J&J Medical Connect
icotrokinra
J&J Medical Connect

Connect with us

Connect with us

This information is intended for US healthcare professionals to access current scientific information about J&J Innovative Medicine products. It is prepared by Medical Information and is not intended for promotional purposes, nor to provide medical advice.

icotrokinra

Medical Information

Icotrokinra – Comparison to Deucravacitinib in the Treatment of Plaque Psoriasis

Last Updated: 02/05/2026

SUMMARY

  • Icotrokinra (JNJ-77242113) is a targeted oral peptide that selectively binds the interleukin-23 (IL-23) receptor and inhibits IL-23 pathway signaling.1 
  • ICONIC-ADVANCE 1 and ICONIC-ADVANCE 2 are ongoing, phase 3, multicenter, randomized, double-blind, placebo (PBO)- and active-comparator (deucravacitinib)-controlled studies (NCT06143878 and NCT06220604) evaluating the efficacy and safety of oral icotrokinra 200 mg once daily in adults with moderate to severe plaque psoriasis (PsO).1 
    • At week 16, a higher proportion of patients in the icotrokinra group achieved Investigator’s Global Assessment (IGA) 0/1 response vs those receiving deucravacitinib (ADVANCE 1: 68% vs 50%, P<0.0001; ADVANCE 2: 70% vs 54%, P<0.0001). Findings were consistent at week 24.
    • In addition, more patients in the icotrokinra cohort experienced clear skin (IGA 0) and Psoriasis Area and Severity Index (PASI) 100 response at week 16 compared to those in the deucravacitinib cohort (ADVANCE 1, IGA 0: 37% vs 16%; ADVANCE 2, IGA 0: 37% vs 17%; ADVANCE 1, PASI 100: 31% vs 11%; ADVANCE 2, PASI 100: 32% vs 14%; all P values were <0.0001). Similar results were obtained at week 24. Other key secondary endpoints for icotrokinra vs deucravacitinib are summarized below.
    • Through week 16, across both studies, 48%, 57%, and 57% of patients receiving icotrokinra, PBO, and deucravacitinib, respectively, reported at least 1 adverse event (AE). The most common AEs were nasopharyngitis and upper respiratory tract infection. Through week 24, across both studies, serious AEs occurred in 3% of the icotrokinra group and 3% of the deucravacitinib group.

CLINICAL DATA

ICONIC-ADVANCE 1 and ICONIC-ADVANCE 2

Stein Gold et al (2025)1 reported results through week 24 from ICONIC-ADVANCE 1 and ICONIC-ADVANCE 2, 2 phase 3, multicenter, randomized, double-blind clinical trials evaluating the efficacy and safety of icotrokinra compared to PBO and deucravacitinib for the treatment of adults with moderate to severe plaque PsO.

Study Design/Methods


Select Inclusion/Exclusion Criteria for ICONIC-ADVANCE 1 and ICONIC-ADVANCE 21 
Inclusion Criteria
Exclusion Criteria
  • Adults (≥18 years of age) with moderate to severe plaque PsO diagnosed for ≥26 weeks at screening
  • Total BSA involvement of ≥10%, PASI score of ≥12, and IGA score of ≥3 at screening
  • Candidate for phototherapy or systemic treatment
  • Nonplaque form of PsO (eg, erythrodermic, guttate, or pustular)
  • Primary efficacy failure or clinically significant side effects related to IL-23 or TYK2 inhibitors (except for prior IL-12/23 biologic failure)
Abbreviations: BSA, body surface area; IGA, Investigator’s Global Assessment; IL, interleukin; PASI, Psoriasis Area and Severity Index; PsO, psoriasis; TYK2, tyrosine kinase 2.
  • Patients were randomized to oral icotrokinra 200 mg once daily, PBO, or deucravacitinib 6 mg, with PBO crossover to icotrokinra at week 16 and deucravacitinib crossover to icotrokinra at week 24. ADVANCE 1 and ADVANCE 2 utilized different randomization ratios (2:1:2 and 4:1:4, respectively). See Figure: ICONIC-ADVANCE Program Study Design.

ICONIC-ADVANCE Program Study Design1,2

Abbreviations: ADV, ADVANCE; Deucra, deucravacitinib; ICO, icotrokinra; PBO, placebo; R, randomized; QD, daily; W, week.


