Table 1.
Assessed responses to selected vaccines in patients receiving DMTs.
| DMT | Study design | Groups compared | Vaccine type | Assessment of immune response | Key findings | References |
|---|---|---|---|---|---|---|
| Teriflunomide | TERIVA Open-label, parallel-group (N = 128) | Patients receiving teriflunomide 7 or 14 mg vs. IFN-β-1 | Influenza | Antibody titers ≥40 at 28 days after vaccination | Post-vaccination titers ≥40 achieved for ≥90% of patients in all groups (H1N1) and ≥90% of patients receiving teriflunomide 7 mg or IFN-β-1 (H3N2; 77% response with teriflunomide 14 mg) | (13) |
| Randomized, double-blind, placebo-controlled (N = 46) | Healthy controls receiving teriflunomide 14 mg vs. placebo | Rabies | Antibody titers (>0.5 IU/mL) | Teriflunomide did not limit the ability to achieve seroprotective titers against neoantigen. However, antibody titers were lower with teriflunomide than with placebo | (14) | |
| IFN-β | Prospective, non-randomized, open-label (N = 163) | Patients receiving IFN-β-1a vs. patients not receiving IFN-β-1a | Influenza | HI titers (≥40 indicated seroprotection) | Similar proportions of patients achieved seroprotection IFN-β-1a, 93.0%; no IFN-β-1a, 90.9%) | (15) |
| Open-label, observational, retrospective-prospective (N = 59) | Patients receiving IFN-β vs. healthy controls | Influenza | Influenza-specific T cells; anti-influenza A and B IgM and IgG titers | Influenza-specific T cell frequencies and IgG titers increased similarly in both groups, indicating a strong immune response | (16) | |
| IFN-β, DMF | Open-label (N = 71) | DMF vs. IFN | Tetanus, diphtheria | Proportion of patients with ≥2-fold increase in antitoxoid titers by 4 weeks after vaccination | Response rates were similar for DMF vs. IFN: tetanus, 68 vs. 73%; diphtheria, 58 vs. 61% | (17) |
| Meningococcal | Response rate was 53% for both groups | |||||
| Pneumococcal | Response rates were similar for DMF vs. IFN: pneumococcal serotype 3, 66 vs. 79%; pneumococcal serotype 8, 95 vs. 88% | |||||
| Fingolimod | Prospective, observational, open-label (N = 32) | Patients receiving fingolimod vs. healthy controls | Influenza | Lymphocyte counts; frequency of influenza-specific cells; virus-specific T cell responses | Lymphocyte counts decreased 64% vs. the lower limit of normal for patients receiving fingolimod Similar frequencies of influenza-specific IFN-γ-secreting T cells were observed between patients receiving fingolimod and healthy controls Patients achieved a normal T cell response to vaccine despite S1PR blockade with fingolimod |
(18) |
| Fingolimod | Blinded, randomized, placebo-controlled (N = 136) | Patients receiving fingolimod vs. placebo | Influenza | Proportion of patients achieving seroconversion or ≥4-fold increase in antibody titers against ≥1 influenza strain or seroconversion against tetanus vaccine | Response rates were 54% (fingolimod) vs. 85% (placebo) at 3 weeks and 43 vs. 75% at 6 weeks post vaccination | (19) |
| Tetanus | Response rates were reduced for fingolimod vs. placebo at 3 weeks (40 vs. 61%) and 6 weeks (38 vs. 49%) after vaccination | |||||
| Natalizumab | Randomized, open-label (N = 60) | Patients receiving natalizumab vs. untreated controls | Tetanus, KLH | Adequate response, defined as ≥2-fold increase in specific serum IgG 28 days after vaccination | All evaluable patients had adequate response to tetanus toxoid; the proportions of responders to tetanus and KLH vaccines were similar with vs. without natalizumab | (20) |
| Ocrelizumab | VELOCE/ Phase 3b, open-label (N = 102) | Patients receiving ocrelizumab vs. controls (IFN-β or no DMT) | Influenza | Hemagglutination inhibition titers (≥40 indicated seroprotection) | Seroprotection was achieved by 55.6–80.0% of patients receiving ocrelizumab vs. 97.0% of controls | (21) |
| Tetanus, KLH | Proportion of patients with a positive response 8 weeks after vaccination (anti-TT IgG antibody titer ≥0.2 IU/mL) | Response rates were reduced with ocrelizumab vs. controls to tetanus (23.9 vs. 54.5%) and Pneumovax (71.6 vs. 100%) vaccines; humoral response to KLH was reduced with ocrelizumab | ||||
| Pneumococcal (13-PCV, 23-PPV) | Proportion of patients with a positive response 4 weeks after vaccination (≥2-fold increase in IgG titers) | Response rates to 23-PPV were reduced with ocrelizumab (71.6%) vs. controls (100%) | ||||
