Deucravacitinib in plaque psoriasis: Four‐year safety and efficacy results from the Phase 3 POETYK PSO‐1, PSO‐2 and long‐term extension trials

April W Armstrong; Mark Lebwohl; Richard B Warren; Howard Sofen; Akimichi Morita; Carle Paul; Kim A Papp; Matthew J Colombo; Julie Scotto; John Vaile; Joe Zhuo; Eleni Vritzali; Victoria Berger; Georgene Schroeder; Subhashis Banerjee; Diamant Thaçi; Bruce Strober

doi:10.1111/jdv.20553

. 2025 Mar 6;39(7):1336–1351. doi: 10.1111/jdv.20553

Deucravacitinib in plaque psoriasis: Four‐year safety and efficacy results from the Phase 3 POETYK PSO‐1, PSO‐2 and long‐term extension trials

April W Armstrong ^1,^*,^✉, Mark Lebwohl ², Richard B Warren ^3,⁴, Howard Sofen ^1,⁵, Akimichi Morita ⁶, Carle Paul ⁷, Kim A Papp ⁸, Matthew J Colombo ⁹, Julie Scotto ⁹, John Vaile ⁹, Joe Zhuo ⁹, Eleni Vritzali ⁹, Victoria Berger ⁹, Georgene Schroeder ⁹, Subhashis Banerjee ^9,^*, Diamant Thaçi ¹⁰, Bruce Strober ¹¹

PMCID: PMC12188513 PMID: 40045918

Abstract

Background

Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, is approved in multiple countries for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy.

Objectives

To evaluate the safety and efficacy of deucravacitinib through 4 years in the Phase 3 POETYK PSO‐1, PSO‐2 and long‐term extension (LTE) trials in psoriasis.

Methods

PSO‐1 and PSO‐2 (parent trials) randomized patients 1:2:1 to oral placebo, deucravacitinib 6 mg once daily (QD) or apremilast 30 mg twice daily. At 52 weeks, patients enrolled in the LTE trial received open‐label deucravacitinib 6 mg QD. Safety was evaluated in patients who received ≥1 dose of deucravacitinib at any time. Clinical and patient‐reported outcomes (PASI, PGA and DLQI) were analysed in patients who received continuous deucravacitinib from Day 1 of the parent trials and enrolled in the LTE trial.

Results

In total, 1519 patients received ≥1 dose of deucravacitinib, with cumulative exposure of 4392.8 person‐years (PY) through the data cut‐off of 1 November 2023. Exposure‐adjusted incidence rates (EAIRs)/100 PY of noted safety measures were comparable or decreased from the 1‐year to 4‐year cumulative period, respectively, for adverse events (AEs) (229.23, 131.68), serious AEs (including COVID‐19) (5.68, 5.01), deaths (0.20, 0.25), discontinuation due to AEs (4.38, 2.20), herpes zoster (0.81, 0.55), malignancies (1.02, 0.89), major adverse cardiovascular events (0.30, 0.32) and venous thromboembolism (0.20, 0.07). In patients who received continuous deucravacitinib (n = 513), clinical and patient‐reported outcome rates were well maintained from 1 year through 4 years (e.g. PASI 90, 1 year, 45.6% [95% CI, 41.3%–50.0%], 4 years, 47.5% [42.6%–52.4%]; DLQI 0/1, 1 year, 51.5% [47.1%–55.9%], 4 years, 49.4% [44.4%–54.4%]).

Conclusions

Deucravacitinib demonstrated a consistent safety profile and durable efficacy through 4 years of treatment in patients with moderate to severe plaque psoriasis.

In this analysis of the long‐term safety and efficacy of deucravacitinib in patients with moderate to severe plaque psoriasis treated through 4 years, no new safety signals were observed compared with the first year. Patients continuously treated with deucravacitinib from Day 1 maintained clinical and patient‐reported outcome response rates.

graphic file with name JDV-39-1336-g006.jpg

Why Was the Study Undertaken?

This study evaluated the safety and efficacy of deucravacitinib through 4 years of treatment in patients with moderate to severe plaque psoriasis.

What Does This Study Add?

No new safety signals were observed through 4 years, and patients continuously treated with deucravacitinib maintained clinical and patient‐reported outcome response rates.

What Are the Implications of This Study for Disease Understanding and/or Clinical Care?

These results support the long‐term safety and efficacy of deucravacitinib for patients with moderate to severe plaque psoriasis.

INTRODUCTION

Tyrosine kinase 2 (TYK2), an intracellular enzyme, mediates signalling of select inflammatory cytokines (e.g. interleukin [IL]‐23, IL‐12 and Type I interferons) known to be involved in immune‐mediated diseases. ¹ IL‐23 and Type I interferons in particular are involved in psoriasis pathogenesis. ¹ , ² Deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, is approved at a dose of 6 mg once daily (QD) in the United States, European Union and other countries for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy. ³ , ⁴ , ⁵ , ⁶ , ⁷ , ⁸ Deucravacitinib binds to the TYK2 regulatory domain rather than to the catalytic domain where Janus kinase (JAK) 1, 2, 3 inhibitors bind and allosterically inhibits the enzyme. ¹ , ⁹ The unique mechanism of action of deucravacitinib drives its selectivity for TYK2 over JAK1, 2, 3 and represents the first in a new class of oral treatments.

Two global Phase 3 trials, POETYK PSO‐1 (NCT03624127) and POETYK PSO‐2 (NCT03611751), demonstrated the efficacy and safety of deucravacitinib versus placebo at Week 16 and apremilast at Weeks 16 and 24 in patients with moderate to severe plaque psoriasis based on the co‐primary endpoints of a ≥ 75% reduction from baseline in the Psoriasis Area and Severity Index (PASI 75) and a static Physician Global Assessment score of 0 (clear) or 1 (almost clear) (sPGA 0/1). ¹⁰ , ¹¹ Patients who completed the PSO‐1 and PSO‐2 parent trials could enrol in the ongoing long‐term extension (LTE) trial (NCT04036435) and receive open‐label deucravacitinib. ¹² The clinical efficacy of deucravacitinib has been shown earlier through 3 years of treatment with no new safety signals compared with results through 1 year. ¹³ Here, we present deucravacitinib safety and efficacy over an additional year through a cumulative period of 4 years (PSO‐1 and PSO‐2 parent trials, 1 year; LTE trial, 3 years).

