Dermatol Ther (Heidelb) (2022) 12:495–510 https://doi.org/10.1007/s13555-021-00649-y ORIGINAL RESEARCH Deucravacitinib in Moderate to Severe Psoriasis: Clinical and Quality-of-Life Outcomes in a Phase 2 Trial Diamant Thaçi . Bruce Strober . Kenneth B. Gordon . Peter Foley . Melinda Gooderham . Akimichi Morita . Kim A. Papp . Lluı́s Puig . M. Alan Menter . Matthew J. Colombo . Yedid Elbez . Renata M. Kisa . June Ye . Andrew A. Napoli . Lan Wei . Subhashis Banerjee . Joseph F. Merola . Alice B. Gottlieb Received: October 4, 2021 / Accepted: November 16, 2021 / Published online: January 13, 2022 Ó The Author(s) 2022 ABSTRACT psoriasis. This analysis was designed to evaluate the effect of deucravacitinib on additional Introduction: Deucravacitinib is an oral, selec- clinical and quality-of-life (QoL) outcomes and tive tyrosine kinase 2 inhibitor that demon- assess the relationship between these outcomes strated therapeutic benefit in a Phase 2 clinical in adults with psoriasis. trial of adults with moderate to severe plaque Methods: Post-hoc analysis of a 12-week Phase 2 trial was conducted for the three most effica- cious dosage groups (3 mg twice daily, 6 mg twice daily, 12 mg once daily) and placebo. Supplementary Information The online version contains supplementary material available at https:// doi.org/10.1007/s13555-021-00649-y. K. A. Papp D. Thaçi (&) Clinical Research and Probity Medical Research, Institute and Comprehensive Center for Waterloo, ON, Canada Inflammation Medicine, University of Luebeck, Ratzeburger Allee 160, 23538 Luebeck, Germany L. Puig e-mail: diamant.thaci@uksh.de Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain B. Strober Yale University, Central Connecticut Dermatology M. A. Menter Research, New Haven, CT, USA Baylor University Medical Center, Dallas, TX, USA K. B. Gordon M. J. Colombo  Y. Elbez  R. M. Kisa  J. Ye  Medical College of Wisconsin, Milwaukee, WI, USA A. A. Napoli  L. Wei  S. Banerjee Bristol Myers Squibb, Princeton, NJ, USA P. Foley St Vincent’s Hospital Melbourne, Probity Medical J. F. Merola Research, Skin Health Institute, The University of Harvard Medical School, Brigham and Women’s Melbourne, Melbourne, VIC, Australia Hospital, Boston, MA, USA M. Gooderham A. B. Gottlieb SKiN Centre for Dermatology, Queen’s University Icahn School of Medicine at Mount Sinai, New York, and Probity Medical Research, Peterborough, ON, NY, USA Canada A. Morita Nagoya City University, Graduate School of Medical Sciences, Nagoya, Aichi, Japan 496 Dermatol Ther (Heidelb) (2022) 12:495–510 Investigator assessments for efficacy included as a treatment for psoriasis. We performed a Psoriasis Area and Severity Index (PASI), body Phase 2 dose-ranging, placebo-controlled, surface area (BSA) involvement, and static 12-week study of deucravacitinib in adults with Physician’s Global Assessment; QoL was asses- moderate to severe psoriasis. Patients in the sed using the Dermatology Life Quality Index USA, Australia, Canada, Germany, Japan, Lat- (DLQI). Treatment responses and their associa- via, Mexico, and Poland participated. The study tions were evaluated over time. showed that oral treatment with deucravaci- Results: Deucravacitinib elicited improvement tinib was effective using a disease severity score versus placebo as early as Week 4 for most effi- (percentage of patients with C 75% reduction cacy measures (including changes in absolute from baseline in Psoriasis Area and Severity PASI and BSA), with efficacy trends observed Index score) at Week 12—placebo 7% and deu- from Week 2 to Week 12. Improvements in cravacitinib 67%–75% for the three highest QoL, assessed by achievement of a DLQI overall dosages—and was generally well tolerated. We score of 0/1 (no effect at all on patient’s life), further analyzed the association between effi- followed a pattern similar to deucravacitinib- cacy and a QoL measure, the Dermatology Life related clinical outcomes over 12 weeks. Over- Quality Index (DLQI), in patients who received all, patients with greater improvements in pso- placebo or the most effective dosages of deu- riasis-related clinical signs and symptoms also cravacitinib (C 3 mg twice daily). Deucravaci- reported greater improvement in QoL. How- tinib was effective at the three dosage levels ever, complete skin clearance was not required tested. Skin improvement occurred early during for achieving DLQI 0/1. treatment and was mirrored by improvements Conclusion: Deucravacitinib treatment pro- in DLQI