[en] OBJECTIVES:
Selective inhibitors of cyclo-oxygenase-2 (COX-2) appear to be safer than conventional NSAIDs on the gastrointestinal (GI) tract. Amtolmetin guacyl (AMG), a NSAID that inhibits both COX-1 and COX-2, has an anti-inflammatory effect comparable to that of traditional NSAIDs, with a better GI safety profile. The primary end-point of this study was to evaluate the gastrointestinal safety of amtolmetin guacyl in comparison with celecoxib in patients affected with rheumatoid arthritis. The assessment of efficacy was the secondary end-point.
Disciplines :
Rheumatology
Author, co-author :
Jajic, Z.
Malaise, Michel ; Université de Liège - ULiège > Département des sciences cliniques > Rhumatologie
Nekam, K.
Koó, E.
Dankó, K.
Kovacs, M.
Scarpignato, C.
Language :
English
Title :
Gastrointestinal safety of amtolmetin guacyl in comparison with celecoxib in patients with rheumatoid arthritis
Publication date :
2005
Journal title :
Clinical and Experimental Rheumatology
ISSN :
0392-856X
eISSN :
1593-098X
Publisher :
Clinical and Experimental Rheumatology SAS, Pisa, Italy
SOKKA T: Work disability in yearly rheumatoid arthritis. Clin Exp Rheumatol 2003; 21 (Suppl. 31): 571-4.
SCOTT DL, SMITH C, KINGSLEY G: Joint damage and disability in rheumatoid arthritis: an updated systematic review Clin Exp Rheumatol 2003; 21 (Suppl. 31): 520-7.
PINCUS T, KAVANAUGH A, SOKKA T: Benefit/risk of therapies for rheumatoid arthritis: underestimation of the "side effects" or risks of RA leads to underestimation of the benefit/risk of therapies. Clin Exp Rheumatol 2004; 22 (Suppl. 35): S2-11.
HENRY DA: Side effects of non steroidal anti-inflammatory drugs. Balliere's Clin Rheumatol 1988; 2: 425-54.
WOLFE MM, LICHTENSTEIN DR, SINGH G: Gastrointestinal toxicity of non-steroidal anti-inflammatory drugs. N Eng J Med 1999; 340: 1888-99.
MACDONALD TM, MORANT SV, ROBINSON GC et al.: Association of upper gastrointestinal toxicity of non-steroidal anti-inflammatory drugs with continued exposure: cohort study. BMJ 1997; 315: 1333-7.
LANGMAN MJ, WEIL J, WAINWRIGHT P et al.: Risks of bleeding peptic ulcer associated with individual non-steroidal anti-inflammatory drugs. Lancet 1994; 343: 1075-8.
HASLOCK I: Review of induced upper gastrointestinal morbidity and mortality. In CHELI R (Ed.): Treatment and Prevention of NSAID-Induced Gastropathy. Royal Society of Medicine Services International Congress and Symposium Series 1989; 147: 3-10.
GARCIA-RODRIGUEZ LA, JICK H: Risk of upper gastrointestinal bleeding and perforation associated with individual non steroidal anti-inflammatory drugs. Lancet 1994; 343: 769-72.
SCARPIGNATO C, PELOSINI I: Prevention and treatment of non-steroidal anti-inflammatory drug-induced gastro-duodenal damage: rationale for the use of antisecretory compounds. Ital J Gastroenterol Hepatol 1999; 31 (Suppl. 1): S63-72.
SCARPIGNATO C: Non steroidal anti-inflammatory drugs: how do they damage gastroduodenal mucosa? Dig Dis 1995; 13 (Suppl. 1): 9-39.
REDFERN JS, FELDMAN M: Role of prostaglandins in preventing gastrointestinal ulceration: Induction of ulcers by antibodies to prostaglandins. Gastroenterology 1989; 96: 596-605.
HALTER F, TARNAWSKI AS, SCHMASSMANN A, PESKAR BM: Cyclooxygenase 2-implications on maintenance of gastric mucosa integrity and ulcer healing: controversial issues and perspectives. Gut 2001; 49: 443-53.
WALLACE JL, DEVCHAND PR: Emerging roles for cyclooxygenase-2 in gastrointestinal mucosal defence. Br J Pharmacol 2005; 145: 275-82.
WU CY, WU MS, CHEN CJ, LI MC, LIN JT, CHEN GH: The interaction of H. pylori infection and NSAIDs in cyclooxygenase-2 mRNA expression in gastric antral, corpus mucosa, and gastric ulcer. J Clin Gastroenterol 2005; 39: 50-5.
SCARPIGNATO C, BJARNASON I, BRETAGNE J-F et al.: Working Team Report: Towards a GI Safer Antiinflammatory Therapy. Gastroenterology Int 1999; 12: 186-215.
BENSEN WG, FIECHTNER JJ, McMILLEN JI et al.: Treatment of osteoarthritis with celecoxib, a cyclooxygenase 2 inhibitor: a randomized, controlled trial. Mayo Clin Proc 1999; 74: 1095-105.
EMERY P, ZEIDLER H, KWIEN T et al.: Celecoxib versus diclofenac in long term management of rheumatoid arthritis: randomized, double blind comparison. Lancet 1999; 354: 2106-11.
SILVERSTEIN FE, FAICH G, GOLDSTEIN JL et al.: Gastrointestinal toxicity with celecoxib vs non steroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis. The CLASS study: a randomized, controlled trial. JAMA 2000; 284 (10):1247-55.
BOMBARDIER C, LAINE L, REICIN A et al.: Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. N Engl J Med 2000; 343: 1520-8.
DEEKS JJ, SMITH LA, BRADLEY MD: Efficacy, tolerability, and upper gastrointestinal safety of celecoxib for treatment of osteoarthritis and rheumatoid arthritis: systematic review of randomised controlled trials. BMJ 2002; 325: 619-24.
WATSON DJ, YU Q, BOLOGNESE JA, REICIN AS, SIMON TJ: The upper gastrointestinal safety of rofecoxib vs. NSAIDs: an updated combined analysis. Curr Med Res Opin 2004; 20: 1539-48.
TUBARO E, BELOGI L, MEZZADRI CM, RUCO L, STOPACCIARO A: Studies on the gastric tolerability of the new non steroidal anti-inflammatory drug amtolmetin guacyl. Arzneim Forsch/Drug Res 1995; 45: 1298-302.
TUBARO E, BELOGI L, MEZZADRI CM: Anti-inflammatory and antiplatelet effect of Amtolmetin Guacyl, a new gastroprotective non-steroidal anti-inflammatory drug. Arzneim Forsch/Drug Res 2001, 51: 737-42.
TUBARO E, BELOGI L, MEZZADRI CM: The mechanism of action of amtolmetin guacyl, a new gastroprotective non-steroidal anti-inflammatory drug. Eur J Pharmacol 2000; 387: 233-44.
BIANCHI PORRO G, MONTRONE F, LAZZARONI M, MANZIONNA G, CARUSO I: Clinical and gastroscopic evaluation of amtolmetin guacyl versus diclofenac in patients with rheumatoid arthritis. Ital J Gastroenterol Hepotol 1999; 3: 378-85.
TAVELLA G, URSINI G: Studio clinico sull'attività antinfiammatoria e sulla tollerabilità gastroenterica di amtolmetin guacil, un nuovo FANS, in confronto a diclofenac, su pazienti anziani con patologie osteoarticolari. Clin Ter 1997; 148: 543-8.
MONTRONE F, SANTANDREA S, CARUSO I et al.: Amtolmetin guacyl versus piroxicam in patients with osteoarthritis. J Int Med Res 2000; 28: 91-100.
MARCOLONGO R, FREDIANI B, BIASI G, MINARI C, BARRECA C: Metanalysis of the tolerability of amtolmetin guacyl, a new, efficacious, non-steroidal anti-inflammatory drug, compared with traditional NSAIDs. Clin Drug Invest 1999; 17: 89-96.
DE PRETIS G, TASINI E: Tollerabilità gastrica dell'antiinfiammatorio Amtolmetina Guacil: meta-analisi dei trials terapeutici. Medicina Terapia 2002.
TUBARO E, BELOGI L, MEZZADRI CM, BETTELLI E: Impact on the bowel of amtolmetin guacyl, a new gastroprotective non-steroidal anti-inflammatory drug. Eur J Pharmacol 2003; 467: 173-83.
RIEZZO G, CHILOIRO M, MONTANARO S: Protective effect of amtolmetin guacyl versus placebo, a typical NSAID and misoprostol in healthy volunteers evaluated as gastric electrical activity in alcohol induced stomach damage. Dig Dis Sci 2001; 46: 1797-804.
PISANO C, GRANDI D, MORINI G et al.: Gastrosparing effect of new anti-inflammatory drug amtolmetin guacyl in the rat: involvement of nitric oxide. Dig Dis Sci 1999; 44: 713-24.
FELSON DT, ANDERSON JJ, BOERS M et al.: The American College of Rheumatology preliminary core Set of disease activity measures for rheumatoid arthritis clinical trials. Arthritis Rheum 1993, 36: 729-40.
FELSON DT et al.: American College of Rheumatology. Preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum 1996, 39: 535-7.
SIMON LS, WEAWER AL, GRAHAM DY et al.: The anti-inflammatory and upper gastrointestinal effects of celecoxib in rheumatoid arthritis: a randomized, controlled trial. JAMA 2000; 82: 1921-8.
MITCHELL JA, WARNER TD: Cyclooxygenase 2: pharmacology, physiology, biochemistry and relevance to NSAID therapy. Br J Pharmacol 1999; 128: 1121-32.
ZHAO SS, McMILLEN JI, MARKENSON JA et al.: Evaluation of functional status aspects of health related quality of life of patients with osteoarthritis treated with celecoxib. Pharmacotherapy 1999; 19: 1269-78.
SILVERSTEIN FE, GRAHAM DY, SENIOR JR et al.: Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving non-steroidal anti-inflammatory drugs: a randomized, double blind, placebo controlled trial. Ann Intern Med 1995; 123: 241-9.
SCARPIGNATO C, LAZZARONI M, PELOSINI I, BIANCHI PORRO G: Selective inhibitors of cyclooxyganase-2: myth or reality? [in Italian]. Arg Gastroenterol Clin 1997; 10: 153-75.
BROOKS P, EMERY P, EVANS JF et al.: Interpreting the clinical significance of the differential inhibition of cyclooxygenase-1 and cyclooxygenase-2. Rheumatology 1999; 38: 779-88.
LIPSKY LP, ABRAMSON SB, CROFFORD L, DUBOIS RN, SIMON LS, van de PUTTE LB: The classification of cyclooxygenase inhibitors. J Rheumatol 1998; 25: 2298-303.
WARNER TD, GIULIANO F, VOJNOVIC I, BUKASA A, MITCHELL JA, VANE JR: Nonsteroid drug selectivities for cyclo-oxygenase-1 rather than cyclo-oxygenase-2 are associated with human gastrointestinal toxicity: a full in vitro analysis. Proc Natl Acad Sci USA 1999; 96: 7563-8.
TACCONELLI S, CAPONE ML, SCIULLI MG, RICCIOTTI E, PATRIGNANI P: The biochemical selectivity of novel COX-2 inhibitors in whole blood assays of COX-isozyme activity. Curr Med Res Opin 2002; 18: 503-11.
LAZZARONI M, ANDERLONI A, BIANCHI PORRO G: The effects on gastroduodenal mucosa of a new non-steroidal anti-inflammatory drug, amtolmetin guacyl, versus piroxicam in healthy volunteers: a short term, double blind, endoscopically controlled study. Eur J Gastroenterol Pathol 2001; 13: 833-9.
HAWKEY CJ, LANGSTROM G, NAESDAL J et al.: Significance of dyspeptic symptoms during healing and maintenance of NSAID associated gastroduodenal lesions with omeprazole, misoprostol and ranitidine. Gastroenterology 1997; 112: A144.
SINGH G, RAMEY DR, MORFELD D, SHI H, HATOUM HT, FRIES JF: Gastrointestinal tract complications of non-steroidal anti-inflammatory drug treatment in rheumatoid arthritis. Arch Intern Med 1996; 156: 1530-6.
CORUZZI G, COPPELLI G, SPAGGIARI S et al:. Gastroprotective effects of amtolmetin guacyl: a new non-steroidal anti-inflammatory drug that activates inducible gastric nitric oxide synthase. Dig Liv Dis 2002; 34:403-10.
BRZOZOWSKI T, KONTUREK PC, KONTUREK SJ et al.: Gastroprotective and ulcer healing effects of nitric oxide releasing non-steroidal anti-inflammatory drugs. Dig Liv Dis 2000; 32: 583-94.
TEPPERMANN BL, SOPER BD: Nitric oxide synthase induction and cytoprotection of rat gastric mucosa from injury by ethanol. Can J Physiol Pharmacol 1994; 72: 1308-12.
