Stop Infliximab in Patients With Crohn's Disease

NCT00571337 | Completed Phase 3

• 1 other identifier: GETAID 2005-1
• Study Type: interventional
• Target: 126
• Locations: 2 countries
• Sites: 23

Brief Summary

1 Project summary 1.1 Rational. Accent 1 study has demonstrated the superiority of Infliximab over placebo in a systematic treatment strategy of Crohn 's disease every 8 weeks during one year. However the optimal strategy beyond one year of treatment is not established. Particularly, the need for carrying on systematic treatment with infliximab in all the patients has not been demonstrated. 1.2 Primary objective. Determine factors associated with a low risk of clinical relapse after stopping infliximab in CD patients in remission (CDAI\<150) and regularly treated with infliximab for at least one year. 1.3 Main objective and main judgement criteria. Determine predictive factors for relapse within one year after stopping infliximab. Main judgement criteria is the clinical relapse after stopping infliximab. Clinical relapse is defined either by a CDAI\>250 or by a CDAI between 150 and 250 if this CDAI is confirmed over two consecutive weeks with an increase of at least 70 points over baseline for the two consecutive measures. 1.4 Secondary objectives and judgement criteria. Determine the time to-relapse Determine predictive factors for short-term relapse (\<2 months)after stopping infliximab. Determine response to infliximab retreatment in these patients. Determine tolerance to infliximab retreatment in these patients. Determine predictive factors for an absence of response to retreatment. Determine predictive factors for infliximab retreatment intolerance. Determine sustained response in the retreated patients. 1.5 Type of study Open-label prospective study of stopping regular treatment. Inclusion period: minimum one year, possibly prolonged to reach 100 patients. Patients will be followed up every two months for at least 18 months after stopping infliximab. 1.6 Justification of the number of patients Number of patients to include is at least 100. This recruitment should be reached within one year. This number should allow to disclose predictive factors associated with a relative risk of at least 2 if this factor is equilibrated (50% at risk patients) or 3 is this factor is disequilibrated (90% at risk patients).

Conditions

Crohn Disease

Keywords

Stop infliximab.

Outcome Measures

Primary Outcomes (2)

• Relapse of Crohn's disease assessed by a CDAI > 250 or a CDAI between 150 and 250 at two consecutive weeks, with an increase of at least 70 points over baseline.

  Time to relapse over one year

• Evaluation of demographic, clinical and endoscopic factors predictive of relapse of Crohn's disease after stopping infliximab, with univariate and multivariate analysis.

  Factors influencing time to relapse over one year.

Secondary Outcomes (3)

• Tolerance and safety of infliximab retreatment in patients experiencing a relapse.

  Follow up over 4 months including 3 infliximab retreatment s.

• predictive factors of short term-relapse (<2 months) after stopping infliximab, in the follow up of the patients.

  at least 12 month and a maximum of 18 months.

• Clinical response to infliximab retreatment, assessed 4 weeks after retreatment using CDAI. A clinical response is defined by a 70 points drop (and at least 25%) as compared to relapse CDAI.

  4 weeks

Interventions

Infliximab DRUG

Stopping infliximab in patients having been treated with this drug for at least one year and in stable remission for at least 6 month.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Crohn's disease.
• Age \> 18 years.
• Patient written informed consent.
• Patient having been treated with infliximab for confirmed Crohn's disease with active intestinal lesions.
• Patient treated with infliximab for at least 1 year, associated with an immunosuppressor for at least one year, with a maximum interval between 2 infliximab infusions of 3 months.
• Patient with continuous remission without steroids for at least 6 months, except IV steroids for infusion reaction prophylaxis.
• CDAI\<150.
• Contraception all over the study.

You may not qualify if:

• Patient having experienced an severe acute infusion reaction to infliximab, defined by an anaphylactoïd reaction (drop in blood pressure, bronchospasm, dyspnea) requiring the arrest of the infliximab infusion.
• Patient having experienced a severe delayed infusion reaction to infliximab, defined by fever, arthralgia, myalgia, requiring a steroid treatment.
• Patient with dominant perianal disease and absence of active intestinal disease at the time of infliximab induction.
• Patient with stoma.
• Non cooperating subjects.
• Pregnant or lactating women.

Sponsors & Collaborators

• Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives: lead

Study Sites (23)

Gent University Hospital

Ghent, 9000, Belgium

Location

CHU LIEGE - Sart Tilman

Liège, 4000, Belgium

Location

Chu Amiens

Amiens, 80054, France

Location

Chu Besancon

Besançon, 25030, France

Location

Hopital Saint Andre

Bordeaux, 33075, France

Location

CHU CAEN

Caen, 14033, France

Location

Hopital Beaujon

Clichy, 92110, France

Location

Hopital Louis Mourier

Colombes, 92700, France

Location

Hopital Henri Mondor

Créteil, 94010, France

Location

CHRU Lille

Lille, France

Location

Chu Marseille - Hopital Nord

Marseille, 13915, France

Location

Ch Le Raincy Montfermeil

Montfermeil, 93370, France

Location

Chu Montpellier

Montpellier, 34295, France

Location

Chu Nantes

Nantes, 44093, France

Location

Hopital Lariboisiere

Paris, 75010, France

Location

Hopital Saint Louis

Paris, 75010, France

Location

Hopital Georges Pompidou

Paris, 75015, France

Location

Hopital Haut Leveque

Pessac, 33604, France

Location

CHU LYON

Pierre-Bénite, 69495, France

Location

Chu Rouen

Rouen, 76031, France

Location

Chu Strasbourg

Strasbourg, 67091, France

Location

Chu Toulouse

Toulouse, 31403, France

Location

Chu Tours

Tours, 37044, France

Location

Related Publications (9)

