Multicenter Canadian case series of pediatric patients less than 12 years of age with moderate-to-severe atopic dermatitis treated with dupilumab.

BACKGROUND: Dupilumab is approved for moderate-severe atopic dermatitis (AD) in patients aged ≥6 months by the US Food and Drug Administration and Health Canada; however, there are little real-world data because providers have limited practical experience with this recently approved therapy. OBJECTIVES: To describe the real-world effectiveness and safety in patients aged <12 years with moderate-severe AD currently receiving or previously having received dupilumab. METHODS: A multicenter retrospective study was conducted at six Canadian sites. Cases were divided into Group 1 ≤2 years old, Group 2 >2 to <6 years old, and Group 3 ≥6 to <12 years old. Medical history and details of dupilumab treatment were collected. The primary outcome was to measure the improvement in eczema area and severity index. Secondary outcomes examined included the children's dermatology life quality index/infant's dermatitis quality of life, peak pruritus numerical rating scale, and delay to dupilumab access for patients who were considered off-label for dupilumab due to their age. RESULTS: Sixty three pediatric patients (37 males) with moderate-to-severe AD were included; the mean age was 6.4 years old (range: 2-11) when dupilumab treatment was started. Overall, 75% (36/48) achieved EASI-75% and 71% (34/48) achieved EASI-90. EASI-75 and EASI-90 were achieved in 90% (17/19) and 73% (12/19) in patients <6 years old, and 76% (22/29) and 59% (17/29) in patients >6 years old, respectively. No serious adverse events were reported. CONCLUSIONS: Dupilumab is safe and effective for patients under the age of 12. However, even for experienced providers, access to the medication was challenging.

A Practical Guide to Using Biologics in Pediatric Dermatology.

Psoriasis, hidradenitis suppurativa (HS), atopic dermatitis (AD), and chronic spontaneous urticaria (CSU), are common, immune-mediated, chronic, inflammatory skin diseases that can affect the pediatric population. While there is adequate evidence supporting the use of biologics in pediatric patients, concerns regarding safety and efficacy amongst healthcare providers are not uncommon. However, new emerging evidence in this population highlights the safety of biologic therapy, making it crucial to review and establish a practical guide for their use. This article describes a methodological framework for initiating biologics in the management of pediatric psoriasis, HS, AD, and CSU, with a special focus on baseline work-up, monitoring, dosing, and considerations in this population.

Brodalumab-Induced Eczematous Reactions in Psoriasis Patients: Management With Switching to Risankizumab.

Biological treatments targeting IL-17 are highly efficacious with rapid onset of action in psoriasis. Cutaneous adverse events are associated with different biological treatments, including paradoxical psoriasis and eczematous reactions. Brodalumab was previously suggested as an alternative treatment option in psoriasis patients who developed dermatitis or paradoxical psoriasis while on a biologic. Here we report three psoriasis patients who developed brodalumab induced eczematous reaction with complete clearance after switching to risankizumab. Early recognition is crucial for appropriate management. We propose switching patients with psoriasis who develop severe eczematous reaction while on a biologic targeting IL-17 to an IL 23 inhibitor due to efficacy in psoriasis and rarely reported eczematous reaction.

Population pharmacokinetic and exposure-efficacy analysis of ixekizumab in paediatric patients with moderate-to-severe plaque psoriasis (IXORA-PEDS).

AIMS: Ixekizumab is a high-affinity monoclonal antibody that selectively targets interleukin-17A used in the treatment of adult and paediatric patients with moderate-to-severe psoriasis. This analysis evaluated the pharmacokinetics (PK) of ixekizumab and the exposure-efficacy relationship in paediatric patients aged 6 to <18 years with psoriasis. METHODS: Population PK and exposure-efficacy models were developed. The models used data from paediatric patients with psoriasis participating in the Phase 3 IXORA-PEDS trial in which patients were dosed according to weight categories. The exposure-efficacy model is a Psoriasis Area and Severity Index (PASI) time course model using data up to Week 12, a co-primary efficacy endpoint. RESULTS: A 2-compartment population PK model describes the PK of ixekizumab in paediatric patients with the effect of body weight incorporated on clearance and volume terms using an allometric relationship. The weight category-based dosing ensured that ixekizumab mean trough serum concentrations in paediatric patients with psoriasis (3.20-3.33 µg/mL) were within the range of concentrations observed in adult patients with psoriasis (mean [standard deviation]: 3.48 [2.16] µg/mL) administered an efficacious dosing regimen. The observed PASI response rates at Week 12 in paediatric patients (91.9/81.8/52.5% for PASI75/90/100) are well predicted by the final exposure-efficacy model and response rates are similar or higher than those achieved in adults (86.2/66.6/35.0% for PASI75/90/100). CONCLUSION: This analysis is the first to describe the PK and exposure-efficacy relationship of ixekizumab in paediatric patients with psoriasis. The analyses support the selection of the weight category-based ixekizumab dosing regimens approved for use in paediatric patients with psoriasis.

