Phase 2 Trial of Topical Thykamine in Adults With Mild to Moderate Atopic Dermatitis.

BACKGROUND: Atopic dermatitis is a common skin disorder for which there remains an unmet need for topical pharmacotherapies that are safe and effective. This phase 2 study assessed the efficacy and safety of 3 dosages of PUR 0110 (Thykamine; Devonian Health Group Inc.) cream (0.05%, 0.1%, and 0.25%) compared to vehicle for treatment of adults with mild to moderate atopic dermatitis. The primary efficacy endpoint was the proportion of patients with an Investigator’s Global Assessment (IGA) of clear/almost clear and with a decrease from baseline score of at least 2 grades at day 29. Key secondary efficacy endpoints included change from baseline to day 29 in IGA, percent body surface area (%BSA) affected, Eczema Area and Severity Index (EASI) score, pruritus, and quality of life. Safety outcomes included the incidence of local and systemic adverse events. The primary efficacy endpoint was met with PUR 0110 cream 0.10% compared to vehicle (30.8% vs 6.7%, respectively, P=.014). Most secondary endpoints also favored PUR 0110 cream 0.10% vs vehicle, including change from baseline to day 29 in IGA score, %BSA affected, pruritus, and patient-reported quality of life. Adverse events occurred at a similar rate in all treatment groups; most were mild to moderate in intensity and were infrequently associated with study withdrawal. PUR 0110 cream 0.10% demonstrated rapid improvement in signs and symptoms of atopic dermatitis. This observation, along with its favorable safety and tolerability profile, could make it a useful therapeutic option for the treatment of atopic dermatitis. J Drugs Dermatol. 2022;21(10):1091-1097. doi:10.36849/JDD.6729.

Reduced risk of mortality associated with systemic psoriasis treatment in the Psoriasis Longitudinal Assessment and Registry (PSOLAR): A nested case-control analysis.

BACKGROUND: The effects of systemic therapy on mortality risk among patients with psoriasis are not fully understood. OBJECTIVE: To evaluate the impact of systemic treatment on mortality risk in patients enrolled in the Psoriasis Longitudinal Assessment and Registry. METHODS: Nested case-control analyses were performed to estimate mortality risk. Cases were defined as patients who died while participating in the Psoriasis Longitudinal Assessment and Registry. Cases were matched (1:4) with controls by age, race, sex, and geographic region. Evaluated treatments included methotrexate, ustekinumab, and tumor necrosis factor α inhibitors. Exposure was defined as at least 1 dose of treatment within 3 months before death and was stratified by duration of therapy. RESULTS: Among 12,090 patients, 341 deaths occurred, matched to 1364 controls. Biologic treatment within the preceding 3 months was protective against mortality versus no exposure: odds ratio (OR) for exposure of less than 1 year, 0.08 (95% confidence interval [CI], 0.03-0.23); OR for exposure of 1 year or longer, 0.09 (95% CI, 0.06-0.13). Methotrexate was protective against mortality only with exposure for 1 year or longer (OR, 0.08; 95% CI, 0.02-0.28). LIMITATIONS: Observational studies are subject to unmeasured confounding. CONCLUSIONS: Biologic therapy was associated with reduced mortality risk in patients with moderate to severe psoriasis, regardless of treatment duration; methotrexate reduced risk only with exposure for 1 year or longer.

Phase 2B randomized study of nemolizumab in adults with moderate-to-severe atopic dermatitis and severe pruritus.

