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

Study Overview
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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.

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

Conditions
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Crohn's Disease

Intervention / Treatment
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* Procedure: Measurement of serum infliximab and anti-infliximab antibodies
* Procedure: Treatment according to current standards without knowledge of serum infliximab and anti-infliximab Ab status


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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). Last infliximab infusion given at least 4 weeks before inclusion. For patients with luminal disease, the CDAI should be above 220 points at inclusion. 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: Any contraindication to continued infliximab treatment Short bowel syndrome Bowel resection within 12 weeks of inclusion. 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. Any other condition, which in the Investigator's judgment would make the patient unsuitable for inclusion in the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Patients with Crohn's disease with secondary loss of response to infliximab. | Procedure: Measurement of serum infliximab and anti-infliximab antibodies<br>* 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: Low s-infliximab in the presence of anti-infliximab Ab: Adalimumab 80 mg s.c. followed by 40 mg every 2 weeks. Low s-infliximab without anti-infliximab Ab: Infliximab 10 mg/kg i.v. every 8 weeks. High s-infliximab without anti-infliximab Ab: Stop infliximab treatment. Review history. Steroids or surgery. High s-infliximab in the presence of anti-infliximab Ab: Same as number 3.<br>|
| Active Comparator: 2<br>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<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Clinical response is defined as decrease of 70 in CDAI (luminal disease) or 50% reduction of active fistulas (fistulizing disease). | Week 4, 8, 20 | 
| Laboratory parameters | Change in laboratory parameters (hemoglobin, crp, albumin) from inclusion to week 12. | Week 12 | 
| Days with subjective feeling of disability due to Crohn's disease | Total number of days with subjective feelinhg of disability due to Crohn's disease from inclusion to week 12. | week 12 | 
| Serious adverse drug reactions | Total number of serious adverse drug reactions from inclusion to week 12. | week 12 | 
| Expenses related to Crohn's diseae at week 20 |  | week 20 | 
| 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 |  | week 12 and 20 |