Zasocitinib (TAK-279), a Highly Selective Oral TYK2 Inhibitor, Demonstrates Skin Clearance in Patients with Moderate-to-Severe Plaque Psoriasis: Post Hoc Analyses of a Randomized Phase IIb Trial

Abstract

Introduction

Zasocitinib (TAK-279) is an investigational, once daily, oral, allosteric, highly selective, and potent tyrosine kinase 2 inhibitor. Post hoc analyses of a 12-week phase IIb trial in patients with moderate-to-severe plaque psoriasis evaluated zasocitinib 15 mg or 30 mg efficacy versus placebo by baseline characteristic subgroups, Psoriasis Area and Severity Index (PASI) improvements by body region and component scores, and patient-reported and other clinical outcomes.

Methods

Disease severity assessments included PASI, Physician’s Global Assessment (PGA), body surface area (BSA), Dermatology Life Quality Index (DLQI) 0/1, and PGA × BSA. Subgroups included weight, sex, age, race, disease duration, prior biologic use, and PASI score. Body regions included head, trunk, and upper and lower extremities. Scoring components included erythema, induration, and desquamation. DLQI 0/1 attainment was assessed by PASI.

Results

At week 12, zasocitinib 15 mg or 30 mg demonstrated greater response rates in PASI 75/90/100 and PGA 0/1 in nearly all patient subgroups versus placebo. A greater proportion of patients receiving zasocitinib achieved PASI 75/90/100 across all PASI body regions and scoring components versus placebo. Reductions in BSA or PASI were greater in zasocitinib groups as early as week 2 and through week 12 versus placebo; most patients attaining PASI ≤ 1 or ≤ 2 or PASI 75/90/100 also achieved DLQI 0/1. Absolute PASI and PGA × BSA improvements were strongly positively correlated (ρ = 0.95), with PGA × BSA 75 and PASI 75 showing high agreement.

Conclusion

Zasocitinib demonstrated consistent improvements in skin clearance, irrespective of baseline disease characteristics, PASI body region, and scoring component, with meaningful quality of life improvements.

Graphical abstract available for this article.

Trial Registration

ClinicalTrials.gov Identifier: NCT04999839.

Graphical Abstract

Supplementary Information

The online version contains supplementary material available at 10.1007/s13555-026-01738-6.

Key Summary Points

Why carry out this study?

Psoriasis remains an area of unmet need for convenient and effective oral therapies.

Zasocitinib, a highly selective and potent oral TYK2 inhibitor, targets key inflammatory pathways implicated in psoriasis; in a phase IIb trial of patients with moderate-to-severe plaque psoriasis, the primary endpoint (PASI 75 response at week 12) was met with once daily zasocitinib ≥ 5 mg doses.

This study assessed the efficacy of once daily oral zasocitinib 15 mg or 30 mg in post hoc analyses of a phase IIb trial in patients with moderate-to-severe plaque psoriasis.

What was learned from the study?

Zasocitinib 15 mg or 30 mg led to improvements in clinical and patient-reported outcomes across patient subgroups, and in PASI body region and component scores versus placebo at week 12.

These post hoc analyses demonstrate early, consistently efficacious, and clinically meaningful improvements in skin clearance, which are correlated with meaningful improvements in quality of life.

Digital Features

This article is published with digital features, including a graphical abstract, to facilitate understanding of the article. To view digital features for this article go to 10.6084/m9.figshare.31802284.

Introduction

Psoriasis is a chronic, debilitating immune-mediated inflammatory skin disease associated with substantial physical, psychological, and social burden [1, 2]. Although several effective therapies exist for psoriasis, there remains an unmet need for approved oral therapies that have a favorable safety profile, are effective, and convenient to administer [3].

