Optimizing Treatment for Patients with Juvenile Idiopathic Arthritis in Sustained Remission: the MOVE-JIA Trial (MOVE-JIA)

Optimizing Treatment for Children and Adolescents with Juvenile Idiopathic Arthritis in Sustained Remission: a Comparison of Three Treatment Strategies. the MOVE-JIA Trial

The goal of this clinical trial is to compare three different maintenance and step-down treatment strategies in children and adolescents with juvenile idiopathic arthritis in sustained remission. The main questions it aims to answer are:

• Is the proportion of study participants with a disease flare different between each of the two drug withdrawal arms and the stable treatment arm during 12 months?
• Does the proportion of study participants with a disease flare differ between the two drug withdrawal arms during 12 months?
• How long time does it take before a disease flare occurs, and how long does it take before disease remission is reestablished for participants in the different treatment arms?

Participants will be randomized to either A) continued stable treatment with methotrexate and tumor-necrosis alpha inhibitor (TNFi); B) gradual withdrawal of methotrexate while continued stable dose TNFi; or C) gradual withdrawal of TNFi.

Participants will be examined every 4 month, and with extra visits if they experience increased symptoms or suspect a disease flare. If a flare occurs, the medications received at study inclusion will be restarted.

Study Overview

• Status: Recruiting
• Conditions: Juvenile Idiopathic Arthritis
• Intervention / Treatment: Drug: Methotrexate; Drug: TNF Inhibitor

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Siri Opsahl Hetlevik, MD PhD; Phone Number: +4795846826; Email: siri.opsahl@gmail.com
• Study Contact Backup: Name: Anna-Birgitte Aga, MD PhD; Phone Number: +4740470692; Email: anna.birgitte.aga@gmail.com

Study Locations

• Norway
  • Bergen, Norway, 5009
    • Recruiting
    • Haukeland University Hospital
    • Contact: Maria Karolina Jonsson, MD PhD; Email: maria.karolina.jonsson@helse-bergen.no
  • Drammen, Norway, 3004
    • Recruiting
    • Drammen Hospital
    • Contact: Cathrine Austad, MD; Email: cataus@vestreviken.no
  • Kristiansand, Norway, 4615
    • Recruiting
    • Hospital of Southern Norway Hospital Trust
    • Contact: Hege Høiberg, MD; Email: hege.hoiberg@sshf.no
  • Oslo, Norway, 0372
    • Recruiting
    • Oslo University Hospital
    • Contact: Siri O Hetlevik, MD PhD; Phone Number: +4723070000; Email: siri.opsahl@gmail.com
    • Contact: Anna-Birgitte Aga, MD PhD; Phone Number: +4723070000; Email: anna.birgitte.aga@gmail.com
    • Contact: Siri O Hetlevik, MD PhD
  • Stavanger, Norway, 4019
    • Recruiting
    • Stavanger University Hospital
    • Contact: Maria Bilstad, MD PhD; Email: maria.bilstad@sus.no
  • Tromsø, Norway, 9019
    • Recruiting
    • University Hospital of North Norway
    • Contact: Ellen Nordal, MD PhD; Email: ellen.berit.nordal@unn.no
  • Trondheim, Norway, 7030
    • Recruiting
    • St. Olavs hospital
    • Contact: Marite Rygg, MD PhD; Email: marite.rygg@ntnu.no

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participant must be 2-<18 years of age at the time of signing the informed consent.
2. Fulfilment of the International League of Associations for Rheumatology (ILAR) classification criteria for non-systemic Juvenile Idiopathic Arthritis (JIA).
3. Inactive disease for ≥12 months documented at a minimum of 2 consecutive visits and documented inactive disease according to Wallace criteria at inclusion, and no active uveitis for ≥24 months.
4. Stable treatment with methotrexate and Tumor Necrosis Factor inhibitor (TNFi) for ≥6 months. Weight adjustments permitted.
5. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF).
6. Male participants: No contraceptive measures necessary.
7. Female participants: contraception guidance for women of childbearing potential (WOCP).

Exclusion Criteria:

1. Chronic widespread pain syndrome
2. Major comorbidity including uncontrolled infectious, neurological or mental disease, malignant disease, severe heart failure, severe renal failure, active ulcus ventriculi, and uncontrolled diabetes mellitus.
3. Use of oral, intra-articular, intramuscular or intravenous corticosteroids due to JIA less than 12 months prior to randomization.
4. Participating in an ongoing clinical randomized study..
5. Drug/alcohol abuse which hampers adherence to the study protocol as based on the investigators judgement.
6. Language barriers that hamper adherence to the study protocol.
7. Pregnancy or breastfeeding.
8. Any condition that in the view of the investigator would suggest that the patient is unable to comply with the study protocol and procedures.
9. Unwillingness to use safe contraception for sexually active WOCP.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Stable treatment; Stable treatment with methotrexate and TNFi	Drug: Methotrexate; Gradual withdrawal of the medication; Drug: TNF Inhibitor; Gradual withdrawal of the medication
Experimental: Methotrexate withdrawal; Gradual withdrawal of methotrexate	Drug: Methotrexate; Gradual withdrawal of the medication
Experimental: TNFi withdrawal; Gradual withdrawal of TNFi	Drug: TNF Inhibitor; Gradual withdrawal of the medication

