Biologic Abatement and Capturing Kids' Outcomes and Flare Frequency in Juvenile Spondyloarthritis (BACK-OFF JSpA)

Biologic Abatement and Capturing Kids' Outcomes and Flare Frequency in Juvenile Spondyloarthritis (BACK-OFF JSpA)

This randomized pragmatic trial will generate knowledge about strategies used to de-escalate tumor necrosis factor inhibitor (TNFi) therapy in patients with juvenile spondyloarthritis with sustained inactive disease and are treated at one of the 31 participating pediatric healthcare systems. This open label study will be conducted in the setting of routine clinical care and will compare the risk and timing of flare (Aim 1) and patients' lived experiences (Aim 2) across three arms.

Study Overview

• Status: Completed
• Conditions: Juvenile Spondyloarthritis
• Intervention / Treatment: Other: Standard TNFi Therapy; Other: TNFi fixed longer dosing intervals; Other: Stop TNFi treatment

Detailed Description

This project is a prospective, 12-month pragmatic randomized trial embedded within routine clinical care. Children with spondyloarthritis who have maintained inactive disease on a clinically prescribed standard dosing of a TNFi for 6 months or longer will be eligible for enrollment. Children will be randomized to one of the following alternative approaches: continued fixed standard dosing (arm 1), fixed longer dosing intervals of TNFi (arm 2), or stopping TNFi (arm 3). The recommended visit frequency is every 3 months through the study endpoint at 12 months. After subjects have followed their treatment assignment for 12 months, those who have not flared may modify their treatment regimen as per shared decision making between themselves and the treating physician. All participants will be monitored for 24 additional months for long-term outcomes after the intervention period.

• Study Type: Interventional
• Enrollment (Actual): 164
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1E8
      • The Hospital for Sick Children
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Phoenix Children's
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
    • Palo Alto, California, United States, 94304
      • Stanford University
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital of Colorado
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Nemours Children's Hospital
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Children's National Health System
  • Florida
    • Orlando, Florida, United States, 32827
      • Nemours Children's Health
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Children's Healthcare of Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital of Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Riley Hospital for Children at IU Health
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Stead Family Children's Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Masonic Children's Hospital
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital
    • St Louis, Missouri, United States, 63110
      • St. Louis Children's Hospital
  • New York
    • New York, New York, United States, 10021
      • Hospital for Special Surgery
    • Queens, New York, United States, 11040
      • Cohen Children's Medical Center
  • Ohio
    • Akron, Ohio, United States, 44302
      • Akron Children's Hospital
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Oregon
    • Portland, Oregon, United States, 97227
      • Randall Children's Hospital at Legacy Emanuel
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15224
      • UPMC Children's Hospital of Pittsburgh
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt Children's Hospital
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital - Baylor College of Medicine
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • Primary Children's Hospital
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Males or females age 8 to 21 years

2. Juvenile SpA diagnosis:

   • Symptom onset before their 16th birthday:

   o International League of Associations for Rheumatology (ILAR) criteria for juvenile idiopathic arthritis enthesitis-related arthritis subtype

   OR;

   • Symptom onset before their 18th birthday:

   o Pediatric Rheumatology International Trials Organization (PRINTO) revision of the ILAR criteria enthesitis spondylitis-related JIA

   • Peripheral arthritis and enthesitis, or
   • Arthritis or enthesitis, plus ≥3 months of inflammatory back pain and sacroiliitis on imaging, or
   • Arthritis or enthesitis plus 2 of the following: (1) sacroiliac joint tenderness; (2) inflammatory back pain; (3) presence of HLA-B27 antigen; (4) acute (symptomatic) anterior uveitis; and (5) history of a SpA in a first-degree relative.
   • If peripheral arthritis is present, it should persist for at least 6 weeks.
3. Currently taking one of the following TNFi therapies (Adalimumab, Certolizumab, Etanercept, Golimumab, Infliximab, or TNFi biosimilar) at standard doses
4. Have reached a clinically inactive disease state for a minimum of six months, as determined by treating physician
5. English speaking or Spanish speaking
6. Subject's treating physician recommended that he/she is a good candidate to participate in the study, which may include a modified therapy
7. Interested and willing to de-escalate TNFi therapy

