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Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, inhibits cytokine signaling in psoriasis pathogenesis.The objective of this study was to demonstrate deucravacitinib superiority versus placebo and apremilast in moderate to severe plaque psoriasis based on ≥75% reduction from baseline in Psoriasis Area and Severity Index and a static Physician's Global Assessment score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline at week 16.POETYK psoriasis second trial (NCT03611751), a 52-week, double-blinded, phase 3 trial, randomized patients 2:1:1 to deucravacitinib 6 mg every day (n = 511), placebo (n = 255), or apremilast 30 mg twice a day (n = 254).At week 16, significantly more deucravacitinib-treated patients versus placebo and apremilast patients achieved ≥75% reduction from baseline in Psoriasis Area and Severity Index (53.0% vs 9.4% and 39.8%; P .0001 vs placebo; P = .0004 vs apremilast) and static Physician's Global Assessment score of 0 or 1 (49.5% vs 8.6% and 33.9%; P .0001 for both). Efficacy was maintained until week 52 with continuous deucravacitinib. The most frequent adverse event with deucravacitinib was nasopharyngitis. Serious adverse events and discontinuations due to adverse events were infrequent. No clinically meaningful changes were observed in laboratory parameters.The study duration was 1 year.Deucravacitinib demonstrated superiority versus placebo and apremilast and was well tolerated in adults with moderate to severe plaque psoriasis.

What is this summary about? This is a summary of a paper published in a medical journal that describes the results of a study called POETYK PSO-2, which investigated a new treatment for plaque psoriasis. Plaque psoriasis appears on the body as dry, discolored, patches of skin that can be flaky and covered in scales. This can make the skin itch, crack or bleed and make it difficult for people with psoriasis to perform basic everyday tasks. Treatments are available, but some do not always reduce symptoms or may need to be injected or taken multiple times a day, which can be difficult to do, or can have undesirable side effects. Researchers are looking for new treatments for psoriasis. What happened in the study? Deucravacitinib is a once-daily pill taken by mouth (orally) that was studied as a treatment for moderate to severe plaque psoriasis in two large studies conducted globally, PSO-1 and PSO-2. POETYK PSO-2 was a Phase 3 research study, which is a study that tests a treatment in a large group of participants, that looked at how well deucravacitinib worked in participants with moderate to severe plaque psoriasis compared to a placebo (an inactive pill that has no effect) and an approved psoriasis treatment called apremilast, which is a pill taken twice a day. These medications were tested in adults with moderate to severe plaque psoriasis, which is psoriasis involving 10% or more of their body (equal to 10 or more handprints). The aims of the POETYK PSO-2 study were to find out if treatment with deucravacitinib could improve psoriasis for the participants in the study and to see if there were any side effects. Side effects are events that happened during treatment that may or may not be caused by that treatment. The study also wanted to find out what would happen after stopping treatment with deucravacitinib in participants who had shown major improvements in their psoriasis. What do the results of the POETYK PSO-2 study show? After 4 months of treatment, more participants taking deucravacitinib had significantly greater improvements in psoriasis than those taking placebo or apremilast. The study also showed that participants continued to see these improvements after taking deucravacitinib for up to 1 year. Some participants maintained the improvements in their psoriasis with deucravacitinib after stopping treatment and switching to a placebo. Side effects for participants taking deucravacitinib were generally mild and occurred in similar numbers to those in participants taking placebo. The most common side effects in participants taking deucravacitinib were inflammation of the nose and throat (a common cold) which occurred at a similar rate in participants who took placebo. Clinical Trial Registration: NCT03611751 (POETYK PSO-2 study) ( ClinicalTrials.gov )

Dupilumab was initially approved in 2017 as the first biologic therapy for atopic dermatitis (AD). We characterized adults with AD initiating dupilumab in a real-world setting in the USA/Canada.PROSE is an ongoing, longitudinal, prospective, observational, multicenter registry of patients with AD initiating dupilumab per country-specific prescribing information. We report baseline data (day of first dupilumab injection) for patients enrolled from April 2018 through July 2019.Among 315 patients (mean age 42.5 years, 55.2% female), the median AD duration was 17.0 years; 65.4% reported a history of type 2 inflammatory comorbidities (e.g., allergic rhinitis, asthma), and 93.3% reported treatment(s) for AD in the previous year, including topical corticosteroids (90.8%), systemic corticosteroids (36.2%), and nonsteroidal systemic therapies (14.0%). In total, 89.2% had an Overall Disease Severity score of 3 (moderate) or 4 (severe). Other mean disease severity scores included the following: Eczema Area and Severity Index 16.9 (range 0-72), body surface area affected 26.8%, Patient-Oriented Eczema Measure 18.5 (range 0-28), Dermatology Life Quality Index 12.7 (range 0-30), and pruritus Numerical Rating Scale score 6.9 (range 0-10).Patients initiating dupilumab have longstanding moderate-to-severe AD with significant disease burden and frequent type 2 comorbidities.NCT03428646.

