The MS therapy with anti-CD20 antibodies (Ocrelizumab – Ocrevus®, Ofatumumab – Kesimpta®, Ublituximab – Briumvi® and off-lable Rituximab) usually proceeds smoothly and without side effects, especially in younger patients – the drugs are all quite well tolerated and, apart from fatigue on the day of infusion/injection, hardly cause any problems. Nevertheless, we require our patients to have regular checks of their differential blood count in the interval between infusions, usually at least once a quarter. This often (but not always) works quite well for patients who are directly under our care. For patients who come to our practice from further afield and have these checks carried out by their GP, it sometimes doesn’t work so well. Even though I understand that regular blood tests are a nuisance, this measure is essential for the safety of our patients. These regular checks are carried out to detect a rare but very serious change in the blood picture that can be caused by anti-CD20 antibodies. This is a reduction in white blood cells, so-called neutrophil granulocytes – technically also known as neutropenia.
Blood checks for early detection
Severe neutropenia caused by anti-CD20 antibodies is said to occur when the absolute number of neutrophil granulocytes drops below 500/µl. This is accompanied by a significant weakening of the innate immune defence against bacteria and fungi. The more pronounced the neutropenia is and the longer it persists, the greater the risk of life-threatening infections. Even minor skin injuries can then become the starting point of a severe infection. Neutrophil granulocytes represent the first line of defence against germs and are thus responsible for the classic inflammatory reaction. In the case of neutropenia, these typical signs of the inflammatory reaction, such as pus formation, redness and swelling of the tissue, are often absent. Often only moderate fever (>38.0 °C) is the only symptom of a severe infection. Therefore, febrile neutropenia is considered a medical emergency and requires immediate treatment with antibiotics to prevent life-threatening complications. It should therefore be clear how important it is to detect this rare but serious complication of anti-CD20 antibodies in good time, for which regular checks of the differential blood count are used.
Why am I addressing this again, even though this problem has been known for years? On the one hand, we see cases of neutropenia under anti-CD20 therapy every now and then, also recently, which fortunately all had a good outcome. On the other hand, colleagues from Portugal published a nice overview on this topic in the MSARD journal (Multiple Sclerosis And Related Disorders) in May 2026 (Silva et al. Mult Scler Relat Disord 2026 May:109:107133).
The colleagues investigated the occurrence of neutropenia after administration of Ocrelizumab based on their own cases and a systematic literature search. According to their survey, the annual incidence was 0.63%. The average age of the affected individuals was 36.2 years; 67.6% were female. The median number of previous disease-modifying therapies was 1. Neutropenia occurred after a median of two cycles since the first Ocrelizumab infusion and 72.5 days after the last infusion. The majority of patients (88.9%) showed late-onset neutropenia and grade 4 neutropenia (88.9% – > 500/µl). Therapeutic intervention involved treatment with granulocyte colony-stimulating factors (G-CSF) and antibiotics. All neutropenia episodes resolved within a median of 4.5 days. In summary, neutropenia occurred relatively early in the course of treatment, most patients had severe neutropenia, but showed a mild clinical course. Interestingly, resumption of Ocrelizumab therapy was possible, although recurrences can occur.
Therefore, particularly strict monitoring should take place in case of re-exposure to anti-CD20 antibodies. However, the occurrence of neutropenia should not initially be a reason to deny MS patients this efficient and highly effective therapy in the long term. Ultimately, the continuation of therapy is always an individual decision.
However, it is important to me that patients who receive anti-CD20 antibodies realize how important regular blood count checks are for their own safety and therefore demand these checks from their doctors.
This post was translated from German to English with the help of AI.
