Immune response to vaccines is maintained in patients treated with dimethyl fumarate

Abstract

Objectives: To investigate the immune response to vaccinations in patients with relapsing forms of MS treated with delayed-release dimethyl fumarate (DMF) vs nonpegylated interferon (IFN).

Methods: In this open-label, multicenter study, patients received 3 vaccinations: (1) tetanus-diphtheria toxoid (Td) to test T-cell-dependent recall response, (2) pneumococcal vaccine polyvalent to test T-cell-independent humoral response, and (3) meningococcal (groups A, C, W-135, and Y) oligosaccharide CRM₁₉₇ conjugate to test T-cell-dependent neoantigen response. Eligible patients were aged 18-55 years, diagnosed with relapsing-remitting MS (RRMS), and either treated for ≥6 months with an approved dose of DMF or for ≥3 months with an approved dose of nonpegylated IFN. Primary end point was the proportion of patients with ≥2-fold rise in antitetanus serum IgG levels from prevaccination to 4 weeks after vaccination.

Results: Seventy-one patients (DMF treated, 38; IFN treated, 33) were enrolled. The mean age was 45.3 years (range 27-55); 86% were women. Responder rates (≥2-fold rise) to Td vaccination were comparable between DMF- and IFN-treated groups (68% vs 73%). Responder rates (≥2-fold rise) were also similar between DMF- and IFN-treated groups for diphtheria antitoxoid (58% vs 61%), pneumococcal serotype 3 (66% vs 79%), pneumococcal serotype 8 (95% vs 88%), and meningococcal serogroup C (53% vs 53%), all p > 0.05. In a post hoc analysis, no meaningful differences were observed between groups in the proportion of responders when stratified by age category or lymphocyte count.

Conclusions: DMF-treated patients mount an immune response to recall, neoantigens, and T-cell-independent antigens, which was comparable with that of IFN-treated patients and provided adequate seroprotection.

Clinicaltrialsgov identifier: NCT02097849.

Classification of evidence: This study provides Class II evidence that patients with RRMS treated with DMF respond to vaccinations comparably with IFN-treated patients.

Figure 1. Responder rates of patients at 4 weeks compared with prevaccinated levels

Responder rates of patients with a (A) ≥2- and (B) ≥4-fold rise in immunoglobulin G titers at 4 weeks compared with prevaccinated levels. The mean responder rate is shown; error bars indicate SE. BID = twice daily; CI = confidence interval; DMF = delayed-release dimethyl fumarate; IFN = interferon.

Figure 2. Individual antibody titers at day 1 and week 4

Antibody titers were assessed for (A) tetanus antitoxoid, (B) Diphtheria antitoxoid, (C) Pneumococcal serotype 3, (D) Pneumococcal serotype 8, and (E) Meningococcal serotype C. BID = twice daily; DMF = delayed-release dimethyl fumarate; IFN = interferon.

Figure 3. Geometric mean titer ratio and seroprotection at week 4

(A) Geometric mean titer ratio and (B) seroprotection at week 4. All patients entering the study had protective levels against diphtheria. The protective level was based on American Academy of Allergy, Asthma & Immunology guidance for diagnostic vaccines; it is an active area of research. Protective levels were 0.15 IU/mL for tetanus, 0.01 IU/mL for diphtheria, 1.3 μg/mL for pneumococcal serotypes 3 and 8, and 2.0 μg/mL for meningococcal serogroup C. The proportion of patients with protective antibody titers/number of patients in the group is shown. BID = twice daily; DMF = delayed-release dimethyl fumarate; IFN = interferon.