Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT06033469 |
| Other study ID # |
RC 01/17 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
March 15, 2018 |
| Est. completion date |
June 30, 2024 |
Study information
| Verified date |
September 2023 |
| Source |
IRCCS Burlo Garofolo |
| Contact |
Giuliana Decorti, MD |
| Phone |
+390403785111 |
| Email |
giuliana.decorti[@]burlo.trieste.it |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Anti tumor necrosis factor (TNF agents), particularly infliximab and adalimumab, changed the
way chronic inflammatory bowel disease (IBD) refractory to conventional therapies is treated,
including in pediatric patients. However, approximately 10-30% of patients do not respond to
initial therapy and up to 50% lose response over time. Variability in response to therapy may
be influenced by multiple interacting factors at different levels. Recent studies showed that
measurement of serum infliximab concentrations during induction therapy predicts treatment
effects at one year. Therefore, therapeutic monitoring of infliximab is proposed as a useful
strategy to improve clinical outcomes and optimize healthcare resources.
Most commercially available methods for infliximab quantification are based on the ELISA
assay, which has an assay time of at least 8 hours. Recently, commercial point-of-care
devices became available with assay times of less than one hour, enabling real-time
therapeutic drug monitoring; however, validation of these devices in clinical settings and
comparison with standard assays are still needed, particularly in pediatric patients. In
addition, some studies suggest that loss of response in patients treated with anti-TNFs may
be partly due to the emergence of specific anti-drug antibodies (AAFs). A limitation of the
most widely used ELISA assays is the inability to quantify drug and AAF when they are
simultaneously present. Recently, innovative ELISA assays have become available to overcome
this problem. However, there is a lack of comparative studies between the classical and the
specific method in terms of clinical response in pediatric patients. In patients who do not
respond to infliximab, especially if they have high levels of AAF, guidelines call for the
use of adalimumab. For this drug, the evidence in the literature regarding therapeutic
monitoring of adalimumab concentrations and association with response in pediatric patients
is still very preliminary. This study, carried out in in pediatric patients with IBD, aims
to:
1. validate the "point of care" infliximab assay by comparing it with reference ELISA
assays;
2. evaluate the correlation of infliximab and AAF levels, as measured by the innovative
ELISA assays, with response to therapy, compared to traditional assays.
3. evaluate the association between adalimumab and AAF levels and response to therapy
Description:
Anti-TNF agents, particularly infliximab and adalimumab, changed the way chronic inflammatory
bowel disease (IBD) refractory to conventional therapies is treated, including in pediatric
patients. These biologic agents also appear promising as first-line treatment even in the
early stages of the disease. However, approximately 10-30% of patients do not respond to
initial therapy and up to 50% lose response over time. In addition, the widespread use of
these drugs is limited by serious side effects and the high cost of therapy. Variability in
response to therapy may be influenced by multiple interacting factors at different levels.
Recent studies showed that measurement of serum infliximab concentrations during induction
therapy predicts treatment effects at one year: in particular, patients with infliximab
concentrations below 3 ug/ml at the end of induction (pre-dose IV infusion) have a reduced
probability of response. Therefore, therapeutic monitoring of infliximab is proposed as a
useful strategy to improve clinical outcomes and optimize healthcare resources.
Currently, most commercially available methods for infliximab quantification are based on the
ELISA assay, which has an assay time of at least 8 hours, delaying therapeutic adjustment to
the next drug infusion. Recently, commercial point-of-care devices became available with
assay times of less than one hour, enabling real-time therapeutic drug monitoring; however,
validation of these devices in clinical settings and comparison with standard assays are
still needed, particularly in pediatric patients. In addition, some studies suggest that loss
of response in patients treated with anti-TNFs, infliximab and adalimumab, may be partly due
to the emergence of specific anti-drug antibodies (AAFs). A limitation of the most widely
used ELISA assays is the inability to quantify drug and AAF when they are simultaneously
present. Data from the literature suggest that in patients who lose response to anti-TNFs,
classical ELISA assays may overestimate the percentage of patients with low levels of both
drug and AAF; the use of specific ELISA assays allows accurate quantification of drug and AAF
levels even in these patients, allowing the clinician to modify therapy accordingly.
Recently, innovative ELISA assays have become available to overcome this problem. However,
there is a lack of comparative studies between the classical and the specific method in terms
of clinical response in pediatric patients. In patients who do not respond to infliximab,
especially if they have high levels of AAF, guidelines call for the use of adalimumab. For
this drug, the evidence in the literature regarding therapeutic monitoring of adalimumab
concentrations and association with response in pediatric patients is still very preliminary.
Thus, the research objectives are three, of equal importance:
1. to validate the "point of care" infliximab assay by comparing it with reference ELISA
assays in pediatric patients with IBD;
2. to evaluate the correlation of infliximab and AAF levels, as measured by the above
innovative ELISA assays, with response to therapy, compared to traditional assays, in
pediatric patients with IBD.
3. to evaluate the association between adalimumab and AAF levels and response to therapy in
pediatric patients with IBD.