score during the 12 weeks of treatment. duced early response and similar trends in Although some patients did not have complete improvements across multiple efficacy assess- clearance of their psoriasis, a large percentage of ments and QoL in moderate to severe plaque those patients still achieved considerable psoriasis. Deucravacitinib has the potential to improvement in QoL as measured by achieving become a promising new oral therapy for this a DLQI score of 0/1 (i.e., no effect at all on the condition. patient’s QoL). Trial Registration: ClinicalTrials.gov identifier; NCT02931838. Keywords: Body surface area; Humans; Psoriasis; Quality of life; TYK2 PLAIN LANGUAGE SUMMARY Psoriasis is a skin disease that affects up to 2% of the population. In psoriasis, red, scaly lesions develop on the skin driven by an aberrant immune response. Psoriasis impacts not only physical and mental health but also quality of life (QoL). Deucravacitinib is being investigated Dermatol Ther (Heidelb) (2022) 12:495–510 497 INTRODUCTION Key Summary Points Several metrics are utilized to assess the severity Why carry out this study? of psoriasis, make appropriate treatment deci- sions, and measure treatment response [1]. The Moderate to severe psoriasis is a chronic, Psoriasis Area and Severity Index (PASI) is a systemic, immune-mediated disease that measure of clinical disease severity that is is known to have a substantial impact on commonly used in clinical trials [2–4]. At least patients’ physical as well as mental health 75% reduction from baseline in PASI (PASI 75) is and quality of life (QoL) considered a clinically relevant treatment Previous results from this Phase 2 trial in response and was the primary endpoint in a patients with moderate to severe plaque Phase 2 dose-ranging, placebo-controlled, psoriasis demonstrated that treatment 12-week study of deucravacitinib in adults with with the three highest dosages of the moderate to severe psoriasis [3, 5, 6]. Static selective tyrosine kinase 2 inhibitor Physician’s Global Assessment (sPGA) is often deucravacitinib led to significant used to assess disease severity at a specific time improvements in clinical signs and point regardless of baseline disease severity symptoms as well as improvements in [1, 7]. Another efficacy measure is body surface QoL measures at 12 weeks compared with area (BSA) involvement, which is regarded as a placebo more practical instrument for assessing treat- ment targets in psoriasis by some dermatolo- This post hoc analysis from the Phase 2 gists and other experts [6]. The Dermatology trial explored temporal response and the Life Quality Index (DLQI) questionnaire, a relationship between patient-reported patient-reported measurement of health-related outcomes and investigator-assessed quality of life (QoL), is often used in clinical clinical measures trials to assess measures of bothersome symp- What was learned from this study? toms, such as itch, stinging, and pain, as well as its impact on daily functioning [8, 9]. This analysis provided additional evidence Deucravacitinib is an oral selective tyrosine that deucravacitinib treatment is kinase 2 (TYK2) inhibitor in development for associated with early improvements in treatment of moderate to severe plaque psoria- clinical outcomes from baseline through sis, psoriatic arthritis, ulcerative colitis, Crohn’s Week 12, as assessed by improvements disease, and lupus (NCT03943147) [10]. The from baseline in absolute Psoriasis Area mechanism of action of deucravacitinib is dis- and Severity Index, static Physician’s tinct from that of other TYK2 or Janus kinase Global Assessment, body surface area inhibitors in that deucravacitinib selectively involvement, and QoL as assessed by binds to a unique pocket in the regulatory Dermatology Life Quality Index domain of TYK2 instead of the highly conserved Improvement in QoL followed a pattern of active site of the catalytic domain [11], allowing response to treatment similar to that of high selectivity of action on TYK2 via allosteric the clinical outcomes assessed in this inhibition versus related kinases. This leads to analysis targeted inhibition of immune pathways that are central to psoriasis while limiting off-target effects [11]. In the previously published Phase 2 trial in moderate to severe plaque psoriasis, deucravacitinib treatment resulted in 67–75% of patients reaching PASI 75 at 12 weeks with the three highest dosages of 3 mg twice daily (BID), 6 mg BID, and 