None of the patients treated with ILARIS had a
disease relapse§ over 24 weeks3
- For patients taking placebo, median time to flare was 100 days
FMF, HIDS/MKD, AND TRAPS
Rapid resolution of index flare at Day 15—with no new flares through Week 16—was achieved by significantly more patients receiving ILARIS1
Percentage of Patients Achieving Complete Response* vs Placebo at Week 161
ILARIS
150 mg
150 mg
Placebo
FMF
61%
(N=31)
(N=31)
6%
(N=32)
(N=32)
(P<.0001)
(OR [95% CI]; 23.75 [4.38, 227.53])
(OR [95% CI]; 23.75 [4.38, 227.53])
HIDS/MKD
35%
(N=37)
(N=37)
6%
(N=35)
(N=35)
(P=.002)
(OR [95% CI]; 8.94 [1.72, 86.41])
(OR [95% CI]; 8.94 [1.72, 86.41])
TRAPS
46%
(N=22)
(N=22)
8%
(N=24)
(N=24)
(P=.005)
(OR [95% CI]; 9.17 [1.51, 94.61])
(OR [95% CI]; 9.17 [1.51, 94.61])
- At Day 15, the majority of patients with FMF (81%, n/N=25/31), HIDS/MKD (65%, n/N=24/37), and TRAPS (64%, n/N=14/22) who received ILARIS achieved resolution of index disease flare vs placebo: FMF (31%, n/N=10/32), HIDS/MKD (37%, n/N=13/35), and TRAPS (21%, n/N=5/24)
Additional Data
In the same study:
After the initial dose at Day 15, ILARIS improved disease activity as measured by PGA, as well as CRP levels1,2
Percentage of Patients Showing No or Minimal Signs of Disease Activity (PGA score <2) vs Placebo at Day 151
ILARIS
150 mg
150 mg
Placebo
FMF
87%
(N=31)
(N=31)
41%
(N=32)
(N=32)
(OR [95% CI]; 10.07 [2.78, 36.49])
HIDS/MKD
70%
(N=37)
(N=37)
40%
(N=35)
(N=35)
(OR [95% CI]; 3.42 [1.28, 9.16])
TRAPS
64%
(N=22)
(N=22)
33%
(N=24)
(N=24)
(OR [95% CI]; 4.06 [1.12, 14.72])
PGA scores at
baseline2:
- 10% of patients with FMF in the ILARIS group had mild disease vs 19% in
the placebo group
- In the ILARIS group, 55% had moderate disease and 36% had severe disease compared with 59% and 22%, respectively, in the placebo group
- 27% of patients with HIDS/MKD in the ILARIS group had mild disease vs 20%
in the placebo group
- In the ILARIS group, 60% had moderate disease and 14% had severe disease compared with 60% and 20%, respectively, in the placebo group
- 41% of patients with TRAPS in the ILARIS group had mild disease vs 46% in
the placebo group
- In the ILARIS group, 50% had moderate disease and 9% had severe
disease compared with 46% and 8%, respectively, in the
placebo group
- In the ILARIS group, 50% had moderate disease and 9% had severe
disease compared with 46% and 8%, respectively, in the
At Day 15, CRP ≤10 mg/L Achieved by1:
FMF
90%
of patients receiving ILARIS (n/N=28/31) vs 28%
receiving placebo (n/N=9/32)
HIDS/MKD
68%
of patients receiving ILARIS (n/N=25/37) vs 26%
receiving placebo (n/N=9/35)
TRAPS
59%
of patients receiving ILARIS (n/N=13/22) vs 33%
receiving placebo (n/N=8/24)
CRP treatment comparisons (OR [95% CI]): FMF (22.51 [5.41, 93.62]), HIDS/MKD (6.05 [2.14, 17.12]), and TRAPS (3.88 [1.05, 14.26]).
Study Design1
The efficacy of ILARIS was assessed in patients with PFS across 3 disease cohorts: FMF, HIDS/MKD, and TRAPS. In the 16-week, double-blind, placebo-controlled treatment period, patients were randomized to receive ILARIS 150 mg (2 mg/kg for a body weight of ≤40 kg) or placebo every 4 weeks for 16 weeks and were allowed uptitration to ILARIS 300 mg (or 4 mg/kg) every 4 weeks for patients whose disease flare did not resolve or who had persistent disease, or active treatment.
The primary endpoint was the proportion of complete responders within each cohort as defined by patients who had resolution of their index disease flare at Day 15 and did not experience a new disease flare during the remainder of the 16-week treatment period.
Complete response was defined as resolution of index flare (PGA <2 and CRP ≤10 mg/L or a ≥70% reduction from baseline) at Day 15 and no new flare (PGA ≥2 and CRP ≥30 mg/L) throughout the 16-week treatment period.
