Effectiveness of First‐Line Treatment With Recombinant Interleukin‐1 Receptor Antagonist in Steroid‐Naive Patients With New‐Onset Systemic Juvenile Idiopathic Arthritis: Results of a Prospective Cohort Study

Abstract

Objective. To conduct a prospective cohort study using anakinra, a recombinant IL-1 receptor antagonist (IL-1Ra), as first-line therapy in patients with newonset systemic juvenile idiopathic arthritis (JIA). Results. We included consecutive patients with new-onset systemic JIA. The mean followup period was 32 months (range 12-54 months). At the 3-month time point, 85% of the patients showed an adapted ACR Pedi 90 response or had inactive disease; 75% of the patients achieved this response while receiving recombinant IL-1Ra alone. After 1 year, 17 of the 20 patients met the criteria for clinically inactive disease, and 13 of these patients met these criteria while receiving monotherapy with recombinant IL-1Ra. However, because of persistent disease activity, 7 of the 20 patients required additional therapy besides recombinant IL-1Ra. According to our stop strategy, 73% of patients with at least an adapted ACR Pedi 90 response at 3 months could stop recombinant IL-1Ra treatment within 1 year. After 2 years, 12 (86%) of 14 patients met the criteria for disease remission, either while receiving (n ‫؍‬ 4) or not receiving (n ‫؍‬ 8) medication. After 3 years, 10 (91%) of 11 patients met the criteria for disease remission, either while receiving (n ‫؍‬ 2) or not receiving (n ‫؍‬ 8) medication.Conclusion. This is the first prospective study in which recombinant IL-1Ra was used as first-line therapy in patients with systemic JIA. We observed excellent responses in nearly all patients within 3 months. In the majority of responding patients, treatment with recombinant IL-1Ra could be stopped within 1 year, with remission being preserved during followup. In approximately one-third of patients, concomitant therapy was required for maintenance of clinical response.Systemic juvenile idiopathic arthritis (JIA) is a severe subtype of JIA that accounts for ϳ10% of JIA cases (1).

First line therapy by Interleukin-1 teceptor antagonist in steroid naive children with systemic juvenile idiopathic arthritis

“…These patients had a median age of 2 years old, a median of three active joint involvements at diagnosis, a mean white cell count of 25 G/L and a mean neutrophilic count of 19 G/L. This was less than was previously reported by Vastert et al where 11 out of 15 of their patients were able to stop therapy during the first year [31]. Tapering attempts off anakinra was unsuccessful in 8 patients with the necessity of adding canakinumab in one patient in order to control disease activity.…”

“…Response rate being highly favourable in these patients when compared to patients with long standing disease having received previous treatment modalities such as steroids and DMARDs. Vastert et al extended these findings by confirming rapid response to anakinra in patients with SJIA with no prior history of corticosteroid therapy, remission was maintained in 80% of their patients after a median follow up of 2 years and 8 months [31]. Although remission was documented at the introduction of anakinra in refractory cases of SJIA who had previously received corticosteroid therapy, Pascual et al obtained remission in seven out of nine of their patients who had failed to control disease on traditional therapeutic modalities [21].…”

“…However this was mostly remarkable on the short run [30]. Furthermore, Vastert et al conducted a study where all their patients were in complete remission once IL-1 receptor antagonist agent was used as a first line therapeutic modality [31]. Nigrovic et al have suggested the use of IL-1 receptor antagonist as a first line therapy prior to the development of well-established SJIA [14].…”

Autoinflammation and autoimmunity in systemic juvenile idiopathic arthritis

“…In many patients, overt systemic features (fevers and rashes) fade over time, leaving behind a chronic and sometimes intractable arthritis. IL-1 blockade is remarkably effective in the acute phase, leading to complete remission in greater than 50% of patients, but treatment efficacy is much more modest in chronic arthritis (7)(8)(9).…”

Immunotherapeutic Biologic Agents to Treat Autoinflammatory Diseases

“…Dysregulation of IL-1 as a key mediator is important in other disorders including systemic JIA and adult-onset Still's disease (AOSD) [38][39][40]. These diseases are also thought to be part of the spectrum of AutoIDx and respond well, sometimes dramatically, to anti-IL-1 agents.…”