Obesity is a common comorbidity of psoriasis and can attenuate response to biologic treatment.To investigate the efficacy, safety and tolerability of secukinumab 300 mg every 2 weeks (Q2W) vs. secukinumab 300 mg every 4 weeks (Q4W) in patients with a higher bodyweight.In this multicentre, double-blind, parallel-group trial, 331 patients with moderate-to-severe chronic plaque psoriasis weighing ≥ 90 kg were randomized to receive secukinumab 300 mg Q2W or secukinumab 300 mg Q4W. Patients who did not achieve Psoriasis Area and Severity Index (PASI) 90 at week 16 on the Q4W regimen were reallocated to remain on the Q4W regimen or uptitrate to Q2W.At week 16, Q2W dosing (n = 165) led to significantly higher PASI 90 responses vs. Q4W [n = 166; 73.2% vs. 55.5%, one-sided P-value = 0.0003, odds ratio estimate (95% confidence intervals): 2.3 (1.4-3.8)]. At week 52, higher efficacy responses were maintained in the Q2W arm (n = 165) vs. Q4W (n = 83); PASI 75: 88.9% vs. 74.8%; PASI 90: 76.4% vs. 52.4%; PASI 100: 46.7% vs. 27.3%; Investigator's Global Assessment 0/1: 75.9% vs. 55.6% and Dermatology Life Quality Index 0/1: 66.1% vs. 48.8%. PASI 90 nonresponders at week 16 who uptitrated to Q2W (n = 31) showed higher efficacy responses at week 32 (16 weeks post-uptitration, PASI 90: 38.7% vs. 16.5%) vs. those who remained on Q4W (n = 40). Safety results were comparable across treatment arms and consistent with the established secukinumab safety profile.Secukinumab 300 mg Q2W demonstrated superior and sustained efficacy compared with Q4W in patients with moderate-to-severe plaque psoriasis weighing ≥ 90 kg. PASI 90 nonresponders derived additional benefits from uptitration to a Q2W regimen (ClinicalTrials.gov identifier: NCT03504852). What is already known about this topic? Obesity is a common comorbidity of psoriasis and can attenuate response to biologic treatment. Secukinumab is a fully human monoclonal antibody that selectively neutralizes interleukin-17A in the treatment of moderate-to-severe plaque psoriasis. Subgroup analyses of previous study results and pharmacokinetic/pharmacodynamic modelling data suggest that heavier patients may benefit from higher exposure to secukinumab through an increased dosing frequency [300 mg every 2 weeks (Q2W) vs. every 4 weeks (Q4W)]. What does this study add? Over 52 weeks, secukinumab 300 mg Q2W demonstrated superior efficacy compared with secukinumab 300 mg Q4W in patients with moderate-to-severe plaque psoriasis weighing ≥90 kg, with comparable safety results, consistent with the established secukinumab safety profile. In patients who did not achieve PASI 90 at week 16 on the Q4W regimen, uptitration to the Q2W regimen at week 16 resulted in improved efficacy responses through week 52 after switching.

Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A.To assess patients' ability to self-inject bimekizumab subcutaneously using a 1 mL safety syringe or auto-injector.DV0002 and DV0006 were sub-studies of BE BRIGHT, a multicenter, phase 3 open-label extension study. Patients with moderate to severe plaque psoriasis received bimekizumab 320 mg (2x160 mg injections) every 4 or 8 weeks and were randomized 1:1 to the safety syringe or the auto-injector. The ability of patients to safely and effectively self-inject bimekizumab was assessed at 8 weeks (primary endpoint) and immediately after self-injection training at Baseline (secondary endpoint). Patient experience was evaluated using the pain visual analog scale (VAS; 0ndash;100 mm; 100 being worst pain), and the Self-Injection Assessment Questionnaire (SIAQ; 0ndash;10; 10 being most positive experience).All evaluable patients in DV0002 (n=125) and DV0006 (n=86) safely and effectively self-injected bimekizumab at Week 8. All evaluable patients in DV0002 who used the safety syringe (n=64) and 97.1% (n=66/68) who used the auto-injector, as well as all evaluable DV0006 patients (n=88) also self-injected bimekizumab safely and effectively at Baseline. Median VAS scores were low (range: 7.0ndash;20.0), and median pre-injection and post-injection SIAQ scores were high (range: 5.8ndash;10.0 and 7.1ndash;10.0, respectively) across both devices, sub-studies, and timepoints.Both devices provide a safe and effective option for patients to self-administer bimekizumab. Furthermore, patients reported a positive self-injection experience.NCT03766685 J Drugs Dermatol. 2022;21(2):162-171. doi:10.36849/JDD.6274THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.

Objective: This study was designed to develop and prospectively validate a machine learning based algorithm that could predict patient response to the most common biologic drug classes used in the management of psoriasis patients. This type of tool would allow clinicians to have greater confidence that a given patient will respond to a specific drug class, which could lead to improved health outcomes and reduced wasted healthcare spend. Methods: Patients were enrolled into one of two observational studies (STAMP studies) where dermal biomarker patches (DBPs) were applied at baseline prior to drug exposure, followed by clinical evaluations at 12 weeks after exposure. PASI measurements were made at baseline and 12 weeks to evaluate clinical response to a clinical phenotype. Responders were defined as those who reached PASI75 at 12 weeks. The transcriptomes obtained from the DBPs were sequenced and analyzed to derive and/or validate classifiers for each biologic class, which were then combined to yield predictive responses for all three biologic drug classes (IL-23i, IL-17i, and TNFai). Results: A total of 242 psoriasis patients were enrolled in these studies, including 118 patients (49.6%) treated with IL-23i, 79 patients (33.2%) treated with IL-17i, 35 patients (14.7%) treated with TNFai, and 6 patients (2.5%) treated with IL-12/23i. The IL-23i predictive classifier was developed from the earlier enrolled patients and independently validated with the latter enrolled patients. IL-17i and TNFai predictive classifiers were developed using publicly available datasets and independently validated with patients from the STAMP studies. In the independent validation, positive predictive values for three classifiers (IL-23i, IL-17i, and TNFai) were 93.1%, 92.3% and 85.7% respectively. Over the entire cohort, 99.5% of patients were predicted to respond to at least one drug class. Conclusion: This study demonstrates the power of using baseline dermal biomarkers and machine learning methods as applied to the prediction of psoriasis biologic prior to drug exposure. Using this test, patients, physicians, and the health care system all can benefit in distinct ways. Precision medicine can be realized for individual patients as most will likely respond to their prescribed biologic the first time. Physicians can prescribe these drugs with increased confidence, and the healthcare system will realize lower net costs as well as greatly reduced wasted spend by significantly improving initial response rates to expensive biologic therapeutics.

Background: Brodalumab is an interleukin-17 receptor A antagonist approved for the treatment of moderate-to-severe plaque psoriasis. Our prior publication reported significant disease improvement with brodalumab in psoriasis patients who had previously failed treatment with an anti-IL-17A agent. Objectives: We set out to investigate factors that differed between the patients who had treatment success with brodalumab and those who did not, including disease severity and underlying comorbidities. Other secondary endpoints included the extent of improvement in non-responders, characterization of the patients who discontinued early from the trial, and time to improvement on brodalumab. Methods: We conducted an Institutional Review Board (IRB)-approved open-label study of a total of 39 subjects enrolled at 3 sites with moderate-to-severe psoriasis. All patients previously failed treatment with an IL-17A agent. Subjects received brodalumab 210 mg via subcutaneous injection at weeks 0, 1, and 2, followed by 210 mg every 2 weeks, up to week 16. Subjects were evaluated monthly for improvement in PASI and sPGA. Results: Of the baseline comorbidities assessed, the only statistically significant difference between responders and non-responders was the presence of higher weight/BMI in non-responders in the AO dataset; this trend disappeared in the NRI dataset. Of the patients that dropped out of the trial early, 3 of the 5 had PASI improvements of >60%. A rapid onset to disease improvement was seen in the trial. Conclusion: These results indicate that brodalumab may be a good treatment choice for psoriasis patients, including those with severe disease and/or underlying comorbidities.