Management of moderate-to-severe plaque psoriasis with biologics: A treat-to-target position paper.

Treat-to-target (T2T) recommendations for the use of systemic therapies (including biologics) in patients with moderate-to-severe plaque psoriasis have been published by a few groups of experts worldwide. However, there remains considerable variability in the choice of target severity measure and timing of milestones. To develop consensus recommendations for implementing T2T strategies for the management of moderate-to-severe plaque psoriasis using biologics. An expert group of Canadian dermatologists (the Committee) convened to develop a T2T consensus statement. They held a virtual meeting during which a preliminary set of criteria was created. These criteria were then reviewed, modified, and recirculated until unanimous agreement was achieved. The Committee agreed that defining treatment target is multidimensional and should reflect objective severity measures, as well as clinician and patient-reported outcomes. The Committee unanimously proposes a criterion-based system for determining the achievement of treatment target. The proposed T2T approach presented here provides a clinical framework for defining treatment success, measuring progress toward treatment success, recognizing when treatment modifications are warranted, and recommending treatment optimization strategies.

Oral Methotrexate Monotherapy for Severe Alopecia Areata: A Single Center Retrospective Case Series.

BACKGROUND: Although several therapeutic options have been suggested for alopecia areata (AA), none of them are consistently effective, thus making the management of severe or refractory cases challenging. Several studies have recently reported the usage of methotrexate (MTX) in AA; however, the pure effect of MTX monotherapy remains elusive. OBJECTIVE: To evaluate efficacy and safety of oral methotrexate monotherapy for AA. METHODS: We retrospectively reviewed the clinical course of AA patients including pediatric cases treated with MTX monotherapy. Their detailed clinical data including original severity of AA, final treatment outcome, the duration until the maximum response, and side effects, were assessed. Statistical analysis was performed to evaluate if the clinical factors including the duration of current alopecia, age, the presence of body hair loss, and sex were associated with treatment response. RESULTS: All included patients had severe AA and failed standard therapies. Thirteen out of 15 cases demonstrated improvement during the monotherapy, and all responders demonstrated the maximum response within 1 year. Female patients had significantly better outcomes than male patients. Other factors did not significantly influence on the treatment outcome. None of the patients experienced side effects that were severe enough to terminate the treatment. CONCLUSIONS: Our results support MTX monotherapy as a feasible option for severe AA patients who fail other standard therapies or for whom systemic corticosteroids are contraindicated.

Management of pediatric plaque psoriasis using biologics.

BACKGROUND: Psoriasis is a chronic inflammatory disease with clinical manifestations of the skin that affect adults and children. In adults, biologics have revolutionized the treatment of moderate to severe plaque psoriasis where clear or almost clear is a tangible goal. Research on biologics has recently been extended to children. The introduction of these new therapeutic options has outpaced the limited guidelines in this population. OBJECTIVE: To provide a review of current data on biologics, with a proposal for a clinically relevant treatment algorithm on the management of moderate to severe plaque psoriasis in the pediatric population. METHODS: A Canadian panel with expertise in psoriasis, pediatric dermatology, and experience with consensus recommendation processes was selected to review the current landscape of pediatric psoriasis and clinical data on biologics plus identify special considerations for baseline workup and monitoring. Recommendations were reviewed and edited by each expert in an iterative process. CONCLUSION: A treatment algorithm for moderate to severe plaque psoriasis in pediatric patients is presented, incorporating approved biologics. Guidance on baseline screening and ongoing monitoring is also provided. Ultimately, treatment choice depends on the patient and his or her caregiver, with consideration of comorbidities, impact on quality of life, and relevant safety aspects.

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.

Undergraduate Dermatology Medical Education: Results of a Large-Scale Patient Viewing Program.