12 mg once daily (QD) 498 Dermatol Ther (Heidelb) (2022) 12:495–510 versus 7% of patients receiving placebo. The 3 mg BID, 6 mg BID, or 12 mg QD) or matching two lowest dosage groups (3 mg every other day oral placebo for 12 weeks. and 3 mg QD) provided limited efficacy com- pared with placebo [5]. Deucravacitinib treat- Study Ethics ment also led to improvements versus placebo at 12 weeks in QoL, as assessed by a DLQI score The trial was conducted in accordance with of 0 or 1 (0/1) [5], and was well tolerated overall. Good Clinical Practice guidelines defined by the Adverse events were reported in 51% of patients International Council for Harmonisation, the in the placebo group and in 55% to 80% of Declaration of Helsinki, and the laws and reg- patients in the deucravacitinib groups, with the ulatory requirements of the countries with highest percentage of adverse events occurring participating study centers [5]. The study pro- in the group receiving deucravacitinib 6 mg tocol, consent form, and all other documents BID. Nasopharyngitis, headache, diarrhea, nau- given to patients were approved by an institu- sea, and upper respiratory tract infection were tional review board or independent ethics the most common adverse events. Serious committee at each site (see Supporting Infor- adverse events and adverse events leading to mation). Written informed patient consent was treatment discontinuation were low and bal- obtained prior to study participation. anced across treatment groups. Deucravacitinib- treated patients (at any dose) did not develop Assessments laboratory abnormalities characteristic of Janus kinase inhibitors such as neutropenia, liver enzyme or serum creatinine elevations, or dys- The assessment tools PASI, sPGA, BSA, and lipidemia [5]. DLQI used in the trial have been previously This analysis of the Phase 2 trial was con- described [5]. The primary efficacy endpoint for ducted to further evaluate the efficacy of deu- the Phase 2 study was PASI 75 response at Week cravacitinib at doses C 3 mg BID using a broad 12. range of clinical assessment tools and to further Mean percentage changes from baseline in assess the impact on a patient-reported QoL absolute PASI score and in BSA were determined measure (DLQI) for up to 12 weeks in patients over time through Week 12. PASI 75, C 90% with moderate to severe plaque psoriasis. reduction from baseline in PASI (PASI 90), and 100% reduction from baseline in PASI (PASI 100) responses and sPGA score of 0 (clear) or 1 METHODS (minimal disease) were previously published [5]. Additional post hoc analyses were the percent- Study Design ages of patients who achieved absolute PASI B 1, absolute PASI B 3, absolute PASI B 5, This was a post hoc analysis of a randomized, BSA B 1%, BSA B 3%, and C 75% improve- double-blind, placebo-controlled, dose-ranging ment in the product of sPGA and BSA (sPGA 9 Phase 2 trial of deucravacitinib in adults with BSA 75). The sPGA 9 BSA measurement is a moderate to severe plaque psoriasis validated composite instrument, which is the (NCT02931838) [5]. The study design has been product of sPGA (range, 0 [clear] to 5 [severe]) described previously [5]. Adults were eligible for and is based on the average of the severity of trial participation if they had moderate to sev- induration, erythema, and scaling over all pso- ere plaque psoriasis, as defined by affected riatic plaques at a given time point) and BSA BSA C 10%, PASI C 12, and sPGA score C 3, [12–15]. The DLQI overall score (range, 0 [no and were candidates for phototherapy or sys- impairment of QoL] to 30 [maximum impair- temic therapy. Patients were randomized ment of QoL]) was analyzed over time. The equally to receive one of five dosages of deu- percentages of patients achieving DLQI 0/1 cravacitinib (3 mg every other day, 3 mg QD, were compared across categories of absolute Dermatol Ther (Heidelb) (2022) 12:495–510 499 PASI values and changes from baseline and with Fig. 2). As with the absolute PASI changes, BSA involvement. improvement was seen as early as Week 2, with similar improvement among the three deu- Statistical Analysis cravacitinib dosage groups (Fig. 2). Responses at Week 12 in patients receiving In analyses of the Phase 2 trial, mean changes in deucravacitinib compared with placebo for the PASI score, as well as PASI 75 and PASI 90 assessments of PASI 90, PASI 100, absolute responses, were similar in the highest dosage PASI B 1, absolute PASI B 3, absolute PASI B 5, groups (3 