Determining Predictors of Safe Discontinuation of Anti-TNF Treatment in JIA

April 13, 2016 updated by: Children's Hospital Medical Center, Cincinnati

Improved Understanding of the Biology and Use of TNF Inhibition in Children With JIA

Polyarticular juvenile idiopathic arthritis (Poly JIA) is a form of juvenile arthritis, which is a chronic disease affecting approximately 250,000 people younger than 16 years of age. Poly JIA can be treated with anti-tumor necrosis factor (anti-TNF), a type of medication that is often effective but also has some toxic side effects and is expensive. Among those with poly JIA who are effectively treated with anti-TNF, some can remain healthy off the medication, but some begin to feel the effects of their disease again once the medication is stopped. This study will attempt to find whether certain tests or signs can predict which people with poly JIA can safely stop their anti-TNF medications.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Juvenile arthritis is a chronic disease affecting approximately 250,000 people younger than 16 years of age in the United States. Its symptoms include swelling, pain, and damage in the joints. Juvenile arthritis can take four different forms, including poly JIA. Poly JIA affects five or more joints, generally the smaller ones in wrists and fingers, causing stiffness, joint damage, and sometimes eye inflammation in the children and adolescents who suffer from it. Approximately 30% of people with juvenile arthritis have Poly JIA.

Treatment for juvenile arthritis involves drugs with escalating strength, depending on what each individual responds to best. The first treatment option is non-steroidal anti-inflammatory drugs (NSAIDs), such as Motrin IB and Aleve. The second treatment option is methotrexate (MTX). About 30% to 50% of poly JIA patients are effectively treated with MTX. Only if the patient does not respond to MTX is an anti-TNF drug used. Anti-TNF drugs often result in profound disease improvement, but unfortunately, they can have toxic side effects and are expensive.

For people whose poly JIA is inactive or minimally active on MTX or anti-TNF drugs, 50% to 80% experience a worsening of symptoms once they stop taking the medications. Most of these flare-ups occur within 8 months of stopping treatment. Currently, there is no way to predict which people with poly JIA can safely stop anti-TNF medications. This study will evaluate two different factors-levels of certain calcium binding proteins and production of TNF-for their use in predicting whether people with poly JIA are likely to experience a disease flare-up once they stop anti-TNF treatment. The study will also look for genetic markers that can serve as predictors of safe discontinuation of anti-TNF treatment.

Participation in this study will last up to 14 months and involve up to nine study visits. Visits will be conducted at study entry and after 3, 6, 7, 8, 9, 10, 12, and 14 months. The first three study visits will involve tests to determine baseline health indicators and to ensure inactive disease. If, after 6 months, participants continue to have inactive disease, they will be taken off their anti-TNF medications. For the remainder of the study, visits will be used to monitor disease activity. If participants experience any clinically defined disease flare-ups, they will immediately stop participating in the study and begin additional treatment as prescribed by their health care providers. At all study visits, participants will undergo a general physical examination, a joint examination, questionnaires about how the disease affects their lives, and blood collection for research samples.

Study Type

Interventional

Enrollment (Actual)

137

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Children's Hospital of Alabama
    • Arizona
      • Phoenix, Arizona, United States, 85016
        • Phoenix Children's Hospital
    • Arkansas
      • Little Rock, Arkansas, United States, 72202
        • Arkansas Children's Hospital Research Institute
    • Connecticut
      • Hartford, Connecticut, United States, 06106
        • Connecticut Children's Medical Center
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Children's National Medical Center
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University School Of Medicine
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Comer Children's Hospital University of Chicago
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • University of Louisville Research Foundation
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Joseph M Sanzari Children's Hospital
    • New York
      • Bronx, New York, United States, 10467
        • Children's Hospital at Montefiore
      • New Hyde Park, New York, United States, 11040
        • Cohen Children's Medical Center of NY
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital and Medical Center
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Foundation
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15224
        • Children's Hospital of Pittsburgh
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Children's Hospital of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

4 years to 20 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Diagnosis of polyarticular JIA (rheumatoid factor + and rheumatoid factor -) or extended oligo JIA by the International League of Associations for Rheumatology (ILAR) criteria
  • Receiving therapy with one of the currently available anti-TNF biologics: infliximab, etanercept, or adalimumab
  • Absence of any of the FDA label exclusions for anti-TNF therapy
  • Receiving slit lamp exams performed at regular intervals in accordance with the published American Academy of Pediatrics guidelines
  • Baseline hemoglobin >10 g/dl
  • Absence of joints with active arthritis, using the American College of Rheumatology (ACR) definition of "active joint"
  • Absence of fever, rash, serositis, splenomegaly, or generalized lymphadenopathy attributable to JIA
  • Absence of active uveitis, as per an exam by an ophthalmologist
  • Normal erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP); if above normal range, must be not attributable to JIA
  • Physician's global assessment of disease activity indicating absence of disease activity, defined as the best score obtainable on the scale used
  • Duration of morning stiffness less than or equal to 15 minutes

Exclusion Criteria:

  • Diagnosis of a type of JIA other than polyarticular JIA
  • Diagnosis of another inflammatory disease that may affect laboratory results or ability to discontinue anti-TNF biologic therapy
  • Concurrent treatment with any biologic agent other than infliximab, etanercept, or adalimumab
  • previous treatment with rituximab
  • concurrent treatment for JIA with corticosteroids >0.2 mg/kg/day OR >10 mg/day

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: 1
Participants taking anti-TNF medications will be monitored for signs of their disease for 6 months. If, after 6 months, their disease has become inactive, they will stop taking anti-TNF medications for up to 8 months. If participants who are no longer taking anti-TNF medications have a disease flare-up, they will begin treatment again.
Other: Withdrawal of anti-TNF therapy
Anti-TNF therapy will be discontinued at the third visit in children who demonstrate persistent inactive disease for at least 6 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Disease flare, defined as demonstrating at least a 30% worsening in at least 3 of the 6 JIA Core Set parameters with no more than 1 improving by more than 30%
Time Frame: Measured at nine study visits over 14 months
Measured at nine study visits over 14 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Hospital Medical Center, Cincinnati

Collaborators

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Investigators

  • Principal Investigator: Daniel J. Lovell, MD, CCHMC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2009

Primary Completion (ACTUAL)

October 1, 2013

Study Completion (ACTUAL)

October 1, 2015

Study Registration Dates

First Submitted

November 14, 2008

First Submitted That Met QC Criteria

November 14, 2008

First Posted (ESTIMATE)

November 17, 2008

Study Record Updates

Last Update Posted (ESTIMATE)

April 15, 2016

Last Update Submitted That Met QC Criteria

April 13, 2016

Last Verified

April 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P60 AR047784-Project 2
  • P60AR047784 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

deidentified subject information and results of testing have already been shared with multiple investigators requesting samples

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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