Treatment Tapering in JIA With Inactive Disease

NCT02840175 | Completed Phase 3

• 2 other identifiers: P 1509022016-000312-15
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

As biologic treatments are expensive and associated with some concerns regarding long-term safety, investigator hypothesize that early tapering and then withdrawal of biological agent, in an homogenous group of children with juvenile idiopathic arthritis achieving inactive disease, is safe and not inferior to the maintenance of stable treatment intensity over 24 weeks. In addition, investigator also hypothesize that an earlier tapering of treatment is associated with a better quality-of-life and a general cost saving effect. MRP8/14 will be studied as a potential biomarker for the risk of relapse. A study for biologic agent, anti-biologic agent antibodies and a pharmacogenomic approach will complete the research, as pharmacokinetic study during withdrawal of biologic treatment are rare in children.

Conditions

Juvenile Idiopathic Arthritis

Keywords

Treatment tapering; Oligoarticular; Juvenile Idiopathic Arthritis; Inactive disease; Biologic therapy

Outcome Measures

Primary Outcomes (1)

• Persistence of inactive disease

  Inactive disease is defined by the criterion of Wallace : * No joints with active arthritis, * No active uveitis as defined by the SUN Working Group2 (The Standardization of Uveitis Nomenclature (SUN) Working Group defines inactive anterior uveitis as "grade zero cells," indicating \<1 cell in field sizes of 1 mm by a 1-mm slit beam), * Erythrocyte sedimentation rate (ESR) ≤ 20 mm or C-reactive protein (CRP) level ≤ 10 mg/L (or ≤ 1 mg/dl or ≤ 100 µg/dl) or, if elevated, not attributable to JIA (if both ESR and CRP are available, both of them should be in the normal range) * Physician's global assessment of disease activity score (\< 10/100 visual analogue scale), * and duration of morning stiffness \< or egal to 15 minutes (within 7 days before the visit). For all the visits, joint counts and physician global assessment of disease activity will be performed by an investigator blinded from patient study group.

  24 weeks

Secondary Outcomes (12)

• Adverse and serious adverse events or of special interest

  Weeks 12, 24, 36, 48, 60, 72

• Persistent inactive disease as defined by Wallace criteria

  72 weeks

• Juvenile Arthritis Disease Activity Score (JADA score)

  Day 0, Weeks 12, 24, 48, 72

• Biological agent concentrations

  Day 0, weeks 12, 24, 36, 48, 60

• Anti-drugs antibodies concentrations

  Day 0, weeks 12, 24, 36, 48, 60

Study Arms (2)

Experimental

EXPERIMENTAL

* Day 0 at Weeks 24 : Increase the interval between 2 doses of the biological agent (etanercept, adalimumab, tocilizumab, abatacept) * Weeks 24 at Weeks 72: Stop the biological agent if inactive disease is maintained.

Drug: etanercept; Drug: adalimumab; Drug: Abatacept; Drug: Tocilizumab

Control

ACTIVE COMPARATOR

* Day 0 at Weeks 24: Maintain the biological agent (etanercept, adalimumab, tocilizumab, abatacept) at the same dose. * Weeks 24 at Weeks 48 : Increase the interval between 2 doses of the biological agent. * Weeks 48 at Weeks 72: Stop the biological agent if inactive disease is maintained.

Drug: etanercept; Drug: adalimumab; Drug: Abatacept; Drug: Tocilizumab

Interventions

etanercept DRUG

will be tapered from every week to every 2 weeks for 12 weeks then to every 3 weeks for 12 weeks

Also known as: Enbrel®

Control; Experimental

adalimumab DRUG

will be tapered from every 2 weeks to every 3 weeks for 12 weeks and to every 4 weeks for 12 weeks

Also known as: Humira®

Control; Experimental

Abatacept DRUG

will be tapered from every 4 weeks to every 6 weeks for 24 weeks

Also known as: Orencia®

Control; Experimental

Tocilizumab DRUG

will be tapered from every 4 weeks to every 6 weeks for 24 weeks

Also known as: RoActemra®

Control; Experimental

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Patient aged 2 to 17 years and treated with etanercept or tocilizumab or adalimumab, or patient aged 6 to 17 years and treated with abatacept.
• Patient with an oligoarticular or polyarticular rheumatoid factor negative JIA
• Patient treated with biologic treatment for persistent arthritis according to the marketing authorization.
• Patient who achieved inactive disease within two years of treatment with the last biologic agent administered, according to Wallace criteria : no joints with active arthritis, no active uveitis (as defined by the SUN Working Group), ESR or CRP level within normal limits in the laboratory where tested (or, if elevated, not attributable to JIA), physician's global assessment of disease activity score (\< 10/100 visual analogue scale), and duration of morning stiffness \< ou = 15 minutes (within 7 days before the visit).
• Patient with inactive disease achieved for less than 12 months.
• Patient without steroids or joint injection or live vaccines injection for at least one month.
• Signed informed consent by both parents (or legal guardian) and patient's agreement.
• Patient affiliated to the National Health Assurance system.

You may not qualify if:

• Patient with systemic form, rheumatoid factor positive, psoriatic or associated with enthesitis related JIA.
• Patient undergoing biologic therapy due to JIA-associated uveitis or with active uveitis at time of randomization.
• Patient with any contraindication to continue ongoing biologic treatment, notably ongoing uncontrolled infection, suspicion or evidence of demyelinating disease of the central nervous system.
• Patient previously treated with the same biotherapy for which dose decreasing or biotherapy withdrawal was already tested in the past for inactive disease and then reintroduced.
• Pregnancy or absence of effective contraception (including abstinence) in a pubertal patient.
• Patient suffering from tuberculosis.
• Patient with moderate to severe cardiac failure (NYHA class III / IV).

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• URC-CIC Paris Descartes Necker Cochin: collaborator

Study Sites (1)

Necker Children's Hospital

Paris, Paris, 75015, France

Location

MeSH Terms

Conditions

Arthritis, Juvenile

Interventions

Etanercept; Adalimumab; Abatacept; tocilizumab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Immunoglobulin Constant Regions; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoconjugates

Study Officials

• Florence UETTWILLER, PhD

  Necker Children's Hospital, Paris, France

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2016
• First Posted: July 21, 2016
• Study Start: May 18, 2017
• Primary Completion: October 29, 2019
• Study Completion: October 1, 2020
• Last Updated: March 23, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)