Ocrelizumab, a monoclonal anti-CD20 antibody, is widely used to treat MS due to its efficacy in reducing disease activity. However, SN (<500/mm³) occurs in approximately 0.1% of patients, increasing the risk of infection and complicating management. Despite the growing use of Ocrelizumab, the risk factors for developing SN are not well understood.

We described five cases with neutropenia (four SN) and compared them with 82 patients without neutropenia regarding variables such as age, MS duration, time on Ocrelizumab, EDSS, relapses in the last year with Ocrelizumab (RLY with Ocre), comorbidities, and previous disease-modifying therapies. Categorical variables were compared using the Chi-square test, and continuous variables were analyzed using the Mann-Whitney U test.

Of the 87 MS-OC patients, neutropenia was detected in five, with four cases being severe. All four patients with SN were women. One case involved primary progressive MS, one case secondary progressive MS (SPMS), and two cases relapsing-remitting MS (RRMS). The SPMS and both RRMS cases had experienced RLY with Ocre. All four patients presented with infections (only two with fever) and responded well to antibiotic treatment. Three required treatment with G-CSF. 

In comparisons with MS-OC patients without neutropenia, the five MS patients with neutropenia showed a significant  increase  in RLY with Ocre (p=0.048). In the comparisons with the four SN cases, there was only a trend (p=0.087) in RLY with Ocre.

The presence of relapses in MS patients treated with Ocrelizumab predisposes them to neutropenia. Severe neutropenia is a serious complication of Ocrelizumab treatment. An urgent blood count should be performed in the event of fever, active infection, or unexplained worsening not attributed to a relapse.