BACKGROUND: Delivering quality dermatologic instruction to medical students can be difficult; time constraints, limited clinical teachers, and a lack of standardization pose challenges. The literature suggests that many trainees and primary care physicians could benefit from increased clinical dermatology teaching. OBJECTIVE: We sought to deliver and analyze the results of a large-scale patient-viewing undergraduate dermatology education program. METHODS: A total of 250 third-year medical students participated in a 32-station patient-viewing program. Voluntary pre- and posttest surveys were administered to evaluate knowledge and self-perceived abilities in dermatology. The identical tests were composed of 20 multiple-choice and 5 self-perception questions. RESULTS: The response rate for completion of pre- and posttests was 24% (N = 59). Pre- and postknowledge test score means were 69.0% and 93.20%, respectively. Pre- and post-self-perception test score means were 3.95/10 and 7.25/10, respectively. Positive student feedback was received on the patient-viewing educational experience. CONCLUSION: Improvements in knowledge scores and self-assessment scores support the potential integration of structured patient-viewing teaching into undergraduate dermatology medical education curricula.

Approach to the Assessment and Management of Pediatric Patients with Atopic Dermatitis: A Consensus Document. Section II: Comorbid Disease in Pediatric Atopic Dermatitis.

Pediatric atopic dermatitis (AD) is one of the most common skin conditions encountered by health-care providers caring for infants, children, and adolescents. Pediatric patients with AD may present with other allergic and nonallergic comorbidities that require appropriate treatment and referral. They may also experience a trajectory of allergic diseases known as the atopic march, which depends on a complex interaction between genetic and environmental factors and likely involves early epidermal barrier dysfunction. Here we provide a review and clinical recommendations on the assessment and referral of comorbidities in pediatric AD.

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

Because atopic dermatitis (AD) is a chronic, relapsing disease, treatment requires the use of both active therapy to control flares and preventative maintenance therapy to promote integrity of the skin barrier. In this third of four sections, important clinical considerations for the treatment of pediatric AD are reviewed. Emerging therapies in development for pediatric AD are introduced.

Approach to the Assessment and Management of Pediatric Patients With Atopic Dermatitis: A Consensus Document. Section I: Overview of Pediatric Atopic Dermatitis.

Pediatric atopic dermatitis (AD) is one of the most common dermatoses encountered by health-care providers treating children. Diagnosis of AD is clinical, with no universally accepted biomarkers or assessment tools. Patient-reported outcomes and subjective assessments of quality of life in both the patient and family are important considerations when treating pediatric AD. Here, we provide an overview of pediatric AD epidemiology, its clinical presentation, burden, diagnosis, and assessment, with a focus on implications for patient counseling in order to optimize care.

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.

Approach to the Assessment and Management of Pediatric Patients With Atopic Dermatitis: A Consensus Document. Section IV: Consensus Statements on the Assessment and Management of Pediatric Atopic Dermatitis.

This document is intended to provide practical guidance to physicians treating pediatric atopic dermatitis (AD), especially dermatologists, pediatricians, allergists, and other health-care professionals. The recommendations contained here were formalized based on a consensus of 12 Canadian pediatric dermatologists, dermatologists, pediatricians, and pediatric allergists with extensive experience managing AD in the pediatric population. A modified Delphi process was adopted with iterative voting on a 5-point Likert scale, with a prespecified agreement cutoff of 75%. Topic areas addressed in the 17 consensus statements reflect areas of practical management, including counselling, assessment, comorbidity management, and therapy.

Approach to the Assessment and Management of Adult Patients With Atopic Dermatitis: A Consensus Document. Section II: Tools for Assessing the Severity of Atopic Dermatitis.

Clinicians rely on clinical measures to define the severity of atopic dermatitis and assess outcomes of therapy. These measures can be objective (ie, physician assessments of disease severity) or subjective (ie, patient-reported symptoms and quality of life outcomes). In this review, the most commonly used tools for assessing atopic dermatitis severity in adult patients are presented and compared. These include Eczema Area and Severity Index (EASI); SCORing Atopic Dermatitis (SCORAD); Physician Global Assessment (PGA); body surface area (BSA); Atopic Dermatitis Severity Index (ADSI); Six Area, Six Sign Atopic Dermatitis (SASSAD); Patient Oriented Eczema Measure (POEM); Dermatology Life Quality Index (DLQI); and pruritus Numerical Rating Scale (NRS). Available severity strata for the tools are summarized, although the use of severity strata in clinical practice is not recommended. Since both objective and subjective assessments of disease severity are important to assess, consideration of clinical characteristics such as disease recurrence or persistence, as well as location of the affected areas, should be considered in the overall judgement of disease severity and consideration of therapy choice.

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.