A 5-point PGA scale was used by physicians to assess overall disease severity, where 0=no disease-associated signs and symptoms, 1=minimal, 2=mild, 3=moderate, and 4=severe. The key signs and symptoms assessed in the PGA for each condition were the following: FMF: abdominal pain, skin rash, chest pain, and arthralgia/arthritis; HIDS/MKD: abdominal pain, lymphadenopathy, and aphthous ulcers; TRAPS: abdominal pain, skin rash, musculoskeletal pain, and eye manifestations.
*Complete response defined as resolution
of index flare (PGA <2 and CRP ≤10 mg/L or a ≥70% reduction from baseline) at
Day 15 and no new flare (PGA ≥2 and CRP ≥30 mg/L) throughout the 16-week
treatment period.
CAPS
In Study Part
1:
The majority of patients achieved complete clinical response at
Weeks 1 and 8 after the first dose of ILARIS1,3
Percentage of Patients Achieving Complete Clinical Response With ILARIS
WEEK 1
71%
(n/N=25/35)
WEEK 8
97%
(n/N=34/35)
Complete clinical response was defined
as meeting all of the following criteria3:
- Physician’s assessment of disease activity ≤ minimal (rated on a 5-point scale consisting of absent, minimal, mild, moderate, and severe)
- Assessment of skin disease ≤ minimal (rated on a 5-point scale consisting of absent, minimal, mild, moderate, and severe)
- Normal serum values of CRP and SAA (<10 mg/L)
Assessment of disease activity included a composite of the following symptoms: urticarial skin rash, headache/migraine, fatigue/malaise, conjunctivitis, arthralgia, myalgia, and other symptoms related or unrelated to CAPS.
In Study Part
2:
After 3 doses† of ILARIS, 100% of patients remained
flare free through 24 weeks1,3‡
Percentage of Patients Who Were Flare Free vs Placebo at Week 32
ILARIS
Placebo
100%
(n/N=15/15)
(n/N=15/15)
19%
(n/N=3/16)
(n/N=3/16)
Additional Data
- During the open-label treatment period (Part 3), 97% (n/N=30/31) of patients were without disease relapse4||
Physician’s Global Assessment of Disease Activity and Assessment of Skin Disease1:
At the end of Study Part 2
- 93% (n/N=14/15) had no rash and 7% (n/N=1/15) had minimal rash after treatment with ILARIS vs 31% (n/N=5/16) and 19% (n/N=3/16), respectively, with placebo
- 100% (n/N=15/15) had no or minimal disease activity after treatment with ILARIS vs 25% (n/N=4/16) with placebo
At the end of Study Part 3
- 94% (n/N=29/31) had no rash and 6% (n/N=2/31) had minimal rash after treatment with ILARIS
- 97% (n/N=30/31) had no or minimal disease activity after treatment with ILARIS
- Analysis has not been adjusted for multiple comparisons. No conclusions of statistical or clinical significance can be drawn
Study Design1,3
A 3-part study in patients with CAPS (MWS) treated with a subcutaneous dose of ILARIS 150 mg (in patients weighing >40 kg) or ILARIS 2 mg/kg (in patients weighing ≥15 kg and ≤40 kg) every 8 weeks.
Part 1
An 8-week open-label treatment period in which 35
patients were treated with a single injection of ILARIS 150 mg.
Part 2
A double-blind, randomized withdrawal phase in
which patients who achieved a complete clinical response and did not relapse
by Week 8 in Part 1 were randomized to ILARIS 150 mg or 2 mg/kg in patients
weighing ≥15 kg and ≤40 kg (n=15) or placebo (n=16) every 8 weeks for 24
weeks. During Part 2, patients continued with blinded treatment unless a
relapse occurred to prompt early entry into Part 3.
Part 3
An open-label treatment period in which patients
received ILARIS 150 mg (n=31) every 8 weeks. Patients entered Part 3 at the
end of Part 2 or at the time of relapse, whichever occurred first. For
patients who completed Part 2 without disease flare, Part 3 had a duration of
16 weeks. For patients who had disease relapse in Part 2, Part 3 had a
duration of up to 40 weeks. The total study duration was 48 weeks.
The primary endpoint was the proportion of patients experiencing relapse in Part 2.
†For patients with CAPS, ILARIS is dosed
once every 8 weeks.
‡Ten patients in the placebo group met the
criteria for clinical relapse, and 3 patients discontinued Part 2 due to
unsatisfactory therapeutic effect.4
§Disease relapse: Defined as CRP and/or
SAA value >30 mg/L and either a score of mild or worse for physician’s assessment
of disease activity, or a score of minimal or worse for physician’s assessment of
disease activity and assessment of skin disease.1
||Includes all 15 patients randomized to
ILARIS in Part 2 and 15 of 16 patients randomized to placebo in Part 2. Disease
relapse was defined as CRP and/or SAA value >30 mg/L and either a score of mild
or worse for physician’s assessment of disease activity, or a score of minimal or
worse for physician’s assessment of disease activity and assessment of skin
disease.1,4
