Research in context
Evidence before this study
We searched PubMed from Jan 1, 2000, to June 16, 2016, for “idiopathic pulmonary fibrosis treatment,” “LOX,” and “LOXL2” and found no other clinical studies.
Added value of this study
Simtuzumab, a specific inhibitor of LOXL2, failed to show efficacy in patients with idiopathic pulmonary fibrosis (IPF) in either the intention-to-treat population or in a subgroup of patients with elevated LOXL2. The study design is novel because it included a blood-based biomarker relevant to the mechanism of action of simtuzumab in the primary endpoints of the study.
Implications of all the available evidence
Further study is required to explain the failure of simtuzumab to show efficacy. Although the results of this clinical trial do not support the clinical use of simtuzumab for the treatment of IPF, future clinical trials should capture all pertinent clinical data that can be adjudicated to assess outcomes for patients with IPF. These include clinically meaningful measures such as validated patient reported respiratory symptoms and respiratory hospitalisations. Furthermore, the use of pre-specified criteria for consideration of hospitalisation for change or decline in respiratory status based on objective findings as a priori will need to be implemented in future well-designed clinical trials for IPF. This will reduce potential concerns regarding decisions for hospitalisations and management in patients based on subjective judgment by site investigators and other varying confounding factors such as differences in clinical practice and cultures across centres worldwide.