Clinical trial NCT00571337: Stop Infliximab in Patients With Crohn's Disease
Official title: Prospective Study of Predictive Factors of Sustained Remission of Crohn's Disease After Stopping Infliximab
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Crohn Disease
Keywords: Stop infliximab.
Lead sponsor: Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives
Sponsor class: OTHER
First posted: 2007-12-12
Enrollment: 126
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: Time to relapse over one year
measure: Evaluation of demographic, clinical and endoscopic factors predictive of relapse of Crohn's disease after stopping infliximab, with univariate and multivariate analysis.
timeFrame: Factors influencing time to relapse over one year.
Secondary outcomes:
measure: Tolerance and safety of infliximab retreatment in patients experiencing a relapse.
timeFrame: Follow up over 4 months including 3 infliximab retreatment s.
measure: predictive factors of short term-relapse (<2 months) after stopping infliximab, in the follow up of the patients.
timeFrame: at least 12 month and a maximum of 18 months.
measure: 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.
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Gent
country: Belgium
facility: Gent University Hospital
city: Liege
country: Belgium
facility: CHU LIEGE - Sart Tilman
city: Amiens
country: France
facility: Chu Amiens
city: Besancon
country: France
facility: Chu Besancon
city: Bordeaux
country: France
facility: Hopital Saint Andre
city: Caen
country: France
facility: CHU CAEN
city: Clichy
country: France
facility: Hopital Beaujon
city: Colombes
country: France
facility: Hopital Louis Mourier
city: Creteil
country: France
facility: Hopital Henri Mondor
city: Lille
country: France
facility: CHRU Lille
city: Marseille
country: France
facility: Chu Marseille - Hopital Nord
city: Montfermeil
country: France
facility: Ch Le Raincy Montfermeil
city: Montpellier
country: France
facility: Chu Montpellier
city: Nantes
country: France
facility: Chu Nantes
city: Paris
country: France
facility: Hopital Lariboisiere
city: Paris
country: France
facility: Hopital Saint Louis
city: Paris
country: France
facility: Hopital Georges Pompidou
city: Pessac
country: France
facility: Hopital Haut Leveque
city: Pierre Benite
country: France
facility: CHU LYON
city: Rouen
country: France
facility: Chu Rouen
city: Strasbourg
country: France
facility: Chu Strasbourg
city: Toulouse
country: France
facility: Chu Toulouse
city: Tours
country: France
facility: Chu Tours
Study officials:
affiliation: Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives
name: Louis Edouard, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.