Zasocitinib (TAK-279) is an investigational, once daily, oral, allosteric, highly selective, and potent tyrosine kinase 2 (TYK2) inhibitor in late stages of clinical development for immune-mediated inflammatory diseases, including psoriasis and psoriatic arthritis [4–8]. Zasocitinib has more than 1-millionfold greater binding selectivity for TYK2 in vitro versus Janus kinase (JAK)1/2/3, thereby selectively inhibiting TYK2-mediated proinflammatory signaling pathways central to the pathophysiology of psoriasis, including interleukin (IL)-23, type I interferon, and IL-12 [4, 5, 9].

In a phase IIb study of zasocitinib in patients with moderate-to-severe plaque psoriasis (NCT04999839), the primary endpoint (proportion of patients achieving 75% or greater improvement in Psoriasis Area and Severity Index score [PASI 75] from baseline to week 12) was met with zasocitinib doses ≥ 5 mg once daily [7]. In addition, 46%, 33%, and 52% of patients receiving zasocitinib 30 mg achieved PASI 90 (near-complete skin clearance), PASI 100 (complete skin clearance), and Physician’s Global Assessment (PGA) 0/1, respectively, after 12 weeks [7]. Zasocitinib demonstrated an acceptable safety and tolerability profile, with no major adverse cardiovascular events, opportunistic infections, or meaningful changes in laboratory parameters associated with JAK1, JAK2, or JAK3 inhibition [7].

These post hoc analyses of the phase IIb study of zasocitinib in patients with moderate-to-severe plaque psoriasis aimed to evaluate the efficacy of the highest doses of zasocitinib (15 mg or 30 mg) versus placebo at week 12 by baseline patient demographics and disease characteristics, improvements in PASI by body regions and scoring components, associations between PASI and Dermatology Life Quality Index (DLQI 0/1), and correlations between PASI and PGA × body surface area (BSA), and change from baseline in BSA or PASI.

Methods

Study Design

Detailed methods of the randomized, multicenter, double-blinded, placebo-controlled, phase IIb study of zasocitinib in patients with moderate-to-severe plaque psoriasis (NCT04999839) have been published previously [7].

In brief, 259 patients were randomized 1:1:1:1:1 to receive oral zasocitinib 2 mg (n = 50), 5 mg (n = 52), 15 mg (n = 53), or 30 mg (n = 52), with or without food, or placebo (n = 52) once daily for 12 weeks. Adults (18–70 years) were eligible to participate in the trial if they had a history of plaque psoriasis for ≥ 6 months and met the following criteria: PASI score ≥ 12, PGA score ≥ 3, and BSA involved with plaque psoriasis ≥ 10% [7].

Efficacy Assessments

The primary endpoint was the proportion of patients achieving PASI 75 at week 12, and has been reported previously [7].

Assessments in these post hoc analyses included PASI 75, 90, and 100, and PGA score of clear (0) or almost clear (1) efficacy analyses by baseline characteristics (weight, sex, age, race, disease duration, prior biologic treatment, and PASI score) at week 12; the proportion of patients who achieved PASI 75, 90, or 100 by body region (head, trunk, upper extremities, and lower extremities) and/or by scoring components (erythema, induration, and desquamation) at week 12; change from baseline through week 12 in PASI score by body region and scoring components; absolute BSA and PASI scores through week 12; the proportion of patients who achieved BSA ≤ 1% at weeks 8 and 12; the proportion of patients who achieved PASI 0, PASI ≤ 1, or PASI ≤ 2 at week 12; the proportion of patients achieving a DLQI 0/1 by PASI responses; the correlation between PASI and DLQI; change from baseline through week 12 in PGA × BSA composite score; the correlation between PGA × BSA and PASI at week 12; and proportion of patients who achieved ≥ 75% improvement in PGA × BSA (PGA × BSA 75) at week 12.

Prespecified analyses of exploratory efficacy endpoints, including change from baseline in BSA and PASI scores through 12 weeks, are also reported.

Statistical Analysis

For all post hoc analyses, multiplicity adjustment was not applied, and P values were nominal. All analyses were conducted on the modified intention-to-treat analysis set, defined as randomized patients who received at least one dose of study treatment.

