1 Weill Cornell Medicine, New York, New York.
2 LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany.
Am J Respir Crit Care Med. 2018 Nov 15;198(10):1268-1278. doi: 10.1164/rccm.201712-2493OC.
Roflumilast reduces exacerbations in patients with severe chronic obstructive pulmonary disease associated with chronic bronchitis and a history of exacerbations. Further characterization of patients most likely to benefit is warranted.
Define characteristics that most robustly identify patients who derive greatest exacerbation risk reduction with roflumilast.
Predefined, pooled analyses of REACT (Roflumilast in the Prevention of COPD Exacerbations While Taking Appropriate Combination Treatment; NCT01329029) and RESPOND (Roflumilast Effect on Exacerbations in Patients on Dual [LABA/ICS] Therapy; NCT01443845) multicenter, randomized, double-blind, placebo-controlled studies. The primary endpoint was rate of moderate or severe exacerbations per patient per year.
In the overall intention-to-treat population (n = 4,287), roflumilast reduced moderate or severe exacerbations by 12.3% (rate ratio, 0.88, 95% confidence interval, 0.80-0.97; P = 0.0086) and severe exacerbations by 16.1% (0.84; 0.71-0.99; P = 0.0409) versus placebo. The reduction in moderate or severe exacerbations with roflumilast was most pronounced in patients who had been hospitalized for an exacerbation in the prior year (0.74; 0.63-0.88; P = 0.0005); had more than two exacerbations in the prior year (0.79; 0.65-0.96; P = 0.0160); or had baseline eosinophils ≥150 cells/μl (0.81; 0.71-0.93; P = 0.0020), ≥150 to <300 cells/μl (0.84; 0.71-0.98; P = 0.0282), or ≥300 cells/μl (0.77; 0.61-0.97; P = 0.0264). Similar subgroup results were noted for severe exacerbations. In patients with prior hospitalization and higher baseline blood eosinophil concentrations, roflumilast reduced moderate or severe exacerbations by 34.5% at ≥150 cells/μl (0.65; 0.52-0.82; P = 0.0003) and 42.7% at ≥300 cells/μl (0.57; 0.37-0.88; P = 0.0111) versus placebo.
This prespecified, pooled analysis confirms the benefit of roflumilast in decreasing exacerbations in patients with prior hospitalization for exacerbation, greater exacerbation frequency, and higher (≥150 cells/μl, ≥150 to <300 cells/μl, or ≥300 cells/μl) baseline blood eosinophil count.
罗氟司特可减少伴有慢性支气管炎病史且既往有加重史的重度慢性阻塞性肺疾病患者的加重次数。因此，有必要进一步明确最有可能从中获益的患者特征。
明确最能明确罗氟司特获益最大的患者特征。
对 REACT（罗氟司特在接受合适联合治疗的 COPD 患者中的预防作用；NCT01329029）和 RESPOND（罗氟司特对接受双重[LABA/ICS]治疗的患者加重的影响；NCT01443845）这两项多中心、随机、双盲、安慰剂对照研究进行预设的汇总分析。主要终点为每位患者每年因中重度加重而需治疗的次数。
在总体意向治疗人群（n = 4287）中，罗氟司特可使中重度加重的发生率降低 12.3%（发生率比值，0.88，95%置信区间，0.80-0.97；P = 0.0086），使重度加重的发生率降低 16.1%（0.84；0.71-0.99；P = 0.0409），与安慰剂相比。罗氟司特使中重度加重的发生率降低，在既往 1 年因加重而住院的患者中最为显著（0.74；0.63-0.88；P = 0.0005）；既往 1 年加重次数超过 2 次的患者（0.79；0.65-0.96；P = 0.0160）；或基线时嗜酸性粒细胞≥150 细胞/μl（0.81；0.71-0.93；P = 0.0020）、≥150 至<300 细胞/μl（0.84；0.71-0.98；P = 0.0282）或≥300 细胞/μl（0.77；0.61-0.97；P = 0.0264）。严重加重也有类似的亚组结果。在有既往住院史和较高基线血嗜酸性粒细胞浓度的患者中，罗氟司特使中重度加重的发生率降低 34.5%（≥150 细胞/μl；0.65；0.52-0.82；P = 0.0003）和 42.7%（≥300 细胞/μl；0.57；0.37-0.88；P = 0.0111），与安慰剂相比。
该预先设定的汇总分析证实，罗氟司特可降低既往因加重而住院、加重频率较高（≥150 细胞/μl、≥150 至<300 细胞/μl 或≥300 细胞/μl）且基线血嗜酸性粒细胞计数较高的患者的加重次数。