MATERIALS AND METHODS

Study design and population

POETYK PSO study designs have been previously reported. ¹⁰ , ¹¹ Briefly, the PSO‐1 and PSO‐2 trials randomized adults with moderate to severe plaque psoriasis (PASI ≥ 12, sPGA ≥ 3 and body surface area involvement ≥10% at baseline) 1:2:1 to oral placebo, deucravacitinib 6 mg QD or apremilast 30 mg twice daily (Figure 1). Blinded treatment switches occurred at Weeks 16 and 24. At Week 52 in both trials, eligible patients could enrol in the ongoing 5‐year LTE trial and receive open‐label deucravacitinib 6 mg QD. ¹²

The POETYK PSO‐1, PSO‐2 and LTE study designs. ^a Apremilast was titrated from 10 mg QD to 30 mg BID over the first 5 days of dosing. ^b Upon relapse (≥50% loss of Week 24 PASI percentage improvement from baseline), patients were to be switched to deucravacitinib 6 mg QD; due to a programming error, however, these patients continued on placebo until Week 52. ^c Data reported through the 208‐day POETYK LTE cut‐off date of 1 November 2023. Reproduced with permission from Lebwohl M, et al. ¹² BID, twice daily; LTE, long‐term extension; PASI 50/75, ≥50%/≥75% reduction from baseline in Psoriasis Area and Severity Index; QD, once daily.

Analysis datasets

Safety and efficacy data were assessed through 1 November 2023 (cumulative Week 208 [4 years]). Safety data are reported in the as‐treated population (patients receiving ≥1 dose of deucravacitinib at any time). Efficacy data are reported for the pooled PSO‐1 and PSO‐2 patient populations who received continuous deucravacitinib treatment from Day 1 of these trials, enrolled in the LTE trial and were treated through a cumulative 208 weeks. Additionally, efficacy was determined in patients receiving continuous deucravacitinib who achieved PASI 75 at Week 16 (primary endpoint) or Week 24 (peak response) in the parent trials and entered the LTE trial.

Assessments

Endpoints assessed in the LTE trial were safety and efficacy. Safety assessments include adverse events (AEs) and serious AEs (SAEs) (primary endpoints), as well as deaths, AEs leading to treatment discontinuation and AEs of interest (AEIs). AEs were ascribed to the treatment group to which patients were assigned when the event first occurred. AEIs were identified based on the deucravacitinib safety and tolerability profile as determined in Phase 1 and 2 trials, comorbidities associated with plaque psoriasis and AEs noted with other psoriasis therapies. AEs were coded per the Medical Dictionary for Regulatory Activities (MedDRA version 26.1). AEIs included serious infections (COVID‐19), select nonserious infections (herpes zoster), malignancies, major adverse cardiovascular events (MACE) (nonfatal stroke, nonfatal myocardial infarction and cardiovascular death), venous thromboembolism events (VTE) (deep vein thrombosis and pulmonary embolism) and certain skin events (e.g. acne). Laboratory analytes in the blood that are known to be impacted by treatment with JAK1, 2, 3 inhibitors, including haematologic (haemoglobin, neutrophils, lymphocytes and platelets), chemistry (alanine aminotransferase [ALT], aspartate aminotransferase [AST], creatinine, creatine phosphokinase [CPK]) and lipid (total cholesterol, high‐density lipoprotein [HDL] cholesterol, low‐density lipoprotein [LDL] cholesterol and triglycerides) parameters were evaluated.

Clinician‐assessed efficacy outcomes included achievement of PASI 75 and sPGA 0/1 (the primary endpoints in POETYK PSO‐1 and PSO‐2), as well as ≥90% reduction from baseline in PASI (PASI 90), 100% reduction from baseline in PASI (PASI 100), sPGA 0 (clear), scalp‐specific PGA score of 0 (clear) or 1 (almost clear) (ss‐PGA 0/1) in patients with a baseline ss‐PGA ≥3, PGA‐Fingernail (PGA‐F) score of 0 (clear) or 1 (almost clear) (PGA‐F 0/1) in patients with a baseline PGA‐F ≥ 3 and per cent change from baseline in PASI score. Patient‐reported outcomes included mean change from baseline in Psoriasis Symptoms and Signs Diary (PSSD) total score, mean change from baseline in Dermatology Life Quality Index (DLQI) and a DLQI of 0 or 1 (DLQI 0/1) in patients with baseline DLQI ≥2. These instruments are further described in Appendix S1. Patient‐reported outcomes, ss‐PGA 0/1 and PGA‐F 0/1 are reported through Week 196 (closest assessment to Week 208) based on a data collection schedule that was slightly different from other safety and efficacy outcomes.

Statistical analysis

Safety data are reported as frequencies and exposure‐adjusted incidence rates per 100 person‐years (EAIRs/100 PY). EAIRs are calculated as 100 multiplied by the number of patients with an AE divided by the total exposure time for all patients at risk (time to initial AE occurrence for patients with an AE + total exposure time for patients without an AE) to account for variable periods of treatment exposure due to treatment switches at Weeks 16 and 24 in the parent trials.

Efficacy outcomes were evaluated using the prespecified as‐observed analysis without imputation of missing data. Additionally, three imputation methods for missing data were used as sensitivity analyses. For binary measures, treatment failure rules (TFR) imputed patients who discontinued treatment due to lack of efficacy or worsening of psoriasis as nonresponders; all other missing data were not imputed. Binary measures were also imputed using modified nonresponder imputation (mNRI), which included patients who either discontinued treatment before Week 208 or reached Week 208; patients with missing data who discontinued treatment due to worsening of psoriasis were imputed as nonresponders and all other missing data were imputed by multiple imputation. For continuous clinical efficacy and patient‐reported measures, multiple imputation with baseline observation carried forward (MI‐BOCF) was used; patients with missing data who discontinued treatment due to worsening psoriasis had the baseline observation carried forward and all other missing data were imputed by multiple imputation. These methods of imputation were performed only for the LTE trial data as has been done in reports for other agents in long‐term extension studies; results with other, more stringent imputation methods for missing data have been reported earlier for the controlled period in the parent trials (Weeks 0–52). ¹⁰ , ¹¹

The Clopper–Pearson method was used to calculate 95% confidence intervals (CIs) when there were no missing data or for NRI. In other instances, the Rubin method was used for multiple imputation.

RESULTS

Patient population and treatment exposure

Baseline patient demographics and disease characteristics for the safety (n = 1519) and efficacy (n = 513) populations (Table 1) were typical of patients with moderate to severe plaque psoriasis. Overall exposure to deucravacitinib was 4392.8 PY. The median (min, max) days of exposure at data cut‐off for the as‐treated population were 1298 (1, 1893) days, with 542 (35.7%) having ≥48 months of total exposure (Table S1). Of the 1519 patients who received at least one dose of deucravacitinib, 811 (53.4%) were receiving ongoing treatment as of the data cut‐off, 409 (26.9%) had discontinued treatment in the LTE trial, 54 (3.6%) completed PSO‐1 or PSO‐2 but did not enrol in the LTE trial and 244 (16.1%) did not complete PSO‐1 or PSO‐2 (Figure S1). Of the 513 patients in the efficacy population who received deucravacitinib from Day 1 and entered the LTE trial, 322 (62.8%) were receiving ongoing treatment as of the data cut‐off, 10 (2.0%) were ongoing but had not reached or had missing Week 208 data and 180 (35.1%) had discontinued treatment, including 71 (13.8%) patients who discontinued treatment before Week 112.

