Background Systemic onset juvenile idiopathic arthritis (SoJIA) is a distinct subtype of juvenile arthritis with a central role for IL-1 and IL-18 mediated inflammation. A retrospective cohort analysis describing recombinant IL-1RA (rec IL-1RA) therapy in steroid refractory and steroid naïve SoJIA patients recently suggested rec IL-1RA to be attractive as a first line drug.
Objectives To prospectively describe the use of rec IL-1RA in a cohort of newly onset SoJIA patients as a first line therapy.
Methods All patients fulfilled the ILAR criteria for SoJIA. Rec IL-1RA (2 mg/kg/day) was started when patients showed insufficient response to NSAIDs. Patients were closely monitored during the first 3 weeks and thereafter every 3 months. Besides clinical and laboratory parameters of disease activity, we sampled plasma for cytokine profiles and myeloid related proteins. The study protocol contained a stop strategy of rec IL-1RA when in remission at timepoint 3 months.
Results We included 18 consecutive newly onset SoJIA patients with a mean age of 8,2 years (range 2-10,3). All patients showed systemic inflammation (mean CRP 186,7 mg/L, mean ferritin 1119 ug/L), spiking fever and arthritis (mean joint count of 4,2, range 1-14) prior to the start of rec IL-1RA. Mean follow up was 26 months (range 4-42 months).
At timepoint 3 months, 94% of patients showed ACRPed90 responses. 67% of patients were in remission on rec IL-1RA alone. However, in 6 patients (33%) concomitant therapy with systemic steroids (1 mg/kg in 4 patients, 0,3 mg/kg in 2 patients) and/or methotrexate was necessary because of recurrence or persistence of systemic inflammation or arthritis.
After 1 year of follow-up (n=16), 11 patients (69%) showed ACRPed 90 responses on rec IL-1RA therapy alone. Rec IL-1RA could be succesfully stopped in 7/11 patients (64%), whereas 4 patients were in remission on rec IL-1RA. Two patients were switched to other biologicals in clinical studies due to refractory disease. Of these, 1 patient showed moderately responses to Canakinumab (ACRPed 50). Unfortunately, the other patient also failed to respond to Tocilizumab and Canakinumab and deceased due to macrophage activation syndrome 2 years after inclusion in our study. The remaining 3 patients showed beneficial responses to methotrexate alone (only mild arthritis), combination therapy of rec IL-1RA and MTX (ACRPed90) or low dose steroids and MTX (ACRPed90) at timepoint 1 year after inclusion.
After 2 years of follow up (n=11), 7 patients (64%) were in remission off medication. One patient showed an ACRPed90 response but was still on rec Il-1RA therapy and two other patients showed ACRPed50 responses to MTX (n=1) and Canakinumab (n=1).
Conclusions This is the first prospective study describing the long term effectiveness of rec IL-1RA as first line therapy. We show quick clinical responses in nearly all patients, with ACRPed90 scores in 94% after 3 months. In the majority of responding patients IL-1RA therapy can be stopped within months with preserved remission during follow up of more than 2 years. However, in a substantial subset of patients, concomitant therapy is necessary to maintain clinical response. We recognize the need for randomized controlled trials comparing the use of rec IL-1RA to systemic steroids.
Disclosure of Interest None Declared