NextGen 2024: Unmet Needs & Clinical Trial Challenges Session Part 2

AI Summary

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Key Insights

IL-1 and IL-6 inhibitors are highly effective in 70-80% of Still's disease patients, becoming a standard early treatment.
Acceptability of experimental drugs and randomization is a key consideration for patients/parents in clinical trials.
Refractory (D2T) Still's disease presents challenges in clinical trials, including persistent arthritis, relapsing MAS, and acute MAS flares.
Different criteria apply to classify and assess response in different scenarios of Refractory (D2T) Still's disease
Clinical trial designs for refractory Still's disease face ethical and practical challenges, particularly for relapsing/smoldering MAS and acute MAS flares.

#Sjiafoundation #Curesjia #Stillsdisease #Sjia

Clinical Trials in Still´s disease (sJIA/AOSD)
Fabrizio de Benedetti
Rheumatology, Children Hospital Bambino Gesu’, Rome - Italy

1/11

2/11

$Clinical trials in Still‘s disease Present scenario •IL-1 or IL-6 inhibitors are very efficacious in 70-80% of patients • Early treatment with biologics is more and more standard of care with IL-1 and IL-6 inhibitors being widely available Patient/Parent perspectives (physicians also) •Acceptability of “experimental” drugs vs established approach •Acceptability of randomization (experimental drug vs placebo or experimental drug vs active control) Refractory or D2T Still‘ disease$

3/11

$Refractory (D2T) Still‘s disease •Persistent chronic arthritis (with or without active syst features) •Relapsing/smouldering MAS with or without LD •Acute MAS flare (with or without LD) • Difficult if not impossible to lump them in the same trial • Overall they are very rare • Only one trial is doable$

4/11

$Refractory (D2T) Still‘s disease 1. persistent chronic arthritis (with or without active systemic features) Classification criteria: OK with ILAR, Yamaguchi, provisional PRINTO Response criteria: • OK with JIA-ACR response + absence of fever, systJADAS (merging adults and children criteria) �• Tapering/withdrawal of background treatment (e.g. GC) Eligible for ongoing trials in pcJIA (e.g. Jak inhibitors), only if systemic symptoms are absent • Need new MoA (limited safety data) • 12 and older 🡪 PK modeling for dosing in <12yo • Sample size • Randomization (placebo? Active control?) • Open label • External (historical) controls$

5/11

$Refractory (D2T) Still‘s disease 1. persistent chronic arthritis (with or without active systemic features) Classification criteria: OK with ILAR, Yamaguchi, provisional PRINTO Response criteria: • OK with JIA-ACR response + absence of fever, systJADAS (merging adults and children criteria • Tapering/withdrawal of background treatment (e.g. GC) • Eligible for ongoing trials in JIA (e.g. Jak inhibitors), only if systemic symptoms are absent • Need new MoA (limited safety data) • 12 and older 🡪 PK modeling for dosing in <12yo • Sample size • Randomization (placebo? Active control?) • Open label • External (historical) controls$

6/11

$Refractory (D2T) Still‘s disease 2. Relapsing/smouldering MAS with or without LD Syst features - little, if any arthritis Lung disease (LD) Relapsing and/or smouldering MAS Classification criteria • NOT OK with ILAR, might be OK with Yamaguchi or provisional PRINTO • Response criteria • NOT OK with JIA-ACR response + absence of fever • MAYBE syst-JADAS (merging adults and children criteria) • Tapering/withdrawal of background treatment (e.g. GC, biologics) • Largely overlapping subset • Mostly IL-18 high • Many reccurrent eosinophilia • Many DRB1*15 carriers$

7/11

$Refractory (D2T) Still‘s disease 2. Relapsing/smouldering MAS with or without LD Syst features - little, if any arthritis Lung disease (LD) Relapsing and/or smouldering MAS Classification criteria • NOT OK with ILAR, OK with Yamaguchi or provisional PRINTO • Response criteria • NOT OK with JIA-ACR response + absence of fever • MAYBE syst-JADAS (merging adults and children criteria?) • Need to capture MAS features (MAS remission?) • Need to capture LD course (O2 requirement, O2 overnight saturation) • Tapering/withdrawal of background treatment (e.g. GC, biologics) • Largely overlapping subset • Mostly IL-18 high • Many recurrent eosinophilia • Many DRB1*15 carriers$

8/11

$Refractory (D2T) Still‘s disease 2. Relapsing/smouldering MAS with or without LD Syst features - little, if any arthritis Lung disease (LD) Relapsing and/or smouldering MAS • Design • Placebo controlled unethical • No active comparable available (no SoC) • Sample size • Historical controls • Largely overlapping subset • Mostly IL-18 high • Many reccurrent eosinophilia • Many DRB1*15 carriers$

9/11

$Refractory (D2T) Still‘s disease 3. Acute MAS flare (with or without LD) Classification criteria • OK with 2016 MAS criteria • NOT OK with ILAR because severe MAS present often at disease onset • OK with Yamaguchi or provisional PRINTO Response criteria • MAS remission as defined in the emapalumab trial -> no formal validation • Tapering/withdrawal of background treatment (e.g. GC, biologics) Design • Placebo controlled unethical • No active comparable available (SoC?) • Background treatment for Still´s disease • Sample size • Historical controls$

10/11

11/11