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ICOTYDE®

(icotrokinra)

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ICOTYDE® (icotrokinra)
Medical Information

ICOTYDE - Occurrence of Cardiovascular Events in Patients with Plaque Psoriasis

Last Updated: 10/15/2026

SUMMARY

  • The safety and efficacy of ICOTYDE (icotrokinra) in patients with moderate to severe plaque psoriasis (PsO) was evaluated in the ICONIC-LEAD (NCT06095115), ICONIC-TOTAL (NCT06095102), ICONIC-ADVANCE 1 (NCT06143878), and ICONIC-ADVANCE 2 (NCT06220604) phase 3 clinical trials.1-3
  • The following summarizes the exposure-adjusted incidence rates (EAIR) of cardiovascular (CV) events per 100 patient-years (PY) of follow-up across these studies.4
  • Through week 52, EAIRs per 100 PY (95% confidence interval [CI]) in patients treated with icotrokinra were 0.87 (0.49-1.37) for all CV events, 0.22 (0.03-0.51) for extended major adverse CV events (MACE), 0.22 (0.03-0.51) for MACE, and 0.71 (0.36-1.16) for other CV events.4

CLINICAL DATA

Pooled Analysis of Phase 3 Clinical Trials

Lebwohl et al (2026)4 evaluated the 1-year safety profile of icotrokinra using pooled data from the ongoing LEAD, TOTAL, ADVANCE 1, and ADVANCE 2 studies.

Study Design/Methods


Overview of Phase 3 Clinical Trials through Week 521-4
LEAD
TOTAL
ADVANCE 1 & ADVANCE 2
Overview
  • Multicenter, randomized, controlled, double-blind, phase 3 clinical trials
Key inclusion criteria
  • Age ≥12 years
  • IGA ≥3
  • PASI ≥12
  • BSA ≥10%
  • Candidate for phototherapy or systemic treatment
  • Age ≥12 years
  • IGA ≥2
  • BSA ≥1%
  • ≥1 high-impact site with at least moderate psoriasis (ss-IGA ≥3, sPGA-G ≥3, or hf-PGA ≥3)
  • Failed ≥1 topical therapy
  • Candidate for phototherapy or systemic treatment
  • Age ≥18 years
  • IGA ≥3
  • PASI ≥12
  • BSA ≥10%
  • Candidate for phototherapy or systemic treatment
Treatment groups
  • ICO (n=456)
    • ICO 200 mg QD W0-24
    • W24–52: randomized withdrawal and retreatmenta
  • PBO (n=228)
    • PBO QD W0-16
    • ICO 200 mg QD W16-52
  • ICO (n=208)
    • ICO 200 mg QD W0-52
  • PBO (n=103)
    • PBO QD W0-16
    • ICO 200 mg QD W16-52
  • ICO (ADVANCE 1, n=311; ADVANCE 2, n=322)
    • ICO 200 mg QD W0-52
  • PBO (ADVANCE 1, n=156; ADVANCE 2, n=82)
    • PBO QD W0-16
    • ICO 200 mg QD W16-52
  • Deucra (ADVANCE 1, n=307; ADVANCE 2, n=327)
    • Deucra 6 mg QD W0-24
    • ICO 200 mg QD W24-52
Abbreviations: BSA, body surface area; Deucra, deucravacitinib; hf-PGA, Physician’s Global Assessment of hands and feet; ICO, icotrokinra; IGA, Investigator’s Global Assessment; PASI, Psoriasis Area and Severity Index; PBO, placebo; QD, once daily; sPGA-G, static Physician’s Global Assessment of Genitalia; ss-IGA, scalp-specific Investigator’s Global Assessment; W, week.aBased on PASI 75 and IGA 0/1 response (adults only; all adolescents continued ICO).

Results

Baseline Characteristics

Select Baseline Demographics and Medical History by Study4
LEAD
n=684
TOTAL
n=311
ADVANCE 1
n=772
ADVANCE 2
n=731
Overall
N=2498
Age, years
42.6 (16.4)
44.7 (14.3)
46.7 (13.4)
46.1 (13.6)
45.2 (14.5)
Male sex, n (%)
447 (65.4)
200 (64.3)
526 (68.1)
496 (67.9)
1669 (66.8)
Race, n (%)
    White
494 (72.2)
243 (78.1)
568 (73.6)
604 (82.6)
1909 (76.4)
    Asian
167 (24.4)
61 (19.6)
180 (23.3)
89 (12.2)
497 (19.9)
    Black or African American
8 (1.2)
2 (0.6)
11 (1.4)
22 (3.0)
43 (1.7)
BMI,a kg/m2
29.3 (7.0)
29.2 (7.1)
29.5 (7.1)
29.8 (6.5)
29.5 (6.9)
Medical history, n (%)
    Hypertension
172 (25.1)
79 (25.4)
240 (31.1)
220 (30.1)
711 (28.5)
    Hyperlipidemia
102 (14.9)
62 (19.9)
153 (19.8)
131 (17.9)
448 (17.9)
    Diabetes mellitus
77 (11.3)
36 (11.6)
91 (11.8)
76 (10.4)
280 (11.2)
    CAD
13 (1.9)
7 (2.3)
20 (2.6)
14 (1.9)
54 (2.2)
    Stroke
3 (0.4)
0
7 (0.9)
3 (0.4)
13 (0.5)
    Current or former nicotine useb
273 (39.9)
142 (45.7)
396 (51.3)
358 (49.0)
1169 (46.8)
Abbreviations: BMI, body mass index; CABG, coronary artery bypass graft; CAD, coronary artery disease; PCI, percutaneous coronary intervention; TIA, transient ischemic attack.aLEAD, n=682; TOTAL, n=304; ADVANCE 2, n=729; Overall, n=2487.bIncludes cigarettes, cigars, pipes, smokeless tobacco, patches/gum, and e-cigarettes or equivalent.
Safety

