From the Authors:We thank Dr. Kobayashi and colleagues for their interest and insightful comments regarding our recent randomized trial (1). We agree that imbalances in some baseline factors could be a limitation of this study.As described in our article, a post hoc baseline adjustment analysis in separate models was conducted, and it was confirmed that there was no change in the conclusion regarding survival. It is well known that post hoc analysis using multiple factors can have issues involving multiplicity and credibility, and may lead to contradictory conclusions simply owing to the play of chance (2). Therefore, the adjusted treatment differences from the post hoc analysis were not shown in our article.Regarding the concurrent use of corticosteroids, as indicated by Dr. Kobayashi and colleagues, corticosteroids could possibly downregulate the expression of anticoagulant factors and cell-surface receptors that mediate the antiinflammatory activity of thrombomodulin alfa.On the other hand, the use of corticosteroids for patients with acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is weakly recommended in the American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association statement (3) and is considered a standard treatment in Japan, although clinical evidence has not been established through controlled studies. Indeed, corticosteroid therapy is used for most patients with AE-IPF in Japan. In addition, in all of the previous clinical studies that suggested the efficacy of thrombomodulin alfa in patients with AE-IPF and provided theoretical support for the implementation of our trial, thrombomodulin alfa was used concomitantly with corticosteroids (4–6). Given these circumstances, and taking ethical issues and the generalizability of the study results into consideration, all of the subjects in our trial were treated with corticosteroids concomitantly.It should be noted that patients with AE-IPF were included in this study, and that the results of the study do not provide evidence regarding the usefulness of thrombomodulin alfa in patients with stable IPF.
Authors: Ganesh Raghu; Harold R Collard; Jim J Egan; Fernando J Martinez; Juergen Behr; Kevin K Brown; Thomas V Colby; Jean-François Cordier; Kevin R Flaherty; Joseph A Lasky; David A Lynch; Jay H Ryu; Jeffrey J Swigris; Athol U Wells; Julio Ancochea; Demosthenes Bouros; Carlos Carvalho; Ulrich Costabel; Masahito Ebina; David M Hansell; Takeshi Johkoh; Dong Soon Kim; Talmadge E King; Yasuhiro Kondoh; Jeffrey Myers; Nestor L Müller; Andrew G Nicholson; Luca Richeldi; Moisés Selman; Rosalind F Dudden; Barbara S Griss; Shandra L Protzko; Holger J Schünemann Journal: Am J Respir Crit Care Med Date: 2011-03-15 Impact factor: 21.405