Trial Outcomes & Findings for Biomarkers of Anti-TNF Treatment in Inflammatory Bowel Disease (IBD) (NCT NCT01971970)
NCT ID: NCT01971970
Last Updated: 2022-01-27
Results Overview
Pre-treatment serum level of endogenous anti-TNF are measured and analyzed in relation to primary clinical response or non-response
Recruitment status
COMPLETED
Target enrollment
45 participants
Primary outcome timeframe
8 weeks
Results posted on
2022-01-27
Participant Flow
Participant milestones
| Measure |
Pediatric IBD Patients
Anti-TNF naive patients with either Crohn's disease or ulcerative colitis will be treated with either Infliximab or Adalimumab
Infliximab: Remission induction in anti-TNF naïve patients will be achieved by administration of 5 mg/kg IFX infusions at week 0, 2 and 6.
Adalimumab: ADA is administered as subcutaneous injections every other week.In children (age below 18 years), remission induction in anti-TNF naïve patients will be achieved by an initial loading dose of 80 mg, followed by 40 mg 2 weeks later.
|
Adult IBD Patients
Anti-TNF naive patients with either Crohn's disease or ulcerative colitis will be treated with either Infliximab or Adalimumab
Infliximab: Remission induction in anti-TNF naïve patients will be achieved by administration of 5 mg/kg IFX infusions at week 0, 2 and 6.
Adalimumab: ADA is administered as subcutaneous injections every other week. In adults, remission is induced by 160 mg at week 0, followed by 80 mg at week 2
|
|---|---|---|
|
Baseline Until Week 6
STARTED
|
24
|
21
|
|
Baseline Until Week 6
Receiving Standard Therapy
|
23
|
21
|
|
Baseline Until Week 6
Therapy Escalation
|
1
|
0
|
|
Baseline Until Week 6
COMPLETED
|
23
|
21
|
|
Baseline Until Week 6
NOT COMPLETED
|
1
|
0
|
|
Week 6 Until Week 8
STARTED
|
23
|
21
|
|
Week 6 Until Week 8
Receiving Standard Therapy
|
23
|
20
|
|
Week 6 Until Week 8
COMPLETED
|
23
|
20
|
|
Week 6 Until Week 8
NOT COMPLETED
|
0
|
1
|
|
Week 8 Until Week 14
STARTED
|
23
|
20
|
|
Week 8 Until Week 14
Receiving Standard Therapy
|
16
|
19
|
|
Week 8 Until Week 14
Therapy Escalation
|
7
|
1
|
|
Week 8 Until Week 14
COMPLETED
|
23
|
20
|
|
Week 8 Until Week 14
NOT COMPLETED
|
0
|
0
|
|
Week 14 Until Week 22
STARTED
|
23
|
20
|
|
Week 14 Until Week 22
Receiving Standard Therapy
|
12
|
16
|
|
Week 14 Until Week 22
Therapy Escalation
|
3
|
2
|
|
Week 14 Until Week 22
COMPLETED
|
23
|
19
|
|
Week 14 Until Week 22
NOT COMPLETED
|
0
|
1
|
|
Week 22 Until Week 52
STARTED
|
23
|
19
|
|
Week 22 Until Week 52
Receiving Standard Therapy
|
5
|
9
|
|
Week 22 Until Week 52
Therapy Escalation
|
6
|
6
|
|
Week 22 Until Week 52
COMPLETED
|
15
|
15
|
|
Week 22 Until Week 52
NOT COMPLETED
|
8
|
4
|
|
Week 52 Until Week 78
STARTED
|
15
|
15
|
|
Week 52 Until Week 78
COMPLETED
|
14
|
12
|
|
Week 52 Until Week 78
NOT COMPLETED
|
1
|
3
|
Reasons for withdrawal
| Measure |
Pediatric IBD Patients
Anti-TNF naive patients with either Crohn's disease or ulcerative colitis will be treated with either Infliximab or Adalimumab
Infliximab: Remission induction in anti-TNF naïve patients will be achieved by administration of 5 mg/kg IFX infusions at week 0, 2 and 6.
Adalimumab: ADA is administered as subcutaneous injections every other week.In children (age below 18 years), remission induction in anti-TNF naïve patients will be achieved by an initial loading dose of 80 mg, followed by 40 mg 2 weeks later.
|
Adult IBD Patients
Anti-TNF naive patients with either Crohn's disease or ulcerative colitis will be treated with either Infliximab or Adalimumab
Infliximab: Remission induction in anti-TNF naïve patients will be achieved by administration of 5 mg/kg IFX infusions at week 0, 2 and 6.
