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Background: Palmoplantar pustulosis (PPP) is a chronic inflammatory condition, that leads to significant functional impairment and reduced quality of life. Despite its low incidence, treatment options are diverse and often ineffective, necessitating a review of recent therapeutic advances., Objective: This review aims to evaluate the efficacy and safety of recent therapeutic options for the treatment of PPP, focusing on phototherapy, systemic therapies, and biologics., Materials and methods: A systematic literature search identified 13 studies evaluating phototherapy and systemic therapies, including biologics. Inclusion criteria focused on randomized controlled trials with participants diagnosed with PPP., Results: Phototherapy showed success: excimer laser demonstrated high efficacy for severe disease [PPP Area and Severity Index (PPPASI)-75 of 95.0%], while psoralen plus ultraviolet A therapy with retinoids or fumaric acid esters worked well in milder disease (PPPASI-90 of 90.0 and 81.8%, respectively). Evidence supports the efficacy and safety of guselkumab, brodalumab, and apremilast over a range of disease severity (PPPASI-50 ranged from 57.4 to 78.3% at week 16). Agents including anakinra, secukinumab, spesolimab, and RIST4721 (primary outcomes not achieved) may not be first-line treatments. By targeting multiple inflammatory pathways in PPP, JAK inhibitors may be more effective than biologics in treating PPP; however, more research is needed to confirm their safety and appropriate use., Conclusions: Multiple new treatments exist for PPP with promising results, however longer-term studies with standardized outcome reporting are needed to determine optimal treatment strategies and their comparative efficacy.

Guttate psoriasis (GP) is a variant of psoriasis characterized by scattered "drop-like" papules and plaques, accounting for up to a quarter of psoriasis cases. Although GP can clear within 3 to 4 months, up to 39% of cases may progress to chronic plaque psoriasis. Currently, there is a paucity of literature investigating the efficacy of different treatment modalities. This systematic review aims to synthesize all available data on GP treatment efficacy. A literature search was conducted using Medline, Embase, Web of Science, and CINAHL with no date limits. A total of 75 studies satisfied eligibility criteria and were analyzed. Most studies were case reports, series, or retrospective studies. Only 5 randomized controlled trials (RCTs) were identified. For topical treatments, corticosteroids and calcipotriol creams had the most evidence for efficacy. Four categories of systemic therapies were identified: traditional immunosuppressants, antibiotics, retinoids, and biologics. Evidence regarding antibiotic therapy suggests minimal connection between underlying infection resolution and GP lesion remission. Phototherapy had the most robust evidence, with narrowband ultraviolet B (UVB) being the most effective. Our findings are limited by high heterogeneity in study design and high risk of bias. Based on our review, we propose the following treatment algorithm. As first-line therapy, we recommend topical corticosteroids and calcipotriol cream, in combination with phototherapy. As supportive therapy, we recommend antibiotics if applicable. For second-line therapy, we recommend methotrexate or cyclosporine. For severe and refractory GP, biologics can be used as third-line treatment. RCTs are needed to provide higher quality evidence to create standardized treatment recommendations., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The use of monoclonal antibodies has changed the treatment of several immune-mediated inflammatory diseases, including psoriasis. However, these large proteins must be administered by injection. JNJ-77242113 is a novel, orally administered interleukin-23-receptor antagonist peptide that selectively blocks interleukin-23 signaling and downstream cytokine production., Methods: In this phase 2 dose-finding trial, we randomly assigned patients with moderate-to-severe plaque psoriasis to receive JNJ-77242113 at a dose of 25 mg once daily, 25 mg twice daily, 50 mg once daily, 100 mg once daily, or 100 mg twice daily or placebo for 16 weeks. The primary end point was a reduction from baseline of at least 75% in the Psoriasis Area and Severity Index (PASI) score (PASI 75 response; PASI scores range from 0 to 72, with higher scores indicating greater extent or severity of psoriasis) at week 16., Results: A total of 255 patients underwent randomization. The mean PASI score at baseline was 19.1. The mean duration of psoriasis was 18.2 years, and 78% of the patients across all the trial groups had previously received systemic treatments. At week 16, the percentages of patients with a PASI 75 response were higher among those in the JNJ-77242113 groups (37%, 51%, 58%, 65%, and 79% in the 25-mg once-daily, 25-mg twice-daily, 50-mg once-daily, 100-mg once-daily, and 100-mg twice-daily groups, respectively) than among those in the placebo group (9%), a finding that showed a significant dose-response relationship (P<0.001). The most common adverse events included coronavirus disease 2019 (in 12% of the patients in the placebo group and in 11% of those across the JNJ-77242113 dose groups) and nasopharyngitis (in 5% and 7%, respectively). The percentages of patients who had at least one adverse event were similar in the combined JNJ-77242113 dose group (52%) and the placebo group (51%). There was no evidence of a dose-related increase in adverse events across the JNJ-77242113 dose groups., Conclusions: After 16 weeks of once- or twice-daily oral administration, treatment with the interleukin-23-receptor antagonist peptide JNJ-77242113 showed greater efficacy than placebo in patients with moderate-to-severe plaque psoriasis. (Funded by Janssen Research and Development; FRONTIER 1 ClinicalTrials.gov number, NCT05223868.)., (Copyright © 2024 Massachusetts Medical Society.)

Generalized pustular psoriasis (GPP) is a rare, immune-mediated inflammatory disease with characteristic cutaneous and systemic manifestations. Mutations in the interleukin-36 receptor antagonist (IL36RN) gene have been implicated in its pathogenesis. Spesolimab is a novel systemic biologic therapy that selectively inhibits interleukin-36. It was recently approved by Health Canada and the US FDA for the treatment of GPP flares in adults. Results from phase 1 and 2 studies have been promising. Herein, we review the efficacy and safety of spesolimab for the treatment of GPP flares, as demonstrated in clinical trials., Competing Interests: Ronald Vender has been an advisor, consultant, speaker, and/or investigator for AbbVie, Actelion, Amgen, Aralez, Arcutis, Astellas, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Cipher, Centocor, Dermira, Dermavant, Eli Lilly, Galderma, GSK, Innovaderm, Janssen, Kabi-Care, LEO Pharma, Merck, Novartis, Palladin, Pfizer, Regeneron, Sandoz, Sun Pharma, Takeda, UCB, and Viatris-Mylan. Jensen Yeung has been an advisor, consultant, speaker, and/or investigator for AbbVie, Allergan, Amgen, Astellas, Boehringer Ingelheim, Celgene, Centocor, Coherus, Dermira, Eli Lilly, Forward, Galderma, GSK, Janssen, LEO Pharma, Medimmune, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Sun Pharma, Takeda, UCB, Valeant, and Xenon. Alim R. Devani has been an advisor, consultant, speaker, and/or investigator for AbbVie, Amgen, AnaptysBio, Arcutis, Arena, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Concert, Dermavant, Dermira, Eli Lilly, Galderma, GSK, Incyte, Janssen, LEO Pharma, Medexus, Nimbus Lakshmi, Novartis, Pediapharm, Pfizer, Regeneron, Reistone, Sanofi Genzyme, Sun Pharma, Takeda, Tribute, UCB, and Valeant. Vimal H. Prajapati has been an advisor, consultant, speaker, and/or investigator for AbbVie, Actelion, Amgen, AnaptysBio, Apogee Therapeutics, Aralez, Arcutis, Arena, Asana, Aspen, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Cipher, Concert, CorEvitas, Dermavant, Dermira, Eli Lilly, Galderma, GSK, Homeocan, Incyte, Janssen, LEO Pharma, Medexus, Nimbus Lakshmi, Novartis, Pediapharm, Pfizer, RAPT Therapeutics, Regeneron, Reistone, Sanofi Genzyme, Sun Pharma, Takeda, Tribute, UCB, and Valeant. Tuba Bukhari, Mariya Markovina, Abrahim Abduelmula, and Brian D. Rankin have no relevant disclosures. Funding sources: None.

