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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.

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.

Introduction Le secukinumab est un anticorps monoclonal entierement humain qui neutralise selectivement l’interleukine-17A. Cette etude randomisee de phase IIIb porte sur l’efficacite et la securite d’une administration de 300 mg de secukinumab toutes les deux semaines (Q2W) par rapport a une administration toutes les quatre semaines (Q4W) en traitement du psoriasis chez les patients pesant 90 kg ou plus. Materiel et methodes Les patients atteints de psoriasis en plaques modere a severe ont recu 300 mg de secukinumab toutes les 2 semaines Q2W ou toutes les 4 semainesQ4W (1:1) pendant 48 semaines. Les criteres d’evaluation primaires (reponse PASI 90 [Psoriasis Area and Severity Index]) et secondaires (reponse IGA [modifie 2011] 0/1 a l’Investigator's Global Assessment) ont ete evalues a la semaine 16. A la semaine 16, les non-repondeurs PASI 90 recevant 300 mg de secukinumab toutes les 4 semaines ont ete randomises a nouveau pour rester dans ce groupe ou passer a une administration de 300 mg de secukinumab toutes les 2 semaines jusqu’a la semaine 48 ; l’efficacite de cette augmentation de posologie a ete evaluee. Resultats A la semaine 16, 73,2 % des patients traites par 300 mg de secukinumab toutes les 2 semaines (n = 165) contre 55,5 % des patients traites par 300 mg de secukinumab toutes les 4 semaines (n = 166) ont obtenu une reponse PASI 90 (p = 0,0003). A la semaine 52, la posologie 300 mg toutes les 2 semaines (n = 165) a montre des reponses PASI 90 (76,4 % vs 52,4 %) et IGA 0/1 (75,9 % vs 55,6 %) plus elevees que la posologie 300 mg toutes les 4 semaines (n = 83). Les non-repondeurs PASI 90 qui sont passes a une dose de 300 mg toutes les 2 semaines (n = 31) ont montre des reponses PASI 90 plus elevees a la semaine 32 (16 semaines apres le passage au regime posologique superieur, 38,7 % vs 16,5 %) par rapport a ceux qui sont restes sous 300 mg de secukinumab toutes les 4 semaines (n = 40). Les resultats de tolerance etaient comparables dans les differents bras de traitement et coherents avec le profil de tolerance etabli du secukinumab. Discussion La posologie de 300 mg de secukinumab toutes les 2 semaines a demontre une efficacite superieure et maintenue par rapport a celle de 300 mg toutes les 4 semaines chez les patients atteints de psoriasis en plaques modere a severe pesant 90 kg ou plus. Dans la population des non-repondeurs PASI 90, les patients ont tire un benefice supplementaire de l’augmentation de posologie a 300 mg de secukinumab toutes les 2 semaines a partir de la semaine 16.

Moderate-to-severe scalp psoriasis has not been evaluated in prospective trials of patients without moderate-to-severe body psoriasis.Evaluate the efficacy and safety of secukinumab in moderate-to-severe scalp psoriasis.In this 24-week, double-blind, phase 3b study, 102 patients were randomized 1:1 to subcutaneous secukinumab 300 mg or placebo at baseline, weeks 1, 2, and 3, and then every 4 weeks from week 4 to 20. The primary efficacy variable was 90% improvement of Psoriasis Scalp Severity Index (PSSI 90) score from baseline to week 12.At week 12, PSSI 90 (secukinumab 300 mg vs placebo, 52.9% vs 2.0%) and Investigator's Global Assessment modified 2011 scalp responses of 0 or 1 (secukinumab 300 mg vs placebo, 56.9% vs 5.9%) were significantly greater with secukinumab 300 mg than placebo (P .001 for both). In addition, significantly more patients achieved complete clearance of scalp psoriasis at week 12 with secukinumab 300 mg than placebo (35.3% vs 0%; P .001). The median time to 50% reduction in PSSI score was 3.29 weeks with secukinumab 300 mg. The safety profile of secukinumab was consistent with previous phase 3 studies.There was no active comparator arm.Secukinumab is efficacious and well-tolerated for patients with extensive moderate-to-severe scalp psoriasis.