Select Safety Results Across Analysis Periods through Week 524,6

PBO-controlled (W0-16)a
Active-controlled (W0-24)b
W0-52c
ICO
n=1296
PBO
n=568
ICO
n=632
Deucra
n=634
ICO
n=2400
Total PY of follow-up
395
170
285
283
1840
Average follow-up, weeks
15.9
15.6
23.5
23.3
40.0
EAIR/100 PY of follow-up (95% CI)d
    All CV events
1.28
(0.79-3.79)
0.54
(0.30-5.78)
1.41
(0.42-3.79)
2.13
(0.87-4.80)
0.87
(0.49-1.37)
    Extended MACEe
0.75
(0.45-3.07)
0
(0.00-5.03)
0.70
(0.03-2.78)
1.42
(0.42-3.82)
0.22
(0.03-0.51)
        MACEf
0.75
(0.45-3.07)
0
(0.00-5.03)
0.70
(0.03-2.78)
1.06
(0.22-3.30)
0.22
(0.03-0.51)
    Other CV eventsg
0.79
(0.46-3.14)
0.54
(0.30-5.78)
1.05
(0.22-3.29)
0.71
(0.03-2.81)
0.71
(0.36-1.16)
Abbreviations: AE, adverse event; CI, confidence interval; CV, cardiovascular; Deucra, deucravacitinib; EAIR, exposure-adjusted incidence rate; ICO, icotrokinra; MACE, major adverse CV events; PBO, placebo; PY, patient-years; W, week.aIncludes LEAD, TOTAL, ADVANCE 1, and ADVANCE 2. To account for the different PBO:ICO randomization ratio in ADVANCE 2 vs the other studies, rates were adjusted by the total follow-up from the combined PBO and ICO treatment groups in a study.bIncludes ADVANCE 1 and ADVANCE 2 only.cIncludes data for patients randomized to ICO, data after W16 for patients randomized to PBO who crossed over to ICO, and data after W24 for patients randomized to Deucra who switched to ICO. For the LEAD study, events that occurred during the withdrawal period (on or after W28 and before re-treatment) were excluded for patients who were re-randomized to PBO at W24.dCalculated as (number of patients with AEs/total PY at risk) x 100. Patients are counted only once for any given event, regardless of the number of times they actually experienced the event.eIncludes all MACE events, hospitalization for unstable angina, and coronary revascularization (without myocardial infarction, unstable angina, or heart failure).fIncludes CV death, nonfatal myocardial infarction, and nonfatal stroke.gIncludes transient ischemic attack, venous and peripheral arterial vascular thrombotic events, congestive heart failure, cardiac arrhythmia (no evidence of ischemia), and other serious non-MACE CV events such as syncope of a CV origin and severe/accelerated hypertension leading to hospitalization.
MACE
  • PBO-controlled period (LEAD, TOTAL, ADVANCE 1, and ADVANCE 2)4,5:
    • Positively adjudicated MACE in the icotrokinra group (n=3) consisted of 1 CV death (63-year-old male with myocardial infarction), 1 nonfatal myocardial infarction (45-year-old male with history of smoking), and 1 nonfatal stroke (49-year-old male with a history of hypertension, obstructive sleep apnea syndrome, psoriatic arthritis, smoking, and alcohol use).
  • Active-controlled period (ADVANCE 1 and ADVANCE 2)5:
    • Positively adjudicated MACE in the icotrokinra group (n=2; CV death and nonfatal myocardial infarction) occurred prior to week 16 and are described above.
  • Through week 52 (LEAD, TOTAL, ADVANCE 1, and ADVANCE 2)4:
    • There was 1 additional MACE (CV death reported as cocaine toxicity-induced hypertensive CV disease).
  • Across all time periods, there were no extended MACE (hospitalization for unstable angina or coronary revascularization without myocardial infarction, unstable angina, or heart failure) in any icotrokinra-treated patients, other than the MACE reported above.4

Literature Search

A literature search of MEDLINE®, EMBASE®, BIOSIS Previews®, and DERWENT® (and/or other resources, including internal/external databases) was conducted on 01 October 2026.

 

References

Show
1 Bissonnette R, Soung J, Hebert AA, et al. Oral icotrokinra for plaque psoriasis in adults and adolescents. N Engl J Med. 2025;393(18):1784-1795.  
2 Gooderham M, Lain E, Bissonnette R, et al. Targeted oral peptide icotrokinra for psoriasis involving high-impact sites. NEJM Evid. 2025;4(12):EVIDoa2500155.  
3 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. Lancet. 2025;406(10510):1363-1374.  
4 Lebwohl MG, Gooderham M, Warren RB, et al. Safety of icotrokinra through 1 year for the treatment of moderate-to-severe plaque psoriasis and psoriasis affecting high-impact sites: pooled results across the ICONIC-LEAD, ICONIC-TOTAL, and ICONIC-ADVANCE 1 and 2 phase 3 trials. [published online ahead of print August 28, 2026]. Dermatol Ther (Heidelb). doi:10.1007/s13555-026-01885-w.  
5 Data on File. Summary of Clinical Safety. Janssen Research & Development, LLC. EDMS-RIM-1147239; 2025.  
6 Data on File. Icotrokinra 120-Day Safety update. Janssen Research & Development, LLC. EDMS-RIM-1606208; 2025.  

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