Background: Treatment of psoriasis with risankizumab has demonstrated superior efficacy to other treatments, such as adalimumab, ustekinumab and secukinumab., Objectives: This study compared the efficacy and safety of risankizumab and apremilast in adults with moderate plaque psoriasis eligible for systemic therapy. It also evaluated the efficacy and safety of switching to risankizumab vs. continuing apremilast in patients who did not achieve ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75 nonresponders) after 16 weeks of treatment with apremilast., Methods: This 52-week, phase IV, multicentre, randomized, open-label, efficacy assessor-blinded study (NCT04908475) enrolled patients (aged ≥ 18 years) with a diagnosis of moderate chronic plaque psoriasis (≥ 6 months) and who were candidates for systemic therapy. The enrolled patients (randomized 1 : 2) received subcutaneous risankizumab (150 mg at weeks 0 and 4) or oral apremilast (30 mg twice daily). At week 16, all patients treated with apremilast were re-randomized (1 : 1) to risankizumab or apremilast, stratified by week-16 PASI 75 response. The co-primary outcomes in period A at week 16 were the achievement of ≥ 90% improvement in Psoriasis Area and Severity Index (PASI 90) and static Physician's Global Assessment (sPGA) 0/1 with a two-grade or better improvement from baseline. At week 52, the primary endpoint in period B was the achievement of PASI 90 in PASI 75 nonresponders with apremilast at week 16. Safety was monitored throughout the study. All patients who received one dose of treatment were included in the efficacy and safety analysis., Results: At baseline, 118 and 234 patients were assigned to receive risankizumab and apremilast, respectively. At week 16, PASI 90 was achieved by 55.9% [95% confidence interval (CI) 47.0-64.9] and 5.1% (95% CI 2.3-8.0), and sPGA 0/1 by 75.4% (95% CI 67.7-83.2) and 18.4% (95% CI 13.4-23.3), respectively. In period B, among PASI 75 nonresponders with apremilast at week 16, 83 switched to risankizumab and 78 continued apremilast. At week 52, 72.3% (95% CI 62.7-81.9) who switched to risankizumab achieved PASI 90 vs. 2.6% (95% CI 0.0-6.1) who continued apremilast. The most frequent adverse events (reported in ≥ 5%) in risankizumab-treated patients were COVID-19 infection and nasopharyngitis. Diarrhoea, nausea and headache were most frequent among apremilast-treated patients., Conclusions: For patients with moderate psoriasis, treatment with risankizumab demonstrated superior efficacy to those treated with apremilast, including those who did not benefit from prior treatment with apremilast. The safety profile of risankizumab was similar to prior studies, and no new safety signals were identified. These results show that, compared with apremilast, risankizumab treatment can significantly improve clinical outcomes in systemic-eligible patients with moderate psoriasis., Competing Interests: Conflicts of interest: L.F.S.G. has received grants and personal fees from AbbVie, Amgen, Arcutis, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Dermavant, Dermira/UCB, Eli Lilly, Janssen Biotech, LEO Pharma, Novartis, Pfizer, Regeneron, Sun Pharma, Taro and Valeant. J.B. has received research funds from Amgen, Arcutis, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, CorEvitas (Corrona) Psoriasis Registry, Dermavant, Dermira/UCB, Eli Lilly, Glenmark, Janssen Biotech, Kadmon, LEO Pharma, Lycera, Menlo Therapeutics, Novartis, Pfizer, Regeneron, Sun Pharma, Taro and Valeant; has served as a consultant for AbbVie, Amgen, Celgene, Eli Lilly, Janssen Biotech, Novartis, Sun Pharma and Valeant; and has served as a speaker for AbbVie, Celgene, Eli Lilly, Janssen Biotech and Novartis. S.K.T. has been an investigator on an AbbVie-funded trial. H.C.H. has been an investigator and/or speaker and/or consultant for AbbVie, Amgen, Arcutis, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Cutanea, Dermira, Dermavant, DS Biopharma, Eli Lilly, Galderma, GSK, Incyte, Janssen, LEO Pharma, Medimmune, Merck, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharma, Roche and UCB. L.P. has been an investigator for AbbVie, Coherus, Novartis, Janssen Biotech and Eli Lilly; and an adviser, consultant and/or invited lecturer for AbbVie, Janssen Biotech, Novartis Pharmaceuticals, Pfizer, Dexcel Pharma and Eli Lilly. R.V. has been a consultant, scientific adviser, investigator or speaker for Amgen, AbbVie, Astellas, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Dermira, Eli Lilly, Galderma, GSK, Janssen, LEO Pharma, MSD, Merck Serono, Novartis, Pfizer, Regeneron, Roche, Sanofi-Aventis/Genzyme, Sun Pharma, Takeda, UCB Pharma and Valeant/Bausch Health. A.P. has been investigator and/or speaker and/or adviser for AbbVie, Almirall-Hermal, Amgen, Biogen Idec, Boehringer Ingelheim, Celgene, GSK, Eli Lilly, Galderma, Hexal, Janssen, LEO Pharma, MC2, Medac, Merck Serono, Mitsubishi, MSD, Novartis, Pascoe, Pfizer, Tigercat Pharma, Regeneron, Roche, Sandoz Biopharmaceuticals, Sanofi Genzyme, Schering-Plough, UCB Pharma and Zuellig Pharma. A.R. has been a consultant or speaker for AbbVie, Bioderma, Celgene, Chema Elektromet, Eli Lilly, Galderma, Janssen, LEO Pharma, Medac, Menlo Therapeutics, Novartis, Pierre-Fabre, Sandoz and Trevi; and a principal investigator or subinvestigator in clinical trials sponsored by AbbVie, Drug Delivery Solutions, Galderma, Genentech, Janssen, Kymab, LEO Pharma, Menlo Therapeutics, MetrioPharm, MSD, Novartis, Pfizer and Trevi. L.D., T.W., M.P., A.M.S., H.P., V.S. and S.R. are employees of AbbVie and may own stock/options and patents. K.A.P. has taken part in speakers’ bureaus for AbbVie, Amgen, Astellas, Celgene, Eli Lilly, Galderma, Janssen, Kyowa Hakko Kirin, LEO Pharma, Merck Sharp & Dohme, Novartis, Pfizer and Valeant; has received grant/research support from AbbVie, Akros, Allergan, Amgen, Anacor, Arcutis, AstraZeneca, Baxalta, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Coherus, Dermira, Dow Pharma, Eli Lilly, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa Hakko Kirin, LEO Pharma, MedImmune, Meiji Seika Pharma, Merck Serono, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Takeda, UCB and Valeant; has served as a consultant for AbbVie, Akros, Amgen, Arcutis, Astellas, AstraZeneca, Baxalta, Baxter, Boehringer Ingelheim, Bristol Myers Squibb, CanFite, Celgene, Coherus, Dermira, Dow Pharma, Eli Lilly, Forward Pharma, Galderma, Genentech, Janssen, Kyowa Hakko Kirin, LEO Pharma, Meiji Seika Pharma, Merck Serono, Merck Sharp & Dohme, Mitsubishi Pharma, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Takeda, UCB and Valeant; has received honoraria from AbbVie, Akros, Amgen, Baxter, Boehringer Ingelheim, Celgene, Coherus, Eli Lilly, Forward Pharma, Galderma, GlaxoSmithKline, Janssen, Kyowa Hakko Kirin, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, Takeda, UCB and Valeant; and has served as a scientific officer, on a steering committee, and an advisory board for AbbVie, Akros, Amgen, Anacor, Astellas, Baxter, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Dow Pharma, Eli Lilly, Galderma, Janssen, Kyowa Hakko Kirin, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron, Sanofi Genzyme and Valeant., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Competing Interests: Conflicts of interest Dr Vender has been a consultant, advisory board member, and investigator for AbbVie, Actelion, Amgen, Astellas, Celgene, Dermira, Eli Lilly, Galderma, Janssen Ortho, Leo, Merck, Novartis, Pfizer, Regeneron, and Takeda. Dr Yeung has been an advisor, consultant, speaker, and/or investigator for AbbVie, Allergan, Amgen, Astellas, Boehringer Ingelheim, Celgene, Centocor, Coherus, Dermira, Eli Lilly, Forward, Galderma, GSK, Janssen, LEO Pharma, Medimmune, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Sun Pharma, Takeda, UCB, Valeant, and Xenon. Dr Prajapati has been an advisor, consultant, speaker, and/or investigator for AbbVie, Actelion, Amgen, AnaptysBio, Apogee Therapeutics, Aralez, Arcutis, Arena, Aspen, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Cipher, Concert, Dermavant, Dermira, Eli Lilly, Galderma, GlaxoSmithKline, Homeocan, Incyte, Janssen, LEO Pharma, Medexus, Nimbus Lakshmi, Novartis, Pediapharm, Pfizer, Regeneron, Reistone, Sanofi Genzyme, Sun Pharma, Tribute, UCB, and Valeant. Author Abduelmula, Dr Rankin, Author Sood, Dr Georgakopoulos, and Dr Mufti have no conflicts of interest to declare.

