Efficacy of recombinant thrombomodulin for poor prognostic cases of acute exacerbation in idiopathic interstitial pneumonia: secondary analysis of the SETUP trial.
Adult
Aged
Aged, 80 and over
Disease Progression
Female
Humans
Idiopathic Interstitial Pneumonias
/ drug therapy
Male
Middle Aged
Multivariate Analysis
Prognosis
Proportional Hazards Models
Recombinant Proteins
/ therapeutic use
Respiratory System Agents
/ therapeutic use
Retrospective Studies
Severity of Illness Index
Thrombomodulin
/ therapeutic use
Treatment Outcome
interstitial fibrosis
Journal
BMJ open respiratory research
ISSN: 2052-4439
Titre abrégé: BMJ Open Respir Res
Pays: England
ID NLM: 101638061
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
05
01
2020
revised:
24
02
2020
accepted:
16
04
2020
entrez:
20
5
2020
pubmed:
20
5
2020
medline:
11
6
2021
Statut:
ppublish
Résumé
Acute exacerbation (AE) in idiopathic pulmonary fibrosis and other idiopathic interstitial pneumonias (IIPs) are poor prognostic events although they are usually treated with conventional therapy with corticosteroids and immunosuppressants. Previously, we demonstrated the safety and efficacy of recombinant human soluble thrombomodulin (rhTM) for AE-IIP in the SETUP trial. Here, we aimed to clarify the efficacy of rhTM for poor-prognosis cases of AE-IIP. In this study, we included 85 patients, in whom fibrin degradation product (FDP)/d-dimer was evaluated at AE, from the 100 patients in the SETUP trial. The AE-IIP patients in the rhTM arm (n=39) were diagnosed using the Japanese criteria from 2014 to 2016 and treated with intravenous rhTM for 6 days in addition to the conventional therapy. The AE-IIP patients in the control arm (n=46) were treated with the conventional therapy without rhTM between 2011 and 2013. The subjects were classified into higher and lower FDP/d-dimer groups based on the Japanese Association for Acute Medicine Disseminated Intravascular Coagulation scoring system. A multivariate Cox proportional hazard regression analysis with stepwise selection was performed to reveal the prognostic factors of AE-IIP. We developed a prognostic scoring system using two significant prognostic factors, higher FDP/d-dimer at AE and prednisolone therapy before AE, with 3 and 2 points assigned for each parameter, respectively. The prognostic scores ranged from 0 to 5. Survival of AE-IIP patients with a prognostic score=0 was significantly better than that of patients with score ≥2. Survival was improved with the rhTM therapy (p<0.05) in the poor prognostic cases (score ≥2), but not in the good prognostic cases (score=0). Treatment with rhTM might improve survival in AE-IIP cases with poor prognoses.
Sections du résumé
BACKGROUND
Acute exacerbation (AE) in idiopathic pulmonary fibrosis and other idiopathic interstitial pneumonias (IIPs) are poor prognostic events although they are usually treated with conventional therapy with corticosteroids and immunosuppressants. Previously, we demonstrated the safety and efficacy of recombinant human soluble thrombomodulin (rhTM) for AE-IIP in the SETUP trial. Here, we aimed to clarify the efficacy of rhTM for poor-prognosis cases of AE-IIP.
METHODS
In this study, we included 85 patients, in whom fibrin degradation product (FDP)/d-dimer was evaluated at AE, from the 100 patients in the SETUP trial. The AE-IIP patients in the rhTM arm (n=39) were diagnosed using the Japanese criteria from 2014 to 2016 and treated with intravenous rhTM for 6 days in addition to the conventional therapy. The AE-IIP patients in the control arm (n=46) were treated with the conventional therapy without rhTM between 2011 and 2013. The subjects were classified into higher and lower FDP/d-dimer groups based on the Japanese Association for Acute Medicine Disseminated Intravascular Coagulation scoring system. A multivariate Cox proportional hazard regression analysis with stepwise selection was performed to reveal the prognostic factors of AE-IIP.
RESULTS
We developed a prognostic scoring system using two significant prognostic factors, higher FDP/d-dimer at AE and prednisolone therapy before AE, with 3 and 2 points assigned for each parameter, respectively. The prognostic scores ranged from 0 to 5. Survival of AE-IIP patients with a prognostic score=0 was significantly better than that of patients with score ≥2. Survival was improved with the rhTM therapy (p<0.05) in the poor prognostic cases (score ≥2), but not in the good prognostic cases (score=0).
CONCLUSIONS
Treatment with rhTM might improve survival in AE-IIP cases with poor prognoses.
Identifiants
pubmed: 32423894
pii: 7/1/e000558
doi: 10.1136/bmjresp-2020-000558
pmc: PMC7239513
pii:
doi:
Substances chimiques
Recombinant Proteins
0
Respiratory System Agents
0
Thrombomodulin
0
Banques de données
UMIN-CTR
['UMIN000014969']
Types de publication
Clinical Trial
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: YI is an advisor of Boehringer Ingelheim, Shionogi Co Ltd and Asahi Kasei. TA received lecture fees from Boehringer Ingelheim and Shionogi Co Ltd for the activities outside the submitted works.
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