However, larger studies are needed to confirm these findings, the researchers noted.
The study, “Efficacy of recombinant human soluble thrombomodulin for acute exacerbation of idiopathic pulmonary fibrosis: A systematic review and meta-analysis,” was published in the journal Experimental and Therapeutic Medicine.
The recombinant (lab-made) version of the human protein thrombomodulin (ART-123, recomodulin, developed by Asahi Kasei) has strong anti-coagulant and anti-inflammatory properties and has been used to treat acute exacerbations in people with IPF.
In IPF, acute exacerbations are characterized by rapid disease worsening, leading to decreased lung function and an increased risk of mortality. Excessive coagulation and inflammation in the lungs are thought to contribute to disease exacerbations.
Several trials have reported the use of thrombomodulin to manage acute exacerbations in IPF patients. While research is still in the early stages, “there is a requirement to summarize the results of these multiple studies to evaluate the quality of evidence and provide a direction for further research,” the researchers wrote.
Thus, investigators in China conducted a review of current studies to evaluate the efficacy and safety of thrombomodulin when used to treat acute exacerbations in people with IPF.
The team searched medical databases and identified six matching studies published until August 2019, which compared treatments with a placebo. In total, 145 IPF patients received thrombomodulin, while 146 patients served as controls.
In all selected studies, patients were given three-day pulse therapy with the anti-inflammatory medicine methylprednisolone before thrombomodulin, and then given a thrombomodulin dose of 380 U/kg (0.06 mg/kg) per day over six to seven days.
Mortality rates at 28 and 90 days after treatment and the number of adverse events were analyzed.
In three of the six studies reviewed, the mortality rate was 29.3% for those receiving thrombomodulin, and 56.7% for those in the control group. A statistical calculation suggested thrombomodulin treatment was associated with a significant reduction in 28-day mortality compared to the control group.
The 90-day mortality rate was reported in five of the six studies, which included 125 patients receiving thrombomodulin and 140 controls. The mortality rate was 33.6% in thrombomodulin-treated patients, and 62.9% in the control group. A pooled analysis indicated that thrombomodulin significantly reduced the 90-day mortality in IPF patients with acute exacerbations.
Regarding safety, adverse events were reported in five of the six trials, and a pooled analysis of these studies found no significant difference between the thrombomodulin and control groups.
Overall, the data suggested that “administration of [thrombomodulin] may reduce the short-term mortality in patients with AE [acute exacerbations]-IPF; however, the quality of evidence was not high,” the researchers wrote.
“The drug appears to be safe without any enhanced risk of adverse events, although high-quality randomized controlled trials with a large sample size are required to further support its use in the treatment of IPF,” the team added.
Of note, a recent Phase 3 randomized trial (NCT02739165), which assessed the safety and efficacy of thrombomodulin in IPF patients experiencing acute exacerbations, was published after the cutoff date (August 2019) of this review and thus was not included in the analysis. The trial found no statistically significant differences in the survival rates at day 90 between the treatment and placebo groups. In that study, IPF patients were treated with the same dose (380 U/kg/day) but for 14 days.
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