Drug MonitoringProa-DQNCT05986903
Influence of HLA-DQA1*05 Genotype in Adults With Anti-TNF Treatment With Proactive Therapeutic Drug Monitoring.
An observational study of Drug Monitoring and Inflammatory Bowel Diseases, run by Hospital del Rio Hortega at 1 site in Spain.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Drug Monitoring, Inflammatory Bowel Diseases
- What is being tested?
- Tumor necrosis factor (TNF)-alpha inhibitors
- How many people
- 280 participants
- Where
- 1 siteSpain
- Study dates
- 11 Jan 2023to 1 Jan 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Spain1 site, 1 recruiting
- Recruiting
Hospital Universitario Rio Hortega
Valladolid
Esteban Fuentes-Valenzuela
About this study
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.
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.
Read the 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
- Being tested
- Tumor necrosis factor (TNF)-alpha inhibitors
- Keywords
- proactive therapeutic drug monitoring, HLA-DQA1*05 genotype, Anti-TNF
- Medical subject headings
- Inflammatory Bowel Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tumor necrosis factor (TNF)-alpha inhibitorsDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| HLA-DQA1*05 variant carriers | Not described Receives: Drug: Tumor necrosis factor (TNF)-alpha inhibitors | |
| HLA-DQA1*05 non-carriers | Not described Receives: Drug: Tumor necrosis factor (TNF)-alpha inhibitors |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Week 54
Secondary outcomes (7)
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
Measured: week 12
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
Measured: 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
Measured: 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
Measured: week 54
Proportions of primary failure between both groups
Measured: 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.
Measured: 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.
Measured: week 54
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2023
- Study start11 Jan 2023
- Primary completion1 Feb 2024 (estimated)
- Study completion1 Jan 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Drug MonitoringStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 280 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospital del Rio Hortega
- Sponsor type
- University, hospital or other
- Collaborators
- Francisco Javier Garcia Alonso, Jesús Barrio
- Responsible party
- Principal investigator, Esteban Fuentes-Valenzuela, Hospital del Rio Hortega
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05986903
- Sponsor's protocol ID
- 22-EO033
- Acronym
- Proa-DQ
- Status last verified
- Aug 2023
- First submitted
- 1 May 2023
- Last updated
- 14 Aug 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT05986903
- Acronym / sponsor ID
- Proa-DQ / 22-EO033
- Conditions
- Drug Monitoring, Inflammatory Bowel Diseases
- Keywords
- proactive therapeutic drug monitoring, HLA-DQA1*05 genotype, Anti-TNF
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 280 participants (estimated)
- Lead sponsor
- Hospital del Rio HortegaUniversity, hospital or other
- Collaborators
- Francisco Javier Garcia Alonso, Jesús Barrio
- Study start
- 11 Jan 2023 (actual)
- Primary completion
- 1 Feb 2024 (estimated)
- Study completion
- 1 Jan 2025 (estimated)
- First posted
- 14 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HLA-DQA1*05 variant carriers | – | Drug: Tumor necrosis factor (TNF)-alpha inhibitors |
| HLA-DQA1*05 non-carriers | – | Drug: Tumor necrosis factor (TNF)-alpha inhibitors |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tumor necrosis factor (TNF)-alpha inhibitorsProactive 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. | Drug | HLA-DQA1*05 non-carriers, HLA-DQA1*05 variant carriers |
Primary outcome
Corticosteroid-free clinical remission and treatment maintenance at week 54
Time frame: 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
7 secondary outcomes
Corticosteroid-free clinical response and remission at week 12.
Time frame: week 12
Proportions of patients with ultrasound remission at week 12 and 24
Time frame: week 12 and 24
Proportions of patients with clinical-biochemical remission at week 54.
Time frame: week 54
Proportions of endoscopic remission at week 54 between both groups.
Time frame: week 54
Proportions of primary failure between both groups
Time frame: week 12
To compare drug levels at week 6 (infliximab) and week 4 (adalimumab) in subjects with a standard induction
Time frame: week 4 or 6
Proportion of subjects with anti-drug antibodies at the end of induction and week 54.
Time frame: week 54
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2023.
Related trials for Drug Monitoring
Enrolling by invitationPhase 4
MOdel-Informed Precision Dosing of Ustekinumab and VEdolizumab in Inflammatory Bowel Disease
Inflammatory Bowel Diseases, Crohn Disease
Not yet recruitingObservational study
Monitoring and Rehabilitation for ICIACI Rehabilitation：A Cohort Study
Immune Checkpoint Inhibitor-Related Myocarditis
Not yet recruitingObservational study
Non-Invasive Biomarker Monitoring in UC on Biologics
Ulcerative Colitis
Active, not recruitingPhase 2
MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
Mucopolysaccharidosis Disorders, Hurler Syndrome
Not yet recruiting
Agentic AI App and Home Bioimpedance Monitoring for Endocrine Therapy Adherence and Lymphedema in Breast Cancer Survivors
Breast Neoplasm Malignant Primary, Lymphedema Arm
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Drug Monitoring and Inflammatory Bowel Diseases, run by Hospital del Rio Hortega at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 14 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Esteban Fuentes-Valenzuela, MD (+34 983 42 04 00, estebanfuentes_2@hotmail.co), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Corticosteroid-free clinical remission and treatment maintenance at week 54 (time frame: Week 54). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2023.