Efficacy and safety of nimesulide long term administration in patients with osteoarthritis: results of 12-months open controlled study DINAMO (long term administration of nimesulide in osteoarthritis multifactor assessment)

Objective. To compare efficacy and safety of nimesulide and paracetamol in treatment of patients with osteoarthritis (OA) during 12 months. Material and methods. 40 women (mean age 66,8±5,1 years) with knee osteoarthritis (II-III stage according to Kellgren-Lawrence) having intensive pain (>40 mm on VAS) were included. Group 1 pts (n=20) received nimesulide 200-100 mg/day. Group 2 pts were treated with paracetamol till 3 g/day. WOMAC was used as efficacy measure. Safety was assessed with endoscopic examination of upper gastrointestinal tract, ECG, blood pressure and ECG Holter monitoring, clinical and biochemical blood parameters. Statistical significance of differences was assessed with Student’s t-test, χ2 and Fisher exact test Results. WOMAC index decreased during treatment from 1182,7±345,9 to 698,4±351,1 for nimesulide and from 1136,4±313,8 to 1031,6±21 for paracetamol (p<0,05). There were 6 cases of gastrointestinal complications and 4 cases of hypertension development or deterioration in each group. Coronary heart disease developed or deteriorated in 4 patients receiving nimesulide but not in control group. Liver function tests did not deteriorated during treatment with nimesulide. Conclusion. Nimesulide was more effective than paracetamol in treatment of OA. But risk of cardiovascular complications development during treatment with NSAIDs requires serious attention. Nimesulide did not induced liver damage during long term treatment.

