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.

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.

Atopic dermatitis treated with tralokinumab and upadacitinib combination therapy: A case report.

A patient presented to clinic with atopic dermatitis that had been previously unresponsive to multiple topical and systemic therapies. They were successfully treated with a combination of tralokinumab and upadacitinib, showing significant improvement after 3 weeks and near-resolution after 6 months.

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.

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.

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.

Systematic Review on the Efficacy and Safety of Oral Janus Kinase Inhibitors for the Treatment of Atopic Dermatitis.

Background: Atopic dermatitis is a chronic, relapsing and remitting disease that can be difficult to treat despite a recently approved biologic therapy targeting IL-4/IL-13 receptor. Oral janus kinase inhibitors (JAKi) represent a novel therapeutic class of targeted therapy to treat moderate-to-severe atopic dermatitis (AD). Objective: To review the efficacy, safety, and pharmacokinetic characteristics of oral JAKi in the treatment of AD. Methods: A PRISMA systematic review was conducted using MEDLINE, EMBASE (Ovid), and PubMed databases for studies assessing the efficacy, safety, and/or pharmacokinetic properties of oral forms of JAKi in the treatment of AD in pediatric or adult populations from inception to June 2021. Results: 496 papers were reviewed. Of 28 articles that underwent full text screening, 11 met our inclusion criteria for final qualitative review. Four studies examined abrocitinib; three studies examined baricitinib; three examined upadacitinib and one examined gusacitinib (ASN002). Significant clinical efficacy and a reassuring safety profile was reported for all JAKi agents reviewed. Rapid symptom control was reported for abrocitinib, baricitinib and upadacitinib. Limitations: Given the relatively limited evidence for each JAKi and the differences in patient eligibility criteria between studies, the data was not deemed suitable for a meta-analysis at this time. Conclusion: Given their ability to achieve rapid symptom control with a reassuring safety profile, we recommend considering the use of JAKi as a reliable systemic treatment option for adult patients with moderate-to-severe AD, who are unresponsive to topical or skin directed treatments.

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 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.