Use of Combined Measurements of Serum Infliximab and Anti-infliximab Antibodies in the Treatment of Patients With Crohns Disease Failing Infliximab Therapy

NCT ID: NCT00851565

Last Updated: 2011-11-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-06-30

Study Completion Date

2014-02-28

Brief Summary

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To compare treatment outcome in patients with Crohn's disease with secondary loss of response to infliximab (i.e. initial good response follow by loss of response) treated according to current standards based only on clinical features versus treatment based on serum levels of infliximab and anti-infliximab antibody (Ab) status.

Detailed Description

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Conditions

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Crohn's Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants

Study Groups

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1

Patients with Crohn's disease with secondary loss of response to infliximab.

Group Type ACTIVE_COMPARATOR

Measurement of serum infliximab and anti-infliximab antibodies

Intervention Type PROCEDURE

In the intervention group treatment of patients with Crohn's disease with secondary loss of response to infliximab is based on serum infliximab and anti-infliximab Ab levels according to following algorithm:

1. Low s-infliximab in the presence of anti-infliximab Ab: Adalimumab 80 mg s.c. followed by 40 mg every 2 weeks.
2. Low s-infliximab without anti-infliximab Ab: Infliximab 10 mg/kg i.v. every 8 weeks.
3. High s-infliximab without anti-infliximab Ab: Stop infliximab treatment. Review history. Steroids or surgery.
4. High s-infliximab in the presence of anti-infliximab Ab: Same as number 3.

2

Patients with Crohn's disease with secondary loss of response to infliximab.

Group Type ACTIVE_COMPARATOR

Treatment according to current standards without knowledge of serum infliximab and anti-infliximab Ab status

Intervention Type PROCEDURE

In the control group patients with Crohn's disease with secondary loss of response to infliximab is treated according to current standard of care which is to increase dose of infliximab to 5 mg/kg every 4 weeks without knowledge of serum infliximab levels and anti-infliximab Ab status.

Interventions

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Measurement of serum infliximab and anti-infliximab antibodies

In the intervention group treatment of patients with Crohn's disease with secondary loss of response to infliximab is based on serum infliximab and anti-infliximab Ab levels according to following algorithm:

1. Low s-infliximab in the presence of anti-infliximab Ab: Adalimumab 80 mg s.c. followed by 40 mg every 2 weeks.
2. Low s-infliximab without anti-infliximab Ab: Infliximab 10 mg/kg i.v. every 8 weeks.
3. High s-infliximab without anti-infliximab Ab: Stop infliximab treatment. Review history. Steroids or surgery.
4. High s-infliximab in the presence of anti-infliximab Ab: Same as number 3.

Intervention Type PROCEDURE

Treatment according to current standards without knowledge of serum infliximab and anti-infliximab Ab status

In the control group patients with Crohn's disease with secondary loss of response to infliximab is treated according to current standard of care which is to increase dose of infliximab to 5 mg/kg every 4 weeks without knowledge of serum infliximab levels and anti-infliximab Ab status.

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

1. Patient must be able to understand the information given to him/her and give written informed consent.
2. Definitive diagnosis of Crohn's disease (confirmed by recent radiological, endoscopic and/or histological evidence according to international criteria) .
3. Age minimum 18 years.
4. Previous good response to at least 3 doses (5mg/kg) of infliximab (as judged by the treating physician).
5. Loss of response to standard doses of infliximab (as judged by the treating physician).
6. Last infliximab infusion given at least 4 weeks before inclusion.
7. For patients with luminal disease, the CDAI should be above 220 points at inclusion.
8. For patients with fistulising disease only, at least one draining perianal fistula (confirmed by radiography, MR, ultrasound or physical examination) should be present.

Exclusion Criteria

1. Any contraindication to continued infliximab treatment
2. Short bowel syndrome
3. Bowel resection within 12 weeks of inclusion.
4. Current or recent history of severe, progressive, and/or uncontrolled renal, hepatic, haematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological, or cerebral disease.
5. Pregnancy
6. History of alcohol or drug abuse within the prior year
7. Patients who do not meet concomitant medication criteria.
8. Any other condition, which in the Investigator's judgment would make the patient unsuitable for inclusion in the study.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Aase and Ejnar Danielsens Foundation

OTHER

Sponsor Role collaborator

Beckett Foundation

OTHER

Sponsor Role collaborator

the Danish Biotechnology Program

UNKNOWN

Sponsor Role collaborator

Colitis-Crohn Foreningen

OTHER

Sponsor Role collaborator

Danish Medical Association

OTHER

Sponsor Role collaborator

Frode V. Nyegaard and wife's Foundation

UNKNOWN

Sponsor Role collaborator

Health Science Research Foundation of Region of Copenhagen

UNKNOWN

Sponsor Role collaborator

Herlev Hospital Research Council

UNKNOWN

Sponsor Role collaborator

Lundbeck Foundation

OTHER

Sponsor Role collaborator

P. Carl Petersens Fund

OTHER

Sponsor Role collaborator

Biomonitor A/S

UNKNOWN

Sponsor Role collaborator

Prometheus Inc.

