Most MS patients currently treated with fingolimod or ocrelizumab will fail to mount an immune response to COVID-19 vaccination, according to the results of the first real-world study of vaccine response in MS patients on disease-modifying therapies (DMT) (Achiron et al. Ther Adv Neurol Disord 2021:14:1-8). An adequate vaccine response was seen in cladribine-treated patients.
The results suggest that MS patients currently on fingolimod should be advised not to get vaccinated against COVID-19, and that ocrelizumab-treated patients should wait at least 9 months before receiving a vaccine.
The observational study examined data for 125 MS patients and 47 healthy subjects receiving the Pfizer-BioNTech vaccine in Israel. The MS group comprised relapsing-remitting (60.8%), secondary-progressive (14.4%), primary-progressive (19.2%) and RIS/CIS (5.6%) patients. An ELISA anti-SARS-CoV-2 IgG immunoassay was performed 4-6 weeks after the second vaccine dose.
Patients in the fingolimod group (n=26) were currently on treatment during the vaccination period in accordance with the current vaccine guidance. Median age was 44.9 years; 46.2% were female; median disease duration was 15.7 years; and median EDSS score was 2.0. The proportion of patients with a protective IgG antibody response was 3.8%. At the time of vaccination, 88.5% of fingolimod-treated subjects had an absolute lymphocyte count (ALC) < 1.0 x 109/L; median ALC was 0.5. ALC was <0.5 in 38.5%, 50% had ALC 0.5 to 1.0, and 11.5% had ALC >1.0. No antibody response was detected in the three patients with ALC >1.0.
In the ocrelizumab group (n=44), the median time from last dose to vaccination was 4.9 months. Median age was 53.2 years; 45.5% were female; median disease duration was 13.4 years; and median EDSS score was 5.5. The proportion of patients that mounted an antibody response was 22.7%. Most patients (77.3%) did not mount a protective antibody titre when vaccinated up to 8.9 months after the last dose of ocrelizumab. The failure to mount an antibody response was not related to ALC; the ALC was >1.0 in 95.5% of patients at the time of vaccination.
In the cladribine group (n=23), the median time from last dose to vaccination was 7.1 months. Median age was 43.1 years; 73.9% were female; median disease duration was 11.0 years; and median EDSS score was 3.0. The proportion of patients that mounted an antibody response was 100.0%. Median ALC at the time of vaccination was 0.9. A protective antibody response was seen even in patients vaccinated as soon as 4.4 months after the last cladribine dose.
In addition, 100% of untreated patients (n=32) and 97.9% of healthy controls (n=47) mounted a protective antibody response to COVID vaccination.
The authors concluded that untreated MS patients and cladribine-treated patients who are vaccinated within 4.4 months of the last treatment dose will have an adequate response to COVID vaccination.
However, most patients receiving ocrelizumab will fail to mount an adequate vaccine response in the 9 months following their last treatment dose. ALC in these patients does not appear to adequately predict vaccine response, suggesting that the depletion of naïve and memory B cells seen with ocrelizumab impairs the protective humoral response.
No patient currently treated with fingolimod would be expected to respond to a vaccine irrespective of their lymphocyte count at the time of vaccination. This suggests that patients currently on fingolimod, and perhaps other S1PR modulators, would need to interrupt treatment for several months to derive any benefit from COVID-19 vaccination.
As a result of these findings, the group is updating its COVID-19 vaccination recommendations to state that untreated MS patients can be vaccinated without limitations and cladribine-treated patients should be vaccinated at least 4.4 months after the last dose. The group does not promote COVID-19 vaccination in fingolimod-treated patients unless the lymphocyte count is >1.0, with the caveat that ALC is not correlated with a protective humoral response. Ocrelizumab-treated patients who are not at high risk of severe COVID are advised to postpone vaccination for at least 9 months after the last dose.
Free download of the full paper by Achiron et al. at https://journals.sagepub.com/doi/pdf/10.1177/17562864211012835.