Exclusion Criteria:

1) History of inflammatory bowel disease, history of uveitis that was not adequately controlled with localized ophthalmic treatment or psoriasis that pre-dates the start of TNFi therapy or psoriasis that started after TNFi therapy and has required more than topical therapy for control

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: TNFi Standard Therapy; Continue fixed standard treatment (i.e., no change from current therapy)	Other: Standard TNFi Therapy; Participants randomly assigned to this arm will continue taking their TNFi medication as currently prescribed.
Experimental: TNFi fixed longer dosing intervals; Fixed longer dosing intervals of TNFi (i.e., increased time between doses)	Other: TNFi fixed longer dosing intervals; Participants randomly assigned to this arm will increase the time between TNFi medication doses.; Adalimumab- from every 2 to 3 weeks; Certolizumab- from every 2 to 4 weeks; Etanercept- from every 1 to 2 weeks; Golimumab- from every 4 to 6 weeks; Infliximab- from baseline to baseline + 2 weeks
Experimental: TNFi Therapy Withdrawal; Stop TNFi treatment	Other: Stop TNFi treatment; Participants randomly assigned to this arm will stop TNFi medication.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Juvenile Spondyloarthritis (JSpA) flare	JSpA flare is defined as clinically meaningful worsening in ≥3 of the following: caregiver/patient assessment of well-being, physician assessment of disease activity, caregiver/patient assessment of pain, physical function, and active joint count. Meaningful change for well-being, disease activity, and pain are an increase of ≥2 on visual analogue scale (range 0-10 with higher scores indicating poorer well-being, higher disease activity, and higher magnitude of pain). Meaningful change in function is defined as ≥3 unit change in the PROMIS mobility or upper extremity T-scores. The Patient-Reported Outcomes Measurement Information System (PROMIS) short forms include 8 questions and a T-score of '50' represents the healthy population mean score with standard deviation of 10. Active joint count is defined as the number of joints with swelling or, in the absence of swelling, limitation of motion accompanied by pain or warmth as per the physician examination.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain interference (as measured by the PROMIS short form)	Pain interference (as measured by the PROMIS short form) of children with spondyloarthritis in the three treatment arms. The PROMIS short form is a validated questionnaire that measures the self-reported consequences of pain on relevant aspects of a person's life.The PROMIS short form includes 8 questions and a T-score of '50' represents the healthy population mean score with standard deviation equal to 10.	12 months

Collaborators and Investigators

• Sponsor: Children's Hospital of Philadelphia
• Collaborators: Patient-Centered Outcomes Research Institute

Publications and helpful links

General Publications

• Weiss PF, Sears CE, Brandon TG, Forrest CB, Neu E, Kohlheim M, Leal J, Xiao R, Lovell D. Biologic Abatement and Capturing Kids' Outcomes and Flare Frequency in Juvenile Spondyloarthritis (BACK-OFF JSpA): study protocol for a randomized pragmatic trial. Trials. 2023 Feb 8;24(1):100. doi: 10.1186/s13063-022-07038-6.

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2021
• Primary Completion (Actual): June 1, 2026
• Study Completion (Actual): June 1, 2026

Study Registration Dates

• First Submitted: May 14, 2021
• First Submitted That Met QC Criteria: May 14, 2021
• First Posted (Actual): May 18, 2021

Study Record Updates

• Last Update Posted (Actual): August 5, 2026
• Last Update Submitted That Met QC Criteria: August 3, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Arthritis; Joint Diseases; Infections; Bone Diseases, Infectious; Spinal Diseases; Spondylitis; Spondylarthritis
• Other Study ID Numbers: 21-018442; : GRT-00001036 (Other Grant/Funding Number: PCORI)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No