NextGen 2024: Unmet Needs & Clinical Trial Challenges Session Part 2
NextGen 2024: Unmet Needs & Clinical Trial Challenges Session Part 2
- 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.
NextGen 2024: Unmet Needs & Clinical Trial Challenges Session Part 2
@SJIA_Foundation3 months ago

Clinical Trials in Still's disease (sJIA/AOSD)
Fabrizio de Benedetti
Rheumatology, Children Hospital Bambino Gesu', Rome - Italy
- · 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
- · Acceptability of 'experimental' drugs vs established approach
- · Acceptability of randomization (experimental drug vs placebo or experimental drug vs active control)
- · 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
- · Acceptability of 'experimental' drugs vs established approach
- · Acceptability of randomization (experimental drug vs placebo or experimental drug vs active control)
- · 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
- · OK with JIA-ACR response + absence of fever, systJADAS (merging adults and children criteria)
- · Tapering/withdrawal of background treatment (e.g. GC)
- · 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 𡪠PK modeling for dosing in <12yo
- · Sample size
- · Randomization (placebo? Active control?)
- · Open label
- · External (historical) controls
- · Largely overlapping subset
- · Mostly IL-18 high
- · Many reccurrent eosinophilia
- · Many DRB1*15 carriers
- · Largely overlapping subset
- · Mostly IL-18 high
- · Many recurrent eosinophilia
- · Many DRB1*15 carriers
- · 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 (O 2 requirement, O 2 overnight saturation)
- · Tapering/withdrawal of background treatment (e.g. GC, biologics)
- · 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
- · OK with 2016 MAS criteria
- · NOT OK with ILAR because severe MAS present often at disease onset
- · OK with Yamaguchi or provisional PRINTO
- · MAS remission as defined in the emapalumab trial -> no formal validation
- · Tapering/withdrawal of background treatment (e.g. GC, biologics)
- · OK with 2016 MAS criteria
- · NOT OK with ILAR because severe MAS present often at disease onset
- · OK with Yamaguchi or provisional PRINTO
- · MAS remission as defined in the emapalumab trial -> no formal validation
- · Tapering/withdrawal of background treatment (e.g. GC, biologics)
- · Placebo controlled unethical
- · No active comparable available (SoC?)
- · Background treatment for Still's disease
- · Sample size
- · Historical controls
Clinical trials in Still's disease
Present scenario
Patient/Parent perspectives (physicians also)
Clinical trials in Still's disease
Present scenario
Patient/Parent perspectives (physicians also)

Refractory or D2T Still' disease
Refractory (D2T) Still's disease
(with or without active systemic features)
Refractory (D2T) Still's disease 1. persistent chronic arthritis
Classification criteria: OK with ILAR, Yamaguchi, provisional PRINTO Response criteria:
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
ð¡ª
PK modeling for dosing in <12yo
·
Sample size
·
Randomization (placebo? Active control?)
·
Open label
·
External (historical) controls
(with or without active systemic features)
Refractory (D2T) Still's disease 1. persistent chronic arthritis
Classification criteria: OK with ILAR, Yamaguchi, provisional PRINTO
Response criteria:
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)
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
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
Refractory (D2T) Still's disease 3. Acute MAS flare (with or without LD)
Classification criteria
Response criteria
Design
·
Placebo controlled unethical
·
No active comparable available (SoC?)
·
Background treatment for Still's disease
·
Sample size
·
Historical controls
Refractory (D2T) Still's disease 3. Acute MAS flare (with or without LD)
Classification criteria
Response criteria
Design











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