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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier:
NCT00792233
First received: November 14, 2008
Last updated: October 15, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Juvenile Idiopathic Arthritis
Other: Withdrawal of anti-TNF therapy
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Improved Understanding of the Biology and Use of TNF Inhibition in Children With JIA

Resource links provided by NLM:


Further study details as provided by Children's Hospital Medical Center, Cincinnati:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 120
Study Start Date: June 2009
Estimated Study Completion Date: October 2013
Estimated Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   4 Years to 20 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00792233

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

No publications provided

Responsible Party: Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT00792233     History of Changes
Other Study ID Numbers: P60 AR047784-Project 2, P60AR047784
Study First Received: November 14, 2008
Last Updated: October 15, 2013
Health Authority: United States: Federal Government

Keywords provided by Children's Hospital Medical Center, Cincinnati:
Poly JIA
TNF
Remission

Additional relevant MeSH terms:
Arthritis, Juvenile
Arthritis
Autoimmune Diseases
Connective Tissue Diseases
Immune System Diseases
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases

ClinicalTrials.gov processed this record on October 22, 2014