Background Treating to absolute treatment targets rather than relative measures such as Psoriasis Area and Severity Index (PASI)-75 is emerging as an important clinical concept included in psoriasis guidelines and clinical practice. Achieving treatment targets is associated with achievement of long-term outcomes. Objective To evaluate the relationship between psoriasis severity, disease characteristics, and achievement of PASI ≤2 with apremilast in a pooled analysis of the phase 3 ESTEEM 1 and 2 (NCT01194219 and NCT01232283), phase 3b LIBERATE (NCT01690299), and phase 4 UNVEIL (NCT02425826) clinical trials. Methods Pooled data from patients with moderate to severe plaque psoriasis randomized to apremilast 30 mg BID were analyzed by baseline PASI quartiles (Q1: 2.4-13.1, Q2: 13.2-15.9, Q3: 16.0-20.0, Q4: 20.1-57.8). Assessments included PASI, Dermatology Life Quality Index (DLQI), Scalp Physician's Global Assessment (ScPGA, ScPGA ≥1), and target (worst) Nail Psoriasis Severity Index (NAPSI, NAPSI ≥1). Results Of 1,062 patients, 963 had ScPGA ≥1 and 643 had NAPSI ≥1, 771 patients with baseline and Week 32 PASI assessments were included in analyses of Week 32 PASI target achievement. Rates of PASI ≤2 at Week 32 were greater in lower PASI quartiles (Q1: 43.5%, Q2: 31.2%, Q3: 26.8%, Q4: 18.4%). Most patients achieving PASI ≤2 target (83.6%) achieved DLQI ≤5 at Week 32, 59.3% of patients who did not achieve PASI ≤2 target achieved DLQI ≤5. At Week 32, mean improvements in ScPGA and NAPSI were similar with more moderate versus more severe disease (ScPGA, range: 1.1-1.4, NAPSI, range: 1.6-2.5). In a subgroup analysis, achievement of PASI ≤2 target was higher in the lowest PASI quartile and with disease duration Conclusions Greater achievement of PASI ≤2 was observed in patients with more moderate versus more severe skin disease. Apremilast may be particularly beneficial in more moderate disease early in the treatment paradigm.

Purpose Guselkumab, an interleukin (IL)-23 inhibitor, effectively treats moderate-to-severe plaque psoriasis. Materials and methods ECLIPSE, was a Phase 3, multicenter, 56-week, double-blinded, active-comparator study of guselkumab vs. secukinumab (IL-17A inhibitor) in patients with moderate-to-severe psoriasis. Patients were treated with guselkumab 100 mg (n = 534) or secukinumab 300 mg (n = 514) through week 44. Efficacy (at least a 90% and 100% improvement from baseline in Psoriasis Area and Severity Index [PASI 90 and PASI 100], Investigator's Global Assessment [IGA] 0/1, and IGA 0) was analyzed across subpopulations defined by baseline: age ( Results Overall, 1048 patients were randomized. At week 48, numerically greater proportions of patients achieved PASI 90, PASI 100, IGA 0/1, and IGA 0 with guselkumab vs. secukinumab regardless of baseline age, body weight, BMI, disease severity, body region, and prior medication. The largest differences were in patients ≥65 years old and patients weighing >100 kg. Conclusions Guselkumab treatment provided greater efficacy vs. secukinumab at week 48 in most subpopulations of patients with psoriasis.

Background Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits interleukin-17A and interleukin-17F. The efficacy and safety of bimekizumab as compared with the tumor necros...

Not all patients with psoriasis achieve a satisfactory response to their initial biologic monotherapy. Switching to a new biologic may be associated with new safety issues and additional costs. In this study, we assessed the effectiveness and safety of adjunctive halobetasol propionate (HP) 0.01%-tazarotene (TAZ) 0.045% lotion in adult patients with moderate to severe plaque psoriasis who had been receiving biologic monotherapy for 24 weeks or more but had inadequate responses. All participants received HP-TAZ lotion once daily for 8 weeks, then once every other day for 4 weeks, in addition to their ongoing biologics. This real-world study demonstrated that HP-TAZ lotion adjunctive to ongoing biologics is safe and effective and potentially a more economical alternative to switching biologics for patients with psoriasis with inadequate responses to biologic monotherapy.

Risankizumab is approved for treatment of moderate to severe plaque psoriasis. Availability of a patient-controlled single self-injection of risankizumab may improve adherence and long-term management of psoriasis.To investigate efficacy, safety, and usability of a new risankizumab 150 mg/mL formulation administered as a single subcutaneous injection via prefilled syringe (PFS) or autoinjector (AI).Efficacy, safety, usability, and acceptability of risankizumab 150 mg/mL PFS or AI were investigated in adults with moderate to severe psoriasis in two phase 3 studies. Study 1 was a multicenter, randomized, double-blinded, placebo-controlled study that investigated 150 mg/mL risankizumab PFS; study 2 was a multicenter, single-arm, open-label study that investigated 150 mg/mL risankizumab AI.At week 16, risankizumab 150 mg/mL demonstrated efficacy vs. placebo (Psoriasis Area and Severity Index ≥90% improvement (PASI 90), 62.9% vs. 3.8%; static Physician Global Assessment (sPGA) 0/1, 78.1% vs. 9.6%; bothThe efficacy, safety, and usability of 150 mg/mL risankizumab delivered as a single PFS or AI injection support use of this new formulation in patients with moderate to severe plaque psoriasis.NCT03875482 and NCT0387508.

