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INMARK試驗結果表明,尼達尼布可有效減緩特發(fā)性肺纖維化疾病進展

2019-07-23 17:44 7126
勃林格殷格翰宣布INMARK試驗結果已于7月17日在柳葉刀醫(yī)學雜志上發(fā)表。研究結果證明,即使在肺功能保持良好的早期IPF患者中,接受尼達尼布和安慰劑治療12周后,兩組患者的用力肺活量(FVC)下降值也存在顯著差異。
  • INMARK®試驗結果已在柳葉刀呼吸醫(yī)學雜志上發(fā)表1
  • 與安慰劑相比,使用尼達尼布治療12周后,并未影響生物標記物--降解C反應蛋白的變化率,但與用力肺活量(FVC)下降率的減少相關1
  • 早期研究表明,肺功能保持良好的患者與入組時肺功能較差的患者 ,兩者用力肺活量下降率相當。1

德國殷格翰2019年7月23日 /美通社/ -- 勃林格殷格翰宣布INMARK®試驗結果已于7月17日在柳葉刀醫(yī)學雜志上發(fā)表。INMARK®是一項隨機、雙盲,在特發(fā)性肺纖維化(IPF)患者中進行的維加特®(尼達尼布)與安慰劑的對照研究(研究持續(xù)12周),隨后為40周的開放性研究,勃林格殷格翰是該試驗的參與方之一。INMARK®試驗是首個在特發(fā)性肺纖維化(IPF)患者中使用抗纖維化治療(尼達尼布),研究生物標記物預測值的的臨床試驗。研究結果進一步證明,即使在肺功能保持良好的早期IPF患者中,接受尼達尼布和安慰劑治療12周后,兩組患者的用力肺活量(FVC)下降值也存在顯著差異。1,2

IPF是一種罕見但嚴重的,具有致命性的肺部疾病,全球約有300萬人受累。3   該疾病可引起肺部瘢痕的不斷加重,導致肺功能持續(xù)且不可逆轉的退化以及呼吸困難。4由于IPF的不可預測性以及肺功能喪失的不可逆性,專家認為患者應獲得及時有效的治療。1,5

INMARK®評估了患者從入組到12周后生物標記物 -- 降解C反應蛋白的變化率。降解C反應蛋白是一種生物標記物,之前被證實可預測特發(fā)性肺纖維化(IPF)患者的死亡率。此外試驗還評估了發(fā)生疾病進展的入組患者比例,其定義為預測用力肺活量絕對下降>=10%,或在52周內死亡。1

與安慰劑相比,接受尼達尼布治療12周后并未影響生物標記物降解C反應蛋白的變化率,但與用力肺活量下降率的降低有關1

29%的入組患者在隨訪52周內,用力肺活量下降>=10%或死亡,強調了特發(fā)性肺纖維化(IPF)疾病進展也存在于用力肺活量≥80%的人群中。

在12周時間內,與安慰劑組相比,尼達尼布組患者的用力肺活量下降率更低(尼達尼布組為5.9(18.5)ml/12周,安慰劑組為?70.2(13.1)ml/12周)。

“即使肺功能維持良好的患者在分別使用尼達尼布與安慰劑治療12周后,也展現(xiàn)出了用力肺活量下降的明顯差異。考慮到特發(fā)性肺纖維化(IPF)的不可預測性以及肺功能喪失的不可逆性,越來越多的證據(jù)表明盡早治療特發(fā)性肺纖維化(IPF)才是最佳方案?!?nbsp;英國倫敦皇家布朗普頓醫(yī)院呼吸內科顧問兼該研究的主要研究者托比·馬赫教授評論道。

