Systematic evaluation of subgroup analyses of inhaled treprostinil in pulmonary hypertension due to interstitial lung disease

Abstract

Background The INCREASE trial introduced a novel therapeutic option for Pulmonary Hypertension caused by Interstitial Lung Disease. Subsequently to this trial, several subgroup analyses were conducted, aiming to explore specific effects within subgroups. Objective This study aimed to evaluate the subgroup analyses performed in the INCREASE trial and to identify potentially reliable subgroup effects. Methods A methodological assessment of the subgroup analyses was performed. Claims of subgroup effect were evaluated using three different tools: Sun, X et al. 2012, Gil-Sierra, M.D et al. 2020, and Schandelmaier, S et al. 2020. Additionally, all statistically significant subgroup effects that were not claimed by the authors were evaluated. Results Five claims of subgroup effect were identified; none of them achieved statistical significance when assessed using an interaction test. The evaluation conducted with the three tools consistently yielded very low credibility for all the claims. During the assessment, a statistically significant subgroup effect of moderate credibility was identified, which the authors did not claim: iTre appeared to improve exercise capacity exclusively in patients with Pulmonary Vascular Resistance ⋝ 4 WUs. Conclusions Due to methodological limitations, the credibility of subgroup claims from the authors of the INCREASE was lacking and, therefore, should not be relied upon to inform decisions on an individual basis.