Drug Evaluation Naproxen/esomeprazole magnesium in the treatment of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis

Osteoarthritis (OA), rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are three common types of arthritis which are routinely treated with NSAIDs. Guidelines and data regarding the treatment of these three diseases will be briefly discussed. The American College of Rheumatology (ACR) in 1995 published guidelines for the medical management of OA which were updated in 2000 [1–3]. In these guidelines, the type of pharmacologic therapy recommended was based on a patient’s risk factors for serious upper gastrointestinal (GI) and renal toxicity. Risk factors for upper GI (UGI) adverse events (AEs) included age of 65 years or older, oral glucocorticoid therapy, history of peptic ulcer disease, history of UGI bleeding, use of anticoagulants, presence of comorbid conditions, use of high dose or multiple NSAIDs and possibly cigarette smoking and excess alcohol consumption. These guidelines recommended that an individual with GI risk factors be treated with a COX-2 selective inhibitor, a nonselective NSAID plus misoprostol (Cytotec; NJ, USA), a proton pump inhibitor (PPI) or a nonacetylated salicylate. In a study of 8843 patients with RA, 200 μg of misoprostol four-times per day reduced the incidence of complicated ulcers, including those with perforation, bleeding and obstruction by 51% [4]. In a 12-week, randomized, placebo (PBO)controlled, double-blind endoscopy study, 200 μg of misoprostol three-times a day had comparable efficacy in preventing both duodenal and gastric ulcers however 200 μg two-times per day was associated with a significantly lower risk reduction. The higher dose was associated with significant side effects including diarrhea, flatulence and abdominal pain [5]. In a German study of patients with AS, 1081 patients completed a written questionnaire [6]. One quarter of the patients reported severe side effects from their treatment, most commonly abdominal pain, headache, dizziness and nausea. The percentage of patients reporting changing their NSAID due to side effects ranged from 10.5% for celecoxib (CEL; Celebrex, Pfizer, NY, USA) to 31.4% for indomethacin (Indocin). Thus, a need exists for effective therapies for OA, RA and AS that are effective but better tolerated in terms of GI AEs and have a convenient dosing schedule.