Juvenile Idiopathic ArthritisPhase 4NCT00792233
Determining Predictors of Safe Discontinuation of Anti-TNF Treatment in JIA
A Phase 4 study testing Withdrawal of anti-TNF therapy in people with Juvenile Idiopathic Arthritis, run by Children's Hospital Medical Center, Cincinnati at 16 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 4 to 20 years
- Conditions the study is for
- Juvenile Idiopathic Arthritis
- What is being tested?
- Withdrawal of anti-TNF therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 137 participants
- Where
- 16 sitesUnited States
- Study dates
- Jun 2009to Oct 2015
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 20 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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"
Show all 11Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
United States16 sites
Emory University School of Medicine
Atlanta, Georgia, 30322
Children's Hospital of Alabama
Birmingham, Alabama, 35233
Medical University of South Carolina
Charleston, South Carolina, 29425
Comer Children's Hospital University of Chicago
Chicago, Illinois, 60637
Cincinnati Children's Hospital and Medical Center
Cincinnati, Ohio, 45229
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Joseph M Sanzari Children's Hospital
Hackensack, New Jersey, 07601
Connecticut Children's Medical Center
Hartford, Connecticut, 06106
Arkansas Children's Hospital Research Institute
Little Rock, Arkansas, 72202
University of Louisville Research Foundation
Louisville, Kentucky, 40202
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
Cohen Children's Medical Center of NY
New Hyde Park, New York, 11040
Phoenix Children's Hospital
Phoenix, Arizona, 85016
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224
Children's Hospital at Montefiore
The Bronx, New York, 10467
Children's National Medical Center
Washington D.C., District of Columbia, 20010
About this study
Official title: 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.
Read the 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.
- Conditions
- Juvenile Idiopathic Arthritis
- Being tested
- Withdrawal of anti-TNF therapy
- Keywords
- Poly JIA, TNF, Remission
- Medical subject headings
- Arthritis, Juvenile
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Withdrawal of anti-TNF therapyOther
Anti-TNF therapy will be discontinued at the third visit in children who demonstrate persistent inactive disease for at least 6 months.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | 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. Receives: Other: Withdrawal of anti-TNF therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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%
Measured: Measured at nine study visits over 14 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2008 (estimated)
- Study startJun 2009
- Primary completionOct 2013
- Study completionOct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Juvenile Idiopathic ArthritisStudies of the same condition, open and under way.
- More trials run by Children's Hospital Medical Center, CincinnatiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 137 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Responsible party
- Sponsor
- Investigators
- Daniel J. Lovell, MD, Principal investigator, CCHMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00792233
- Sponsor's protocol ID
- P60 AR047784-Project 2
- Other IDs
- P60AR047784
- Status last verified
- Apr 2016
- First submitted
- 14 Nov 2008
- Last updated
- 15 Apr 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: deidentified subject information and results of testing have already been shared with multiple investigators requesting samples
Publications
Hinze CH, Foell D, Johnson AL, Spalding SJ, Gottlieb BS, Morris PW, Kimura Y, Onel K, Li SC, Grom AA, Taylor J, Brunner HI, Huggins JL, Nocton JJ, Haines KA, Edelheit BS, Shishov M, Jung LK, Williams CB, Tesher MS, Costanzo DM, Zemel LS, Dare JA, Passo MH, Ede KC, Olson JC, Cassidy EA, Griffin TA, Wagner-Weiner L, Weiss JE, Vogler LB, Rouster-Stevens KA, Beukelman T, Cron RQ, Kietz D, Schikler K, Mehta J, Ting TV, Verbsky JW, Eberhard AB, Huang B, Giannini EH, Lovell DJ. Serum S100A8/A9 and S100A12 Levels in Children With Polyarticular Forms of Juvenile Idiopathic Arthritis: Relationship to Maintenance of Clinically Inactive Disease During Anti-Tumor Necrosis Factor Therapy and Occurrence of Disease Flare After Discontinuation of Therapy. Arthritis Rheumatol. 2019 Mar;71(3):451-459. doi: 10.1002/art.40727. Epub 2019 Jan 24.
