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

NCT00851565 | Unknown Phase 4 DMC

• 1 other identifier: 01MA
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 8

Brief Summary

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.

Conditions

Crohn's Disease

Outcome Measures

Primary Outcomes (2)

• Proportion of patients with response at week 12, i.e. CDAI decrease of 70 or more for patients with luminal disease, or reduction of 50 percent or more from base line in the number of draining fistulas for patients with fistulising disease.

  Clinical response rates at week 12 should be non-inferior in the intervention group as compared to the control group. Both primary end-points should be met in order to declare the primary end-points succesfully archived.

  12 weeks

• Total expenses related to Crohn's disease during the study (inclusion to week 12).

  Crohn related expenses at week 12 should be less in the intervention group as compared to the control group. Both primary end-points should be met in order to declare the primary end-points succesfully archived.

  12 weeks

Secondary Outcomes (10)

• Mean change compared to baseline in WPAI score at week 12.

  12 weeks

• Mean change compared to baseline in IBDQ score at week 12.

  12 weeks

• Mean change compared to baseline in CDAI score at week 4,8, 12,20.

  4, 8, 12, 20 weeks

• Mean change compared to baseline in PDAI score at week 4, 8, 12, and 20.

  4, 8, 12, 20 weeks

• Clinical response at week 4, 8, 20

  Week 4, 8, 20

Study Arms (2)

1

ACTIVE COMPARATOR

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

Procedure: Measurement of serum infliximab and anti-infliximab antibodies

2

ACTIVE COMPARATOR

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

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

Interventions

Measurement of serum infliximab and anti-infliximab antibodies 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.

1

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

2

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• Any contraindication to continued infliximab treatment
• Short bowel syndrome
• Current or recent history of severe, progressive, and/or uncontrolled renal, hepatic, haematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological, or cerebral disease.
• Pregnancy
• History of alcohol or drug abuse within the prior year
• Patients who do not meet concomitant medication criteria.

Sponsors & Collaborators

• Copenhagen University Hospital at Herlev: lead
• Aase and Ejnar Danielsens Foundation: collaborator
• Beckett Foundation: collaborator
• the Danish Biotechnology Program: collaborator
• Colitis-Crohn Foreningen: collaborator
• Danish Medical Association: collaborator
• Frode V. Nyegaard and wife's Foundation: collaborator
• Health Science Research Foundation of Region of Copenhagen: collaborator
• Herlev Hospital Research Council: collaborator
• Lundbeck Foundation: collaborator
• P. Carl Petersens Fund: collaborator
• Biomonitor A/S: collaborator
• Prometheus Inc.: collaborator
• The Danish Institute for Health Services Research: collaborator

Study Sites (8)

Dept of Medical Gastroenterology, Ålborg University Hospital

Aalborg, 9000, Denmark

Location

Dept of Hepatology and Medical Gastroenterology, Århus University Hospital

Aarhus, 8000, Denmark

Location

Institute for Inflammation Research, Copenhagen University Hospital, Rigshospitalet

Copenhagen, 2100, Denmark

Location

Esbjerg Hospital

Esbjerg, 6700, Denmark

Location

Herlev University Hospital

Herlev, 2730, Denmark

Location

Department of Gastroenterology, Hvidovre University Hospital

Hvidovre, 2650, Denmark

Location

Department of Medical Gastroenterology, Køge University Hospital

Køge, 4600, Denmark

Location

Dept of Medical Gastroenterology, Odense University Hospital

Odense, 5000, Denmark

Location

Related Publications (7)

• 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.

  PMID: 18028512 BACKGROUND

• 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.

  PMID: 19140087 BACKGROUND

• 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.

  PMID: 17133559 BACKGROUND

• 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.

  PMID: 18032541 BACKGROUND

• 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.

  PMID: 26245216 DERIVED

• 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.

  PMID: 25576753 DERIVED

• 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.

  PMID: 23878167 DERIVED

MeSH Terms

Conditions

Crohn Disease

Condition Hierarchy (Ancestors)

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

Study Officials

• Mark Ainsworth, M.D., Ph.D. DMSci

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: February 24, 2009
• First Posted: February 26, 2009
• Study Start: June 1, 2009
• Primary Completion: February 1, 2012
• Study Completion: February 1, 2014
• Last Updated: November 28, 2011

Record last verified: 2011-11

Locations

DK (8)