Original Article Nabumetone Induces Less Gastrointestinal Mucosal Changes Than Diclofenac Retard R. Bec ˇva ´rˇ 1 , Z. Urbanova ´ 1 , V. Vlasa ´kova ´ 2 , J. Vı ´tova ´ 2 , I. Ryba ´r 3 , H. Maldyk 4 , A. Filipowicz- Sosnowska 4 , K. Bernacka 5 , S. Mackiewicz 6 , B. Go ¨mo ¨r 7 , B. Rojkovich 7 , B. Siro 8 , J. Bereczki 9 , K. Toth 9 , S. Sukenik 10 , L. Green 11 , M. Ehrenfeld 12 and K. Pavelka 1 1 Institute of Rheumatology, Prague, Czech Republic; 2 Regional Hospital, C ˇ eske ´ Bude ˇjovice, Czech Republic; 3 Research Institute of Rheumatic Diseases, Pies ˇt’any, Slovakia; 4 Institute of Rheumatology, Warsaw, Poland; 5 Medical Academy A.M. Curie- Sklodowska, Bialystok, Poland; 6 Medical Academy, Poznan, Poland; 7 National Institute of Rheumatology and Physiotherapy, Budapest, Hungary; 8 Department of Internal Medicine, Debrecen, Hungary; 9 Medical Academy, Eger, Hungary; 10 Soroka Medical Center, Beer-Sheba, Israel; 11 Kaplan Hospital, Rehovot, Israel; 12 Chaim Sheba Medical Center, Tel-Hashomer, Israel Abstract: The aim of the study was to compare the efficacy and the effects on the mucosa of the gastrointestinal tract (GIT) of nabumetone and diclofe- nac retard in patients with osteoarthritis (OA). An open, multicentre, randomised, comparative, endoscopy-blind parallel group study included 201 patients with nabumetone and 193 patients with diclofenac retard suffering from moderate to severe OA of the knee or hip joint. Twelve clinical efficacy variables were assessed and a portion of the population underwent gastroduode- noscopy. All patients exhibited significant improvement in pain severity and pain relief (p50.001 and p50.0001, respectively) but there were no differences between the groups for all the efficacy variables. Eleven per cent of patients on nabumetone and 19% on diclofenac experienced GIT side-effects. Sixty-nine patients with nabumetone and 61 with diclofenac underwent gastroduodenoscopy. The differences in the mucosal grade for the oesophagus, stomach and duodenum at baseline were not significant. In the oesophagus there were significantly less changes after treatment with nabumetone (p = 0.007) than with diclofenac; there were similar findings in the stomach (p50.001) but the difference in the duodenum was not significant. This study indicates that nabumetone and diclofenac retard have similar efficacy in the treatment of OA, but nabumetone has significantly fewer GIT side- effects. Keywords: Diclofenac; Efficacy; Endoscopy; Nabume- tone; Osteoarthritis; Safety Introduction Osteoarthritis (OA) is a common cause of joint pain and disability, and uniformly accompanies ageing. Gener- ally, it has an insidious onset and a variable relationship between symptoms and functional impairment with slow development of radiographic changes [1]. This disease usually has inflammatory periods. Most patients with OA are treated with non-steroidal anti-inflammatory drugs (NSAIDs) over a long period of time. It is therefore important that the NSAIDs should be effective and well tolerated. Not all NSAIDs fulfil both these criteria and gastrointestinal (GIT) side-effects ranging from dyspepsia to perforated peptic ulcers have been particularly associated with this type of drug [2]. Nabumetone, a non-acidic compound, is the first of a new alkanone class of NSAIDs and is itself a weak inhibitor of prostaglandin synthesis. It is well absorbed after oral administration and undergoes extensive hepatic first-pass metabolism to form the major metabolite, Clin Rheumatol (1999) 18:273–278 ß 1999 Clinical Rheumatology Clinical Rheumatology Correspondence and offprint requests to: Radim Bec ˇva ´rˇ, MD, Institute of Rheumatology, Na slupi 4, CZ-128 50 Praha 2, Czech Republic.