BACKGROUND: Nemolizumab targets the IL-31 receptor α subunit involved in atopic dermatitis (AD) pathogenesis. OBJECTIVE: We sought to evaluate a new dosing strategy of nemolizumab in patients with AD. METHODS: We performed a 24-week, randomized, double-blind, multicenter study of nemolizumab (10, 30, and 90 mg) subcutaneous injections every 4 weeks versus placebo, with topical corticosteroids in adults with moderate-to-severe AD, severe pruritus, and inadequate control with topical treatment (n = 226). The Eczema Area and Severity Index (EASI), the peak pruritus (PP) numeric rating scale (NRS), and the Investigator's Global Assessment (IGA) were assessed. Standard safety assessments were performed. RESULTS: Nemolizumab improved EASI, IGA, and/or NRS-itch scores, with the 30-mg dose being most effective. Nemolizumab (30 mg) reduced EASI scores versus placebo at week 24 (-68.8% vs -52.1%, P = .016); significant differences were observed by week 8 (P ≤ .01). With significant improvement (P = .028) as early as week 4, IGA 0/1 rates were higher for 30 mg of nemolizumab versus placebo at week 16 (33.3% vs 12.3%, P = .008) but not week 24 because of an increased placebo/topical corticosteroid effect (36.8% vs 21.1%, P = .06). PP-NRS scores were improved for 30 mg of nemolizumab versus placebo at week 16 (-68.6% vs -34.3%, P < .0001) and week 24 (-67.3% vs -35.8%, P < .0001), with a difference by week 1 (P < .001). NRS response rates (≥4-point decrease) were greater for 30 mg of nemolizumab versus placebo at week 16 (P ≤ .001) and week 24 (P ≤ .01). Nemolizumab was safe and well tolerated. The most common adverse events were nasopharyngitis and upper respiratory tract infection. CONCLUSIONS: Nemolizumab resulted in rapid and sustained improvements in cutaneous signs of inflammation and pruritus in patients with AD, with maximal efficacy observed at 30 mg. Nemolizumab had an acceptable safety profile.

Ixekizumab Results in Persistent Clinical Improvement in Moderate-to-Severe Genital Psoriasis During a 52 Week, Randomized, Placebo-Controlled, Phase 3 Clinical Trial.

Ixekizumab was efficacious in treating moderate-to-severe genital psoriasis over 12 weeks. We evaluated the long-term efficacy and safety of ixekizumab for up to 52 weeks. Patients were randomized to 80 mg ixekizumab every 2 weeks or to placebo through Week 12, then received 80 mg open-label ixekizumab every 4 weeks through Week 52. In patients initially randomized to ixekizumab, clear or almost clear genital skin was achieved for 73% of patients at Week 12 and 75% at Week 52. Persistent improvements were also observed for overall psoriasis, genital itch, and the impact of genital psoriasis on the frequency of sexual activity. The safety profile was consistent with studies of ixekizumab in patients with moderate-to-severe plaque psoriasis. Ixekizumab provided rapid and persistent improvements in the signs and symptoms of genital psoriasis for up to 52 weeks of treatment.

Real-World Experience With Apremilast in the Treatment of Adults With Moderate to Severe Plaque Psoriasis in Québec: A Claims-Based Analysis of Drug Utilization and Healthcare Resource Utilization.

BACKGROUND: In Québec, targeted biologic therapies for moderate to severe plaque psoriasis are restricted to patients who have not responded to phototherapy or conventional systemic treatment, primarily due to high drug costs. Apremilast, an oral treatment for plaque psoriasis, was added to the Québec provincial health insurance plan (Régie de l'assurance maladie du Québec; RAMQ) formulary in 2015, making this the only province in Canada with public drug plan reimbursement for apremilast. OBJECTIVES: The aim of this study is to describe patients' characteristics, treatment patterns, healthcare resource utilization (HCRU), and associated costs and to measure real-world budget impact of using apremilast before biologics in plaque psoriasis. METHODS: This study was performed using RAMQ drug claims and medical services data. Patients diagnosed with psoriasis between January 2015 and December 2017 were identified. Medical services and prescription claims were categorized as all-cause and psoriasis-related. Using RAMQ database estimates, a 3-year budget impact analysis was developed comparing treatment cost with and without the addition of apremilast to the formulary. RESULTS: In all, 540 patients were identified (apremilast: n = 92; biologics: n = 448). Comorbidity burden and treatment persistence and adherence were comparable between apremilast and biologic users. The year following the index date, all-cause HCRU was lower for apremilast versus biologic users (CAN$19 763 vs CAN$28 025; P < .01), mainly driven by drug cost. Using apremilast before biologics resulted in an estimated RAMQ net savings of CAN$49 290 (2015), CAN$746 856 (2016), and CAN$1 216 512 (2017), and a total savings of CAN$2 012 658 since apremilast's addition to the formulary. CONCLUSION: Adding apremilast to the drug formulary of other Canadian provinces could result in significant healthcare savings.