Adalimumab: ADA is administered as subcutaneous injections every other week. In adults, remission is induced by 160 mg at week 0, followed by 80 mg at week 2
|
|---|---|---|
|
Baseline Until Week 6
Stopped anti-TNF use
|
1
|
0
|
|
Week 6 Until Week 8
Stopped anti-TNF use
|
0
|
1
|
|
Week 14 Until Week 22
Lost to Follow-up
|
0
|
1
|
|
Week 22 Until Week 52
Stopped anti-TNF use
|
7
|
3
|
|
Week 22 Until Week 52
Stopped anti-TNF use without escalation because of antibody-to-infliximab (ATI) formation
|
1
|
0
|
|
Week 22 Until Week 52
Stopped anti-TNF due to endoscopic improvement 1 year after start
|
0
|
1
|
|
Week 52 Until Week 78
Stopped anti-TNF use
|
1
|
3
|
Baseline Characteristics
Biomarkers of Anti-TNF Treatment in Inflammatory Bowel Disease (IBD)
Baseline characteristics by cohort
| Measure |
Pediatric IBD Patients
n=24 Participants
Anti-TNF naive patients with either Crohn's disease or ulcerative colitis will be treated with either Infliximab or Adalimumab
Infliximab: Remission induction in anti-TNF naïve patients will be achieved by administration of 5 mg/kg IFX infusions at week 0, 2 and 6.
Adalimumab: ADA is administered as subcutaneous injections every other week.In children (age below 18 years), remission induction in anti-TNF naïve patients will be achieved by an initial loading dose of 80 mg, followed by 40 mg 2 weeks later.
|
Adult IBD Patients
n=21 Participants
Anti-TNF naive patients with either Crohn's disease or ulcerative colitis will be treated with either Infliximab or Adalimumab
Infliximab: Remission induction in anti-TNF naïve patients will be achieved by administration of 5 mg/kg IFX infusions at week 0, 2 and 6.
Adalimumab: ADA is administered as subcutaneous injections every other week. In adults, remission is induced by 160 mg at week 0, followed by 80 mg at week 2
|
Total
n=45 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
Age at Diagnosis
|
13.24 years
n=5 Participants
|
25.34 years
n=7 Participants
|
15.47 years
n=5 Participants
|
|
Age, Continuous
Age at start anti-TNF
|
15.18 years
n=5 Participants
|
33.46 years
n=7 Participants
|
17.67 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
|
Diagnosis Crohn's Disease
|
16 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
32 Participants
n=5 Participants
|
|
Disease Duration at start of anti-TNF
|
1.025 years
n=5 Participants
|
5.97 years
n=7 Participants
|
1.69 years
n=5 Participants
|
|
Number of participants on Infliximab at start
|
23 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
41 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 8 weeksPopulation: The pre-treatment serum levels of endogenous anti-TNF were zero in all 11 adult patients in whom endogenous anti-TNF was measured. Therefore, pre-treatment serum level of endogenous anti-TNF could not be fully analyzed in relation to primary clinical response or non-response.
Pre-treatment serum level of endogenous anti-TNF are measured and analyzed in relation to primary clinical response or non-response
Outcome measures
| Measure |
Pediatric IBD Patients
Anti-TNF naive patients with either Crohn's disease or ulcerative colitis will be treated with either Infliximab or Adalimumab
Infliximab: Remission induction in anti-TNF naïve patients will be achieved by administration of 5 mg/kg IFX infusions at week 0, 2 and 6.
Adalimumab: ADA is administered as subcutaneous injections every other week.In children (age below 18 years), remission induction in anti-TNF naïve patients will be achieved by an initial loading dose of 80 mg, followed by 40 mg 2 weeks later. In adults, remission is induced by 160 mg at week 0, followed by 80 mg at week 2
|
Adult IBD Patients
n=11 Participants
Anti-TNF naive patients with either Crohn's disease or ulcerative colitis will be treated with either Infliximab or Adalimumab
Infliximab: Remission induction in anti-TNF naïve patients will be achieved by administration of 5 mg/kg IFX infusions at week 0, 2 and 6.
Adalimumab: ADA is administered as subcutaneous injections every other week.In children (age below 18 years), remission induction in anti-TNF naïve patients will be achieved by an initial loading dose of 80 mg, followed by 40 mg 2 weeks later. In adults, remission is induced by 160 mg at week 0, followed by 80 mg at week 2
|
Overall
Overall combined data for pediatric and adult IBD patients
|
|---|---|---|---|
|
Pre-treatment Serum Level of Endogenous Anti-TNF in Relation to Primary Clinical Response or Non-response
|
—
|
NA endogenous anti-TNF serum level (µg/mL)
below the level of detection
|
—
|
PRIMARY outcome
Timeframe: 8 weeksPopulation: Changes in week 0 and week 8 RNA expression profiles were analyzed within a subgroup of 29 patients (15 children and 14 adults) on infliximab treatment with samples taken at both week 0 and week 8. The number of genes with a 1.5 fold change (FDR value ≤ 0.05; paired t-test) from week 0 to week 8 were assessed for pediatric IBD or adult IBD patients.
