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.

Figure 1

Flow chart showing the disposition of the patients with systemic juvenile idiopathic arthritis (sJIA) and their response to first‐line recombinant interleukin‐1 receptor antagonist (rIL‐1Ra) therapy. Values in circles are the number of patients. * = The 2 patients with recent flares experienced recurrent disease activity after ~1 year; no therapy had been initiated. GR = good response; NSAIDs = nonsteroidal antiinflammatory drugs; ID = inactive disease; AD = active disease.

Figure 2

Response of patients with systemic juvenile idiopathic arthritis (JIA) to recombinant interleukin‐1 receptor antagonist (rIL‐1Ra). A, Kaplan‐Meier curve of the time to achieve inactive disease (ID). Curves are shown for all patients with systemic JIA (n = 42), patients receiving rIL‐1Ra monotherapy (n = 30), and patients who needed prednisolone in addition to rIL‐1Ra to achieve inactive disease (n = 12). 95% CI = 95% confidence interval. B, Kaplan‐Meier curve of flare‐free survival time, defined as the time until first flare, censored at the last follow‐up if no flare occurred. Data are included for 31 patients who stopped receiving rIL‐1Ra due to inactive disease. C, Glucocorticoid use in the first 3 years of IL‐1Ra therapy. Circles represent individual patients, except for the circles shown for 0.0 mg/kg/day, which each represent 31–35 patients who were not receiving prednisolone at the indicated time point, as indicated by the numbers below the figure.

Figure 3

Relationship between neutrophil count, disease duration, and response to recombinant interleukin‐1 receptor antagonist (rIL‐1Ra) in patients with systemic juvenile idiopathic arthritis. A, Correlation between neutrophil count at the start of rIL‐1Ra treatment and disease duration (time between first symptom and start of rIL‐1Ra treatment) in patients with inactive disease (ID) at 1 year and patients with active disease (AD) at 1 year. Circles represent individual patients. B, Receiver operating characteristic curve of the whole data set (black line) and leave‐one‐out cross‐validation (red line) with neutrophil count as the variable and inactive disease at 1 year as the outcome. AUC = area under the curve (with the 95% confidence interval shown in parentheses).