Management of Plaque Psoriasis With Biologic Therapies in Women of Child-Bearing Potential Consensus Paper.

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.

Efficacy and safety of risankizumab in moderate-to-severe plaque psoriasis (UltIMMa-1 and UltIMMa-2): results from two double-blind, randomised, placebo-controlled and ustekinumab-controlled phase 3 trials.

BACKGROUND: Risankizumab is a humanised IgG1 monoclonal antibody that binds to the p19 subunit of interleukin-23, inhibiting this key cytokine and its role in psoriatic inflammation. We aimed to assess the efficacy and safety of risankizumab compared with placebo or ustekinumab in patients with moderate-to-severe chronic plaque psoriasis. METHODS: UltIMMa-1 and UltIMMa-2 were replicate phase 3, randomised, double-blind, placebo-controlled and active comparator-controlled trials done at 139 sites in Australia, Austria, Belgium, Canada, Czech Republic, France, Germany, Japan, Mexico, Poland, Portugal, South Korea, Spain, and the USA. Eligible patients were 18 years or older, with moderate-to-severe chronic plaque psoriasis. In each study, patients were stratified by weight and previous exposure to tumour necrosis factor inhibitor and randomly assigned (3:1:1) by use of interactive response technology to receive 150 mg risankizumab, 45 mg or 90 mg ustekinumab (weight-based per label), or placebo. Following the 16-week double-blind treatment period (part A), patients initially assigned to placebo switched to 150 mg risankizumab at week 16; other patients continued their originally randomised treatment (part B, double-blind, weeks 16-52). Study drug was administered subcutaneously at weeks 0 and 4 during part A and at weeks 16, 28, and 40 during part B. Co-primary endpoints were proportions of patients achieving a 90% improvement in the Psoriasis Area Severity Index (PASI 90) and a static Physician's Global Assessment (sPGA) score of 0 or 1 at week 16 (non-responder imputation). All efficacy analyses were done in the intention-to-treat population. These trials are registered with ClinicalTrials.gov, numbers NCT02684370 (UltIMMa-1) and NCT02684357 (UltIMMa-2), and have been completed. FINDINGS: Between Feb 24, 2016, and Aug 31, 2016, 506 patients in UltIMMa-1 were randomly assigned to receive 150 mg risankizumab (n=304), 45 mg or 90 mg ustekinumab (n=100), or placebo (n=102). Between March 1, 2016, and Aug 30, 2016, 491 patients in UltIMMa-2 were randomly assigned to receive 150 mg risankizumab (n=294), 45 mg or 90 mg ustekinumab (n=99), or placebo (n=98). Co-primary endpoints were met for both studies. At week 16 of UltIMMa-1, PASI 90 was achieved by 229 (75·3%) patients receiving risankizumab versus five (4·9%) receiving placebo (placebo-adjusted difference 70·3% [95% CI 64·0-76·7]) and 42 (42·0%) receiving ustekinumab (ustekinumab-adjusted difference 33·5% [22·7-44·3]; p<0·0001 vs placebo and ustekinumab). At week 16 of UltIMMa-2, PASI 90 was achieved by 220 (74·8%) patients receiving risankizumab versus two (2·0%) receiving placebo (placebo-adjusted difference 72·5% [95% CI 66·8-78·2]) and 47 (47·5%) receiving ustekinumab (ustekinumab-adjusted difference 27·6% [16·7-38·5]; p<0·0001 vs placebo and ustekinumab). In UltIMMa-1, sPGA 0 or 1 at week 16 was achieved by 267 (87·8%) patients receiving risankizumab versus eight (7·8%) receiving placebo (placebo-adjusted difference 79·9% [95% CI 73·5-86·3]) and 63 (63·0%) receiving ustekinumab (ustekinumab-adjusted difference 25·1% [15·2-35·0]; p<0·0001 vs placebo and ustekinumab). In UltIMMa-2, 246 (83·7%) patients receiving risankizumab versus five (5·1%) receiving placebo (placebo-adjusted difference 78·5% [95% CI 72·4-84·5]) and 61 (61·6%) receiving ustekinumab achieved sPGA 0 or 1 at week 16 (ustekinumab-adjusted difference 22·3% [12·0-32·5]; p<0·0001 vs placebo and ustekinumab). The frequency of treatment-emergent adverse events in UltIMMa-1 and UltIMMa-2 was similar across risankizumab (part A: 151 [49·7%] of 304 and 134 [45·6%] of 294; part B: 182 [61·3%] of 297 and 162 [55·7%] of 291), placebo (part A: 52 [51·0%] of 102 and 45 [45·9%] of 98), ustekinumab (part A: 50 [50·0%] of 100 and 53 [53·5%] of 99; part B: 66 [66·7%] of 99 and 70 [74·5%] of 94), and placebo to risankizumab (part B: 65 [67·0%] of 97 and 61 [64·9%] of 94) treatment groups throughout the study duration. INTERPRETATION: Risankizumab showed superior efficacy to both placebo and ustekinumab in the treatment of moderate-to-severe plaque psoriasis. Treatment-emergent adverse event profiles were similar across treatment groups and there were no unexpected safety findings. FUNDING: AbbVie and Boehringer Ingelheim.

Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis.

BACKGROUND: Dupilumab, a human monoclonal antibody against interleukin-4 receptor alpha, inhibits signaling of interleukin-4 and interleukin-13, type 2 cytokines that may be important drivers of atopic or allergic diseases such as atopic dermatitis. METHODS: In two randomized, placebo-controlled, phase 3 trials of identical design (SOLO 1 and SOLO 2), we enrolled adults with moderate-to-severe atopic dermatitis whose disease was inadequately controlled by topical treatment. Patients were randomly assigned in a 1:1:1 ratio to receive, for 16 weeks, subcutaneous dupilumab (300 mg) or placebo weekly or the same dose of dupilumab every other week alternating with placebo. The primary outcome was the proportion of patients who had both a score of 0 or 1 (clear or almost clear) on the Investigator's Global Assessment and a reduction of 2 points or more in that score from baseline at week 16. RESULTS: We enrolled 671 patients in SOLO 1 and 708 in SOLO 2. In SOLO 1, the primary outcome occurred in 85 patients (38%) who received dupilumab every other week and in 83 (37%) who received dupilumab weekly, as compared with 23 (10%) who received placebo (P<0.001 for both comparisons with placebo). The results were similar in SOLO 2, with the primary outcome occurring in 84 patients (36%) who received dupilumab every other week and in 87 (36%) who received dupilumab weekly, as compared with 20 (8%) who received placebo (P<0.001 for both comparisons). In addition, in the two trials, an improvement from baseline to week 16 of at least 75% on the Eczema Area and Severity Index was reported in significantly more patients who received each regimen of dupilumab than in patients who received placebo (P<0.001 for all comparisons). Dupilumab was also associated with improvement in other clinical end points, including reduction in pruritus and symptoms of anxiety or depression and improvement in quality of life. Injection-site reactions and conjunctivitis were more frequent in the dupilumab groups than in the placebo groups. CONCLUSIONS: In two phase 3 trials of identical design involving patients with atopic dermatitis, dupilumab improved the signs and symptoms of atopic dermatitis, including pruritus, symptoms of anxiety and depression, and quality of life, as compared with placebo. Trials of longer duration are needed to assess the long-term effectiveness and safety of dupilumab. (Funded by Sanofi and Regeneron Pharmaceuticals; SOLO 1 ClinicalTrials.gov number, NCT02277743 ; SOLO 2 ClinicalTrials.gov number, NCT02277769 .).

North American clinical management guidelines for hidradenitis suppurativa: A publication from the United States and Canadian Hidradenitis Suppurativa Foundations: Part II: Topical, intralesional, and systemic medical management.

