Search

Importance: Safe, effective, and well-tolerated topical treatment options available for long-term use in patients with atopic dermatitis (AD) are limited and associated with low adherence rates., Objective: To evaluate efficacy and safety of once-daily roflumilast cream, 0.15%, vs vehicle cream in patients with AD., Design, Setting, and Participants: Two phase 3, randomized, double-blind, vehicle-controlled trials (Interventional Trial Evaluating Roflumilast Cream for the Treatment of Atopic Dermatitis 1 and 2 [INTEGUMENT-1 and INTEGUMENT-2]), included patients from sites in the US, Canada, and Poland. Participants were 6 years or older with mild to moderate AD based on Validated Global Assessment for Atopic Dermatitis (assessed on a 5-point scale ranging from 0 [clear] to 4 [severe])., Intervention: Patients were randomized 2:1 to receive roflumilast cream, 0.15%, or vehicle cream once daily for 4 weeks., Main Outcomes and Measures: The primary efficacy end point was Validated Investigator Global Assessment for Atopic Dermatitis success at week 4, defined as a score of 0 or 1 plus at least a 2-grade improvement from baseline. Secondary end points included Eczema Area and Severity Index and Worst Itch Numeric Rating Scale. Safety and local tolerability were also evaluated., Results: Among 1337 patients (654 patients in INTEGUMENT-1 and 683 patients in INTEGUMENT-2), the mean (SD) age was 27.7 (19.2) years, and 761 participants (56.9%) were female. The mean body surface area involved was 13.6% (SD = 11.6%; range, 3.0% to 88.0%). Significantly more patients treated with roflumilast than vehicle achieved the primary end point (INTEGUMENT-1: 32.0% vs 15.2%, respectively; P < .001; INTEGUMENT-2: 28.9% vs 12.0%, respectively; P < .001). At week 4, statistically significant differences favoring roflumilast also occurred for the achievement of at least 75% reduction in the Eczema Area and Severity Index (INTEGUMENT-1: 43.2% vs 22.0%, respectively; P < .001; INTEGUMENT-2: 42.0% vs 19.7%, respectively; P < .001). Roflumilast was well tolerated with low rates of treatment-emergent adverse events. At each time point, investigators noted no signs of irritation at the application site in 885 patients who were treated with roflumilast (≥95%), and 885 patients who were treated with roflumilast (90%) reported no or mild sensation at the application site., Conclusions and Relevance: In 2 phase 3 trials enrolling adults and children, once-daily roflumilast cream, 0.15%, improved AD relative to vehicle cream, based on multiple efficacy end points, with favorable safety and tolerability., Trial Registration: ClinicalTrials.gov Identifiers: NCT04773587, NCT04773600.

Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: EYL has received speaker honorarium from Sanofi and AstraZeneca. IT: none. AWC: none. JB: none. RB is an advisory board member, consultant, speaker, and/or investigator for and receives honoraria and/or grant from AbbVie, Amgen, Arcutis, Asana BioSciences, Bellus Health, BioMimetix, Bluefin Biomedicine, Boehringer-Ingelheim, Boston, CARA Therapeutic, Clexio, Dermavant, Eli Lilly, Escient, Evidera, Fresh Tracks (Brickell), Galderma, GlaxoSmithKline, Incyte, Inmagene Bio, Janssen, LEO Pharma, Novartis, Opsidio, Pfizer, RAPT Therapeutic, Regeneron, Sanofi, Target RWE and Vyne Therapeutics. RB is also an employee and shareholder of Innovaderm Research. HC: none. ACM: none. MG has been an investigator, speaker, and/or advisor for: AbbVie, Amgen, Akros, Arcutis, Aristea, AnaptysBio, Apogee, Bausch Health, BMS, Boehringer Ingelheim, Celgene, Dermira, Dermavant, Eli Lilly, Galderma, GSK, Incyte, Janssen, Kyowa Kirin, LEO Pharma, MedImmune, Meiji, Merck, Moonlake, Nimbus, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Sun Pharma, Tarsus, Takeda, UCB, Union and Ventyx. NH was on the advisory board/ round table honoraria for L’Oreal, Abbvie, Leo, Sun, Eucerin, Lilly, J&J, Arcutis, Sanofi, and Regeneron. HCHH has been an investigator for and/or speaker for and/or received honoraria from the following companies: Abbvie, Amgen, Arcutis, Bausch Health, Boehringer-Ingelheim, Bristol Meyers Squibb, Celgene, Cutanea, Dermira, Dermavant, DS Biopharma, Eli Lilly, Galderma, GSK, Incyte, Janssen, Leo Pharma, Medimmune, Merck, Mirimar, Novartis, Pfizer, Regeneron, Sanofi-Genzyme, Roche, and UCB. NJL: none. JALM: none. RM: none. KP received honoraria from AbbVie, Acelyrin, Akros, Amgen, Aralez Pharmaceuticals, Bausch Health/Valeant, Boehringer Ingelheim Celgene, Celltrion, Coherus, Dermavant, Dice Pharmaceuticals, Eli Lilly, Forbion, Galderma, Janssen, Kyowa Hakko Kirin, Leo, Meiji Seika Pharma, Merck (MSD), Mitsubishi Pharma, Novartis, Pfizer, Reistone, Sanofi-Aventis/Genzyme, Sandoz, Sun Pharma, Takeda, UCB, and vTv Therapeutics. KP received clinical research grants from AbbVie, Akros, Amgen, Anacor, Arcutis, Avillion, Bausch Health/Valeant, Boehringer Ingelheim, Bristol-Myers Squibb, Can-Fite Biopharma, Celgene, Coherus, CorEvitas, Dermavant, Dermira, Dow Pharma, Eli Lilly, Evelo, Galderma, Gilead, GSK, Incyte, Janssen, Kyowa Hakko Kirin, Leo, Merek (MSD), Novartis, Pfizer, Regeneron, Roche, Sanofi-Aventis/Genzyme, Sun Pharma, Takeda, and UCB. AMD has received compensation from the British Journal of Dermatology (reviewer and Section Editor), American Academy of Dermatology (guidelines writer), National Eczema Association (grant reviewer), Canadian Dermatology Today (manuscript writer), and Canadian Agency for Drugs and Technologies in Health (consultant). Dr Drucker has received research grants to his institution from the National Eczema Association, Eczema Society of Canada, Canadian Dermatology Foundation, Canadian Institutes for Health Research, US National Institutes of Health, and Physicians Services Incorporated Foundation.

Secukinumab is a fully human IgG1 antibody that selectively binds to and neutralizes the proinflammatory cytokine interleukin-17A. Secukinumab is an effective and well-tolerated treatment for plaque psoriasis. There is a limited real-word evidence for dose optimisation of secukinumab based on clinical response. PURE is a multi-national, prospective, observational study in patients with moderate to severe chronic plaque psoriasis in Canada and Latin America, assessing the real-world safety and effectiveness of secukinumab and other indicated therapies. The aim of the current snapshot analysis was to evaluate the effectiveness and safety of on-label dose and updosed secukinumab in patients with plaque psoriasis enrolled in the PURE study. At the time of analysis, 676 patients received secukinumab, of which 84.6% (n = 572) remained on the on-label dose, while 15.4% (n = 104) were updosed. With on-label secukinumab, the absolute Psoriasis Area and Severity Index (PASI) score was reduced from 13.6 at baseline to 1.2 over 36 months, with treatment persistence of 73% at 40 months. At Month 36, 73.2% of the patients receiving on-label secukinumab achieved Investigator's Global Assessment (IGA) 0/1. With updosed secukinumab (300 mg every 2 weeks, 300 mg every 3 weeks, 450 mg every 4 weeks, or 450 mg every 3 weeks), 57.9% of the patients showed improvement in the absolute PASI score at the first visit after updosing, with treatment persistence of 50% at 12 months after updosing. At Month 15, 40% of patients receiving updosed secukinumab achieved IGA 0/1. Patients with previous biologic exposure (odds ratio [OR]: 3.25; 95% confidence interval [CI]: 2.03, 5.18, p < 0.0001) were more likely to be updosed while those with a body weight < 90 kg (OR: 0.49; 95% CI [0.31, 0.77], p = 0.0019) were less likely to be updosed. Previous biologic exposure (HR [hazard ratio]: 1.47; 95% CI [1.24, 1.75], p < 0.0001) and current biologic exposure (secukinumab vs. other indicated therapies: HR 0.57; 95% CI [0.43, 0.75], p = 0.0001) were significantly associated with time to secukinumab updosing. No new or unexpected safety signals were observed with updosed secukinumab. Secukinumab updosing was efficacious and well-tolerated in patients with psoriasis who failed to respond to the approved on-label regimen, suggesting that updosing may be a useful therapeutic option for approved dose non-responders., (© 2024. The Author(s).)