TABLE 1.

Baseline patient demographics and disease characteristics.

Parameter	Safety population (n = 1519) ^a	Efficacy population ^b (n = 513)
Age, mean (SD), y	46.6 (13.4)	46.9 (13.3)
Weight, mean (SD), kg	90.6 (21.6)	89.9 (22.2)
Body mass index, mean (SD), kg/m²	30.5 (6.8)	30.3 (7.0)
Female, n (%)	493 (32.5)	159 (31.0)
Race, n (%)
White	1325 (87.2)	440 (85.8)
Asian	153 (10.1)	64 (12.5)
Black or African American	23 (1.5)	5 (1.0)
Other	18 (1.2)	4 (0.8)
Disease duration, mean (SD), y	18.7 (12.7)	18.8 (12.6)
PASI, mean (SD)	21.1 (8.1)	21.1 (7.9)
sPGA score, n (%)
3 (moderate)	1211 (79.7)	401 (78.2)
4 (severe)	308 (20.3)	112 (21.8)
BSA involvement, mean (SD), %	26.2 (15.8)	26.9 (15.8)
PSSD total score, mean (SD)	‐	52.9 (23.5)
DLQI, mean (SD)	‐	11.8 (6.6)

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Abbreviations: BSA, body surface area; DLQI, Dermatology Life Quality Index; LTE, long‐term extension; PASI, Psoriasis Area and Severity Index; PSSD, Psoriasis Symptoms and Signs Diary; SD, standard deviation; sPGA, static Physician Global Assessment.

^{^a}

Patients who received at least one dose of deucravacitinib across the parent trials (POETYK PSO‐1 and PSO‐2) and the POETYK LTE trial.

^{^b}

Patients who were randomized to deucravacitinib in the parent trials and who entered the POETYK LTE trial.

Overall safety

The most common AEs (EAIR ≥5/100 PY) through the 4‐year cumulative period were nasopharyngitis (EAIR/100 PY [95% CI], 9.72/100 PY [8.72–10.81]), COVID‐19 (8.29/100 PY [7.41–9.25]) and upper respiratory tract infection (6.11/100 PY [5.36–6.94]) (Table 2). SAEs occurring in two or more patients treated with deucravacitinib are outlined in Table S2. The most common SAEs (EAIRs ≥ 5/100 PY) reported were related to COVID‐19 (EAIR/100 PY [95% CI], 1.22/100 PY [0.92–1.60]), as the LTE trial was conducted during the global pandemic. A total of 11 deaths were reported over the 4‐year cumulative period, 10 of which were reported through the 3‐year cumulative period and of which 7 were COVID‐19–related. ¹² , ¹³ , ¹⁴ Overall incidence rates of non‐COVID‐19–related AEs decreased from 1 year in PSO‐1 and PSO‐2 through the 4‐year cumulative period.

TABLE 2.

Cumulative safety summary through 1 year and 4 years (as‐treated population).

AE category	Cumulative through 1 year ^a (POETYK PSO‐1 + PSO‐2)						Cumulative through 4 years ^b (POETYK PSO‐1 + PSO‐2 + LTE)
	Placebo (n = 666)		Apremilast 30 mg BID (n = 422)		Deucravacitinib (n = 1364)		Deucravacitinib (n = 1519)
	Total PY = 240.9		Total PY = 221.1		Total PY = 969.0		Total PY = 4392.8
	1‐Year cumulative, n (%)	EAIR/100 PY (95% CI)	1‐Year cumulative, n (%)	EAIR/100 PY (95% CI)	1‐Year cumulative, n (%)	EAIR/100 PY (95% CI)	4‐Year cumulative, n (%)	EAIR/100 PY (95% CI)
AEs	347 (52.1)	217.37 (195.66–241.49)	299 (70.9)	281.06 (250.94–314.79)	995 (72.9)	229.23 (215.42–243.93)	1301 (85.6)	131.68 (124.62–139.03)
SAEs	14 (2.1)	5.66 (3.35–9.55)	9 (2.1)	4.01 (2.09–7.71)	55 (4.0)	5.68 (4.36–7.39)	205 (13.5)	5.01 (4.35–5.75)
Discontinued treatment due to AEs	23 (3.5)	9.31 (6.18–14.01)	26 (6.2)	11.64 (7.93–17.10)	43 (3.2)	4.38 (3.25–5.91)	97 (6.4)	2.20 (1.78–2.68)
Deaths	1 (0.2)	0.40 (0.06–2.84)	1 (0.2)	0.44 (0.06–3.14)	2 (0.1) ^c	0.20 (0.05–0.81)	11 (0.7) ^d	0.25 (0.12–0.44)
Most common AEs (EAIR ≥5/100 PY)
Nasopharyngitis	54 (8.1)	22.72 (17.40–29.66)	54 (12.8)	25.95 (19.87–33.88)	229 (16.8)	26.14 (22.97–29.76)	343 (22.6)	9.72 (8.72–10.81)
Upper respiratory tract infection	33 (5.0)	13.54 (9.63–19.05)	27 (6.4)	12.37 (8.48–18.03)	124 (9.1)	13.42 (11.25–16.00)	240 (15.8)	6.11 (5.36–6.94)
Headache	21 (3.2)	8.56 (5.58–13.12)	53 (12.6)	25.98 (19.85–34.01)	80 (5.9)	8.47 (6.81–10.55)	117 (7.7)	2.83 (2.34–3.39)
Diarrhoea	28 (4.2)	11.51 (7.95–16.67)	54 (12.8)	26.48 (20.28–34.58)	69 (5.1)	7.27 (5.75–9.21)	99 (6.5)	2.36 (1.92–2.87)
Arthralgia	21 (3.2)	8.55 (5.57–13.11)	17 (4.0)	7.66 (4.76–12.32)	55 (4.0)	5.71 (4.38–7.43)	117 (7.7)	2.80 (2.32–3.36)
COVID‐19 ^e	2 (0.3)	0.80 (0.20–3.20)	0	0	5 (0.4)	0.51 (0.21–1.22)	321 (21.1)	8.29 (7.41–9.25)

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Note: Not all patients were receiving deucravacitinib 6 mg QD continuously throughout this period. Total PY corresponds to the total exposure time to deucravacitinib during the indicated time period.

Abbreviations: AE, adverse event; BID, twice daily; CI, confidence interval; EAIR, exposure‐adjusted incidence rate; LTE, long‐term extension; PY, person‐years; QD, once daily; SAE, serious adverse event.

^{^a}

This represents the pooled patient population of POETYK PSO‐1 and PSO‐2 (Weeks 0–52).

^{^b}

This represents the pooled patient population of POETYK PSO‐1, PSO‐2 and LTE through the cut‐off date of 1 November 2023.

