A NOVEL, SINGLE-TABLET FORMULATION THAT DELIVERS IMMEDIATE-RELEASE OMEPRAZOLE FOLLOWED BY ENTERIC-COATED (EC) NAPROXEN SIGNIFICANTLY REDUCES THE INCIDENCE OF GASTRIC ULCERS COMPARED WITH EC NAPROXEN ALONE: RESULTS OF A PROSPECTIVE, RANDOMISED, DOUBLE-BLI

Background: Co-prescribed enteric-coated (EC) proton-pump inhibitors (PPIs) reduce the incidence of gastric ulcers (GUs) associated with NSAID use. Long-term adherence to such co-therapy is often low, thus novel approaches are needed to reliably reduce upper gastrointestinal (UGI) ulcers and their complications. PN200 is a single-tablet formulation providing coordinated delivery of non-EC omeprazole 20 mg + EC naproxen 500 mg.Objectives: To compare the safety and tolerability of PN200 with EC naproxen 500 mg alone (both administered twice daily)Methods: A 6-month, randomised, double-blind, parallel-group, multicentre study included H. pylori-seronegative patients who required chronic NSAID therapy and were at risk of NSAID-associated GUs (aged 18-49 y/o with a history of GU or duodenal ulcer [DU] within the past 5 yrs or ≥50 y/o). Major exclusion criteria included use of antisecretory agents/misoprostol within 14 days prior to the baseline endoscopy (EGD). Patients were stratified on use of low-dose (≤325 mg) aspirin and then randomised to either PN200 BID or EC naproxen 500 mg BID. EGD was performed at baseline, 1, 3 and 6 months. The primary endpoint was the cumulative proportion of patients developing a GU (≥3 mm diameter with depth) during the 6-month study. Secondary endpoints included cumulative incidence of DU, tolerability and safety.Results: Of 648 patients screened, 409 comprised the ITT population (randomised patients who had no baseline GU/DU ulcer and received ≥1 dose of study drug): PN200 (n=206), EC naproxen (n=203). Baseline demographic factors were similar between groups: mean (SD) age PN200 60.8 yrs (8.5), EC naproxen 60.7 yrs (8.2); % female PN200 64.6%, EC naproxen 70.4%; % white PN200 85.0%, EC naproxen 85.2%. Reasons for chronic NSAID use included OA (83%) and RA (5%). PN200 use was associated with a significantly reduced incidence of GUs and DUs at all time points compared with EC naproxen. At 6 months, the cumulative number of GUs (survival analysis) was 15 (8.3%) for PN200 vs 48 (29.4%) for EC naproxen (p<0.001; RRR 72%). The cumulative number of DUs (survival analysis) was 1 (0.5%) for PN200 vs 18 (10.8%) for EC naproxen alone (p<0.001; RRR 94%). A post hoc analysis of patients who received low-dose aspirin (PN200 [56]; EC naproxen [52]), showed a similar magnitude reduction in the number of GUs (survival analysis) at 6 months; 5 (10.4%) for PN200 vs 15 (39.0%) for EC naproxen (p=0.012; RRR 73%). The proportion of patients discontinuing therapy due to UGI adverse events was 4.4% for PN200 and 10.8% for EC naproxen (p=0.012).Conclusion: This multicentre trial demonstrates that a non-EC PPI added to an EC-NSAID in a single-tablet formulation significantly reduces the incidence of GUs and DUs, even in patients taking low-dose aspirin therapy. This approach may add to the treatment armamentarium for patients at risk of NSAID-associated GUs or DUs and directly addresses issues of adherence to the use of gastroprotective agents in arthritis patients who are expected to benefit from such therapy.Citation: Ann Rheum Dis, volume 67, supplement II, year 2008, page 168Session: RA – Other clinical aspects and comorbidity