Biologic treatments have taken the forefront in treating moderate-to-severe psoriasis. Although numerous randomized, controlled trials have demonstrated the efficacy of these agents, there is limited data suggesting that clinical trial outcomes are reproducible in real-world patients.Obtain real-world evidence for the use of biologics that target different segments of the immune system in patients with moderate-to-severe psoriasis.A retrospective chart review was conducted for 100 patients who initiated biologic therapy and had a follow-up visit within a 4- to 12-month period. Efficacy assessments included body surface area (BSA), Physicianrsquo;s Global Assessment (PGA) scores, composite BSAtimes;PGA scores, and the National Psoriasis Foundation (NPF) Treat to Target (TTT) goal ofle;1% BSA.Biologic treatment led to notable reductions in BSA, PGA, and BSAtimes;PGA relative to baseline, with the majority (67.0%) of the population achieving NPF TTT goals at follow-up. Disease improvements were observed in all patients, regardless of baseline body weight, prior experience with biologics, or the specific immune target of the prescribed biologic.Long-term biologic therapy demonstrated effectiveness in treating patients with moderate-to-severe psoriasis. J Drugs Dermatol. 20(4):442-449. doi:10.36849/JDD.2021.5823Visit the Psoriasis Resource Center for more.

Introduction: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved by the US Food and Drug Administration for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. In the phase 3 POETYK PSO-1 and PSO-2 trials, deucravacitinib was significantly more efficacious than placebo and apremilast and was well tolerated in moderate to severe plaque psoriasis. PSO-1 and PSO-2 completers could enroll in the ongoing open-label POETYK long-term extension (LTE) trial. Changes in blood laboratory parameters with deucravacitinib in the PSO-1, PSO-2, and LTE trials were compared with signature changes seen with JAK 1/2/3 inhibitors. Methods: The 52-week, double-blind PSO-1 (NCT03624127) and PSO-2 (NCT03611751) trials randomized adults with moderate to severe plaque psoriasis 2:1:1 to deucravacitinib 6 mg once daily, placebo, or apremilast 30 mg twice daily. At Week 52, eligible patients enrolled in POETYK LTE (NCT04036435) and received deucravacitinib. Changes from baseline in hematologic parameters (lymphocytes, neutrophils, platelets, hemoglobin) and lipid and chemistry parameters (cholesterol, creatinine, CPK, ALT) were assessed through Week 100 (LTE Week 48). CTCAE grade ≥3 laboratory abnormalities and treatment discontinuations due to laboratory abnormalities were evaluated. Results: 1519 patients received ≥1 dose of deucravacitinib in all 3 trials. In total, 1179 (77.6%) and 584 (38.4%) patients had ≥52 and ≥104 weeks, respectively, of continuous deucravacitinib exposure; median duration of exposure was 682.0 days (97 weeks). No trends in clinically meaningful changes from baseline were observed in these parameters from Weeks 0–52 or in the LTE. Grade 3 or 4 abnormalities over 100 weeks of deucravacitinib treatment were rare, with incidence rates comparable to placebo and apremilast through Week 52; no increases were seen in the LTE. Two patients discontinued deucravacitinib due to lymphopenia and abnormal hepatic function. Conclusion: No trends in clinically meaningful changes from baseline were observed with deucravacitinib in laboratory parameters, including signature changes associated with JAK 1/2/3 inhibitors. Treatment discontinuations and grade 3 or 4 laboratory abnormalities were rare and comparable to incidence rates seen with placebo and apremilast. These results suggest laboratory monitoring is not warranted with deucravacitinib.

Introduction: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved by the US FDA for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. Deucravacitinib was significantly more efficacious than placebo or apremilast and was well tolerated in previous reports from the phase 3 POETYK PSO-1 trial. Here, we examined response rates through Week 52 from this trial in subgroups defined by previous biologic, systemic (biologic/nonbiologic), and/or oral systemic treatment. Methods: PSO-1, a multicenter, double-blind trial, enrolled adults with moderate to severe plaque psoriasis. Patients with previous phototherapy, systemic treatment, and/or biologic treatment completed washout periods (4 weeks–6 months) before study entry, depending on treatment. Patients were randomized 2:1:1 to deucravacitinib 6 mg QD, placebo, or apremilast 30 mg BID; this analysis focused on deucravacitinib and placebo patients. Placebo patients switched to deucravacitinib at Week 16. PASI 75 and sPGA 0/1 were evaluated through Week 52 by prior treatment (biologic, systemic [biologic/nonbiologic], oral systemic) and by biologic- and systemic-naive patients. Nonresponder imputation was used for all reported endpoints. Results: 332 patients were randomized to deucravacitinib and 166 to placebo. At baseline, 34.3% of deucravacitinib patients and 44.0% of placebo patients received prior oral systemic treatment, 60.2% and 65.7% received prior systemic (biologic/nonbiologic) treatment, and 39.2% and 38.0% received prior biologic treatment, respectively. Week 52 PASI 75 response rates were similar in patients receiving deucravacitinib from baseline (65.1%) and placebo patients switching to deucravacitinib at Week 16 (68.3%). Findings with deucravacitinib were similar to those in placebo patients switching to deucravacitinib regardless of prior systemic (65.5%/68.1%), oral (70.2%/69.2%), or biologic (61.5%/61.8%) treatment, and in patients with no prior systemic (64.4%/68.6%) or biologic (67.3%/72.2%) treatment. Similarly, sPGA 0/1 response rates were comparable in deucravacitinib versus placebo patients in the overall population (52.7%/53.8%) and in the prior systemic (53.0%/55.3%), prior oral systemic (57.0%/53.8%), prior biologic (47.7%/45.5%), systemic-naive (52.3%/51.0%), and biologic-naive (55.9%/58.9%) cohorts. Conclusion: Deucravacitinib was effective through 52 weeks for moderate to severe plaque psoriasis regardless of previous systemic treatment. Placebo patients switching to deucravacitinib at Week 16 achieved PASI 75 and sPGA 0/1 similar to patients continuously treated with deucravacitinib.

To examine the effectiveness and safety of adjunctive treatment with calcipotriene 0.005%/betamethasone dipropionate 0.064% (Cal/BD) foam in adult patients with chronic plaque psoriasis who have localized residual plaques afterge;24 weeks of treatment with ixekizumab biologic therapy.This study was a prospective, open-label, single-arm study of adult patients with moderate-to-severe chronic plaque psoriasis who had suboptimal response afterge;24 weeks of treatment with ixekizumab (residual 3ndash;8% body surface area [BSA] involvement). All patients continued treatment with ixekizumab and received once-daily Cal/BD foam for 4 weeks, followed by every other day for weeks 8 to 12. The primary endpoint was treat-to-target BSAle;1% at week 4. Additional endpoints included the Physicianrsquo;s Global Assessment (PGA) score, PGAtimes;BSA, and the patient-reported Dermatology Life Quality Index (DLQI). Safety evaluations included assessments of adverse events (AEs) and local skin reactions.Among 25 enrolled patients, 36% were female, and the mean age was 50 years. After 4 weeks of daily Cal/BD foam, 56% of patients achieved the treat-to-target goal ofle;1% BSA. Mean % BSA involvement, mean PGA score, and composite PGAtimes;BSA score decreased 4 weeks after the addition of Cal/BD foam. Improvements in disease severity outcomes were maintained after reducing Cal/BD dosing frequency. Cal/BD was generally safe and well-tolerated, with no serious AEs reported.In real-world clinical practice, for patients with moderate-to-severe plaque psoriasis who had residual plaques followingge;24 weeks of ixekizumab monotherapy, adjunctive treatment with Cal/BD foam was associated with notable and sustained improvements in disease control. J Drugs Dermatol. 2022;21(3): 235-240. doi:10.36849/JDD.6396.