^{^c}

In POETYK PSO‐1 and PSO‐2 through 1 year, one patient discontinued deucravacitinib after 4 days of treatment due to prohibited medication (leflunomide) and died 9 days later reportedly due to heart failure and sepsis without medical records being available. Another death occurred between Weeks 16 and 52 and was due to hepatocellular carcinoma in a patient with a history of hepatitis C virus infection and liver cirrhosis. Both deaths were considered unrelated to treatment by the investigator.

^{^d}

After Week 52, seven deaths were due to COVID‐19 (all in patients with risk factors for severe disease; two deaths were considered related to treatment and the other five deaths were considered unrelated to treatment by the investigator). One death due to a ruptured aortic aneurysm occurred in a patient with cardiovascular risk factors, which was considered unrelated to treatment by the investigator. One sudden death due to an unknown cause occurred in the time between the preceding 3‐year data cut‐off of 15 June 2022, and the current data cut‐off in a 76‐year‐old male with a history of type 2 diabetes mellitus with neuropathy, hypertension and hypercholesterolaemia; this death was not considered related to treatment by the investigators.

^{^e}

The POETYK PSO‐1, PSO‐2 and LTE trials were conducted during the COVID‐19 pandemic.

AEs of interest

In the 4‐year cumulative period, EAIRs (incidence/100 PY [95% CI]) for AEIs remained comparable or were decreased compared with those in the 1‐year period, including MACE (0.32/100 PY [0.17–0.53]), VTE (0.07/100 PY [0.01–0.20]), malignancies (0.89/100 PY [0.63–1.22]), malignancies excluding nonmelanoma skin cancer (NMSC; 0.50/100 PY [0.31–0.75]), herpes zoster (0.55/100 PY [0.35–0.82]), acne (1.04/100 PY [0.76–1.40]), folliculitis (0.80/100 PY [0.56–1.12]) and oral ulcer (0.93/100 PY [0.66–1.26]) (Table 3). No trends in individual types of malignancies were observed. For NMSCs, the ratio of basal cell carcinoma to squamous cell carcinoma events remained at least 2:1. Of note, no VTE or lymphoma events were observed in Year 3 or Year 4; rates of MACE remained stable. The serious infection rate was higher in the 4‐year cumulative period (1.99/100 PY [1.59–2.46]) compared with 1 year (1.73/100 PY [1.08–2.79]) due to COVID‐19, as the peak of the global COVID‐19 pandemic occurred during Years 2 and 3 of the LTE trial. The rate of serious infections when excluding COVID‐19 was lower at 4 years (0.80/100 PY [0.56–1.11]) compared with 1 year (1.53/100 PY [0.86–2.52]).

TABLE 3.

Cumulative AEs of interest through 1 year and 4 years (as‐treated population).

AE category	1 year ^a (POETYK PSO‐1 + PSO‐2)						4 years ^b (POETYK PSO‐1 + PSO‐2 + LTE)
	Placebo (n = 666)		Apremilast 30 mg BID (n = 422)		Deucravacitinib (n = 1364)		Deucravacitinib (n = 1519)
	Total PY = 240.9		Total PY = 221.1		Total PY = 969.0		Total PY = 4392.8
	1‐year cumulative n (%)	EAIR/100 PY (95% CI)	1‐year cumulative n (%)	EAIR/100 PY (95% CI)	1‐year cumulative n (%)	EAIR/100 PY (95% CI)	4‐year cumulative n (%)	EAIR/100 PY (95% CI)
Serious infections	2 (0.30)	0.80 (0.20–3.20)	4 (0.95)	1.78 (0.67–4.73)	17 (1.25)	1.73 (1.08–2.79)	85 (5.60)	1.99 (1.59–2.46)
Serious COVID‐19/COVID‐19 pneumonia	0	0	1 (0.24)	0.44 (0.01–2.46)	2 (0.15)	0.20 (0.02–0.73)	54 (3.55)	1.25 (0.94–1.63)
Serious infections excluding COVID‐19	2 (0.30)	0.80 (0.10–2.89)	3 (0.71)	1.33 (0.27–3.89)	15 (1.10)	1.53 (0.86–2.52)	35 (2.30)	0.80 (0.56–1.11)
Herpes zoster
Herpes zoster ^c	1 (0.2)	0.40 (0.06–2.84)	0	0	8 (0.6)	0.81 (0.41–1.63)	24 (1.6)	0.55 (0.35–0.82)
Ophthalmic herpes zoster ^d	0	0	0	0	1 (0.1)	0.10 (0.01–0.72)	1 (0.1)	0.02 (0.0–0.13)
MACE ^e	3 (0.5)	1.20 (0.39–3.73)	2 (0.5)	0.89 (0.22–3.54)	3 (0.2)	0.30 (0.10–0.94)	14 (0.9)	0.32 (0.17–0.53)
VTE ^f	0	0	0	0	2 (0.1)	0.20 (0.05–0.81)	3 (0.2)	0.07 (0.01–0.20)
Malignancies	0	0	2 (0.5)	0.89 (0.22–3.54)	10 (0.7)	1.02 (0.55–1.89)	39 (2.6)	0.89 (0.63–1.22)
NMSC	0	0	1 (0.2)	0.44 (0.06–3.14)	7 (0.5)	0.71 (0.34–1.49)	18 (1.2)	0.41 (0.24–0.65)
Basal cell carcinoma	0	0	0	0	4 (0.3)	0.41 (0.15–1.08)	13 (0.9)	0.30 (0.16–0.51)
Squamous cell carcinoma ^g	0	0	1 (0.2)	0.44 (0.06–3.14)	2 (0.1)	0.20 (0.05–0.81)	5 (0.3)	0.11 (0.04–0.26)
Malignancies excluding NMSC	0	0	1 (0.2)	0.44 (0.06–3.14)	3 (0.2)	0.30 (0.10–0.94)	22 (1.4) ^h	0.50 (0.31–0.75)
Lymphoma	0	0	0	0	1 (0.1)	0.10 (0.01–0.72)	3 (0.2)	0.07 (0.01–0.20)
Hodgkin's disease	0	0	0	0	1 (0.1)	0.10 (0.01–0.72)	1 (0.1)	0.02 (0.0–0.13)
Leukaemia	0	0	0	0	0	0	1 (0.1)	0.02 (0.0–0.13)
Acne	1 (0.2)	0.40 (0.06–2.84)	0	0	28 (2.1)	2.88 (1.99–4.18)	45 (3.0)	1.04 (0.76–1.40)
Folliculitis	0	0	2 (0.5)	0.89 (0.22–3.54)	27 (2.0)	2.77 (1.90–4.04)	35 (2.3)	0.80 (0.56–1.12)
Oral ulcer	0	0	0	0	18 (1.3)	1.84 (1.16–2.93)	40 (2.6)	0.93 (0.66–1.26)

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Abbreviations: AE, adverse event; BID, twice daily; CI, confidence interval; EAIR, exposure‐adjusted incidence rate; LTE, long‐term extension; MACE, major adverse cardiovascular event; NMSC, nonmelanoma skin cancer; PY, person‐years; QD, once daily; VTE, venous thromboembolism.