勃林格殷格翰呼吸醫(yī)學副主管Susanne Stowasser博士說道:“生物標記物研究是現(xiàn)代醫(yī)學的一個關鍵驅動力,對了解健康和疾病狀態(tài)、診斷、藥物開發(fā)以及疾病進程或治療效果的預測都有著巨大的影響。INMARK是首個在使用抗纖維治療的特發(fā)性肺纖維化(IPF)患者中探索生物標志物預測值的臨床試驗。由于對IPF知之甚少,多年來生物標志物研究一直是該病的研究熱點,其主要研究方向是識別疾病預后的標記物。”她補充道:“肺纖維化持續(xù)對人們的生活造成毀滅性的影響。勃林格殷格翰致力于諸如INMARK試驗之類的研究,以便讓我們更好地了解間質性肺疾?。ㄈ鏘PF)在個體患者中的進展情況,并識別出那些可以獲得最佳治療效果的患者?!?/p>

關于INMARK®

INMARK®試驗包含347名患者(其中116名使用尼達尼布治療,另外231名對照組患者使用安慰劑治療),評估從入組到第12周(以ng/mL/月表示)的降解C反應蛋白變化率(斜率),以及疾病進展的受試者比例。疾病進展的定義為在52周內FVC預測值的絕對下降>=10%或死亡。1

與安慰劑相比,接受尼達尼布治療12周并未影響新表位CRPM血藥濃度的變化率。1與安慰劑組相比,在12周內,使用尼達尼布治療的患者的用力肺活量下降率較低。1在接受安慰劑治療12周的患者中, 12周內降解C反應蛋白水平的升高與52周內疾病進展相關。1

此次試驗患者入組時平均用力肺活量預測值為97.5%,被認為肺容量保持良好。超過四分之一的患者在52周內出現(xiàn)疾病進展(FVC預測值下降≥10%或死亡)。1 用力肺活量是一項肺功能測試,用于測量最大程度深呼吸后從肺部用力呼出的空氣量。5肺功能會隨著特發(fā)性肺纖維化(IPF)的進展而逐步、不可逆轉地惡化,這就是用用力肺活量下降來衡量的。

關于維加特(尼達尼布)

尼達尼布(維加特),是一種小分子的酪氨酸激酶抑制劑,由勃林格殷格翰開發(fā)用于治療特發(fā)性肺纖維化(IPF)成人患者。6 2015年,尼達尼布被納入更新版的特發(fā)性肺纖維化(IPF)國際治療指南。在各種IPF患者類型中,維加特均可延緩疾病進展,降低肺功能年下降率達50%。8-16維加特已在全球超過70個國家及地區(qū)獲批上市用于治療特發(fā)性肺纖維化(IPF)。

