Dupilumab Safety and Efficacy up to 1 Year in Children Aged 6 Months to 5 Years with Atopic Dermatitis: Results from a Phase 3 Open-Label Extension Study.

BACKGROUND: Pediatric patients with moderate-to-severe atopic dermatitis (AD) often experience a high disease burden and have a high risk of persistent disease. Standard-of-care immunosuppressive systemic treatments have been used off-label for AD in pediatric patients despite concerns for suboptimal safety with continuous use and risk of relapse upon discontinuation. The biologic agent dupilumab is the first systemic treatment approved for moderate-to-severe AD in children as young as 6 months. Long-term safety and efficacy data in this patient population are needed to inform continuous AD management. OBJECTIVES: The purpose of this work was to determine the long-term safety and efficacy of dupilumab treatment up to 1 year in an open-label extension (OLE) study [LIBERTY AD PED-OLE (NCT02612454)] in children aged 6 months to 5 years with moderate-to-severe AD who previously participated in the 16-week, double-blind, phase 3 LIBERTY AD PRESCHOOL trial (NCT03346434 part B; parent study) and were subsequently enrolled in PED-OLE. METHODS: In PED-OLE, patients received dupilumab every 4 weeks according to a weight-tiered regimen (body weight ≥ 5 kg to < 15 kg: 200 mg; ≥ 15 kg to < 30 kg: 300 mg). RESULTS: Data for 142 patients were analyzed, 60 of whom had completed the 52-week visit at time of database lock. Mean age at baseline was 4.1 y [SD, 1.13; range, 1.0-5.9 years]. A majority (78.2%) of patients reported ≥ 1 treatment-emergent adverse event (TEAE), most of which were mild or moderate and transient. The most frequently reported TEAEs were nasopharyngitis (19.7%), cough (15.5%), and pyrexia (14.1%). One TEAE led to treatment discontinuation (severe urticaria, which resolved in 1 day). By week 52, 36.2% of patients had achieved an Investigator's Global Assessment score of 0/1 (clear/almost clear skin), and 96.6%, 79.3%, and 58.6% had at least 50%, 75%, or 90% improvement, respectively, in Eczema Area and Severity Index scores. CONCLUSIONS: Consistent with results seen in adults, adolescents, and older children (aged 6-11 years), treatment with dupilumab for up to 1 year in children aged 6 months to 5 years with inadequately controlled moderate-to-severe AD demonstrated an acceptable long-term safety profile and sustained efficacy. These results support the long-term continuous use of dupilumab in this patient population. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT02612454 and NCT03346434 (part B).

Atopic dermatitis (AD) is a chronic inflammatory skin disease that often results in a high disease burden in young children and their families. Patients often need long-term treatment to control their disease symptoms, including itch and rash. Dupilumab treatment for 16 weeks has shown benefits in children aged 6 months to 5 years with moderate-to-severe AD, with an acceptable safety profile. As AD is likely to continue from childhood into adolescence and adulthood, there is a need for data supporting long-term use of dupilumab in young children. In this study, children who completed the 16-week study continued dupilumab treatment for up to 1 year, receiving 200 mg or 300 mg of dupilumab (depending on the child's bodyweight) every 4 weeks. Through the year of treatment, 78.2% of patients reported at least one side effect, most of which were mild or moderate. Only one patient interrupted treatment because of severe skin rash (hives), which was resolved in 1 day. At the end of the year, 36.2% of patients had clear or almost clear skin, and almost all (96.6%) achieved at least 50% improvement in their extent and severity of disease. Additionally, 79.3%, and 58.6% had at least 75% or 90% improvement in their extent and severity of disease. In summary, consistent with results seen in adults, adolescents, and older children, this study showed that 1-year dupilumab treatment provides continued benefits with an acceptable safety profile. These results support long-term continuous use of dupilumab in children aged 6 months to 5 years with moderate-to-severe AD. What is the long-term safety and efficacy profile in young children with moderate-to-severeatopic dermatitis treated with dupilumab?

Guidelines of care for the management of atopic dermatitis in adults with phototherapy and systemic therapies.