Select Outcomes in the ICONIC-ADVANCE Program1
Co-primary Endpoints
Time Frame
Icotrokinra vs PBO
Percentage of patients who achieved an IGA score of 0 (clear skin) or 1 (almost clear skin) with a ≥2-grade improvement from baseline
Week 16
Percentage of patients who achieved PASI 90 response
Week 16
Key Secondary Endpoints
Icotrokinra vs deucravacitinib
Percentage of patients who achieved an IGA score of 0 (clear skin) or 1 (almost clear skin) with a ≥2-grade improvement from baseline
Weeks 16 and 24
Percentage of patients who achieved IGA score of 0 (clear skin)
Weeks 16 and 24
Percentage of patients who achieved PASI 75, PASI 90, and PASI 100 responses
Weeks 16 and 24
Percentage of patients who achieved PSSD symptom score of 0
Week 16
Abbreviations: IGA, Investigator’s Global Assessment; PASI, Psoriasis Area and Severity Index; PBO, placebo; PSSD, Psoriasis Symptoms and Signs Diary.
Note: Additional details regarding study outcomes can be found on clinicaltrials.gov (ADVANCE 1 and ADVANCE 2).
  • In both studies, the efficacy analysis included all randomized patients, with a composite strategy (non-responder imputation) being utilized for the co-primary endpoints. The safety analysis set in both studies included all randomized and treated patients. Of note, safety data from ICONIC-ADVANCE 1 and ICONIC-ADVANCE 2 were combined to identify any uncommon AEs.1

Results

Patient Characteristics


Select Baseline Demographics and Clinical Characteristics1
ICONIC-ADVANCE 1
ICONIC-ADVANCE 2
ICO
(n=311)
PBO
(n=156)
Deucra
(n=307)
ICO
(n=322)
PBO
(n=82)
Deucra
(n=327)
Demographics
Age, years, mean (SD)
47.1 (13.19)
46.9 (12.78)
46.3 (13.87)
45.9 (13.78)
48.4 (13.90)
45.6 (13.22)
Male sex, n (%)
223 (72)
105 (67)
200 (65)
218 (68)
55 (67)
223 (68)
White race, n (%)
231 (74)
118 (76)
221 (72)
274 (85)
65 (79)
265 (81)
Disease Characteristics
Duration of PsO, years, mean (SD)
17.52 (11.10)
17.88 (12.75)
16.81 (12.81)
17.43 (13.38)
21.21 (15.17)
16.82 (12.03)
PASI total score (0-72), median (IQR)
18.60 (15.50, 22.70)
17.15 (14.40, 21.65)
18.00 (15.00, 23.40)
18.00 (15.10, 22.20)
17.95 (14.30, 23.60)
17.60 (15.20, 21.40)
IGA score of 3 (moderate), n (%)
251 (81)
123 (79)
242 (79)
252 (78)
67 (82)
267 (82)
IGA score of 4 (severe), n (%)
60 (19)
33 (21)
65 (21)
70 (22)
15 (18)
60 (18)
Previous PsO Therapy
Systemic therapy, n (%)a
236 (76)
110 (71)
225 (73)
225 (70)
58 (71)
230 (70)
   Phototherapyb
112 (36)
53 (34)
97 (32)
98 (30)
31 (38)
109 (33)
   Conventional non-biological
   systemic therapyc
171 (55)
79 (51)
152 (50)
165 (51)
39 (48)
163 (50)
   Novel non-biological systemic
   therapyd
22 (7)
12 (8)
38 (12)
16 (5)
3 (4)
12 (4)
   Biologic therapye
86 (28)
42 (27)
80 (26)
78 (24)
26 (32)
77 (24)
Abbreviations: Deucra, deucravacitinib; ICO, icotrokinra; IGA, Investigator’s Global Assessment; IQR, interquartile range; PASI, Psoriasis Area and Severity Index; PBO, placebo; PsO, psoriasis; PUVA, psoralen and ultraviolet A radiation; SD, standard deviation; UVB, ultraviolet B.
aIncludes conventional nonbiologic systemics, novel nonbiologic systemics, 1,25-vitamin D3 and analogues, phototherapy, and biologics.
bIncludes PUVA and UVB.
cIncludes PUVA, methotrexate, cyclosporine, acitretin, azathioprine, and fumarate.
dIncludes apremilast and tofacitinib.
eIncludes etanercept, infliximab, adalimumab, ustekinumab, briakinumab, secukinumab, ixekizumab, brodalumab, guselkumab, risankizumab, tildrakizumab, alefacept, efalizumab, natalizumab, and cetolizumab pegol.

