Abstract 2597: Celecoxib fixed dose combinations - patient level data analyses

Abstract

Abstract Background: Celecoxib is a highly effective anti-inflammatory drug. However, its use is associated with adverse events including edema and hypertension (HTN). High dose celecoxib has been shown to be effective against familial adenomatous polyposis (FAP). However, it was discontinued because of safety concerns. Here we examined the impact of celecoxib intake on HTN and edema. The concomitant intake of celecoxib and one of the antihypertensives (AH) was also evaluated as means to suppress the side effects of celecoxib. Methods: This is a retrospective study that uses two patient level data (PLD) sources: (1) anonymous PLD from Symphony from Jan 2012 to Dec 2014 (3 years), and (2) Pinnacle registry data from American College of Cardiology (ACC) over the same time period with detailed clinical data such as blood pressure (BP) readings, peripheral edema flags, etc. In Symphony dataset there are 162 million (M) unique patients, 4.3M patients on celecoxib, 16.3M patients with osteoarthritis (OA)(15.4M only OA) ,and 2.3M patients with rheumatoid arthritis (RA) (1.4M only RA). In ACC dataset, there are 1.58M unique patients with BP readings, 870K patients with edema flag. Results: There was no impact of celecoxib consumed on the change in BP readings. There were as many increases as decreases, regardless of the amount of celecoxib consumed between BP readings. A breakdown by baseline BP readings did not reveal any trends. Concomitant use of AH with celecoxib did not impact BP. Onset of edema was not correlated with total dose of celecoxib. Less than 10% of the observations indicated a change in edema status. However, unlike BP, increasing % of edema was observed for increment in doses and days of treatment with celecoxib plus any other drug combination, suggesting drug induced edema. Edema was baselined with concomitant consumption of angiotensin receptor blocker (ARB) or angiotensin converting enzyme (ACE) or hydrochlorothiazide. It was further aggravated by non-thiazide diuretics and minimally impacted by calcium channel blocker. Conclusion: Previous analysis has shown that dose increment of celecoxib to more than 200mg/day did not improve treatment efficacy, but significantly increased the edema rate but not BP in OA patients. Here we confirmed our meta-analysis using PLD data. Celecoxib with ARB exhibited the lowest incidence of edema and with non-thiazide diuretics the highest incidence (Odds ratio = 3.34 (95% CI = 2.85-3.94), p<0.0001). ARB with celecoxib displayed a significant reduction in edema incidence compared to celecoxib alone (Odds ratio = 0.626 (95% CI = 0.539-0.724), p<0.0001). The celecoxib-ARB and celecoxib-ACE FDCs are being investigated further as therapy for FAP and more broadly for colorectal cancers. Citation Format: Sanjive Qazi, Lynne Murphy, Anshuma Mehta, Wen Wang, Mihir Munsif, Zachary Yim, Vuong Trieu. Celecoxib fixed dose combinations - patient level data analyses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2597. doi:10.1158/1538-7445.AM2017-2597