RESUMO
BACKGROUND: Immunogenicity of influenza and pneumococcal vaccines varies and requires further elucidation in patients with multiple sclerosis (MS) under treatment with disease-modifying therapies (DMTs). METHODS: Adult MS patients who consented with vaccination after standard-of-care consultation by their treating physicians were enrolled. All received a single dose of an inactivated quadrivalent influenza vaccine and of the 23-valent pneumococcal vaccine. A blood sample was collected before and after four weeks of vaccination for measurement of antibodies against Influenza A, B and S. pneumoniae. Patients were followed-up for adverse events and MS relapse for 12 months. RESULTS: One hundred and seventy-two patients (65.7 % female, mean age 42 ± 13 years old, mean MS duration 7.6 ± 7.2 years, 81.4 % under DMTs) were enrolled from November 2019 to March 2020. Antibody measurements were available for 151 patients. Seropositivity for anti-PPSV23 did not differ between baseline and at 4 weeks of follow-up (n = 56, 37.1 %). There was a significant increase of absolute antibody titers post-vaccination for both influenza A and B (p < 0.001). For Influenza A, seropositivity was evident for 57 (37.7 %) patients at 4 weeks compared to 19 (12.6 %) patients at baseline (pMcNemar < 0.001). For Influenza Β, 110 (72.8 %) seroconverted 4 weeks after vaccination compared to 12 (7.9 %) at baseline (pMcNemar < 0.001). Interferon and fumarate did not affect influenza seroconversion while rituximab was associated with lower titers. Mild local AEs (pain, edema) were observed in 23.8 %; no severe AE was reported. Thirty-four patients (19.8 %) had a relapse during the 12-month follow-up; none was attributed to the vaccination. CONCLUSIONS: Seroconversion in MS patients on treatment was more frequent following influenza compared to PPSV23 vaccination. Rituximab had an effect on the height of the immune response. Better immunization coverage as well as future evaluation of the breadth of immune response elicited by immunization is necessary for these patients.
RESUMO
BACKGROUND: Seroconversion rate of vaccines varies and requires further elucidation in patients with multiple sclerosis (MS) under treatment with disease-modifying therapies (DMTs). We aimed to investigate this in a systematic review and meta-analysis. METHODS: MEDLINE(PubMed) and Cochrane databases were searched based on a pre-specified protocol (PROSPERO: CRD42020202018). Studies reporting on patients with MS, diagnosed with McDonald criteria getting vaccinated with any type of vaccine were included in the analysis. The primary endpoint was the incidence of patients being seropositive and experience adverse events after vaccination. Outcomes were expressed as proportions with respective 95% confidence interval (CI). Two reviewers independently screened and reviewed existing literature and assessed study quality with the Methodological index for non-randomized studies. RESULTS: Of 295 articles, 45 studies were analyzed. Seroconversion after COVID-19 vaccines was 76% (95% CI, 70-80; I2 = 95%; 20 studies including 5601 patients. Protection was lower in patients treated with anti-CD20 antibodies and sphingosine-1-phosphate receptor (S1PR) modulators compared to untreated patients or treatment with other DMTs. Relapse occurred in 2% (95% CI, 1-3; I2 = 86%; 16 studies including 7235 patients). Seroconversion after seasonal influenza vaccines was 82% (95% CI, 65-91; I2 = 90%; 6 studies including 490 patients). Relapse rate was similar to this after COVID-19 vaccination. CONCLUSION: The majority of MS patients vaccinated for COVID-19 or seasonal influenza mount an adequate immune response without safety concerns. Data on other vaccines are limited.