Fevipiprant对严重难治的气喘有效


  【24drs.com】在线发表于8月5日Lancet Respiratory Medicine期刊的一篇单一中心随机试验指出,中度到重度气喘与痰液嗜酸性球增多的患者,可受益于fevipiprant治疗。
  
  第一作者、英国Leicester大学Sherif Gonem博士等人解释,这些最新的研究结果认为,目标性治疗可用于治疗特定的气喘患者。在这案例,fevipiprant是前列腺素D2受体的拮抗剂,此受体在重症气喘患者之数量增加,这个受体会调节免疫反应,也可能会增强呼吸道发炎症状。
  
  为了探讨针对这个受体是否有助于严重气喘患者,研究者招募了61名有持续中度到重度气喘、且痰液嗜酸性球数量大于或等于2%的研究对象。这些患者全部都继续使用吸入型类固醇,先接受单盲安慰剂2周,之后随机指派接受每天2次的口服药物或安慰剂,患者接受fevipiprant 或安慰剂共12周,接著是6周的单盲安慰剂洗清期。
  
  接受fevipiprant的这组,痰液嗜酸性球百分比降低了4.5倍,从平均5.4% (95%信赖区间[CI], 3.1% - 9.6%)降低到1.1% (95% CI, 0.7% - 1.9%);安慰剂组降低了1.3倍,从4.6% (95% CI, 2.5% - 8.7%)降低到3.9% (95% CI, 2.3% - 6.7%),fevipiprant这组没有死亡或严重副作用报告。
  
  作者们写道,Fevipiprant减少了持续中度到重度气喘患者的嗜酸性呼吸道发炎,且耐受良好,且改善了痰液嗜酸性球数量,尽管有使用吸入型皮质类固醇治疗。
  
  作者们报告指出,相较于安慰剂组,Fevipiprant治疗的患者,支气管粘膜下层的嗜酸性发炎也减少、比较好的气喘控制与气喘相关生活质量,也改善了吸入药剂后的一秒用力呼气量。
  
  作者们写道,嗜酸性发炎的治疗效果和mepolizumab相当,mepolizumab是一种针对介白素5的单株抗体,但是,不同于mepolizumab和其它生物制制剂,fevipiprant不会改变血中的嗜酸性球数量。
  
  在一篇相关评论中,比利时Ghent大学医院呼吸治疗科主任Guy G. Brusselle博士等人形容该研究为:一篇「为一个有前途之新成份验证概念」的研究,可望满足控制不佳、部份原因是对皮质类固醇治疗有抗药性之严重气喘患者的治疗需求。
  
  Brusselle博士等人写道,有效疗法一个尚未满足的需求是,经口服给药或者是针对特定的皮质类固醇抗药性致病途径。
  
  南佛罗里达大学医学教授、美国过敏气喘暨免疫学学院执行副理事长Thomas B. Casale医师指出,这个方法的一个好处是,fevipiprant对嗜酸性球之外其它发炎细胞也有效。作者们指出,举例而言,DP2受体对于T-helper-2细胞和第2型先天淋巴细胞有影响,这些都会释出发炎细胞激素。
  
  Casale医师表示,如果证明这是个有效疗法,将可减少呼吸道发炎,且不只针对嗜酸性球,还包括其它主要的发炎细胞。
  
  不过,Bruselle博士等人指出,该试验样本数少、单一中心设计、研究期间短,使它难以做出fevipiprant之长期安全性与效果、或此药是否可预防随著时间而恶化的结论。
  
  Bruselle博士等人写道,因此,需要大型的长期多中心研究,探讨fevipiprant是否改善控制不佳之气喘患者的临床结果与减少气喘恶化。
  
  Casale医师同意,需要大型的长期研究来确认效果,以及更进一步评估药品的安全资料。
  
  资料来源:http://www.24drs.com/
  
  Native link:Fevipiprant Shows Promise for Severe, Refractory Asthma

Fevipiprant Shows Promise for Severe, Refractory Asthma

By Bridget M. Kuehn
Medscape Medical News

Patients with moderate-to-severe asthma and sputum eosinophilia benefited from fevipiprant in a single-center, randomized trial published online August 5 in Lancet Respiratory Medicine.