Hidradenitis suppurativa is a severe and debilitating dermatologic disease. Clinical management is challenging and consists of both medical and surgical approaches, which must often be combined for best outcomes. Therapeutic approaches have evolved rapidly in the last decade and include the use of topical therapies, systemic antibiotics, hormonal therapies, and a wide range of immunomodulating medications. An evidence-based guideline is presented to support health care practitioners as they select optimal medical management strategies and is reviewed in this second part of the management guidelines. A therapeutic algorithm informed by the evidence available at the time of the review is provided.

North American clinical management guidelines for hidradenitis suppurativa: A publication from the United States and Canadian Hidradenitis Suppurativa Foundations: Part I: Diagnosis, evaluation, and the use of complementary and procedural management.

Hidradenitis suppurativa is a chronic inflammatory disorder affecting hair follicles, with profoundly negative impact on patient quality of life. Evidence informing ideal evaluation and management of patients with hidradenitis suppurativa is still sparse in many areas, but it has grown substantially in the last decade. Part I of this evidence-based guideline is presented to support health care practitioners as they select optimal management strategies, including diagnostic testing, comorbidity screening, and both complementary and procedural treatment options. Recommendations and evidence grading based on the evidence available at the time of the review are provided.

Off-Label Use of Topical Calcineurin Inhibitors in Dermatologic Disorders.

Off-label prescribing is a common practice in dermatology, particularly when uncommon dermatologic diseases have limited or no approved treatment options. Topical calcineurin inhibitors are approved for the treatment of eczema, and their anti-inflammatory, immunomodulatory, and steroid-sparing effects make them an attractive therapeutic option for a wide variety of other dermatologic diseases. This review summarizes and qualifies the available evidence supporting the clinical effectiveness of tacrolimus ointment and pimecrolimus cream in non-eczema indications. There is high-quality evidence supporting the effectiveness of topical calcineurin inhibitors in multiple dermatological disorders including vitiligo; psoriasis of the face, folds, and genitals; seborrheic dermatitis; chronic hand dermatitis; contact dermatitis; oral lichen planus; lichen sclerosus; morphea; and cutaneous lupus erythematosus. Lower-quality evidence suggests they may be considered as an option in many other cutaneous disorders.

Checklist for the Systemic Treatment of Psoriasis Using Biologics: A Delphi Study.

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.

Certolizumab pegol for the treatment of chronic plaque psoriasis: Results through 48 weeks from 2 phase 3, multicenter, randomized, double-blinded, placebo-controlled studies (CIMPASI-1 and CIMPASI-2).

BACKGROUND: Certolizumab pegol, the only Fc-free, PEGylated anti-tumor necrosis factor biologic, demonstrated clinically meaningful improvements suggestive of a positive risk-benefit balance in phase 2 studies in adults with moderate-to-severe chronic plaque psoriasis. OBJECTIVE: Assess certolizumab efficacy and safety versus placebo in phase 3 studies. METHODS: Patients with moderate-to-severe chronic plaque psoriasis were randomized 2:2:1 to certolizumab 400 mg, certolizumab 200 mg, or placebo every 2 weeks. At week 16, certolizumab-treated patients achieving a 50% reduction in Psoriasis Area and Severity Index continued treatment through week 48. Coprimary endpoints were week 16 responder rates, defined as a 75% reduction in Psoriasis Area and Severity Index and Physician's Global Assessment 0/1 (clear/almost clear) and ≥2-point improvement. Safety was assessed by treatment-emergent adverse events. RESULTS: Week-16 endpoints were significantly greater for both doses of certolizumab versus placebo, and the responses were maintained through week 48. For most measures, improvement was numerically greater for certolizumab 400 mg. No unexpected safety signals were identified. LIMITATION: There was no active comparator. CONCLUSION: Treatment with either certolizumab 400 mg or 200 mg every 2 weeks was associated with significant and clinically meaningful improvements in moderate-to-severe psoriasis. The 400-mg dose could provide additional clinical benefit. The safety profile was consistent with the therapeutic class.

Adalimumab for nail psoriasis: Efficacy and safety from the first 26 weeks of a phase 3, randomized, placebo-controlled trial.

