Short-Term Evaluation of the Real-World Efficacy and Safety of Dupilumab for the Treatment of Moderate-to-Severe Atopic Dermatitis: A Canadian Multicenter Retrospective Cohort Study [Formula: see text].

BACKGROUND: Systemic therapy for atopic dermatitis (AD) has been challenging with limited safe and efficacious long-term treatment options. In 2017, dupilumab was approved in the United States, Europe, and Canada as the first targeted therapy for patients with moderate-to-severe AD. Despite promising efficacy and safety results in clinical trials, our understanding of dupilumab in clinical practice remains limited with few studies outside clinical trials in literature. OBJECTIVE: The aim of this study is to evaluate the efficacy and safety of dupilumab in clinical practice and discuss any differences in results between clinical trials and real-world results. METHODS: A retrospective chart review was conducted of consecutive patients receiving dupilumab treatment at two tertiary hospitals in Toronto, Canada, between December 2017 and May 2019. The primary efficacy endpoint was measured by Investigator's Global Assessment (IGA) score of 0/1 at 16 weeks and all adverse events (AEs) experienced by patients were recorded. RESULTS: Of the 93 patients included in the study, 51 (55%) reached IGA 0/1 and 38 (41%) experienced ≥1 AE. There were no severe AEs or discontinuation prior to 16 weeks due to an AE. CONCLUSIONS: These findings suggest a higher IGA-based efficacy profile with no newly identified safety concerns in patients treated with dupilumab at two tertiary hospitals in Toronto, Canada, compared to those in randomized controlled trials.

Tofacitinib for the treatment of psoriasis and psoriatic arthritis.

INTRODUCTION: Tofacitinib is a novel oral janus kinase (JAK) inhibitor approved for the treatment of psoriatic arthritis. It was also investigated for the treatment of plaque psoriasis, although it is not approved by the Food and Drug Administration for this indication. This article aimed to summarize the efficacy and safety data of tofacitinib for treatment of psoriatic disease. EVIDENCE ACQUISITION: A comprehensive review of literature was conducted on the PubMed database using the search terms: "((tofacitinib) AND (psoriasis)) OR ((tofacitinib) AND (psoriatic arthritis))". Data from the pivotal clinical trials evaluating tofacitinib in the treatment of psoriatic disease were summarized. EVIDENCE SYNTHESIS: The Oral-treatment Psoriasis Trial (OPT) study series demonstrated that tofacitinib is efficacious in the treatment of plaque psoriasis with an acceptable safety profile. The OPT studies also demonstrated the non-inferiority of tofacitinib 10 mg twice daily compared to etanercept. The Oral Psoriatic Arthritis Trial (OPAL) study series demonstrated that tofacitinib significantly improved psoriatic arthritis outcomes compared to placebo and had an acceptable safety profile. Its efficacy is comparable to adalimumab in psoriatic arthritis. CONCLUSIONS: Patients treated with tofacitinib should be monitored for herpes zoster, malignancies, blood clots, and changes in laboratory values. Overall, tofacitinib is a useful new systemic agent in the treatment of psoriatic disease. Its oral route of administration, novel JAK pathway target, short half-life, and strong recapture rates after treatment interruption make it a unique new tool for psoriatic disease management. Further long-term studies will help determine its role in the treatment algorithm for psoriatic arthritis and its indication for plaque psoriasis.

Biologic Treatment in Elderly Patients With Psoriasis: A Systematic Review.

With our aging population, an increasing number of psoriasis patients are classified as elderly. However, psoriasis treatment in older adults can be challenging, given an increased number of comorbid conditions and immunosenescence. Biologic agents present a solution to this treatment dilemma because of their high efficacy and favorable tolerability. The objective of this systematic review was to summarize the findings of clinical trial and real-world studies exploring the safety and efficacy of biologic agents in elderly patients with moderate-to-severe psoriasis. We searched MEDLINE, Embase, the Cochrane Library, and clinical trial databases. Studies analyzing biologics for psoriasis were included if elderly patients were the main population of interest or were a separate subgroup in their analysis. Eighteen articles met inclusion criteria after screening. Across all biologic classes, efficacy for biologics between nonelderly adult patient and elderly patients was similar. Adverse events (AEs) and infections occured at a similar frequency between both groups. However, serious AEs were more common in the elderly. The available literature on the safety and efficacy of biologic agents in elderly patients supports the use of these agents in this population. However, serious AEs and discontinuation due to AEs were more common in older patients. As elderly patients have a higher burden of comorbid conditions and an increased baseline vulnerability for AE, physicians should continue to be prudent in screening before initiating biologics and monitor patients more closely as AEs tend to be more severe.

