nnpNeurology, Neuropsychiatry, PsychosomaticsНеврология, нейропсихиатрия, психосоматика2074-27112310-1342"IMA-Press", LLC10.14412/2074-2711-2010-123nnp-307Research ArticlePHARMACOTHERAPYФАРМАКОТЕРАПИЯGastrointestinal events during treatment with nonsteroidal anti-inflammatory drugs (according to the data of the CONDOR study)Желудочно-кишечные осложнения при лечении нестероидными противовоспалительными препаратами (по материалам исследования CONDOR)АлексеевВ. В.AlekseevV. V.alekseevvalery@mail.ruПервый МГМУ им. И.М.СеченоваРоссияI.M. Sechenov First Moscow State Medical UniversityRussian Federation20101512201024NO4 (2010)8185Copyright © Alekseev V.V., 20102010Алексеев В.В.Alekseev V.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://nnp.ima-press.net/nnp/article/view/307

The paper presents the results of a randomized double-blind study of the impact of therapy with celecoxib and a combination of diclofenac and omeprazole in patients with osteoarthrosis and rheumatoid arthritis on a risk for developing gastrointestinal diseases. The study was conducted at health care facilities in 196 centers of 32 countries and covered 18-to-60-year-old patients who belonged to an increased gastrointestinal risk group and had a history of gastroduodenal ulcers and a negative Helicobacter pylori test at screening. The included patients were randomized by a computer program in a 1: 1 ratio to treatment groups receiving celecoxib in a dose of 200 mg twice daily or sustained-release diclofenac 75 mg twice daily + omeprazole 20 mg once daily. The primary efficacy criterion was assessed as the development of clinically relevant changes in the upper or lower gastrointestinal tract (GIT). 4484 patients were randomized to treatment groups (2238 took celecoxib; 2246 received diclofenac + omeprazole). Twenty (0.9%) patients who took celecoxib and 81 (3.8%) who used diclofenac + omeprazole achieved the primary assessment criterion (p<0.0001). One hundred and fourteen (6%) patients who received celecoxib and 167 (8%) who took diclofenac + omeprazole were withdrawn from the study prematurely because of adverse reactions in the GIT (p = 0.0006). The risk of clinically relevant GIT changes was lower in the patients treated with celecoxib, that is a selective cyclooxygenase 2 (COX-2) inhibitor, than in the patients who received diclofenac, a nonselective COX inhibitor, and omeprazole, the proton pump inhibitor. The findings should contribute to the revision of approaches to reducing the gastrointestinal risk in nonsteroidal anti-inflammatory drugs treatment.

Представлены результаты рандомизированного двойного слепого исследования влияния терапии целекоксибом и комбинации диклофенака с омепразолом у пациентов с остеоартрозом и ревматоидным артритом на риск развития желудочно-кишечных осложнений. Исследование проводилось на клинических базах в 196 центрах 32 стран и включало пациентов в возрасте от 18 до 60 лет, относящихся к группе повышенного желудочно-кишечного риска и имевших указание в анамнезе на гастродуоденальные язвы и отрицательный результат теста на Helicobacter pylori на момент скрининга. Пациенты, включенные в исследование, с помощью компьютерной программы были рандомизированы в соотношении 1: 1 в группы лечения: группа пациентов, получавших целекоксиб в дозе 200 мг 2 раза в день, и группа пациентов, которым был назначен диклофенак медленного высвобождения в дозе 75 мг 2 раза в день + омепразол 20 мг 1 раз в день. Первичный критерий эффективности терапии оценивали как развитие клинически значимых изменений в верхних или нижних отделах желудочно-кишечного тракта (ЖКТ). 4484 пациента были рандомизированы в группы лечения (2238 получали целекоксиб; 2246 - диклофенак+омепразол). 20 (0,9%) пациентов, которые получали целекоксиб, и 81 (3,8%) пациент, принимавший диклофенак+омепразол, достигли первичного критерия оценки (p<0,0001). 114 (6%) пациентов, которые принимали целекоксиб, и 167 (8%) пациентов, которые получали диклофенак+омепразол, были преждевременно исключены из исследования из-за развития нежелательных явлений со стороны ЖКТ (p=0,0006). Риск развития клинически значимых изменений ЖКТ был ниже у пациентов, которые получали селективный ингибитор циклооксигеназы 2 (ЦОГ 2) целекоксиб, по сравнению с теми, кто получал неселективный ингибитор ЦОГ диклофенак и ингибитор протонной помпы омепразол. Данные, полученные в результате исследования, должны способствовать пересмотру подходов к снижению риска желудочно-кишечных осложнений при лечении нестероидными противовоспалительными препаратами.

