Stop Infliximab in Patients With Crohn's Disease (STORI)

Prospective Study of Predictive Factors of Sustained Remission of Crohn's Disease After Stopping Infliximab

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).

Study Overview

• Status: Completed
• Conditions: Crohn Disease
• Intervention / Treatment: Drug: Infliximab

• Study Type: Interventional
• Enrollment (Actual): 126
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Gent, Belgium, 9000
    • Gent University Hospital
  • Liege, Belgium, 4000
    • CHU Liège - Sart Tilman
• France
  • Amiens, France, 80054
    • CHU Amiens
  • Besancon, France, 25030
    • CHU Besançon
  • Bordeaux, France, 33075
    • Hopital Saint André
  • Caen, France, 14033
    • CHU Caen
  • Clichy, France, 92110
    • Hopital Beaujon
  • Colombes, France, 92700
    • Hôpital Louis Mourier
  • Creteil, France, 94010
    • Hopital Henri Mondor
  • Lille, France
    • CHRU Lille
  • Marseille, France, 13915
    • Chu Marseille - Hopital Nord
  • Montfermeil, France, 93370
    • Ch Le Raincy Montfermeil
  • Montpellier, France, 34295
    • CHU Montpellier
  • Nantes, France, 44093
    • CHU Nantes
  • Paris, France, 75010
    • Hopital Saint Louis
  • Paris, France, 75010
    • Hôpital Lariboisière
  • Paris, France, 75015
    • Hopital Georges Pompidou
  • Pessac, France, 33604
    • Hopital Haut Lévêque
  • Pierre Benite, France, 69495
    • Chu Lyon
  • Rouen, France, 76031
    • CHU Rouen
  • Strasbourg, France, 67091
    • CHU Strasbourg
  • Toulouse, France, 31403
    • CHU Toulouse
  • Tours, France, 37044
    • CHU Tours

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• 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.

Exclusion criteria:

• 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 active perianal disease at the time of inclusion.
• Patient with stoma.
• Patient with debilitating extra-intestinal manifestation at the time of inclusion.
• Non cooperating subjects.
• Pregnant or lactating women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives
• Investigators: Principal Investigator: Louis Edouard, PhD, Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2005
• Primary Completion (Actual): July 1, 2010
• Study Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: July 25, 2007
• First Submitted That Met QC Criteria: December 11, 2007
• First Posted (Estimate): December 12, 2007

Study Record Updates

• Last Update Posted (Estimate): July 23, 2010
• Last Update Submitted That Met QC Criteria: July 22, 2010
• Last Verified: July 1, 2010

More Information

Terms related to this study

• Keywords: Stop infliximab.
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease; Antirheumatic Agents; Gastrointestinal Agents; Dermatologic Agents; Infliximab
• Other Study ID Numbers: GETAID 2005-1