NCT05986903

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

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.

• Status: Unknown
• Phase: —
• Study type: Observational
• Enrollment: 280 (estimated)
• Sponsor: Hospital del Rio Hortega · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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

Interventions

Type	Name	Description
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.

Timeline

• Start date: 2023-01-11
• Primary completion: 2024-02-01
• Completion: 2025-01-01
• First posted: 2023-08-14
• Last updated: 2023-08-14

Locations

1 site across 1 country: Spain

Regulatory

• FDA-regulated drug study