Over the past two decades, promising advancements have emerged in the field of psoriasis management. Most notably, highly effective targeted biologic therapies that offered significant breakthroughs in the management of psoriasis have been developed. One of the most challenging components of marketing and prescribing these biologic therapies has been in classifying them as immunomodulators or immunosuppressants. The purpose of this narrative review was to discuss the features that distinguish immunomodulators from immunosuppressants to successfully categorize the biologic therapies used for psoriasis management and subsequently enhance patient and physician understanding of the risks associated with the use of these drugs.

Cytokines in the interleukin (IL)-23/IL-17 axis are central to psoriasis pathogenesis. Janus kinase (JAK) signal transducer and activator of transcription (STAT) regulates intracellular signalling of several cytokines (including IL-12, 23, 22, 6, 17, and interferon (IFN)-γ) in the IL-23/IL-17 axis, and, as a result, has become a therapeutic target for psoriasis treatment. Although several JAK1-3 inhibitors, with varying degrees of selectivity, have been developed for immune-mediated inflammatory diseases, use in psoriasis is limited by a low therapeutic index as anticipated by signals from other disease indications. More selective inhibition of the JAK family is an area of interest. Specifically, selective tyrosine kinase (TYK)2 inhibition suppresses IL-23/IL-17 axis signalling, and at therapeutic doses, has a favorable safety profile compared to therapeutic doses of JAK1-3 inhibitors. Phase III efficacy and safety data for the selective allosteric TYK2-inhibitor, deucravacitinib, in adult patients with moderate-to-severe plaque psoriasis is promising. Furthermore, phase II clinical trials for ropsacitinib (PF-06826647), a selective TYK2 inhibitor, and brepocitinib (PF-06700841), a JAK1/TYK2 inhibitor, have also demonstrated efficacy and an acceptable safety profile in adult patients with moderate-to-severe plaque psoriasis. Other novel TYK2 allosteric inhibitors, NDI-034858 and ESK-001, are currently being investigated in adult patients with plaque psoriasis. This article reviews the details of the JAK-STAT pathway in psoriasis pathophysiology, the rationale for selective targeting of JAKs in the treatment of psoriasis, and provides clinical perspective on clinical trial data for JAK and TYK2 inhibitors.

Nail psoriasis is a chronic, difficult-to-treat condition affecting almost half of patients with psoriasis. It is associated with considerable social stigma and impairment of patients' quality of life. The aim of this study was to assess improvements in objective measures of nail psoriasis among patients from the long-term extension of the UNCOVER-3 study who received the interleukin-17A inhibitor ixekizumab and had either any degree of nail psoriasis (Nail Psoriasis Severity Index (NAPSI) >=1) or significant nail psoriasis (fingernail NAPSI ≥ 16 and ≥ 4 fingernails involved) at baseline. Efficacy outcomes reported through week 264 included the mean percentage improvements from baseline in NAPSI score and the proportion of patients achieving nail psoriasis resolution (NAPSI=0). In UNCOVER-3, 56.9% (219/385) of patients had nail psoriasis at baseline; of those, 61.2% (134/219) had significant nail psoriasis. At week 60, a total of 66.9% and 59.1% of patients with baseline nail psoriasis and significant baseline nail psoriasis, respectively, reported complete clearance of nail psoriasis, an effect which was sustained through week 264. This analysis demonstrates that continuous treatment with ixekizumab in adult patients with moderate-to-severe-psoriasis through 264 weeks was associated with improvements and clearance of fingernail psoriasis, irrespective of the severity of nail psoriasis at baseline.

Competing Interests: Conflicts of interest Dr Yeung has been an advisor, consultant, speaker, and/or investigator for AbbVie, Allergan, Amgen, Astellas, Boehringer Ingelheim, Celgene, Centocor, Coherus, Dermira, Eli Lilly, Forward, Galderma, GSK, Janssen, LEO Pharma, Medimmune, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Sun Pharma, Takeda, UCB, Valeant, and Xenon. Dr Vender has been an advisor, consultant, speaker, and/or investigator for AbbVie, Amgen, Boehringer Ingelheim, Celgene, Centocor, Dermira, Eli Lilly, Galderma, GSK, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharma, Takeda, UCB, and Valeant. Dr Devani has been an advisor, consultant, speaker, and/or investigator for AbbVie, Amgen, Arcutis, Arena, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Concert, Dermira, Eli Lilly, Galderma, GSK, Incyte, Janssen, LEO Pharma, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharma, Tribute, and UCB. Dr Prajapati has been an advisor, consultant, speaker, and/or investigator for AbbVie, Actelion, Amgen, AnaptysBio, Aralez, Arcutis, Arena, Aspen, Bausch Health, Boehringer Ingelheim, Celgene, Cipher, Concert, Dermavant, Dermira, Eli Lilly, Galderma, GSK, Homeocan, Incyte, Janssen, Kymab, LEO Pharma, Medexus, Novartis, Pediapharm, Pfizer, Regeneron, Reistone, Sanofi Genzyme, Sun Pharma, Tribute, UCB, and Valeant. Author Sachdeva and Drs Rankin, Mufti, Luca, Miettunen, and Stevenson have no conflicts of interest to declare.

The IL-17 signalling pathway is a major target in treatment of plaque psoriasis. IL-17 signalling contributes to chronic inflammation and epidermal hyperplasia seen in psoriatic lesions. Blocking the IL-17 signalling cascade is an effective method in treating this disease. However, IL-17 also plays a role in the immunological protection against fungal infections and therefore, patients on IL-17 biologics experience an increased rate of fungal infections, specifically Candida albicans . It is prudent that patients and physicians are aware of this risk and understand how to recognize and manage Candida infections. In this review, we examine the Candida infection rates associated with IL-17 biologics, both in clinical trials and real-world practice. We discuss common presentations associated with various types of candidiasis and propose a recommended management approach to treating these infections.