Off-label Uses of Topical Pimecrolimus.

Pimecrolimus is a topical calcineurin inhibitor currently approved for second-line use in the management of mild-to-moderate atopic dermatitis in patients age 2 years and older. Given the safety profile and nonsteroidal mechanism of pimecrolimus, there has been significant interest in its use in the treatment of a variety of dermatological conditions. This article reviews research that has been published on the off-label uses of topical pimecrolimus, with a focus on published RCTs. Convincing evidence exists supporting pimecrolimus' efficacy in oral lichen planus and seborrheic dermatitis. For other conditions studied to date, pimecrolimus may prove to be a useful treatment alternative when conventional agents fail. Adverse events seen with its off-label use were typically application site reactions, the most common being a transient burning sensation. In summary, pimecrolimus appears to be an effective agent in the treatment of multiple dermatological conditions and may be worth considering as a pharmacologic alternative in several conditions when first-line treatment fails, or for areas that are more susceptible to the adverse effects of topical corticosteroids.

Off-Label High-Dose Secukinumab for the Treatment of Moderate-to-Severe Psoriasis.

BACKGROUND: Secukinumab is an anti-IL-17A monoclonal antibody approved for the treatment of moderate-to-severe psoriasis in adult patients. Despite its favourable safety and efficacy profile in clinical trials, some patients in clinical practice fail to respond adequately to the approved maintenance regimen of 300 mg subcutaneous monthly. Some clinicians manage these patients by using off-label high-dose secukinumab regimens, which include shortening the dosing interval to 300 mg every 2 or 3 weeks instead of monthly, or increasing the monthly dose to 450 mg. OBJECTIVE: This study aims to investigate the safety and efficacy of high-dose secukinumab regimens for the treatment of psoriasis to inform real-world clinical practice. METHODS: We performed a retrospective chart review at 5 dermatology clinics for adult patients diagnosed with moderate-to-severe psoriasis treated with an off-label high-dose secukinumab regimen. Efficacy was measured using the Psoriasis Area and Severity Index or a Physician Global Assessment score of 0 or 1 after dose escalation. Adverse events were recorded to assess safety outcomes. RESULTS: Twenty-five patients were included in this case series, and 14 of them achieved efficacy from dose escalation with secukinumab based on our study endpoints. There was 1 case of the common cold and 1 upper respiratory tract infection reported after dose escalation. CONCLUSION: Our study provides evidence that dose escalation with secukinumab results in clinical benefit and is well tolerated among patients with moderate-to-severe psoriasis who failed to respond adequately to the approved regimen. This work necessitates larger studies to fully characterize the efficacy and long-term safety profile of secukinumab dose escalation.

Satisfaction and Awareness of Systemic Psoriasis Treatments: A National Survey Comparing Biologic and Nonbiologic Users.

BACKGROUND:: There is ongoing development of new therapies for psoriasis, including biologic and systemic agents such as interleukin-17, interleukin-23, and phosphodiesterase-4 inhibitors. The development of these agents has changed the landscape of psoriasis treatment options. OBJECTIVE:: The objective of this study was to characterize the impact of newer biologic and systemic agents approved by June 2016 on patient outcomes. We sought to evaluate and compare biologic users and nonbiologic systemic users with respect to their treatment awareness and satisfaction. METHODS:: We conducted a national Canadian survey from July to September 2016 on adult patients with moderate-to-severe psoriasis using biologic agents or nonbiologic systemic agents as their current primary treatment modality. Patients were asked to evaluate their overall satisfaction with their treatment agent and their awareness of other treatment options. Responses from biologic and nonbiologic systemic users were compared. RESULTS:: Overall, 343 participants were included (biologic users: n = 218; nonbiologic users: n = 125). Treatment satisfaction: Biologic users had a higher overall satisfaction score than nonbiologic users ( P < .001). Among nonbiologic agents, apremilast (62%) was associated with the highest satisfaction proportion. Among biologic agents, ustekinumab (77%) and adalimumab (72%) were associated with the highest proportions of satisfaction. With respect to treatment awareness, 30% of nonbiologic patients did not have enough information to form an opinion about biologics. CONCLUSIONS:: This study demonstrates the greater treatment satisfaction of biologic users compared with nonbiologic users for moderate-to-severe psoriasis. Given that nearly one-third of nonbiologic users did not have enough information to form an opinion about biologic agents, physicians may consider counselling these patients on the use of biologic agents for psoriasis management.

Comparison of Management Guidelines for Moderate-to-Severe Plaque Psoriasis: A Review of Phototherapy, Systemic Therapies, and Biologic Agents.