Efficacy

  • At week 16, a significantly higher proportion of patients in the icotrokinra group achieved the co-primary endpoint of IGA 0/1, with a ≥2-grade improvement from baseline, compared to those in the PBO group (ADVANCE 1: 68% vs 11%, P<0.0001; ADVANCE 2: 70% vs 9%, P<0.0001).
  • Similarly, for the co-primary endpoint of PASI 90, significantly more patients receiving icotrokinra achieved PASI 90 response at week 16 vs those receiving PBO (ADVANCE 1: 55% vs 4%, P<0.0001; ADVANCE 2: 57% vs 1%, P<0.0001).
  • The key secondary endpoints comparing icotrokinra to deucravacitinib are described in Table: Key Secondary Endpoints (Icotrokinra vs Deucravacitinib).

Key Secondary Endpoints (Icotrokinra vs Deucravacitinib)1,3 
% (n)
ICONIC-ADVANCE 1
ICONIC-ADVANCE 2
ICO
(n=311)
Deucra
(n=307)
Difference
(95% CI)
Adjusted
P-value
ICO
(n=322)
Deucra
(n=327)
Difference
(95% CI)
Adjusted
P-value
IGA 0/1 at Week 16a
68 (213)
50 (154)
18 (11, 26)
P<0.001
70 (227)
54 (177)
16 (9, 24)
P<0.001
PASI 75 at Week 16
74 (231)
57 (176)
17 (10, 24)
P<0.001
77 (249)
61 (198)
17 (10, 24)
P<0.001
IGA 0 at Week 16a
37 (114)
16 (48)
21 (14, 28)
P<0.001
37 (118)
17 (57)
19 (13, 26)
P<0.001
PASI 90 at Week 16
55 (171)
30 (91)
25 (18, 33)
P<0.001
57 (184)
34 (111)
23 (16, 30)
P<0.001
PASI 100 at Week 16
31 (97)
11 (34)
20 (14, 26)
P<0.001
32 (102)
14 (46)
18 (11, 24)
P<0.001
PSSD Symptom score 0 at Week 16b
24 (68)
9 (25)
14 (8, 21)
P<0.001
21 (64)
13 (36)
9 (3, 15)
P=0.004
IGA 0 at Week 24a
48 (150)
21 (63)
28 (20, 35)
P<0.001
40 (128)
21 (68)
19 (12, 26)
P<0.001
PASI 90 at Week 24
66 (205)
41 (127)
24 (17, 32)
P<0.001
65 (208)
43 (141)
22 (14, 29)
P<0.001
PASI 100 at Week 24
41 (129)
16 (49)
26 (19, 32)
P<0.001
33 (107)
16 (52)
17 (11, 24)
P<0.001
IGA 0/1 at Week 24a
74 (230)
52 (161)
22 (14, 29)
P<0.001
68 (220)
55 (179)
14 (6, 21)
P<0.001
PASI 75 at Week 24
82 (254)
64 (196)
18 (11, 25)
P<0.001
83 (266)
66 (216)
17 (10, 23)
P<0.001
Abbreviations: CI, confidence interval; Deucra, deucravacitinib; ICO, icotrokinra; IGA, Investigator’s Global Assessment; PASI, Psoriasis Area and Severity Index; PSSD, Psoriasis Symptoms and Signs Diary.
aAmong the 311 and 307 patients with an IGA score ≥2 at baseline in the ICO and Deucra groups, respectively, in ADVANCE 1, and 322 and 327, respectively, in ADVANCE 2.
bAmong the 286 and 272 patients with a baseline PSSD Symptom score >0 in the ICO and Deucra groups, respectively, in ADVANCE 1, and 298 and 287 patients, respectively, in ADVANCE 2.
Note: Endpoints are listed in accordance with the order in which they were tested for statistical significance.