INDUSTRY

Sponsor Role collaborator

The Danish Institute for Health Services Research

UNKNOWN

Sponsor Role collaborator

Copenhagen University Hospital at Herlev

OTHER

Sponsor Role lead

Responsible Party

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Department of Medical Gastroenterology, Copenhagen University Hospital Herlev

Principal Investigators

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Mark Ainsworth, M.D., Ph.D. DMSci

Role: PRINCIPAL_INVESTIGATOR

Locations

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Dept of Medical Gastroenterology, Ålborg University Hospital

Aalborg, , Denmark

Site Status

Dept of Hepatology and Medical Gastroenterology, Århus University Hospital

Aarhus, , Denmark

Site Status

Institute for Inflammation Research, Copenhagen University Hospital, Rigshospitalet

Copenhagen, , Denmark

Site Status

Esbjerg Hospital

Esbjerg, , Denmark

Site Status

Herlev University Hospital

Herlev, , Denmark

Site Status

Department of Gastroenterology, Hvidovre University Hospital

Hvidovre, , Denmark

Site Status

Department of Medical Gastroenterology, Køge University Hospital

Køge, , Denmark

Site Status

Dept of Medical Gastroenterology, Odense University Hospital

Odense, , Denmark

Site Status

Countries

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Denmark

References

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Ainsworth MA, Bendtzen K, Brynskov J. Tumor necrosis factor-alpha binding capacity and anti-infliximab antibodies measured by fluid-phase radioimmunoassays as predictors of clinical efficacy of infliximab in Crohn's disease. Am J Gastroenterol. 2008 Apr;103(4):944-8. doi: 10.1111/j.1572-0241.2007.01638.x. Epub 2007 Nov 19.

Reference Type BACKGROUND
PMID: 18028512 (View on PubMed)

Bendtzen K, Ainsworth M, Steenholdt C, Thomsen OO, Brynskov J. Individual medicine in inflammatory bowel disease: monitoring bioavailability, pharmacokinetics and immunogenicity of anti-tumour necrosis factor-alpha antibodies. Scand J Gastroenterol. 2009;44(7):774-81. doi: 10.1080/00365520802699278.

Reference Type BACKGROUND
PMID: 19140087 (View on PubMed)

Bendtzen K, Geborek P, Svenson M, Larsson L, Kapetanovic MC, Saxne T. Individualized monitoring of drug bioavailability and immunogenicity in rheumatoid arthritis patients treated with the tumor necrosis factor alpha inhibitor infliximab. Arthritis Rheum. 2006 Dec;54(12):3782-9. doi: 10.1002/art.22214.

Reference Type BACKGROUND
PMID: 17133559 (View on PubMed)

Svenson M, Geborek P, Saxne T, Bendtzen K. Monitoring patients treated with anti-TNF-alpha biopharmaceuticals: assessing serum infliximab and anti-infliximab antibodies. Rheumatology (Oxford). 2007 Dec;46(12):1828-34. doi: 10.1093/rheumatology/kem261.

Reference Type BACKGROUND
PMID: 18032541 (View on PubMed)

Steenholdt C, Brynskov J, Thomsen OO, Munck LK, Christensen LA, Pedersen G, Kjeldsen J, Ainsworth MA. Implications of Infliximab Treatment Failure and Influence of Personalized Treatment on Patient-reported Health-related Quality of Life and Productivity Outcomes in Crohn's Disease. J Crohns Colitis. 2015 Nov;9(11):1032-42. doi: 10.1093/ecco-jcc/jjv139. Epub 2015 Aug 5.

Reference Type DERIVED
PMID: 26245216 (View on PubMed)

Steenholdt C, Bendtzen K, Brynskov J, Thomsen OO, Munck LK, Christensen LA, Pedersen G, Kjeldsen J, Ainsworth MA. Changes in serum trough levels of infliximab during treatment intensification but not in anti-infliximab antibody detection are associated with clinical outcomes after therapeutic failure in Crohn's disease. J Crohns Colitis. 2015 Mar;9(3):238-45. doi: 10.1093/ecco-jcc/jjv004. Epub 2015 Jan 9.

Reference Type DERIVED
PMID: 25576753 (View on PubMed)

Steenholdt C, Brynskov J, Thomsen OO, Munck LK, Fallingborg J, Christensen LA, Pedersen G, Kjeldsen J, Jacobsen BA, Oxholm AS, Kjellberg J, Bendtzen K, Ainsworth MA. Individualised therapy is more cost-effective than dose intensification in patients with Crohn's disease who lose response to anti-TNF treatment: a randomised, controlled trial. Gut. 2014 Jun;63(6):919-27. doi: 10.1136/gutjnl-2013-305279. Epub 2013 Jul 22.

Reference Type DERIVED
PMID: 23878167 (View on PubMed)

Other Identifiers

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01MA

Identifier Type: -

Identifier Source: org_study_id