^{^a}

This represents the pooled patient population of POETYK PSO‐1 and PSO‐2 (Weeks 0–52).

^{^b}

This represents the pooled patient population of POETYK PSO‐1, PSO‐2 and LTE through the cut‐off date of 1 November 2023.

^{^c}

One patient who was coded as having herpes zoster had corneal/ocular disease related to herpes virus infection diagnosed by an ophthalmologist with a positive qualitative chickenpox virus antigen (epithelial cells).

^{^d}

One patient who was coded as having ophthalmic herpes zoster with swelling of eyelids was referred for ophthalmology consultation, which was noted as normal; there was no corneal/ocular disease related to herpes virus infection.

^{^e}

MACE were adjudicated and were defined as nonfatal stroke, nonfatal myocardial infarction or cardiovascular death. MACE in deucravacitinib‐treated patients through 1 year: cardiac failure leading to death; cerebrovascular accident; myocardial infarction. Through Year 4: acute myocardial infarction, n = 5; cerebrovascular accident, n = 2; myocardial infarction, n = 2; aortic aneurysm rupture; cardiac arrest; cardiac failure leading to death; cerebral haemorrhage; ischaemic stroke; sudden death.

^{^f}

VTE was defined as deep vein thrombosis and pulmonary embolism. VTE events in deucravacitinib‐treated patients through 1 year: deep vein thrombosis; pulmonary embolism. Through Year 4: deep vein thrombosis, n = 2; pulmonary embolism.

^{^g}

Includes preferred terms of squamous cell carcinoma, squamous cell carcinoma of skin and Bowen's disease.

^{^h}

Includes events of (n = 1 unless otherwise noted): breast cancer (n = 2), invasive ductal breast carcinoma, intraductal proliferative breast lesion, lung adenocarcinoma (n = 2), colon cancer (n = 2), colon cancer metastatic, adenocarcinoma of colon, colorectal cancer, pancreatic carcinoma, hepatocellular carcinoma, B‐cell lymphoma, nodal marginal zone B‐cell lymphoma, Hodgkin's disease, acute promyelocytic leukaemia, malignant melanoma (n = 2), oesophageal carcinoma, prostate cancer, squamous cell carcinoma of the tongue and squamous cell carcinoma of the oral cavity.

Laboratory parameters

No clinically meaningful mean changes from baseline were observed through 4 years in any of the evaluated haematology, chemistry or lipid laboratory parameters (Figure 2a–l). Laboratory parameters remained within normal ranges for the vast majority of patients throughout this period. A minimal increase (<10 mg/dL) in the mean change from baseline (146.9 mg/dL) in serum triglycerides was observed with deucravacitinib during the first year of treatment. This increase was not considered clinically relevant (within the upper limit of normal of 150 mg/dL) and was not associated with increases in LDL cholesterol levels; mean triglyceride values were then stable over time (Week 196, 152.5 mg/dL).

Changes in haematology, chemistry and lipid parameters (a‐l) over 4 years in patients receiving deucravacitinib. ALT, alanine aminotransferase; AST, aspartate aminotransferase; CPK, creatine phosphokinase; LLN, lower limit of normal; LTE, long‐term extension; SD, standard deviation; ULN, upper limit of normal.

Efficacy

Clinical efficacy response rates were maintained from 1 year through 4 years in patients treated continuously with deucravacitinib from Day 1 of the parent trials (PASI 75, 1 year, 72.0% [95% CI, 68.1%–75.9%], 4 years, 71.7% [67.0%–76.3%]; PASI 90, 45.6% [41.3%–50.0%], 47.5% [42.6%–52.4%]; PASI 100, 20.1% [16.6%–23.6%], 21.2% [16.9%–25.4%]; sPGA 0/1, 57.7% [53.4%–62.0%], 57.2% [52.1%–62.2%]; sPGA 0, 24.3% [20.6%–28.0%], 23.5% [19.1%–28.0%]; using the stringent mNRI methodology) (Figure 3a–e). Results were consistent with as‐observed values and by imputation by TFR methodology. Patients maintained a mean per cent change from baseline in PASI scores from Week 52 (−82.4% [95% CI, −84.3% to −80.4%]) to Week 208 (−81.1% [−83.9% to −78.4% (Figure 4). Improvement in scalp psoriasis assessed by ss‐PGA 0/1 response rates was maintained from Week 52 (74.0% [95% CI, 69.2%–78.9%]) through 4 years (Week 196) (70.8% [64.7%–76.8%]; mNRI) (Figure 5a). PGA‐F 0/1 response rates improved from Week 52 (50.0% [95% CI, 37.4%–62.6%]) through 4 years (57.9% [44.3%–71.5%]; mNRI) (Figure 5b).

Adjusted mean per cent change from baseline in PASI score through 4 years with MI‐BOCF imputation. Data callouts represent mean percent change from baseline (95% CI). CI, confidence interval; LTE, long‐term extension; MI‐BOCF, baseline observation carried forward with multiple imputation; PASI, Psoriasis Area and Severity Index; SD, standard deviation.

(a) ss‐PGA 0/1 and (b) PGA‐F 0/1 response rates with continuous deucravacitinib treatment from Day 1–4 years. Data callouts represent the response rate (95% CI). CI, confidence interval; LTE, long‐term extension; mNRI, modified nonresponder imputation; PGA‐F, Physician Global Assessment‐Fingernail; ss‐PGA, scalp‐specific Physician Global Assessment; TFR, treatment failure rules.

Clinical efficacy was maintained through 4 years with continuous deucravacitinib treatment in patients who achieved PASI 75 at Week 16 or Week 24 (Figures S2–S5).

Patient‐reported outcomes

From a mean (standard deviation) PSSD total score of 52.9 (24.1) and mean DLQI of 11.8 (6.6) at baseline, patients had substantial improvements in score after 1 year of deucravacitinib treatment, which were maintained through 4 years of continuous treatment after entering the LTE trial. At Week 196, using the MI‐BOCF imputation method, mean improvement from baseline in PSSD total score was −32.2 (95% CI, −34.8 to −29.6) (Figure 6) and mean improvement in DLQI was −8.5 (95% CI, −9.1 to −7.9) (Figure S6). In patients with a baseline DLQI ≥2, the DLQI 0/1 response rate using mNRI at Week 52 (51.5% [95% CI, 47.1%–55.9%]) was maintained at Week 196 (49.4% [44.4%–54.4%]) (Figure 7).