Treatment differences between the zasocitinib groups and placebo group for all subgroups, except prior biologic treatment, were calculated using the Mantel–Haenszel method, and the associated 95% confidence intervals were calculated using the Wald test. For the subgroup analysis by prior biologic treatment, treatment difference estimates were unadjusted.

Least-squares (LS) mean percent changes from baseline in PASI body region and scoring components, and in PGA × BSA, were calculated using a mixed model for repeated measures, which included treatment group, visit (week), treatment-by-visit interaction, and prior treatment with biologics as fixed effects and baseline score as the covariate.

Proportions of patients who achieved with PASI 75, 90, and 100 by body region and/or scoring component scores at week 12, and those who achieved BSA ≤ 1%, PASI ≤ 1, PASI ≤ 2, and PGA × BSA 75 were calculated using the Cochran–Mantel–Haenszel method, with prior treatment with biologics included as a stratification factor.

The relationship between PGA × BSA and PASI scores and DLQI and PASI scores were calculated using Spearman’s correlation coefficients (ρ).

Ethics Approval

This study was performed in accordance with ethical principles originating from the Declaration of Helsinki, which are consistent with Good Clinical Practice and applicable regulatory requirements. Patients provided written, informed consent before starting the study. The clinical study protocol (and amendments), investigator brochure, samples of informed consent forms and other study-related documents were reviewed and approved by institutional review boards or independent ethics committees of all study sites. Consent for publication was not applicable as no identifying information is included in this manuscript.

Results

Patients

In total, 287 patients were randomized; of those, 259 patients received at least one dose of the study treatment [7].

Patient demographic and baseline disease characteristics were comparable across treatment groups and have been reported previously [7]. In summary, the majority of patients were male (68%) and White (83%); patients had a mean (standard deviation [SD]) age of 47 (13) years, median (range) duration of psoriasis of 12 (6–22) years; and approximately 16% of patients were previously treated with biologics. Overall, the mean (SD) PASI score was 18 (6), mean (SD) PGA score was 3 (0), and mean (SD) BSA was 22% (13%).

Efficacy by Demographic and Baseline Disease Characteristics

Zasocitinib 15 mg or 30 mg demonstrated greater response rates in PASI 75, 90, and 100, and PGA 0/1 versus placebo at week 12 in nearly all subgroups of demographics or baseline disease characteristics assessed (Fig. 1). Treatment effects consistently favored zasocitinib 30 mg versus placebo in all endpoints across all subgroups.

Fig. 1.

Response rates for zasocitinib 15 or 30 mg versus placebo at week 12 across demographic and disease characteristic subgroups in patients achieving a PASI 75, b PASI 90, c PASI 100, and d PGA 0/1. n represents the number of responders in each subgroup. All subgroups refer to baseline status. CI, confidence interval; NE, not estimable; PASI, Psoriasis Area and Severity Index; PGA, Physician’s Global Assessment; QD, once daily

Efficacy by Body Region and Scoring Component

Zasocitinib 15 mg or 30 mg treatment led to more patients achieving PASI 75, 90, or 100 versus placebo at week 12 across all body regions (head, trunk, upper extremities, and lower extremities (Fig. 2); P ≤ 0.001 for all) and across all PASI scoring components (erythema, induration, and desquamation (Fig. 3); P ≤ 0.001 for all, except for erythema at PASI 100 [zasocitinib 15 mg versus placebo; P ≤ 0.01]).

Fig. 2.

PASI response rates by body region at week 12 for zasocitinib versus placebo for patients achieving a PASI 75, b PASI 90, and c PASI 100. ***P ≤ 0.001 versus placebo. All P values were nominal. PASI, Psoriasis Area and Severity Index; QD, once daily

Fig. 3.