mg BID [n = 45], 6 mg BID [n = 45], and sPGA 0/1 are shown in Fig. 3a–f. The pro- 12 mg QD [n = 44]); efficacy was limited in the portions of patients who achieved BSA B 1% two lowest deucravacitinib dosage groups (3 mg (26.7% [3 mg BID], 37.8% [6 mg BID], 38.6% every other day and 3 mg QD) compared with [12 mg QD]) and BSA B 3% (51.1%, 44.4%, and placebo [5]. These findings provided the ratio- 56.8%, respectively) were higher in the deu- nale for combining data from the three highest cravacitinib groups than in the placebo group dosage groups in subsequent analyses [5, 16]. (0% for BSA B 1% and 2.2% for BSA B 3%; The placebo group (n = 45) was also included in Fig. 3g). The deucravacitinib dosage groups had the analyses for comparative purposes. a higher percentage of patients who achieved Improvement from baseline is presented as sPGA 9 BSA 75 (C 75% improvement from percentage change from baseline for absolute baseline), which has previously been used as an PASI and BSA involvement through Week 12. assessment of psoriasis severity and response to Other outcomes (PASI 90, PASI 100, absolute therapy [12, 15] versus the placebo group PASI B 1, absolute PASI B 3, absolute PASI B 5, (Fig. 3h). sPGA, BSA, sPGA 9 BSA) at Week 12 are Treatment with deucravacitinib was associ- expressed as percentages of patients. All missing ated with greater improvement from baseline in values were imputed as nonresponse. QoL versus placebo at each time point, as assessed by the percentage of patients achieving a DLQI overall score of 0/1, which reflects no RESULTS impact at all on the patient’s life [17] (Fig. 4). The percentage of patients achieving a DLQI 0/1 A total of 267 patients were randomized and increased by Week 4 for each of the three deu- treated, and 224 (84%) completed the 12-week cravacitinib dosage groups versus placebo and treatment period [5]. The treatment groups were continued to increase through Week 12 in the comparable in baseline patient demographics two highest dosage groups; the percentage of and disease characteristics, as previously repor- patients achieving a DLQI 0/1 in the three ted for absolute PASI score, DLQI score, and BSA deucravacitinib dosage groups combined was involvement [5]. 17.9% at Week 4, 41.8% at Week 8, and 55.2% Deucravacitinib treatment groups had a at Week 12 versus the placebo group, which was greater mean percentage change from baseline 6.7%, 4.4%, and 4.4%, respectively (Fig. 4). in absolute PASI score than the placebo group at Improvements in QoL over 12 weeks fol- each time point through Week 12, with changes lowed a similar pattern to the improvements evident as early as the first visit at Week 1; observed for clinical outcomes (PASI 75, PASI decreases were similar among the three dosage 90, and sPGA score of 0 or 1 [0/1]; Fig. 5). The groups (Fig. 1). Mean changes from baseline in DLQI 0/1 responses were concurrent with BSA percentage were greater in the deucravaci- increases in the percentages of patients from all tinib groups versus the placebo group at Week three deucravacitinib dosage groups combined 12, - 18.6 (75.9% decrease from base- achieving PASI 75 (0% at Week 1, 70.1% at line), - 17.2 (69.4% decrease), and - 15.2 Week 12), PASI 90 (0% at Week 1, 44.0% at (73.7% decrease) in the 3 mg BID, 6 mg BID, Week 12), and sPGA 0/1 (0% at Week 0, 71.6% and 12 mg QD treatment groups, respectively, at Week 12). compared with - 7.7 in the placebo group; 500 Dermatol Ther (Heidelb) (2022) 12:495–510 Agreement between QoL and PASI improve- Foundation (BSA B 1% at 12 weeks) [6, 18] and ments were also observed when the achieve- acceptable response (BSA B 3% or BSA ment of DLQI 0/1 was stratified by absolute PASI improvement C 75% at 12 weeks of treatment). bands (B 1; B 2; B 3; B 5) at Week 12, suggest- At Week 12, the percentages of patients with ing that the percentage of patients achieving PASI 75, PASI 90, PASI 100, and sPGA 0/1 were DLQI 0/1 was highest in those with absolute substantially higher in the deucravacitinib PASI B 1 (Fig. 6a) and PASI 100 (Fig. 6b). Simi- dosage groups than in the placebo group. In the larly, higher rates of achievement of DLQI 0/1 main analysis of this Phase 2 trial, an sPGA score were observed in the BSA B 1% group (78.3%) of 0/1 was achieved in 7% of the placebo group and the BSA B 3% group (70.6%) compared and in 76% of the deucravacitinib 3 mg BID with the BSA [ 3% group (44.8%; Fig. 6c). group, 75% of the 12 mg QD group, and 64% of the 6 mg BID group