PSSD total score change from baseline with continuous deucravacitinib treatment through 4 years. Data from Weeks 0–52 reflect the weekly average of daily scores using the 24‐hour recall PSSD. Weeks 68–196 reflect the 7‐day recall PSSD score. Patient‐reported outcomes were recorded on a different schedule than clinical efficacy and safety outcomes; therefore, they are reported through Week 196 (the closest timepoint to Week 208). Data callouts represent mean score change from baseline (95% CI). CI, confidence interval; LTE, long‐term extension; MI‐BOCF, baseline observation carried forward with multiple imputation; PSSD, Psoriasis Symptoms and Signs Diary; SD, standard deviation.

DLQI 0/1 response rate with continuous deucravacitinib treatment through 4 years in patients with parent study baseline DLQI ≥2. Patient‐reported outcomes were recorded on a different schedule than clinical efficacy and safety outcomes; therefore, they are reported through Week 196 (the closest timepoint to Week 208). Data callouts represent response rate (95% CI). CI, confidence interval; DLQI 0/1, Dermatology Life Quality Index of 0 or 1; LTE, long‐term extension; mNRI, modified nonresponder imputation.

DISCUSSION

In this 4‐year analysis of the POETYK PSO‐1, PSO‐2 and LTE trials, deucravacitinib demonstrated a consistent safety profile with no increases in AE or SAE rates over time, aside from COVID‐19–related events during the concurrent global pandemic, and no overall emergence of any new safety signals. The most common AEs, excluding COVID‐19, remained nasopharyngitis and upper respiratory tract infection from 1 year through 4 years. Serious AEs and AEs leading to discontinuation remained low through 4 years.

AEI incidence rates, including serious infections, MACE and malignancies, decreased or were comparable from the 1‐year through the 4‐year analysis. These rates at the 4‐year analysis remained comparable to the results (where available) from long‐term clinical trial safety studies, disease registries and real‐world claims data of other approved psoriasis treatments (Figure 8). ¹⁵ , ¹⁶ , ¹⁷ , ¹⁸ , ¹⁹ , ²⁰ , ²¹ , ²² , ²³ , ²⁴ , ²⁵ , ²⁶ , ²⁷ While these long‐term comparative safety data versus other agents should be interpreted with caution due to the lack of direct head‐to‐head comparisons, they provide some relevant context for the safety findings reported herein.

Incidence rates of AEs of interest (a‐c), deucravacitinib versus other systemic psoriasis treatments. The deucravacitinib data represent the phase 3 safety pool through the LTE cut‐off date of 01 November 2023. Published data on malignancies excluding NMSC were not available for secukinumab. Incidence rates for patients with psoriasis stratified by therapy are from the Optum Claims Analysis; data on file [Bristol Myers Squibb, 2024]. BADBIR, British Association of Dermatologists Biologic and Immunomodulators Register; CI, confidence interval; EAIR, exposure‐adjusted incidence rate; IL, interleukin; LTE, long‐term extension; MACE, major adverse cardiovascular event; NMSC, nonmelanoma skin cancer; PsoBest, the German Psoriasis Registry; PSOLAR, the Psoriasis Longitudinal Assessment and Registry; PY, person‐years; SEER, Surveillance, Epidemiology, and End Results programme; TNF, tumour necrosis factor.

Serious infection rates at 1 year (EAIR 1.73/100 PY [95% CI, 1.08–2.79]) were comparable to pre‐pandemic rates of other approved psoriasis therapies. ²⁸ , ²⁹ , ³⁰ , ³¹ , ³² , ³³ , ³⁴ , ³⁵ , ³⁶ , ³⁷ Serious infection rates at 4 years were similar (1.99/100 PY [1.59–2.46]) or lower when COVID‐19 cases were excluded (0.80/100 PY [0.56–1.11]). COVID‐19 rates increased due to the timing of the pandemic following the first year; however, rates of COVID‐19 remained similar to those of Year 3 of the cumulative 4 years and were consistent with background rates in the general population. ¹³ , ³⁸ Herpes zoster incidence rates decreased from 1 year (EAIR 0.81/100 PY [95% CI, 0.41–1.63]) to 4 years (0.55/100 PY [0.35–0.82]) and remained comparable to rates in patients receiving various systemic treatments for psoriasis, including anti‐IL‐17, anti‐IL‐23, anti‐IL‐12/23 and tumour necrosis factor (TNF) inhibitors (0.5–1.3/100 PY). ³⁹

The EAIR for MACE with deucravacitinib treatment through 4 years (0.32/100 PY [95% CI, 0.17–0.53]) was comparable to that in the first year and to that in long‐term extension studies of other psoriasis treatments, including ustekinumab, guselkumab, risankizumab and secukinumab (0.3–0.4/100 PY) (Figure 8). ¹⁵ , ¹⁶ , ¹⁷ , ¹⁸ , ²² , ²³ VTE events (n = 3) were previously reported over the first 2 years (none was considered drug‐related); and no new VTE events were reported in the 3‐year or 4‐year data cuts (4‐year, 0.07/100 PY [95% CI, 0.01–0.20]). ¹² The incidence rate for VTEs was consistent with published background rates in patients with mild to severe psoriasis (0.19–0.32/100 PY) and the general population (0.1–0.2/100 PY). ⁴⁰ , ⁴¹ , ⁴² , ⁴³

The rate of malignancy (excluding NMSC, EAIR 0.50/100 PY [95% CI, 0.31–0.75]) with deucravacitinib treatment through 4 years remained low and was consistent with the expected rate based on the US general population Surveillance, Epidemiology, and End Results (SEER) database (standardized incidence ratio [SIR], 1.1; 95% CI, 0.7–1.6) (Figure 8). ²⁷ No trends or clusters of malignancy types were noted. The rate of NMSC (EAIR 0.41/100 PY [95% CI, 0.24–0.65]) in patients treated with deucravacitinib was consistent with other trials (0.3–0.5/100 PY). ¹⁵ , ¹⁶ , ¹⁷ The rate of basal cell carcinoma to squamous cell carcinoma, which was nearly 2:1, remained similar to that reported through Year 1. The rate for lymphoma decreased from 1 year (0.10/100 PY [0.01–0.72]) to 4 years (0.07/100 PY [0.01–0.20]). Per US SEER data, the SIR for lymphoma through 4 years was not significantly higher than in the general US population (SIR 2.3/100 PY [0.46–6.69]). ²⁷ Additionally, the risk of lymphoma in patients with psoriasis (EAIR 0.04–0.14/100 PY) has been shown to be higher than the general population (EAIR 0.02–0.03/100 PY). ⁴⁴ , ⁴⁵ , ⁴⁶ , ⁴⁷ , ⁴⁸ , ⁴⁹ , ⁵⁰ , ⁵¹ , ⁵²

No clinically meaningful mean changes were noted through 4 years in haematology, chemistry or lipid laboratory parameters. Changes in mean laboratory parameters known to be impacted on treatment with JAK1, 2, 3 inhibitors, such as decreases in lymphocytes, haemoglobin and platelets, and increases in ALT, AST, creatinine and cholesterol, were not observed with long‐term deucravacitinib treatment. ⁵³ Baseline levels of cholesterol and triglycerides were elevated, as is expected with dysmetabolic comorbidities seen in patients with psoriasis. ⁵⁴ A minimal, nonclinically significant increase in triglyceride levels (<10 mg/dL) from baseline (146.9 mg/dL) was seen during the parent trials. Triglyceride levels remained stable through 4 years and this increase was not associated with any concurrent increases in LDL cholesterol.