BACKGROUND: For people with atopic dermatitis (AD) refractory to topical therapies, treatment with phototherapy and systemic therapies can be considered. Multiple biologic therapies and Janus kinase (JAK)inhibitors have been approved since 2014 to treat AD. These guidelines update the 2014 recommendations for management of AD with phototherapy and systemic therapies. OBJECTIVE: To provide evidence-based recommendations on the use of phototherapy and systemic therapies for AD in adults. METHODS: A multidisciplinary workgroup conducted a systematic review and applied the GRADE approach for assessing the certainty of evidence and formulating and grading recommendations. RESULTS: The workgroup developed 11 recommendations on the management of AD in adults with phototherapy and systemic agents, including biologics, oral JAK inhibitors, and other immunomodulatory medications. LIMITATIONS: Most randomized controlled trials of phototherapy and systemic therapies for AD are of short duration with subsequent extension studies, limiting comparative long-term efficacy and safety conclusions. CONCLUSIONS: We make strong recommendations for the use of dupilumab, tralokinumab, abrocitinib, baricitinib, and upadacitinib. We make conditional recommendations in favor of using phototherapy, azathioprine, cyclosporine, methotrexate, and mycophenolate, and against the use of systemic corticosteroids.

Executive summary: Guidelines of care for the management of atopic dermatitis in adults with phototherapy and systemic therapies.

BACKGROUND: The summarized guidelines update the 2014 recommendations for the management of AD with phototherapy and systemic therapies. METHODS: A multidisciplinary workgroup conducted a systematic review and applied the GRADE approach for assessing the certainty of the evidence and formulating and grading recommendations. RESULTS: The workgroup developed 11 recommendations on the management of AD in adults with phototherapy and systemic therapies, including biologics, oral Janus Kinase inhibitors, and other immunomodulatory medications. CONCLUSIONS: The evidence supported strong recommendations for the use of dupilumab, tralokinumab, abrocitinib, baricitinib, and upadacitinib and conditional recommendations in favor of using phototherapy, azathioprine, cyclosporine, methotrexate, and mycophenolate, and against the use of systemic corticosteroids.

Golimumab in Children with Chronic Recurrent Multifocal Osteomyelitis: A Case Series and Review of the Literature.

BACKGROUND: Chronic recurrent multifocal osteomyelitis (CRMO) is a rare autoinflammatory bone disease requiring immunosuppressive treatment in half of patients. Monoclonal tumor necrosis factor inhibitors (TNFi) are often used as effective second-line off-label therapies. However, paradoxical psoriasis can occur in a subset of patients exposed to monoclonal TNFi and can prompt conversion to alternate therapy if severe. OBJECTIVE: The aim of this study was to determine the efficacy and safety of golimumab, a fully humanized TNFi, in children with CRMO, including those who develop paradoxical psoriasis after exposure to other monoclonal TNFi. METHODS: A retrospective chart review was conducted of patients with CRMO who received golimumab in a single center between 01 June, 2018 and 31 December, 2020. Patients who were diagnosed before 21 years of age and followed up for CRMO at least once after receiving ≥ 3 months of golimumab were included. Extracted data included patient demographics, whole-body MRI lesion counts, clinically relevant data, laboratory results, patient-reported outcomes, and psoriasis burden. Linear mixed models with log-transformed outcomes were used to assess changes in the outcomes over time. The random effect is included in the model to account for the within-subject correlation of repeated measures. p-values and 95% confidence intervals were reported. RESULTS: Eighteen patients were included. Patients were observed for a median of 9.95 months [interquartile range 3.84-15.64]. The median age at the initiation of golimumab was 10.95 years [9.86-13.77] and the median duration of disease between the disease onset and the initiation of golimumab was 2.60 years [1.66-3.62]. Ten patients received golimumab via intravenous route and eight patients received golimumab via subcutaneous route. The median dose was 1.64 mg/kg/month [1.46, 2]. Fourteen patients were previously treated with disease-modifying antirheumatic drugs and 17 with other TNFi. Patients treated with golimumab showed significant improvement in median physician global assessment for CRMO from 2.00 [1.00-3.00] to 0.00 [0.00-0.25] by the fourth visit (p < 0.001), with median erythrocyte sedimentation rate (ESR) decreasing significantly from 12.00 [6.75-23.75] to 5.00 [3.00-10.00] by the fourth visit (p < 0.05). The median number of lesions on MRI decreased significantly from 3.50 [2.00-5.50] to 0.50 [0.00-4.25] lesions per patient (p < 0.01). Nine out of 12 patients who had previous paradoxical psoriasis associated with adalimumab or infliximab had persistent active psoriasis at study baseline. For patients with psoriasis at study baseline, the prevalence of psoriasis had decreased from 100% to approximately 50-57% at the following visits. Of the 18 patients initiated on golimumab in this study, there was only one new case of mild psoriasis in a patient with previously resolved infliximab-associated paradoxical psoriasis. No serious infections or adverse events were noted during the study. Two patients in the study showed clinical improvement with concomitant golimumab and ustekinumab with no reported adverse side effects or increased effects in these patients over a 16-month interval, showing that this combination can be safe and effective for children with CRMO. CONCLUSION: In our experience, golimumab has been shown to be a safe and effective therapy for CRMO and demonstrated improvement in paradoxical psoriasis in many patients. Longer follow-up periods would be helpful to develop longer term outcomes data for patients with CRMO and overall paradoxical psoriasis risk.