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with disease flare	Disease flare is defined as a combination of: A clinical significant increase in Juvenile Arthritis Disease Activity Score 27 (JADAS-27*) ≥1.7 from baseline AND active joints ≥1 (swollen, or tender + limited range of motion) OR consensus between treating physician and participant/parents that a clinically significant flare has occurred with need of intensification of antirheumatic treatment. *JADAS-27 is a composite measure of juvenile idiopathic arthritis (JIA) disease activity, calculated as a sum of scores from four components giving a score of 0-57. The components included are physician global assessment of disease activity, parent/patient's global assessment of well-being, active joint count of 27 joints and erythrocyte sedimentation rate (ESR) normalized to a 0-10 scale.	4, 8 and 12 months
Proportion of patients with disease flare between two different withdrawal strategies	Disease flare is defined as a combination of: A clinical significant increase in Juvenile Arthritis Disease Activity Score 27 (JADAS-27*) ≥1.7 from baseline AND active joints ≥1 (swollen, or tender + limited range of motion) OR consensus between treating physician and participant/parents that a clinically significant flare has occurred with need of intensification of antirheumatic (DMARD) treatment. *JADAS-27 is a composite measure of JIA disease activity, calculated as a sum of scores from four components giving a score of 0-57. The components included are physician global assessment of disease activity, parent/patient's global assessment of well-being, active joint count of 27 joints and ESR normalized to a 0-10 scale.	4, 8 and 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to disease flare	JADAS-27, physician's global assessment of diseasae activity, paren't/patient's global assessment, swollen, tender and range of motion joint count (assessed in 71 joints), ESR/CRP, consensus between treating physiciand and patient/parents (uveitis, arthritis on imaging, psoriasis, inflammatory back pain, enthesitis, other; yes/no) *JADAS-27 is a composite measure of JIA disease activity, calculated as a sum of scores from four components giving a score of 0-57. The components inculded are physician global assessment of disease activity, parent/patient's global assessment of well-being, active joint count of 27 joints and ESR normalized to a 0-10 scale.	4, 8 and 12 months
Time to regain inactive disease by the Wallace definition* after flare	JADAS-27, Wallace inactive disease*, physician's global assessment of disease activity, paren't/patient's global assessment, swollen, tender and range of motion joint count (assessed in 71 joints), ESR/CRP, consensus between treating physiciand and patient/parents (uveitis, arthritis on imaging, psoriasis, inflammatory back pain, enthesitis, other; yes/no). *Wallace inactive disease: No active arthritis, no active uveitis, no morning stiffness >15 minutes, no systemic features (fever/rash/serositis/splenomegaly/lymphadenopathy due to JIA), a physician global assessment of disease activity 0 on a 0-100 scale) and normalization of C-reactive protien (CRP) and ESR.	4, 8 and 12 months
Physician global assessment of disease activity	Physician global assessment of disease activity is measured on a 100 mm visual analogue scale (VAS). The anchors of the scale are "very well" to "very poor".	4, 8 and 12 months
Disease activity assessed by joint count	In total 68 joints will be evaluated for swelling, 75 joints/joint areas will be evaluated for tenderness and 70 joints/joint areas will be examined for limitation of motion. JADAS10, JADAS27 and JADAS71 and 71-joint count will be computed from this examination	4, 8 and 12 months
Patient's/parent's global assessment of well-being	Patient's/parent's global assessment of well-being will be assessed on a 100 mm visual analouge scale.	4, 8 and 12 months
Concentration of Erythrocyte sedimentation rate (ESR),	Erythrocyte sedimentation rate (ESR), will be measured at all clinical visits	4, 8 and 12 months
Concentration of C-reactive protein (CRP)	C-reactive protein (CRP) will be measured at all clinical visits	4, 8 and 12 months
Numbers and type of adverse events (AE)	Assessment of AE, serious AE and suspected unexpected serious adverse reactions	4, 8 and 12 months

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Collaborators: The Research Council of Norway; South-Eastern Norway Regional Health Authority; Remedy
• Investigators: Principal Investigator: Anna-Birgitte Aga, MD PhD, Oslo University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 24, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: October 17, 2024
• First Submitted That Met QC Criteria: October 20, 2024
• First Posted (Actual): October 22, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 19, 2025
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: JIA; withdrawal; maintenance treatment; medication withdrawal
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Arthritis; Arthritis, Juvenile; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Enzyme Inhibitors; Antirheumatic Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Reproductive Control Agents; Antimetabolites, Antineoplastic; Antimetabolites; Dermatologic Agents; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors; Tumor Necrosis Factor Inhibitors; Methotrexate
• Other Study ID Numbers: 2024-513017-12-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: A de-identified patient data set can be made available to researchers upon reasonable request.
• IPD Sharing Time Frame: 10 years
• IPD Sharing Access Criteria: The data will only be made available after submission of a project plan outlining a reasonable request and any proposed analyses, and will have to be approved by the the MOVE-JIA steering group. Project proposals can be submitted to the corresponding author. Data sharing will have to follow appropriate regulations.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No