er;‡b
1.3b
21.4b
57.7‡c
55.5‡c
29.4 c
PASI 100 (%)
11.8†‡b
12.4†‡b
0
4.8b
27.0‡c
22.8‡c
10.7c
DLQI Score 0 or 1 (%)
47.4†¥
40.2†
8.0
35.5
65.0‡c
54.1‡c
39.4c
a Co-primary efficacy endpoint at week 12.
b Non responder imputation for missing data.
c No imputation for missing data.
*The number of doses administered refers only to tildrakizumab groups.
n = number of patients in the full analysis set for which data was available, after imputation when applicable.
p-values calculated using the Cochran-Mantel-Haenszel (CMH) test stratified by body weight (≤90 kg, >90 kg) and prior exposure to biologic therapy for psoriasis (yes/no).
† p≤0.001 versus placebo; ‡ p≤0.001 versus etanercept; ¥ p≤0.05 versus etanercept.
Maintenance of Response
The maintenance of response in studies reSURFACE1 and reSURFACE2 are presented in Table 3. Maintenance and durability of PASI 90 response over time is presented in Figure 1.
Table 3. Maintenance of Response in Studies reSURFACE 1 and reSURFACE 2
Long term responsea,b
200 mg
100 mg
reSURFACE 1
Week 28
Week 64
Week 28
Week 64
Number of patients
116
114
115
112
PGA of “clear” or “minimal” with ≥2 grade improvement from Baseline (%)
80.2
76.3
80.9
61.6
PASI 90 (%)
70.7
74.6
65.2
58.0
PASI 100 (%)
38.8
40.4
25.2
32.1
reSURFACE 2
Week 28
Week 52
Week 28
Week 52
Number of patients
108
105
213
204
PGA of “clear” or “minimal” with ≥2 grade improvement from Baseline (%)
88.0
84.8
84.0
79.4
PASI 90 (%)
75.0
81.9
74.2
78.4
PASI 100 (%)
34.3
46.7
30.2
35.3
a Long-term response in patients who were responders (had achieved at least PASI 75) to tildrakizumab at week 28.
b No imputation for missing data.
Figure 1. Maintenance and durability of PASI 90 Response. Proportion of Patients with PASI 90 response over time up to Week 64 (Full Analysis Set Part 3*)
Patients randomised to tildrakizumab 100 mg or tildrakizumab 200 mg in Part 1 who were PASI 75 responders at week 28 (reSURFACE1).
*No imputation of missing data.
**These patients were switched to placebo at week 28.
Quality of Life/Patient-reported Outcomes
At week 12 and across studies, tildrakizumab was associated with statistically significant improvement in Health-related Quality of Life as assessed by the DLQI (Table 2). Improvements were maintained over time with at week 52, 63.7% (100 mg) and 73.3% (200 mg) in reSURFACE 1, and 68.8% (100 mg) and 72.4% (200 mg) in reSURFACE 2 of patients who were PASI 75 responder at week 28 having a DLQI of 0 or 1.
Paediatric population
The European Medicines Agency has deferred the obligation to submit the results of studies with Ilumetri in one or more subsets of the paediatric population in the treatment of plaque psoriasis (see section 4.2 for information on paediatric use).
5.2 Pharmacokinetic properties
Absorption
The subcutaneous formulation of tildrakizumab showed an absolute bioavailability ranging from 73% (90% CI: 46% - 115%, 200 mg SC vs. 3 mg/kg IV) to 80% (90% CI: 62% - 103%, 50 mg SC vs. 0.5 mg/kg IV) in healthy subjects, as a result of cross study single dose comparison. Maximum concentration was reached at 6.2 days after injection. Population PK analysis indicated a 31% higher bio |