Background: Psoriasis is commonly classified as either mild or moderate to severe, without specific parameters to differentiate moderate versus severe disease. This may lead to patients with moderate psoriasis being underrecognized and undertreated., Objective: An online survey was conducted to assess Canadian dermatologists&rsquo; perspectives on the definition and treatment of psoriasis., Method: Dermatologists included in the survey were regional and national leaders with expertise in psoriasis. Questions were developed based on feedback from a steering committee of Canadian dermatologists., Results: Of 88 dermatologists contacted, 69 responded; 42.0% were in practice for &gt;20 years. Most dermatologists reported using the percentage of psoriasis-affected body surface area (BSA) to describe disease severity (90.8% for moderate and 87.5% for severe psoriasis). The lower and upper median cutoffs for moderate psoriasis were reported as 5.0% and 10.0% for BSA and 7.0 and 11.5 for the Dermatology Life Quality Index. Most dermatologists also consider psoriasis location (eg, palms, scalp, genital area, face) as an important indicator of disease severity. The majority of Canadian dermatologists (87.5%) identified access to treatment as one of the biggest challenges for patients with moderate psoriasis. Most dermatologists estimated that &le;40% of their patients with moderate plaque psoriasis were being treated with traditional oral systemics, targeted oral systemics, or biologics., Conclusions: This is the first survey of Canadian dermatologists on moderate psoriasis. Efforts are needed to implement a clinically useful definition of moderate plaque psoriasis to improve patient care and to raise awareness of the definition among regulatory agencies and reimbursement authorities. J Drugs Dermatol. 2021;20(2):126-132. doi:10.36849/JDD.5531.

The interleukin (IL)-17 inhibitors have proven to be highly effective in the treatment of psoriasis. The most recently approved agent, brodalumab, had few cases of suicidal behavior, including completed suicide, in the phase 3 clinical program leading both the US FDA and Health Canada to add a boxed warning to its label. This raises the importance of identifying the psychiatric comorbidities associated with psoriasis. It is also necessary to critically examine the data from the brodalumab clinical trial program to determine whether there is enough information to establish causality and whether other factors, other than the drug, could be playing a role., Competing Interests: Fabian Rodriguez-Bolanos has no conflicts of interest. Melinda Gooderham and Kim Papp have been an investigator, speaker, advisory board member and consultant for Valeant Pharmaceuticals.

The use of immunosuppressive therapies for immune-mediated disease is associated with an elevated risk of infections and related comorbidities. While many infectious diseases can generally be prevented by vaccines, immunization rates in this specific patient population remain suboptimal, due in part to uncertainty about their efficacy or safety under these clinical situations. To address this concern, a multidisciplinary group of Canadian physicians with expertise in dermatology, gastroenterology, infectious diseases, and rheumatology developed evidence-based clinical guidelines on vaccinations featuring 13 statements that are aimed at reducing the risk of preventable infections in individuals exposed to immunosuppressive and immunomodulatory agents.

Background: Treatment options for the management of moderate to severe plaque psoriasis include phototherapy, oral systemic agents, and biologic therapy. Secukinumab, a fully human monoclonal antibody that selectively targets IL-17A, is the first IL-17 antagonist approved for this patient population. Long-term observational data are required for establishing the true population-based benefit-risk ratio of approved treatments. PURE is a multinational registry that will assess the real-world safety and effectiveness of secukinumab and other approved therapies in the management of patients with moderate to severe psoriasis., Methods: This is a multinational (Canadian and Latin American), prospective, observational study of adult patients with moderate to severe psoriasis that initiate treatment with secukinumab or other approved therapies as per local standard of care. A total of 2500 patients (1250 per cohort) will be recruited in the practices of hospital and community dermatologists. Decision regarding treatment must have been reached prior to and independent of patient enrollment in the study. The study includes a 5-year follow-up with recommended assessments at Baseline, 3 and 6 months post-Baseline, and every 6 months thereafter. The primary objective of the study is safety. Secondary outcome measures relate to effectiveness (Investigator's Global Assessment -IGA mod 2011-, Psoriasis Areas and Severity Index, Body Surface Area), patient reported outcomes (Dermatology Life Quality Index, Work Productivity and Activity Impairment Questionnaire, Hospital Anxiety and Depression Scale, Psoriasis Epidemiology Screening Tool, Psoriasis Symptom Diary, and Treatment Satisfaction Questionnaire), and healthcare resource utilization., Discussion: This is the first observational study in Canada and Latin America assessing the real-world safety and effectiveness of secukinumab in the management of moderate to severe psoriasis. The extensive clinical, patient-reported and health economic outcomes collected will allow the comprehensive evaluation of this new treatment in comparison to other approved therapies., Trial Registration: ClinicalTrials.gov Identifier: NCT02786186 ; date of registration: May 30, 2016.