Proportion of patients achieving a PASI 75, b PASI 90, and c PASI 100 versus placebo at week 12 across all PASI scoring components. **P ≤ 0.01, ***P ≤ 0.001 versus placebo. All P values were nominal. PASI, Psoriasis Area and Severity Index; QD, once daily

At week 12, LS mean reductions in baseline PASI scores in the zasocitinib 15 mg or 30 mg treatment groups ranged from −11.4 to −15.8 across body regions (versus −3.3 to −6.0 for placebo; Table 1) and −4.5 to −4.9 across scoring components (versus −1.5 to −1.7 for placebo; Table 2). Improvements in LS mean percent change from baseline in PASI component scores with zasocitinib 15 mg or 30 mg versus placebo were also consistent across all body regions and were observed as early as week 2, with effects maintained through week 12 (Fig. 4). Nominally significant differences versus placebo were generally observed from week 2 (P ≤ 0.01) and from week 4 onward (P < 0.001) for both zasocitinib doses across all domains.

Table 1.

Change from baseline in PASI scores by body region at week 12

LS mean (SE)	Placebo (n = 52)	Zasocitinib 15 mg QD (n = 53)	Zasocitinib 30 mg QD (n = 52)
Head	−5.2 (1.09)	−13.9 (1.08)	−11.4 (1.09)
Trunk	−3.3 (1.06)	−12.6 (1.05)	−12.0 (1.06)
Upper extremities	−6.0 (0.96)	−14.3 (0.95)	−14.8 (0.96)
Lower extremities	−5.3 (1.14)	−14.3 (1.14)	−15.8 (1.15)

LS means and SE are from a mixed model for repeated measurements on the change from baseline in PASI. Baseline is defined as the last non-missing assessment prior to or on the first study treatment dosing if time is available, and prior to or on the first study treatment dosing date otherwise

LS, least-squares; PASI, Psoriasis Area and Severity Index; QD, once daily; SE, standard error

Table 2.

Change from baseline in PASI scores by scoring component at week 12

LS mean (SE)	Placebo (n = 52)	Zasocitinib 15 mg QD (n = 53)	Zasocitinib 30 mg QD (n = 52)
Erythema	−1.5 (0.32)	−4.7 (0.32)	−4.9 (0.32)
Induration	−1.6 (0.30)	−4.5 (0.30)	−4.5 (0.30)
Desquamation	−1.7 (0.29)	−4.5 (0.29)	−4.7 (0.29)

LS means and SE are from a mixed model for repeated measurements on the change from baseline in PASI. Baseline is defined as the last non-missing assessment prior to or on the first study treatment dosing if time is available, and prior to or on the first study treatment dosing date otherwise

LS, least-squares; PASI, Psoriasis Area and Severity Index; QD, once daily; SE, standard error

Fig. 4.

Mean percent reductions from baseline to week 12 in PASI by body region and a erythema, b induration, and c desquamation. *P < 0.05, ***P ≤ 0.001 versus placebo. All P values were nominal. LS means, SE, and P values are from a mixed model for repeated measurements on percent change from baseline in PASI. Baseline is defined as the last non-missing assessment prior to or on the first study treatment dosing if time is available, and prior to or on the first study treatment dosing date otherwise. BL, baseline; CfB, change from baseline; LS, least-squares; PASI, Psoriasis Area and Severity Index; QD, once daily; SE, standard error

BSA and PASI Outcomes

Reductions from baseline in BSA or PASI score observed in the zasocitinib groups versus placebo over 12 weeks have been shown previously [7]. Reductions from baseline in BSA or PASI score were greater in the zasocitinib 15 mg or 30 mg groups versus placebo as early as week 2, and through to week 12 (Supplementary Tables 1 and 2). Median BSA and PASI reductions with zasocitinib versus placebo over time through week 12 are shown in Supplementary Figs. 1a and 2a.

