Gastroenterology

Gastroenterology

Volume 118, Issue 2, February 2000, Pages 264-273
Gastroenterology

Alimentary Tract
Prophylaxis of postoperative relapse in Crohn's disease with mesalamine: European cooperative Crohn's disease study VI,☆☆,

https://doi.org/10.1016/S0016-5085(00)70208-3Get rights and content

Abstract

Background & Aims: This study investigated if long-term treatment with high-dose mesalamine reduces the risk of clinical relapse of Crohn's disease after surgical resection. Methods: In a prospective, randomized, double-blind, multicenter study, 4 g of mesalamine (Pentasa; Ferring A/S, Vanløse, Denmark) daily was compared with placebo in 318 patients. Treatment was started within 10 days after resective surgery and continued for 18 months. Primary outcome parameter was clinical relapse as defined by an increase in Crohn's Disease Activity Index, reoperation, septic complication, or newly developed fistula. Risk factors for recurrence were prospectively defined to be analyzed in a stepwise proportional hazards model. Results: Cumulative relapse rates (±SE) after 18 months were 24.5% ± 3.6% and 31.4% ± 3.7% in the mesalamine (n = 152) and placebo (n = 166) groups, respectively (P = 0.10, log-rank test, 1-sided). Retrospective analysis showed a significantly reduced relapse rate with mesalamine only in a subgroup of patients with isolated small bowel disease (n = 124; 21.8% ± 5.6% vs. 39.7% ± 6.1%; P = 0.02, log-rank test). Probability of relapse was predominantly influenced by the duration of disease (P = 0.0006) and steroid intake before surgery (additional risk, P = 0.0003). Conclusions: Eighteen months of mesalamine, 4 g daily, did not significantly affect the postoperative course of Crohn's disease. Some relapse-preventing effect was found in patients with isolated small bowel disease.

GASTROENTEROLOGY 2000;118:264-273

Section snippets

Study design

The study was a prospective, randomized, double-blind multicenter study with a parallel group design comparing the efficacy of 4 g mesalamine (Pentasa) daily with placebo in preventing postoperative recurrence after resective surgery for CD. Twenty-nine centers in Austria, Denmark, Germany, Norway, Sweden, and Switzerland participated. Patient recruitment was started on July 23, 1992. The last patient treatment was completed on June 30, 1996. The trial protocol and the 4 subsequent amendments

Study population

A total of 617 patients were screened between July 1992 and April 1995. One hundred fifty-two patients were not enrolled because of violation of inclusion or applicability of exclusion criteria. Furthermore, 141 eligible patients refused to participate in the study. Thus, 324 patients (70% of the eligible population) were randomized, 154 to mesalamine and 170 to placebo.

Six randomized patients (2 mesalamine, 4 placebo) did not start treatment in time because of postoperative complications and,

Discussion

Prevention of recurrence is still one of the major goals in the treatment of patients with CD. Several studies have either included surgical patients or specifically dealt with the prevention of postoperative relapse.6, 11, 12, 13 In a recent meta-analysis, mesalamine has been shown to exhibit a small therapeutic advantage over placebo; however, the number of patients to be treated for the prevention of a single relapse is quite high.7 This unsatisfactory therapeutic scenario of a burning

References (31)

  • MV Tobin et al.

    Cigarette smoking and inflammatory bowel disease

    Gastroenterology

    (1987)
  • L Bergmann et al.

    Post-operative treatment with corticosteroids and salazosulphapyridine (Salozopyrin) after resection for Crohn's disease

    Scand J Gastroenterol

    (1976)
  • P Rutgeerts et al.

    Controlled trial of metronidazole treatment for prevention of Crohn's recurrence after ileal resection

    Gastroenterology

    (1995)
  • BI Korelitz et al.

    Long-term experience with 6-mercaptopurine in the treatment of Crohn's disease

    Am J Gastroenterol

    (1993)
  • B Korelitz et al.

    Post-operative with 6-MP, 5-ASA or placebo in Crohn's disease. A 2 year multicenter trial (abstr)

    Gastroenterology

    (1998)
  • Cited by (0)

    Supported by a grant from Ferring AS, Denmark, and Ferring Arzneimittel, Germany.