Clinical (including scalp and fingernail) and patient‐reported efficacy outcomes were maintained through 4 years in patients treated continuously with deucravacitinib from Day 1 in the parent trials and for many of the clinical outcomes studied in patients who achieved PASI 75 response by Week 16 (primary endpoint) or Week 24 (peak response) in the parent trials. PASI 75, PASI 90, sPGA 0/1 and ss‐PGA 0/1 response rates were sustained from Year 1 through 4 years. In addition, PGA‐F 0/1 response rates improved through 4 years, demonstrating long‐term efficacy in the hard‐to‐treat area of fingernail psoriasis.

Psoriasis carries a high symptom burden that may profoundly affect patients' quality of life. ⁵⁵ , ⁵⁶ Patients receiving deucravacitinib reported substantial improvements from baseline in their self‐assessed psoriasis symptoms and signs (as measured by the PSSD total score) and quality of life (as measured by the DLQI) over Year 1 that were maintained over 4 years. Approximately half of patients reported no impact of psoriasis on their quality of life (DLQI 0/1) after 1 year of deucravacitinib treatment, and this rate was maintained through Week 196.

In conclusion, deucravacitinib demonstrated a consistent long‐term safety profile and maintained clinical and patient‐reported efficacy outcomes through 4 years. These data support the long‐term safety and durable efficacy profile of treatment with deucravacitinib, the first‐in‐class, allosteric TYK2 inhibitor treatment in psoriasis.

AUTHOR CONTRIBUTIONS

AWA, ML, RBW, HS, AM, CP, KAP, MJC, JS, JV, JZ, EV, VB, SB, DT and BS contributed to the study concept and design. KAP, MJC, JS, JV, JZ, VB and SB contributed to the data acquisition. MJC, JS, JV, JZ, VB, GS and SB contributed to the statistical analysis. All authors contributed to the data interpretation, critically reviewed the manuscript for intellectual content and provided final approval for publication.

FUNDING INFORMATION

This study was funded by Bristol Myers Squibb.

CONFLICT OF INTEREST STATEMENT

Dr. Armstrong has served as a research investigator, scientific advisor and/or speaker for AbbVie, Almirall, Arcutis, Aslan, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Dermira, EPI Health, Incyte, Janssen, Leo Pharma, Lilly, Mindera Health, Nimbus, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sanofi, Sun Pharma and UCB. Dr. Lebwohl has received research funds on behalf of Mount Sinai from AbbVie, Amgen, Arcutis, Avotres, Boehringer Ingelheim, Cara Therapeutics, Dermavant, Incyte, Janssen, Lilly, Ortho Dermatologics, Regeneron and UCB, and has served as a consultant for Almirall, AltruBio, AnaptysBio, Arcutis, Avotres, Boehringer Ingelheim, Brickell Biotech, Bristol Myers Squibb, Castle Biosciences, Celltrion, CorEvitas Psoriasis Registry, Dermavant, EPI Health, Evommune, Forte Biosciences, Galderma, Genentech, Incyte, Leo Pharma, Meiji Seika Pharma, Mindera Health, Pfizer, Seanergy, Strata, Trevi and Verrica. Dr. Warren has received research grants from AbbVie, Almirall, Amgen, Celgene, Janssen, Leo Pharma, Lilly, Novartis, Pfizer and UCB, and consulting fees from AbbVie, Almirall, Amgen, Astellas, Boehringer Ingelheim, Celgene, Dice Therapeutics, GSK, Janssen, Leo Pharma, Lilly, Novartis, Pfizer, Sanofi, UCB and Union Therapeutics. Dr. Sofen has served as a clinical investigator for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, Leo Pharma, Lilly, Novartis and Sun Pharma. Dr. Morita has received honoraria as meeting chair/lecturer for AbbVie, AYUMI Pharmaceutical, Boehringer Ingelheim Japan, Celgene K.K., Eisai, Eli Lilly Japan K.K., Inforward, Janssen Pharmaceutical K.K., Kyowa Kirin, Maruho Co., Mitsubishi Tanabe Pharma, Nippon Kayaku, Novartis Pharma K.K., Taiho Pharmaceutical, Torii Pharmaceutical and Ushio; has received funding from AbbVie G.K., Eisai, Eli Lilly Japan K.K., Kyowa Hakko Kirin, Leo Pharma K.K., Maruho, Mitsubishi Tanabe Pharma, Novartis Pharma K.K., Taiho Pharmaceutical and Torii Pharmaceutical; and has received consulting fees from AbbVie GK, Boehringer Ingelheim Japan, Bristol Myers Squibb, Celgene K.K., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Janssen Pharmaceutical K.K., Kyowa Kirin, Maruho, Mitsubishi Tanabe Pharma, Nichi‐Iko Pharmaceutical, Nippon Kayaku, Novartis Pharma K.K., Pfizer Japan, Sun Pharma, Torii Pharmaceutical and UCB Japan. Dr. Paul has received grants and served as consultant for AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Leo Pharma, Merck, Mylan, Novartis, Pfizer, Sandoz and UCB. Dr. Papp has received honoraria and/or grants from AbbVie, Acelyrin, Akros, Alumis, Amgen, Arcutis, Bausch Health/Valeant, Boehringer Ingelheim, Bristol Myers Squibb, Can‐Fite Biopharma, Celltrion, Concert Pharmaceuticals, Dermavant, Dermira, Dice Pharmaceuticals, Dice Therapeutics, Evelo Biosciences, Forbion, Galderma, Horizon Therapeutics, Incyte, Janssen, Kymab, Kyowa Hakko Kirin, Leo Pharma, Lilly, Meiji Seika Pharma, Mitsubishi Pharma, Nimbus Therapeutics, Novartis, Pfizer, Reistone, Sanofi‐Aventis/Genzyme, Sandoz, Sun Pharma, Takeda, Tarsus Pharmaceuticals, UCB and Zai Lab. Dr. Colombo, Ms. Scotto, Dr. Vaile, Dr. Zhou, Dr. Vritzali and Dr. Berger are employees of and stockholders in Bristol Myers Squibb. Ms. Schroeder is a consultant for Bristol Myers Squibb via Syneos Health. Dr. Banerjee was an employee of and stockholder in Bristol Myers Squibb at the time of the study. Dr. Thaçi has received research support from and a principal investigator (clinical trial funds to institution) for AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Galderma, Janssen‐Cilag, Leo Pharma, Lilly, Novartis, Pfizer, Regeneron, Sanofi and UCB; has served as a consultant for AbbVie, Almirall, Boehringer Ingelheim, Bristol Myers Squibb, Leo Pharma, Novartis, Pfizer and UCB; has served as a lecturer for AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, Leo Pharma, Lilly, Novartis, Pfizer, Roche‐Posay, Sanofi, Target RWE and UCB; and has served on a scientific advisory board for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Janssen‐Cilag, Leo Pharma, Lilly, Novartis, Pfizer, Sanofi and UCB. Dr. Strober has served as a consultant with honoraria for AbbVie, Acelyrin, Alamar, Almirall, Alumis, Amgen, Arcutis, Arena, Aristea, Asana, Boehringer Ingelheim, Bristol Myers Squibb, Capital One, Celltrion, CorEvitas Psoriasis Registry, Dermavant, Imagenebio, Janssen/J&J Innovative Medicine, Kangpu Biopharmaceuticals, Leo Pharma, Lilly, Maruho, Meiji Seika Pharma, Monte Carlo, Novartis, Pfizer, Protagonist, Rapt Therapeutics, Regeneron, Sanofi, SG Cohen, Sun Pharma, Takeda, UCB, Union Therapeutics, Ventyx Biosciences and vTv Therapeutics; has served as a speaker for AbbVie, Arcutis, Dermavant, Incyte, Janssen/J&J Innovative Medicine, Lilly, Regeneron and Sanofi; has served a co‐scientific director (with consulting fee) and investigator for CorEvitas Psoriasis Registry; has served the editor‐in‐chief with an honorarium for Journal of Psoriasis and Psoriatic Arthritis; and has stock options in Connect Biopharma and Mindera Health.