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.

Summary: Tildrakizumab is a fairly new type of medicine called a biologic, used for the treatment of moderate‐to‐severe psoriasis. The drug prevents the action of a specific molecule in the body involved in inflammation, known as cytokine interleukin (IL)‐23p19. Previous studies have shown it to be superior to a placebo (an inactive substance, like a "sugar pill") and to an older biologic drug, the TNF inhibitor etanercept. However, trials rarely reflect real‐world experience, where patients may switch from one drug to another, change drug dosage or interrupt treatment, e.g. because of an infection. The authors, based in U.S.A., Canada and Germany, reviewed results from two studies, one comparing two different doses of tildrakizumab (100mg or 200mg per day) with placebo, and the other comparing it with etanercept, including a total of 1862 adults with moderate‐to‐severe plaque psoriasis. Treatments were re‐randomised during the course of the study. They found that the response to tildrakizumab was sustained (meaning it kept working), without the secondary failure (decreasing responsiveness to a drug after an initial satisfactory response) seen in some patients on etanercept, and the drug regained effective control of the psoriasis after treatment was interrupted. Overall the drug was well tolerated, meaning that side effects were minimal. This is a summary of the study: Efficacy and safety of tildrakizumab for plaque psoriasis with continuous dosing, treatment interruption, dose adjustments and switching from etanercept: results from phase III studies Linked Article: Kimball et al. Br J Dermatol 2020; 182:1359–1368 [ABSTRACT FROM AUTHOR]

Introduction: An expert panel of Canadian dermatologists was assembled to develop consensus statements regarding the current landscape of topical therapies for plaque psoriasis and the place in therapy of the recently approved fixed-dose combination halobetasol propionate (HP)/tazarotene (TAZ) lotion (HP/TAZ) in the treatment algorithm for plaque psoriasis. Method: A modified nominal group technique, which combined both independent and group input from the expert panel, was used to develop the consensus statements. The expert panel completed surveys to elicit their independent views on the current landscape of topical therapies for plaque psoriasis in Canada. The first expert panel session was held to discuss the existing body of literature and develop draft consensus statements about topical therapies and the place in therapy of HP/TAZ. Independent feedback on the draft consensus statements was solicited from expert panel members prior to another expert panel session where the amended consensus statements were further discussed, edited and, finally, voted on. Results: The expert panel reached consensus on 20 statements. Conclusion: Expert panel members agreed, based on the existing body of literature, that there is a place in therapy for HP/TAZ to address several current unmet treatment needs of patients with plaque psoriasis. Studies have shown that HP/TAZ is an effective and safe first-line treatment for moderate-to-severe plaque psoriasis. Due to its cosmetically pleasing vehicle and once-daily administration, HP/TAZ may improve patient acceptance and treatment adherence. [ABSTRACT FROM AUTHOR]

Introduction: The association between physician-reported and patient-reported outcomes in patients with psoriasis is not adequately explored. Trends in PASI scores across body regions and the descriptive correspondence between physician-reported PASI components and patient-reported Psoriasis Symptom Diary are reported here. Methods: PURE is a prospective observational study in adult patients from Canada and Latin America with moderate-to-severe chronic plaque psoriasis. The study enrolled 2362 adult patients treated with secukinumab versus other approved therapies (1:1 ratio). The PASI total score, PASI sub-scores for erythema, thickening, and scaling, and PASI scores for each body region were evaluated and further correlated with disease impact using the Psoriasis Symptom Diary. Results: Secukinumab treatment showed early reduction in the PASI total score (mean ± SD) from 13.3 ± 9.02 at baseline to 2.3 ± 3.99 at 3 months; a similar trend was observed for PASI sub-scores for erythema (4.8 ± 3.21 to 0.9 ± 1.44), thickening (4.3 ± 3.00 to 0.7 ± 1.33) and scaling (4.2 ± 3.04 to 0.7 ± 1.30). The reduction in PASI total and sub-scores were sustained up to 36 months. Psoriasis Symptom Diary component scores related to redness, cracking, and scaling showed a similar reduction from baseline at 3 months that was also sustained up to 36 months. PASI regional scores for each body region showed reduction at 3 months with disease in the lower limbs being more treatment resistant. Safety profile of secukinumab was consistent with its established safety profile without any new or unexpected signals. Conclusions: Overall, an early and sustained resolution of erythema, thickening, and scaling was observed. Improvements were evident across all body regions, with the most persistent disease seen in the lower limbs. Trends in disease severity, as assessed by physicians using PASI, broadly reflected the trend in the comparable questions of the Psoriasis Symptom Diary assessed by patients. [ABSTRACT FROM AUTHOR]