Introduction L’ixekizumab (IXE), anticorps monoclonal de haute affinite ciblant de facon selective l’IL-17A, a precedemment montre lors d’un suivi de plus de 3 ans, le maintien d’une reduction du PASI absolu et une securite d’emploi satisfaisante dans le traitement du psoriasis modere a severe. L’etude UNCOVER-3 rapporte des donnees a 4 ans (204 semaines) du PASI absolu chez des patients traites a la dose recommandee d’IXE. Materiel et methodes Les patients ont ete traites a la dose recommandee d’IXE (160 mg, puis 80 mg toutes les 2 semaines [Q2W] jusqu’a la semaine 12 incluse, puis 80 mg toutes les 4 semaines [Q4W]). La dose pouvait, apres la semaine 60, etre augmentee a Q2W a la discretion de l’investigateur. Les donnees d’efficacite presentees sont celles des patients ayant recu la dose recommandee (n = 385), les donnees des autres patients ayant ete exclues. L’efficacite a ete evaluee en pourcentage de patients ayant obtenu un score PASI de 75/90/100 et un score de PASI absolu ≤ 5/3/2/1. L’analyse statistique mNRI a ete utilisee, c’est-a-dire que les donnees manquantes pour absence de reponse, pour interruption de traitement en raison d’evenements indesirables, pour un manque d’efficacite ou une rechute ont ete imputees en non-repondeur. Les autres donnees manquantes ont ete imputees par imputation multiple. Resultats Sur les 385 patients randomises dans le groupe IXEQ2W, 362 etaient encore dans l’etude durant la periode d’extension a long terme ; 74 ont eu un ajustement de dose a Q2W entre les semaines 60 et 204 ; plus de la moitie (54,1 %) avait atteint un PASI 75 avant ajustement de la dose. A la semaine 204, le pourcentage de patients ayant recu la dose recommandee IXEQ2W/IXEQ4W, avec un PASI 75/90/100 etait de 82,8 %, 66,4 % et 48,3 % respectivement. Le pourcentage de patients avec un score de PASI absolu ≤ 5/3/2/1 etait de 82,3 %, 73,2 %, 67,3 % et 59,6 %, respectivement. Aucun nouveau signal en terme de tolerance n’a ete identifie pour l’IXE. Conclusion L’efficacite de l’IXE sur 4 ans a ete demontree chez des patients atteints de psoriasis en plaques modere a severe. Le profil de tolerance est conforme aux precedents resultats, sans signal nouveau ou inattendu.

Introduction ECLIPSE est une etude de phase 3, multicentrique, en double aveugle, controlee vs comparateur actif, comparant le guselkumab, un anticorps monoclonal anti-IL23, et le secukinumab, un anticorps monoclonal anti-IL17A, dans le traitement a long terme de patients adultes atteints de psoriasis en plaques modere a severe. Cette analyse a evalue la constance de la reponse sous guselkumab par rapport au secukinumab dans des sous-groupes de patients predefinis en fonction de l’âge a l’inclusion. Materiel et methodes Les patients adultes (≥ 18 ans) ont ete randomises pour recevoir 100 mg de guselkumab aux semaines 0, 4 et 12, puis toutes les 8 semaines (n = 534), ou 300 mg de secukinumab aux semaines 0, 1, 2, 3, 4, puis toutes les 4 semaines (n = 514) ; jusqu’a la semaine 44. Les patients randomises pour le guselkumab ont egalement recu des injections de placebo afin de faire correspondre le nombre et la frequence des injections a celles du secukinumab afin de maintenir l’aveugle. Les proportions de patients obtenant a la semaine 48 une reponse PASI 90, une reponse PASI 100 et un score IGA 0 ont ete analysees par categorie d’âge a l’inclusion : Resultats Les proportions de patients dans chaque categorie d’âge au debut de l’etude etaient globalement comparables entre les groupes guselkumab (n = 534) et secukinumab (n = 514) : Tableau 1 ). Les taux de reponse PASI 100 et le score IGA de 0 etaient aussi numeriquement plus eleves pour le guselkumab que pour le secukinumab, pour toutes les categories d’âge ( Tableau 1 ). Conclusion A la semaine 48, le groupe guselkumab a obtenu des taux de reponse numeriquement plus eleves que le secukinumab dans le traitement du psoriasis modere a severe quelles que soient les categories de patients definies par l’âge.

