Effect of the Number of Vaccine Doses Before Starting Anti-CD20 Therapy on Seroprotection Rates Against Hepatitis B Virus in People With MS.

BACKGROUND AND OBJECTIVES Hepatitis B vaccination (HBV) requires 6 months to complete and is recommended for patients with multiple sclerosis (PWMS), particularly those who are candidates for anti-CD20 therapy. However, limited data exist on HBV immunogenicity in PWMS receiving disease-modifying therapies (DMTs) and the impact of starting anti-CD20 therapy during immunization. We aimed to evaluate HBV immunogenicity in PWMS starting anti-CD20 therapy during vaccination, focusing on the number of doses received before anti-CD20 initiation. METHODS We conducted a retrospective analysis of a prospective cohort of adult PWMS at a single center in Spain, from April 2015 to May 2023. Eligible participants completed a 4-dose HBV course and underwent postvaccination serologic testing. We assess seroprotection rates (SRs), defined as the percentage of patients achieving anti-hepatitis B surface antibody titers ≥10 IU/L, focusing on those who switched to anti-CD20 therapy during vaccination, based on doses received before starting anti-CD20 and type of DMT at vaccination start. A multivariate generalized linear model (GLM) was used to identify factors associated with higher seroconversion. RESULTS A total of 289 PWMS (median [interquartile range (IQR)] age, 47.7 [42.8-54.4] years; 65.7% female; median [IQR] disease duration, 14.8 [6.7-21.2] years) were included. SRs progressively declined with fewer doses before anti-CD20 initiation, from 92.8% (95% CI 87.1-96.5) for 4 doses to 24.0% (95% CI 9.4-45.1) for 1 dose. Patients transitioning from sphingosine 1-phosphate (S1P) modulators showed the lowest SR at 25.0% (95% CI 7.3-52.4). The multivariate GLM confirmed these findings, with 3 doses (SR ratio 3.23 [95% CI 1.68-6.23]; p = 0.0005) or 4 doses (SR ratio 3.76 [95% CI 1.96-7.24]; p < 0.0001) before anti-CD20 therapy significantly associated with higher SRs, while starting S1P modulators at vaccination onset was significantly associated with lower SRs (SR ratio 0.42 [95% CI 0.23-0.78]; p = 0.0058). Female sex (SR ratio 1.15 [95% CI 1.01-1.32]; p = 0.0389) and younger age (SR ratio 0.90 [95% CI 0.83-0.97]; p = 0.0036) were also significantly associated with higher SRs. DISCUSSION Initiating anti-CD20 therapy during HBV negatively affects SRs, with a direct correlation with the number of doses received before anti-CD20 initiation. Early planning and execution of required vaccinations are crucial in managing PWMS. CLASSIFICATION OF EVIDENCE This study provides Class III evidence that HBV during initiation of anti-CD20 therapy is less effective in establishing seroprotection to hepatitis B than in patients in whom HBV is completed before initiation of anti-CD20 therapy.