of the FAERS database identified 70 cases of neutropenia associated with ofatumumab, with 92.9% classified as serious. Ten cases involved agranulocytosis, though none were fatal.