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| Name | Class |
|---|---|
| Francisco Javier Garcia Alonso | UNKNOWN |
| Jesús Barrio | UNKNOWN |
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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.
Population study: patients with inflammatory bowel disease and initiation of anti-TNF therapy
Inclusion and exclusion criteria
The inclusion criteria are:
The exclusion criteria are:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| HLA-DQA1*05 variant carriers |
| ||
| HLA-DQA1*05 non-carriers |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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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.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Esteban Fuentes-Valenzuela, MD | Contact | +34 983 42 04 00 | estebanfuentes_2@hotmail.co |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Universitario Rio Hortega | Recruiting | Valladolid | Spain |
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| ID | Term |
|---|---|
| D015212 | Inflammatory Bowel Diseases |
| ID | Term |
|---|---|
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D007410 | Intestinal Diseases |
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| ID | Term |
|---|---|
| D014409 | Tumor Necrosis Factor-alpha |
| ID | Term |
|---|---|
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D015846 | Monokines |
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|
| 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 |
| 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 |
| 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 |
| Proportions of primary failure between both groups | week 12 |
| 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 |
| 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 |
| D016207 |
| Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D048069 | Tumor Necrosis Factors |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D001685 | Biological Factors |