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

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

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.

Study Overview

• Status: Unknown
• Conditions: Juvenile Idiopathic Arthritis

Detailed 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.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Miha Kosmač, PhD; Phone Number: +386 1 5438 146; Email: miha.kosmac@ztm.si
• Study Contact Backup: Name: Tadej Avčin, MD, PhD; Phone Number: +386 1 522 96 42; Email: tadej.avcin@kclj.si

Study Locations

• Slovenia
  • Ljubljana, Slovenia
    • University Medical Centre
    • Principal Investigator: Tadej Avčin, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 16 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

primary care clinic

Description

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 Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
anti-TNF treatment; Children or young adolescents with juvenile idiopathic arthritis receiving either infliximab, adalimumab or etanercept.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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.
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.

Collaborators and Investigators

• Sponsor: Blood Transfusion Centre of Slovenia
• Collaborators: University Medical Centre Ljubljana
• Investigators: Principal Investigator: Miha Kosmač, PhD, Blood Transfusion Centre of Slovenia; Study Director: Tadej Avčin, MD, PhD, University Medical Centre, Ljubljana, Slovenia; Study Chair: Vladka Čurin Šerbec, PhD, Blood Transfusion Centre of Slovenia

Publications and helpful links

General Publications

• Kosmac M, Avcin T, Toplak N, Simonini G, Cimaz R, Curin Serbec 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Anticipated): October 1, 2012
• Study Completion (Anticipated): December 1, 2012

Study Registration Dates

• First Submitted: September 13, 2011
• First Submitted That Met QC Criteria: September 16, 2011
• First Posted (Estimate): September 19, 2011

Study Record Updates

• Last Update Posted (Estimate): September 19, 2011
• Last Update Submitted That Met QC Criteria: September 16, 2011
• Last Verified: September 1, 2011

More Information

Terms related to this study

• Keywords: Antibodies; Juvenile idiopathic arthritis; Rheumatic diseases; Biological therapy
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Juvenile
• Other Study ID Numbers: BTC-PK-1