BACKGROUND: Previous clinical trials have not evaluated improvement in nail psoriasis as a primary end point. OBJECTIVE: This phase 3 trial evaluated the safety and efficacy of adalimumab in patients with moderate-to-severe fingernail psoriasis and moderate-to-severe plaque psoriasis. METHODS: Patients were randomized 1:1 to 40 mg adalimumab every other week or placebo. The primary efficacy end point was at least 75% improvement in total-fingernail modified Nail Psoriasis Severity Index (NAPSI75) response rate at week 26. Ranked secondary end point scores evaluated at week 26 were total-fingernail NAPSI and modified NAPSI, nail pain, Nail Psoriasis Physical Functioning Severity, Brigham Scalp Nail Inverse Palmo-Plantar Psoriasis Index, and Physician's Global Assessment (fingernail psoriasis). RESULTS: Of the 217 randomized patients (108 received placebo and 109 received adalimumab), 188 (86.6%) completed 26 weeks of treatment (period A) or escaped early to the open-label period. The study met the primary end point (response rate of 3.4% with placebo vs 46.6% with adalimumab [P < .001]) and all ranked secondary end points. The serious adverse event rates (placebo vs adalimumab) in period A were 4.6% versus 7.3%; the serious infections rates were 1.9% versus 3.7%. LIMITATIONS: Patients with less than 5% BSA involvement were not eligible for enrollment. CONCLUSIONS: After 26 weeks of adalimumab treatment, significant improvements were seen in the primary and all ranked secondary end points and in signs and symptoms of moderate-to-severe nail psoriasis versus with placebo and no new safety risks were identified.

Approach to the Assessment and Management of Adult Patients With Atopic Dermatitis: A Consensus Document. Section IV: Treatment Options for the Management of Atopic Dermatitis.

The objectives of therapy for atopic dermatitis (AD) are to reduce skin inflammation and pruritus, restore skin barrier function, and improve quality of life (QoL). Treatments can be classified as moisturizing and basic care, topical therapy, phototherapy, and systemic therapy. In this review, we summarize the treatments for AD and recommendations for their use.

OBSERVE-5: Comparison of Etanercept-Treated Psoriasis Patients From Canada and the United States.

BACKGROUND: OBSERVE-5 surveillance registry results evaluating etanercept safety and effectiveness in patients with moderate to severe psoriasis from Canada and the United States have been reported from data collected between May 2006 and December 2012. Although both countries have an identical indicated starting dose, the maintenance dose can differ and thus affect management strategies and outcomes. OBJECTIVE: To compare the long-term safety and effectiveness outcomes of etanercept in the Canadian and US cohorts. METHODS: Primary end points included exposure-adjusted event incidence rates of serious adverse events and serious infectious events. Secondary end points included exposure-adjusted event incidence rates of events of medical interest and efficacy outcomes. RESULTS: Over 5 years, Canadian patients received a higher maintenance dose of etanercept (50 mg twice/week) more frequently than those from the United States. Safety outcome comparisons revealed that Canadian patients had a significantly lower occurrence of serious adverse events than patients from the United States, with an overall exposure-adjusted event incidence rate per 100 patient-years of 4.46 (95% confidence interval [CI], 3.05-6.29) vs 7.76 (95% CI 7.04-8.54), respectively. Serious infectious event rates were not significantly different between the 2 countries. Secondary outcomes of events of medical interest and effectiveness also did not reveal significant differences between the 2 cohorts. CONCLUSION: After 5 years of etanercept use, safety and effectiveness outcomes were similar between patients from Canada and the United States, with the exception of a significantly lower rate of serious adverse events in the Canadian population.

A Treatment Algorithm for Moderate to Severe Atopic Dermatitis in Adults.

