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

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

• 1. IL-18 testing in the diagnosis and management of Still’s disease: Game-changer or Red Herring? A manufactured conflict moderated by Scott Canna, MD 13 November 2024 Rheumatology

• 2. 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

• 3. IL-18 testing

• 4. 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

• 5.

• 6. Which is the Still’s Rash?

• 7. Still’ s FMF TRA PS HID S Kawasa ki CAP S ??? Stre p

• 8. Presentation continued EBV/CMV/Adeno/HHV 6 - PCR neg Perforin/GranyzmeB: elevated by % & MCF CD107a mobilization: normal Rapid WES sent: TAT ~ 2 weeks Remains stable

• 9. FUO with HLH • Prolonged viral syndrome • Still’s • Atypical KD • Autoinflammatory To ‘Roid Or Not To ‘Roid • Occult leukemia • Neuroblastoma • Cutaneous T-cell lymphoma Bone Marrow Biopsy Pan-Scan Further workup Empiric Treatment

• 10. FUO with HLH • Prolonged viral syndrome • Atypical KD • Autoinflammatory • Still’s • Monogenic IL-18opathies To ‘Roid Or Not To ‘Roid • Occult leukemia • Neuroblastoma • Cutaneous T-cell lymphoma Bone Marrow Biopsy Pan-Scan Further workup Treatment IL-18* > 20,000 – 40,000 Genetic workup if indicated Treatment 🡪 DC

• 11. OK, so it’s IL-18 = 128,000 Still’s 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 …?

• 12. Flare upon GC wean Recheck IL-18 to determine: Fever, ferritin, LFTs don’t tolerate < 0.5 mg/kg/day prednisolone • canakinumab up to 8mg/kg/dose q4week Need for sJIA-LD workup? Change in therapy? Prognosis?

• 13. Remission on medication Still’s MRD biomarkers • LDH/aldolase • D-dimer • Ferritin • sIL-2Ra • CXCL9 • S100A8/A9 • S100A12 • IL-18 Does great on ruxolitinib (10mg/m2/dose) and canakinumab (4mg/kg/month) - Normal CBC diff, ferritin X 18 month