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

Specific Aims: The goal of this pragmatic clinical trial is to improve the available evidence regarding withdrawal of tumor necrosis factor inhibitors (TNFi) in children with spondyloarthritis who have inactive disease so families and clinicians can make more informed care decisions.

Aim 1. To compare the rates of disease flare associated with fixed standard dosing, fixed longer dosing intervalsor stopping TNFi in children with spondyloarthritis who have inactive disease. Hypotheses: 1) The rate of flare for children who have the fixed longer dosing interval will be not inferior to those who stay on fixed standard dosing. 2) Children who stop TNFi will have higher rates of flare than the other 2 arms.

Aim 2. To compare patients’ lived experiences in the three treatment arms. Using measures from the Patient-Reported Outcomes Measurement Information System (PROMIS), we will assess a patient prioritized profile of pediatric patient-reported outcomes (PROs) to evaluate children’s self-assessments of their health in the three treatment arms.

Background: Although spondyloarthritisis one of the most common forms of juvenile arthritis, accounting for as much as 1/3 of all cases, it is a rare disease in the USA. Spondyloarthritisis characterized by inflammatory arthritis, enthesitis (tender tendon insertions), dactylitis (swollen fingers), back pain, inflammatory bowel disease, eye inflammation, and psoriasis. Since the introduction of biologic disease modifying agents such as TNFi, inactive disease is a realistic goal. However, it is unknown if these high-cost medicines with short-and long-term effects on the immune system should be withdrawn after inactive disease is achieved, with no evidence on expected outcomes if de-escalation is attempted. This pragmatic trial will test maintenance of fixed standard dosing and two alternative approaches to de-escalate TNFi therapy in children with spondyloarthritis who have inactive disease in the everyday clinical setting.

Significance: 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 children with spondyloarthritis who have inactive disease. Pediatric rheumatologists are variable in their TNFi withdrawal strategies due to lack of evidence. Embedding this research in real-world clinical settings will ensure our results are directly translatable to usual patient care and highly impactful because the 20 participating healthcare centers that treat hundreds of children with spondyloarthritis have agreed to implement the findings of this study into their everyday practices. If we can successfully de-escalate TNFi therapy in this population, we may save unnecessary medication exposure, improve patient quality of life, and reduce medication expenditure. 

Study Design: The proposed project is a prospective, 18-month, pragmatic randomized trial embedded within routine clinical care. Children with spondyloarthritis who have maintained inactive disease on TNFi standard dosing for at least 6 months and are interested in medication de-escalation are eligible for enrollment. Subjects will follow their usual care schedule of every 3 months for an exam and PRO evaluation. Using a randomized study design will mitigate the bias and unmeasured confounding inherent to observational studies. Randomization will be stratified by presence or absence of axial (sacroiliac or spine disease), as this may influence the risk of flare.