Safety

  • A total of 632, 237, and 634 patients in the icotrokinra, PBO, and deucravacitinib groups were included in the combined safety analysis set.1
  • Through week 16, 48%, 57%, and 57% of patients receiving icotrokinra, PBO, and deucravacitinib, respectively, reported ≥1 AE(s).1
    • The most common AEs were nasopharyngitis and upper respiratory tract infection.
    • Infections occurred in 23%, 31%, and 32% of patients in the icotrokinra, PBO, and deucravacitinib groups, respectively.2 
  • Through week 24, AE rates were lower in the icotrokinra group versus the deucravacitinib group (57% vs 65%), and no safety signals were identified (see Table: Combined AEs from the ICONIC-ADVANCE 1 and ICONIC-ADVANCE 2 Safety Analysis Sets).1

Combined AEs from the ICONIC-ADVANCE 1 and ICONIC-ADVANCE 2 Safety Analysis Sets1
PBO-controlled
(W0-16)
Active-comparator controlled (W0-24)
Crossover
(W16-24)
ICO
PBO
Deucra
ICO
Deucra
PBO→ICO
Number of participants
632
237
634
632
634
215
Mean weeks of follow up (SD)
15.9 (1.88)
15.5 (2.69)
15.8 (2.25)
23.5 (3.26)
23.3 (3.94)
8.1 (0.58)
≥1 AE, n (%)
303 (48)
136 (57)
360 (57)
359 (57)
411 (65)
60 (28)
AEs occurring in ≥5% of patients in any treatment group, n (%)
   Headache
26 (4)
11 (5)
19 (3)
28 (4)
20 (3)
3 (1)
   Nasopharyngitis
37 (6)
13 (5)
58 (9)
56 (9)
77 (12)
8 (4)
   Upper respiratory
   tract infection
23 (4)
8 (3)
33 (5)
32 (5)
49 (8)
7 (3)
Serious AE, n (%)
14 (2)
4 (2)
14 (2)
18 (3)
20 (3)
3 (1)
   Serious infectionb
1 (<1)
1 (<1)
4 (1)
3 (<1)
4 (1)
0 (0)
AE resulting in discontinuation, n (%)
13 (2)
12 (5)
14 (2)
15 (2)
17 (3)
0 (0)
GI AEs, n (%)
45 (7)
15 (6)
63 (10)
55 (9)
80 (13)
5 (2)
Malignancy, n (%)c
3 (<1)
1 (<1)
1 (<1)
3 (<1)
2 (<1)
0 (0)
Active TB, n (%)
0 (0)
0 (0)
0(0)
0 (0)
0 (0)
0 (0)
Abbreviations: AE, adverse events; Deucra, deucravacitinib; GI, gastrointestinal; ICO, icotrokinra; PBO, placebo; SD, standard deviation; TB, tuberculosis; W, weeks.
aThe safety analysis set included all randomized and treated patients.
bSerious infections included bacterial arthritis (PBO group), campylobacter colitis (Deucra group), viral infection (Deucra group), infection exacerbated by chronic obstructive airways disease (ICO group), lower respiratory tract infection (Deucra group), viral upper respiratory tract infection (Deucra group), and pneumonia (ICO group).
cDetails on malignancies reported through Week 24 of both studies are provided as early as week 4.3 
  • Through week 24, there were 6 instances of malignancy reported across ICONIC-ADVANCE 1 and ICONIC-ADVANCE 23:
    • Three in the icotrokinra group (pancreatic carcinoma, invasive breast carcinoma, and keratoacanthoma).
    • One in the PBO group (invasive ductal breast carcinoma).
    • Two in the deucravacitinib group (right buccal squamous cell carcinoma and malignant melanoma in situ).
    • All events were considered unrelated to study treatments by investigators.

Literature Search

A literature search of MEDLINE®, EMBASE®, BIOSIS Previews®, and DERWENT® (and/or other resources, including internal/external databases) was conducted on 03 December 2025.

References

Show
1 Stein Gold L, Armstrong AW, Bissonnette R, et al. Once-daily oral icotrokinra versus placebo and once-daily oral deucravacitinib in participants with moderate-to-severe plaque psoriasis (ICONIC-ADVANCE 1 & 2): two phase 3, randomised, placebo-controlled and active-comparator-controlled trials. The Lancet. 2025;406(10510):1363-1374.  
2 Stein Gold L, Armstrong AW, Bissonnette R, et al. Icotrokinra demonstrated superior responses compared with placebo and deucravacitinib in the treatment of moderate-to-severe plaque psoriasis. Oral presentation presented at: European Academy of Dermatology and Venereology (EADV); September 17-20, 2025; Paris, France.  
3 Stein Gold L, Armstrong AW, Bissonnette R, et al. Supplement to: Once-daily oral icotrokinra versus placebo and once-daily oral deucravacitinib in participants with moderate-to-severe plaque psoriasis (ICONIC-ADVANCE 1 & 2): two phase 3, randomised, placebo-controlled and active-comparator-controlled trials. The Lancet. 2025;406(10510):1363-1374.