Therapeutic Monitoring of Infliximab and Adalimumab

Sponsor

IRCCS Burlo Garofolo (Other)

Overall Status

Recruiting

CT.gov ID

NCT06033469

Collaborator

(none)

100

Enrollment

Location

Anticipated Duration (Months)

1.4

Patients Per Site Per Month

Study Details

Study Description

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:

validate the "point of care" infliximab assay by comparing it with reference ELISA assays;
evaluate the correlation of infliximab and AAF levels, as measured by the innovative ELISA assays, with response to therapy, compared to traditional assays.
evaluate the association between adalimumab and AAF levels and response to therapy

Condition or Disease	Intervention/Treatment	Phase
Inflammatory Bowel Diseases	Drug: Infliximab Drug: Adalimumab

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:

to validate the "point of care" infliximab assay by comparing it with reference ELISA assays in pediatric patients with IBD;
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.
to evaluate the association between adalimumab and AAF levels and response to therapy in pediatric patients with IBD.

Study Design

Study Type:

Observational

Anticipated Enrollment :

100 participants

Observational Model:

Other

Time Perspective:

Prospective

Official Title:

Therapeutic Monitoring of Infliximab and Adalimumab in Pediatric Chronic Inflammatory Diseases: Innovative Pharmacological Strategies for Predicting Response and Adverse Effects

Actual Study Start Date :

Mar 15, 2018

Anticipated Primary Completion Date :

Apr 15, 2024

Anticipated Study Completion Date :

Apr 15, 2024

Arms and Interventions

Arm	Intervention/Treatment
IBD group Pediatric patients with IBD	Drug: Infliximab Pediatric patients with IBD suitable for treatment with infliximab Drug: Adalimumab Pediatric patients with IBD suitable for treatment with adalimumab

Arm

Intervention/Treatment

IBD group

Pediatric patients with IBD

Drug: Infliximab

Pediatric patients with IBD suitable for treatment with infliximab

Drug: Adalimumab

Pediatric patients with IBD suitable for treatment with adalimumab

Outcome Measures

Primary Outcome Measures

Infliximab concentration [Through study completion, an average of 5 years]
Assessed with the point-of-care assay and with the ELISA assay
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
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