Background Pruritus, a common symptom of psoriasis, negatively affects quality of life; however, treatment of lesional skin does not consistently alleviate psoriatic itch. Objective To examine the effects of serlopitant, an oral, once-daily neurokinin 1 receptor antagonist, for treatment of psoriatic pruritus in a phase 2, randomized clinical trial (NCT03343639). Methods Patients (n = 204) were randomized to receive serlopitant, 5 mg, or placebo daily for 8 weeks. Eligible adult patients had plaque psoriasis for ≥6 months, plaques covering ≤10% of body surface area, pruritus for ≥4 weeks, and Worst Itch Numeric Rating Scale (WI-NRS) score ≥7 at the initial screening. Results Participants (54.2% women) had a mean age of 47.5 years and 85.2% were white. Mean baseline WI-NRS scores were 8.3 for serlopitant and 8.1 for placebo. The WI-NRS 4-point response rate at 8 weeks (primary end point) was 33.3% for serlopitant vs 21.1% for placebo (P = .028); at 4 weeks the rates were 20.8% for serlopitant vs 11.5% for placebo (P = .039). Treatment-related adverse events were reported for 4.9% of serlopitant-treated and 4.0% of placebo-treated patients. Limitations This was a phase 2 study with a small study population. Patients with severe psoriasis were excluded. Conclusion Serlopitant significantly reduced pruritus associated with mild to moderate psoriasis, supporting continued development of serlopitant for this patient population.

Background Antidrug antibodies (ADAs) may change pharmacokinetic or pharmacodynamic profiles of biologic therapies, potentially decreasing efficacy. Objective To evaluate the potential effects of brodalumab immunogenicity on safety, efficacy, and retreatment. Methods Data from 1 phase 2 and 3 phase 3 studies of brodalumab in psoriasis were analyzed. Results Overall, 2.7% of patients had positive test results for binding ADAs after receiving brodalumab; ADAs were transient in 1.4% of patients, and there were no neutralizing ADAs. Among ADA-positive patients, 60.0% (3/5) achieved a static physician's global assessment score of 0 or 1 at week 12 in the group receiving the brodalumab 210 mg every 2 weeks, compared with 79.1% (1131/1429) of ADA-negative patients. All patients (100%) who experienced return of disease and were retreated with brodalumab 210 mg every 2 weeks (none were ADA positive) achieved at least a 75% improvement in Psoriasis Area And Severity Index, ≥90% of whom regained response by week 8 of retreatment. Hypersensitivity reactions were less frequent with brodalumab than with placebo. Injection site reactions occurred in 1.8% of patients treated with brodalumab versus 2% of patients treated with ustekinumab. Limitations Retreatment could be assessed in only 1 phase 3 brodalumab study. Conclusion Brodalumab compares favorably with other biologics in terms of immunogenicity and high rates of efficacy recapture upon retreatment.

Tapinarof cream is a topical aryl hydrocarbon receptor-modulating agent under investigation for the treatment of psoriasis. Tapinarof modulates the expression of interleukin-17 and the skin-barrier proteins filaggrin and loricrin.We conducted two identical phase 3 randomized trials of tapinarof in patients with mild-to-severe plaque psoriasis. Adults with a baseline Physician's Global Assessment (PGA) score of 2 (mild) to 4 (severe) (on a scale from 0 to 4, with higher scores indicating more severe psoriasis) and a percent of total body-surface area affected of 3 to 20% were randomly assigned in a 2:1 ratio to use tapinarof 1% cream or vehicle cream once daily for 12 weeks. The primary end point, PGA response, was a PGA score of 0 (clear) or 1 (almost clear) and a decrease from baseline of at least 2 points at week 12. Secondary efficacy end points at week 12 were a reduction of at least 75% in the Psoriasis Area and Severity Index (PASI) score, a PGA score of 0 or 1, the mean change from baseline in the percent of body-surface area affected, and a reduction of at least 90% in the PASI score. Patient-reported outcomes were the mean changes from baseline to week 12 in the proportion of patients who had a decrease of at least 4 points in the Peak Pruritus Numeric Rating Scale (PP-NRS) score (range, 0 [no itch] to 10 [worst imaginable itch]), the PP-NRS total score, the Dermatology Life Quality Index total score, and the Psoriasis Symptom Diary score.In trials 1 and 2, a total of 692 and 674 patients, respectively, were screened, with 510 and 515 patients being enrolled. A PGA response occurred in 35.4% of the patients in the tapinarof group and in 6.0% of those in the vehicle group in trial 1 and in 40.2% and 6.3%, respectively, in trial 2 (P0.001 for both comparisons). Results for secondary end points and patient-reported outcomes were generally in the same direction as those for the primary end point. Adverse events with tapinarof cream included folliculitis, nasopharyngitis, contact dermatitis, headache, upper respiratory tract infection, and pruritus.Tapinarof 1% cream once daily was superior to vehicle control in reducing the severity of plaque psoriasis over a period of 12 weeks but was associated with local adverse events and headache. Larger and longer trials are needed to evaluate the efficacy and safety of tapinarof cream as compared with existing treatments for psoriasis. (Funded by Dermavant Sciences; PSOARING 1 and 2 ClinicalTrials.gov numbers, NCT03956355 and NCT03983980, respectively.).