at Week 12 [5]. Addition- ally, up to 38.6% and 56.8% of patients com- DISCUSSION bined across the three deucravacitinib dosage groups achieved BSA B 1% and B 3%, respec- This analysis demonstrated that deucravacitinib tively. As would be expected in this patient treatment produced early, clinically meaning- population, at Week 12 a similar proportion of ful, and similar improvements across several patients in the combined deucravacitinib assessments of clinical response (PASI, BSA, dosage group achieved sPGA 9 BSA 75 and PASI sPGA). These improvements were mirrored by 75. Comparable findings from other studies that QoL improvements, as measured by DLQI. At also used a composite assessment with BSA the three highest dosages tested, a substantial suggest sPGA 9 BSA may be a viable alternative percentage of the deucravacitinib-treated to PASI that may be used in both clinical trials patients met thresholds of clinically meaningful and clinical practice settings to assess severity of improvement in PASI (PASI 75, PASI 90, PASI psoriasis [12, 19–21]. Treatment with deu- 100) as well as treat-to-target BSA values rec- cravacitinib resulted in greater improvements in ommended by the National Psoriasis QoL (as assessed by DLQI) versus placebo, which Fig. 1 Mean percentage change from baseline in PASI scores over time for placebo and the deucravacitinib 3 mg BID, 6 mg BID, and 12 mg QD dosage groups. BID twice daily; PASI Psoriasis Area and Severity Index; PBO placebo; QD once daily Dermatol Ther (Heidelb) (2022) 12:495–510 501 Fig. 2 Mean absolute change from baseline in BSA percentage over time for placebo and the deucravacitinib 3 mg BID, 6 mg BID, and 12 mg QD dosage groups. BID twice daily; BSA body surface area; PBO placebo; QD once daily occurred by Week 4. The improvements in QoL dermatology-specific measure DLQI vs generic paralleled increases in the rates of PASI 75, PASI health status measures) [26], ethnicity [36, 37], 90, PASI 100, and sPGA 0/1 and were com- sex [38], culture [36], and socioeconomic status mensurate with improvements in absolute PASI [36, 38]. The current analysis and other studies and BSA scores over time through Week 12. in psoriasis highlight the importance of patient- Consistency between clinical and QoL out- reported outcomes, in addition to clinician-re- comes is not unexpected, given the association ported outcomes and other traditional clinical between disease severity and QoL and the vol- severity tools, when assessing treatment efficacy ume of literature reporting a substantial nega- and the impact of psoriasis on daily life with tive impact of psoriasis on QoL and, conversely, effective agents [6, 25–27, 31, 39–43]. greater improvement in QoL mirroring an The limitations of this post hoc analysis increase in skin clearance [3, 9, 22–27]. Previous must be considered. Differences between deu- studies have demonstrated consistency between cravacitinib and placebo in clinical and patient- physician-reported clinical outcomes and reported outcomes were not multiplicity-ad- patient-reported outcomes such as QoL justed for statistical significance. Analysis of the [25, 28–33]. In addition to the similar pattern of rate of achievement of DLQI 0/1 by PASI responses for clinical and QoL outcomes repor- response bands was limited by the relatively ted here, the current analysis also showed that a small number of patients in individual PASI large percentage of patients achieved DLQI 0/1 categories [5]. It should also be noted that all of despite absence of complete skin clearance (see the instruments available for assessing clinical Fig. 6) and despite having BSA involve- outcomes or QoL have limited precision and ment [ 3% [6]. Awareness has increased over truncation associated with the limitations of the last decade that patients with psoriasis data capture. Finally, the relatively short experience effects on QoL beyond their level of 12-week treatment period and small sample size skin involvement [25, 34]. Furthermore, the in the Phase 2 trial presented another limitation association between objective clinical response for this analysis. Larger, longer-term Phase 3 and QoL may vary depending on BSA affected trials of deucravacitinib in psoriasis are ongoing [23], QoL domain (e.g., mental vs. physical) or have been completed (POETYK PSO-1 [35], QoL assessment tool (e.g., the [NCT03624127] [44]; POETYK PSO-2 502 Fig. 3 Response rates at Week 12 for a PASI 90, b PASI 100, c sPGA 0/1, d absolute PASI B 