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icotrokinra
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Icotrokinra - Treatment of Hand and Foot Psoriasis
Last Updated: 03/12/2026
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
- The safety and efficacy of icotrokinra in patients with moderate to severe plaque psoriasis (PsO) were evaluated in the ICONIC-ADVANCE 1 (NCT06143878), ICONIC-ADVANCE 2 (NCT06220604), ICONIC-TOTAL (NCT06095102) and ICONIC-LEAD (NCT06095115) phase 3 clinical trials. Summarized below are data specific to hand and foot PsO across the ICONIC-TOTAL and ICONIC-LEAD studies.1-
6 - In ICONIC-TOTAL, at week 16, 42% vs 26% of patients in the icotrokinra vs placebo (PBO) groups achieved a Physician’s Global Assessment of hands and feet (hf-PGA) score of 0 or 1 (hf-PGA 0/1; clear or almost clear; treatment difference, 16.7%; 95% confidence interval [CI], -6.2 to 36.8; adjusted P=0.14).1,
3 - At week 16, 25% and 13% of patients in the icotrokinra and PBO groups, respectively, achieved an hf‑PGA score of 0.
- In a subgroup analysis of ICONIC-LEAD, at week 16, 74.0% vs 23.4% of patients in the icotrokinra vs PBO groups achieved an hf-PGA 0/1 response (treatment difference, 50.6%; 95% CI, 34.2-63.6; nominal P<0.001).2
,4 - At week 16, 58.7% vs 17.0% of patients in the icotrokinra vs PBO groups achieved an hf-PGA 0 response (adjusted treatment difference, 42.0%; 95% CI, 25.9-54.8; nominal P<0.001).
- In ICONIC-TOTAL, at week 16, 42% vs 26% of patients in the icotrokinra vs placebo (PBO) groups achieved a Physician’s Global Assessment of hands and feet (hf-PGA) score of 0 or 1 (hf-PGA 0/1; clear or almost clear; treatment difference, 16.7%; 95% confidence interval [CI], -6.2 to 36.8; adjusted P=0.14).1,
CLINICAL DATA
ICONIC-TOTAL
Gooderham et al (2025)1 and Lain et al (2025)3 evaluated the efficacy and safety of oral icotrokinra 200 mg once daily in patients ≥12 years of age with plaque PsO affecting special sites (scalp, genitals, and/or hands/feet) in an ongoing phase 3, multicenter, randomized, double-blind, PBO-controlled study.
Study Design/Methods
- Key inclusion criteria1:
- Age ≥12 years with plaque PsO diagnosed for ≥26 weeks at screening; candidate for phototherapy or systemic therapy with an inadequate response to ≥1 topical therapies
- Total body surface area (BSA) involvement ≥1% and an Investigator’s Global Assessment (IGA) score ≥2
- Involvement of ≥1 high-impact sites with at least moderate severity (scalp-specific IGA score ≥3, static Physician’s Global Assessment of Genitalia score ≥3, and hf-PGA ≥3)
- Patients were randomized (2:1) to receive oral icotrokinra 200 mg or PBO once daily, with PBO crossover to icotrokinra at week 16.1
- The primary and select secondary outcome measures are described in Table: Select ICONIC-TOTAL Outcome Measures at Week 16.1
| Primary Endpoint |
|---|
| Percentage of patients who achieved an IGA score of clear (0) or minimal (1) and a ≥2-grade improvement from baseline |
| Select Secondary Endpoints |
| Percentage of patients who achieved an hf-PGA score of clear (0) or almost clear (1) |
| Abbreviations: hf-PGA, Physician’s Global Assessment of hands and feet; IGA, Investigator’s Global Assessment. |
Patient Characteristics
- A total of 311 patients (icotrokinra, n=208; PBO, n=103) were included in the study, with 64.3% being male and 78.1% being White. The mean age was 44.7 years (6 patients were ≥12 to <18 years).1
- In the icotrokinra and PBO groups, respectively, 23.1% (n=48) and 22.3% (n=23) of patients had at least moderate severity of hand/foot PsO at baseline (hf-PGA score ≥3).1
Efficacy
- Primary endpoint: At week 16, 56.7% (118/208) vs 5.8% (6/103) of patients receiving icotrokinra vs PBO, respectively, achieved an IGA 0/1 response (adjusted treatment difference, 51.1%; 95% CI, 42.1-58.8; P<0.001).1
- Select endpoints are described in Table: Select ICONIC-TOTAL Endpoints.
