Clinical trial NCT01436019: Study of Antibodies to Anti-TNF Agents in Juvenile Idiopathic Arthritis
Official title: Analysis of Anti-infliximab, Anti-adalimumab and Anti-etanercept Antibodies in Children and Young Adolescents With Juvenile Idiopathic Arthritis
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Juvenile Idiopathic Arthritis
Keywords: Juvenile idiopathic arthritis
Rheumatic diseases
Antibodies
Biological therapy
Lead sponsor: Blood Transfusion Centre of Slovenia
Sponsor class: OTHER_GOV
Collaborators: name: University Medical Centre Ljubljana
First posted: 2011-09-19
Enrollment: 100
Sex: ALL
Minimum age (years): 1
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: primary care clinic

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Determination of the presence and quantification of anti-drug antibodies by ELISA or other immunoassay.
timeFrame: Up to one year
Secondary outcomes:
measure: Determination of the presence and quantification of the serum level of the anti-TNF agent used for JIA therapy by ELISA or other immunoassay.
timeFrame: Up to one year
measure: Determination of the presence and quantification of the isotypes and subtypes of the anti-drug antibodies by ELISA or other immunoassay.
timeFrame: Up to one year.
measure: Time to first detection of anti-drug antibodies.
timeFrame: Up to one year.
Other outcomes:
Locations:
city: Ljubljana
country: Slovenia
facility: University Medical Centre
Study officials:
affiliation: Blood Transfusion Centre of Slovenia
name: Miha Kosmač, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Medical Centre, Ljubljana, Slovenia
name: Tadej Avčin, MD, PhD
role: STUDY_DIRECTOR
affiliation: Blood Transfusion Centre of Slovenia
name: Vladka Čurin Šerbec, PhD
role: STUDY_CHAIR
References:
citation: 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.