How does immunotherapy for MS and the COVID-19 vaccination relate? This question is currently being asked frequently by my patients. As already mentioned in some blog posts about vaccination and MS, the COVID-19 vaccination poses no danger even during ongoing immunotherapy, as the currently available vaccines are exclusively so-called “dead vaccines”. However, it should be noted that immunotherapies usually downregulate the readiness of the immune system and therefore a vaccination theoretically cannot lead to the desired and sufficient protective immunity. This problem is less pronounced with certain MS drugs such as a therapy with interferons, Copaxone, Teriflunomid, Dimethylfumarat or Natalizumab, with Cladribin, Fingolimod or Ozanimod probably somewhat stronger. There are also MS drugs whose effect is based on the reduction of certain immune cells, namely the B cells, which also play an important role in the formation of a vaccination response. Therefore, the main question at present is how to behave with Ocrelizumab therapy in relation to the COVID-19 vaccination.
Therefore, I would like to focus on answering this question, although practical experiences with Ocrelizumab and the COVID-19 vaccination are still completely lacking. However, one can derive some valuable information from the existing scientific studies on Ocrelizumab. Since vaccinations represent an important prophylactic measure of the health care system, there are experimental series for almost every MS drug that have tested the response to vaccinations – usually to the flu vaccine. Such a study was also conducted on vaccination in patients treated with Ocrelizumab. The results of the study were published in the journal NEUROLOGY in fall 2020 – those interested can read the results here (Bar Or et al. Effect of ocrelizumab on vaccine responses in patients with multiple sclerosis: The VELOCE study. Neurology 2020 Oct 6;95(14):e1999-e2008).
Study result on Ocrelizumab and vaccines
In summary, patients were injected with various vaccines 12 weeks after treatment with Ocrelizumab (Ocrevus) and their vaccination response was compared to that of patients who had been pretreated with interferon-beta preparations. The test groups were vaccinated against tetanus, pneumococci and influenza. In addition, all subjects were immunized with a so-called neoantigen, a protein that was immunologically “new” for all subjects. This is particularly important because no immunity has yet been built up in the population against SARS-CoV2, so we are immunologically naive for the spike protein of SARS-CoV2.
The positive response rate to the tetanus vaccine after 8 weeks was 23.9% in the Ocrelizumab group compared to 54.5% in the control group (where a ≥4-fold increase in the antibody titer due to the vaccination was defined as a positive response rate – fortunately, all subjects in the Ocrelizumab and control group achieved serum protection). The positive response rate to ≥5 serotypes of the polyvalent pneumococcal vaccine after 4 weeks was 71.6% in the Ocrelizumab group and 100% in the control group. The response rates after 4 weeks against the 5 administered influenza strains ranged in the Ocrelizumab group between 55.6% and 80.0% and in the control group between 75.0% and 97.0%. A humoral response to the neoantigen KLH (keyhole limpet hemocyanin – a protein complex from the hemolymph of the large California keyhole limpet, does not occur in the human organism) was detectable in the Ocrelizumab group, but significantly lower than in the control group.
Vaccination also recommended under Ocrelizumab
On the basis of these results, the authors of the study come to the following conclusion: Whenever possible, vaccination requirements should be completed as per local prescribing information before the initiation of Ocrelizumab, which will optimize vaccine effectiveness. Nonetheless, vaccination even after Ocrelizumab initiation is likely to generate a meaningful vaccine response in most patients and may be considered when vaccination is deemed useful. (Whenever possible, patients should be vaccinated according to local recommendations before starting therapy with Ocrelizumab in order to take full advantage of the optimal effectiveness of the vaccine. Nevertheless, it is likely that vaccination even after the start of therapy with Ocrelizumab will lead to a sufficient vaccination reaction in most patients, accordingly vaccination should be carried out if there is a sensible indication).
And this situation is currently given by the COVID-19 vaccination. To put it positively – and thus also set a counterpoint against overly fatalistic portrayals on television (see WISO from 18.01.2021) – vaccination with Ocrelizumab therapy is possible and will also lead to the desired success in most cases. It is probably wise – if one can influence it – to keep as long a distance as possible from the last infusion, a distance of 12 weeks as in the study would be scientifically substantiated. However, since one can probably only influence the timing of the vaccination to a limited extent at present, I would advise all those willing to be vaccinated to simply get vaccinated when the opportunity arises.
This recommendation is now first and foremost a snapshot, we will certainly continue to learn, but it is currently what we know.
