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, in‰iximab, 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 in‰iximab 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. In‰iximab, trastuzumab and tocilizumab, and denosumab were estimated toˆt the early failure type proˆle of the Weibull distribution parameters. Cetuximab, nivolumab, panitumumab, bevacizumab, golimumab, and adalimumab were estimated toˆt the random failure type proˆle. Pembrolizumab was estimated toˆt the wear out failure type proˆle. Cluster analysis was performed to classify the time-to-onset patterns of DILD. Hierarchical cluster analysis showed 3 clusters. Theˆndings 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.

A rare presentation of panitumumab-involved interstitial lung disease: Spontaneous pneumomediastinum

“…In this study, the median onset time was 49 days. 10 Likewise, Osawa et al 5 determined that the onset time varies between 2-313 days and did not find a specific onset time. Additionally, there were no significant correlations between the onset time of ILD and the radiological findings.…”

“…5 Generally, ILD's pathophysiological mechanism is defined as the induction of fibrosis due to direct toxicity, phospholipoid accumulation in alveolar immune cells, and immune-mediated lung toxicity. 10 Osawa et al 5 identified the risk factors of panitumumab induced ILD as history or complication of ILD, male sex, poor general condition, age of 65 or above. In this study, previous chemotherapy regimens and smoking history were not considered apparent risk factors.…”

Evaluation of the Expression Time of Ganciclovir-Induced Adverse Events Using JADER and FAERS

“…Recently, the Weibull distribution is used to detect the signals for adverse events by utilizing time-to-events date. [14][15][16][17] Thus, we evaluated the time-to-onset of ganciclovir-induced adverse events using Weibull distribution parameters. The results of both scale parameter α and shape parameter β of total adverse events in JADER suggested that ganciclovir-induced adverse reactions including cytopenia, leukopenia and liver damage develop early in most cases (the early failure type) ( Table 2).…”

Interstitial Lung Disease in a Patient Treated with Denosumab

“…However, on the other hand, a study on ILD related to the administration of monoclonal antibodies which includes denosumab has been recently reported [ 6 ] . The aim of this analysis was to investigate the time-to-onset and onset pattern of drug-induced ILD after the administration of monoclonal antibodies through the use of the spontaneous adverse reaction reporting system of the Japanese Adverse Drug Event Report (JADER) database.…”