INTRODUCTION:: Many international guidelines for management of psoriasis exist and most have variations in grading evidence quality, strength of recommendations, and dosing. The objective of our review is to compare international guidelines published in the United Kingdom, Canada, Europe, and the United States for the management of moderate-to-severe plaque psoriasis. METHODS:: We conducted a literature review on systemic therapies and phototherapy for moderate-to-severe plaque psoriasis in adult patients. The British, Canadian, European, and American guidelines served as the key comparators in our review. To identify relevant supporting clinical trials not referenced in the guidelines, we conducted literature searches in PubMed and EMBASE. Two authors independently extracted data on indications, dosing, efficacy, evidence grade, and strength of clinical recommendation for each therapy. RESULTS:: Monoclonal antibodies directed toward tumour necrosis factor and interleukin (IL)-12/23 received the strongest recommendations for treatment of moderate-to-severe plaque psoriasis, supported by robust, high-quality randomized controlled trials (RCTs). Newer agents such as IL-17 and IL-23 inhibitors are not referenced in most guidelines. There are fewer RCTs for conventional therapies and few head-to-head comparisons with biologics, making it difficult to draw direct comparisons. Among older agents, methotrexate is most strongly recommended for long-term maintenance and cyclosporine is recommended for short-term control of flares. CONCLUSION:: Physicians should individualize psoriasis-management strategies based on medication tolerance, efficacy, safety, patient comorbidities, availability of the medication, and patient preference.

Ixekizumab (Interleukin 17A Antagonist): 12-week Efficacy and Safety Outcomes in Real-world Clinical Practice.

BACKGROUND:: Current knowledge of the efficacy and safety of ixekizumab is limited to data from phase III randomized controlled trials (RCTs). A gap exists in our understanding of treatment outcomes of this newly available biologic in real-world clinical practice. OBJECTIVE:: This study explores the efficacy and safety of ixekizumab in non-RCT patients to compare real-world outcomes to those reported in RCTs. METHODS:: We conducted a multicentre, retrospective chart review of patients treated with ixekizumab therapy for moderate-to-severe plaque psoriasis. Efficacy (Psoriasis Area and Severity Index score of 75 or Physician Global Assessment of 0 or 1) and safety (reported adverse events [AEs]) were assessed following a 12-week treatment period. RESULTS:: Of the 60 patients included, 45 (75.0%) achieved efficacious outcomes after 12 weeks of ixekizumab treatment. Twenty-two (36.7%) patients experienced one or more AEs, of whom only 3 (5.0%) withdrew from treatment as a result. Common AEs included injection site reaction/erythema/pain (13.3%) and dermatitis (5.0%). CONCLUSION:: Ixekizumab has shown to be a safe and effective therapeutic option for plaque psoriasis in real-world practice. It does not appear that patients experience more AEs in real-world clinics than those in clinical trials.

Numerous asymptomatic dermal cysts: Diagnosis and treatment of steatocystoma multiplex.

OBJECTIVE: To provide family physicians with the information needed to recognize, diagnose, and discuss available treatment options for steatocystoma multiplex (SM). SOURCES OF INFORMATION: A comprehensive PubMed search using steatocystoma multiplex as either a text word or a MeSH term was conducted, and articles reporting on treatment outcomes were included. MAIN MESSAGE: Steatocystoma multiplex is a benign disorder often characterized by numerous asymptomatic dermal cysts on the trunk, arms, axillae, face, thighs, and scalp. Psychological distress due to these undesirable lesions is not uncommon for this condition. A literature review identified the following SM treatments, all of which were associated with limitations: carbon dioxide laser, modified surgical techniques, cryotherapy, and medical management. Steatocystoma multiplex is challenging to treat and, at this time, effective management is most often achieved through patient education. CONCLUSION: Family physicians play a critical role in the early diagnosis and management of SM. Education about treatment options and managing patient expectations might greatly alleviate the psychosocial implications of this disease.

Nombreux kystes dermiques asymptomatiques: Diagnostic et traitement des stéatocystomes multiples.

OBJECTIF: Renseigner les médecins de famille pour les rendre aptes à reconnaître et à diagnostiquer les stéatocystomes multiples, et à discuter des options thérapeutiques. SOURCES D'INFORMATION: Une recherche exhaustive sur PubMed a été réalisée à l'aide des titres MeSH ou des mots clés anglais steatocystoma multiplex, et les articles ayant rapporté les résultats du traitement ont été inclus. MESSAGE PRINCIPAL: Les stéatocystomes multiples sont un trouble bénin souvent caractérisé par de nombreux kystes dermiques asymptomatiques sur le tronc, les bras, les aisselles, le visage, les cuisses et le cuir chevelu. La détresse psychologique causée par ces lésions indésirables est fréquente. Une revue des publications a relevé les traitements suivants, tous assortis de limites : laser au gaz carbonique, techniques chirurgicales modifiées, cryothérapie et prise en charge médicale. Les stéatocystomes multiples sont difficiles à traiter et, pour l'heure, la prise en charge efficace passe le plus souvent par l'éducation du patient. CONCLUSION: Les médecins de famille sont au centre du diagnostic et de la prise en charge précoces des stéatocystomes multiples. L'éducation relative aux options thérapeutiques et à la gestion des attentes du patient pourrait grandement alléger le fardeau psychosocial de la maladie.

