title: Randomized trial of vaccination in fingolimod-treated patients with multiple sclerosis.
abstract: 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.
  
  
  CONCLUSIONS
  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.
  
  
  METHODS
  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: 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.
authors: Ludwig
authors: L
authors: Kappos
authors: 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.
authors: Matthias
authors: M
authors: Mehling
authors: 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.
authors: Rafael
authors: R
authors: Arroyo
authors: 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.
authors: Guillermo
authors: G
authors: Izquierdo
authors: 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.
authors: Krzysztof
authors: K
authors: Selmaj
authors: 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.
authors: Valentina
authors: V
authors: Curovic-Perisic
authors: 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.
authors: Astrid
authors: A
authors: Keil
authors: 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.
authors: Mahendra
authors: M
authors: Bijarnia
authors: 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.
authors: Arun
authors: A
authors: Singh
authors: 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.
authors: Philipp
authors: P
authors: von Rosenstiel
mesh_terms: D000293:Adolescent; D000328:Adult; D004311:Double-Blind Method; D005260:Female; D000068876:Fingolimod Hydrochloride; D006801:Humans; D007166:Immunosuppressive Agents / Q000276:immunology / Q000627:therapeutic use*; D007252:Influenza Vaccines / Q000276:immunology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology; D011409:Propylene Glycols / Q000276:immunology / Q000627:therapeutic use*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000276:immunology / Q000627:therapeutic use; D016896:Treatment Outcome; D014611:Vaccination / Q000379:methods; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D007252:Influenza Vaccines; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine