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Aktuelle Rheumatologie 2001; 26(2): 75-81
DOI: 10.1055/s-2001-14217
ORIGINALARBEIT
© Georg Thieme Verlag Stuttgart · New York

Klinische Studien zum selektiven Cyclooxygenase-2-Inhibitor Celecoxib

Clinical Data on the Selective Cyclooxygenase-2-Inhibitor CelecoxibU. W. Fisch1 , G. Mahr2 , H. Vergin1
  • 1 Pharmacia GmbH, Erlangen
  • 2 mcp, Erlangen
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Publication History

Publication Date:
31 December 2001 (online)

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Zusammenfassung

Die vorliegende Übersichtsarbeit fasst die wesentlichen klinischen Daten zur Wirksamkeit, Sicherheit und Verträglichkeit von Celecoxib bei der Therapie von Arthrose und rheumatoider Arthritis zusammen. Darüber hinaus werden für das Sicherheitsprofil des Arzneimittels relevante hämatologische, immunologische, hepatische, renale und kardiovaskuläre Daten präsentiert. Celecoxib erwies sich in kontrollierten klinischen Studien Plazebo als signifikant überlegen und als gleich wirksam wie Diclofenac oder Naproxen. Die Häufigkeit schwerer gastrointestinaler Nebenwirkungen (Blutung, Perforation, Magenobstruktion) unter Celecoxib war der von Plazebo vergleichbar und statistisch signifikant niedriger als unter Diclofenac, Ibuprofen und Naproxen. Celecoxib ist ein selektiver COX-2-Hemmer mit sehr günstigem Nutzen-Risiko-Verhältnis.

Clinical Data on the Selective Cyclooxygenase-2-Inhibitor Celecoxib

This review presents the essential clinical data on efficacy, safety and tolerability of celecoxib in the therapy of osteoarthritis and rheumatoid arthritis. Moreover hematologic, immunologic, hepatic, renal and cardiovascular data which are relevant for the safety profile are shown. In controlled clinical trials celecoxib was found to be significantly superior to placebo and equally efficacious as diclofenac or naproxen. On celecoxib therapy the frequency of severe gastrointestinal adverse events (bleeding, perforation, gastric outlet obstruction) was comparable to placebo and significantly lower than on diclofenac, ibuprofen and naproxen. The presented data prove celecoxib to be a selective COX-2 inhibitor with a very favourable benefit-risk-ratio.

Literatur

  • 1 Bensen W G, Fiechtner J J, McMillen J I, Zhao W W, Yu S S, Woods E M, Hubbard R C, Isakson P C, Verburg K M, Geis G S. Treatment of osteoarthritis with celecoxib, a cyclooxygenase-2 inhibitor: A randomized controlled trial.  Mayo Clin Proc. 1999;  74 1095-1105
    PubMedSearch in Google Scholar
  • 2 Bensen W G, Agrawal N M, Zhao S Z, Burke T A, Zabinski R A, Maurath C J, Geis G S. Upper gastrointestinal (UGI) tolerability of celecoxib, a COX-2 specific inhibitor, compared to naproxen and placebo.  Arthritis Rheum. 1999;  42 abstract 430
    PubMedSearch in Google Scholar
  • 3 Bensen W G, Zhao S Z, Burke T A, Zabinski R A, Makuch R W, Maurath C J, Agrawal N M, Geis G S. Upper gastrointestinal tolerability of celecoxib, a cox-2 specific inhibitor, compared to naproxen and placebo.  J Rheumatol,. 2000;  27 1876-1883
    PubMedSearch in Google Scholar
  • 4 Boyce E G, Breen G A. Celecoxib: A COX-2 inhibitor for the treatment of osteoarthritis and rheumatoid arthritis.  Formulary. 1999;  34 405-417
    PubMedSearch in Google Scholar
  • 5 Burke T A, Goldstein J L, Pettitt A D, Maurath C J, Zhao S Z, Zabinski R A. Increased upper gastrointestinal (UGI) distress among arthritis patients treated with NSAIDs compared to celecoxib and placebo.  Value Health. 1999;  2 154-155
    PubMedSearch in Google Scholar
  • 6 Burr A M, Yu S S, Zhao W W, Hubbard R C, Geis G S. Serial endoscopies confirm lower incidence of gastroduodenal ulceration with celecoxib as compared to naproxen.  Am J Gastroenterol. 1999;  94 2606, abstract 116
    PubMedSearch in Google Scholar
  • 7 Caspi A. Celecoxib: A new treatment for the pain of osteoarthritis and rheumatoid arthritis.  P & T. 1999;  24 211-212, 217
    PubMedSearch in Google Scholar
  • 8 Clemett D, Goa K L. Celecoxib. A review of its use in osteoarthritis, rheumatoid arthritis and acute pain.  Drugs. 2000;  59 957-980
    CrossrefPubMedSearch in Google Scholar
  • 9 Dougados M, Béhier J M, Jolchine I, Calin A, van der Heijde D, Dolivieri I, Zeidler H, Herman H. Efficacy of celecoxib, a cox-2 specific inhibitor in ankylosing spondylitis: a placebo and conventional NSAID (ketoprofen) six-week control study.  Ann Rheum Dis. 2000;  59 204, abstract POS-605
    PubMedSearch in Google Scholar
  • 10 Emery P, Zeidler H, Kvien T K, Guslandi M, Naudin R, Stead H, Verburg K M, Isakson P C, Hubbard R C, Geis G S. Celecoxib versus diclofenac in long-term management of rheumatoid arthritis: randomized double-blind comparison.  Lancet. 1999;  354 2106-2111
    CrossrefPubMedSearch in Google Scholar
  • 11 Fisch U W, Brauer H G, Mahr G, Vergin H. Cyclooxygenase-2-spezifische Inhibitoren: Grundlegende Aspekte des Wirkmechanismus.  Akt Rheumatol. 1999;  24 63-68
    PubMedSearch in Google Scholar
  • 12 Fort J. Celecoxib, a COX-2-specific inhibitor: the clinical data.  Am J Orthop. 1999;  28 13-18
    PubMedSearch in Google Scholar
  • 13 Geba G P, Weaver A L, Schnitzer T J, Fleischmann R M, Polis A B, Matzura-Wolfe D M, Dixon M E, Gormley G J. A comparison of rofecoxib to celecoxib and acetaminophen in the treatment of osteoarthritis.  Arthritis Rheum. 2000;  43 (9, Suppl.) S384
    PubMedSearch in Google Scholar
  • 14 Geis G S, Hubbard R C, Woods E M, Lefkowith J B, Yu S, Zhao W W. Efficacy of celecoxib, a COX-2 specific inhibitor, in osteoarthritis of the hip.  Arthritis Rheum. 1999;  42 abstract 441
    PubMedSearch in Google Scholar
  • 15 Geis G S, Hubbard H C, Woods E M, Lefkowith J B, Yu S, Zhao W W. Efficacy and safety of celecoxib, a specific cyclooxygenase-2 (COX-2)inhibitor, in rheumatoid arthritis.  Ann Rheum Dis. 1999;  99 abstract 854
    PubMedSearch in Google Scholar
  • 16 Goldenberg M M. Celecoxib, a selective cyclooxygenase-2 inhibitor for the treatment of rheumatoid arthritis and osteoarthritis.  Clin Ther. 1999;  21 1497-1513
    CrossrefPubMedSearch in Google Scholar
  • 17 Goldstein J L, Agrawal N, Silverstein F, Burr A, Maurath C J, Verburg K M, et al. Effect of celecoxib (CEL) versus placebo (PBO) or NSAIDs in healing of gastric or duodenal erosions in arthritis patients: analysis of controlled endoscopic studies.  Am J Gastroenterol. 1999;  94 2608, abstract 126
    PubMedSearch in Google Scholar
  • 18 Goldstein J L, Silverstein F E, Agrawal N M, Hubbard R C, Kaiser J, Maurath C J, Verburg K M, Geis G S. Reduced risk of upper gastrointestinal ulcer complications with celecoxib, a novel COX-2 inhibitor.  Am J Gastroenterol. 2000;  95 1681-1690
    PubMedSearch in Google Scholar
