Long Term Safety of an NSAID With Built-in Gastroprotection for Treatment of Pain and Inflammation Related to Oa and RA: Comparative Results From Blinded and Open Label One Year Safety Trials of a Single-Tablet Combination of Ibuprofen-Famotidine

Abstract

Background: Little is known about the upper gastrointestinal (UGI) protective effect of gastroprotective agents (GPAs) in COX-2-specific inhibitors (coxib)-users. Objectives: To study the association between GPA adherence and UGI complications among coxib-users. Methods: We used primary care data from the United Kingdom's (UK) General Practice Research Database , the Dutch (NL) Integrated Primary Care Information database, and the Italian (IT) Health Search/Thales Database. A case-control study was conducted within a cohort of coxib+GPA users aged ≥ 50 yrs. Episodes of coxib use were defined as a period of coxib use with gaps between subsequent prescriptions that were no longer than 100% of the duration of the previous coxib prescription. Patients could have more than one episode of coxib use during follow-up, but only if at least a 180-days NSAID-free period was present prior to the start of each episode. Cases with UGI complications (UGI bleeding and diagnosed symptomatic UGI ulcers) during or within 60 days after coxib use were matched to controls on age, gender, database, and calendar time. Adherence to GPAs was calculated over the most recent episode of coxib use prior to the index date as the proportion of coxib treatment days covered (PDC) by a GPA prescription. Adherence was expressed as a continuous variable as well as categorical (low (PDC 80%)). Adjusted odds ratios (OR) with 95% confidence intervals (95%CI) were calculated using conditional logistic regression. Results: 98,940 coxib episodes were counted in the coxib user cohort (UK: 52,698; NL: 7,201, IT: 39,041). In 16,442 (16.6%) of the eligible coxib episodes a GPA was prescribed (UK: 21.2%; NL: 13.4%, IT: 11.0%). Of the GPA users, 7.2% had low adherence (PDC 80%). Overall, mean pooled adherence was 0.76±0.30 (UK: 0.79±0.29; NL: 0.85±0.27; IT: 0.66±0.30). Only 18% used coxibs >90 days. In those patients, mean adherence dropped to 0.65 ± 0.34. Within the coxib+GPA users, we identified 74 cases with an UGI complication (30 UGI bleedings and 44 (un)complicated UGI ulcers). Mean adherence (PDC) to GPA was 0.72±0.32 for UGI complication cases compared to 0.78±0.30 for controls. Among low adherers, the risk was 1.97 (95%CI 0.84-4.60) for all UGI complications, compared with high adherers. For every 10% decrease in adherence, the risk of all UGI complications increased by 9% (OR: 1.09, 95%CI: 1.001.18). Conclusions: The risk of UGI complications increased by 9% in all coxib users ≥ 50 years for every 10% decrease in adherence of GPAs. Patients benefit from GPAs in addition to coxibs to lower their increased risk of UGI complications.