Therapeutic Monitoring of Infliximab and Adalimumab
- Registration Number
- NCT06033469
- Lead Sponsor
- IRCCS Burlo Garofolo
- Brief 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
- Detailed 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 100
- IBD subjects
- age between 0 and 17 years
- suitable for treatment with infliximab or adalimumab
- Pediatric subjects with IBD not suitable for treatment with infliximab or adalimumab
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description IBD group Infliximab Pediatric patients with IBD IBD group Adalimumab Pediatric patients with IBD
- Primary Outcome Measures
Name Time Method Response to therapy assessed with validated score Through study completion, an average of 5 years Assessed by Pediatric Crohn's disease activity index (PCDAI) and Pediatric UlcerativeColitis Activity Index (PUCAI). PCDAI ranges from 0 to 100; higher scores indicate more active disease. Clinical remission was defined as PCDAI ≤ 10. PUCAI score ranges from 0 to 85, with disease remission less than 10, mild disease activity between 10-35, moderate disease activity from 35-65, and severe disease activity above 65
Adalimumab concentration Through study completion, an average of 5 years Assessed with ELISA assay
AAF concentration Through study completion, an average of 5 years Assessed by the novel ELISA assays
Infliximab concentration Through study completion, an average of 5 years Assessed with the point-of-care assay and with the ELISA assay
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (3)
Ospedale Maggiore
🇮🇹Bologna, Italy
IRCCS Burlo Garofolo
🇮🇹Trieste, Italy
Ospedale Ca' Foncello
🇮🇹Treviso, Italy