  • 19 Isakson P, Zweifel B, Masferrer J, Koboldt C, Seibert K, Hubbard R, Geis S, Needleman P. Specific COX-2 inhibitors: from bench to bedside. In: Vane J, Botting J, editors Selective COX-2 inhibitors. Pharmacology, clinical effects and therapeutic potential. Proceedings of a conference held on March 20 - 21, 1997 in Cannes, France. Dordrecht: Kluwer Academic Publishers and London; William Harvey Press 1998: 127-133
    Search in Google Scholar
  • 20 Leese P T, Hubbard R C, Karim A, Isakson P C, Yu S S, Geis G S. Effects of celecoxib, a novel cyclooxygenase-2 inhibitor, on platelet function in healthy adults: A randomized, controlled trial.  J Clin Pharmacol. 2000;  40 124-132
    CrossrefPubMedSearch in Google Scholar
  • 21 McKenna F. Summary of Faculty Presentations - Satellite Symposium at the XV European League Against Rheumatism (EULAR) Congress, Nice, 22 June 2000. 
  • 22 Patterson R, Bello A E, Lefkowith J. Immunologic tolerability profile of celecoxib.  Clin Ther. 1999;  21 2065-2079
    CrossrefPubMedSearch in Google Scholar
  • 23 Rossat J, Maillard M, Nussberger J, Brunner H R, Burnier M. Renal effects of selective cyclooxygenase-2 inhibitors in normotensive salt-depleted subjects.  Clin Pharmacol Ther. 1999;  66 76-84
    CrossrefPubMedSearch in Google Scholar
  • 24 Silverstein F E, Faich G, Goldstein J L, Simon L S, Pincus T, Whelton A, Mackich R, Eisen G, Agrawal N M, Stenson W F, Burr A M, Zhao W W, Kent J D, Lefkowith J B, Verburg K M, Geis G S. Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis. The CLASS study: a randomized controlled trial.  JAMA. 2000;  284 1247-1255
    CrossrefPubMedSearch in Google Scholar
  • 25 Simon L S, Lanza F L, Lipsky P E, Hubbard R C, Talwalker S, Schwartz B D, Isakson P C, Geis S G. Preliminary study of the safety and efficacy of SC-58 635, a novel cyclooxygenase 2 inhibitor: Efficacy and safety in two placebo controlled trials in osteoarthritis and rheumatoid arthritis, and studies of gastrointestinal and platelet effects.  Arthritis Rheum. 1998;  41 1591-1602
    PubMedSearch in Google Scholar
  • 26 Simon L S, Weaver A L, Graham D Y, Kivitz A J, Lipsky P E, Hubbard R C, Isakson P C, Verburg K M, Yu S S, Zhao W W, Geis G S. Anti-inflammatory and upper gastrointestinal effects of celecoxib in rheumatoid arthritis. A randomized controlled trial.  JAMA. 1999;  282 1921-1928
    CrossrefPubMedSearch in Google Scholar
  • 27 SHEP Cooperative Research Group . Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP).  JAMA . 1991;  295
    PubMedSearch in Google Scholar
  • 28 Singh G, Ramey D R, Triadafilopoulos G. Experience with selective COX-2 inhibitors: Safety profile in over 780,000 patient years of use. Poster American Congress of Rheumatology, 63rd Annual Scientific Meeting, November 13 - 17,. Boston, USA; 1999
    Search in Google Scholar
  • 29 Stucki G, Meier D, Stucki S, Michel B A, Tyndall A G, Dick W, Theiler R. Evaluation einer deutschen Version des WOMAC (Western Ontario und McMaster Universities) Arthroseindex.  Z Rheumatol. 1996;  55 40-49
    PubMedSearch in Google Scholar
  • 30 Whelton A, Maurath C J, Verburg K M, Geis G S. Renal safety and tolerability of celecoxib, a novel cyclooxygenase-2 inhibitor.  Am J Ther. 2000;  7 159-175
    PubMedSearch in Google Scholar
  • 31 Whelton A, Schulman G, Wallemark C, Drower E J, Isakson P C, Verburg K M, Geis G S. Effects of celecoxib and naproxen on renal function in the elderly.  Arch Intern Med. 2000;  160 1465-1470
    PubMedSearch in Google Scholar
  • 32 Whelton A, Fort J, Puma J, Normandin D, Ello A, Verburg K. Cyclooxygenase-2 specific inhibitors and cardiorenal function. A randomized controlled trial of celecoxib and rofecoxib in elderly hypertensive osteoarthritis patients.  Am J Ther. 2001;  8 85-95
    PubMedSearch in Google Scholar
  • 33 Williams G W, Ettlinger R E, Ruderman E M, Hubbard R C, Lonien M E, Yu S S, Zhao W, Geis G S. Treatment of osteoarthritis with a once-daily dosing regimen of celecoxib.  J Clin Rheumatol. 2000;  6 65-74
    PubMedSearch in Google Scholar
  • 34 Zhao S Z, Dedhiya S D, Verburg K, Fort J, Osterhaus J T. Celecoxib improves health related quality of life (HRQOL) of elderly patients with osteoarthritis (OA).  Arthritis Rheum. 1999;  42 abstract 1356
    PubMedSearch in Google Scholar
  • 35 Zhao S Z, McMillen J I, Markenson J A, Dedhiya S D, Zhao W W, Osterhaus J T, Yu S S. Evaluation of the functional status aspects of health-related quality of life of patients with osteoarthritis treated with celecoxib.  Pharmacotherapy. 1999;  19 1269-1278
    CrossrefPubMedSearch in Google Scholar

Dr. med. U. W. Fisch

Pharmacia GmbH

Am Wolfsmantel 46
91058 Erlangen