Treatment to Target Using Recombinant Interleukin‐1 Receptor Antagonist as First‐Line Monotherapy in New‐Onset Systemic Juvenile Idiopathic Arthritis: Results From a Five‐Year Follow‐Up Study

Abstract

Objective Systemic juvenile idiopathic arthritis (JIA) is a multifactorial autoinflammatory disease with a historically poor prognosis. With current treatment regimens, approximately half of patients still experience active disease after 1 year of therapy. This study was undertaken to evaluate a treat‐to‐target approach using recombinant interleukin‐1 receptor antagonist (rIL‐1Ra; anakinra) as first‐line monotherapy to achieve early inactive disease and prevent damage. Methods In this single‐center, prospective study, patients with new‐onset systemic JIA with an unsatisfactory response to nonsteroidal antiinflammatory drugs received rIL‐1Ra monotherapy according to a treat‐to‐target strategy. Patients with an incomplete response to 2 mg/kg rIL‐1Ra subsequently received 4 mg/kg rIL‐1Ra or additional prednisolone, or switched to alternative therapy. For patients in whom inactive disease was achieved, rIL‐1Ra was tapered after 3 months and subsequently stopped. Results Forty‐two patients, including 12 who had no arthritis at disease onset, were followed up for a median of 5.8 years. The median time to achieve inactive disease was 33 days. At 1 year, 76% had inactive disease, and 52% had inactive disease while not receiving medication. High neutrophil counts at baseline and a complete response after 1 month of rIL‐1Ra were highly associated with inactive disease at 1 year. After 5 years of follow‐up, 96% of the patients included had inactive disease, and 75% had inactive disease while not receiving medication. Articular or extraarticular damage was reported in <5%, and only 33% of the patients received glucocorticoids. Treatment with rIL‐1Ra was equally effective in systemic JIA patients without arthritis at disease onset. Conclusion Treatment to target, starting with first‐line, short‐course monotherapy with rIL‐1Ra, is a highly efficacious strategy to induce and sustain inactive disease and to prevent disease‐ and glucocorticoid‐related damage in systemic JIA.

Th17 reprogramming of T cells in systemic juvenile idiopathic arthritis

“…patients, whereas treatment of established arthritis was often less successful (22)(23)(24). This observation has proven robust (25,26). Furthermore, a genome-wide association study identified a haplotype containing the HLA class II allele DR-B1*11 as the strongest carrier of sJIA risk, suggesting a role for antigen-driven CD4 + T cells (27,28).…”

Storm Warning: Lung Disease in Systemic Juvenile Idiopathic Arthritis

“…In this childhood arthritis that was previously deemed to have the most dismal prognosis in terms of disability and even death, the identification of interleukin‐1β (IL‐1β) and IL‐6 as key disease mediators has led to therapeutic interventions of remarkable efficacy . Observational studies defining the utility of cytokine blockade early in the course of disease have enabled treatment regimens that avoid glucocorticoids altogether, with previously unheard‐of levels of disability‐free and even drug‐free remission . Yet, while the landscape of systemic JIA was being thus transformed, clouds appeared on the horizon.…”

“…Patients in the Schulert series who developed lung involvement during treatment with biologics often remained on the treatment, with subsequent stabilization or even improvement, especially if systemic disease could be controlled. As the authors note, SJIA‐LD is not as common in parts of Europe where biologics use in patients with systemic JIA is comparable, including the recent Utrecht series of 42 systemic JIA patients treated with first‐line anakinra (recombinant IL‐1 receptor antagonist), of whom only 1 developed pulmonary manifestations in the course of dying from refractory MAS .…”

Comparison of Early vs. Delayed Anakinra Treatment in Patients With Adult Onset Still's Disease and Effect on Clinical and Laboratory Outcomes

“…Therefore, the identification of clinical or laboratory predictors of response currently accounts for a primary need to establish when and to whom IL-1 inhibitors should be started. In this regard, an early treatment with IL-1 blockade has been associated with a better outcome in the pediatric context (25)(26)(27)(28).…”