Background: Certolizumab pegol (CZP) is a TNF-ɑ inhibitor used to treat moderate-to-severe plaque psoriasis (PsO) in adult patients, including women of childbearing potential (WOCBP) and patients with psoriatic arthritis (PsA). There are currently limited real-world data on CZP for treatment of PsO., Objectives: To examine the use of CZP for treatment of PsO in clinical practice at two dermatology clinics in Canada., Methods: We conducted a retrospective chart analysis of 59 patients with moderate-to-severe psoriasis receiving CZP. Clinical efficacy was measured using the Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA), and Physician Global Assessment (PGA). Drug survival was analyzed using Kaplan-Meier plots., Results: Of the 59 patients, 36 (61%) were female, of whom 23 (63.9%) were WOCBP. Twenty-three (39.0%) patients received CZP as their first biologic treatment. The main reasons for choosing CZP were its efficacy in both PsO and PsA, and for WOCBP due to little or no cross-placental transfer. Improvement of symptoms was observed after 3 months of treatment and was maintained for the 12-month analysis period. After 12 months of treatment, the patients' mean PASI score decreased from 13.0 (±5.8) at baseline to 2.3 (±4.3), mean BSA score from 13.1% (±6.7%) to 1.7% (±2.6%), and mean PGA score from 3.0 (±0.6) to 0.8 (±0.6). Overall CZP drug survival rate was 76.3% at 12 months, with no difference between biologic-naive and biologic-experienced patients., Conclusions: CZP was effective and well tolerated in this cohort of patients with moderate-to-severe PsO in a real-world setting.

A novel topical corticosteroid, halobetasol propionate (HP) 0.01% lotion (Bryhali™), has recently been introduced for the treatment of plaque psoriasis and corticosteroid-responsive dermatoses in adults. Once daily application of HP 0.01% lotion is indicated for use up to 8 weeks. Treatment success for plaque psoriasis in the pivotal phase 3 clinical trials (defined as an Investigator Global Assessment [IGA] of clear/almost clear [IGA 0/1] with ≥2-grade improvement from baseline) occurred in over one-third of patients by week 8. Treatment-emergent adverse events were typically mild-to-moderate in intensity and usually limited to the application site(s). No treatment-related cases of skin atrophy have been reported from the studies. Counselling should be considered to optimize treatment outcomes., Competing Interests: Abrahim Abduelmula and Brian D. Rankin have no relevant disclosures. Ronald Vender has been an advisor, consultant, speaker, and/or investigator for AbbVie, Actelion, Amgen, Astellas, Celgene, Dermira, Eli Lilly, Galderma, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Regeneron, and Takeda. Jensen Yeung has been an advisor, consultant, speaker, and/or investigator for AbbVie, Allergan, Amgen, Astellas, Boehringer Ingelheim, Celgene, Centocor, Coherus, Dermira, Eli Lilly, Forward, Galderma, GSK, Janssen, LEO Pharma, Medimmune, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Sun Pharma, Takeda, UCB, Valeant, and Xenon. Alim R. Devani has been an advisor, consultant, speaker, and/or investigator for AbbVie, Amgen, AnaptysBio, Arcutis, Arena, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Concert, Dermavant, Dermira, Eli Lilly, Galderma, GSK, Incyte, Janssen, LEO Pharma, Medexus, Nimbus Lakshmi, Novartis, Pediapharm, Pfizer, Regeneron, Reistone, Sanofi Genzyme, Sun Pharma, Tribute, UCB, and Valeant. Vimal H. Prajapati has been an advisor, consultant, speaker, and/or investigator for AbbVie, Actelion, Amgen, AnaptysBio, Aralez, Arcutis, Arena, Aspen, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Cipher, Concert, Dermavant, Dermira, Eli Lilly, Galderma, GSK, Homeocan, Incyte, Janssen, LEO Pharma, Medexus, Nimbus Lakshmi, Novartis, Pediapharm, Pfizer, Regeneron, Reistone, Sanofi Genzyme, Sun Pharma, Tribute, UCB, and Valeant. Funding sources: None.

Importance: A clear dosing regimen for methotrexate in psoriasis is lacking, and this might lead to a suboptimal treatment. Because methotrexate is affordable and globally available, a uniform dosing regimen could potentially optimize the treatment of patients with psoriasis worldwide., Objective: To reach international consensus among psoriasis experts on a uniform dosing regimen for treatment with methotrexate in adult and pediatric patients with psoriasis and identify potential future research topics., Design, Setting, and Participants: Between September 2020 and March 2021, a survey study with a modified eDelphi procedure that was developed and distributed by the Amsterdam University Medical Center and completed by 180 participants worldwide (55 [30.6%] resided in non-Western countries) was conducted in 3 rounds. The proposals on which no consensus was reached were discussed in a conference meeting (June 2021). Participants voted on 21 proposals with a 9-point scale (1-3 disagree, 4-6 neither agree nor disagree, 7-9 agree) and were recruited through the Skin Inflammation and Psoriasis International Network and European Academy of Dermatology and Venereology in June 2020. Apart from being a dermatologist/dermatology resident, there were no specific criteria for participation in the survey. The participants worked mainly at a university hospital (97 [53.9%]) and were experienced in treating patients with psoriasis with methotrexate (163 [91.6%] had more than 10 years of experience)., Main Outcomes and Measures: In a survey with eDelphi procedure, we tried to reach consensus on 21 proposals. Consensus was defined as less than 15% voting disagree (1-3). For the consensus meeting, consensus was defined as less than 30% voting disagree., Results: Of 251 participants, 180 (71.7%) completed all 3 survey rounds, and 58 participants (23.1%) joined the conference meeting. Consensus was achieved on 11 proposals in round 1, 3 proposals in round 2, and 2 proposals in round 3. In the consensus meeting, consensus was achieved on 4 proposals. More research is needed, especially for the proposals on folic acid and the dosing of methotrexate for treating subpopulations such as children and vulnerable patients., Conclusions and Relevance: In this eDelphi consensus study, consensus was reached on 20 of 21 proposals involving methotrexate dosing in patients with psoriasis. This consensus may potentially be used to harmonize the treatment with methotrexate in patients with psoriasis.

Background: Psoriatic patients who are actively receiving biologic treatment have protocols in place to achieve optimal immunity. Inactivated vaccines are safe to use during biological treatment, without interruption. Conversely, live vaccines are used with caution and likely interruption of treatment. Given the novel coronavirus (SARS-CoV-2), nation-wide administration of vaccinations is underway., Objective: This survey gathered information on the level of education psoriatic patients have concerning vaccinations., Methods: An electronic survey was sent to 661 patients suffering from psoriasis. Patients originated from a single solo-practitioner community-based dermatology practice., Results: The average percentage of patients who understand the difference between live and inactivated vaccines between the control and study group was 36.6%. The average response to not knowing the difference between the vaccines was 36.6% and 26.6% were "unsure." When asked if it was possible to receive inactivated vaccines while on a biologic, the mass response amidst the control and study group was "unsure" (66.9%)., Conclusion: This questionnaire demonstrates that there is a need for supplementary education about vaccines for psoriatic patients on a biologic. Physicians will need to counsel their patients on the use of potential vaccines for SARS-Cov2 while on biologics.