BACKGROUND: Atopic dermatitis (AD) is a common and chronic inflammatory skin disease. Approximately 10% of adults with AD do not respond adequately to topical therapies and require phototherapy and/or systemic therapy. OBJECTIVE: To provide a patient-focused approach to the identification and management of adults with AD who require systemic treatment. METHODS: A working group of clinicians experienced in managing AD was convened to review and discuss current evidence on the identification and clinical management of adults with moderate to severe AD. RESULTS: We propose a set of simple and practical clinical criteria for selecting candidates for systemic treatment of AD based on their response to first-line topical therapy and 4 clinical measures that are easily incorporated into routine practice. We also suggest a framework for evaluating systemic treatments according to attributes that are important from both a clinician's and a patient's perspective. An algorithm was developed proposing a pathway for treatment of moderate to severe AD in adults. CONCLUSION: Adults with moderate to severe AD that does not respond adequately to topical therapies currently have few safe and effective treatment options. A clinical algorithm could help guide treatment decisions.

Approach to the Assessment and Management of Adult Patients With Atopic Dermatitis: A Consensus Document.

BACKGROUND:: Atopic dermatitis (AD) is a chronic, relapsing, and remitting inflammatory skin disease with complex pathophysiology, primarily driven by type 2 inflammation. Existing guidelines often do not reflect all current therapeutic options and guidance on the practical management of patients with AD is lacking. OBJECTIVES:: To develop practical, up-to-date guidance on the assessment and management of adult patients with AD. METHODS:: An expert panel of 17 Canadian experts, including 16 dermatologists and 1 allergist, with extensive clinical experience managing moderate-to-severe AD reviewed the available literature from the past 5 years using a defined list of key search terms. This literature, along with clinical expertise and opinion, was used to draft concise, clinically relevant reviews of the current literature. Based on these reviews, experts developed and voted on recommendations and statements to reflect the practical management of adult patients with AD as a guide for health care providers in Canada and across the globe, using a prespecified agreement cutoff of 75%. RESULTS:: Eleven consensus statements were approved by the expert panel and reflected 4 key domains: pathophysiology, assessment, comorbidities, and treatment. CONCLUSIONS:: These statements aim to provide a framework for the assessment and management of adult patients with AD and to guide health care providers in practically relevant aspects of patient management.

Approach to the Assessment and Management of Adult Patients With Atopic Dermatitis: A Consensus Document. Section V: Consensus Statements on the Assessment and Management of Adult Patients With Moderate-to-Severe Atopic Dermatitis.

This document is a concise, current, and practical guide for dermatologists and other health care providers managing adult patients with moderate-to-severe atopic dermatitis (AD). The recommendations made here are based on a consensus of specialists with extensive experience managing patients with AD. Topics reviewed in this publication include AD pathophysiology, assessment, comorbidities, and treatment options.

Olumacostat glasaretil, a novel topical sebum inhibitor, in the treatment of acne vulgaris: A phase IIa, multicenter, randomized, vehicle-controlled study.

BACKGROUND: Olumacostat glasaretil (OG) inhibits acetyl-coenzyme A carboxylase, the enzyme responsible for the first, rate-limiting step in de novo fatty acid synthesis. OG inhibited in vitro human sebocyte lipid production and reduced in vivo sebaceous gland size in hamster ears. OBJECTIVES: Safety and efficacy of OG 7.5% gel were evaluated in patients with moderate to severe facial acne vulgaris. METHODS: Patients were randomized (1:1) to twice-daily application of OG or vehicle for 12 weeks. Efficacy was measured through changes in lesion counts and improvement in acne severity scores. RESULTS: A total of 108 patients received OG (n = 53) or vehicle (n = 55); these groups had mean baseline counts of 29.7 and 28.6 inflammatory and 40.9 and 38.8 noninflammatory lesions, respectively. At week 12, OG treatment showed greater reductions from baseline in inflammatory lesions (-63.9% vs -45.9%; P = .0006) and noninflammatory lesions (-48.1% vs -28.8%; P = .0025), and more patients with greater than or equal to 2-grade improvement in investigator global assessment score (24.5% vs 7.3%; P = .0070) than vehicle. Application-site adverse events (typically mild or moderate intensity) were more common with OG. LIMITATIONS: Larger trials are needed to optimize OG dosing and confirm the current results. CONCLUSION: OG was well tolerated and showed evidence of efficacy, suggesting further development is warranted.