Risk of Infection in Children With Psoriasis Receiving Treatment With Ustekinumab, Etanercept, or Methotrexate Before and After Labeling Expansion.

Importance: Psoriasis in children is increasingly treated with systemic medications, yet their risk of serious infection is not well characterized in clinical practice. Pediatric clinical trials for these medications were often small and placebo controlled. Objective: To estimate the 6-month rate of infections among children with psoriasis who started treatment with ustekinumab, etanercept, or methotrexate. Design, Setting, and Participants: This cohort study used insurance claims data from clinical practices across the US on children aged 17 years or younger with psoriasis who were receiving treatment with a topical medication for psoriasis and started new treatment with ustekinumab, etanercept, or methotrexate. The analysis was stratified by the time before pediatric labeling (2009-2015) and after pediatric approval (2016-2021). Patient follow-up started 1 day after initiating treatment and ended at 6 months. Exposures: New treatment with ustekinumab, etanercept, and methotrexate. Main Outcomes and Measures: During follow-up, the frequency of inpatient serious infections and outpatient infections requiring treatment was compared. Event rates and rate ratios were estimated after propensity score decile stratification. Results: After exclusions, we identified 2338 patients (1368 girls [57.8%]) who initiated new treatment with a targeted immunomodulating agent. In all, 379 patients started treatment with ustekinumab, 779 patients started treatment with etanercept, and 1180 patients started treatment with methotrexate from 2009 through 2021. The propensity score-adjusted incidence rate of serious infection was 18.4 per 1000 person-years (3 events) for ustekinumab users, 25.6 per 1000 person-years (9 events) for etanercept users, and 14.9 per 1000 person-years (8 events) for methotrexate users. The adjusted rate of outpatient infections was 254.9 per 1000 person-years (39 events) for ustekinumab users, 435.7 per 1000 person-years (139 events) for etanercept users, and 433.6 per 1000 person-years (209 events) for methotrexate users. The adjusted rate ratio of outpatient infections was 0.58 (95% CI, 0.41-0.83) for ustekinumab vs etanercept, 0.66 (95% CI, 0.48-0.91) for ustekinumab vs methotrexate, and 0.95 (95% CI, 0.75-1.21) for etanercept vs methotrexate. Rate ratios were similar during the off-label use era and after pediatric labeling. Conclusions and Relevance: Among children with psoriasis who started treatment with immunomodulating agents, serious infections were infrequent. This cohort study suggests that there was no increase in the risk of outpatient infections for children who started treatment with ustekinumab compared with etanercept or methotrexate.

Executive summary: American Academy of Dermatology guidelines of care for the management of atopic dermatitis in adults with topical therapies.

