Biologic Abatement and Capturing Kids' Outcomes and Flare Frequency in Juvenile Spondyloarthritis (BACK-OFF JSpA): study protocol for a randomized pragmatic trial.

2023

100

02/2023

1745-6215

BACKGROUND: The effectiveness of biologic therapies, primarily tumor necrosis factor inhibitors (TNFi), for children with spondyloarthritis (SpA) has made inactive disease a realistic patient outcome. However, biologic therapies are costly, primarily delivered by subcutaneous or intravenous route, and have non-trivial side effects. Many patients and families want to know if biologic medications can be discontinued after inactive disease is achieved. It remains unclear whether medication dose should remain unchanged, tapered (increase the time between doses), or discontinued once when inactive disease is attained.

METHODS: The Biologic Abatement and Capturing Kids' Outcomes and Flare Frequency in Juvenile SpA (BACK-OFF JSpA) trial is a multicenter pragmatic trial that will randomize 198 participants ages 8-21 years old with SpA and sustained inactive disease on standard TNFi dosing to (1) continue standard TNFi dosing, (2) fixed longer dosing intervals of TNFi, or (3) stop TNFi. The trial will compare the hazard rate of protocol-defined flare and participants' emotional health among the 3 groups over 12 months. Innovative aspects of this trial are the involvement of patient and parent stakeholders in the design and conduct of the study as well as an electronic health record-based enhanced recruitment strategy.

DISCUSSION: This is the first randomized pragmatic trial to assess the efficacy of TNFi de-escalation strategies in children with JSpA with sustained inactive disease. This research will improve the evidence base that patients, caregivers, and rheumatologists use to make shared decisions about continued treatment versus de-escalation of TNFi therapy in this population.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04891640. Registered on 18 May 2021.

10.1186/s13063-022-07038-6

Trials

36755328

Development and validation of the juvenile spondyloarthritis disease flare (JSpAflare) measure: Ascertaining flare in patients with inactive disease.

2021

2021 Aug 07

2151-4658

<p><strong>OBJECTIVE: </strong>Our objective was to develop and validate a composite disease flare definition for juvenile spondyloarthritis that would closely approximate the clinical decision made to reinitiate/not reinitiate systemic therapy after therapy de-escalation.</p>

<p><strong>METHODS: </strong>Retrospective chart reviews of children with spondyloarthritis who underwent systemic therapy de-escalation of biologic or conventional disease-modifying antirheumatic drugs (bDMARDs; cDMARDs) were used to develop and validate the flare outcome. Independent cohorts for development (1 center) and validation (4 centers) were collected from large tertiary healthcare systems. Core measure thresholds and candidate disease flare outcomes were assessed using sensitivity, specificity, positive (PPV) and negative predictive values (NPV), and area under the receiver operating characteristic (AUROC) curve with physician assessment of "active disease" plus re-initiation of standard dose of systemic therapy as the reference standard.</p>

<p><strong>RESULTS: </strong>Of the candidate definitions, clinically meaningful worsening in ≥3 of the following five core measures performed best: caregiver/patient assessment of well-being, physician assessment of disease activity, caregiver/patient assessment of pain, physical function, and active joint count. AUROC was 0.91, PPV 87.5%, NPV 98.1%, sensitivity 82.4%, and specificity 98.7%. Cronbach's α was 0.81, signifying internal consistency and factor analysis demonstrated the outcome measured one construct. "JSpAflare" had face validity according to 21 surveyed pediatric rheumatologists. JSpAflare had AUROC 0.85, PPV 92.3%, and NPV 96.8% in the validation cohort.</p>

<p><strong>CONCLUSIONS: </strong>There is initial support for the validity of JSpAflare as a tool to identify disease flare in juvenile spondyloarthritis patients de-escalating therapy and is potentially applicable in clinical practice, observational studies, and therapeutic trials.</p>

10.1002/acr.24763

Arthritis Care Res (Hoboken)

34363343

Children with enthesitis-related arthritis could benefit from treatments targeted for adults with spondyloarthritis.

2020

2020 Dec 05

2151-4658

<p>This review will summarize clinical, genetic and pathophysiologic characteristics that are shared between children with enthesitis related arthritis (ERA) with axial involvement and adults with non-radiographic, and in some cases radiographic, axial spondyloarthritis (SpA); and between children with ERA and primarily peripheral disease manifestations and adults with peripheral SpA. Due to the differences in classification criteria for children with ERA and adults with axial and peripheral SpA, the FDA granted automatic full waivers of studies in children for new medications for "axial spondyloarthropathies including ankylosing spondylitis" up until July 2020. Thus, although current juvenile idiopathic arthritis (JIA) treatment guidelines recommend the use of biologic disease modifying anti-rheumatic drugs (DMARDs) as part of the early treatment for patients with ERA, none of the FDA-approved therapies for peripheral SpA or non-radiographic axial SpA (certolizumab pegol, ixekizumab, and secukinumab) have been studied or are labelled for use in children with ERA. Considering the similarities between adult spondyloarthritis and ERA in terms of etiology, genetics, pathogenesis and clinical manifestations summarized in this review, medications approved for axial SpA or peripheral SpA should also be studied in children with active ERA involving axial or peripheral joints, respectively, with the intent to achieve labeling for use in children. Considering the current lack of effective FDA-approved therapies for ERA, the FDA should also consider requiring pediatric studies for medications that have already been approved for the treatment of adults with SpA.</p>

10.1002/acr.24529

Arthritis Care Res (Hoboken)

33278336

The American English version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR).

2018

35-42

2018 Apr

1437-160X

<p>The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient-reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the American English language. The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the 3 Likert assumptions, floor/ceiling effects, internal consistency, Cronbach's alpha, interscale correlations, test-retest reliability, and construct validity (convergent and discriminant validity). A total of 315 JIA patients (5.1% systemic, 31.1% oligoarticular, 34% RF negative polyarthritis, 29.8% other categories) and 98 healthy children, were enrolled in three centres. The JAMAR components discriminated well healthy subjects from JIA patients. All JAMAR components revealed good psychometric performances. In conclusion, the American English version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and clinical research.</p>

10.1007/s00296-018-3984-6

29637338

2013 update of the 2011 American College of Rheumatology recommendations for treatment of juvenile idiopathic arthritis: recommendations for medical therapy of children with systemic JIA and TB screening among children receiving biologic medications.

2013

2499-512

2013 Oct

1529-0131

10.1002/art.38092

Arthritis Rheum.

24092554