(194) Optic Neuritis Associated with PD-1 /PD-L1 Checkpoint Inhibitors: Case Series Utilizing the WHO Global Database of Individual Case Safety Reports (ICSRs)

Publication Number: 525

Background: Programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) checkpoint inhibitors (nivolumab, pembrolizumab atezolizumab, avelumab, and durvalumab) are used to treat several types of cancer. Optic neuritis (ON) is an inflammatory optic neuropathy affecting optic nerves, causing vision loss, reduced color vision, and pain on movement of the eye with recovery over weeks to a month, in most cases.

Objectives: To describe and assess the causality of ON cases reported with the use of PD-1/ PD-L1 immune checkpoint inhibitors.

Methods: We searched the World Health Organization (WHO) database (VigiBase) for all reported cases between 2015 and 2022 using a signal detection tool (VigiLyze). The author used (“Optic neuritis” OR “Optic neuropathy (Preferred Term (PT) (MedDRA)) AND (“Nivolumab” OR “Pembrolizumab” OR “Atezolizumab” OR “Avelumab” OR “Durvalumab” (substance (WHO drug))”. The case causality was assessed using the WHO- Uppsala causality assessment system. Microsoft Excel 2019 was used to perform the descriptive analysis of the cases.

Results: The search of WHO global database resulted in 124 Individual Case Safety Reports (ICSRs) of ON as following: nivolumab (N=56), pembrolizumab (N=54), atezulimumab (N= 9), avelumab (N=3), duravelumab (N=2). Of these, 119 (96%) reports were classified as “serious”. Nearly half the cases were elderly age group ≥65 years (N =43, 47%) and originated from United States (46%). Among 115 of analyzed cases, males accounted for 61% and females for 39%. Concomitant medicines which known to cause ocular toxicity were reported in 41 (33%) cases such as ipilimumab, binimetinib, and osimertinib. Based on the WHO causality assessment of the included cases, 17 (14%) ICSRs of ON were probably associated with PD-1/ PD-L1 inhibitors while 19 (15.3%) ICSRs were considered possible. Moreover, the majority of ICSRs (n=88, 71%) considered un-assessable due to lack of information such as time of onset.

Conclusions: We suggest that there is a potential association between ON and the use of immune checkpoint inhibitors. Further epidemiological studies are needed to assess this risk with the use of immune checkpoint inhibitors.