Changes in week 0 and week 8 RNA expression profiles were evaluated in relation to the overall population and by study arm, i.e. either pediatric IBD or adult IBD.
Outcome measures
| Measure |
Pediatric IBD Patients
n=15 RNA expression profile samples
Anti-TNF naive patients with either Crohn's disease or ulcerative colitis will be treated with either Infliximab or Adalimumab
Infliximab: Remission induction in anti-TNF naïve patients will be achieved by administration of 5 mg/kg IFX infusions at week 0, 2 and 6.
Adalimumab: ADA is administered as subcutaneous injections every other week.In children (age below 18 years), remission induction in anti-TNF naïve patients will be achieved by an initial loading dose of 80 mg, followed by 40 mg 2 weeks later. In adults, remission is induced by 160 mg at week 0, followed by 80 mg at week 2
|
Adult IBD Patients
n=14 RNA expression profile samples
Anti-TNF naive patients with either Crohn's disease or ulcerative colitis will be treated with either Infliximab or Adalimumab
Infliximab: Remission induction in anti-TNF naïve patients will be achieved by administration of 5 mg/kg IFX infusions at week 0, 2 and 6.
Adalimumab: ADA is administered as subcutaneous injections every other week.In children (age below 18 years), remission induction in anti-TNF naïve patients will be achieved by an initial loading dose of 80 mg, followed by 40 mg 2 weeks later. In adults, remission is induced by 160 mg at week 0, followed by 80 mg at week 2
|
Overall
n=29 RNA expression profile samples
Overall combined data for pediatric and adult IBD patients
|
|---|---|---|---|
|
RNA Expression Profiles in Relation to Clinical Endpoints
|
180 Genes with 1.5 fold change (FDR value ≤
|
0 Genes with 1.5 fold change (FDR value ≤
|
523 Genes with 1.5 fold change (FDR value ≤
|
SECONDARY outcome
Timeframe: Duration of study (start anti-TNF until 1 year after start of anti-TNF)Clinical endpoints of Interest were the following: * Primary non-response was defined as no effect of anti-TNF after induction. * Remission and response were assessed at week 8 based on the appropriate disease activity scores for either children with Crohn's disease or ulcerative colitis (PCDAI and PUCAI respectively), or adults with Crohn's disease or ulcerative colitis (CDAI or Mayo score, respectively). * Continued use of anti-TNF was assessed 12 months and 18 months after start of anti-TNF.
Outcome measures
| Measure |
Pediatric IBD Patients
n=24 Participants
Anti-TNF naive patients with either Crohn's disease or ulcerative colitis will be treated with either Infliximab or Adalimumab
Infliximab: Remission induction in anti-TNF naïve patients will be achieved by administration of 5 mg/kg IFX infusions at week 0, 2 and 6.
Adalimumab: ADA is administered as subcutaneous injections every other week.In children (age below 18 years), remission induction in anti-TNF naïve patients will be achieved by an initial loading dose of 80 mg, followed by 40 mg 2 weeks later. In adults, remission is induced by 160 mg at week 0, followed by 80 mg at week 2
|
Adult IBD Patients
n=21 Participants
Anti-TNF naive patients with either Crohn's disease or ulcerative colitis will be treated with either Infliximab or Adalimumab
Infliximab: Remission induction in anti-TNF naïve patients will be achieved by administration of 5 mg/kg IFX infusions at week 0, 2 and 6.
Adalimumab: ADA is administered as subcutaneous injections every other week.In children (age below 18 years), remission induction in anti-TNF naïve patients will be achieved by an initial loading dose of 80 mg, followed by 40 mg 2 weeks later. In adults, remission is induced by 160 mg at week 0, followed by 80 mg at week 2
|
Overall
n=45 Participants
Overall combined data for pediatric and adult IBD patients
|
|---|---|---|---|
|
Number of Participants With Clinical Endpoints of Interest.
Primary non-response
|
1 Participants
|
1 Participants
|
2 Participants
|
|
Number of Participants With Clinical Endpoints of Interest.
Remission at week 8
|
15 Participants
|
15 Participants
|
30 Participants
|
|
Number of Participants With Clinical Endpoints of Interest.
Response at week 8
|
20 Participants
|
17 Participants
|
37 Participants
|
|
Number of Participants With Clinical Endpoints of Interest.
Continued anti-TNF after 12 months
|
15 Participants
|
15 Participants
|
30 Participants
|
|
Number of Participants With Clinical Endpoints of Interest.