1,3
| ICO (n=48) | PBO (n=23) | Adjusted Difference (95% CI); Adjusted P-Valuea | PBO→ICO Crossoverb (n=19) | |
|---|---|---|---|---|
| Proportion of patients achieving endpoint, % | ||||
| hf-PGA 0/1c | ||||
| Week 16 | 42 | 26 | - | |
| Week 52 | 62 | - | - | 68 |
| hf-PGA 0c | ||||
| Week 16 | 25 | 13 | - | - |
| Week 52 | 58 | - | - | 58 |
| Abbreviations: CI, confidence interval; hf-PGA, Physician’s Global Assessment of hands and feet; ICO, icotrokinra; PBO, placebo. aP-values for key secondary endpoints were adjusted for multiplicity. bPatients crossed over from PBO to ICO at week 16. cAmong patients with a baseline hf-PGA score ≥3. | ||||
Safety
- Through week 16, 50% (105/208) of patients receiving icotrokinra and 45% (46/103) of patients receiving PBO reported ≥1 adverse events (AEs).3
- Through week 52, 74% (153/208) of patients receiving icotrokinra and 68% (204/300) of patients in the icotrokinra combined group reported ≥1 AE (see Table: Adverse Events in ICONIC-TOTAL through Week 52).3
- No new safety signals were identified through week 52.3
| Weeks 0-16 | Weeks 16-52 | Through Week 52 | |||
|---|---|---|---|---|---|
| ICO (n=208) | PBO (n=103) | PBO→ICO (n=92) | ICO (n=208) | ICO Combineda (n=300) | |
| Mean weeks/total PYs of follow-up | 16.0/63.6 | 15.6/30.8 | 36.2/63.9 | 49.3/196.4 | 45.3/260.2 |
| Any AE, n (%) | 105 (50) | 46 (45) | 51 (55) | 153 (74) | 204 (68) |
| SAEs, n (%) | 1 (<1) | 2 (2) | 1 (1) | 6 (3) | 7 (2) |
| AEs leading to discontinuation, n (%) | 6 (3) | 4 (4) | 0 | 7 (3) | 7 (2) |
| Infections, n (%) | 59 (28) | 23 (22) | 39 (42) | 106 (51) | 145 (48) |
| Serious infections, n (%) | 0 | 1 (1) | 0 | 0 | 0 |
| Gastrointestinal AEs, n (%) | 15 (7) | 8 (8) | 7 (8) | 21 (10) | 28 (9) |
| Malignancyb, n (%) | 1 (<1) | 0 | 0 | 2 (1) | 2 (1) |
| Abbreviations: AE, adverse event; ICO, icotrokinra; PBO, placebo; SAE, serious adverse event; PY, patient-year. aIncludes data for ICO-randomized patients through week 52 and for PBO→ICO patients from week 16 through week 52. bMalignancy includes chronic lymphocytic leukemia and malignant melanoma in situ. | |||||
ICONIC-LEAD
Bissonnette et al (2025)2 and Soung et al (2025)4,5
Study Design/Methods
- Key inclusion criteria2:
- Age ≥12 years with moderate to severe plaque PsO diagnosed for ≥26 weeks before screening; candidate for phototherapy or systemic therapy
- Total BSA involvement ≥10%
- Psoriasis Area and Severity Index (PASI) score ≥12
- IGA score ≥3
- Patients were randomized (2:1) to receive either oral icotrokinra 200 mg once daily or PBO, with PBO crossover to icotrokinra at week 16.2
- Coprimary endpoints: IGA 0/1 response with a ≥2-grade reduction from baseline to week 16 and PASI 90 response at week 16.2
- Select subgroup analysis outcomes: hf-PGA 0/1 and hf-PGA 0 responses among patients with a baseline hf-PGA score ≥3.4
Results
Patient Characteristics
Efficacy – Overall Population
- Coprimary endpoints: At week 16, in the icotrokinra and PBO groups, respectively, 65% (295/456) and 8% (19/228) of patients achieved an IGA 0/1 response (adjusted treatment difference, 56.4 percentage points; 95% CI, 50.4-61.7; P<0.001). For PASI 90 response at week 16, 50% (226/456) of patients in the icotrokinra group and 4% (10/228) of patients in the PBO group achieved a response (adjusted treatment difference, 45.1 percentage points; 95% CI, 39.5-50.4; P<0.001).2
Efficacy - High-Impact Site Involvement Subgroup Analysis
- The results of a subgroup analysis evaluating icotrokinra in patients ≥12 years of age with plaque PsO and high-impact site involvement (hand/foot) are described in Table: ICONIC-LEAD Subgroup Analysis – Select High-Impact Site Response Rates.4
| ICO (n=104) | PBO (n=47) | Treatment Difference, % (95% CI) | |
|---|---|---|---|
| Proportion of patients achieving endpoint, % | |||
| hf-PGA 0/1a | |||
| Week 16 | 74 | 23 | Nominal P<0.001c |
| Week 24 | 76 | - | - |
| hf-PGA 0a | |||
| Week 16 | 59 | 17 | Nominal P<0.001c |