At week 12, 35.8% and 44.2% of patients treated with zasocitinib 15 mg or 30 mg, respectively, achieved BSA ≤ 1%, versus 0% for placebo (P ≤ 0.001; Supplementary Fig. 1b). In addition, 15.1% and 32.7% of patients treated with zasocitinib 15 mg or 30 mg, respectively, achieved PASI 0; 32.1% and 32.7% achieved PASI ≤ 1; and 56.6% and 55.8% achieved PASI ≤ 2 at week 12 (P ≤ 0.001 for all, with the exception of zasocitinib 15 mg at PASI 0). No responses were observed in the placebo group (Supplementary Fig. 2b).

DLQI and PASI Outcomes

Attainment of DLQI 0/1 was greater in the zasocitinib 15 mg or 30 mg groups versus placebo, with most patients achieving absolute (≤ 1 or ≤ 2) or relative (PASI 75, 90, and 100) PASI scores also attaining a DLQI 0/1 at week 12.

At week 12, 94.1% (15 mg) and 58.8% (30 mg) of patients attaining PASI ≤ 1, and 83.3% (15 mg) and 65.5% (30 mg) of patients attaining PASI ≤ 2, achieved DLQI 0/1 following zasocitinib treatment; no patients attaining PASI ≤ 1 or PASI ≤ 2 in the placebo group achieved DLQI 0/1 (Fig. 5a). Similarly, of the patients achieving PASI 75, 90, or 100 responses, 77.8%, 83.3%, and 87.5% of patients receiving zasocitinib 15 mg and 62.9%, 66.7%, and 58.8% receiving zasocitinib 30 mg, respectively, attained DLQI 0/1 at week 12. No patients in the placebo group who met these thresholds achieved DLQI 0/1 (Fig. 5b).

Fig. 5.

Proportion of patients achieving a DLQI 0/1 at week 12 by a absolute PASI score of ≤ 1 and ≤ 2 and b PASI 75, 90, and 100. Percentages are based on the patients with a result in each treatment group from the subgroup specified. DLQI, Dermatology Life Quality Index; PASI, Psoriasis Area and Severity Index; QD, once daily

Both observed DLQI and PASI scores (ρ = 0.54) and percent change from baseline in DLQI and percent change from baseline in PASI score (ρ = 0.56) had moderately positive correlations (Supplementary Fig. 3).

PGA × BSA Composite Tool

Zasocitinib 15 mg or 30 mg treatment led to greater LS mean percent reductions from baseline in composite PGA × BSA score versus placebo at week 12 (Fig. 6). At week 12, both PASI and PGA × BSA score, and percent change from baseline in PASI and percent change from baseline in PGA × BSA were positively correlated and demonstrated strong linearity across treatment groups (both ρ = 0.95; Fig. 7).

Fig. 6.

LS mean percent reductions from baseline to week 12 in composite PGA × BSA score. **P < 0.01. ***P < 0.001. All P values are nominal and are reported for comparisons versus placebo. Baseline is defined as the last non-missing assessment prior to or on the first study treatment dosing if time is available, and prior to or on the first study treatment dosing date otherwise. BSA, body surface area; LS, least-squares; PGA, Physician’s Global Assessment; QD, once daily

Fig. 7.

Correlations between a PGA × BSA and PASI score, and b percent change from baseline in PGA × BSA and percent change from baseline in PASI score at week 12. n represents the number of patients with non-missing scores (observed cases without missing data imputation). Baseline is defined as the last non-missing assessment prior to or on the first study treatment dosing if time is available, and prior to or on the first study treatment dosing date otherwise. BSA, body surface area; PASI, Psoriasis Area and Severity Index; PGA, Physician’s Global Assessment; QD, once daily

Similar proportions of zasocitinib-treated patients (15 mg or 30 mg) achieved responses in both PGA × BSA 75 and PASI 75 at week 12 (15 mg: 68.0%; 30 mg: 67.0%) (Fig. 8).

Fig. 8.