Continued anti-TNF after 18 months
|
14 Participants
|
12 Participants
|
26 Participants
|
SECONDARY outcome
Timeframe: Duration of study (start anti-TNF until 1 year after start of anti-TNF)Anti-TNF treatment specific outcomes that were considered were: * Dose intensification; increase in dose of anti-TNF compared to standard therapy * Interval shortening; shortening of the interval of anti-TNFadministration compared to standard therapy. * Overall treatment intensification, the number of participants who underwent either dose intensification, interval shortening or both. * Development of Antibodies to infliximab during the course of follow-up * An infliximab serum trough level ≤ 3 mg/ml threshold (standard accepted therapeutic lower threshold) at week 14
Outcome measures
| Measure |
Pediatric IBD Patients
n=24 Participants
Anti-TNF naive patients with either Crohn's disease or ulcerative colitis will be treated with either Infliximab or Adalimumab
Infliximab: Remission induction in anti-TNF naïve patients will be achieved by administration of 5 mg/kg IFX infusions at week 0, 2 and 6.
Adalimumab: ADA is administered as subcutaneous injections every other week.In children (age below 18 years), remission induction in anti-TNF naïve patients will be achieved by an initial loading dose of 80 mg, followed by 40 mg 2 weeks later. In adults, remission is induced by 160 mg at week 0, followed by 80 mg at week 2
|
Adult IBD Patients
n=21 Participants
Anti-TNF naive patients with either Crohn's disease or ulcerative colitis will be treated with either Infliximab or Adalimumab
Infliximab: Remission induction in anti-TNF naïve patients will be achieved by administration of 5 mg/kg IFX infusions at week 0, 2 and 6.
Adalimumab: ADA is administered as subcutaneous injections every other week.In children (age below 18 years), remission induction in anti-TNF naïve patients will be achieved by an initial loading dose of 80 mg, followed by 40 mg 2 weeks later. In adults, remission is induced by 160 mg at week 0, followed by 80 mg at week 2
|
Overall
n=45 Participants
Overall combined data for pediatric and adult IBD patients
|
|---|---|---|---|
|
Anti-TNF Treatment Specific Outcomes
Overall treatment intensification
|
17 Participants
|
9 Participants
|
26 Participants
|
|
Anti-TNF Treatment Specific Outcomes
Dose intensification
|
14 Participants
|
4 Participants
|
18 Participants
|
|
Anti-TNF Treatment Specific Outcomes
Interval shortening
|
16 Participants
|
10 Participants
|
26 Participants
|
|
Anti-TNF Treatment Specific Outcomes
Antibodies to infliximab Development
|
4 Participants
|
3 Participants
|
7 Participants
|
|
Anti-TNF Treatment Specific Outcomes
Infliximab serum trough level ≤ 3 mg/ml at week 14
|
7 Participants
|
4 Participants
|
11 Participants
|
SECONDARY outcome
Timeframe: Duration of study (start anti-TNF until 1 year after start of anti-TNF)Number of participants with concommitant treatment during the study was assessed. Concomitant treatment was defined as: * Additional use of immunomodulators such as methotrexate or azathioprine were registered. * Need for systemic prednisone, for instance in the case of an exacerbation, was assessed.
Outcome measures
| Measure |
Pediatric IBD Patients
n=24 Participants
Anti-TNF naive patients with either Crohn's disease or ulcerative colitis will be treated with either Infliximab or Adalimumab
Infliximab: Remission induction in anti-TNF naïve patients will be achieved by administration of 5 mg/kg IFX infusions at week 0, 2 and 6.
Adalimumab: ADA is administered as subcutaneous injections every other week.In children (age below 18 years), remission induction in anti-TNF naïve patients will be achieved by an initial loading dose of 80 mg, followed by 40 mg 2 weeks later. In adults, remission is induced by 160 mg at week 0, followed by 80 mg at week 2
|
Adult IBD Patients
n=21 Participants
Anti-TNF naive patients with either Crohn's disease or ulcerative colitis will be treated with either Infliximab or Adalimumab
Infliximab: Remission induction in anti-TNF naïve patients will be achieved by administration of 5 mg/kg IFX infusions at week 0, 2 and 6.
Adalimumab: ADA is administered as subcutaneous injections every other week.In children (age below 18 years), remission induction in anti-TNF naïve patients will be achieved by an initial loading dose of 80 mg, followed by 40 mg 2 weeks later. In adults, remission is induced by 160 mg at week 0, followed by 80 mg at week 2
|
Overall
n=45 Participants
Overall combined data for pediatric and adult IBD patients
|
|---|---|---|---|
|
Number of Participants With Concommitant Treatment
Addition of immunomodulators
|
5 Participants
|
5 Participants
|
10 Participants
|
|
Number of Participants With Concommitant Treatment
Need for systemic prednisone
|
3 Participants
|
0 Participants
|
3 Participants
|
Adverse Events
Pediatric IBD Patients
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Adult IBD Patients
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Overall
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Professor J.C. Escher
Erasmus University Medical Centre - Sophia Childrens Hospital
Phone: +31107036076
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place