Background: The efficacy and safety of secukinumab in patients with psoriasis has been established in randomised clinical trials. However, data on effectiveness and safety of secukinumab in Latin American real-world settings are scarce. Objectives: To evaluate the effectiveness and safety of secukinumab in real-world settings in patients with psoriasis in Latin America. Methods: PURE is an ongoing multinational, prospective, observational study in patients with moderate-to-severe chronic plaque psoriasis in Canada and Latin America assessing the real-world safety and effectiveness of secukinumab and other approved therapies. The study enrolled (1:1) patients treated with secukinumab versus other approved therapies (other Tx) per local standard of care from 81 community- and hospital-based speciality sites (21 in Latin America). Here, we report effectiveness and safety outcomes with secukinumab and other Tx for plaque psoriasis for up to 12 months in a Latin American population. Results: Overall, 187 patients were included in the analysis, 89 of whom initiated secukinumab treatment and 98 of whom received other Tx. At month 12, 84.4%, 71.1% and 53.3% of patients treated with secukinumab achieved Psoriasis Area and Severity Index (PASI) 75/90/100, respectively, compared with 66.7%, 47.9% and 29.2% of patients who received other Tx. Investigator Global Assessment (IGA) 0/1 responders in secukinumab versus other Tx were 78.3% versus 36.7% at month 3 and 81.8% versus 66.7% at month 12, respectively. Overall, the proportion of patients achieving Dermatology Life Quality Index (DLQI) 0/1 improved from 6.9% at baseline to 76.5% at month 12 in patients treated with secukinumab versus 5.6% at baseline to 54.5% at month 12 in patients on other Tx. No unexpected adverse events were reported during the 12-month observation period. Conclusion: Secukinumab demonstrated real-world effectiveness and improved dermatology quality-of-life in chronic plaque psoriasis patients from Latin America. Trial Registration: PURE: NCT02786186. [ABSTRACT FROM AUTHOR]

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

Real‐world data for psoriasis includes registries, and meta‐analyses could help guide biologic therapy choice. The objective was to determine the prevalence and reason for discontinuation of biologic or PD4 inhibitor therapy in patients with moderate‐to‐severe psoriasis in Newfoundland and Labrador, Canada from 2001 to 2017. A retrospective cohort study was conducted on data collected between 2001 and 2017, to determine the type of biologic therapy or PD4 inhibitor, length of treatment, prevalence of and reason for discontinuation. As multiple patients have been on more than one therapy (ie, an average of 1.8), the 459 patients included in the registry have had a total of 913 exposures to biologic or PD4 inhibitors. The treatment mean time was 37 months (SD 39.95). A total of 180 patients remained on their first biologic of which 75% were male. The average number of biologics per patient was 1.99. The reasons for discontinuation were primary failure (28.5%), adverse events (26.4%), secondary failure (24.3%), patient choice (4.4%), other/unknown in (6.6%), drug withdrawal from market (6.8%), and drug coverage issues (3%). The most common reasons for discontinuation of biologics or PD4 inhibitors include primary failure, adverse events, and secondary failures. Males were more likely to remain on their first biologic. [ABSTRACT FROM AUTHOR]

Environmentalists and ecologists typically regard invasive species as ecologically detrimental and undesirable. Although the ecological impacts of invasive species are well documented, less attention has been devoted to the sociocultural contexts guiding responses to species invasion. In this study the roles of invasive species are reconsidered through three prominent green spaces in Toronto, Canada: the Don Valley Brick Works, High Park, and the Leslie Street Spit. The case studies challenge popular negative assumptions about invasive species and suggest that they can serve important functions both for local ecosystems and for human communities. The case studies also provide lessons on the tension between and within different environmental imaginaries informing invasive species management. Invasives are often compatible with recreational interests, whereas naturalization efforts are ecologically sensitive and costly. Invasives can help restore human-made wastelands, and naturalization efforts often benefit wealthy rather than poor neighborhoods. Keywords: Canada, invasive species, public spaces, Toronto. [ABSTRACT FROM AUTHOR]