L-23 is a naturally occurring cytokine that is involved in inflammatory and immune responses. Tildrakizumab inhibits the release of proinflammatory cytokines and chemokines.
Clinical efficacy and safety
The multicentre, randomised, double-blind, placebo-controlled trials reSURFACE 1 and reSURFACE 2 studies enrolled a total of 1,862 patients 18 years of age and older with plaque psoriasis who had a minimum body surface area involvement of 10%, a Physician Global Assessment (PGA) score of ≥3 in the overall assessment (plaque thickness, erythema, and scaling) of psoriasis on a severity scale of 0 to 5, a Psoriasis Area and Severity Index (PASI) score ≥12, and who were candidates for phototherapy or systemic therapy.
In these studies, patients were randomised to either placebo or tildrakizumab (including 200 mg and 100 mg at 0, 4 and every twelve weeks thereafter [Q12W]), up to 52 or 64 weeks. In the active comparator study (reSURFACE 2), patients were also randomised to receive etanercept 50 mg twice weekly for 12 weeks, and weekly thereafter up to 28 weeks.
Overall demographic and baseline characteristics in reSURFACE1 and reSURFACE2 studies were consistent across individual trials. Patients were 18 to 82 years old, with a mean age of 45.9. The median baseline PASI score ranged from 17.7 to 18.4 across treatment groups. Baseline PGA score was marked or severe in 33.4% of patients. Of all patients, 35.8% had received prior phototherapy, 41.1% had received prior conventional systemic therapy, 16.7% had received prior biologic therapy for the treatment of plaque psoriasis. A total of 15.4% of study patients had a history of psoriatic arthritis. Mean baseline Dermatology Life Quality Index (DLQI) ranged from 13.0 to 14.8.
Studies reSURFACE 1 and reSURFACE 2 assessed the changes from baseline at Week 12 in the two co-primary endpoints: 1) PASI 75 and 2) PGA of “0” (cleared) or “1” (minimal), with at least a 2-point improvement from baseline. Other eva luated outcomes included the proportion of patients who achieved PASI 90, PASI 100, the proportion of patients with DLQI 0 or 1, and maintenance of efficacy up to 52/64 weeks.
Results obtained at weeks 12, 28 and beyond (up to week 64 in reSURFACE 1 and up to week 52 in reSURFACE 2) are presented in Table 2 and Table 3.
Table 2. Summary of Response Rates in Studies reSURFACE 1 and reSURFACE 2
Week 12 (2 doses)*
Week 28 (3 doses)*
200 mg
100 mg
Placebo
Etanercept
200 mg
100 mg
Etanercept
reSURFACE1
Number of patients
308
309
154
-
298
299
-
PASI 75a (%)
62.3†b
63.8†b
5.8b
-
81.9c
80.4c
-
PGA of “clear” or “minimal” with ≥2 grade improvement from Baselinea (%)
59.1†b
57.9†b
7.1b
-
69.1c
66.0c
-
PASI 90 (%)
35.4†b
34.6†b
2.6b
-
59.0c
51.6c
-
PASI 100 (%)
14.0†b
13.9†b
1.3b
-
31.5c
23.5c
-
DLQI Score 0 or 1 (%)
44.2†
41.5 †
5.3
-
56.7c
52.4c
-
reSURFACE2
Number of patients
314
307
156
313
299
294
289
PASI 75a (%)
65.6†‡b
61.2†‡b
5.8b
48.2b
72.6‡b
73.5‡b
53.6b
PGA of “clear” or “minimal” with ≥2 grade improvement from Baselinea (%)
59.2†¥b
54.7†b
4.5b
47.6b
69.2‡b
64.6‡b
45.3b
PASI 90 (%)
36.6†‡b
38.8&dagg |