osteoarthritis, nimesulide, paracetamol, NSAID-gastropathy

1. <div><p>Алексеева Л. А. Остеоартроз. В изд.: «Ревматология. Национальное руководство». Под ред. Насонова Е.Л., Насоновой В.А., М., Геотар-Медиа, 2008, 573-89.</p><p>Zhang W., Doherty M., Leeb B., Alekseeva L., Arden N., et al. EULAR evidence based recommendations for the management of hand osteoarthritis: report of a Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann. Rheum Dis., 2007, 66(3), 377-88.</p><p>Zhang W., Doherty M., Arden N., et al. EULAR evidence based recommendations for the management of hip osteoarthritis: report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann. Rheum. Dis., 2005, 64(4), 655-66.</p><p>Jordan K., Arden N., Doherty M., et al. EULAR Recommendations 2003: an evidence based approach to the management of knee osteoarthritis: Report of a Task Force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT). Ann. Rheum. Dis., 2003, 62(12), 1145-55.</p><p>Emery P., Koncz T., Pan S., Lowry S. Analgesic effectiveness of celecoxib and diclofenac in patients with osteoarthritis of the hip requiring joint replacement surgery: a 12-week, multicenter, randomized, double- blind, parallel-group, double-dummy, noninferiority study. Clin. Ther., 2008, 30(1), 70-83.</p><p>Denoeud L., Mazieres B., Payen-Champeneis C., Ravaud P. First line treatment of knee osteoarthritis in outpatients in France: adherence to the EULAR 2000 recommendations and factors influencing adherence. Ann. Rheum. Dis., 2005, 64, 70-4</p><p>Bonnet C., Turner E., McWilliams P., Walsh D. Osteohondral angiogenesis and synovial inflammation are features of osteoarthritis and may contribute to the severety of cartilage changes (abstract). Rheumatology, 2005, 44 (suppl. 1), 43-4.</p><p>Alvarez-Soria M., Largo R., Santillana J. et al. Long term NSAID treatment inhibits COX-2 synthesis in the knee synovial membrane of patients with osteoar- thritis: differential proinflammatory cytokine profile between celecoxib and aceclofenac. Ann. Rheum. Dis., 2006, 65(8), 998-1005.</p><p>Насонов Е. Л., Лазебник Л. Б., Беленков Ю. М. и сотр. Применение нестероидных противовоспалительных препаратов. Клинические рекомендации, М., 2006.</p><p>Алексеева Л. И., Верткин А. Л., Иванов В. С., и др. Остеоартроз в практике врача-терапевта. РМЖ, 2008, 7, 476-81.</p><p>Wang P., Avorn J., Brookhart M., et al. Effects of noncardiovascular comorbidities on antihypertensive use in elderly hypertensives. Hypertension, 2005, 46(2), 273-9.</p><p>Насонов Е. Л. Эффективность и переносимость нестероидного противовоспалительного препарата. Нимесулид: новые данные. РМЖ, 2001, 15, 6-8</p><p>Каратеев А. Е., Барскова В. Г. Безопасность нимесулида: эмоции или взвешенная оценка? Consilium Мedicum, 2007, 9, 60-4.</p><p>Rainsford K. Nimesulide – a multifactorial approach to inflammation and pain: scientific and clinical consensus. Curr. Med. Res. Opin., 2006, 22(6), 1161-70.</p><p>Schnitzer T., Weaver A., Polis A. Efficacy of rofecoxib, celecoxib, and acetaminophen in patients with osteoarthritis of the knee. A combined analysis of the VACT studies. J. Rheumatol., 2005, 32, 1093-105.</p><p>Pincus T., Koch G., Lei H., et al. Patient Preference for Placebo, Acetaminophen (paracetamol) or Celecoxib Efficacy Studies (PACES): two randomised, double blind, placebo controlled, crossover clinical trials in patients with knee or hip osteoarthritis. Ann. Rheum. Dis., 2004, 63, 931-9.</p><p>Boureau F., Schneid H., Zeghari N., et al. The IPSO study: ibuprofen, paracetamol study in osteoarthritis. A randomised comparative clinical study comparing the efficacy and safety of ibuprofen and paracetamol analgesic treatment of osteoarthritis of knee or hip. Ann. Rheum. Dis., 2004, 63, 1028-35.</p><p>Kullich W., Niksic F., Klein G. Effect of nimesulide on metalloproteinases and matrix degradation in osteoarthritis: a pilot clinical study. Int. J. Clin. Pract., 2002, suppl. 128, 24-30.</p><p>Huskisson E., Macciocchi A., Rahlfs V., et al. Nimesulide versus diclofenac in the treatment of osteoarthritis of the hip or knee: an active controlled equivalence study. Curr. Ther. Res., 1999, 60, 253-65.</p><p>Каратеев А. Е., Каратеев Д. Е., Лучихина Е. Л. и др. Эффективность и безопасность монотерапии высокими дозами НПВП при раннем артрите. РМЖ, 2006, 16, 24-9.</p><p>Bradbury F. How important is the role of the physician in the correct use of a drug? An observational cohort study in general practice. Int. J. Clin. Pract. (suppl). 2004, 144, 27-32.</p><p>Conforti A., Leone R., Moretti U., et al. Adverse drug reactions related to the use of NSAIDs with a focus on nimesulide: results of spontaneous reporting from a Northern Italian area. Drug Saf., 2001, 24, 1081-90.</p><p>Laporte J., Ibanez L., Vidal X., Vendrell L., Leone R. Upper gastrointestinal bleeding associated with the use of NSAIDs: newer versus older agents. Drug Saf., 2004, 27, 411-20.</p><p>Минушкин ОН. Использование препарата “Найз” у больных, страдающих сочетанной патологией суставов и поражением верхних отделов желудочно-кишечного тракта. Научно-практич. ревматол. 2003, 5, 72-6.</p><p>Каратеев А. Е., Каратеев Д. Е., Насонов Е. Л. Гастродуоденальная переносимость нимесулида (НИМЕСИЛ, Berlin Chemie) у больных с язвенным анамнезом: первое проспективное исследование безопасности селективных ЦОГ-2 ингибиторов у больных с высоким риском развития НПВП-индуцированных гастропатий. Научно-практич. ревматол. 2003, 1, 45-8.</p><p>McGettigan P., Henry D. Cardiovascular risk and inhibition of cyclooxygenase. JAMA, 2006, 296, 633-44</p><p>Helin-Salmivaara A., Virtanen A., Vesalainen R., et al. NSAID use and the risk of hospitalization for first myocardial infarction in the general population: a nationwide case-control study from Finland. Eur Heart J., 2006, 27(14), 1657-63.</p><p>Huang W., Hsiao F., Tsai Y., et al. Cardiovascular events associated with long-term use of celecoxib, rofecoxib and meloxicam in Taiwan: an observational study. Drug Saf., 2006, 29(3), 261-72.</p><p>Каратеев А. Е., Насонов Е. Л. Как избежать развития кардиоваскулярных осложнений при лечении боли? Consilium Мedicum, 2008, 10, 44-50.</p><p>Lazerow S., Abdi M., Lewis J. Drug-induced liver disease 2004. Curr. Opin. Gastroenterol. 2005, 21(3), 283-92.</p><p>Boelsterli U. Nimesulide and hepatic adverse affects: roles of reactive metabolites and host factors. Int. J. Clin. Pract., 2002, suppl. 128, 30-6.</p><p>Каратеев А. Е., Насонова В. А. НПВП – ассоциированная гепатопатия: проблема нимесулида. Научно-практич. ревматол., 2004, 1, 34-7</p><p>Press release. European Medicines Agency recommends restricted use of nimesulid-containing medicinal products. Doc. Ref. EMEA/432604/2007 На сайте: http://www.emea.europa.eu.</p><p>Traversa G., Bianchi C., Da Cas R., et al. Cohort study of hepatotoxity associated with nimesulide and other non-steroidal anti-inflammatory drugs. BMJ, 2003, 327, 18-22.</p></div><br />