PubMed 30225949Lovell DJ, Johnson AL, Huang B, Gottlieb BS, Morris PW, Kimura Y, Onel K, Li SC, Grom AA, Taylor J, Brunner HI, Huggins JL, Nocton JJ, Haines KA, Edelheit BS, Shishov M, Jung LK, Williams CB, Tesher MS, Costanzo DM, Zemel LS, Dare JA, Passo MH, Ede KC, Olson JC, Cassidy EA, Griffin TA, Wagner-Weiner L, Weiss JE, Vogler LB, Rouster-Stevens KA, Beukelman T, Cron RQ, Kietz D, Schikler K, Schmidt KM, Mehta J, Wahezi DM, Ting TV, Verbsky JW, Eberhard BA, Spalding S, Chen C, Giannini EH. Risk, Timing, and Predictors of Disease Flare After Discontinuation of Anti-Tumor Necrosis Factor Therapy in Children With Polyarticular Forms of Juvenile Idiopathic Arthritis With Clinically Inactive Disease. Arthritis Rheumatol. 2018 Sep;70(9):1508-1518. doi: 10.1002/art.40509. Epub 2018 Jul 25.
PubMed 29604189
Study at a glance
From the registry record, last updated by the sponsor on 15 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Improved Understanding of the Biology and Use of TNF Inhibition in Children With JIA
- ClinicalTrials.gov ID
- NCT00792233
- Acronym / sponsor ID
- P60 AR047784-Project 2
- Conditions
- Juvenile Idiopathic Arthritis
- Keywords
- Poly JIA, TNF, Remission
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 137 participants (actual)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Study start
- Jun 2009
- Primary completion
- Oct 2013 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 17 Nov 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Other: Withdrawal of anti-TNF therapyParticipants 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. |
Who may qualify
- Ages
- 4 to 20 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Withdrawal of anti-TNF therapyAnti-TNF therapy will be discontinued at the third visit in children who demonstrate persistent inactive disease for at least 6 months. | Other | 1 |
Primary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Apr 2016.
- Derived from this study: PubMed 30225949Hinze CH, Foell D, Johnson AL, Spalding SJ, Gottlieb BS, Morris PW, Kimura Y, Onel K, Li SC, Grom AA, Taylor J, Brunner HI, Huggins JL, Nocton JJ, Haines KA, Edelheit BS, Shishov M, Jung LK, Williams CB, Tesher MS, Costanzo DM, Zemel LS, Dare JA, Passo MH, Ede KC, Olson JC, Cassidy EA, Griffin TA, Wagner-Weiner L, Weiss JE, Vogler LB, Rouster-Stevens KA, Beukelman T, Cron RQ, Kietz D, Schikler K, Mehta J, Ting TV, Verbsky JW, Eberhard AB, Huang B, Giannini EH, Lovell DJ. Serum S100A8/A9 and S100A12 Levels in Children With Polyarticular Forms of Juvenile Idiopathic Arthritis: Relationship to Maintenance of Clinically Inactive Disease During Anti-Tumor Necrosis Factor Therapy and Occurrence of Disease Flare After Discontinuation of Therapy. Arthritis Rheumatol. 2019 Mar;71(3):451-459. doi: 10.1002/art.40727. Epub 2019 Jan 24.
- Derived from this study: PubMed 29604189Lovell DJ, Johnson AL, Huang B, Gottlieb BS, Morris PW, Kimura Y, Onel K, Li SC, Grom AA, Taylor J, Brunner HI, Huggins JL, Nocton JJ, Haines KA, Edelheit BS, Shishov M, Jung LK, Williams CB, Tesher MS, Costanzo DM, Zemel LS, Dare JA, Passo MH, Ede KC, Olson JC, Cassidy EA, Griffin TA, Wagner-Weiner L, Weiss JE, Vogler LB, Rouster-Stevens KA, Beukelman T, Cron RQ, Kietz D, Schikler K, Schmidt KM, Mehta J, Wahezi DM, Ting TV, Verbsky JW, Eberhard BA, Spalding S, Chen C, Giannini EH. Risk, Timing, and Predictors of Disease Flare After Discontinuation of Anti-Tumor Necrosis Factor Therapy in Children With Polyarticular Forms of Juvenile Idiopathic Arthritis With Clinically Inactive Disease. Arthritis Rheumatol. 2018 Sep;70(9):1508-1518. doi: 10.1002/art.40509. Epub 2018 Jul 25.
- Individual participant dataSharing planned: Yes. deidentified subject information and results of testing have already been shared with multiple investigators requesting samples
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniel J. Lovell, MD principal investigator
CCHMC
16 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Withdrawal of anti-TNF therapy in people with Juvenile Idiopathic Arthritis, run by Children's Hospital Medical Center, Cincinnati at 16 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00792233, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Apr 2016; AzTrials last refreshed its copy on 8 Nov 2026.