    ☆☆

    Address requests for reprints to: Herbert Lochs, M.D., Universitaetsklinikum Charité, Medizinische Klinik, Schumannstrasse 20/21, D-10117 Berlin, Germany. e-mail: [email protected]; fax: (49) 2802-8978.

    The investigators and centers that participated in this study are as follows: Austria: D. Genser, Abteilung für Gastroenterologie und Hepatologie, Universitätsklinik für Innere Medizin, Vienna; W. Petritsch and T. Hinterleitner, Klinische Abteilung für Gastroenterologie und Hepatologie, Medizinische Universitätsklinik Graz, Graz. Germany: M. Raithel, Medizinische Klinik I der Universität Erlangen, Erlangen; R. Hoffmann, Abteilung für Gastroenterologie, Städtische Krankenanstalten, Esslingen; J. Holtz and K. Plein, Klinik für Gastroenterologie, Allgemeines Krankenhaus Celle, Celle; P. Otto and A. Thilo, Abteilung für Innere Medizin, Kreiskrankenhaus Groβburgwedel, Burgwedel; A. Raedler, Medizinische Klinik, Universitätskrankenhaus Eppendorf, Hamburg; H. Jenss and B. Kaskas, Abteilung Innere Medizin I, Medizinische Universitätsklinik, Tübingen; I. Koop and M. Frank, Abteilung Gastroenterologie, Klinikum Lahnberge, Marburg; K. Loeschke, Medizinische Klinik Innenstadt der LMU, München; W. Dotzel, Abteilung Gastroenterologie, Städtische Kliniken, Darmstadt; C. Scheurlen, I. Medizinische Klinik der Universität Bonn, Bonn; V. Gross and I. Caesar, Medizinische Klinik I, Klinikum der Universität, Regensburg; A. Reissmann, Klinik und Poliklinik für Innere Medizin I, Martin-Luther-Universität, Halle; B. A. Volk, Medizinische Klinik der Universität, Freiburg; J. Körber, Medizinische Klinik, Charité Campus Virchow-Klinikum, Berlin; H. Lorenz-Meyer, Medizinische Klinik, Städtisches Krankenhaus, Friedrichshafen; B. May and A. Tromm, Klinik Bergmannsheil, Bochum; E. Stange and S. Schwarting, Medizinische Klinik, Universität Lübeck, Lübeck; J. Emmrich and A. Schwager, Klinik für Innere Medizin, Universität Rostock, Rostock; H. Bossekert, Klinik für Innere Medizin I, Universität Jena, Jena. Denmark: P. Broebech Mortensen and Michael Staun, Med. Gastroenterol. afd. A 2101, Rigshospitalet, Copenhagen; S. N. Rasmussen and Jan Fallingborg, Med. Gastroenterol. Afd. M, Ålborg Sygehus Syd, Ålborg; Lone Astrup and F. Bendtsen, Med. afd V, Århus Universitetshospital, Kommunehospitalet, Århus; Ellinor Hylander Møller, Roskilde Amts Sygehus Køge, Med. Dept. C-3, Køge; Ole Østergaard Thomsen and O. H. Nielsen, Med. Gastroenterol. Afd. C, Amtssygehuset i Herlev, Herlev. Sweden: M. Bohe and C. Benoni, Kirurgkliniken, Malmö Allmänna Sjukhus, Malmö. Norway: Lars Birger Nesje and A. Berstad, Division of Gastroenterology, Department of Medicine/Surgery, Haukeland University Hospital, Bergen. Switzerland: M. Cunningham, Departement de Gastroenterologie, Hôpital Cantonal Universitaire de Genève, Geneva; P. Netzer, J. Binek, and B. Hammer, Abteilung Gastroenterologie, Kantonsspital, St. Gallen. Industrial Cooperation: R. Gödde, Ferring Arzneimittel GmbH, Kiel, Germany; Ch. Guldberg, Ferring AS, Kopenhagen, Denmark.

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