These guidelines update the 2014 recommendations for management of atopic dermatitis in adults with topical therapies. A multidisciplinary workgroup employed best practices for guideline development, including a systematic review of the evidence and application of the Grading of Recommendations, Assessment, Development, and Evaluation approach for assessing the certainty of the evidence and formulating and grading recommendations. The evidence on atopic dermatitis treatment supported strong recommendations for the use of nonprescription moisturizers, topical calcineurin inhibitors, topical corticosteroids, and topical PDE-4 and JAK inhibitors. Conditional recommendations are made for the use of bathing and wet wrap therapy and against the use of topical antimicrobials, antiseptics, and antihistamines.

Guidelines of care for the management of atopic dermatitis in adults with topical therapies.

BACKGROUND: New evidence has emerged since the 2014 guidelines that further informs the management of atopic dermatitis (AD) with topical therapies. These guidelines update the 2014 recommendations for management of AD with topical therapies. OBJECTIVE: To provide evidence-based recommendations related to management of AD in adults using topical treatments. METHODS: A multidisciplinary workgroup conducted a systematic review and applied the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) approach for assessing the certainty of evidence and formulating and grading recommendations. RESULTS: The workgroup developed 12 recommendations on the management of AD in adults with topical therapies, including nonprescription agents and prescription topical corticosteroids (TCS), calcineurin inhibitors (TCIs), Janus kinase (JAK) inhibitors, phosphodiesterase-4 inhibitors (PDE-4), antimicrobials, and antihistamines. LIMITATIONS: The pragmatic decision to limit the literature review to English-language randomized trials may have excluded data published in other languages and relevant long-term follow-up data. CONCLUSIONS: Strong recommendations are made for the use of moisturizers, TCIs, TCS, and topical PDE-4 and JAK inhibitors. Conditional recommendations are made for the use of bathing and wet wrap therapy and against the use of topical antimicrobials, antiseptics, and antihistamines.

Dupilumab in children aged 6 months to younger than 6 years with uncontrolled atopic dermatitis: a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Current systemic treatments for children younger than 6 years with moderate-to-severe atopic dermatitis that is uncontrolled with topical therapies might have suboptimal efficacy and safety. Dupilumab is approved for older children and adults with atopic dermatitis and for other type 2 inflammatory conditions. We aimed to evaluate efficacy and safety of dupilumab with concomitant low-potency topical corticosteroids in children aged 6 months to younger than 6 years with moderate-to-severe atopic dermatitis. METHODS: This randomised, double-blind, placebo-controlled, parallel-group, phase 3 trial was conducted in 31 hospitals, clinics, and academic institutions in Europe and North America. Eligible patients were aged 6 months to younger than 6 years, with moderate-to-severe atopic dermatitis (Investigator's Global Assessment [IGA] score 3-4) diagnosed according to consensus criteria of the American Academy of Dermatology, and an inadequate response to topical corticosteroids. Patients were randomly assigned (1:1) to subcutaneous placebo or dupilumab (bodyweight ≥5 kg to <15 kg: 200 mg; bodyweight ≥15 kg to <30 kg: 300 mg) every 4 weeks plus low-potency topical corticosteroids (hydrocortisone acetate 1% cream) for 16 weeks. Randomisation was stratified by age, baseline bodyweight, and region. Patient allocation was done via a central interactive web response system, and treatment allocation was masked. The primary endpoint at week 16 was the proportion of patients with IGA score 0-1 (clear or almost clear skin). The key secondary endpoint (coprimary endpoint for the EU and EU reference market) at week 16 was the proportion of patients with at least a 75% improvement from baseline in Eczema Area and Severity Index (EASI-75). Primary analyses were done in the full analysis set (ie, all randomly assigned patients, as randomly assigned) and safety analyses were done in all patients who received any study drug. This study was registered with ClinicalTrials.gov, NCT03346434. FINDINGS: Between June 30, 2020, and Feb 12, 2021, 197 patients were screened for eligibility, 162 of whom were randomly assigned to receive dupilumab (n=83) or placebo (n=79) plus topical corticosteroids. At week 16, significantly more patients in the dupilumab group than in the placebo group had IGA 0-1 (23 [28%] vs three [4%], difference 24% [95% CI 13-34]; p<0·0001) and EASI-75 (44 [53%] vs eight [11%], difference 42% [95% CI 29-55]; p<0·0001). Overall prevalence of adverse events was similar in the dupilumab group (53 [64%] of 83 patients) and placebo group (58 [74%] of 78 patients). Conjunctivitis incidence was higher in the dupilumab group (four [5%]) than the placebo group (none). No dupilumab-related adverse events were serious or led to treatment discontinuation. INTERPRETATION: Dupilumab significantly improved atopic dermatitis signs and symptoms versus placebo in children younger than 6 years. Dupilumab was well tolerated and showed an acceptable safety profile, similar to results in older children and adults. FUNDING: Sanofi and Regeneron Pharmaceuticals.

