Fevipiprant對嚴重難治的氣喘有效


  【24drs.com】線上發表於8月5日Lancet Respiratory Medicine期刊的一篇單一中心隨機試驗指出,中度到重度氣喘與痰液嗜酸性球增多的患者,可受益於fevipiprant治療。
  
  第一作者、英國Leicester大學Sherif Gonem博士等人解釋,這些最新的研究結果認為,目標性治療可用於治療特定的氣喘患者。在這案例,fevipiprant是前列腺素D2受體的拮抗劑,此受體在重症氣喘患者之數量增加,這個受體會調節免疫反應,也可能會增強呼吸道發炎症狀。
  
  為了探討針對這個受體是否有助於嚴重氣喘患者,研究者招募了61名有持續中度到重度氣喘、且痰液嗜酸性球數量大於或等於2%的研究對象。這些患者全部都繼續使用吸入型類固醇,先接受單盲安慰劑2週,之後隨機指派接受每天2次的口服藥物或安慰劑,患者接受fevipiprant 或安慰劑共12週,接著是6週的單盲安慰劑洗清期。
  
  接受fevipiprant的這組,痰液嗜酸性球百分比降低了4.5倍,從平均5.4% (95%信賴區間[CI], 3.1% - 9.6%)降低到1.1% (95% CI, 0.7% - 1.9%);安慰劑組降低了1.3倍,從4.6% (95% CI, 2.5% - 8.7%)降低到3.9% (95% CI, 2.3% - 6.7%),fevipiprant這組沒有死亡或嚴重副作用報告。
  
  作者們寫道,Fevipiprant減少了持續中度到重度氣喘患者的嗜酸性呼吸道發炎,且耐受良好,且改善了痰液嗜酸性球數量,儘管有使用吸入型皮質類固醇治療。
  
  作者們報告指出,相較於安慰劑組,Fevipiprant治療的患者,支氣管粘膜下層的嗜酸性發炎也減少、比較好的氣喘控制與氣喘相關生活品質,也改善了吸入藥劑後的一秒用力呼氣量。
  
  作者們寫道,嗜酸性發炎的治療效果和mepolizumab相當,mepolizumab是一種針對介白素5的單株抗體,但是,不同於mepolizumab和其他生物製製劑,fevipiprant不會改變血中的嗜酸性球數量。
  
  在一篇相關評論中,比利時Ghent大學醫院呼吸治療科主任Guy G. Brusselle博士等人形容該研究為:一篇「為一個有前途之新成份驗證概念」的研究,可望滿足控制不佳、部份原因是對皮質類固醇治療有抗藥性之嚴重氣喘患者的治療需求。
  
  Brusselle博士等人寫道,有效療法一個尚未滿足的需求是,經口服給藥或者是針對特定的皮質類固醇抗藥性致病途徑。
  
  南佛羅里達大學醫學教授、美國過敏氣喘暨免疫學學院執行副理事長Thomas B. Casale醫師指出,這個方法的一個好處是,fevipiprant對嗜酸性球之外其他發炎細胞也有效。作者們指出,舉例而言,DP2受體對於T-helper-2細胞和第2型先天淋巴細胞有影響,這些都會釋出發炎細胞激素。
  
  Casale醫師表示,如果證明這是個有效療法,將可減少呼吸道發炎,且不只針對嗜酸性球,還包括其他主要的發炎細胞。
  
  不過,Bruselle博士等人指出,該試驗樣本數少、單一中心設計、研究期間短,使它難以做出fevipiprant之長期安全性與效果、或此藥是否可預防隨著時間而惡化的結論。
  
  Bruselle博士等人寫道,因此,需要大型的長期多中心研究,探討fevipiprant是否改善控制不佳之氣喘患者的臨床結果與減少氣喘惡化。
  
  Casale醫師同意,需要大型的長期研究來確認效果,以及更進一步評估藥品的安全資料。
  
  資料來源: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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