Systemic Monotherapy Treatments for Generalized Pustular Psoriasis: A Systematic Review.

Generalized pustular psoriasis (GPP) is a rare but serious and difficult to treat cutaneous disease, with high morbidity and mortality rates. Despite the numerous treatment regimens available, the overall quality of evidence-based research is limited with a lack of an algorithmic approach available. In this review, we aim to evaluate the current level of evidence regarding the efficacy and safety/tolerability of systemic monotherapies available in the treatment of GPP. A comprehensive MEDLINE, EMBASE, and PubMed search of clinical studies examining systemic monotherapy treatment options for GPP was conducted. In total, 31 studies met eligibility criteria. Described treatment modalities included retinoids, cyclosporine, biologics, and dapsone. Despite the lack of high-quality evidence or a well-accepted treatment algorithm for GPP, systemic retinoids, cyclosporine, biologics, and dapsone are all possible first-line agents, with retinoids being one of the best-supported treatment options and biologics as an emerging therapeutic field with great potential requiring additional data. However, the final choice of treatment should be considered within the unique context of each patient.

Medical, Surgical, and Wound Care Management of Ulcerated Infantile Hemangiomas: A Systematic Review [Formula: see text].

Ulcerated infantile hemangiomas may present a therapeutic challenge, especially if there is concurrent hemorrhage or infection. The aim of this study was to systematically review the published evidence on the treatment of ulcerated hemangiomas, focusing on wound healing as the outcome of interest. We searched MEDLINE, Embase, SCOPUS, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science from inception to July 2016. Seventy-seven studies met our inclusion criteria. One study was a randomized controlled trial, 30 were observational studies, and 46 were case reports or case series. There is significant heterogeneity among the methods used. We reviewed 1239 patients in total. Of the 197 treated with oral propranolol, 191 (97.0%) achieved complete ulcer healing. Thirty-one patients failed corticosteroid therapy (oral, intralesional, or topical) and were subsequently successfully treated with other therapies. Surgical resections were typically performed for larger hemangiomas and those causing complications. None of the therapies discussed appear to offer significant advantages over others. Therefore, treatment decisions should be individualized based on location of disease, extent, symptoms, feasibility, cost, and parental preference.

Efficacy and Safety of Apremilast Monotherapy for Moderate to Severe Psoriasis: Retrospective Study.

BACKGROUND: Apremilast is a new oral drug for the treatment of moderate to severe plaque psoriasis that reduces inflammation by inhibiting phosphodiesterase 4. Its efficacy and safety data are limited; hence, real-world outcomes are important for elucidating the full spectrum of its adverse events (AEs) and expanding generalizability of clinical trial findings. OBJECTIVE: Assess the efficacy and safety of apremilast monotherapy in real-world practice. METHODS: A retrospective chart review was conducted in 2 academic dermatology practices. Efficacy was measured as the proportion of patients achieving a ≥75% reduction from baseline Psoriasis Area and Severity Index score (PASI-75) or a Psoriasis Global Assessment (PGA) score of 0 (clear) or 1 (almost clear) at 16 weeks. Safety was measured as the proportion of patients reporting ≥1 AE at 16 weeks. RESULTS: Thirty-four patients were included. EFFICACY: 19 patients (55.9%) achieved PASI-75 or PGA 0/1. SAFETY: 23 patients (67.6%) experienced ≥1 AEs. Five patients (14.7%) withdrew treatment prior to week 16 due to AEs. One patient withdrew treatment due to mood lability and depression. Common AEs included headache (32.4%), nausea (20.6%), diarrhoea (14.7%), weight loss (8.8%), and loose stool (8.8%). CONCLUSION: Apremilast monotherapy had higher efficacy with similar safety outcomes in the real world compared to clinical trials. There were higher proportions of reported headaches compared to clinical trials. This study supports the apremilast monotherapy clinical trial findings, suggesting that it has an acceptable safety profile and significantly reduces the severity of moderate to severe plaque psoriasis. Limitations include the retrospective nature of the study.