Accurate assessment of atopic dermatitis (AD) severity is critical when initiating and monitoring therapy. Use of existing research tools such as the Eczema Area and Severity Index (EASI) and Scoring Atopic Dermatitis (SCORAD) is complex and time-consuming in clinical practice. A previous analysis found the product of validated Investigator's Global Assessment (vIGA) and affected body surface area (BSA) to be an accurate and practical tool for routine assessment of paediatric AD.To evaluate the IGAxBSA composite as an alternative to EASI or SCORAD for assessment of AD disease severity and disease responsiveness.The relationship between IGAxBSA, EASI and SCORAD was assessed in a post hoc analysis of pooled data from the dupilumab clinical trial programme in adult and paediatric patients with moderate-to-severe AD who had received dupilumab or placebo, with or without topical corticosteroids (TCS). The trials are registered at ClinicalTrials.gov and EudraCT: LIBERTY AD SOLO 1 (NCT02277743, 2014-001198-15), LIBERTY AD SOLO 2 (NCT02277769, 2014-002619-40), LIBERTY AD SOLO-CONTINUE (NCT02395133, 2014-003384-38), LIBERTY AD CHRONOS (NCT02260986, 2013-003254-24), LIBERTY AD CAFÉ (NCT02755649, 2015-002653-35), LIBERTY AD ADOL (NCT03054428, 2015-004458-16), LIBERTY AD PEDS (NCT03345914, 2016-004997-16), LIBERTY AD OLE (NCT01949311, 2013-001449-15) and LIBERTY AD PEDS OLE (NCT02612454, 2015-001396-40).Using datapoints from pooled dupilumab randomized controlled trials (n = 3473) and open-label extension trials (n = 3045), we found that IGAxBSA correlated well with EASI and SCORAD, irrespective of treatment group and race (white, Asian, black). IGAxBSA correlated better with objective measures (EASI, SCORAD) than with patient- or caregiver-reported subjective measures. IGAxBSA correlated strongly with EASI and SCORAD in assessing disease change over time (r = 0·90, r = 0·76, respectively; P 0·0001), and concordance between IGAxBSA-50/75/90 and EASI-50/75/90 was excellent (88-94%).IGAxBSA is a valid alternative for assessment of AD disease severity and response over time, compared with EASI or SCORAD in patients with AD, irrespective of race.

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ImportanceOnce-daily roflumilast cream, 0.3%, a potent phosphodiesterase 4 inhibitor, demonstrated efficacy and was well tolerated in a phase 2b trial of patients with psoriasis.ObjectiveTo evaluate the efficacy of roflumilast cream, 0.3%, applied once daily for 8 weeks in 2 trials of patients with plaque psoriasis.Design, Setting, and ParticipantsTwo phase 3, randomized, double-blind, controlled, multicenter trials (DERMIS-1 [trial 1; n = 439] and DERMIS-2 [trial 2; n = 442]) were conducted at 40 centers (trial 1) and 39 centers (trial 2) in the US and Canada between December 9, 2019, and November 16, 2020, and between December 9, 2019, and November 23, 2020, respectively. Patients aged 2 years or older with plaque psoriasis involving 2% to 20% of body surface area were enrolled. The dates of final follow-up were November 20, 2020, and November 23, 2020, for trial 1 and trial 2, respectively.InterventionsPatients were randomized 2:1 to receive roflumilast cream, 0.3% (trial 1: n = 286; trial 2: n = 290), or vehicle cream (trial 1: n = 153; trial 2: n = 152) once daily for 8 weeks.Main Outcomes and MeasuresThe primary efficacy end point was Investigator Global Assessment (IGA) success (clear or almost clear status plus ≥2-grade improvement from baseline [score range, 0-4]) at week 8, analyzed using a Cochran-Mantel-Haenszel test stratified by site, baseline IGA score, and intertriginous involvement. There were 9 secondary outcomes, including intertriginous IGA success, 75% reduction in Psoriasis Area and Severity Index (PASI) score, and Worst Itch Numeric Rating Scale score of 4 or higher at baseline achieving 4-point reduction (WI-NRS success) at week 8 (scale: 0 [no itch] to 10 [worst imaginable itch]; minimum clinically important difference, 4 points).ResultsAmong 881 participants (mean age, 47.5 years; 320 [36.3%] female), mean IGA scores in trial 1 were 2.9 [SD, 0.52] for roflumilast and 2.9 [SD, 0.45] for vehicle and in trial 2 were 2.9 [SD, 0.48] for roflumilast and 2.9 [SD, 0.47]) for vehicle. Statistically significantly greater percentages of roflumilast-treated patients than vehicle-treated patients had IGA success at week 8 (trial 1: 42.4% vs 6.1%; difference, 39.6% [95% CI, 32.3%-46.9%]; trial 2: 37.5% vs 6.9%; difference, 28.9% [95% CI, 20.8%-36.9%]; P P P P Conclusions and RelevanceAmong patients with chronic plaque psoriasis, treatment with roflumilast cream, 0.3%, compared with vehicle cream resulted in better clinical status at 8 weeks. Further research is needed to assess efficacy compared with other active treatments and to assess longer-term efficacy and safety.Trial RegistrationClinicalTrials.gov Identifiers: NCT04211363, NCT04211389

Psoriasis is a complex immune disorder associated with substantial metabolic and psychological comorbidities, posing challenges to treatment. Interleukin (IL)-23 inhibitors, the newest class of biologics for the treatment of moderate to severe psoriasis, are more selective mechanistically than previous biologic classes and may have utility in management of patients with comorbidities, particularly those with metabolic syndrome (MetS). Moreover, recent long-term data suggest that IL-23 inhibitors offer unique advantages in both safety and efficacy. As the relationship between psoriasis and MetS continues to be elucidated, the availability of agents that are safe and effective in patients with and without comorbidities represents an important step in the spectrum of treatment.

