托法替布对类风湿关节炎患者肺炎球菌和流感疫苗应答的影响。
The effect of tofacitinib on pneumococcal and influenza vaccine responses in rheumatoid arthritis.
作者信息
Winthrop Kevin L, Silverfield Joel, Racewicz Arthur, Neal Jeffrey, Lee Eun Bong, Hrycaj Pawel, Gomez-Reino Juan, Soma Koshika, Mebus Charles, Wilkinson Bethanie, Hodge Jennifer, Fan Haiyun, Wang Tao, Bingham Clifton O
机构信息
Division of Infectious Diseases, Oregon Health and Science University, Portland, Oregon, USA.
Department of Internal Medicine and Rheumatology, Healthpoint Medical Group, Tampa, Florida, USA.
出版信息
Ann Rheum Dis. 2016 Apr;75(4):687-95. doi: 10.1136/annrheumdis-2014-207191. Epub 2015 Mar 20.
OBJECTIVE
To evaluate tofacitinib's effect upon pneumococcal and influenza vaccine immunogenicity.
METHODS
We conducted two studies in patients with rheumatoid arthritis using the 23-valent pneumococcal polysaccharide vaccine (PPSV-23) and the 2011-2012 trivalent influenza vaccine. In study A, tofacitinib-naive patients were randomised to tofacitinib 10 mg twice daily or placebo, stratified by background methotrexate and vaccinated 4 weeks later. In study B, patients already receiving tofacitinib 10 mg twice daily (with or without methotrexate) were randomised into two groups: those continuing ('continuous') or interrupting ('withdrawn') tofacitinib for 2 weeks, and then vaccinated 1 week after randomisation. In both studies, titres were measured 35 days after vaccination. Primary endpoints were the proportion of patients achieving a satisfactory response to pneumococcus (twofold or more titre increase against six or more of 12 pneumococcal serotypes) and influenza (fourfold or more titre increase against two or more of three influenza antigens).
RESULTS
In study A (N=200), fewer tofacitinib patients (45.1%) developed satisfactory pneumococcal responses versus placebo (68.4%), and pneumococcal titres were lower with tofacitinib (particularly with methotrexate). Similar proportions of tofacitinib-treated and placebo-treated patients developed satisfactory influenza responses (56.9% and 62.2%, respectively), although fewer tofacitinib patients (76.5%) developed protective influenza titres (≥1:40 in two or more of three antigens) versus placebo (91.8%). In study B (N=183), similar proportions of continuous and withdrawn patients had satisfactory responses to PPSV-23 (75.0% and 84.6%, respectively) and influenza (66.3% and 63.7%, respectively).
CONCLUSIONS
Among patients starting tofacitinib, diminished responsiveness to PPSV-23, but not influenza, was observed, particularly in those taking concomitant methotrexate. Among existing tofacitinib users, temporary drug discontinuation had limited effect upon influenza or PPSV-23 vaccine responses.
TRIAL REGISTRATION NUMBERS
NCT01359150, NCT00413699.
目的
评估托法替布对肺炎球菌疫苗和流感疫苗免疫原性的影响。
方法
我们对类风湿关节炎患者进行了两项研究，分别使用23价肺炎球菌多糖疫苗（PPSV-23）和2011-2012三价流感疫苗。在研究A中，未使用过托法替布的患者按背景甲氨蝶呤分层，随机分为每日两次服用10毫克托法替布组或安慰剂组，并在4周后接种疫苗。在研究B中，已每日两次服用10毫克托法替布（无论是否联用甲氨蝶呤）的患者被随机分为两组：继续（“持续用药”）或中断（“停药”）托法替布2周，然后在随机分组后1周接种疫苗。在两项研究中，均在接种疫苗35天后测量抗体滴度。主要终点是肺炎球菌（针对12种肺炎球菌血清型中的6种或更多血清型，滴度升高两倍或更多）和流感（针对三种流感抗原中的两种或更多抗原，滴度升高四倍或更多）达到满意反应的患者比例。
结果
在研究A（N = 200）中，与安慰剂组（68.4%）相比，托法替布组患者出现满意肺炎球菌反应的比例较低（45.1%），且托法替布组的肺炎球菌滴度较低（尤其是联用甲氨蝶呤时）。托法替布治疗组和安慰剂治疗组出现满意流感反应的患者比例相似（分别为56.9%和62.2%），尽管托法替布组出现保护性流感滴度（三种抗原中的两种或更多种≥1:40）的患者比例低于安慰剂组（分别为76.5%和91.8%）。在研究B（N = 183）中，持续用药组和停药组对PPSV-23（分别为75.0%和84.6%）和流感（分别为66.3%和63.7%）出现满意反应的比例相似。
结论
在开始使用托法替布的患者中，观察到对PPSV-23的反应性降低，但对流感疫苗的反应性未降低，尤其是在联用甲氨蝶呤的患者中。在已使用托法替布的患者中，暂时停药对流感疫苗或PPSV-23疫苗反应的影响有限。
试验注册号
NCT01359150，NCT00413699。
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