Proportion of patients achieving PGA × BSA 75 and PASI 75 at week 12. ***P < 0.001. All P values are nominal and are reported for comparisons versus placebo. BSA, body surface area; PASI, Psoriasis Area and Severity Index; PGA, Physician’s Global Assessment; QD, once daily

Discussion

These post hoc analyses of the zasocitinib phase IIb trial in patients with moderate-to-severe plaque psoriasis extend previously published data, which showed improvements with zasocitinib versus placebo in key efficacy endpoints at week 12 [7].

Responsiveness to psoriasis treatments may be influenced by several factors, including patient demographics, disease characteristics, and response to prior treatment [10–12]. Zasocitinib demonstrated robust and consistent skin clearance response versus placebo, as assessed by achievement of PASI 75, 90, and 100, and PGA 0/1 at week 12, across nearly all demographic and disease-related subgroups assessed, including weight, sex, age, race, disease duration, prior biologic treatment, and PASI score in this 12-week post hoc analysis. Notably, a favorable response to zasocitinib 30 mg was observed for all endpoints irrespective of shorter (≤ 10 years) or longer (> 10 years) psoriasis duration and prior biologic treatment, indicating that zasocitinib may have comparable benefit in early- and long-standing disease and in biologic-naive and biologic-experienced patients.

Psoriasis treatments often exhibit variable skin clearance across different regions of the body, with certain sites responding more rapidly to treatment compared with others. In particular, faster skin clearance has been observed in the trunk and head compared with the upper and lower extremities [13–15]. In this post hoc study, zasocitinib appeared to demonstrate faster onset of skin clearance in the trunk and head regions than in the lower extremities, consistent with findings from previous studies [16, 17]. However, by week 12, the proportion of patients achieving PASI 75 response in the zasocitinib 15 or 30 mg groups was significantly higher than those of the placebo group at week 12 regardless of body region, suggesting that any potential variability in skin clearance speed between body regions does not endure beyond 12 weeks. Similar trends of improvement in skin clearance were also observed in PASI 90 and PASI 100 compared with placebo across all body regions assessed. While skin clearance response in the placebo group appeared higher in the head (range: 13.5–23.1% in PASI 75, 90, and 100) than in other body regions assessed, such body region-specific placebo group effects have similarly been reported in other studies, including two phase III studies of deucravacitinib [18], and are generally modest and remain lower than improvements in skin clearance seen with zasocitinib. Improvements in erythema, induration, and desquamation PASI components with zasocitinib were also consistent irrespective of body region and were observed as early as week 2 and maintained through week 12.

Zasocitinib 15 mg or 30 mg demonstrated improvements from baseline in PASI and BSA versus placebo from week 2 that were maintained through week 12. These patterns are consistent with rapid onset of efficacy, which remains an unmet need for treatments and are considered predictive of improved skin clearance and treatment adherence in individuals with moderate-to-severe plaque psoriasis [19, 20]. Absolute PASI is a clinically meaningful and useful measure of individual patient disease severity in real-world practice as it does not rely on knowledge of baseline PASI score [21]. Low absolute PASI values are correlated with improved health-related quality of life, with a PASI threshold of ≤ 2 proposed as a relevant endpoint to inform treat-to-target psoriasis management strategies [21–23].

Absolute PASI endpoints may therefore be used in conjunction with relative PASI and DLQI thresholds, which can help provide a comprehensive assessment of treatment efficacy, depicting both the extent of improvement and residual disease burden [24, 25].

At week 12, approximately one-third of patients receiving zasocitinib 15 mg or 30 mg achieved an absolute PASI threshold ≤ 1 (15 mg, 32.1%; 30 mg, 32.7%), with the vast majority of these achieving PASI 0, and approximately half achieved PASI ≤ 2 (15 mg, 56.6%; 30 mg, 55.8%), indicating that zasocitinib offers promise as an oral option that achieves low PASI thresholds over a short duration.

