nts with return of disease and rescue treatment was available after 12 weeks of retreatment.
AMAGINE-2 and AMAGINE-3 were identical placebo- and ustekinumab-controlled trials conducted in 1831 and 1881 patients, respectively. Both trials included a 12-week double-blind, placebo- and ustekinumab-controlled induction phase followed by a double-blind maintenance phase up to 52 weeks. Patients randomised to Kyntheum in the induction phase received 210 mg or 140 mg at Week 0 (day 1), Week 1, and Week 2 followed by same dose every 2 weeks. Patients randomised to ustekinumab received 45 mg for patients ≤100 kg and 90 mg for patients >100 kg at Weeks 0, 4, and 16 followed by same dose every 12 weeks. At Week 12, patients originally randomised to Kyntheum were re-randomised to receive either 210 mg every 2 weeks, or 140 mg every 2 weeks, or 140 mg every 4 weeks, or 140 mg every 8 weeks during the maintenance phase. Patients originally randomised to placebo received Kyntheum 210 mg every 2 weeks beginning at Week 12. At Week 12, patients in the ustekinumab group continued to receive ustekinumab and then were switched to Kyntheum 210 mg every 2 weeks at Week 52. Rescue treatment was available at or after Week 16 for patients with an inadequate response single sPGA ≥3 or persistent sPGA of 2 over at least a 4-week period.
Table 2: Overview of the main efficacy results
AMAGINE-1
AMAGINE-2 and AMAGINE-3
Placebo
Kyntheum
210 mg Q2W
Placebo
Kyntheum
210 mg Q2W
Ustekinumab
n-randomised
220
222
624
1236
613
n-completed Week 12
209
212
601
1205
594
n-in maintenance
84
83
NA
339
590
n-completed Week 52
2
74
NA
236
300
PASI
PASI Baseline score (mean±SD)
19.7±7.7
19.4±6.6
20.2±8.4
20.3±8.3
20.0±8.4
PASI 75 Week 12 (%)
3
83*
7
86*
70*
PASI 75 Week 52 (%)
0
87*
NA
65
48
sPGA (%)
sPGA 0 or 1 Week 12
1
76*
4
79*
59*
sPGA 0 or 1 Week 52
0
83*
NA
65
45
PSI
PSIBaseline score (mean±SD)
19.0±6.7
18.9±6.7
18.8±6.9
18.7±7.0
18.8±6.9
PSIresponder Week 12 (%)
4
61*
7
64*
54*
Q2W = every 2 weeks
PSI = Psoriasis Symptom Inventory. PSI responder: total score ≤8 with no item scores >1; SD: standard deviation.
Non-responder imputation is used to impute missing data.
Due to re-randomisation to other explored dose regimens, n-in maintenance is substantially lower than n-randomised in several arms. The maintenance phase in AMAGINE-2 and -3 did not include placebo.
*p-value vs. corresponding placebo, adjusted for stratification factors <0.001
PASI 75 response at 2 weeks ranged between 20% and 25% in the Phase 3 trials compared to placebo (0% to 0.6%) and ustekinumab (3% to 3.5%).
Figure 1: PASI 100 during induction and maintenance phase for Kyntheum and ustekinumab (AMAGINE-2 and AMAGINE-3, pooled)
N = number of patients, which are presented at baseline, Week 12, and Week 52
Q2W = every 2 weeks
*Patients were administered ustekinumab in the induction phase and continued on ustekinumab in the maintenance phase
**Patients were administered Kyntheum 210 mg every 2 weeks in the induction phase and re-randomised to Kyntheum 210 mg every 2 weeks in the maintenance phase
NRI= Non-responder imputation
In all three clinical trials, examination of age, gender, race, use of prior systemic or photo therapy, use of prior biologics, and biologic failures did not |