ETHICAL APPROVAL

The study protocol and patient informed consent received appropriate approval before initiation of the study at each site by an institutional review board or independent ethics committee.

ETHICS STATEMENT

The trials described in this manuscript were conducted in compliance with Good Clinical Practice, ethical principles and applicable regulatory requirements. Trial protocols were approved by an independent institutional review board or ethics committee at the study site and patients provided written informed consent before study‐related procedures were performed.

Supporting information

Data S1.

JDV-39-1336-s001.pdf^{(701KB, pdf)}

ACKNOWLEDGEMENTS

Writing and editorial assistance was provided by Kimberly MacKenzie, PhD, and Eleanor Bush, MA, of Peloton Advantage, LLC, an OPEN Health company, funded by Bristol Myers Squibb. The authors thank Brandon Becker, Kim Hoyt, Angela Aggrey‐Amable, Emmanuel Edusei, Alessandra Alió Saenz and Katrina Bandeli of Bristol Myers Squibb for their contributions to the trial analysis. This research was sponsored by BMS and was supported by the National Institute for Health and Care Research Manchester Biomedical Research Centre (NIHR203308).

Armstrong AW, Lebwohl M, Warren RB, Sofen H, Morita A, Paul C, et al. Deucravacitinib in plaque psoriasis: Four‐year safety and efficacy results from the Phase 3 POETYK PSO‐1, PSO‐2 and long‐term extension trials. J Eur Acad Dermatol Venereol. 2025;39:1336–1351. 10.1111/jdv.20553

Linked article: I. Birkenmaier et al. J Eur Acad Dermatol Venereol 2025;39:1220–1221. https://doi.org/10.1111/jdv.20751

DATA AVAILABILITY STATEMENT

The Bristol Myers Squibb policy on data sharing may be found at https://www.bms.com/researchers‐and‐partners/independent‐research/data‐sharing‐request‐process.html.

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53. Winthrop KL. The emerging safety profile of JAK inhibitors in rheumatic disease. Nat Rev Rheumatol. 2017;13:234–243. [DOI] [PubMed] [Google Scholar]
54. Greb JE, Goldminz AM, Elder JT, Lebwohl MG, Gladman DD, Wu JJ, et al. Psoriasis. Nat Rev Dis Primers. 2016;2:16082. [DOI] [PubMed] [Google Scholar]
55. Griffiths CEM, Jo SJ, Naldi L, Romiti R, Guevara‐Sangines E, Howe T, et al. A multidimensional assessment of the burden of psoriasis: results from a multinational dermatologist and patient survey. Br J Dermatol. 2018;179:173–181. [DOI] [PubMed] [Google Scholar]
56. Loft N, Nguyen TT, Kristensen LE, Thyssen JP, Egeberg A. Disease burden, symptoms, and use of analgesics in patients with psoriasis with or without psoriatic arthritis: a cross‐sectional study. J Am Acad Dermatol. 2022;86:590–597. [DOI] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Data S1.

JDV-39-1336-s001.pdf^{(701KB, pdf)}

Data Availability Statement

The Bristol Myers Squibb policy on data sharing may be found at https://www.bms.com/researchers‐and‐partners/independent‐research/data‐sharing‐request‐process.html.

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PERMALINK

Deucravacitinib in plaque psoriasis: Four‐year safety and efficacy results from the Phase 3 POETYK PSO‐1, PSO‐2 and long‐term extension trials

April W Armstrong

Mark Lebwohl

Richard B Warren

Howard Sofen

Akimichi Morita

Carle Paul

Kim A Papp

Matthew J Colombo

Julie Scotto

John Vaile

Joe Zhuo

Eleni Vritzali

Victoria Berger

Georgene Schroeder

Subhashis Banerjee

Diamant Thaçi

Bruce Strober

Abstract

Background

Objectives

Methods

Results

Conclusions

Why Was the Study Undertaken?

What Does This Study Add?

What Are the Implications of This Study for Disease Understanding and/or Clinical Care?

INTRODUCTION

MATERIALS AND METHODS

Study design and population

FIGURE 1.

Analysis datasets

Assessments

Statistical analysis

RESULTS

Patient population and treatment exposure

TABLE 1.

Overall safety

TABLE 2.

AEs of interest

TABLE 3.

Laboratory parameters

FIGURE 2.

Efficacy

FIGURE 3.

FIGURE 4.

FIGURE 5.

Patient‐reported outcomes

FIGURE 6.

FIGURE 7.

DISCUSSION

FIGURE 8.

AUTHOR CONTRIBUTIONS

FUNDING INFORMATION

CONFLICT OF INTEREST STATEMENT

ETHICAL APPROVAL

ETHICS STATEMENT

Supporting information

ACKNOWLEDGEMENTS

DATA AVAILABILITY STATEMENT

REFERENCES

Associated Data

Supplementary Materials

Data Availability Statement

ACTIONS

PERMALINK

RESOURCES

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Cited by other articles

Links to NCBI Databases