Background: Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A. This study investigated the efficacy and safety of bimekizumab in patients with moderate to severe plaque psoriasis, the effects of treatment withdrawal, and two maintenance dosing schedules over 56 weeks., Methods: BE READY was a phase 3, multicentre, randomised, double-blind, placebo-controlled trial done at 77 sites (hospitals, clinics, private doctor's practices, and dedicated clinical research centres) in nine countries across Asia, Australia, Europe, and North America. Adult patients aged 18 years or older with moderate to severe plaque psoriasis were stratified by region and previous biologic exposure, and randomly assigned (4:1) to receive bimekizumab 320 mg every 4 weeks or placebo every 4 weeks by use of interactive response technology. Coprimary endpoints were the proportion of patients achieving 90% or greater improvement from baseline in the Psoriasis Area Severity Index (PASI90) and the proportion of patients achieving a score of 0 (clear) or 1 (almost clear) on the five-point Investigator's Global Assessment (IGA) scale at week 16 (non-responder imputation). Bimekizumab-treated patients achieving PASI90 at week 16 were re-allocated (1:1:1) to receive bimekizumab 320 mg every 4 weeks, every 8 weeks, or placebo for weeks 16-56. Efficacy analyses were done in the intention-to-treat population; the safety analysis set comprised all patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov (NCT03410992), and is now completed., Findings: Between Feb 5, 2018, and Jan 7, 2020, 435 patients were randomly assigned to receive either bimekizumab 320 mg every 4 weeks (n=349) or placebo every 4 weeks (n=86). Coprimary endpoints were met: at week 16, 317 (91%) of 349 patients receiving bimekizumab 320 mg every 4 weeks achieved PASI90, compared with one (1%) of 86 patients receiving placebo (risk difference 89·8 [95% CI 86·1-93·4]; p<0·0001); and 323 (93%) of 349 patients receiving bimekizumab 320 mg every 4 weeks achieved an IGA score of 0 or 1 versus one (1%) of 86 patients receiving placebo (risk difference 91·5 [95% CI 88·0-94·9]; p<0·0001). Responses were maintained through to week 56 with bimekizumab 320 mg every 8 weeks and every 4 weeks. Treatment-emergent adverse events in the initial treatment period (up to week 16) were reported in 213 (61%) of 349 patients receiving bimekizumab 320 mg every 4 weeks and 35 (41%) of 86 patients receiving placebo every 4 weeks. From week 16 to week 56, treatment-emergent adverse events were reported in 78 (74%) of 106 patients receiving bimekizumab 320 mg every 4 weeks, 77 (77%) of 100 patients receiving bimekizumab 320 mg every 8 weeks, and 72 (69%) of 105 patients receiving placebo., Interpretation: Bimekizumab showed high levels of response, which were durable over 56 weeks, with both maintenance dosing schedules (every 4 weeks and every 8 weeks). Moreover, bimekizumab was well tolerated, with no unexpected safety findings. Data presented here further support the therapeutic value of bimekizumab and inhibition of IL-17F in addition to IL-17A for patients with moderate to severe plaque psoriasis., Funding: UCB Pharma., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Biologic drugs are increasingly being prescribed for the treatment of psoriasis. Very little information is available in the literature regarding potential drug interactions with these medications. This paper serves as a guide for prescribers to be aware of possible interactions between biologic drugs approved for the treatment of psoriasis in North America and concomitant therapies., Objective: To provide an overview of reported drug interactions between biologic drugs and concomitant therapies., Methods: Reports of potential drug interactions were compiled through a search of Micromedex, drug monographs (Canadian, American, and European), as well as a PubMed search of each biologic drug with the term "drug interaction.", Conclusion: Generally, caution should be exercised when multiple immunosuppressive therapies are prescribed due to increased risk of infection. However, this is more the result of a synergistic effect as opposed to a true drug interaction. There have been cases where multiple biologic therapies have been concomitantly used without adverse events, as their mechanisms involved different pathways. The sources used to compile this guide were often comprised of low levels of evidence, reinforcing the idea that further studies are required to better direct prescribers.

Background: The systemic effects and comorbidities of psoriasis include ocular disorders, such as uveitis. Patients with psoriatic arthritis in particular have been demonstrated to have an elevated risk for developing uveitis. Presently, the risk of uveitis in psoriasis has yet to be fully elucidated and this systematic review seeks to address this gap., Objective: To examine the prevalence and incidence of uveitis in psoriasis patients compared to non-psoriasis patients., Methods: We conducted a systematic review search on MEDLINE, Embase, and CENTRAL electronic databases with no lower limit on year of publication., Results: Fourteen articles met our inclusion criteria, with a total of 234 143 psoriasis subjects. Two studies found that participants with severe psoriasis were at a greater risk of uveitis than those with mild psoriasis. A random-effects meta-analysis of the 3 studies, which reported risk of incidence of uveitis in psoriasis patients compared to non-psoriasis controls, found a pooled risk ratio of 1.29 (95% CI, 1.10-1.51), indicating an increased risk of uveitis in psoriasis. Three studies compared risk of uveitis in psoriatic arthritis with psoriasis-only participants, all finding that psoriatic arthritis was associated with a greater risk of uveitis., Conclusions: In summary, our findings suggest that psoriasis is associated with an increased risk of uveitis, with or without psoriatic arthritis.

Background: Plaque psoriasis (PsO) is a chronic inflammatory disease that often presents at peak reproductive age in women of child-bearing potential (WOCBP). With the emergence of biologic therapies to treat PsO, guidance on disease management in WOCBP is needed to inform treatment decisions before, during, and after pregnancy., Objectives: To develop a practical, up-to-date consensus document, based on available evidence and expert opinion where evidence was lacking, in order to guide both Canadian and international clinicians treating PsO in WOCBP., Methods: A panel of 9 Canadian dermatologists with extensive clinical experience managing PsO reviewed the relevant literature from the past 25 years in 3 key domains: overview of PsO in WOCBP and clinical considerations, treatment considerations, and postpartum considerations. The structured literature search focused on WOCBP treated with TNF-alpha inhibitors (adalimumab, certolizumab, etanercept, golimumab, infliximab), IL-23 inhibitors (guselkumab, risankizumab, tildrakizumab), IL-12/23 inhibitors (ustekinumab), and IL-17 inhibitors (brodalumab, ixekizumab, secukinumab). This literature review, along with clinical expertise and opinion, was used to develop concise and clinically relevant consensus statements to guide practical management of PsO in WOCBP. Experts voted on the statements using a modified Delphi process and prespecified agreement cut-off of 75%., Results and Implications: After review, discussion, and voting on 19 draft consensus statements at an in-person meeting and remotely, 12 consensus statements were approved by the expert panel. The statements presented here will guide healthcare providers in practical disease management using biologic therapies for the treatment of PsO in WOCBP.

Background: Despite the complexity of psoriasis treatment using biologic therapy, there does not exist a standardized synoptic reporting form for the initiation of this population. The purpose of this study was to use a modified Delphi approach to develop a standard checklist for the standardized documentation of patients receiving systemic biologic therapy for psoriasis., Methods: A modified Delphi survey was conducted over 3 rounds (February 2017 through January 2018). An expert panel generated a 51-item checklist that was proposed to participants. Items were rated on an anchored 1-7 Likert scale. Consensus was defined apriori as ≥ 70% agreement by respondents., Results: A total of 58, 17, and 18 dermatologists participated in 3 consecutive Delphi rounds, respectively. Only half of the dermatologists surveyed reported using a checklist for the management of psoriasis. The final checklist comprised 19, 5, 6, and 9 items pertaining to patient history; physical exam and history of systemic therapy; vaccinations; and lab investigations and bloodwork, respectively., Conclusions: Given the increasing availability and complexity of biologic agents for psoriasis treatment, there is a need to promote standardized documentation for this population. The Checklist for the Systemic Treatment of Psoriasis presents 38 items that should be considered when initiating patients with psoriasis on biologic therapy.

Background: Patients with psoriasis of all severities employ topical treatment, either alone or in combination. Promoting Patient Engagement at the Leading Edge of Topical Psoriasis Treatment (PROPEL) surveyed Canadian dermatologists and their patients about their attitudes toward topical care., Objectives: To identify gaps between patients and dermatologists regarding the burden of psoriasis, the burden of treatment, and priorities for topical care to Canadian patients with psoriasis., Methods: Two parallel surveys explored patient attitudes toward psoriasis and their experience with topical care, as expressed by patients or as perceived by their dermatologists. A third survey, addressed to patients, included additional questions regarding treatment adherence to current topical treatment regimens., Results: PROPEL dermatologists underestimated the burden associated with psoriatic itch. Otherwise, they were well aligned with patients' views, including their preference for maintaining topical care of their psoriasis over other treatment modalities, the nature of good psoriasis control, and desirable features of topical medications. Despite holding generally positive views of topical therapy, many patients self-identified as poorly adherent., Conclusions: Long-term adherence to psoriasis topical care remains a challenge. Formulations with improved acceptability might help patients maintain good adherence.