нестероидные противовоспалительные препаратыцелекоксибдиклофенакжелудочно-кишечные осложненияnonsteroidal anti-inflammatory drugscelecoxibdiclofenacgastrointestinal eventsReferences<div><p>Lanas A., Perez-Aisa M.A., Feu F. et al. A nationwide study of mortality associated with hospital admission due to severe gastrointestinal events and those associated with non-steroidal antiinflammatory drug use. Am J Gastroenterol 2005;100:1685-93.</p><p>Bjarnason I., Zanelli G., Prouse P. et al. Effect of non-steroidal anti-inflammatory drugs on the human small intestine. Drugs 1986;32(Suppl.):35-41.</p><p>Langman M.J.S., Morgan L., Worall A. Use of inflammatory drugs by patients admitted with small or large bowel perforations and haemorrhage. Br Med J 1985;290:347-9.</p><p>Morris A.J., Wasson L.A., Mackenzie J.F. Small bowel enteroscopy in undiagnosed gastrointestinal blood loss. Gut 1992;887-9.</p><p>Kessler W.F., Shires G.T. 3rd, Fahey T.J. 3rd. Surgical complications of nonsteroidal antiinflammatory drug-induced small bowel ulceration. J Am Coll Surg 1997;185(3):250-4.</p><p>Bjarnason I., Zanelli G., Smith T. et al. Nonsteroidal antiinflammatory drug-induced intestinal inflammation in humans. Gastroenterology 1987;93:480-9.</p><p>Bjarnason I., Zanelli G., Smith T. et al. The pathogenesis and consequence of non-steroidal anti-inflammatory drug induced small intestinal inflammation. Scand J Rheumat 1987;64(Suppl.):55-62.</p><p>Bjarnason I., O'Morain C., Levi A.J. et al. Absorption of 51chromium-labeled ethylenediaminetetraacetate in infammatory bowel disease. Gastroenterology 1983;85:318-22.</p><p>Goldstein J.L., Silverstein F.E., Agrawal N.M. et al. Reduced risk of upper gastrointestinal ulcer complications with celecoxib, a novel COX-2 inhibitor. Am J Gastroenterol 2000;95:1681-90.</p><p>Chan F.K., Abraham N.S.,Scheiman J.M. et al. Management of patients on nonsteroidal anti-infammatory drugs: a clinical practice recommendation from the First International Working Party on Gastrointestinal and Cardiovascular Efects of Nonsteroidal Antiinfammatory Drugs and Anti-platelet Agents. Am J Gastroenterol 2008;103:2908-18.</p><p>Zhang W., Moskowitz R.W., Nuki G. et al. OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthr Cartilage 2008;16:137-62.</p><p>Scheiman J.M., Fendrick A.M. Summing the risk of NSAID therapy. Lancet 2007;369:1580-1.</p><p>Chan F.K., Hung L.C., Suen B.Y. et al. Celecoxib versus diclofenac and omeprazole in reducing the risk of recurrent ulcer bleeding in patients with arthritis. N Engl J Med 2002;347:2104-10.</p><p>Lanas A., Bajador E., Serrano P. et al. Nitrovasodilators, low-dose aspirin, other nonsteroidal antiinfammatory drugs, and the risk of upper gastrointestinal bleeding. N Engl J Med 2000;343:834-9.</p><p>Lai K.C., Chu K.M., Hui W.M. et al. Celecoxib compared with lansoprazole and naproxen to prevent gastrointestinal ulcer complications. Am J Med 2005;118:1271-8.</p><p>Ray W.A., Chung C.P., Stein C.M. et al. Risk of peptic ulcer hospitalizations in users of NSAIDs with gastroprotective cotherapy versus coxibs. Gastroenterology 2007;133:790-8.</p><p>Allison M.C., Howatson A.G., Torrance C.J. et al. Gastrointestinal damage associated with the use of nonsteroidal antiinfammatory drugs. N Engl J Med 1992;327:749-54.</p><p>Graham D.Y., Opekun A.R., Willingham F.F. et al. Visible small-intestinal mucosal injury in chronic NSAID users. Clin Gastroenterol Hepatol 2005;3:55-9.