Introduction L’evaluation globale par l’investigateur (Investigator Global Assessment [IGA]) des symptomes de la dermatite atopique permet de determiner la severite (echelle de 0 a 4) ; elle n’inclut pas la surface corporelle atteinte ni les resultats rapportes par le patient. L’IGA est un critere d’evaluation pour les autorites reglementaires, mais n’a jamais ete valide. Le dupilumab, un anticorps monoclonal anti-IL-4Rα entierement humain, a ete developpe dans le traitement de la DA moderee a severe chez l’adulte. Dans deux etudes de phase III controlees versus placebo ([PBO] ; LIBERTY AD SOLO 1/SOLO 2 : NCT02277743 / NCT02277769 ) sur le dupilumab en monotherapie dans la DA de l’adulte moderee a severe, le critere d’evaluation principal etait IGA = 0 (blanchi)/1 (quasi-blanchi) a la 16e semaine. Materiel et methodes Ce resume decrit une analyse post-hoc de donnees poolees des etudes SOLO 1 et 2 pour evaluer la variation selon des scores valides et cliniquement pertinents, chez les patients ayant recu 300 mg de dupilumab toutes les 2 semaines ou un PBO. L’IGA et les autres criteres d’evaluation sont bases sur les valeurs observees et les valeurs de p sont nominales. Resultats A la 16e semaine, 107, 131 et 24 patients traites par dupilumab et 72, 215 et 83 patients sous PBO presentaient respectivement un IGA de 2, 3, ou 4. Le dupilumab permettait une amelioration plus importante par rapport a l’inclusion avec le score EASI (indice de surface et de severite de l’eczema) par rapport au PBO ( % de variation par rapport a l’inclusion : IGA = 2 : −57,1 % vs −45,7 % ; IGA = 3 : −32,4 % vs −21,1 % ; IGA = 4 : −11,5 % vs −1,6 % ; p Discussion Meme chez les patients non repondeurs selon l’IGA, dupilumab a montre une amelioration significative et cliniquement pertinente des scores EASI, du NRS de prurit et DLQI. Conclusion En raison des limitations de l’IGA pour l’evaluation des benefices cliniques associes au traitement de la DA, d’autres criteres d’efficacite doivent etre envisages pour les etudes a venir.

Background Many studies have identified cardiovascular risk factors in patients with psoriasis. Some psoriasis therapies may increase cardiovascular disease (CVD) and others may decrease CVD. Objective We reviewed the literature to define the impact of common psoriasis therapies on cardiovascular measures and outcomes. Results Phototherapy has no major cardiovascular impact and may reduce levels of proinflammatory cytokines. Acitretin increases serum lipids and triglycerides, but has not been shown to increase cardiovascular risk. Cyclosporine A increases blood pressure, serum triglycerides, and total cholesterol. Methotrexate is associated with a decreased risk of CVD morbidity and mortality. Among the biologics, data for tumor necrosis factor inhibitors suggest an overall reduction in cardiovascular events. Most data on short-term ustekinumab use suggest no effect on major adverse cardiovascular events, however some authorities remain concerned. Nevertheless, ustekinumab use over a 4-year period shows a decrease in major adverse cardiovascular events when compared both with the general US population and with psoriatics in Great Britain. Limitations Most studies lack the power and randomization of large clinical trials and long-term follow-up periods. In addition, the increased risk of CVD associated with psoriasis itself is a confounding factor. Conclusion Some therapies for moderate to severe psoriasis, including methotrexate and tumor necrosis factor inhibitors, may reduce cardiovascular events in psoriatic patients. Ustekinumab appears to be neutral but there may be a long-term benefit. Appropriate patient counseling and selection and clinical follow-up are necessary to maximize safety with these agents. Further long-term study is necessary to quantify the benefits and risks associated with biologic therapies.