Background Patients with psoriatic arthritis (PsA) have increased risk of adverse events, including serious infections (SI), compared with psoriasis patients. Methods Patients eligible for, or receiving conventional systemic and biologic agents for psoriasis were followed prospectively using PSOLAR. Cohorts included: ustekinumab, tumor necrosis factor (TNF) inhibitors; infliximab; etanercept; adalimumab; non-biologic/methotrexate (MTX) (reference group); and non-biologic/non-MTX. Multivariate analyses using Cox hazard regression were used to identify factors associated with time to first SI. Rates of SI in PSOLAR psoriasis patients with self-reported PsA and possible risks with biologic therapy were evaluated. Results PSOLAR enrolled 4315 psoriasis patients with self-reported PsA. The overall population (N = 2401) included patients (n): 628 ustekinumab; 1413 TNF inhibitors; 258 infliximab; 481 etanercept; 674 adalimumab; 54 other biologics, 98 non-biologic/MTX; 208 non-biologic/non-MTX. Overall, 138 SI were reported with incidence rates per 100 patient-years as follows: a) ustekinumab: 1.00; b) TNF inhibitors: 2.22; c) infliximab: 2.12; d) etanercept: 2.58; e) adalimumab: 1.99; f) non-biologic/MTX: 3.01; g) and non-biologic/non-MTX: 2.31. Age, time-dependent disease activity Physician’s Global Assessment (PGA) of 4, 5, history of infection, and diabetes were associated with increased risk for SI (p Conclusions PSOLAR psoriasis patients with self-reported PsA in the TNF inhibitors, infliximab, adalimumab, etanercept, and MTX cohorts had numerically higher SI rates than the ustekinumab cohort, although not statistically significant. Age, PGA 4, 5, history of infection, and diabetes were associated with an increased risk for SI, irrespective of biologic exposure. Trial registration NCT00508547; Registered July 30, 2007.

Elderly patients are a group with a high frequency of psoriasis. Their disease burden has negative impacts on their quality of life. While there is a clear need to treat these patients, there are challenges in doing so. This work seeks to define the challenges that exist in treating elderly Medicare patients, as well as to provide treatment suggestions for providers to follow if they encounter one or more of these challenges. Providers face the following challenges when creating treatment plants for elderly patients with psoriasis: difficulty in obtaining drug coverage through Medicare, increased medical comorbidities, and polypharmacy. Providers aim for regimens that are affordable, safe, and efficacious, but it is not always clear how to achieve this combination, especially in elderly Medicare patients. This work is relevant in that it aims to explain the logistical roadblocks posed by Medicare coverage and provide solutions for commonly encountered issues in the treatment of a disabling and common disease in a high-risk population. Specifically, alternative treatment options to biologics and small-molecule inhibitors are discussed and include topical therapies, phototherapy, methotrexate, acitretin, and cyclosporine and for psoriatic arthritis include corticosteroids and leflunomide. The specific risks and benefits of these therapies in the elderly population are provided, allowing providers to make patient-specific decisions about optimal regimens.

Summary Background In the U.S.A., an Investigator's Global Assessment (IGA) score of ≤ 1 (clear or almost clear skin) has been the standard measure in regulatory outcomes for registration clinical trials in atopic dermatitis (AD), including those supporting the recent approval of dupilumab. Objectives To evaluate the treatment effect of dupilumab in patients with IGA > 1 at the end of treatment, using other validated outcome measures for AD signs, symptoms and quality of life. Methods LIBERTY AD SOLO 1 and 2 were two 16‐week, randomized, double‐blind trials enrolling adult patients with moderate‐to‐severe AD (IGA ≥ 3) inadequately controlled with topical treatment. We performed a post hoc analysis in patients receiving dupilumab 300 mg every 2 weeks (q2w) or placebo. Outcome measures in patients with IGA > 1 included Eczema Area and Severity Index (EASI), pruritus numerical rating scale (NRS), affected body surface area (BSA), Patient‐Oriented Eczema Measure (POEM) and Dermatology Life Quality Index (DLQI). The trials were registered at ClinicalTrials.gov: NCT02277743 and NCT02277769. Results At week 16, 278 of 449 dupilumab q2w‐treated patients (median age 36·0 years) and 396 of 443 placebo‐treated patients had IGA > 1. Among patients with IGA > 1 at week 16, dupilumab significantly improved several outcome measures compared with placebo: EASI (−48·9% vs. −11·3%, P < 0·001), pruritus NRS (−35·2% vs. −9·1%, P < 0·001), affected BSA (−23·1% vs. −4·5%, P < 0·001), POEM score ≥ 4‐point improvement (57·4% vs. 21·0%, P < 0·001) and DLQI score ≥ 4‐point improvement (59·3% vs. 24·4%, P < 0·001). Conclusions In patients with IGA > 1 at week 16, dupilumab induced statistically significant benefits in multiple validated outcome measures compared with placebo. The IGA ≤ 1 end point significantly underestimates clinically relevant dupilumab treatment effects., What's already known about this topic? An Investigator's Global Assessment (IGA) score of 0 or 1 (clear or almost clear skin) is considered the regulatory standard for treatment success in trials of patients with atopic dermatitis in the U.S.A.It is currently unknown whether patients receiving dupilumab treatment for moderate‐to‐severe atopic dermatitis derive clinical and quality‐of‐life benefit even if they have an end‐of‐treatment IGA score > 1. What's does this study add? This post hoc analysis of patients with an end‐of‐treatment IGA score > 1 from two randomized, placebo‐controlled trials showed that after 16 weeks of treatment dupilumab significantly improved their outcome measures compared with placebo, including measures of signs, symptoms and quality of life.These results show that the regulatory IGA ≤ 1 end point used in clinical trials significantly underestimates clinically relevant dupilumab treatment effects, underscoring potential limitations of the IGA scale. Linked Comment: https://doi.org/10.1111/bjd.18037. https://www.bjdonline.com/article/

Background About 20% of patients taking apremilast alone obtain PASI 75 by week 8. This single-center, pilot study aimed to determine whether add-on topical therapy with calcipotriene/betamethasone dipropionate (C/BD) could improve responses of partial apremilast responders by week 12. Methods Adults (g18 years of age) with moderate to severe plaque psoriasis (baseline PGA g3, BSA affected g10%, PASI g12) took oral apremilast (30 mg twice daily) for 8 weeks. Patients who achieved between PASI 25n74 at week 8 used add-on, daily topical C/BD (.005%/.064%) foam up to week 12; those with lPASI 25 at week 8 were discontinued. Results Of 50 patients enrolled, 26 achieved PASI 25m74 and 8 PASI 75 at week 8. At week 12, 29 achieved PASI 75, and 24 at week 16. Of the week-8 partial responders, 21/26 achieved PASI 75 at week 12 on combination therapy and 15 maintained PASI 75 through week 16 on apremilast alone (4 did not maintain; 2 lost to follow up). In partial responders, mean PGA and BSA affected improved by 30% and 33% on apremilast, respectively, and by 67% and 86% at week 12 on the combination therapy, respectively. The most commonly reported adverse events (AEs; g5% occurrence) were headache (14%), diarrhea (10%), and nausea (8%); majority were mild. No related serious AEs occurred. Conclusion We show that most week-8 partial apremilast responders can achieve PASI 75 at week 12 with combination C/BD topical therapy, and maintain PASI 75 through week 16 with apremilast monotherapy. J Drugs Dermatol. 2020;19(12): doi:10.36849/JDD.2020.5435.