5, e absolute PASI B 3, f absolute PASI B 1, g BSA (B 1% and B 3%), and h sPGA 9 BSA 75 for placebo and the deucravacitinib 3 mg BID, 6 mg BID, and 12 mg QD dosage groups. BID twice daily; BSA, body surface area; PASI 75 at least 75% reduction from baseline in Psoriasis Area and Severity Index; PASI 90 at least 90% reduction from baseline in Psoriasis Area and Severity Index; PASI 100 100% reduction from baseline in Psoriasis Area and Severity Index; PBO placebo; QD every day; sPGA 9 BSA 75 at least 75% improvement from baseline in the product of the static Physician’s Global Assessment and body surface area involvement Dermatol Ther (Heidelb) (2022) 12:495–510 Dermatol Ther (Heidelb) (2022) 12:495–510 503 Fig. 4 Percentage of patients with a DLQI overall score of QD dosage groups. BID twice daily; DLQI Dermatology 0/1, which reflects no impact on patient’s life, for placebo Life Quality Index; QD every day; QoL quality of life and the deucravacitinib 3 mg BID, 6 mg BID, and 12 mg Fig. 5 Time course of PASI 75, PASI 90, sPGA 0/1, and baseline in Psoriasis Area and Severity Index; PASI 90 at DLQI overall score of 0/1 response rates for the combined least 90% reduction from baseline in Psoriasis Area and deucravacitinib 3 mg BID, 6 mg BID, and 12 mg QD Severity Index; QD every day; sPGA static Physician’s dosage groups. BID twice daily; DLQI Dermatology Life Global Assessment Quality Index; PASI 75 at least 75% reduction from [NCT03611751]; POETYK PSO-3 data regarding consistency between clinical [NCT04167462]; POETYK PSO-4 outcomes and QoL in a larger population of [NCT03924427]; POETYK PSO-LTE psoriasis patients over longer follow-up periods. [NCT04036435]) and will provide important 504 Dermatol Ther (Heidelb) (2022) 12:495–510 Fig. 6 DLQI 0/1 at Week 12 by absolute PASI (a), PASI Severity Index; PASI 25 to \ 50 25% to \ 50% improve- response band (b), and BSA response band (c) for the ment; PASI 50 to \ 75 50% to \ 75% improvement; combined patient groups of deucravacitinib 3 mg BID, PASI 75 to \ 90 75% to \ 90% improvement; PASI 90 6 mg BID, and 12 mg QD dosage groups. BID twice daily; to \ 100 90% to \ 100% improvement; PASI 100 100% BSA body surface area; DLQI Dermatology Life Quality improvement from baseline Psoriasis Area and Severity Index; PASI Psoriasis Area and Severity Index; PASI \ Index; QD once daily 25 \ 25% improvement from baseline Psoriasis Area and Dermatol Ther (Heidelb) (2022) 12:495–510 505 CONCLUSION data analysis. All authors reviewed the manu- script and gave final approval for publication. This post hoc analysis of the Phase 2 trial demonstrated that deucravacitinib at doses Disclosures. Diamant Thaçi has received of C 3 mg BID provided early improvements honoraria and lecture fees from AbbVie, Almi- across multiple assessments of clinical efficacy rall, Amgen, Biogen Idec, Boehringer Ingelheim, as well as QoL in patients with moderate to Bristol Myers Squibb, Janssen, Leo Pharma, severe plaque psoriasis, suggesting that deu- Novartis, Pfizer, Roche-Posay, Sandoz-Hexal, cravacitinib may be a promising therapy for this Sanofi, Target-Solution, and UCB. Bruce Strober population. Early concurrent trends in has received honoraria from AbbVie, Almirall, improvement occurred over the 12-week trial Amgen, Arcutis, Arena, Aristea, Boehringer across different assessments, with no impact on Ingelheim, Bristol Myers Squibb, Connect Bio- life (DLQI 0/1) observed in many patients who pharma, Dermavant, Eli Lilly, Equillium, did not achieve complete skin clearance. GlaxoSmithKline, Immunic Therapeutics, Jans- sen, Leo Pharma, Maruho, Meiji Seika Pharma, Mindera, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharma, and ACKNOWLEDGEMENTS UCB; has served as an investigator for AbbVie, Cara, CorEvitas’ (Corrona) Psoriasis Registry, The authors thank the patients for their partic- Dermavant, Dermira, and Novartis; has served ipation, as well as the investigators and their as a scientific director (consultant fee) for teams, and biostatisticians for their CorEvitas’ (Corrona) Psoriasis Registry; and has contributions. served as a speaker for AbbVie, Amgen, Eli Lilly, Janssen, and Sanofi Genzyme. Kenneth B. Gor- Funding. This analysis was sponsored by don has served as a consultant for AbbVie, Bristol Myers Squibb. Bristol Myers Squibb also Amgen, Almirall, Arcutis, Arena Pharma, Boeh- funded the journal’s Rapid Service Fees. ringer Ingelheim, Bristol Myers Squibb, Cel- gene, Dermavant, Dermira, Eli