NEXTGEN THERAPIES IN SJIA STILL'$ & MAS

• IL-18 testing in the diagnosis and management of Still's disease: Game-changer or Red Herring?

Disclosures

• · Industry funded research
• · Site PI (completed): Novartis, AB2Bio
• · In-kind support: Simcha
• · Advisor/Consultant
• · AB2Bio, Apollo, Sobi, Bristol-Myers Squibb
• · Educational Speaker
• · PracticePoint CME, Sobi, Johnson & Johnson, Bristol-Myers Squibb
• · Advisory Committee/Board: none
• · Stock/ownership: none
• · Relevant patents: none
IL-18 testing



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• 1a dricd smoked smoke.
• 2 somcthing; esp. a misleading or distracting cluc,

A common clinical conundrum

6 mos prev healthy male

• -Born FT, no preg/perinatal issues
• -Presented to ED for fever x 3d, rash prior but not present in ED
• -Noted to have anemia (Hgb 9), ANC 730, Plt 65 🡪 dx'd virus/viral suppression and DC'd
• -10 days later at Pediatrician for repeat labs
• -No more fevers. Modest cough (parents say has been there a while)
• -ANC 790, Hgb stable, Plt 150
• -A few days after some vaccinations 🡪 Fever 39
• -ED: ANC 260, Hgb 8.5, Plt 138, LDH 742, Uric Acid normal.
• -Admission: Blood Cx neg, peripheral smear without blasts, a few atypical lymphs
• -CRP 3.2 mg/dL
• -AST 243, ALT 347, normal bilirubin
• -Spleen tip palpable🡪 sl enlarged on US
• -Ferritin 3537, Fibrinogen 105, TG 398
• -Multiple consults: Exam o/w normal. Echo normal (no other KD stigmata). No arthritis. No uveitis.
• -Febrile one night - resident reported a red hive-like rash





s


Presentation continuedEBV/CMV/Adeno/HHV

6

• -PCR neg

Perforin/GranyzmeB: elevated by % & MCF CD107a mobilization: normal

Rapid WES sent: TAT ~ 2 weeks

Remains stable



FUO with HLH


OK, so it's Still's

IL-18 = 128,000 pg/mL CXCL9 = 14,000 pg/mL sIL-2Ra = 2300 pg/mL Anakinra 4mg/kg

GC 2mg/kg

Good initial response!

• • Fevers
• • CBC
• • ferritin

Recheck IL-18 in

…?

Flare upon GC wean

Fever, ferritin, LFTs don't tolerate < 0.5 mg/kg/day

prednisolone

• · canakinumab up to 8mg/kg/dose q4week

Recheck IL-18 to determine:

Need for sJIA-LD workup?

Change in therapy?

Prognosis?

Remission on medication

Does great on ruxolitinib (10mg/m 2 /dose) and canakinumab

(4mg/kg/month)

• -Normal CBC diff, ferritin X 18 month

Still's MRD

biomarkers

• · LDH/aldolase
• · D-dimer
• · Ferritin
• · sIL-2Ra
• · CXCL9
• · S100A8/A9
• · S100A12
• · IL-18