Lorentzen K A, Van Helmond J L, Bauer K, Langaker K E, Bonifazi F, Harris T A
Morten Borupsgade 10, Aarhus, Denmark.
Respir Med. 1996 Nov;90(10):609-17. doi: 10.1016/s0954-6111(96)90019-0.
This study was designed primarily to assess the safety and tolerability of fluticasone propionate (FP) 1 mg day-1 by comparison with beclomethasone dipropionate (BDP) 2 mg day-1 over a 12-month study period. Lung function data were also recorded and used to determine whether the potency ratio between the two inhaled corticosteroids observed in previous studies was maintained in the long-term. Two hundred and thirteen patients with an established clinical history of severe chronic asthma and who were currently receiving between 1000 micrograms and 2000 micrograms day-1 of inhaled steroids were randomized to treatment in a ratio of 3:1 for FP:BDP (159 patients FP; 54 patients BDP), both via metered dose inhalers. Both treatments were well tolerated with a similar adverse event profile. No unexpected adverse events were recorded. Most adverse events were related to the patients' asthma, an intercurrent infection or underlying atopy. The incidence of pharmacologically predictable adverse events was equally low in both treatment groups as was the incidence of events suggestive of systemic steroid effect. Mean serum cortisol levels remained within the normal range at all visits for both treatments. At 12 months, however, the mean cortisol levels for the FP group had risen 4% above the baseline value but had dropped 15% below for the BDP group, giving a ratio of FP:BDP of 1.22; P = 0.01; 95% confidence limits (CL) 1.05-1.43. Fluticasone propionate 1 mg day-1 was at least as effective as BDP 2 mg day-1 in improving lung function (PEF, FEV1 and FVC) over this period. Moreover, the difference in FEV1 values at 6 months was significantly greater for the FP group than for the BDP group (P = 0.04; difference = 0.12 1; 95% CL = 0.01, 0.24 1). The difference between treatments in the amount of FEV1 reversibility was also significantly greater for FP at 12 months (difference in treatments = -3%; 95% CL = - 7-0%; P = 0.044). This study supports previous studies and suggests that FP is likely to be of benefit in the long-term treatment of chronic severe asthma.
本研究的主要目的是在12个月的研究期内，通过与二丙酸倍氯米松（BDP）每日2毫克对比，评估丙酸氟替卡松（FP）每日1毫克的安全性和耐受性。还记录了肺功能数据，以确定在先前研究中观察到的两种吸入性皮质类固醇之间的效价比在长期内是否保持。213例有严重慢性哮喘临床病史且目前每日吸入1000微克至2000微克类固醇的患者，以3:1的比例随机接受FP或BDP治疗（159例患者接受FP治疗；54例患者接受BDP治疗），均通过定量吸入器给药。两种治疗的耐受性均良好，不良事件谱相似。未记录到意外不良事件。大多数不良事件与患者的哮喘、并发感染或潜在特应性有关。两个治疗组中，药理学上可预测的不良事件发生率以及提示全身类固醇效应的事件发生率均同样低。两种治疗在所有访视时的平均血清皮质醇水平均保持在正常范围内。然而，在12个月时，FP组的平均皮质醇水平比基线值升高了4%，而BDP组则比基线值下降了15%，FP与BDP的比值为1.22；P = 0.01；95%置信区间（CL）为1.05 - 1.43。在此期间，每日1毫克的丙酸氟替卡松在改善肺功能（呼气峰流速、第1秒用力呼气容积和用力肺活量）方面至少与每日2毫克的BDP一样有效。此外，在6个月时，FP组的第1秒用力呼气容积值差异比BDP组显著更大（P = 0.04；差异 = 0.12升；95% CL = 0.01, 0.24升）。在12个月时，FP组的第1秒用力呼气容积可逆性差异也比BDP组显著更大（治疗差异 = -3%；95% CL = -7 - 0%；P = 0.044）。本研究支持先前的研究，并表明FP可能对慢性重度哮喘的长期治疗有益。