References

1.  REF TO BE UPDATED WHEN FULL DETAILS AVAILABLE 
2.  Kolb M, et al. Nintedanib in patients with idiopathic pulmonary fibrosis and preserved lung function. Thorax, 2017; 72(4): 340-346.
3.  Ley B, et al. Clinical course and prediction of survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2011;183(4):431-40.
4.  NHLBI, NIH. What Is Idiopathic Pulmonary Fibrosis? Accessed at: www.nhlbi.nih.gov/health/health-topics/topics/ipf/ Accessed April 2017.
5.  Data on file. Boehringer Ingelheim. 2016.
6.  Hilberg F, et al. BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res. 2008;68:4774-4782.
7.  Raghu G, et al. An Official ATS/ERS/JRS/ALAT Clinical Practice Guidelines: Treatment of Idiopathic Pulmonary Fibrosis: Executive Summary. Am J Respir Crit Care Med. 2015; 192(2)238 – 248.
8. OFEV Summary of Product Characteristics. Boehringer lngelheim International GmbH. July 2017.
9.  Richeldi L, et al; for the INPULSIS Trial Investigators. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Eng J Med. 2014;370(22):2071-2082.
10.  Kolb M, et al. Nintedanib in patients with idiopathic pulmonary fibrosis and preserved lung volume. Thorax. 2016. doi:l0.1136/thoraxjnl-2016-208710.
11.  Raghu G, et al. Effect of nintedanib in subgroups of idiopathic pulmonary fibrosis by diagnostic criteria. Am Journal Respir and Critl Care Med. 2016. doi:l0.1164/rccm.201602-04020C.
12.  Cottin V, et al. Effect of baseline emphysema on reduction in FVC decline with nintedanib in the INPULSIS® trials. Abstract presented at: the 18th International Colloquium on Lung and Airway Fibrosis; Mont Tremblant, Canada, September 20-24, 2014.
13.  Ryerson CJ, et al. Effect of baseline GAP index stage on decline in lung function with nintedanib in patients with idiopathic pulmonary fibrosis (IPF). Abstract presented at: the lllth American Thoracic Society Conference; San Francisco, California, May 13-18, 2016..
14.  Wells A, et al. Effect of baseline composite physiologic index on benefit of nintedanib in IPF. Abstract presented at: the European Respiratory Society International Congress; London, England, September 3-7, 2015.
15.  Maher TM, et al. No effect of baseline diffusing capacity of lung for carbon monoxide on benefit of nintedanib. Abstract presented at: the European Respiratory Society International Congress; London, England, September 3-7, 2015.
16.  Keating GM. Nintedanib: a review of its use in patients with idiopathic pulmonary fibrosis. Drugs. 2015;75(10):1131-1140.
17.  REF TO BE UPDATED WHEN FULL DETAILS AVAILABLE 
18.  Kolb M, et al. Nintedanib in patients with idiopathic pulmonary fibrosis and preserved lung function. Thorax, 2017; 72(4): 340-346.
19.  Ley B, et al. Clinical course and prediction of survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2011;183(4):431-40.
20.  NHLBI, NIH. What Is Idiopathic Pulmonary Fibrosis? Accessed at: www.nhlbi.nih.gov/health/health-topics/topics/ipf/ Accessed April 2017.
21.  Data on file. Boehringer Ingelheim. 2016.
22.  Hilberg F, et al. BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res. 2008;68:4774-4782.
23.  Raghu G, et al. An Official ATS/ERS/JRS/ALAT Clinical Practice Guidelines: Treatment of Idiopathic Pulmonary Fibrosis: Executive Summary. Am J Respir Crit Care Med. 2015; 192(2)238 – 248.
24.  OFEV Summary of Product Characteristics. Boehringer lngelheim International GmbH. July 2017.
25.  Richeldi L, et al; for the INPULSIS Trial Investigators. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Eng J Med. 2014;370(22):2071-2082.
26.  Kolb M, et al. Nintedanib in patients with idiopathic pulmonary fibrosis and preserved lung volume. Thorax. 2016. doi:l0.1136/thoraxjnl-2016-208710.
27.  Raghu G, et al. Effect of nintedanib in subgroups of idiopathic pulmonary fibrosis by diagnostic criteria. Am Journal Respir and Critl Care Med. 2016. doi:l0.1164/rccm.201602-04020C.
28.  Cottin V, et al. Effect of baseline emphysema on reduction in FVC decline with nintedanib in the INPULSIS® trials. Abstract presented at: the 18th International Colloquium on Lung and Airway Fibrosis; Mont Tremblant, Canada, September 20-24, 2014.
29.  Ryerson CJ, et al. Effect of baseline GAP index stage on decline in lung function with nintedanib in patients with idiopathic pulmonary fibrosis (IPF). Abstract presented at: the lllth American Thoracic Society Conference; San Francisco, California, May 13-18, 2016..
30.  Wells A, et al. Effect of baseline composite physiologic index on benefit of nintedanib in IPF. Abstract presented at: the European Respiratory Society International Congress; London, England, September 3-7, 2015.
31.  Maher TM, et al. No effect of baseline diffusing capacity of lung for carbon monoxide on benefit of nintedanib. Abstract presented at: the European Respiratory Society International Congress; London, England, September 3-7, 2015.
32.  Keating GM. Nintedanib: a review of its use in patients with idiopathic pulmonary fibrosis. Drugs. 2015;75(10):1131-1140.

 

消息來源:勃林格殷格翰
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