Ludwig Kappos1, Matthias Mehling2, Rafael Arroyo2, Guillermo Izquierdo2, Krzysztof Selmaj2, Valentina Curovic-Perisic2, Astrid Keil2, Mahendra Bijarnia2, Arun Singh2, Philipp von Rosenstiel2. 1. From the University Hospital Basel (L.K., M.M.), Basel, Switzerland; Hospital Clínico San Carlos (R.A.), Madrid, Spain; Virgen Macarena Hospital (G.I.), Seville, Spain; Medical University of Lodz (K.S.), Lodz, Poland; Novartis Pharmaceuticals Corporation (V.C.-P.), Hanover, NJ; Novartis Pharma AG (A.K., P.v.R.), Basel, Switzerland; and Novartis Healthcare Pvt. Ltd. (M.B., A.S.), Hyderabad, India. ludwig.kappos@usb.ch. 2. From the University Hospital Basel (L.K., M.M.), Basel, Switzerland; Hospital Clínico San Carlos (R.A.), Madrid, Spain; Virgen Macarena Hospital (G.I.), Seville, Spain; Medical University of Lodz (K.S.), Lodz, Poland; Novartis Pharmaceuticals Corporation (V.C.-P.), Hanover, NJ; Novartis Pharma AG (A.K., P.v.R.), Basel, Switzerland; and Novartis Healthcare Pvt. Ltd. (M.B., A.S.), Hyderabad, India.
Abstract
OBJECTIVE: To evaluate immune responses in fingolimod-treated patients with multiple sclerosis (MS) againstinfluenza 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.
RCT Entities:
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.
Authors: G Redelman-Sidi; O Michielin; C Cervera; C Ribi; J M Aguado; M Fernández-Ruiz; O Manuel Journal: Clin Microbiol Infect Date: 2018-02-07 Impact factor: 8.067
Authors: Heinz Wiendl; Ralf Gold; Thomas Berger; Tobias Derfuss; Ralf Linker; Mathias Mäurer; Martin Stangel; Orhan Aktas; Karl Baum; Martin Berghoff; Stefan Bittner; Andrew Chan; Adam Czaplinski; Florian Deisenhammer; Franziska Di Pauli; Renaud Du Pasquier; Christian Enzinger; Elisabeth Fertl; Achim Gass; Klaus Gehring; Claudio Gobbi; Norbert Goebels; Michael Guger; Aiden Haghikia; Hans-Peter Hartung; Fedor Heidenreich; Olaf Hoffmann; Zoë R Hunter; Boris Kallmann; Christoph Kleinschnitz; Luisa Klotz; Verena Leussink; Fritz Leutmezer; Volker Limmroth; Jan D Lünemann; Andreas Lutterotti; Sven G Meuth; Uta Meyding-Lamadé; Michael Platten; Peter Rieckmann; Stephan Schmidt; Hayrettin Tumani; Martin S Weber; Frank Weber; Uwe K Zettl; Tjalf Ziemssen; Frauke Zipp Journal: Nervenarzt Date: 2021-07-23 Impact factor: 1.214
Authors: Christoph Metze; Alexander Winkelmann; Micha Loebermann; Michael Hecker; Brunhilde Schweiger; Emil Christian Reisinger; Uwe Klaus Zettl Journal: CNS Neurosci Ther Date: 2018-07-25 Impact factor: 5.243