NextGen 2024: Refractory SJIA & MAS Session Part 2

NextGen 2024: Refractory SJIA & MAS Session Part 2

• 1. Systemic Juvenile Idiopathic Arthritis: Resistant disease, UK experience Paul Brogan Professor of vasculitis and consultant paediatric rheumatologist

• 2. .…Changing therapeutic landscape 2015 “interim” NHS Clinical Commissioning Policy 2005 2021 Methotrexate - Woo P et al. Arthritis Rheum. 2000;43(8):1849–57. Anakinra ANAJIS trial - Quartier et al. Ann Rheum Dis 2011;70:747–754. TocilizumabTENDER Trial - De Benedetti et al. N Engl J Med 2012;367:2385-95. Canakinumab - Ruperto et al; N Engl J Med. 2012 Dec 20;367(25):2396-406. Emapalumab - Ann Rheum Dis. 2023 Jun;82(6):857-865.

• 3. Summary - GOSH experience of sJIA (n=76) Overall sJIA outcome good – at last review (median 4.7 years, 0.2-16); • 88% - Clinically Inactive Disease (CID) • 84% - Glucocorticoid free CID • 32% - Remission Biologic treatment < 3 months results in significantly better outcome at 1 year • Clinically inactive disease 90% versus 53%, p = 0.002 No difference in longer term outcomes (CID and GC free CID) in relation to timing of bDMARD in our series Foley C et al; Front. Pediatr., Vol 11 (2023) https://doi.org/10.3389/fped.2023.1218312

• 4. Complications: 2005-2021 Macrophage Activation Syndrome • 46% (n=35/76) – At least one episode of suspected MAS throughout disease course • Treatments received: • Glucocorticoids • Anakinra • Ciclosporin • Etoposide • Emapalumab (clinical trial) Resistant disease: Bone marrow transplant • Four patients • All achieved clinically inactive disease sJIA – Lung disease • One patient (1%) Mortality • No patients died during study period (2005-2021) • One patient died from MAS, 7-months after data collection completed Underdiagnosed

• 5. Resistant disease: treatment Arthritis Systemic inflammation Smouldering/recurrent MAS sJIA-Lung disease Lots of options as per poly JIA Anakinra Tocilizumab Canakinumab JAK-inhib Ciclosporin MTX Glucocorticoids Anakinra Tocilizumab Canakinumab Emapalumab JAK-inhib Ciclosporin Glucocorticoids Etoposide Allo-HSCT Anti-IL18? Anti-IL18/IL1? Anakinra Tocilizumab Canakinumab Emapalumab? JAK-inhib Ciclosporin Glucocorticoids Allo-HSCT Anti-IL18? Anti-IL18/IL1?

• 6. Thank you Front. Pediatr., Vol 11 (2023) https://doi.org/10.3389/fped.2023.1218312

• 7. sJIA/Still’s Switch to SC or IV Tocilizumab10 Active systemic features? YES NO Anakinra8,11,13,19,26,49,50,51 2-8 mg/kg/day SC (usual max 100 mg/day), *usually with glucocorticoids: • Prednisolone 1-2 mg/kg/day • +/- IV methylprednisolone 10-30 mg/kg/day (max 1000 mg) for 3 doses • Add MTX for active arthritis if not on already • Switch to anti-TNF • Switch to Canakinumab12 (compassionate use) or consider other **biologic48 • Consider addition of Ciclosporin • If fails, consider allogeneic HSCT Inadequate response after 3 months Inadequate response after 3 months Inadequate response after 3-6 months