Clinical trial NCT00851565: Use of Combined Measurements of Serum Infliximab and Anti-infliximab Antibodies in the Treatment of Patients With Crohns Disease Failing Infliximab Therapy
Official title: Use of Combined Measurements of Serum Infliximab and Anti-infliximab Antibodies in the Treatment of Patients With Crohns Disease Failing Infliximab Therapy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Crohn's Disease
Lead sponsor: Copenhagen University Hospital at Herlev
Sponsor class: OTHER
Collaborators: name: Aase and Ejnar Danielsens Foundation
name: Beckett Foundation
name: the Danish Biotechnology Program
name: Colitis-Crohn Foreningen
name: Danish Medical Association
name: Frode V. Nyegaard and wife's Foundation
name: Health Science Research Foundation of Region of Copenhagen
name: Herlev Hospital Research Council
name: Lundbeck Foundation
name: P. Carl Petersens Fund
name: Biomonitor A/S
name: Prometheus Inc.
name: The Danish Institute for Health Services Research
First posted: 2009-02-26
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: 12 weeks
measure: Total expenses related to Crohn's disease during the study (inclusion to week 12).
timeFrame: 12 weeks
Secondary outcomes:
measure: Mean change compared to baseline in WPAI score at week 12.
timeFrame: 12 weeks
measure: Mean change compared to baseline in IBDQ score at week 12.
timeFrame: 12 weeks
measure: Mean change compared to baseline in CDAI score at week 4,8, 12,20.
timeFrame: 4, 8, 12, 20 weeks
measure: Mean change compared to baseline in PDAI score at week 4, 8, 12, and 20.
timeFrame: 4, 8, 12, 20 weeks
measure: Clinical response at week 4, 8, 20
timeFrame: Week 4, 8, 20
measure: Laboratory parameters
timeFrame: Week 12
measure: Days with subjective feeling of disability due to Crohn's disease
timeFrame: week 12
measure: Serious adverse drug reactions
timeFrame: week 12
measure: Expenses related to Crohn's diseae at week 20
timeFrame: week 20
measure: Expenses related to Crohn's disease compared to change in CDAI-score (luminal disease) or PDAI-score (fistulizing disease), and IBD-score at week 12 and 20
timeFrame: week 12 and 20
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Institute for Inflammation Research, Copenhagen University Hospital, Rigshospitalet
city: Esbjerg
country: Denmark
facility: Esbjerg Hospital
city: Herlev
country: Denmark
facility: Herlev University Hospital
city: Hvidovre
country: Denmark
facility: Department of Gastroenterology, Hvidovre University Hospital
city: Køge
country: Denmark
facility: Department of Medical Gastroenterology, Køge University Hospital
city: Odense
country: Denmark
facility: Dept of Medical Gastroenterology, Odense University Hospital
city: Ålborg
country: Denmark
facility: Dept of Medical Gastroenterology, Ålborg University Hospital
city: Århus
country: Denmark
facility: Dept of Hepatology and Medical Gastroenterology, Århus University Hospital
Study officials:
name: Mark Ainsworth, M.D., Ph.D. DMSci
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.