Objective: To develop preliminary treat-to-target (T2T) recommendations for psoriasis and psoriatic arthritis (PsA) for Canadian daily practice., Methods: A task force composed of expert Canadian dermatologists and rheumatologists performed a needs assessment among Canadian clinicians treating these diseases as well as an extensive literature search on the outcome measures used in clinical trials and practice., Results: Based on results from the needs assessment and literature search, the task force established 5 overarching principles and developed 8 preliminary T2T recommendations., Conclusion: The proposed recommendations should improve management of psoriasis and PsA in Canadian daily practice. However, these recommendations must be further validated in a real-world observational study to ensure that their use leads to better longterm outcomes.

Background: Secukinumab demonstrated superior efficacy to ustekinumab at week 4 and week 16 of the CLEAR study, with comparable safety, in subjects with moderate-to-severe plaque psoriasis., Objective: To compare the efficacy and safety of secukinumab and ustekinumab use over 52 weeks., Methods: Analysis of 52-week data from CLEAR, a randomized, double-blind, phase 3b study., Results: Among 676 randomized subjects, secukinumab demonstrated superiority to ustekinumab at week 52 in the proportion of subjects with ≥90% improvement in Psoriasis Area and Severity Index (PASI 90) (76% vs 61% [P < .0001]); PASI 100 responses were 46% versus 36% (P = .0103) and Investigator's Global Assessment responses of clear/almost clear skin were 80% versus 65% (P < .0001). Subjects on secukinumab reported greater reductions in psoriasis-related pain, itching, and scaling, and greater improvement across all quality-of-life measures evaluated (Dermatology Life Quality Index [DLQI], EuroQoL 5-Dimension Health Questionnaire, Work Productivity and Activity Impairment Questionnaire-Psoriasis, and Health Assessment Questionnaire-Disability Index). At week 52, 72% of subjects on secukinumab versus 59% on ustekinumab (P = .0008) reported no impact of skin disease on their lives (DLQI 0/1 response). Safety and tolerability was comparable., Limitations: There was no placebo arm., Conclusion: In this head-to-head, double-blind study, secukinumab demonstrated sustained superior efficacy in comparison with ustekinumab in clearing skin through week 52, greater improvement in quality of life, and a favorable and comparable safety profile., (Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Biologics have changed the way we treat moderate to severe psoriasis. Clinical trials for these patients offer the chance for those suffering from psoriasis to volunteer their time for the advancement of science while possibly gaining benefit from the efficacy of these medications.
, Objective: All clinical trials have an ending by study design. In the past, trials ended abruptly but it is more common now for transitioning to the approved or another biologic to be offered. Sometimes, study subjects leave clinical trials suddenly for reasons of lack of efficacy, safety, withdrawing consent, being lost to follow-up, or personal reasons. Presenting early experience in transitioning is important for clinicians.
, Methods: A retrospective case series of 11 patients who were exposed to brodalumab from clinical trials that ended abruptly and transitioned to secukinumab is presented.
, Results: This is an early descriptive experience of transitioning between two IL-17 antagonists.
, Limitations: A small number of patients were available and a short follow up limited the data presented.
, Conclusion: Transitioning between two IL-17 antagonists is an option for those patients requiring such a change.

J Drugs Dermatol. 2016;15(8):941-943.

Occasionally, psoriatic nail changes are seen in psoriatic patients. The prevalence of psoriasis of the nails has been reported to range from 15% to 79%. Even with effective systemic treatment for psoriasis, the nails may not improve, and these nails are considered nonresponsive psoriatic nails. Psoriatic nails are rarely investigated, and it is assumed that the nail changes are simply attributed to psoriasis because of their clinical similarity. Even patients with nails unresponsive to systemic treatment, or psoriasis treated topically or with phototherapy, onychomycosis is often forgotten, and patients may be left with both onychomycosis and psoriasis or onychomycosis alone. A retrospective chart review of 361 patients was carried out. The investigators report the prevalence of psoriasis and onychomycosis as less than 1%. A new term, "psoronychomycosis," is suggested to denote the rare combination of psoriasis and onychomycosis., (© The Author(s) 2016.)

Background: Cupping therapy is a traditional Chinese medicine used to heal psoriasis. The Koebner phenomenon is the occurrence of psoriatic lesions at the site of cutaneous injury., Objective: To describe the first case of biopsy-proven cupping-induced localized psoriasis, an example of the Koebner phenomenon., Methods: The histopathology of the lesions is described. A brief review of the literature regarding cupping therapy and its efficacy are discussed., Results: A 45-year-old Asian male presented himself to the dermatology clinic for further treatment of his psoriasis. Four unusually circular plaques on the lower back were discovered. Pathologic diagnosis revealed an early lesion of psoriasis. on further inquiry, the patient admitted to undergoing a recent "cupping" procedure in an attempt to cure his condition., Conclusion: The efficacy of cupping therapy is controversial, and psoriatic patients may develop localized psoriasis through koebnerization as a result of cupping therapy rather than achieve desirable therapeutic benefits., (© 2014 Canadian Dermatology Association.)

Objective: Explore the feasibility of Treat to Target in the area of psoriasis as seen in other therapeutic areas such as hypertension, hyperlipidemia, diabetes and rheumatoid arthritis., Methods: Review validated, measurable targets for psoriasis, including physician global assessment (PGA), psoriasis area and severity index (PASI) and dermatology life quality index (DLQI). Examine principles brought forth in the published European consensus on psoriasis and develop a Canadian consensus on Treat to Target in psoriasis., Results: As PASI and DLQI are not routinely used in the community setting, we are recommending target at a PGA of zero (clear)., Conclusion: Recommend that the target is a PGA of zero (clear) as it provides a simple and measurable result that the patient and physician can clearly understand., (© 2014 Canadian Dermatology Association.)

Molecular and cellular understanding of psoriasis pathogenesis has evolved considerably over the last 30 years beginning in the early 1980s when psoriasis was thought to be a skin disease driven by keratinocyte hyperproliferation. During the next 20 years, the role of the immune system and T-helper (Th) cells in psoriasis pathogenesis was recognized. The presence of the interleukin (IL)-12 cytokine in psoriatic lesions led to the postulate that psoriasis is mediated by Th1 cells. Recent evidence has revealed a role for Th17 cells, and other immune cells, as proximal regulators of psoriatic skin inflammation. IL-17A, the principal effector cytokine of Th17 cells, stimulates keratinocytes to produce chemokines, cytokines, and other proinflammatory mediators thereby enabling IL-17A to bridge the innate and adaptive immune systems to sustain chronic inflammation. This model underlies the rationale for inhibiting IL-17A signaling as a potential therapeutic approach to disrupt the psoriatic inflammatory loop. Several monoclonal antibodies that inhibit the IL-17 pathway are in clinical development. These agents exhibit promising clinical efficacy and tolerability profiles including immunohistochemical improvement in psoriatic plaques. Results from clinical trials with IL-17 pathway inhibitors are refining our understanding of psoriasis pathogenesis and may provide a new therapeutic approach for patients with moderate to severe psoriasis., (Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Background: Little is known about the impact of long-term use of immunosuppressive agents on immune response., Objectives: Assess the impact of continuous maintenance ustekinumab treatment on patients' ability to mount immune responses to pneumococcal (T-cell-independent) and tetanus toxoid (T-cell-dependent) vaccines., Patients and Methods: Ustekinumab-treated patients with moderate-to-severe psoriasis treated in the long-term extension of the Phase 3 PHOENIX 2 trial (n=60) were compared with control psoriasis patients not receiving systemic therapy (n=56). Patients were vaccinated with both 23-valent pneumococcal and tetanus toxoid vaccines. Serum samples collected pre-vaccination and 4 weeks post-vaccination were assessed for antibody responses., Results: No differences in the ability of ustekinumab-treated patients to respond to pneumococcal or tetanus toxoid vaccinations were observed compared with controls. A ≥2-fold increase in antibody levels in ≥7 of 14 serotypes of the pneumococcal vaccine was observed in ustekinumab-treated (96.6%) and untreated control (92.6%) patients following vaccination. Ustekinumab-treated patients achieved a ≥4-fold increase (84.7%) in anti-tetanus antibody vs. 77.8% in the control group. No differences were detected in ex-vivo responses to anti-CD3/CD28 or tetanus toxoid between ustekinumab-treated and control groups., Conclusion: Long-term treatment (≥3 years) with ustekinumab does not compromise the immune response to T-cell-dependent/-independent vaccines in patients with moderate-to-severe psoriasis.

