Influence of HLA-DQA1*05 Genotype in Adults With Anti-TNF Treatment With Proactive Therapeutic Drug Monitoring.

NCT ID: NCT05986903

Last Updated: 2023-08-14

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 280 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-01-11
• Study Completion Date: 2025-01-01

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.

Conditions

Drug Monitoring; Inflammatory Bowel Diseases

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

HLA-DQA1*05 variant carriers

Tumor necrosis factor (TNF)-alpha inhibitors

Intervention Type: DRUG

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.

HLA-DQA1*05 non-carriers

Tumor necrosis factor (TNF)-alpha inhibitors

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Francisco Javier Garcia Alonso

UNKNOWN

Sponsor Role: collaborator

Jesús Barrio

UNKNOWN

Sponsor Role: collaborator

Hospital del Rio Hortega

OTHER

Sponsor Role: lead

Responsible Party

Esteban Fuentes-Valenzuela

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Hospital Universitario Rio Hortega

Valladolid, , Spain

Site Status: RECRUITING

Countries

Spain

Central Contacts

Esteban Fuentes-Valenzuela, MD

Role: CONTACT

estebanfuentes_2@hotmail.co

+34 983 42 04 00

Facility Contacts

Esteban Fuentes-Valenzuela

Role: primary

Other Identifiers

22-EO033

Identifier Type: -

Identifier Source: org_study_id