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THU0333 Effectiveness and long-term follow up of recombinant IL-1RA as first line therapy in newly onset juvenile idiopathic arthritis
  1. S. Vastert1,
  2. W. De Jager2,
  3. B.J. Noordman2,
  4. D. Holzinger3,
  5. W. Kuis1,
  6. B. Prakken1,
  7. N. Wulffraat1
  1. 1Pediatric rheumatology, University Medical Center
  2. 2Pediatric immunology, University Medical Center, Utrecht, Netherlands
  3. 3Institut für Immunologie, Universitätsklinikum Münster, Münster, Germany


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

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