Abstract
Purpose :
Immune checkpoint inhibitors (ICIs) are a popular class of immunotherapy drugs used for the treatment of cancer treatment. Despite a number of reported adverse events, data on ocular adverse events with these drugs is lacking. We performed a disproportionate analysis using the FDA's FAERS database. We hypothesized that use of ICIs will be strongly associated with an increased reporting odds ratio (ROR) of ocular adverse events compared to all other drugs reported to the FDA.
Methods :
Data from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) within Q4 2003 – Q3 2018 were used to conduct a disproportionality analysis (DA). Using the OpenVigil 2.1 platform, RORs and 95% confidence intervals for the following ICIs – (i) ipilimumab, (ii) nivolumab, (iii) pembrolizumab, (iv) atezolizumab, (v) avelumab, (vi) durvalumab and (vii) cemiplimab were computed for the outcomes of uveitis, dry eye syndrome, ocular myasthenia and eye inflammation. RORs were deemed significant if the lower bound of the 95% confidence interval exceeded a value of 1.0.
Results :
We identified 113 ocular adverse events between all ICI drugs of interest and all ocular adverse events of interest including uveitis, dry eye, ocular myasthenia and eye inflammation. Nivolumab had the highest number of adverse events (N=68) associated with use of the ICI. Nivolumab had the highest association with ocular myasthenia (ROR = 22.82, 95% CI [7.18 – 72.50]) followed by pembrolizumab (ROR = 20.17, 95% CI [2.80 – 145.20]). Additionally, use of nivolumab had a strong association with uveitis (ROR = 8.73, 95% CI [6.25 – 12.20]) and a moderate association with eye inflammation (ROR = 2.68, 95% CI [1.34 – 5.36]). Among all ICIs approved in North America, atezolizumab had the highest association with eye inflammation (ROR = 18.89, 95% CI [6.07 – 58.81]) and ipilmumab had the highest association with uveitis (ROR = 10.54, 95% CI [7.30 – 15.22]).
Conclusions :
The results of this disproportionality analysis are consistent with our hypothesis and suggest use of ICIs are associated with an increase risk for ocular adverse reactions. Large epidemiologic studies are needed to confirm these findings. In the mean time, these results can help ophthalmologists make informed decision regarding suspected ocular adverse events with ICIs in their patients.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.