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

NCT05986903 | Unknown FDA Drug

• 1 other identifier: 22-EO033
• Study Type: observational
• Target: 280
• Locations: 1 country
• Sites: 1

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.

Conditions

Drug Monitoring; Inflammatory Bowel Diseases

Keywords

proactive therapeutic drug monitoring; HLA-DQA1*05 genotype; Anti-TNF

Outcome Measures

Primary Outcomes (1)

• Corticosteroid-free clinical remission and treatment maintenance at week 54

  Corticosteroid-free clinical remission was defined as Harvey Bradshaw score \<5 for Crohn's disease or partial Mayo score ≤2 for ulcerative colitis with no item exceeding one point, without corticosteroid

  Week 54

Secondary Outcomes (7)

• Corticosteroid-free clinical response and remission at week 12.

  week 12

• Proportions of patients with ultrasound remission at week 12 and 24

  week 12 and 24

• Proportions of patients with clinical-biochemical remission at week 54.

  week 54

• Proportions of endoscopic remission at week 54 between both groups.

  week 54

• Proportions of primary failure between both groups

  week 12

Study Arms (2)

HLA-DQA1*05 variant carriers

Drug: Tumor necrosis factor (TNF)-alpha inhibitors

HLA-DQA1*05 non-carriers

Drug: Tumor necrosis factor (TNF)-alpha inhibitors

Interventions

Tumor necrosis factor (TNF)-alpha inhibitors 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; HLA-DQA1*05 variant carriers

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hospital del Rio Hortega: lead
• Francisco Javier Garcia Alonso: collaborator
• Jesús Barrio: collaborator

Study Sites (1)

Hospital Universitario Rio Hortega

Valladolid, Spain

RECRUITING

MeSH Terms

Conditions

Inflammatory Bowel Diseases

Interventions

Tumor Necrosis Factor-alpha

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Glycoproteins; Glycoconjugates; Carbohydrates; Monokines; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Tumor Necrosis Factors; Blood Proteins; Proteins; Biological Factors

Central Study Contacts

Esteban Fuentes-Valenzuela, MD

CONTACT

+34 983 42 04 00; estebanfuentes_2@hotmail.co

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: May 1, 2023
• First Posted: August 14, 2023
• Study Start: January 11, 2023
• Primary Completion: February 1, 2024
• Study Completion: January 1, 2025
• Last Updated: August 14, 2023

Record last verified: 2023-08

Locations

ES (1)