PDB17 Time to Onset Analysis of Ipilimumab Associated Hypophysitis Using DATA from FDA Adverse Event Reporting System (FAERS) Database

Ipilimumab, an inhibitor of cytotoxic T-lymphocyte antigen 4 (CTLA-4), as a single agent is used in the treatment of unresectable/metastatic melanoma in patients above the age of 12 or as an adjuvant treatment for cutaneous melanoma with regional lymph node involvement. Hypophysitis associated with the use of ipilimumab is established in the past. However, the time of onset of this event is relatively unexplored. The purpose of this study was to examine the onset profile of Ipilimumab Associated Hypophysitis using the FAERS database. A systematic data mining was performed in the FAERS Database (2011Q2 to 2019Q4). To access the FAERS data, a pharmacovigilance analytical tool named OpenVigil 2.0 was used. The signal strength of ipilimumab induced hypophysitis was computed using Reporting Odds Ratio (ROR). A positive signal was considered to show a value ROR-1.96SE <1. The Weibull shape parameter (WSP) test was employed to analyze the time-to-onset profile, which is computed using date of event – drug start date. The time-to-onset profile of ipilimumab induced hypophysitis was defined by shape and scale parameters. A total of 700 reports was found for hypophysitis in FAERS database. Ipilimumab induced hypophysitis was associated with 551 (78.7%) reports. 48% of the reports from males, 30% from females and gender was not mentioned in the rest. The signal strength of ipilimumab induced hypophysitis was 2327.49 (1940.46 – 2791.71) which is above the threshold. The median time-to-onset of hypophysitis associated with ipilimumab use was 62 (range: 45-83) days. WSP test indicated early failure-type profile with shape parameter: 0.89 (95% C.I 0.76-1.02) and scale parameter: 97.79 (95% C.I 74.65-127.38). Ipilimumab followed an early failure-type profile, suggesting requirement of close monitoring during first 90 days of treatment. However, due to widely distributed onset data, it is suggestive to monitor patients for hypophysitis throughout ipilimumab treatment.