RT Journal Article
SR Electronic
T1 Randomized trial of vaccination in fingolimod-treated patients with multiple sclerosis
JF Neurology
JO Neurology
FD Lippincott Williams & Wilkins
SP 872
OP 879
DO 10.1212/WNL.0000000000001302
VO 84
IS 9
A1 Ludwig Kappos
A1 Matthias Mehling
A1 Rafael Arroyo
A1 Guillermo Izquierdo
A1 Krzysztof Selmaj
A1 Valentina Curovic-Perisic
A1 Astrid Keil
A1 Mahendra Bijarnia
A1 Arun Singh
A1 Philipp von Rosenstiel
YR 2015
UL http://n.neurology.org/content/84/9/872.abstract
AB Objective: To evaluate immune responses in fingolimod-treated patients with multiple sclerosis (MS) against influenza vaccine (to test for responses against anticipated novel antigens in seronegative patients) and recall (tetanus toxoid [TT] booster dose) antigens.Methods: This was a blinded, randomized, multicenter, placebo-controlled study. Patients aged 18 to 55 years with relapsing MS were randomized (2:1) to fingolimod 0.5 mg or placebo for 12 weeks. At week 6, patients received seasonal influenza vaccine (containing antigens of California, Perth, and Brisbane virus strains) and TT booster dose. Antibody titers against influenza and TT were estimated at baseline (prevaccination) and 3 and 6 weeks postvaccination. The primary efficacy variable was responder rate (proportion of patients showing seroconversion or significant increase [≥4-fold] in antibody titers against at least one influenza virus strain) at 3 weeks postvaccination and vs placebo.Results: Of 138 randomized patients (fingolimod 95, placebo 43), 136 completed the study (2 discontinued in fingolimod group). The responder rates (odds ratio; 95% confidence interval) for influenza vaccine (fingolimod vs placebo) were 54% vs 85% (0.21; 0.08–0.54) at 3 weeks and 43% vs 75% (0.25; 0.11–0.57) at 6 weeks postvaccination. For TT, responder rates were 40% vs 61% (0.43; 0.20–0.92) at 3 weeks and 38% vs 49% (0.62; 0.29–1.33) at 6 weeks postvaccination. Adverse events were reported in 86.3% and 79.1% of patients receiving fingolimod and placebo, respectively.Conclusion: Most fingolimod-treated patients with MS were able to mount immune responses against novel and recall antigens and the majority met regulatory criteria indicating seroprotection. However, response rates were reduced compared with placebo-treated patients. This should be kept in mind when vaccinating patients on fingolimod.Classification of evidence: This study provides Class I evidence that in some patients with MS receiving immunizations, concurrent fingolimod treatment in comparison to placebo decreases vaccination-induced immune responses.CCR7=C-C chemokine receptor 7; CI=confidence interval; HAI=hemagglutination inhibition; Ig=immunoglobulin; KLH=keyhole limpet hemocyanin; MS=multiple sclerosis; OR=odds ratio; PPV-23=23-valent pneumococcal polysaccharides vaccine; S1P=sphingosine 1-phosphate; TT=tetanus toxoid