Clinical trial
Influence of HLA-DQA1*05 Genotype in Adults With Inflammatory Bowel Disease and Anti-TNF Treatment With Proactive Therapeutic Drug Monitoring. A Prospective Multicenter Study.
Name
22-EO033
Description
HLA-DQA1\*05 variant carriers are at risk of developing antibodies against infliximab and adalimumab with reduced TNF antagonist persistence.
The impact of proactive therapeutic drug monitoring (PTDM) on this association has been barely assessed.
Therefor, we propose a cohort study including adult patients with Crohn's disease and ulcerative colitis treated with TNF antagonists under proactive therapeutic drug monitoring.
Our hypothesis is that, proactive therapeutic drug monitoring could be an alternative to combination treatment with immunomodulators to increase TNF-antagonists' persistence in HLA-DQA1\*05 carriers.
Trial arms
Trial start
2023-01-11
Estimated PCD
2024-02-01
Trial end
2025-01-01
Status
Recruiting
Treatment
Tumor necrosis factor (TNF)-alpha inhibitors
Proactive drug monitoring was defined as the assessment of trough concentrations to optimize dosing during induction therapy and intermittently thereafter regardless of symptoms or inflammatory markers.
During induction, the following target concentrations are employed: 25-30 mcg/ml (week 2) and 20 mcg/ml (week 6) for Infliximab and \> 10 mcg/ml (week 2 and 4) for Adalimumab. Checks are performed systematically at week 2 and 6 (infliximab) and at week 4 (adalimumab).
During the maintenance, the targets are 5-10 mcg/ml for Infliximab and 8-12 mcg/ml for Adalimumab. In case of perianal disease, the targets are 7-20 mcg/ml.
Arms:
HLA-DQA1*05 non-carriers, HLA-DQA1*05 variant carriers
Size
280
Primary endpoint
Corticosteroid-free clinical remission and treatment maintenance at week 54
Week 54
Eligibility criteria
Inclusion Criteria:
* Diagnosis of inflammatory bowel disease according to ECCO criteria.
* Older than 18 years
* Subjects naïve to biological treatment
* Anti-TNF treatment initiation (infliximab or adalimumab) due to intestinal activity and/or perianal disease.
* Avaibility to evaluate HLA DQA1\*05 status
* Proactive therapeutic drug monitoring of anti-TNF levels
Exclusion Criteria:
* Initiation of anti-TNF treatment as prevention of post-surgical recurrence in Crohn's disease during the first 12 months after surgery or, afterwards, if endoscopic recurrence with a Rutgeerts 0-1.
* Initiation of anti-TNF treatment under combo treatment with immunomodulator. Prior initiation of immunomodulator or prior use and suspension would not be a contraindication.
* Initiation of anti-TNF treatment due to extraintestinal activity.
* Initiation of anti-TNF treatment by a non-gastroenterologist specialist.
* Initiation of anti-TNF treatment during pregnancy.
Protocol
{'studyType': 'OBSERVATIONAL', 'patientRegistry': False, 'designInfo': {'observationalModel': 'COHORT', 'timePerspective': 'PROSPECTIVE'}, 'enrollmentInfo': {'count': 280, 'type': 'ESTIMATED'}}
Updated at
2023-08-14
1 organization
1 product
2 indications
Organization
Hospital del Rio HortegaIndication
Therapeutic Drug MonitoringIndication
Inflammatory Bowel Disease