Clinical trial NCT05986903: Influence of HLA-DQA1*05 Genotype in Adults With Anti-TNF Treatment With Proactive Therapeutic Drug Monitoring.
Official title: 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.
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Drug Monitoring
Inflammatory Bowel Diseases
Keywords: proactive therapeutic drug monitoring
HLA-DQA1*05 genotype
Anti-TNF
Lead sponsor: Hospital del Rio Hortega
Sponsor class: OTHER
Collaborators: name: Francisco Javier Garcia Alonso
name: Jesús Barrio
First posted: 2023-08-14
Enrollment: 280
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with a diagnosis of inflammatory bowel disease (Crohn's disease, ulcerative colitis and indeterminate colitis), who require starting anti-TNF for the first time.

Brief summary: 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.

Detailed description: Population study: patients with inflammatory bowel disease and initiation of anti-TNF therapy

Inclusion and exclusion criteria

The inclusion criteria are:

* Patient diagnosed with inflammatory bowel disease based on clinical, endoscopic, and pathological criteria according to ECCO criteria.
* Initiation of anti-TNf, including infliximab and adalimumab.
* Subjects naïve to biological treatment
* Age \>18 years.

The exclusion criteria are:

* No determination of HLA DQA1\*5 allele.
* No proactive drug monitoring
* Initiation of anti-TNF treatment as prevention of post-surgical recurrence in Crohn's disease during the first 12 months after surgery or, after that time, with a colonoscopy with a Rutgeerts 0-1
* Anti-TNF treatment with combined treatment with immunomodulator. Prior initiation of immunomodulator or prior use and suspension would not be a contraindication
* Initiation of anti-TNF treatment for extraintestinal manifestation
* Initiation of anti-TNF treatment during pregnancy.

Proactive drug monitoring was defined as standardized determination of drug levels during induction and maintenance, with optimization independently of the patient's clinical status, until reaching target levels.

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.

Primary outcomes:
measure: Corticosteroid-free clinical remission and treatment maintenance at week 54
timeFrame: Week 54
Secondary outcomes:
measure: Corticosteroid-free clinical response and remission at week 12.
timeFrame: week 12
measure: Proportions of patients with ultrasound remission at week 12 and 24
timeFrame: week 12 and 24
measure: Proportions of patients with clinical-biochemical remission at week 54.
timeFrame: week 54
measure: Proportions of endoscopic remission at week 54 between both groups.
timeFrame: week 54
measure: Proportions of primary failure between both groups
timeFrame: week 12
measure: To compare drug levels at week 6 (infliximab) and week 4 (adalimumab) in subjects with a standard induction
timeFrame: week 4 or 6
measure: Proportion of subjects with anti-drug antibodies at the end of induction and week 54.
timeFrame: week 54
Other outcomes:
Locations:
city: Valladolid
country: Spain
facility: Hospital Universitario Rio Hortega
Study officials:
References: