Analysis of Time-to-onset and Onset-pattern of Interstitial Lung Disease after the Administration of Monoclonal Antibody Agents

Abstract

The aim of this study has been to investigate the time-to-onset and onset-pattern of drug-induced interstitial lung disease (DILD) after the administration of monoclonal antibodies through the use of the spontaneous adverse reaction reporting system of the Japanese Adverse Drug Event Report database. DILD datasets for adalimumab, bevacizumab, cetuximab, denosumab, golimumab, infliximab, nivolumab, panitumumab, pembrolizumab, tocilizumab, and trastuzumab were used to calculate the median time-to-onset of DILD, as well as the Weibull distribution parameters. The median time-to-onset of DILD for pembrolizumab and infliximab was within 1 month. The median time-to-onset of DILD for cetuximab, nivolumab, panitumumab, bevacizumab, golimumab, trastuzumab, and tocilizumab ranged from 1 to 2 months. The median time-to-onset of DILD for denosumab and adalimumab was more than 2 months. Infliximab, trastuzumab and tocilizumab, and denosumab were estimated to fit the early failure type profile of the Weibull distribution parameters. Cetuximab, nivolumab, panitumumab, bevacizumab, golimumab, and adalimumab were estimated to fit the random failure type profile. Pembrolizumab was estimated to fit the wear out failure type profile. Cluster analysis was performed to classify the time-to-onset patterns of DILD. Hierarchical cluster analysis showed 3 clusters. The findings of this study established both the most likely time period and onset-pattern of DILD that can occur in patients after the administration of monoclonal antibody agents.