Phototherapy is a mainstay in the treatment of psoriasis and is available as psoralen plus UVA (PUVA), broadband UVB (BB-UVB), and narrowband UVB (NB-UVB). Phototherapy can be administered in the hospital, outpatient clinic, or in the patient's home. The purpose of this review is to provide some practical guidance to general dermatologists and residents on the specifics of using phototherapy, which, despite its decreasing use, remains one of our most safe and effective treatment strategies for psoriasis care. We conducted a literature review of home phototherapy, BB-UVB, NB-UVB, and PUVA phototherapy using PubMed, MD Consult, and reference lists. A variety of protocols for BB-UVB, NB-UVB, and PUVA have been used in clinical trials. NB-UVB is more effective than BB-UVB and safer than PUVA. Typical regimens for NB-UVB involve dosing 3 times per week for at least 3 months. Treatment must be independently developed to suit each participant's needs. Ultraviolet light is an effective, relatively safe modality that is a valuable tool in the treatment of psoriasis. NB-UVB phototherapy is considered the first-line treatment for extensive plaque type psoriasis.

Introduction L’apremilast (APR), un inhibiteur oral de phosphodiesterase 4, agit par voie intracellulaire pour reguler les mediateurs inflammatoires. Les patients atteints de psoriasis indiquent que le prurit constitue leur symptome cutane le plus genant. Materiel et methodes Des patients atteints de psoriasis en plaques modere a severe (score PASI [Psoriasis Area and Severity Index] ≥ 12 ; surface corporelle (SC) ≥ 10 %, Score d’evaluation globale par le medecin statique ≥ 3) ont ete randomises (2 :1) pour recevoir APR 30 mg 2 ×/j (APR30) ou un placebo (PBO). A la semaine 16, les patients sous PBO sont passes a APR30 jusqu’a la semaine 32. Une evaluation par les patients du prurit et de la gene cutanee a ete conduite avec une echelle visuelle analogique (EVA) de 100 mm. Observations Le prurit et la gene/douleur cutanee ont ete evalues dans ESTEEM 1 et ESTEEM 2. Resultats L’ensemble de l’analyse globale a inclus 844 patients d’ESTEEM 1 (PBO : n = 282 ; APR30 : n = 562) et 411 d’ESTEEM 2 (PBO : n = 137 ; APR30 : n = 274). Les caracteristiques demographiques et pathologiques initiales ont ete generalement bien equilibrees entre les groupes de traitement. A la semaine 16, un nombre significativement superieur de patients ont atteint un score PASI-75 (critere principal) avec APR30 (ESTEEM 1 : 33,1 % ; ESTEEM 2 : 28,8 %) vs PBO (ESTEEM 1 : 5,3 % ; ESTEEM 2 : 5,8 %) (p Discussion APR30 a reduit de maniere significative la severite du prurit et de la gene/douleur cutanee vs PBO a la semaine 16. Conclusion Des ameliorations du prurit et de la gene/douleur cutanee ont ete observees avec APR30 des la semaine 2 et se sont maintenues jusqu’a la semaine 32 chez des patients atteints de psoriasis en plaques modere a severe. Ces etudes ont ete promues par Celgene Corporation.

