Across the world, spondyloarthritis (SpA) is the most common form of juvenile arthritis, accounting for as much as one-third of all cases. These children are at risk of progression to ankylosing spondylitis, which is characterized by fusion of the joints, functional impairment, and psychologic impact that lasts into adulthood. We lack effective therapy for this condition and fewer than 20% of children with juvenile-onset SpA achieve remission within five years of diagnosis. The major impediment to advancing the care of children with SpA and axial arthritis is an absence of randomized clinical trials (RCTs) despite an increasing number of potential therapies. The over-arching premise of this application is that the presence of valid, comprehensive, and easily employable disease classification criteria as well as well-researched outcome criteria will permit the successful implementation of clinical trials for this population. There are 2 major obstacles to conducting clinical trials in this understudied population, both of which are addressed in this application. The first is the lack of pediatric classification criteria for axial arthritis (arthritis of the spine or sacroiliac joints). Algorithms used for adults are inadequate for children due to the rarity of back pain as a prominent clinical symptom in children. Our inability to classify axial involvement presents a distinct obstacle to the evaluation of therapy effectiveness and efficacy. The second major obstacle is the outcome measures to assess response in juvenile idiopathic arthritis (JIA) trials are not designed to assess the unique disease features of children with SpA and axial arthritis. Without measures to objectively quantify the severity of disease in the pediatric sacroiliac joint or to assess axial symptoms, assessment of interval change and response to medication is not possible. While there are similarities between juvenile and adult SpA, there are also distinct phenotypic differences that merit specific focus on classification and trials in juvenile disease. Our objective is to obtain the data necessary to measure meaningful clinical and subclinical changes in disease activity for use in future clinical trials on children with juvenile SpA and axial arthritis. This application has 2 specific aims: 1) Establish comprehensive classification criteria for axial juvenile SpA, and 2) Define a core-set of outcome measures for pragmatic trials of children with axial SpA. The work proposed in this application will enable the field to conduct not only clinical trials of promising new therapies such as inhibitors of the IL-17/IL-23 and JAK-STAT pathways, but also pragmatic trials embedded within routine clinical care.
The proposed research is relevant to public health because spondyloarthritis is the most common form of childhood arthritis in large parts of the world and we lack effective therapy for this condition. There is a critical need for clinical trials to evaluate existing and emerging targeted therapies for this understudied condition. This project is directly aligned with the program announcement (PAR-18-597) as the primary goal is to enable the field to conduct not only clinical trials of promising new therapies such as inhibitors of the IL-17/IL-23 and JAKSTAT pathways, but also pragmatic trials embedded within routine clinical care.