• Vermeire S, Louis E, Carbonez A, Van Assche G, Noman M, Belaiche J, De Vos M, Van Gossum A, Pescatore P, Fiasse R, Pelckmans P, Reynaert H, D'Haens G, Rutgeerts P; Belgian Group of Infliximab Expanded Access Program in Crohn's Disease. Demographic and clinical parameters influencing the short-term outcome of anti-tumor necrosis factor (infliximab) treatment in Crohn's disease. Am J Gastroenterol. 2002 Sep;97(9):2357-63. doi: 10.1111/j.1572-0241.2002.05991.x.

  PMID: 12358256 BACKGROUND

• Parsi MA, Achkar JP, Richardson S, Katz J, Hammel JP, Lashner BA, Brzezinski A. Predictors of response to infliximab in patients with Crohn's disease. Gastroenterology. 2002 Sep;123(3):707-13. doi: 10.1053/gast.2002.35390.

  PMID: 12198696 BACKGROUND

• Farrell RJ, Alsahli M, Jeen YT, Falchuk KR, Peppercorn MA, Michetti P. Intravenous hydrocortisone premedication reduces antibodies to infliximab in Crohn's disease: a randomized controlled trial. Gastroenterology. 2003 Apr;124(4):917-24. doi: 10.1053/gast.2003.50145.

  PMID: 12671888 BACKGROUND

• Baert F, Noman M, Vermeire S, Van Assche G, D' Haens G, Carbonez A, Rutgeerts P. Influence of immunogenicity on the long-term efficacy of infliximab in Crohn's disease. N Engl J Med. 2003 Feb 13;348(7):601-8. doi: 10.1056/NEJMoa020888.

  PMID: 12584368 BACKGROUND

• Tampo Y, Yonaha M. Antioxidant mechanism of Mn(II) in phospholipid peroxidation. Free Radic Biol Med. 1992;13(2):115-20. doi: 10.1016/0891-5849(92)90072-o.

  PMID: 1516837 BACKGROUND

• Parsi MA, Lashner BA. Safety of infliximab: primum non nocere. The safety profile of infliximab in patients with Crohn's disease: the Mayo Clinic experience in 500 patients. Inflamm Bowel Dis. 2004 Jul;10(4):486-7. doi: 10.1097/00054725-200407000-00028. No abstract available.

  PMID: 15475765 BACKGROUND

• Keane J, Gershon S, Wise RP, Mirabile-Levens E, Kasznica J, Schwieterman WD, Siegel JN, Braun MM. Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med. 2001 Oct 11;345(15):1098-104. doi: 10.1056/NEJMoa011110.

  PMID: 11596589 BACKGROUND

• Pierre N, Huynh-Thu VA, Baiwir D, Mazzucchelli G, Fleron M, Trzpiot L, Eppe G, De Pauw E, Laharie D, Satsangi J, Bossuyt P, Vuitton L, Vieujean S, Colombel JF, Meuwis MA, Louis E; GETAID and the SPARE-Biocycle research group. External validation of serum biomarkers predicting short-term and mid/long-term relapse in patients with Crohn's disease stopping infliximab. Gut. 2024 Nov 11;73(12):1965-1973. doi: 10.1136/gutjnl-2024-332648.

  PMID: 39134391 DERIVED

• Louis E, Mary JY, Vernier-Massouille G, Grimaud JC, Bouhnik Y, Laharie D, Dupas JL, Pillant H, Picon L, Veyrac M, Flamant M, Savoye G, Jian R, Devos M, Porcher R, Paintaud G, Piver E, Colombel JF, Lemann M; Groupe D'etudes Therapeutiques Des Affections Inflammatoires Digestives. Maintenance of remission among patients with Crohn's disease on antimetabolite therapy after infliximab therapy is stopped. Gastroenterology. 2012 Jan;142(1):63-70.e5; quiz e31. doi: 10.1053/j.gastro.2011.09.034. Epub 2011 Sep 22.

  PMID: 21945953 DERIVED

MeSH Terms

Conditions

Crohn Disease

Interventions

Infliximab

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Louis Edouard, PhD

  Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: July 25, 2007
• First Posted: December 12, 2007
• Study Start: December 1, 2005
• Primary Completion: July 1, 2010
• Study Completion: July 1, 2010
• Last Updated: July 23, 2010

Record last verified: 2010-07

Locations

FR (21); BE (2)