Background: Denileukin diftitox, a fusion protein targeting both malignant and normal activated lymphocytes, has been shown previously to have antipsoriatic activity. However, the ideal dosing regimen for treating psoriasis was not established. Objective: We examined the safety and efficacy of denileukin diftitox in patients with severe plaque-type psoriasis. Methods: This was a cohort dose-escalation trial. Patients were administered denileukin diftitox on 3 consecutive days every other week. Patients were evaluated for toxicity, improvement in psoriasis, immunogenicity, and serum levels. Results: Thirty-five patients were treated at 3 dose levels. Eight patients had a 50% decrease or more in Psoriasis Area and Severity Index score from baseline (0/10 at 0.5 μg/kg per day, 1/10 at 1.5 μg/kg per day, and 7/15 at 5 μg/kg per day). Adverse events primarily consisted of constitutional events and skin reactions. Conclusions: The potential antipsoriatic activity of denileukin diftitox demonstrated in this study was comparable to that observed in other psoriasis studies with this agent. However, this dosing regimen was better tolerated than the dosing regimen used in the last study with denileukin diftitox in psoriasis patients. (J Am Acad Dermatol 2001;45:871-81.)

Not until the end of the twentieth century has success in the treatment of psoriasis been predictable. The use of state-of-the-art technologies and improved therapeutic programs often leads to a clearing on all affected areas of the body. Today, many patients are benefiting from prolonged remission lasting up to 1 year; with major pharmaceutical companies offering patient participation in clinical trials, the likelihood of finding even more treatment options is increasing. One of the greatest challenges dermatologists currently face is managing a medically effective center that is cost-effective enough to remain open. Establishing a successful psoriasis treatment center involves a number of practical considerations: personnel, equipment, space, economics, reimbursements, and patients. At the Psoriasis Center of Central New Jersey, which the author set up 14 years ago, patients who have moderate-to-severe psoriasis on more than 10% of the body are treated. The goal is to provide each patient with the best risk-to-benefit ratio possible. Whether in a university setting or private practice, providing patients with all currently available therapeutic options can only be achieved using an array of technologic equipment operated by well-educated, highly trained medical staff.

Background: Current therapies for recalcitrant psoriasis focus on immunoregulation and targeting of activated T-lymphocytes rather than keratinocytes. Previous studies with low doses of the lymphocyte-selective fusion protein DAB 389 IL-2 have shown benefit to patients with psoriasis. Objective: We examined the safety and efficacy of DAB 389 IL-2 in 41 volunteers receiving more frequent and higher doses than in a previous trial. Methods: Patients were randomized to receive either placebo or 5, 10, or 15 mg/kg daily of DAB 389 IL-2 intravenously for 3 consecutive days each week for 4 consecutive weeks with a subsequent 4-week observation period. Results: Of the placebo group, 17% (2 of 12) exhibited at least 50% improvement from baseline Psoriasis Area and Severity Index scores at the end of the study, whereas 24% of all treated patients (7 of 29) showed the same improvement. Overall, 3 of 12 (25%) patients given placebo as opposed to 12 of 29 (41%) patients treated with DAB 389 IL-2 improved to this same extent at some point during the study. The rate of improvement for treated patients was significantly greater than for placebo patients ( p = 0.04; repeated measures ANOVA). Among treated patients, decreases in Psoriasis Area and Severity Index scores were paralleled by changes in the Physician's Global Assessment and the Dermatology Life Quality Index. Treatment in ten patients was discontinued because of adverse events. Flu-like symptoms were the most common with severity increasing at the two higher doses. Only one serious adverse event was reported. This occurred in a patient receiving 5 mg/kg daily who experienced vasospasm and a coagulopathy resulting in arterial thrombosis. Conclusion: Our findings are consistent with the potential antipsoriatic activity of DAB 389 IL-2 demonstrated in an earlier study. However, DAB 389 IL-2 was less well tolerated at this dosing regimen, particularly at the highest dose, and it was too toxic at these doses and schedules to be considered in the routine treatment of psoriasis. (J Am Acad Dermatol 1998;38:938-44.)

To our knowledge this is the first case of hemorrhagic bullae caused by Morganella morganii septicemia. The presence of organisms in the bullae, demonstrated by Gram strain and culture, and the acral location of the bullae suggest that the skin lesions were due directly to blood-borne infection. Multiple factors predisposed this patient to gram-negative bacteremia, including lymphoma, chemotherapy, neutropenia, systemic steroids, multiple hospitalizations, and treatment with broad-spectrum antibiotics.