| Alemtuzumab | Pilot, historical case-control (N = 23) | Influenza | Rates of seroprotection (≥2-fold increase in antibodies) | 100% of patients who received the influenza vaccine achieved seroprotection; 95% achieved ≥4-fold increase in antibody titers, compared with 82–90% of historical controls | (22) | |
| (N = 22) | Diphtheria, tetanus, polio-myelitis | Post-vaccine rates of seroprotection were 95–100% for patients receiving alemtuzumab | ||||
| (N = 23) | Meningococcal group C | 91% of patients achieved seroprotection vs. 97.6–100% of historical controls | ||||
| (N = 21) | Pneumococcal (23-PPV) | Serotype 3: 73% of patients achieved seroconversion vs. 35–47% of historical controls Serotype 8: 95% of patients achieved seroconversion vs. 81–85% of historical controls |
||||
| Daclizumab-β | SELECTED Open-label, single-arm, prospective (N = 90) | Daclizumab-β | Influenza | Hemagglutination inhibition titers (≥40 indicated seroprotection) | Seroprotection achieved for 92% (strain A/H1N1), 91% (A/H3N2), and 67% (B) of patients | (23) |
| Multiple | Prospective, non-randomized, observational (N = 108) | Patients receiving IFNs, glatiramer acetate, natalizumab, fingolimod, or other DMTs | Influenza | Proportion of patients achieving seroconversion or seroprotection; mean geometric titer increase; proportion of patients achieving HI titer ≥40 | Rates of seroprotection were highest in H1N1 strain (71.4–100%), compared with H3N2 (28.6–33.3%) or B strains (57.1–88.9%) Overall seroprotection was highest in patients receiving IFNs (73.3%) and glatiramer acetate (57.7%) and lowest in those receiving natalizumab (14.3%) and fingolimod (33.3%) |
(24) |
| Multiple | Prospective, non-randomized, open-label (N = 152) | Patients receiving fingolimod, glatiramer acetate, IFN-β-1a/b, natalizumab, or no DMT vs. healthy controls | Influenza | Seroprotection rates at 3, 6, and 12 months | At 3–12 months post vaccination, seroprotection rates were reduced for patients receiving natalizumab (55.6–75.0% protected) or fingolimod (22.2–71.4%) vs. healthy controls (70.4–94.6%); patients receiving glatiramer acetate (77.3–91.3%) or IFN-β-1a/b (79.0–88.0%) achieved similar protection to controls | (25) |
| Multiple | Observational, prospective (N = 329) | Patients receiving IFN-β, glatiramer acetate, natalizumab, or mitoxantrone vs. controls | Influenza | Seroprotection rates (defined as HI ≥ 40) | Rates of seroprotection varied by DMT and influenza strain (H1N1, H3N2); patients receiving IFN-β had similar response rates as healthy controls, whereas rates were generally lower with glatiramer acetate, natalizumab (except for 2010 H1N1 strain), and mitoxantrone | (26) |
| Multiple | Observational multicenter prospective cohort (N = 780) | Patients with MS receiving ocrelizumab, natalizumab, fingolimod, IFNs, teriflunomide, other DMTs, or untreated | SARS-CoV-2 | SARS-CoV-2 antibodies before 1st vaccination and 4 weeks after 2nd vaccination | Compared with untreated patients, post-vaccination antibody levels were significantly lower for patients receiving ocrelizumab (201-fold reduction), fingolimod (26-fold reduction), or rituximab (20-fold) (P < 0.001 for all). No significant difference was observed with teriflunomide or other DMTs | (27) |
| Multiple | Observational cohort (N = 172) | Patients with MS receiving DMTs vs. healthy controls | SARS-CoV-2 IgG antibody titers | Sufficient antibody response to vaccination was observed for 97.9–100% of healthy controls, untreated MS patients, and patients receiving cladribine, but for only 3.8% receiving fingolimod and 22.7% receiving ocrelizumab | (7) | |
| Multiple | Observational cohort (N = 120) | Patients with MS receiving DMTs | SARS-CoV-2 IgG antibody titers | Compared with patients receiving no MS therapy, the IgG antibody response to vaccination was reduced for those receiving anti-CD20 antibodies (β = −2.19; P < 0.001) or sphingosine-1-phosphate modulators (β = −1.92; P < 0.001); no difference was observed for patients receiving teriflunomide (β = −0.01; P = 0.98) or cladribine (β = −0.39; P = 0.44) | (28) |
13-PCV, 13-valent pneumococcal conjugate; 23-PPV, 23-valent pneumococcal polysaccharide; DMF, dimethyl fumarate; DMT, disease-modifying therapy; HI, hemagglutination inhibition; IFN, interferon; Ig, immunoglobulin; KLH, keyhole limpet hemocyanin; MS, multiple sclerosis; S1PR, sphingosine-1-phosphate inhibitor.