Improvement in patient-reported outcomes following treatment with zasocitinib 15 mg or 30 mg, as measured by increased proportions of patients reporting DLQI 0/1, was consistent with the observed reductions in absolute and relative PASI score. A higher proportion of patients achieving near-complete or complete skin clearance (PASI ≤ 1 and PASI ≤ 2, and PASI 90 and 100) reported DLQI 0/1, compared with placebo. These findings align with previous studies, which highlight that greater PASI responses correlate with improvement in quality of life, demonstrating the effect of incremental improvements in skin clearance and their association with proportionally higher rates of DLQI 0/1 [26, 27]. DLQI 0/1 rates were numerically higher after treatment with zasocitinib 15 mg versus zasocitinib 30 mg in some PASI strata; however, these post hoc analyses involve small subgroups of patients and were not powered for dose comparisons. Therefore, differences between zasocitinib doses in DLQI 0/1 response rates should be interpreted with caution.

Although PASI remains the most widely used efficacy endpoint in clinical trials, its complexity can limit use in clinical practice [28]. The PGA × BSA composite tool correlates well with PASI and provides a simpler method of assessing the extent and severity of psoriasis [29, 30]. In this study, the PGA × BSA score showed improvements with zasocitinib and was strongly correlated with PASI, further indicating the suitability and potential of this tool to simplify calculations of treatment benefit used by real-world practitioners.

Strengths of this study are that it demonstrates consistent efficacy of zasocitinib across various patient characteristic subgroups, body regions, scoring components, and in multiple complementary endpoints, including PASI 90 and PASI 100, which are increasingly viewed as optimal targets that closely reflect improvements in patient quality of life [26]. However, limitations of this study include the post hoc nature of all efficacy assessments, which covered a relatively short study duration of 12 weeks, were not powered for formal comparisons or multiplicity-adjusted analysis, and had limited sample sizes. Therefore, findings may not be generalizable to larger and more diverse populations.

Results from phase III trials further investigating the safety and efficacy of zasocitinib 30 mg compared with apremilast or placebo in patients with moderate-to-severe plaque psoriasis will provide more information about zasocitinib across multiple endpoints, over a longer duration, and in a larger patient population (NCT06088043 and NCT06108544). The safety and efficacy of zasocitinib in patients with moderate-to-severe plaque psoriasis will also be compared with deucravacitinib in an ongoing head-to-head study (NCT06973291).

Conclusions

In these post hoc analyses of a phase IIb trial, zasocitinib demonstrated consistent improvements over placebo in skin clearance results in patients with moderate-to-severe plaque psoriasis irrespective of body region, scoring components, and baseline disease characteristics, with higher PASI responses associated with DLQI 0/1, demonstrating meaningful improvements in quality of life.

Supplementary Information

Below is the link to the electronic supplementary material.

