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Treating new and refractory SJIA patients - Jennifer Huggins

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This talk was given by Dr. Jennifer Huggins of Cincinnati Childrens Hospital, at the Systemic Juvenile Idiopathic Arthritis (or SJIA) Family Day, on July 22nd, 2017.

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Treating new and refractory SJIA patients - Jennifer Huggins

  1. 1. Treating New & Refractory Systemic Onset Juvenile Idiopathic Arthritis(SJIA) Patients Jennifer L. Huggins, MD Associate Professor of Pediatrics Cincinnati Children’s Hospital Medical Center
  2. 2. Objectives 1. Be familiar with the approach to management of a child with new onset SJIA 2. Identify the most common treatment options for SJIA 3. Discuss the evidence for current treatment approaches in SJIA
  3. 3. Approach to Management • Usually acutely ill so often requires hospitalization for diagnosis and management • Evaluation: – Joints – Anemia – Cardiac – Pulmonary – Possible MAS (present in ~ 1/3 of SJIA at diagnosis)
  4. 4. Approach to Management • NSAIDs (Naprosyn,Ibuprofen, Meloxicam etc) – First line for those without severe disease – Helpful while diagnosis is being confirmed – Control fever (systemic inflammatory manifestations) – Modulate joint pain and inflammation – Seldom satisfactory alone • Subsequent treatment choices take into account – Severity of systemic features – Severity of arthritis – MAS features – Poor prognostic features
  5. 5. J Peds 2016;177:19-26
  6. 6. J Peds 2016;177:19-26 Disease Modifying Anti-Rheumatic Drugs Biologics
  7. 7. Biologic Response Modifiers: Examples: TNF inhibitors etanercept, adalimumab, infliximab Cytokine Inhibition
  8. 8. Biologic Response Modifiers: Examples: Abatacept, IL-1 and IL-6 inhibitors Cytokine Inhibition
  9. 9. -ximab -zumab -umab Arth Res &Ther 2009;11:225 Therapeutic Monoclonal Antibody
  10. 10. Nature Rev/Drug Disc 2007;6:75 Fusion Protein -cept
  11. 11. Biologics: Targets & Therapy 2008;2:229 Anakinra
  12. 12. IL-1 BLOCKADE FOR SYSTEMIC JIA Biologic Information Co-culture of healthy PBMCs with soJIA pt serum • IL-1b gene transcription (Affymetrix microarrays) was induced by 4/4 soJIA sera from 4- to 40-fold (median 8.2-fold) • IL-1a expression up-regulated by 3/4 of the soJIA sera (median 13-fold) • IL-1R1 and IL-1R2 upregulated 4- and 2-fold, respectively • IL-6 was up-regulated by 1/4 soJIA sera. Pascual V, et al., J Exp Med 2005; 201:1479-86
  13. 13. IL-1 BLOCKADE FOR SYSTEMIC JIA Biologic Information Ability of co-culture of sera & healthy PBMCs to induce actual production of IL-1b • Febrile soJIA sera vs normal sera P = 0.017 • Febrile soJIA sera vs Afebrile soJIA sera P = 0.005 • Afebrile soJIA sera vs normal sera P = 0.003 Pascual V, et al., J Exp Med 2005; 201:1479-86
  14. 14. Tocilizumab is an Anti-IL6 Receptor Monoclonal Antibody
  15. 15. Fever Joint Inflammation Growth Impairment Osteoporosis IL-6 in thepathogenesis ofJIA- Systemic (P Woo2008) Anemia Thrombocytosiss
  16. 16. Challenges to Management • Evidence is lacking to delineate the best treatment approach • Diversity of SJIA • Many trials of biologics do not include new-onset SJIA
  17. 17. American College of Rheumatology Treatment Recommendations • Based on rigorous evidence-based literature review – Core expert panel composed of experienced Pediatric Rheumatologists from the US, Canada, and Europe • 2011- Arthritis Care and Research, Vol 63, pages 465-482 • 2013 – Update fo the 2011 American College of Rheumatology Recommendations. Arthritis and Rheumatism, Vol 65, pages 2499-2512
  18. 18. Childhood Arthritis and Rheumatology Research Alliance (CARRA) • Comparative Effectiveness Studies aimed at identifying the best therapy(ies) for new-onset SJIA • Consensus Treatment Plans for New-Onset Systemic Juvenile Idiopathic Arthritis. Arthritis Care and Research,2012; Vol 64, pages 1001-1010. • Pilot Study Comparing the CARRA Systemic JIA Consensus Treatment Plans. Pediatric Rheumatology 2017
  19. 19. Effectiveness of First-Line Treatment with Recombinant Interleukin-1 Receptor Antagonist in Steroid-Naïve Patients with New-Onset SJIA • Arthritis & Rheumatology 2014;Vol 66:1034-1043 • First prospective study in which anakinra was used as first-line therapy in patients with SJIA. • Excellent response in nearly all patients within 3 months • 1/3 needed concomitant therapy (usually steroids) • Majority therapy could be stopped within one year

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