Study of Antibodies to Anti-TNF Agents in Juvenile Idiopathic Arthritis

Juvenile Idiopathic Arthritis Clinical Trial

Official title:

Analysis of Anti-infliximab, Anti-adalimumab and Anti-etanercept Antibodies in Children and Young Adolescents With Juvenile Idiopathic Arthritis

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01436019
• Other study ID #: BTC-PK-1
• Status: Not yet recruiting
• Phase: N/A
• First received: September 13, 2011
• Last updated: September 16, 2011
• Start date: October 2011
• Est. completion date: December 2012

Study information

• Verified date: September 2011
• Source: Blood Transfusion Centre of Slovenia
• Contact: Miha Kosmac, PhD
• Phone: +386 1 5438 146
• Email: miha.kosmac[@]ztm.si
• Is FDA regulated: No
• Health authority: Slovenia: Agency for Medicinal Products - Ministry of Health
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to analyze the frequency of the formation of antibodies against three different anti-TNF biologic agents used for the therapy of juvenile idiopathic arthritis.

Description:

Juvenile idiopathic arthritis (JIA) is the umbrella term for a heterogeneous group of inflammatory arthropathies that can affect children and young adults and is the most common rheumatic disease of the pediatric population. In high-income countries it has a yearly incidence of 2-20 cases per 100 000 population and a prevalence of 16-150 cases per 100 000 population. Treatment of JIA includes a combination of pharmacological interventions, physical and occupational therapy, and psychosocial support. Although a definitive cure is still not available, the prognosis for patients with JIA has improved greatly in recent years due to improved disease management and with the introduction of biologics that can provide an efficient alternative for patients who are nonresponsive to other treatments. Traditionally, biologic treatments in JIA have focused on blocking one of the central mediators of the inflammatory response, the cytokine tumor necrosis factor (TNF). Currently there are three anti-TNF agents available for the treatment of JIA: infliximab, adalimumab and etanercept. One of the major drawbacks of these therapeutics is the production of anti-drug antibodies (ADA) that have been correlated with an increased risk of adverse events and loss of drug efficacy. The study will evaluate the frequency of the formation of anti-infliximab antibodies in patients treated with infliximab, anti-adalimumab antibodies in patients treated with adalimumab and anti-etanercept antibodies in patients treated with etanercept. A common practice in cases nonresponsive to one of the described anti-TNF agents is the discontinuation of therapy and switching to a different ant-TNF agent. Therefore, the frequency of the formation of antibodies to each of the described anti-TNF agents will also be compared between patients who have previously received a different anti-TNF agent and patients who have not received any previous anti-TNF therapy. The results of this study will highlight the risks of formation of antibodies to three different anti-TNF biologic agents used for the therapy of JIA either alone or after the previous discontinuation of a different anti-TNF agent.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: December 2012
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year to 16 Years

Eligibility

Inclusion Criteria:

• Clinical diagnosis of juvenile idiopathic arthritis

• Must be treated either with infliximab, adalimumab or etanercept

Exclusion Criteria:

• Contraindications to anti-TNF therapy

• Concurrent treatment with any biologic agent other than infliximab, etanercept, or adalimumab

• Previous treatment with rituximab

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Juvenile
• Juvenile Idiopathic Arthritis

Locations

Country	Name	City	State
Slovenia	University Medical Centre	Ljubljana

Sponsors (2)

Lead Sponsor	Collaborator
Blood Transfusion Centre of Slovenia	University Medical Centre Ljubljana

Country where clinical trial is conducted

Slovenia, 

References & Publications (1)

Kosmac M, Avcin T, Toplak N, Simonini G, Cimaz R, Curin Šerbec V. Exploring the binding sites of anti-infliximab antibodies in pediatric patients with rheumatic diseases treated with infliximab. Pediatr Res. 2011 Mar;69(3):243-8. doi: 10.1203/PDR.0b013e318208451d. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determination of the presence and quantification of anti-drug antibodies by ELISA or other immunoassay.	In patients receiving infliximab anti-infliximab antibodies will be measured, in patients receiving adalimumab anti-adalimumab antibodies will be measured and in patients receving etanercept anti-etanercept antibodies will be measured. In all cases the primary outcome measure will be the determination of the presence of these antibodies (YES/NO) and their quantification (in EqU compared to a reference serum) using ELISA or other suitable immunoassay.	Up to one year	Yes
Secondary	Determination of the presence and quantification of the serum level of the anti-TNF agent used for JIA therapy by ELISA or other immunoassay.	In patients receiving infliximab the trough serum level of infliximab will be measured, in patients receiving adalimumab the trough serum level of adalimumab will be measured and in patients receiving etanercept the trough serum level of etanercept will be measured by ELISA or other suitable immunoassay.	Up to one year	No
Secondary	Determination of the presence and quantification of the isotypes and subtypes of the anti-drug antibodies by ELISA or other immunoassay.	In samples where the presence of anti-infliximab, anti-adalimumab or anti-etanercept antibodies will be confirmed, the isotypes and/or subtypes of the antibodies will be determined by ELISA or other suitable immunoassay.	Up to one year.	No
Secondary	Time to first detection of anti-drug antibodies.	The elapsed time from start of therapy until first detection of anti-drug antibodies will assessed.	Up to one year.	No