| Week 24 | 62 | - | - |
| Abbreviations: CI, confidence interval; CMH, Cochran-Mantel-Haenszel; hf-PGA, Physician’s Global Assessment of hands and feet; ICO, icotrokinra; PBO, placebo. aAmong patients with a baseline hf-PGA score ≥3. bTreatment difference and 95% CI (using Miettinen-Nurminen method) were calculated adjusting for age group, baseline weight category for adults using Mantel-Haenszel weights. cP-values were based on CMH chi-square test stratified by age group and baseline weight category for adults. The endpoint was not controlled for multiple comparisons. Therefore, the P-value is nominal, and statistical significance has not been established. | |||
Safety – Overall Population
- Through week 16, 50% and 49% of patients in icotrokinra and PBO groups, respectively, reported ≥1 AE, with nasopharyngitis and upper respiratory tract infections being the most common.5
- Through week 16, 23% (107/456) and 22% (51/228) of patients in the icotrokinra and PBO groups, respectively, reported an infection.2
- The icotrokinra AE profile through week 52 was consistent with that observed through week 16 (see Table: Adverse Events in the Overall ICONIC-LEAD Population through Week 52).2,5,6
| PBO-Controlled (Adults and Adolescents) | Active Treatment (Adults and Adolescents) | ICO Responders Rerandomized at Week 24 (Adults) | ||||
|---|---|---|---|---|---|---|
| Weeks 0-16 | Weeks 16-52 | Weeks 0-52 | Weeks 24-52 | |||
| ICO (n=456) | PBO (n=228) | ICOa (n=213) | ICO (n=456) | ICO→ICO (n=168) | ICO→PBOb (n=172) | |
| Follow-up duration, weeks, mean | 15.9 | 15.8 | 35.3 | 43.4 | 27.7 | 27.8 |
| Any AE, n (%) | 226 (50) | 112 (49) | 132 (62) | 313 (69) | 92 (55) | 82 (48) |
| Most common AEs (≥5%) | ||||||
| Nasopharyngitis, n (%) | 31 (7) | 15 (7) | 23 (11) | 64 (14) | 21 (12) | 20 (12) |
| URTI, n (%) | 30 (7) | 16 (7) | 24 (11) | 52 (11) | 9 (5) | 15 (9) |
| SAEc, n (%) | 6 (1) | 6 (3) | 4 (2) | 16 (4) | 3 (2) | 5 (3) |
| Serious infection, n (%) | 1 (<1) | 0 | 1 (<1) | 1 (<1) | 0 | 1 (1) |
| AE leading to discontinuationd | 6 (1) | 1 (<1) | 4 (2) | 10 (2) | 1 (1) | 3 (2) |
| Gastrointestinal AEe | 26 (6) | 13 (6) | 9 (4) | 51 (11) | 7 (4) | 8 (5) |
| Active tuberculosis, n (%) | 0 | 0 | 0 | 0 | 0 | 0 |
| Malignancyf | 2 (<1) | 0 | 0 | 2 (<1) | 0 | 0 |
| Abbreviations: AE, adverse event; ICO, icotrokinra; PBO, placebo; SAE, serious adverse event; URTI, upper respiratory tract infection. aIncludes data after week 16 for PBO-randomized patients who crossed over to receive ICO. bCombined withdrawal and retreatment group. cSAEs through week 16 included acute cholecystitis, concussion, craniofacial fracture, pelvic fracture, worsening psoriasis, and hypertensive urgency in the PBO group; and adenocarcinoma of the colon, prostate cancer, pancreatitis, bacterial gastroenteritis, arthralgia, and subarachnoid hemorrhage in the ICO group. dAEs leading to discontinuation through week 16 included blood glucose increase in the PBO group; and adenocarcinoma of the colon, prostate cancer, hypertriglyceridemia, subarachnoid hemorrhage, erectile dysfunction, and psoriasis in the ICO group. eBased on gastrointestinal disorders system organ class.fIncluded adenocarcinoma of the colon (1 patient who had a history of smoking; the patient reported mild gastroenteritis during screening, severe colitis starting on study day 7, and severe ileus on day 14 leading up to the diagnosis of grade 3 adenocarcinoma of the colon on day 19) and prostate cancer (1 patient who had a history of smoking and a family history of prostate cancer; this participant had an elevated prostate-specific antigen level before baseline and received a diagnosis of grade 1 prostate cancer on day 48). | ||||||
LITERATURE SEARCH
A literature search of MEDLINE®
References
| 1 | Gooderham M, Lain E, Bissonnette R, et al. Targeted oral peptide icotrokinra for psoriasis involving high-impact sites. NEJM Evid. 2025;4(12):EVIDoa2500155. |
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