Children With Enthesitis‐Related Arthritis and Possible Benefits From Treatments for Adults With Spondyloarthritis

Abstract

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 nonradiographic (and in some cases radiographic) axial spondyloarthritis (SpA), as well as 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 US Food and Drug Administration (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 treatment guidelines recommend the use of biologic disease‐modifying antirheumatic drugs as part of the early treatment for patients with ERA, none of the FDA‐approved therapies for peripheral SpA or nonradiographic axial SpA (certolizumab pegol, ixekizumab, and secukinumab) have been studied or are labeled for use in children with ERA. Considering the similarities between adult SpA 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.

Secukinumab in enthesitis-related arthritis and juvenile psoriatic arthritis: a randomised, double-blind, placebo-controlled, treatment withdrawal, phase 3 trial

“…The responses in children with JPsA receiving secukinumab in this study are consistent with the findings from studies in patients with PsA where secukinumab has demonstrated sustained improvements in ACR responses, in resolution of enthesitis and dactylitis, in skin clearance with sustained improvement across the six key manifestations of PsA through 5 years. 24–26 ERA is considered the paediatric counterpart of nr-axSpA 2 and children with ERA also experienced a profound improvement of signs and symptoms of their disease. The role of IL-17A in spondyloarthritide manifestations of skin, joints and entheses is well known, and profound improvement with secukinumab was reported in patients with PsO, PsA and AS.…”

Enthesitis Related Arthritis: A Single Center Experience

“…According to the ILAR criteria, JIA is divided into seven mutually exclusive subgroups and ERA is one of the most controversial subtypes of JIA, which differ from other types of inflammatory arthritis in genetic predisposition, pathogenesis, and risk of axial involvement [7]. Since the studies specifically performed on ERA are limited, the knowledge regarding ERA is based mainly on data from adults with spondyloarthritis (SpA) [8]. The largest study, which included 312 ERA patients, was reported from northern India in 2016 [9].…”

“…Moreover, all our patients with axial involvement needed anti-TNF treatment. Since ERA patients tend to have higher disease activity, and risk of axial involvement, the treatment of ERA should be more aggressive than other subtypes of JIA [3,8]. Previous studies have clearly shown that methotrexate alone is not an effective treatment in adult SpA [5,21].…”

Spondyloarthritides: Theories and beyond

“…Reactive arthritis, IBD-related arthritis, and psoriatic arthritis are not among the diagnostic criteria in ERA. While psoriatic arthritis in children is a different subgroup of JIA, both psoriatic arthritis, reactive arthritis, and IBD are included in the SpA group in adults (23). Secondly, the ILAR classification criteria focus on the importance of extra-axial manifestations such as peripheral arthritis and enthesitis, while SpA classification pays attention to the presence of axial and spinal involvement.…”