Kappos Ludwig, Mehling Matthias, Arroyo Rafael, Izquierdo Guillermo, Selmaj Krzysztof, Curovic-Perisic Valentina, Keil Astrid, Bijarnia Mahendra, Singh Arun, von Rosenstiel Philipp
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.
Neurology. 2015 Mar 3;84(9):872-9. doi: 10.1212/WNL.0000000000001302. Epub 2015 Jan 30.
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.
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.
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.
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.
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.
评估用芬戈莫德治疗的多发性硬化症（MS）患者对流感疫苗（用于检测血清阴性患者对预期新抗原的反应）和回忆抗原（破伤风类毒素[TT]加强剂量）的免疫反应。
这是一项双盲、随机、多中心、安慰剂对照研究。年龄在18至55岁的复发型MS患者被随机（2:1）分为接受0.5mg芬戈莫德或安慰剂治疗12周。在第6周时，患者接受季节性流感疫苗（包含加利福尼亚、珀斯和布里斯班病毒株的抗原）和TT加强剂量。在基线（接种疫苗前）以及接种疫苗后3周和6周时评估针对流感和TT的抗体滴度。主要疗效变量是接种疫苗后3周时以及与安慰剂相比的应答率（针对至少一种流感病毒株抗体滴度出现血清转化或显著升高[≥4倍]的患者比例）。
138例随机分组的患者（芬戈莫德组95例，安慰剂组43例）中，136例完成了研究（芬戈莫德组2例退出）。接种疫苗后3周时流感疫苗的应答率（优势比；95%置信区间）（芬戈莫德组与安慰剂组相比）分别为54%对85%（0.21；0.08 - 0.54），接种疫苗后6周时为43%对75%（0.25；0.11 - 0.57）。对于TT，接种疫苗后3周时应答率为40%对61%（0.43；0.20 - 0.92），接种疫苗后6周时为38%对49%（0.62；0.29 - 1.33）。分别有86.3%和79.1%接受芬戈莫德和安慰剂治疗的患者报告了不良事件。
大多数用芬戈莫德治疗的MS患者能够对新抗原和回忆抗原产生免疫反应，且大多数符合表明血清保护的监管标准。然而，与安慰剂治疗的患者相比，应答率有所降低。在为接受芬戈莫德治疗的患者接种疫苗时应牢记这一点。
本研究提供了I类证据，即在一些接受免疫接种的MS患者中，与安慰剂相比，同时使用芬戈莫德治疗会降低疫苗诱导的免疫反应。