Background: Although etanercept is well tolerated and effective in moderate-to-severe plaque psoriasis, data are limited in Canadian practice settings., Objective: To assess the effectiveness and safety of etanercept in Canadian patients with moderate-to-severe plaque psoriasis (Physician Global Assessment [PGA] ≥ 3) in routine practice., Methods: A 1-year, multicenter, open-label trial of 246 patients enrolled from March 2006 to July 2009 was conducted. Patients received etanercept 50 mg subcutaneously twice weekly for 3 months and then 50 mg once weekly for 9 months. The primary end point was the proportion of patients achieving a PGA score ≤ 2 at month 12. Secondary end points included the proportion of patients achieving PGA score ≤ 2 at months 3, 6, and 9 and change from baseline at month 12 for Patient Global Assessment (PtGA), body surface area, and Dermatology Life Quality Index (DLQI). Adverse events were reported., Results: At month 12, 73.5% (95% CI 67.2-79.1) achieved a PGA score ≤ 2. The response was similar regardless of the previous response to systemic or phototherapy. The proportion of patients achieving this score improved from 2.2% (95% CI 0.3-4.2) at baseline to 73.5% (95% CI 67.2-79.1) at 12 months. At 12 months, patients with a DLQI score of 0 or ≥ 5-point improvement was 28.8% (95% CI 22.9-34.7) and 47.3% (95% CI 40.8-53.9), respectively. No new safety signals were reported., Conclusion: The majority of this Canadian population demonstrated a meaningful improvement in PGA and DLQI scores over 1 year.

Background: Data investigating the effect of etanercept on work productivity and healthcare resource utilization in Canadian patients in a clinical setting is limited., Objective: The aim of the study was to describe work productivity and healthcare resource utilization in patients with psoriasis prescribed etanercept., Methods: A 12-month, phase IV, non-randomized, multicentre, open-label, single-arm prospective trial of patients with moderate-to-severe plaque psoriasis was conducted between March 2006 and July 2009 in 37 community dermatology practice sites across Canada. A total of 246 patients were enrolled. Major eligibility criteria: ≥18 years of age; diagnosis of moderate-to-severe plaque psoriasis at baseline (Physician Global Assessment [PGA] ≥3, scale 0-5); able to start etanercept therapy as per product monograph. Patients received etanercept (Enbrel(®)) 50 mg subcutaneously twice weekly for 3 months, then 50 mg once weekly for 9 months. Outcomes were measured by average change and average percent change from baseline at months 3, 6, 9 and 12 on the Work Productivity and Activity Impairment (WPAI) and Healthcare Resource Utilization (HRU) questionnaires., Results: The mean degree of impairment while working ± standard deviation (SD) in the total population decreased from 22.7% ± 23.2 at baseline to 6.6% ± 14 after 3 months of treatment (p < 0.0001). From baseline to 3 months, overall work impairment ± SD decreased from 23.7% ± 23.7 to 8.3% ± 16.5 (p < 0.0001) and mean activity impairment outside the workplace decreased from 31.4% ± 26.4 to 12.9% ± 22.4 (p < 0.0001). All these improvements were sustained to month 12. Other variables that decreased on average from baseline to month 3, sustained to month 12, included physician office visits (2.3/month ± 3.5 at baseline to 0.6/month ± 1.0 at month 3; p < 0.0002), hours of assistance required of family and friends to assist with psoriasis (1.1 hours/week ± 2.6 at baseline to 0.3 hours/week ± 1.5 at month 3; p = 0.0002) and amount of time spent on activities to manage psoriasis (5.5 hours/week ± 6.2 at baseline to 1.9 hours/week ± 3.7 at month 3; p < 0.0001). Also, the amount of out-of-pocket expenses to manage psoriasis decreased from $Can94.9/month ± 331.6 at baseline to $Can35.7 ± 69.1 at month 12 (p = 0.0153)., Conclusions: Use of etanercept in Canadian patients in a clinical practice setting correlated with improvement in work productivity and reduced HRU after 3 months of treatment, and improvement was sustained up to 12 months.

Background: Although the range of therapeutic options has expanded dramatically in recent years, topical agents remain ubiquitous and indispensable tools for treating psoriasis at all levels of severity. The 2009 Canadian psoriasis guidelines considered evidence supporting various monotherapies and combination regimens., Objective: Here we review all approved topical agents, including corticosteroids, calcineurin inhibitors, vitamin D analogues, and retinoids, used in psoriasis and develop additional treatment recommendations, using the Scottish Intercollegiate Guidelines Network (SIGN) system to evaluate strength of evidence, as in the original guidelines., Conclusion: We propose that topical treatments have a place in the long-term management of patients with moderate to severe plaque psoriasis, including those receiving concomitant photo- or systemic therapy. Topical agents are effective and appropriate treatments for psoriasis as long as the physician is attentive to signs of local adverse events and seeks opportunities to reduce the dose or treatment frequency during chronic use.

Objective: To determine the efficacy, safety, and sustainability of response to adalimumab therapy for moderate to severe chronic plaque psoriasis involving hands and/or feet., Design: Sixteen-week, randomized, double-blind, placebo-controlled evaluation of adalimumab therapy for moderate to severe chronic plaque psoriasis involving the hands and/or feet with a 12-week open-label extension (Randomized Controlled Evaluation of Adalimumab in Treatment of Chronic Plaque Psoriasis of the Hands and Feet [REACH])., Setting: Multicenter outpatient study in the United States and Canada., Participants: Patients with chronic plaque psoriasis on the hands and/or feet with a Physician's Global Assessment of hands and/or feet (hfPGA) score of "moderate" or above., Intervention: Patients were randomized 2:1 to adalimumab (80 mg at week 0, then 40 mg every other week starting at week 1) or to matching placebo., Main Outcome Measure: Percentage of patients achieving an hfPGA score of "clear" or "almost clear" at week 16., Results: Seventy-two patients (adalimumab [n = 49];placebo [n = 23]) were evaluated. Baseline percentages of patients with moderate and severe hfPGA scores were 76% and 24%, respectively, for the adalimumab group and 74% and 26%, respectively, for the placebo group. At week 16, 31% and 4% of patients randomized to adalimumab and placebo, respectively, achieved an hfPGA score of clear or almost clear (P = .01). At week 28, 80% of the hfPGA clear or almost clear response was maintained from week 16 (25% for patients randomized to adalimumab). Adverse events in both groups were generally mild to moderate. In both periods combined, nasopharyngitis (27% and 13% for adalimumab- and placebo-treated patients, respectively) was most frequently reported., Conclusion: Adalimumab is efficacious and well tolerated for treatment of chronic plaque psoriasis of hands and/or feet, with efficacy largely maintained to 28 weeks. Trial Registration clinicaltrials.gov Identifier: NCT00735787.