The results are the latest to suggest targeted therapies may be useful in treating select subgroups of patients with asthma. In this case, fevipiprant is an antagonist of the prostaglandin D2 receptor, which is found in increased numbers in patients with severe asthma, explain lead author Sherif Gonem, PhD, from the University of Leicester, United Kingdom, and colleagues. The receptor modulates the immune response and may boost airway inflammation.

To test whether targeting this receptor would benefit patients with severe asthma, the researchers recruited 61 participants with persistent, moderate to severe asthma and a sputum eosinophil count greater than or equal to 2%. All patients, who continued inhaled steroids, received a single-blind placebo for 2 weeks before being randomly assigned to the twice-daily oral drug or a placebo. Participants received the fevipiprant or placebo for 12 weeks, followed by a 6-week washout period with a single-blind placebo.

The sputum eosinophil percentage decreased by 4.5 times from an average of 5.4% (95% confidence interval [CI], 3.1% - 9.6%) to 1.1% (95% CI, 0.7% - 1.9%) in the group that received fevipiprant and decreased by 1.3 times from 4.6% (95% CI, 2.5% - 8.7%) to 3.9% (95% CI, 2.3% - 6.7%) in the placebo group. No deaths or serious adverse events were reported in the fevipiprant group.

"Fevipiprant reduces eosinophilic airway inflammation and is well tolerated in patients with persistent, moderate-to-severe asthma and raised sputum eosinophil counts despite inhaled corticosteroid treatment," the authors write.

Fevipiprant-treated patients also had reduced eosinophilic inflammation in the bronchial submucosa, better asthma control and asthma-related quality of life, and improved postinhaler forced expiratory volume in 1 second scores compared with patients in the placebo group, the authors report.

The effect on eosinophilic inflammation was similar in magnitude to that seen with mepolizumab, a monoclonal antibody that targets interleukin 5, the authors write. But unlike mepolizumab and other biologics, fevipiprant did not change the blood eosinophil count.

In an accompanying comment, Guy G. Brusselle, MD, PhD, head of the respiratory medicine clinic at Ghent University Hospital in Belgium, and colleagues describe the results as a "proof-of-concept" study for a "promising new compound" that could fill an unmet need for a subgroup of patients who have uncontrolled severe asthma that is partly resistant to corticosteroid treatment.

"There is an unmet need for effective therapies that can be delivered orally or that target specific corticosteroid-resistant pathogenic pathways," write Dr Brusselle and colleagues.

One advantage of this approach might be that fevipiprant also has effects on inflammatory cells other than eosinophils, noted Thomas B. Casale, MD, executive vice president of the American Academy of Allergy Asthma and Immunology and a professor of medicine at the University of South Florida in Tampa. For example, the authors note, the DP2 receptor has effects on T-helper-2 cells and type 2 innate lymphoid cells, which release inflammatory cytokines.

"If this turns out to be effective therapy, it could be a way to decrease airway inflammation that's not just specific to eosinophils, but [targets] these other key inflammatory cells as well," Dr Casale said.

However, Dr Bruselle and colleagues note the trial's small size, single-center design, and short duration make it impossible to draw conclusions about the long-term safety and efficacy of the fevipiprant or whether the drug will prevent exacerbations over time.

"Therefore, large, long-term, multicenter studies are needed to investigate whether fevipiprant improves clinical outcomes and reduces asthma exacerbations in patients with uncontrolled asthma," Dr Brusselle and colleagues write.

Dr Casale agreed that larger, longer-term studies are needed to confirm the efficacy and better assess the drug's safety profile.

The AirPROM project and the UK National Institute for Health provided funding for the study. Several of the authors report employment by Novartis, which also funded the study. The remaining authors report a variety of relationships with pharmaceutical companies and medical organizations including Novartis, Chiesi, GlaxoSmithKline, the European Respiratory Society, AstraZeneca, Almirall, Boehringer Ingelheim, Aerocrine, Genentec, Regeneron, Teva, Roche, Pulmacide, Pfizer, MedImmune, and Vectura. The editorialists have disclosed no relevant financial relationships. Dr Casale reports consulting for or receiving funding from Genetech, MedImmune/Astra Zeneca, Novartis, Teva, and Sanofi/Regeneron. Dr Casale's consulting honoraria are given to the University of South Florida.

Lancet Respir Med. Published online August 5, 2016.

    
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