Devillier Philippe, Dreyfus Jean-François, Demoly Pascal, Calderón Moisés A
UPRES EA 220 & Clinical Research Department, Foch Hospital, University of Versailles Saint-Quentin, Suresnes, France.
BMC Med. 2014 May 1;12:71. doi: 10.1186/1741-7015-12-71.
The capacity of sublingual allergen immunotherapy (SLIT) to provide effective symptom relief in pollen-induced seasonal allergic rhinitis is often questioned, despite evidence of clinical efficacy from meta-analyses and well-powered, double-blind, placebo-controlled randomized clinical trials. In the absence of direct, head-to-head, comparative trials of SLIT and symptomatic medication, only indirect comparisons are possible.
We performed a meta-analysis of classes of products (second-generation H1-antihistamines, nasal corticosteroids and grass pollen SLIT tablet formulations) and single products (the azelastine-fluticasone combination MP29-02, and the leukotriene receptor antagonist montelukast) for the treatment of seasonal allergic rhinitis in adults, adolescents and/or children. We searched the literature for large (n >100 in the smallest treatment arm) double-blind, placebo-controlled randomized clinical trials. For each drug or drug class, we performed a meta-analysis of the effect on symptom scores. For each selected trial, we calculated the relative clinical impact (according to a previously published method) on the basis of the reported post-treatment or season-long nasal or total symptom scores: 100 × (scorePlacebo - scoreActive)/scorePlacebo.
Twenty-eight publications on symptomatic medication trials and ten on SLIT trials met our selection criteria (total number of patients: n = 21,223). The Hedges' g values from the meta-analyses confirmed the presence of a treatment effect for all drug classes. In an indirect comparison, the weighted mean (range) relative clinical impacts were -29.6% (-23% to -37%) for five-grass pollen SLIT tablets, -19.2% (-6% to -29%) for timothy pollen SLIT tablets, -23.5% (-7% to -54%) for nasal corticosteroids, -17.1% (-15% to -20%) for MP29-02, -15.0% (-3% to -26%) for H1-antihistamines and -6.5% (-3% to -10%) for montelukast.
In an indirect comparison, grass pollen SLIT tablets had a greater mean relative clinical impact than second-generation antihistamines and montelukast and much the same mean relative clinical impact as nasal corticosteroids. This result was obtained despite the presence of methodological factors that mask the clinical efficacy of SLIT for the treatment of seasonal allergic rhinitis.
尽管荟萃分析以及设计合理的双盲、安慰剂对照随机临床试验均证明了临床疗效,但舌下变应原免疫疗法(SLIT)缓解花粉诱发的季节性变应性鼻炎症状的能力仍常受到质疑。由于缺乏SLIT与对症药物的直接、头对头比较试验,只能进行间接比较。
我们对用于治疗成人、青少年和/或儿童季节性变应性鼻炎的各类产品(第二代H1抗组胺药、鼻用糖皮质激素和草花粉SLIT片剂)和单一产品(氮卓斯汀-氟替卡松复方制剂MP29-02以及白三烯受体拮抗剂孟鲁司特)进行了荟萃分析。我们检索文献以查找大型(最小治疗组n>100)双盲、安慰剂对照随机临床试验。对于每种药物或药物类别,我们对症状评分的影响进行了荟萃分析。对于每项入选试验,我们根据报告的治疗后或整个季节的鼻部或总症状评分,按照先前发表的方法计算相对临床影响:100×(安慰剂评分-活性药物评分)/安慰剂评分。
28篇关于对症药物试验的出版物和10篇关于SLIT试验的出版物符合我们的选择标准(患者总数:n = 21223)。荟萃分析得出的Hedges' g值证实所有药物类别均存在治疗效果。在间接比较中,五种草花粉SLIT片剂的加权平均(范围)相对临床影响为-29.6%(-23%至-37%),梯牧草花粉SLIT片剂为-19.2%(-6%至-29%),鼻用糖皮质激素为-23.5%(-7%至-54%),MP29-02为-17.1%(-15%至-20%),H1抗组胺药为-15.0%(-3%至-26%),孟鲁司特为-6.5%(-3%至-10%)。
在间接比较中,草花粉SLIT片剂的平均相对临床影响大于第二代抗组胺药和孟鲁司特,与鼻用糖皮质激素的平均相对临床影响大致相同。尽管存在一些方法学因素掩盖了SLIT治疗季节性变应性鼻炎的临床疗效,但仍得出了这一结果。