Background Atopic dermatitis (AD) is a chronic inflammatory skin disease. Interleukin (IL) 13 is a type 2 cytokine that is key to the inflammation underlying AD. Tralokinumab is a first-in-class, fully human, monoclonal antibody that specifically binds with high affinity to IL-13, neutralizing it in AD. Immunomodulatory treatments may impair vaccine-induced immune responses. Objective Assess the immune responses to standard vaccines in adults with moderate-to-severe AD who are undergoing treatment with tralokinumab. Methods ECZema TRAlokinumab Trial No. 5 (ECZTRA 5; NCT03562377 ) was a phase 2, double-blind, randomized, placebo-controlled trial taking place over 30 weeks. Eligible adults were randomized 1:1, with 107 patients receiving tralokinumab 300 mg and 108 patients receiving a placebo every 2 weeks for 16 weeks. All patients received Tdap (tetanus/diphtheria/pertussis) and meningococcal vaccines at week 12. The primary end points were positive antitetanus and antimeningococcal responses between weeks 12 and 16 (noninferiority margin, −25%; responder, >3-fold increase in IgG). Results The noninferiority of tralokinumab versus placebo for immune response to Tdap (91.9% vs 96.1%) and meningococcal (86.0% vs 84.2%) vaccines was demonstrated at week 16. During treatment, the rates of adverse events were lower for tralokinumab than for the placebo, with most events being mild or moderate. Limitations Responses to other vaccines (including influenza) were not examined. Conclusions Treatment with tralokinumab 300 mg every 2 weeks did not affect immune responses to Tdap and meningococcal vaccines. Treatment was well tolerated when administered concomitantly with the vaccines and demonstrated a safety profile comparable to phase 3 trials.

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Background: Patients with moderate-to-severe psoriasis can have symptoms resulting in significant impact on patient-reported outcomes (PROs). The effect of etanercept (ETN) in moderate-to-severe psoriasis patients who previously received apremilast (APR) was studied, including impact on PRO endpoints. Methods: In this multicenter, open-label, single-arm, phase 4 estimation study, patients with moderate-to-severe psoriasis who did not have adequate response to APR in the opinion of the investigator received ETN 50mg subcutaneous (SC) twice weekly for 12 weeks, followed by ETN 50mg SC once weekly for an additional 12 weeks. Analysis was conducted for PROs directly and by the Psoriasis Area and Severity Index (PASI) achievement thresholds. Results: Of the 80 patients enrolled, the Psoriasis Symptom Inventory (PSI; total and individual items) had substantial improvement at weeks 12 and 24. Improvement in PSI total score (percent; mean [SD]) in patients who achieved PASI 50, -75, and -90 at week 12 was 57% (30), 67% (24), and 83% (18), respectively and at week 24 was 56% (40), 68% (29), and 80% (25). DLQI responders by PASI 50, -75, and 90 achievements were 69%, 68%, and 90%, respectively, at week 12 and 68%, 77%, and 82% at week 24. The percent of patients reported being "very satisfied" or "satisfied" with treatment at week 12 was 79%, 81%, and 100%, respectively, and at week 24 was 77%, 86%, and 88%. Conclusion: Patient-reported symptoms are important outcomes to consider in psoriasis management. ETN provided benefits in patients who did not have adequate response with APR, with improvements seen in both psoriasis symptoms and patient impact. Clinical Trial Number: NCT02749370 J Drugs Dermatol. 2020;19(4):378-383. doi:10.36849/JDD.2020.4910.

The use of superpotent topical corticosteroids (TCSs) for the treatment of psoriasis is widely practiced, especially for expedient lesion resolution. However, their continued use in managing this chronic condition is limited because of labelling restrictions, concerns of side effects, and a paucity of data to support long-term management strategies. Halobetasol propionate (HP) is an effective short-term superpotent TCS. A novel HP lotion 0.01% formulation has been developed using a polymeric matrix technology that allows for uniform delivery of optimally sized particles onto the skin surface. The polymeric matrix and emulsion help to keep the skin hydrated and provide more efficient delivery of halobetasol into the epidermis.

Background Secukinumab demonstrated superior efficacy over ustekinumab in the treatment of moderate to severe plaque psoriasis over 16 weeks in the CLARITY study and over 52 weeks in the CLEAR study. Objective To compare the efficacy and safety of secukinumab vs. ustekinumab over 52 weeks in CLARITY. Methods Analysis of 52‐week data from CLARITY (NCT02826603), a phase 3b study in which patients were randomized to receive secukinumab 300 mg (n = 550) or ustekinumab 45/90 mg (n = 552) per label. Results At week 52, secukinumab was superior to ustekinumab in the proportion of patients who achieved ≥ 90% improvement in Psoriasis Area and Severity Index (73.2% vs. 59.8%; odds ratio [OR], 1.84 [95% CI, 1.41–2.41]; P

Introduction Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, has demonstrated superior efficacy to ustekinumab in the phase 3b CLEAR study of moderate to severe plaque psoriasis. Here, we report 16-week results from CLARITY, a second head-to-head trial comparing secukinumab with ustekinumab. Methods In the phase 3b CLARITY study, patients were randomized 1:1 to receive subcutaneous secukinumab 300 mg or ustekinumab per label. The co-primary objectives were to demonstrate the superiority of secukinumab over ustekinumab at Week 12 in relation to the proportion of patients with (1) 90% or more improvement from baseline Psoriasis Area and Severity Index (PASI 90) and (2) a score of 0/1 (clear/almost clear) on the modified Investigator’s Global Assessment (IGA mod 2011 0/1). Key secondary objectives were also assessed, as was Dermatology Life Quality Index (DLQI) 0/1 (no impact of skin disease on patients’ quality of life) response. Missing values were handled by multiple imputation except for DLQI 0/1, where last observation carried forward techniques were utilized. Results Both co-primary objectives were met: secukinumab was superior to ustekinumab for the proportion of patients achieving a PASI 90 (66.5% vs. 47.9%) and IGA mod 2011 0/1 response (72.3% vs. 55.4%) at Week 12 (p