LOPEZ-BELMONTE J, WHITTLE BJR, MONCADA S: The actions of nitric oxide donors in the prevention or induction of injury to the rat gastric mucosa. Br J Pharmacol 1993; 108: 73-8.
MORINI G, GUAIATA E, LAZZARETTI M, GRANDI D, CORUZZI G: Morphological features of rat gastric mucosa after acute and chronic treatment with amtolmetin guacyl: comparison with non-selective and COX2 selective NSAIDs. Digestion 2003; 68: 124-32.
SCHNITZER TJ: Cyclooxygenase-2-specific inhibitors: are they safe? Am J Med 2001; 110 (1A): 46S-49S.
NICCOLI L, BELLINO S, CANTINI F: Renal tolerability of three commonly employed non-steroidal anti-inflammatory drugs in elderly patients with osteoarthritis. Clin Exp Rheumatol 2002; 20: 201-7.
AW TJ, HAAS SJ, LIEW D, KRUM H: Meta-analysis of cyclooxygenase-2 inhibitors and their effects on blood pressure. Arch Intern Med 2005; 165: 490-6.
JUSTICE E, CARRUTHERS DM: Cardiovascular risk and COX-2 inhibition in rheumatology practice. J Hum Hypertens 2005; 19: 1-5.
WONG D, WANG M, CHENG Y, FITZGERALD GA: Cardiovascular hazard and non-steroidal anti-inflammatory drugs. Curr Opin Pharmacol 2005; 5: 204-10.
WALLBERG-JONSSON S, CEDERFELT M, RANTAPAA DAHLQVISP S: Hemostatic factors and cardiovascular disease in active rheumatoid arthritis: an 8-year follow-up study. J Rheumatol 2000; 27: 71-5.
FITZGERALD GA: COX-2 and beyond: approaches to prostaglandin inhibition in human disease. Nat Rev Drug Discov 2003; 2: 879-99.
SCHROR K, WEBER AA: Roles of vasodilatatory Prostaglandins in mitogenesis of vascular smooth muscle cells. Agents Actions 1997; 48 (Suppl.): 63-91.
EGAN KM, LAWSON JA, FRIES S et al.: Cyclooxygenase-2-derived prostacyclin confers atheroprotection on female mice. Obstet Gynecol Surv 2005; 60: 309-10.
McADAM BF, CATELLA-LAWSON F, MARDINI IA, KAPOOR S, LAWSON JA, FITZGERALD GA: Systemic biosynthesis of prostacyclin by cyclooxygenase (COX)-2: the human pharmacology of a selective inhibitor of COX. Proc Natl Acad Sci USA 1999; 96: 272-7.
FITZGERALD GA: Coxibs and cardiovascular disease. N Eng J Med 2004; 351: 1709-11.
MUKHERJEE D, NISSEN SE, TOPOL EJ: Risk of cardiovascular events associated with selective Cox-2 inhibitors. JAMA 2001; 286, 954-9.
RAY WA, STEIN CM, DAUGHERTY JR, HALL K, ARBOGAST PG, GRIFFIN MR: COX-2 selective non-steroidal anti-inflammatory drugs and risk of serious coronary heart disease. Lancet 2002; 360: 1071-3.
EMEA/62838/2005 Public statement: European Medicines Agency announces regulatory action on COX-2 inhibitors [http://www.emea.eu.int/htms/hotpress/d6275705.htm].
FDA Public Health Advisory: FDA announces important changes and additional warnings for COX-2 selective and non-selective non-steroidal anti-inflammatory drugs (NSAIDs) [http://www.fda.gov/cder/drug/advisory/COX2.htm].
AIFA: Comunicato n. 5 del 17 febbraio 2005. COX 2, AIFA adotta misure a tutela salute cittadini [http://www.agenziafarmaco.it/com_n5_17_02_2005.html].
LEESE PT, HUBBARD RC, KARIM A, ISAKSON PC, YU SS, GEIS GS: Effects of celecoxib, a novel cyclooxygenase-2 inhibitor, on platelet function in healthy adults: a randomized, controlled trial. J Clin Pharmacol 2000; 40: 124-32.
WILNER KD, RUSHING M, WALDEN C et al.: Celecoxib does not affect the antiplatelet activity of aspirin in healthy volunteers. J Clin Pharmacol 2002; 42: 1027-30.
CATELLA-LAWSON F, REILLY MP, KAPOOR SC et al.: Cyclooxygenase inhibitors and the antiplatelet effects of aspirin. N Engl J Med 2001; 345: 1809-17.
