Ocrelizumab (Ocrevus®) is a monoclonal antibody and belongs to the group of so-called B-cell-depleting therapies, which currently play a very important role in the immunotherapy of Multiple Sclerosis. They are used quite frequently. This article discusses potential side effects of Ocrelizumab therapy.
Ocrelizumab is administered as an infusion at 6-month intervals with a dose of 600 mg and binds to molecule CD20 on the surface of B lymphocytes mainly in the peripheral bloodstream. This binding leads to the activation of complement factors and killer cells, which kill the attacked B cell.
Due to the mechanism of action, the most important side effect of Ocrelizumab is the infusion reaction that occurs immediately during administration. It can cause itching, rash, circulatory problems, and shortness of breath. However, efforts are generally made to reduce these infusion reactions, which are directly related to the killing of B lymphocytes, through certain accompanying medications.
Infusion prophylaxis reduces direct side effects
Just before the infusion, an antipyretic, an antiallergic, and cortisone are administered. With the help of these accompanying medications, the infusion reactions are effectively mitigated in most patients. Although patients often complain of fatigue and exhaustion on the day of infusion, serious infusion reactions are extremely rare. Perhaps it should be added here that one should not drive on the day of the infusion (due to the side effects, including those of the accompanying medication), and that the infusion reactions are usually most unpleasant at the first administration and tend to become less and milder over time.
In addition, despite being a quite invasive therapy principle, Ocrelizumab is very well tolerated. The further side effects are manageable both in clinical trials and in practical application – although they are certainly significant.
Corona & Co.
Registry data show that the administration of B-cell-depleting drugs increases susceptibility to infection. Therefore, attention should be paid to infections of the upper and lower respiratory tract. During the Corona pandemic, it was observed at the group level that B-cell depletion was associated with severe Covid-19 courses. Therefore, chronic infections should be excluded before starting therapy, and increased susceptibility to infection should be monitored during therapy.
In this context, it is also important that a certain percentage of Ocrelizumab patients experience a decrease in the immunoglobulin G fraction (IgG) in peripheral blood. In the long term, this value should be kept in mind (see also DocBlog Immunoglobulin levels and B-cell depletion (2)), regular checks are recommended.
Initially, there were also concerns about the cancer risk when using Ocrelizumab, which was related to the fact that in the ORATORIO study, which included patients with progressive MS, significantly more cancers occurred in the Ocrelizumab group. Meanwhile, no evidence of an increased malignancy risk when using Ocrelizumab has been found, but caution should be exercised when using Ocrelizumab in the presence of cancer.
Regular blood count checks under Ocrelizumab
From time to time, significant changes in the blood count are observed when administering Ocrelizumab, and not only a decrease in lymphocytes. Other blood cells can also be affected. Therefore, regular checks of the blood count during therapy are recommended. Here, particular attention should be paid to early-onset neutropenia.
Ocrelizumab was the first B-cell-depleting antibody to be approved in Europe in 2018 and has since been an effective and (initially) safe alternative to Natalizumab due to its good efficacy. Unlike Natalizumab, PML cases only occurred sporadically, and most of these as so-called carry-over PML after switching from Tysabri. However, it should also be kept in mind that Ocrelizumab has only been widely used for the therapy of MS for just under 5 years, so new findings regarding drug safety are still possible.
By the way: General information on the immunological therapy of Multiple Sclerosis is provided in a clear and neutral manner by „MS treat“, a knowledge platform of AMSEL.
