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

Inflammatory Bowel Diseases Clinical Trial

— Proa-DQ  

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05986903
• Other study ID #: 22-EO033
• Status: Recruiting
• Start date: January 11, 2023
• Est. completion date: January 1, 2025

Study information

• Verified date: August 2023
• Source: Hospital del Río Hortega
• Contact: Esteban Fuentes-Valenzuela, MD
• Phone: +34 983 42 04 00
• Email: estebanfuentes_2[@]hotmail.co
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 280
• Est. completion date: January 1, 2025
• Est. primary completion date: February 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Drug Monitoring
• Inflammatory Bowel Diseases
• Intestinal Diseases

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
Spain	Hospital Universitario Rio Hortega	Valladolid

Sponsors (3)

Lead Sponsor	Collaborator
Hospital del Río Hortega	Francisco Javier Garcia Alonso, Jesús Barrio

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Corticosteroid-free clinical response and remission at week 12.	Corticosteroid-free clinical response was defined as Harvey Bradshaw score < 5 or a decrease = 3 points from baseline in Crohn's disease. For ulcerative colitis, a decrease in the partial Mayo Index of at least 3 points or 30% accompanied by a decrease in rectal bleeding by one point, without corticosteroid	week 12
Secondary	Proportions of patients with ultrasound remission at week 12 and 24	Ultrasound remission was defined as SUS-CD 0 for Crohn's disease or a bowel wall thickness < 2.1 mm for ulcerative colitis	week 12 and 24
Secondary	Proportions of patients with clinical-biochemical remission at week 54.	Clinical-biochemical remission was defined as CRP = 5 mg/L and fecal calprotectin < 150 mg/kg	week 54
Secondary	Proportions of endoscopic remission at week 54 between both groups.	For Crohn's disease endoscopic remission was defined as a SES-CD <3 points or absence of ulcerations (e.g. SES-CD ulceration subscores ¼ 0) For ulcerative colitis, a Mayo endoscopic subscore of 0 points, or UCEIS =1 points	week 54
Secondary	Proportions of primary failure between both groups		week 12
Secondary	To compare drug levels at week 6 (infliximab) and week 4 (adalimumab) in subjects with a standard induction	Drug monitoring at week 6 for infliximab and week 4 for adalimumab.	week 4 or 6
Secondary	Proportion of subjects with anti-drug antibodies at the end of induction and week 54.	Anti-infliximab and anti-adalimumab antibodies at week 4 for adalimumab, at week 6 for infliximab and at week 54 for both.	week 54