Immune response to influenza vaccine in patients with relapsing multiple sclerosis treated with ofatumumab: Results from an open-label, multicenter, phase 4 study

Background: There is currently a need for data regarding whether treatment with ofatumumab (OMB) impacts humoral immune response to vaccines, including the influenza vaccine, in patients with relapsing multiple sclerosis (RMS). Methods: Patients with RMS aged 18–55 years were grouped into three cohorts: cohort 1 (C1) received the influenza vaccine ≥2 weeks before starting OMB; cohort 2 (C2) received the vaccine ≥4 weeks after starting OMB; and cohort 3 (C3) was currently being treated with interferon/glatiramer acetate and received the influenza vaccine ≥4 weeks after enrollment. Patients with recent major infections were excluded. All groups underwent a hemagglutination inhibition (HI) titer before vaccination and 4 weeks after vaccination. The primary endpoint was achieving seroprotection to influenza at week 4 (post-vaccination antibody titer ≥40). Secondary endpoints included achieving seroconversion (post-vaccination HI titers ≥4-fold increase or ≥40 in those with pre-vaccination titers ≥10 or <10, respectively), change in HI titer, and adverse events (AEs). Results: Sixty-three patients (mean [standard deviation] age, 41.1 [8.5] years; 76.2 % female; 85.7 % White) were included (C1, n = 22; C2, n = 22; C3, n = 19). At week 4, seroprotection rates for influenza A Cambodia (C1, 86.7 %, 13/15; C2, 80.0 %, 4/5; C3, 66.7 %, 6/9) and influenza A Victoria (C1, 86.7 %, 13/15; C2, 100 %, 5/5; C3, 77.8 %, 7/9) were generally high. Seroprotection rates for influenza A Wisconsin (C1, 53.3 %, 8/15; C2, 40.0 %, 8/20; C3, 61.1 %, 11/18), influenza B Phuket (C1, 63.6 %, 14/22; C2, 68.2 %, 15/22; C3, 68.4 %, 13/19), and influenza B Washington (C1, 66.7 %, 10/15; C2, 20.0 %, 1/5; C3, 55.6 %, 5/9) were lower across all cohorts. Seroconversion rates at week 4 were variable across vaccine influenza strains. However, trends for lower rates of seroconversion in cohort 2 vs. cohorts 1 and 3 were broadly consistent across strains. Over the entire study, 16/22 (72.7 %) patients from cohort 1, 6/22 (27.3 %) patients from cohort 2, and 2/19 (10.5 %) patients from cohort 3 experienced one or more AEs. The higher frequency of AEs in cohort 1 is likely related to OMB initiation (i.e., systemic and injection-related reactions). One patient from cohort 2 experienced a serious AE (MS pseudo-relapse). No AEs resulting in discontinuation were reported. Conclusion: Some OMB-treated patients with RMS were able to mount an immune response following inactivated influenza vaccination. Patients who were vaccinated before OMB initiation generally had a better immune response than those vaccinated after OMB initiation. No T-cell analyses were performed. Clinical trial registration: ClinicalTrials.gov: NCT04667117 (https://clinicaltrials.gov/study/NCT04667117)