Background: The past several years have seen the approval of five different biologic agents for the treatment of moderate to severe plaque psoriasis in the United States and Canada. Psoriasis has proven to be a difficult disease to treat and treatment failures, even with newer biologic therapies, are not uncommon. The vast majority of clinical data for these medications is derived from treatment of biologic-naive patients, or patients who have not responded to, or lost response to, or not tolerated systemic therapy for psoriasis. There is currently little data available on therapeutic response of a second biologic therapy after loss of response, or no response, to the first biologic therapy initiated. It has become common clinical practice to switch medications that are structurally distinct but therapeutically similar in order to achieve an improved clinical outcome. Therapeutic interchange now is being applied to the biologic agents used to treat psoriasis., Objectives: Using a proof of concept study, describe the response of etanercept after adalimumab has failed to produce a satisfactory response in moderate to severe plaque psoriasis., Methods: A total of 10 biologically naive patients with moderate to severe psoriasis who were initiated on adalimumab for at least 12 weeks but had a Physician's Global Assessment (PGA) of mild or worse were transitioned to commercial etanercept 50 mg twice weekly (BIW) for 12 weeks followed by a dose reduction to 50 mg once weekly (OW) for an additional 12 weeks. Ethics approval was obtained and the study registered with ClinicalTrials.gov (NCT00833729). The primary outcome measured was the mean change in Physician?s Global Assessment (PGA) score (range 0-5) from baseline (when the first etanercept injection is given) to 12 weeks of etanercept therapy. The secondary outcomes measures included the mean change in Dermatology Quality of Life Index (DLQI), mean change in body surface area (BSA) covered in psoriasis, Subject's Global Assessment of disease (SGA), proportion of patients achieving an improvement in PGA score from baseline to 12 weeks and again at 24 weeks and safety., Results: Overall, there were significant favorable changes in all outcomes measured (PGA, SGA, BSA and DLQI) with respect to etanercept's efficacy after an inadequate response to at least 12 weeks of adalimumab therapy. There were no significant safety issues noted especially during the transition period from adalimumab to etanercept. ClinicalTrials.gov identifier: NCT00833729.

Background: Quality of life assessments are important in the evaluation of new therapies for psoriasis., Objective: To determine the effect of voclosporin (VCS) treatment on quality of life in patients with psoriasis., Patients and Methods: 451 plaque psoriasis patients with ≥  10% body surface area involvement were randomly assigned in a double-blind fashion to 1 of 4 treatment groups (placebo, VCS 0.2 mg kg(-1) BID, VCS 0.3 mg kg(-1) BID, and VCS 0.4 mg kg(-1) BID) for up to 12 weeks of treatment. Quality of life was assessed using the Dermatology Life Quality Index (DLQI) and the Psoriasis Disability Index (PDI)., Results: At 12 weeks, patients treated with VCS 0.4 mg kg(-1) BID had statistically significantly more favourable assessments than placebo-treated patients in all domains of the DLQI and the PDI. Patients treated with VCS 0.3 mg kg(-1) BID had statistically significant improvements in 5 of 10 domains of the DLQI and all domains of the PDI. Patients treated with VCS 0.2 mg kg(-1) BID had statistically significant improvements in 4 of 10 domains of the DLQI and 2 of 4 domains of the PDI., Conclusion: Treatment with VCS 0.4 mg kg(-1) BID significantly improves the quality of life of patients with psoriasis.

Background: With recent advancements in the understanding of psoriasis, treatment has evolved toward more targeted therapy in the form of biologics. Although generally safe and well tolerated, various adverse reactions may occur with the use of biologics., Objectives: The objective of this article is to present a case of a biologic-induced drug eruption initially presenting with histopathologic features of mycosis fungoides (MF)., Methods and Results: A 47-year-old male presented with an extensive erythematous macular eruption approximately 14 hours after a single dose of etanercept. Histopathology initially revealed a lichenoid dermatitis with features of MF, but immunohistopathology later refuted the presence of MF., Conclusions: It is important for clinicians to be aware that adverse cutaneous reactions with biologic therapy may initially present with histopathologic features of MF.

Background: Alefacept has demonstrated efficacy in clinical trials of patients with chronic plaque psoriasis, either as monotherapy or combined with other treatment modalities such as phototherapy., Objective: AWARE (Amevive Wisdom Acquired from Real-World Evidence) is a multicenter, observational, phase IV Canadian registry of psoriasis patients treated with alefacept., Methods: Patients with chronic plaque psoriasis were treated with at least one course of alefacept, either alone or added on to their existing antipsoriatic treatment regimen. Each course of alefacept was followed by a period of at least 12 weeks off treatment. Efficacy outcomes included physicians' and patients' assessments of response at week 18, as well as change in percent body surface area (BSA) involvement with psoriasis. The time to retreatment was assessed in patients receiving a second course of alefacept during at least 60 weeks of prospective follow-up., Results: The majority of patients received alefacept in combination with other antipsoriatic therapies. Physicians' and patients' assessments of response at 18 weeks showed that 42% and 41% of patients, respectively, had a "cleared to marked response" and a further 42% had a "moderate to some response." Among those patients whose psoriasis was moderately controlled or not controlled at baseline, 49 to 51% and 33 to 36%, respectively, improved to "cleared to marked response" at 18 weeks. A substantial shift in percent BSA involvement with psoriasis was observed at 18 weeks, with 55% of patients having a BSA involvement of < 10% at week 18 compared to only 20% having this level of BSA involvement at baseline. The mean time to retreatment among the 60% of patients who received a second course of alefacept was 19.3 weeks (range 2-47 weeks)., Conclusion: A single course of alefacept therapy improved outcomes in this broad population of real-world chronic plaque psoriasis patients., Study Limitations: The limitations of this study include its nonrandomized, noncontrolled, noncomparative design, which allowed multiple different treatment approaches across all patients. The rating scales used in this study have not been previously validated, and ranges were assigned to baseline control and response data that are not specifically defined. Clinicians did not receive specific training in using these scales; therefore, interrater variability could not be assessed.

Background: Adalimumab, a fully human monoclonal antibody, binds to and neutralizes tumor necrosis factor., Objective: To provide an integrated review of efficacy and safety from adalimumab clinical trials in psoriasis., Methods: Pooled analyses were conducted of three placebo-controlled clinical trials of adalimumab (40 mg every other week) in psoriasis patients. The primary efficacy measure was the Psoriasis Area Severity Index (PASI). The Physician's Global Assessment (PGA) was also assessed., Results: At Week 16, mean percentage PASI improvement was 78.3% for adalimumab-treated patients versus 15.1% for placebo-treated patients. A PGA of "Clear" or "Minimal" was achieved in 63.4% of adalimumab-treated patients versus 5.1% of placebo-treated patients. The response to adalimumab was rapid, with significant improvements for adalimumab-treated patients in most efficacy measures by Week 4. Adverse event incidence was similar between treatment groups and consistent with adalimumab safety profiles in other indications., Conclusion: Adalimumab improved psoriasis and was generally safe and well-tolerated.

Background: The results of long-term studies on the efficacy and safety profiles of the biologics for patients with psoriasis are starting to appear in the literature. Not only are the results promising for the biologics as a whole, but the high number of patients remaining in these clinical trials after extended periods of time, or retention, may also reflect additional benefits of these biologics. The aim of this review was to manuscript aims to compare rates of attrition for the various biologic therapies in pivotal clinical trials in order to assess and compare adherence of patients to long-term use of the different biologic agents, also known as biologic survival., Methods: An in-depth literature review was conducted using PubMed and MEDLINE. Randomized, controlled trials utilizing biologic agents as monotherapy for the treatment of psoriasis were analyzed for patient numbers over time. Studies which provided data on patient retention for at least 24 weeks were selected, graphed, and compared. Reasons for discontinuation were noted., Results: Nineteen trials were selected, graphed and charted to compare attrition rates of the various biologic therapies. Due to differences in sample size, study design, dosing regimens, study duration and limited data with regards to patient numbers, it is difficult to reach a definitive conclusion as to which biologic agent is associated with the lowest rate of discontinuation. However, given the data available, etanercept appears to be the most successful therapy in terms of patient retention in studies both greater than and less than 30 weeks. For the studies using various dosing regimens, intrastudy attrition rates are also compared., Conclusion: While the data available thus far on patient retention for the biologic therapies are very limited, preliminary conclusions can be drawn. Among the available biologic agents, etanercept appears to be associated with the lowest rate of discontinuation. This may be due to greater superior effiacy and to a decreased likelihood of experiencing adverse events.