Immune response to influenza vaccine in patients with relapsing multiple sclerosis treated with ofatumumab: Results...

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).

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).

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.

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.

ClinicalTrials.gov: NCT04667117 (https://clinicaltrials.gov/study/NCT04667117).