The efficacy of recombinant human soluble thrombomodulin (rhsTM) treatment for acute exacerbation of idiopathic pulmonary fibrosis: a systematic review and meta-analysis

Hiroyuki Kamiya,Ogee Mer Panlaqui

doi:10.1186/s12890-020-1092-3

Abstract

BackgroundAcute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) is devastating with no established treatment. This phenomenon involves disordered coagulation and excessive inflammatory reactions. As recombinant human soluble thrombomodulin (rhsTM) possesses anti-coagulative and anti-inflammatory properties, the medicine is expected to improve the prognosis of the disease. The aim of this study was to summarize current evidence regarding benefits and harms of rhsTM treatment for AE of IPF.MethodPatients with AE of IPF were eligible for the review and all of the other types of interstitial pneumonias were excluded. The effect of rhsTM treatment on the outcomes such as all-cause mortality was estimated in comparison to conventional therapy. Primary studies of any design aside from a case report were reviewed. Electronic databases such as Medline and EMBASE were searched from 2002 through August 14, 2019. Two reviewers independently selected eligible reports and extracted relevant data. A risk of bias of individual studies was assessed similarly. Meta-analysis was conducted for univariate results if at least three studies were available for the same outcome.ResultOut of a total of 390 records identified, eight studies were first deemed eligible and four of them were finally focused for the review. Only one study was a prospective trial and a historical control was employed in all studies. An overall risk of bias was rated as serious in three out of four studies. A total of 169 subjects were included. Two out of three studies that reported 3-month all-cause mortality by univariate analysis demonstrated beneficial effects of rhsTM treatment and a pooled analysis demonstrated that rhsTM treatment improved 3-month all-cause mortality with a risk ratio of 0.50 (95% confidence interval (CI): 0.35–0.72). All two studies reporting multivariate results demonstrated that rhsTM treatment improved 3-month all-cause mortality with odds ratios of 0.21 (95% CI: 0.05–0.91) and 0.25 (95% CI: 0.09–0.68), respectively. There were no serious adverse events.ConclusionThe rhsTM treatment was demonstrated to improve 3-month all-cause mortality of AE of IPF with no serious adverse events. However, these findings should be interpreted with caution due to a small number of studies and serious risk of bias.

Highlights

Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) is devastating with no established treatment
It was defined as worsening or development of dyspnoea manifested within 30 days, which is accompanied by newly emerging bilateral ground glass opacities and/or consolidation superimposed on underlying usual interstitial pneumonia (UIP) on high resolution computed tomography (HRCT) scan
One study (Arai 2019 [33]), which was composed of a total of 100 subjects including both IPF and non-IPF, was excluded from further analysis because non-IPF group did not undergo pathological diagnosis all cases in the group were non-IPF Idiopathic interstitial pneumonia (IIP) according to the authors

Summary

Introduction

Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) is devastating with no established treatment. AE of IPF was initially defined as acute respiratory worsening beyond its usually anticipated gradual progression triggered by no identifiable causes [4] This overwhelming phenomenon was noted to be not unique to IPF and complicate other types of IPs such as idiopathic NSIP, connective tissue disease-associated interstitial pneumonia (CTD-IP) and chronic hypersensitivity pneumonitis [5,6,7]. The frequency of AE and its prognosis varies depending on underlying IPs [5,6,7], IPF is the most prevalent among others [8], and the prognosis of AE of IPF is uniformly poor with 90-day mortality of 40 to 50% [9] This devastating outcome is mostly because the pathogenesis of this phenomenon has yet to be fully elucidated and there is currently no established treatment that has been proved beneficial [10].

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