Lilly, Incyte, Medical writing assistance. Professional Janssen, Kyowa Hakko Kirin, Leo Pharma, medical writing from Barbara Zeman, PhD, and Novartis, Pfizer, Sanofi Genzyme, Sun Pharma, editorial assistance were provided by Peloton and UCB, and has received research grants from Advantage, LLC, an OPEN Health company, AbbVie, Boehringer Ingelheim, Bristol Myers Parsippany, NJ, and were funded by Bristol Squibb, Celgene, Eli Lilly, Janssen, Novartis, and Myers Squibb. UCB. Peter Foley has received grant support from AbbVie, Amgen, Celgene, Eli Lilly, Jans- Authorship. All named authors meet the sen, Leo Pharma, Merck, Novartis, Pfizer, Sanofi, International Committee of Medical Journal and Sun Pharma; has served as an investigator Editors (ICMJE) criteria for authorship for this for AbbVie, Amgen, AstraZeneca, Arcutis, Aslan, article, take responsibility for the integrity of Bristol Myers Squibb, Boehringer Ingelheim, the work as a whole, and have given their Botanix, Celgene, Celtaxsys, CSL, Cutanea, approval for this version to be published. Dermira, Eli Lilly, Galderma, Genentech, GlaxoSmithKline, Hexima, Janssen, Leo Author contributions. DT, BS, LP, MAM, Pharma, Merck, Novartis, Pfizer, Regeneron, MJC, RMK, AAN, SB, JFM, and ABG contributed Reistone, Roche, Sanofi, Sun Pharma, UCB, and to the conception and study design and data Valeant; has served as an advisory board mem- interpretation. KBG, PF, MG, AM, and KAP ber for AbbVie, Amgen, Bristol Myers Squibb, contributed to data acquisition and data inter- Boehringer Ingelheim, Celgene, Eli Lilly, Gal- pretation. YE and JY contributed to data analy- derma, GlaxoSmithKline, Janssen, Leo Pharma, sis. LW contributed to conception or design or Merck, Novartis, Pfizer, Sanofi, Sun Pharma, UCB, and Valeant; has served as a consultant for 506 Dermatol Ther (Heidelb) (2022) 12:495–510 Bristol Myers Squibb, Eli Lilly, Galderma, Jans- Kayaku, Novartis Pharma K.K., NPO Health sen, Leo Pharma, Novartis, Pfizer, Roche, and Institute Research of Skin, Pfizer Japan, Sun UCB; has received travel grants from AbbVie, Eli Pharmaceutical Industries, Torii Pharmaceuti- Lilly, Galderma, Janssen, Leo Pharma, Merck, cal, and UCB Japan. Kim A. Papp has served as a Novartis, Pfizer, Roche, Sun Pharma, and Sanofi; consultant for AbbVie, Akros, Amgen, Arcutis, and has served as a speaker for or received Astellas, AstraZeneca, Baxalta, Baxter, Boehrin- honoraria from AbbVie, Celgene, Eli Lilly, Gal- ger Ingelheim, Bristol Myers Squibb, CanFite, derma, GlaxoSmithKline, Janssen, Leo Pharma, Celgene, Coherus, Dermira, Dow Pharma, Eli Merck, Novartis, Pfizer, Roche, and Valeant. Lilly, Forward Pharma, Galderma, Genentech, Melinda Gooderham has served as an advisory Janssen, Kyowa Hakko Kirin, Leo Pharma, Meiji board member for AbbVie, Amgen, Arcutis, Seika Pharma, Merck Sharp & Dohme, Merck Bausch Health, Boehringer Ingelheim, Bristol Serono, Mitsubishi Pharma, Novartis, Pfizer, Myers Squibb, Eli Lilly, Galderma, Janssen, Leo Regeneron, Roche, Sanofi Genzyme, Takeda, Pharma, Novartis, Pfizer, Regeneron, Sanofi UCB, and Valent; has received honoraria from Genzyme, Sun Pharma, and UCB; has served as AbbVie, Akros, Amgen, Baxter, Boehringer a consultant for AbbVie, Akros, Amgen, Arcutis, Ingelheim, Celgene, Coherus, Eli Lilly, Forward Boehringer Ingelheim, Eli Lilly, Galderma, Pharma, Galderma, GlaxoSmithKline, Janssen, Janssen, Kyowa Kirin, Leo Pharma, Novartis, Kyowa Hakko Kirin, Merck Sharp & Dohme, Pfizer, Sanofi Genzyme, and UCB; has served as Merck Serono, Novartis, Pfizer, Takeda, UCB, an investigator for AbbVie, Akros, Amgen, and Valeant; has received research grants from Arcutis, Bausch Health, Boehringer Ingelheim, AbbVie, Akros, Allergan, Amgen, Anacor, Arcu- Bristol Myers Squibb, Celgene, Dermira, Der- tis, AstraZeneca, Baxalta, Boehringer Ingelheim, mavant, Eli Lilly, Galderma, GlaxoSmithKline, Bristol Myers Squibb, Celgene, Coherus, Der- Incyte, Janssen, Kyowa Kirin, Leo Pharma, mira, Dow Pharma, Eli Lilly, Galderma, Merck, MedImmune, Novartis, Pfizer, Regen- Genentech, GlaxoSmithKline, Janssen, Kyowa eron, Roche, Sanofi Genzyme, Sun Pharma, Hakko Kirin, Leo Pharma, MedImmune, Meiji Takeda, and UCB; and has served on a speakers Seika Pharma, Merck Serono, Novartis, Pfizer, bureau for AbbVie, Amgen, Arcutis, Boehringer Regeneron, Roche, Sanofi-Aventis/Genzyme, Ingelheim, Bristol Myers Squibb, Celgene, Eli Takeda, UCB, and Valeant; has served on a sci- Lilly, Galderma, Janssen, Leo Pharma, Novartis, entific