Maintenance treatment with esomeprazole following initial relief of non-steroidal anti-inflammatory drug-associated upper gastrointestinal symptoms: the NASA2 and SPACE2 studies

Christopher J Hawkey¹ , Nicholas J Talley² , James M Scheiman³ , Roger H Jones⁴ , Göran Långström⁵ , Jorgen Næsdal⁵ and Neville D Yeomans⁶ for the NASA/SPACE author group

¹Institute of Clinical Research, Trials Unit, Wolfson Digestive Diseases Centre, University Hospital, Derby Road, Nottingham, NG7 2UH, UK

²Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA

³Division of Gastroenterology, Department of Internal Medicine, University of Michigan Medical Center, 3912 Taubman Center, Ann Arbor, MI 48109-0362, USA

⁴GKT Department of General Practice, King's College, 5 Lambeth Walk, London, SE11 6SP, UK

⁵AstraZeneca R&D, Karragatan 5, Pepparedsleden 1, Mölndal 431 83, Sweden

⁶Medical School, University of Western Sydney, Locked Bag 1797, Penrith South DC, NSW 1797, Australia

author email corresponding author email

Arthritis Research & Therapy 2007, 9:R17doi:10.1186/ar2124


Published:	9 February 2007

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs), including selective cyclo-oxygenase-2 (COX-2) inhibitors, cause upper gastrointestinal (GI) symptoms that are relieved by treatment with esomeprazole. We assessed esomeprazole for maintaining long-term relief of such symptoms. Six hundred and ten patients with a chronic condition requiring anti-inflammatory therapy who achieved relief of NSAID-associated symptoms of pain, discomfort, or burning in the upper abdomen during two previous studies were enrolled and randomly assigned into two identical, multicentre, parallel-group, placebo-controlled studies of esomeprazole 20 mg or 40 mg treatment (NASA2 [Nexium Anti-inflammatory Symptom Amelioration] and SPACE2 [Symptom Prevention by Acid Control with Esomeprazole] studies; ClinicalTrials.gov identifiers NCT00241514 and NCT00241553, respectively) performed at various rheumatology, gastroenterology, and primary care clinics. Four hundred and twenty-six patients completed the 6-month treatment period. The primary measure was the proportion of patients with relapse of upper GI symptoms, recorded in daily diary cards, after 6 months. Relapse was defined as moderate-to-severe upper GI symptoms (a score of more than or equal to 3 on a 7-grade scale) for 3 days or more in any 7-day period. Esomeprazole was significantly more effective than placebo in maintaining relief of upper GI symptoms throughout 6 months of treatment. Life-table estimates (95% confidence intervals) of the proportion of patients with relapse at 6 months (pooled population) were placebo, 39.1% (32.2% to 46.0%); esomeprazole 20 mg, 29.3% (22.3% to 36.2%) (p = 0.006 versus placebo); and esomeprazole 40 mg, 26.1% (19.4% to 32.9%) (p = 0.001 versus placebo). Patients on either non-selective NSAIDs or selective COX-2 inhibitors appeared to benefit. The frequency of adverse events was similar in the three groups. Esomeprazole maintains relief of NSAID-associated upper GI symptoms in patients taking continuous NSAIDs, including selective COX-2 inhibitors.