</p><p>Goldstein J.L., Eisen G.M., Lewis B. et al. Video capsule endoscopy to prospectively assess small bowel injury with celecoxib, naproxen plus omeprazole, and placebo. Clin Gastroenterol Hepatol 2005;3:133-341.</p><p>Goldstein J.L., Eisen G.M., Lewis B. et al. Small bowel mucosal injury is reduced in healthy subjects treated with celecoxib compared with ibuprofen plus omeprazole, as assessed by video capsule endoscopy. Aliment Pharmacol Ther 2007;25:1211-22.</p><p>Chan F.K.L., Lanas A., Scheiman J. et al. Celecoxib versus omeprazole and diclofenac in patients with ostheoarthritis and rheumatoid arthritis (CONDOR): a randomised trial. The Lancet 2010;376(9736):173-9.</p><p>Arnett F.C., Edworthy S.M., Bloch D.A. et al. The American Rheumatism Association 1987 revised criteria for the classifcation of rheumatoid arthritis. Arthr Rheum 1988;31:315-24.</p><p>Chan F.K.L., Cryer B., Goldstein J.L. et al. A novel composite endpoint to evaluate the gastrointestinal (GI) efects of nonsteroidal antiinfammatory drugs through the entire GI tract. J Rheumatol 2010;37:167-74.</p><p>Spiegel B.M., Farid M., Dulai G.S. et al. Comparing rates of dyspepsia with coxibs vs NSAID+PPI: a meta-analysis. Am J Med 2006;119(448):e27-e36.</p><p>Silverstein F.E., Faich G., Goldstein J.L. et al. Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-infammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: a randomised controlled trial. JAMA 2000;284:1247-55.</p><p>Singh G., Fort J.G., Goldstein J.L. et al. For the SUCCESS-I Investigators. Celecoxib versus naproxen and diclofenac in osteoarthritis patients: SUCCESS-I Study. Am J Med 2006;119:255-66.</p></div><br /><div><p>Lanas A., Perez-Aisa M.A., Feu F. et al. A nationwide study of mortality associated with hospital admission due to severe gastrointestinal events and those associated with non-steroidal antiinflammatory drug use. Am J Gastroenterol 2005;100:1685-93.</p><p>Bjarnason I., Zanelli G., Prouse P. et al. Effect of non-steroidal anti-inflammatory drugs on the human small intestine. Drugs 1986;32(Suppl.):35-41.</p><p>Langman M.J.S., Morgan L., Worall A. Use of inflammatory drugs by patients admitted with small or large bowel perforations and haemorrhage. Br Med J 1985;290:347-9.</p><p>Morris A.J., Wasson L.A., Mackenzie J.F. Small bowel enteroscopy in undiagnosed gastrointestinal blood loss. Gut 1992;887-9.</p><p>Kessler W.F., Shires G.T. 3rd, Fahey T.J. 3rd. Surgical complications of nonsteroidal antiinflammatory drug-induced small bowel ulceration. J Am Coll Surg 1997;185(3):250-4.</p><p>Bjarnason I., Zanelli G., Smith T. et al. Nonsteroidal antiinflammatory drug-induced intestinal inflammation in humans. Gastroenterology 1987;93:480-9.</p><p>Bjarnason I., Zanelli G., Smith T. et al. The pathogenesis and consequence of non-steroidal anti-inflammatory drug induced small intestinal inflammation. Scand J Rheumat 1987;64(Suppl.):55-62.</p><p>Bjarnason I., O'Morain C., Levi A.J. et al. Absorption of 51chromium-labeled ethylenediaminetetraacetate in infammatory bowel disease. Gastroenterology 1983;85:318-22.</p><p>Goldstein J.L., Silverstein F.E., Agrawal N.M. et al. Reduced risk of upper gastrointestinal ulcer complications with celecoxib, a novel COX-2 inhibitor. Am J Gastroenterol 2000;95:1681-90.