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. 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. 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. 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. J Peds 2016;177:19-26

6. J Peds 2016;177:19-26
Disease Modifying Anti-Rheumatic Drugs
Biologics

7. Biologic Response
Modifiers:
Examples: TNF
inhibitors etanercept,
adalimumab, infliximab
Cytokine Inhibition

8. Biologic Response
Modifiers:
Examples: Abatacept,
IL-1 and IL-6 inhibitors
Cytokine Inhibition

9. -ximab
-zumab
-umab
Arth Res &Ther 2009;11:225
Therapeutic Monoclonal Antibody

10. Nature Rev/Drug Disc 2007;6:75
Fusion Protein
-cept

11. Biologics: Targets & Therapy 2008;2:229
Anakinra

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. 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. Tocilizumab is an Anti-IL6 Receptor
Monoclonal Antibody

15. Fever
Joint Inflammation
Growth Impairment
Osteoporosis
IL-6 in thepathogenesis ofJIA-
Systemic
(P Woo2008)
Anemia
Thrombocytosiss

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. 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

23. 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

30. 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