Influence of disease modifying treatment and anti-CD20 infusion timing on humoral response to SARS-CoV-2 vaccines in multiple sclerosis patients

Introduction: Recently developed vaccines can prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, but vaccine-induced immune responses can be impaired by disease modifying treatments (DMTs) commonly used in multiple sclerosis (MS). Objectives: To investigate the humoral response to SARS-CoV-2 mRNA vaccines in MS patients under different DMTs, and provide indications on potential strategies to optimize SARS-CoV-2 vaccination. Methods: this was a prospective single center observational cohort study performed at the Neurocenter of Southern Switzerland (Lugano Switzerland). MS patients were consecutively recruited between 25/02/2021 and 16/04/2021 during routine clinical visits. Inclusion criteria were: A diagnosis of MS according to the 2017 McDonald criteria;age >18 years;scheduled mRNA COVID-19 vaccination. IgG antibodies against the spike receptor-binding domain of SARS-CoV-2 were measured by chemiluminescence microparticle immunoassay (CMIA) at 21-35 days after the second vaccine dose. Results: A total of 107 patients were included (56 under anti-CD20 therapy, 14 under cladribine, 20 under teriflunomide, 7 under sphingosine- 1-phosphate receptor [S1P] modulators, and 10 untreated). Post-vaccine SARS-CoV-2 IgG titers were high among untreated patients (median=8,003 [QR=1,792-21,137] mAU/ml), patients under treatment with cladribine (6,175 [IQR=3,982-10,194] mAU/ ml), and teriflunomide (5,630 [2,596-14,087] mAU/ml). Titers were significantly lower under anti-CD20 therapy (68 [0-808] mAU/ml;β=-2.009, p 6 months before vaccination, and with higher CD19+ B cell counts at vaccination. Conclusions: The humoral response to SARS-CoV-2 mRNA vaccines is preserved in untreated MS patients and those treated with cladribine and teriflunomide, but reduced under anti-CD20 therapies and S1P-modulators. Within patients under treatment with anti-CD20 therapies, delaying vaccinations to more than 6 months after last infusion and waiting for B cell repopulation are potential strategies to optimize humoral response to vaccines.