</p><p>Chan F.K., Abraham N.S.,Scheiman J.M. et al. Management of patients on nonsteroidal anti-infammatory drugs: a clinical practice recommendation from the First International Working Party on Gastrointestinal and Cardiovascular Efects of Nonsteroidal Antiinfammatory Drugs and Anti-platelet Agents. Am J Gastroenterol 2008;103:2908-18.</p><p>Zhang W., Moskowitz R.W., Nuki G. et al. OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthr Cartilage 2008;16:137-62.</p><p>Scheiman J.M., Fendrick A.M. Summing the risk of NSAID therapy. Lancet 2007;369:1580-1.</p><p>Chan F.K., Hung L.C., Suen B.Y. et al. Celecoxib versus diclofenac and omeprazole in reducing the risk of recurrent ulcer bleeding in patients with arthritis. N Engl J Med 2002;347:2104-10.</p><p>Lanas A., Bajador E., Serrano P. et al. Nitrovasodilators, low-dose aspirin, other nonsteroidal antiinfammatory drugs, and the risk of upper gastrointestinal bleeding. N Engl J Med 2000;343:834-9.</p><p>Lai K.C., Chu K.M., Hui W.M. et al. Celecoxib compared with lansoprazole and naproxen to prevent gastrointestinal ulcer complications. Am J Med 2005;118:1271-8.</p><p>Ray W.A., Chung C.P., Stein C.M. et al. Risk of peptic ulcer hospitalizations in users of NSAIDs with gastroprotective cotherapy versus coxibs. Gastroenterology 2007;133:790-8.</p><p>Allison M.C., Howatson A.G., Torrance C.J. et al. Gastrointestinal damage associated with the use of nonsteroidal antiinfammatory drugs. N Engl J Med 1992;327:749-54.</p><p>Graham D.Y., Opekun A.R., Willingham F.F. et al. Visible small-intestinal mucosal injury in chronic NSAID users. Clin Gastroenterol Hepatol 2005;3:55-9.</p><p>Goldstein J.L., Eisen G.M., Lewis B. et al. Video capsule endoscopy to prospectively assess small bowel injury with celecoxib, naproxen plus omeprazole, and placebo. Clin Gastroenterol Hepatol 2005;3:133-341.</p><p>Goldstein J.L., Eisen G.M., Lewis B. et al. Small bowel mucosal injury is reduced in healthy subjects treated with celecoxib compared with ibuprofen plus omeprazole, as assessed by video capsule endoscopy. Aliment Pharmacol Ther 2007;25:1211-22.</p><p>Chan F.K.L., Lanas A., Scheiman J. et al. Celecoxib versus omeprazole and diclofenac in patients with ostheoarthritis and rheumatoid arthritis (CONDOR): a randomised trial. The Lancet 2010;376(9736):173-9.</p><p>Arnett F.C., Edworthy S.M., Bloch D.A. et al. The American Rheumatism Association 1987 revised criteria for the classifcation of rheumatoid arthritis. Arthr Rheum 1988;31:315-24.</p><p>Chan F.K.L., Cryer B., Goldstein J.L. et al. A novel composite endpoint to evaluate the gastrointestinal (GI) efects of nonsteroidal antiinfammatory drugs through the entire GI tract. J Rheumatol 2010;37:167-74.</p><p>Spiegel B.M., Farid M., Dulai G.S. et al. Comparing rates of dyspepsia with coxibs vs NSAID+PPI: a meta-analysis. Am J Med 2006;119(448):e27-e36.</p><p>Silverstein F.E., Faich G., Goldstein J.L. et al. Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-infammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: a randomised controlled trial. JAMA 2000;284:1247-55.</p><p>Singh G., Fort J.G., Goldstein J.L. et al. For the SUCCESS-I Investigators. Celecoxib versus naproxen and diclofenac in osteoarthritis patients: SUCCESS-I Study. Am J Med 2006;119:255-66.</p></div><br />

The authors declare that there are no conflicts of interest present.