officer/steering committee/advisory Pfizer, Regeneron, Roche, Sanofi Genzyme, Sun board for AbbVie, Akros, Amgen, Anacor, Pharma, and UCB. Akimichi Morita has Astellas, Baxter, Boehringer Ingelheim, Bristol received honoraria from AbbVie GK, Ayumi Myers Squibb, Celgene, Dow Pharma, Eli Lilly, Pharmaceutical, Boehringer Ingelheim Japan, Galderma, Janssen, Kyowa Hakko Kirin, Merck Celgene K.K., Eisai, Eli Lilly Japan K.K., Infor- Sharp & Dohme, Merck Serono, Novartis, Pfizer, ward, Janssen Pharmaceutical K.K., Kyowa Regeneron, Sanofi Genzyme, and Valeant; and Kirin, Maruho, Mitsubishi Tanabe Pharma, has served on the speakers bureau for AbbVie, Nippon Kayaku, Novartis Pharma K.K., Taiho Amgen, Astellas, Celgene, Eli Lilly, Galderma, Pharmaceutical, Torii Pharmaceutical, and Janssen, Kyowa Hakko Kirin, Leo Pharma, Ushio; has received research support for AbbVie Merck Sharp & Dohme, Novartis, Pfizer, and GK, Eisai, Eli Lilly Japan K.K., Kyowa Hakko Valeant. Lluı́s Puig has received honoraria or Kirin, Leo Pharma KK, Maruho, Mitsubishi consultation fees from AbbVie, Almirall, Tanabe Pharma, Novartis Pharma K.K., Taiho Amgen, Baxalta, Biogen, Boehringer Ingelheim, Pharmaceutical, and Torii Pharmaceutical; and Celgene, Eli Lilly, Fresenius Kabi, Gebro, Jans- has served as a consultant for AbbVie GK, sen, Leo Pharma, Merck-Serono, Merck Sharp & Boehringer Ingelheim Japan, Bristol Myers Dohme, Mylan, Novartis, Pfizer, Regeneron, Squibb, Celgene K.K., Eli Lilly Japan K.K., Roche, Samsung Bioepis, Sandoz, Sanofi, and GlaxoSmithKline K.K., Janssen Pharmaceutical UCB; has received research grants from or par- K.K., Kyowa Kirin, Maruho, Mitsubishi Tanabe ticipated in clinical trials (paid to institution) Pharma, Nichi-Iko Pharmaceutical, Nippon for AbbVie, Almirall, Amgen, Boehringer Dermatol Ther (Heidelb) (2022) 12:495–510 507 Ingelheim, Celgene, Eli Lilly, Janssen, Leo patients provided written informed consent Pharma, Novartis, Pfizer, Regeneron, Roche, prior to any study procedures in accordance Sanofi, and UCB; and has served on the speakers with Good Clinical Practice and local bureau for Celgene, Eli Lilly, Janssen, Merck legislation. Sharp & Dohme, Novartis, and Pfizer. M. Alan Menter has served on the advisory board for Data availability. The Bristol Myers Squibb Abbott Labs, Amgen, Boehringer Ingelheim, policy on data sharing may be found at https:// Janssen Biotech, and Leo Pharma; has served as www.bms.com/researchers-and-partners/ a consultant for AbbVie, Amgen, Eli Lilly, Jans- independent-research/data-sharing-request- sen Biotech, Leo Pharma, Novartis, Sun Pharma, process.html. and UCB; has received honoraria from AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly, Janssen Open Access. This article is licensed under a Biotech, Leo Pharma, Novartis, Sun Pharma, Creative Commons Attribution-NonCommer- and UCB; has served as an investigator for cial 4.0 International License, which permits AbbVie, Amgen, Boehringer Ingelheim, Cel- any non-commercial use, sharing, adaptation, gene, Eli Lilly, Janssen Biotech, Leo Pharma, distribution and reproduction in any medium Merck, Novartis, Sun Pharma, and UCB; has or format, as long as you give appropriate credit received research grants from AbbVie, Amgen, to the original author(s) and the source, provide Boehringer Ingelheim, Celgene, Janssen Bio- a link to the Creative Commons licence, and tech, Leo Pharma, Merck, and Sun Pharma; and indicate if changes were made. The images or has served as a speaker for AbbVie, Amgen, other third party material in this article are Janssen Biotech, Leo Pharma, Sun Pharma, and included in the article’s Creative Commons UCB. Matthew J. Colombo, Yedid Elbez, Renata licence, unless indicated otherwise in a credit M. Kisa, June Ye, Andrew A. Napoli, Lan Wei, line to the material. If material is not included and Subhashis Banerjee are employees of and in the article’s Creative Commons licence and shareholders in Bristol Myers Squibb. Joseph F. your intended use is not permitted by statutory Merola has served as a consultant and/or regulation or exceeds the permitted use, you investigator for AbbVie, Amgen, Biogen, Bristol will need to obtain permission directly from the Myers Squibb, Dermavant, Eli Lilly, Janssen, Leo copyright holder. To view a copy of this licence, Pharma, Novartis, Pfizer, Regeneron, Sanofi, visit http://creativecommons.org/licenses/by- Sun Pharma, and UCB. Alice B. 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