After 25 years of biologics in juvenile arthritis, new approaches are ‘not being explored’

The approval of etanercept for juvenile idiopathic arthritis in 1999 heralded a new era for children with arthritis. However, despite subsequent approvals for JIA, many patients with other types of childhood arthritis remain without options.

Since May of 1999, the FDA has approved several biologic disease-modifying antirheumatic drugs and targeted synthetic DMARDs for JIA. However, over that time, childhood-onset systemic lupus erythematosus has seen only one approval, while there have been no approvals for juvenile dermatomyositis.

“Although I am optimistic about more biologics achieving FDA approval in JIA, new mechanisms of actions are not being explored currently,” Michael Shishov, MD, division chief of rheumatology, and Kim and Steve Robson endowed chair in rheumatology, at Phoenix Children’s Hospital, told Healio. “In addition, there remains only one FDA approved option in the treatment of enthesitis-related arthritis, and none for oligoarticular JIA, which happens to be the most common type of JIA.”

In a paper published in Arthritis Care & Research, Shishov and colleagues reviewed the current treatment landscape for JIA and other conditions. According to the authors, approximately 300,000 children in the United States have been diagnosed with a pediatric rheumatic disease. And although the treatment and outcomes of patients with JIA have improved markedly in the past 25 years, the lack of FDA-approved options — with standardized doses and documented safety and efficacy data — “remains a central challenge in the treatment of all” pediatric rheumatic diseases and their associated complications.

Healio sat down with Shishov to discuss the current landscape of approvals and trials for juvenile arthritic conditions, the mechanisms of action being explored for these patients and what the future may hold.

Healio: What is the current landscape of approved biologic therapies in JIA? What medications are available?

Shishov: In 1999, etanercept (Enbrel, Amgen) was the first biologic FDA approved for JIA. There was a pause until 2008, at which time adalimumab (Humira, AbbVie) and abatacept (Orencia, Bristol Myers Squibb) were approved. Since 2008, an additional seven biologics have been approved for JIA.

There have been seven approvals for polyarticular JIA, which is defined as JIA affecting five or more joints, while there have been six approvals for juvenile psoriatic arthritis. Systemic JIA only has two approvals, while enthesitis related arthritis — the pediatric equivalent of adult spondyloarthropathy — only has one, and oligoarticular JIA — defined as four or fewer impacted joints — has none.

Healio: What are those medications targeting in the JIA disease process?

Shishov: Biologics used to treat JIA target TNF-alpha, interleukin-1, IL-6, CTLA-4, IL-12/IL-23, and IL-17. In addition, small molecule inhibitors target the Janus kinase.

Healio: What medications/modes of action are currently in the pipeline? Could you discuss some of the key clinical trials that may lead to FDA approval?

Shishov: JAK inhibition, an example of targeted therapy in JIA, is the mechanism of action that is attracting the most attention currently. There is a phase 3 clinical trial investigating baricitinib (Olumiant, Eli Lilly & Co.) in polyarticular JIA.

Healio: Are you optimistic about the next wave of JIA therapies? Why or why not?

Shishov: Although I am optimistic about more biologics achieving FDA approval in JIA, new mechanisms of actions are not being explored currently. In addition, there remains only one FDA approved option in the treatment of enthesitis-related arthritis, and none for oligoarticular JIA, which happens to be the most common type of JIA.

Healio: How have the current wave of biologic therapies improved outcomes in JIA?

Shishov: Prior to the introduction of biologics in 1999, children with JIA were at risk for severe arthropathy and permanent disability.

Since 1999, far fewer children with JIA experience joint damage and disability if they are treated aggressively and early with biologics.

Healio: What have we learned from clinical trials in other chronic pediatric autoimmune and musculoskeletal conditions that can be applied to JIA treatment?

Shishov: I would turn the question around. JIA features by far the most clinical trials within the pediatric rheumatic diseases, and the design of the trial can be instructive when designing trials for other diseases, including SLE.

References:

Shishov M, et al. Arth Care & Res. 2025;doi:10.1002/acr.25482.