Declarations

Conflicts of Interest

Nada Elbuluk: consultant, advisory board member, and/or speaker for AbbVie, Allergan, Avita, Beiersdorf, Canfield, Dior, Eli Lilly, Galderma, Incyte, Janssen, Kao USA, Kenvue, La Roche Posay, L’Oreal, McGraw-Hill, Medscape, Pfizer, Sanofi, Takeda, and VisualDx; grant funding from Pfizer and Eli Lilly; royalties from McGraw-Hill; stock options in VisualDx. April W. Armstrong: research investigator, scientific adviser, and/or speaker for AbbVie, Almirall, Arcutis Biotherapeutics, ASLAN Therapeutics, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Dermira, EPI, Incyte, Janssen, LEO Pharma, Eli Lilly, Mindera, Nimbus, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sanofi, Sun Pharma, and UCB. Ronald Vender: grants/research support and speaker bureau/honoraria from AbbVie, Alumis, Amgen, Arcutis Biotherapeutics, Bausch Health, Bristol Myers Squibb, Celltrion, JAMP Pharma, Janssen, LEO Pharma, Lilly, Meiji, Novartis, Organon, Orka, Sandoz, Sun Pharma, Takeda, and UCB; speaker bureau fees from AbbVie, Actelion, Amgen, Arcutis Biotherapeutics, Bausch Health, Bristol Myers Squibb, Celgene, Cipher, Eli Lilly, Galderma, GSK, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Sun Pharma, and UCB; consulting fees from AbbVie, Actelion, Amgen, Aralez, Arcutis Biotherapeutics, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Cipher, Eli Lilly, Galderma, GSK, Janssen, Kabi-Care, LEO Pharma, Merck, Novartis, Paladin, Pfizer, Sandoz, Sun Pharma, UCB, and Viatris-Mylan. Tina Bhutani: research funding from Amgen, Castle Biosciences, CorEvitas, Novartis, Pfizer, and Regeneron; adviser for AbbVie, Arcutis Biotherapeutics, ASLAN Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Galderma, Incyte, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, Sanofi, Sun Pharma, Takeda, and UCB; speaker for Amgen, Arcutis Biotherapeutics, Galderma, Janssen, Lilly, and LEO Pharma. Lawrence Green: investigator, adviser, and/or speaker for AbbVie, Alumis, Amgen, Arcutis Biotherapeutics, Bristol Myers Squibb, Dermavant, Eli Lilly, Highlightll Pharmaceutical, Janssen, Ortho Dermatologics, Sun Pharma, Takeda, UCB, and Ventyx Biosciences. Laura K. Ferris: research funding from AbbVie, Acelyrin, Amgen, Arcutis Biotherapeutics, Aristea, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, Dermasensor, DermTech, Eli Lilly, Galderma, Incyte, Janssen, LEO Pharma, Moberg, Mobius, Novartis, Regeneron, SkinAnalytics, UCB, and Verrica; consultant and/or speaker for AbbVie, Amgen, Arcutis Biotherapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Dermavant, DermTech, Janssen, LEO Pharma, Novartis, Pfizer, Regeneron, and Sanofi. Vivian Laquer: research for AbbVie, Acelyrin, Acrotech, Amgen, Argenx, Arcutis Biotherapeutics, ASLAN Therapeutics, Biofrontera, Bristol Myers Squibb, Cara Therapeutics, Dermavant, Eli Lilly, Galderma, Horizon Therapeutics, Incyte, Janssen, LEO Pharma, Novartis, Padagis, Pfizer, Q32 Bio, Rapt, Sun Pharma, UCB, and Ventyx Biosciences. Angela Moore: research funds from AbbVie, Arcutis Biotherapeutics, Bristol Myers Squibb, Dermavant, Eli Lilly, Janssen, Takeda, and UCB. Jamie Weisman: research grants from AbbVie, Alumis, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Dermira, Eli Lilly, Galderma, Merck, Pfizer, Regeneron, Sanofi, and Takeda. Wenwen Zhang and Warren Winkelman: employees and equity holders in Takeda Development Center Americas, Inc. Melinda J. Gooderham: investigator, speaker, and/or adviser for AbbVie, Akros, Alumis, Amgen, AnaptysBio, Apogee Therapeutics, Arcutis Biotherapeutics, Aristea, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Dermira, Eli Lilly, Galderma, GSK, Incyte, Inmagene, JAMP Pharma, Janssen, Kyowa Kirin, LEO Pharma, MedImmune, Meiji, MoonLake Immunotherapeutics, Nimbus, Novartis, Pfizer, Q32 Bio, Regeneron, Sanofi Genzyme, Sun Pharma, Takeda, Tarsus Pharmaceuticals, UCB, Union Therapeutics, Ventyx Biosciences, and Vyne Therapeutics.

Ethical Approval

This study was performed in accordance with ethical principles originating from the Declaration of Helsinki, which are consistent with Good Clinical Practice and applicable regulatory requirements. Patients provided written informed consent before starting the study. The clinical study protocol (and amendments), investigator brochure, samples of informed consent forms and other study-related documents were reviewed and approved by institutional review boards or independent ethics committees of all study sites. Consent for publication was not applicable as no identifying information is included in this manuscript.