Atopic Dermatitis and Food Allergy: Best Practices and Knowledge Gaps-A Work Group Report from the AAAAI Allergic Skin Diseases Committee and Leadership Institute Project.

Allergists are often asked to evaluate children with atopic dermatitis (AD) for allergen triggers to disease. Testing, particularly for food triggers, often leads to elimination diets in an effort to improve AD control. However, the dual exposure hypothesis suggests that oral tolerance to food antigens is promoted through high-dose oral exposure, where sensitization occurs through lower dose cutaneous exposure. This suggests that strict elimination diets may pose some risks in children with AD. In addition, emerging evidence suggests an important role of skin inflammation in further allergic disease and the importance of dietary exposure to maintain oral tolerance. This work group report reviews current guidelines-based management for children with moderate-to-severe AD, the evidence for current recommendations for the evaluation and management of these children, provides a nuanced examination of these studies, and addresses current knowledge gaps in the care of these children.

Pharmacokinetics, Safety, Efficacy, and Biomarker Profiles During Nemolizumab Treatment of Atopic Dermatitis in Adolescents.

INTRODUCTION: Nemolizumab, a new monoclonal antibody that targets the receptor alpha of the neuroimmune cytokine interleukin-31 (IL-31), has shown efficacy in atopic dermatitis (AD) in adults. This study evaluated the pharmacokinetics (PK) and safety of nemolizumab in adolescents with moderate to severe AD as well as the relationship between nemolizumab concentrations and clinical efficacy and the effect of nemolizumab on protein biomarkers. METHODS: Open-label, 16-week study of nemolizumab in patients aged 12-17 years with moderate to severe AD (baseline EASI ≥ 16, IGA ≥ 3, and BSA ≥ 10%) and associated pruritus with baseline average daily peak pruritus numeric rating scale (PP-NRS) intensity of at least 4. Nemolizumab was administered subcutaneously as a loading dose of 60 mg at baseline, followed by 30 mg every 4 weeks until week 12 with background topical corticosteroids (TCS) or calcineurin inhibitors (TCI). Subsequently patients were followed for 8 weeks more. Stratum corneum (SC) and plasma samples were collected for biomarker assessments. RESULTS: Twenty patients participated, with a mean age of 14.8 ± 1.6 years. The PK of nemolizumab was described by a one-compartment model with linear elimination, a first-order absorption, and a mean half-life of 16.7 ± 4.1 days. Mean trough concentrations ranged from 2935 ± 1029 ng/mL to 3292 ± 2018 ng/mL over the 16-week treatment period. There was a marked improvement in rash, itch, and sleep with a decrease from baseline to week 16 in EASI by 66.5 ± 32.5%, in PP-NRS by 43.2 ± 37%, and in sleep disturbance numeric rating scale by 53.5 ± 47.8%. The popPK and PK/PD analyses confirmed that model-predicted exposure and efficacy of nemolizumab were similar in adolescents compared to adults receiving the same dosing regimens. Age did not impact PK parameters, while the main source of PK variability was body weight. Analyses of SC samples identified a panel of AD-related pro-inflammatory biomarkers that were upregulated in lesional skin (compared to non-lesional skin) and correspondingly downregulated in clinical responders to nemolizumab (based on EASI75 and PP-NRS ≥ 4). Four biomarkers (CCL20, CCL22, CCL27, and VEGF) had changes that were 1.9-3.5-fold higher in EASI responders than in EASI non-responders (all p < 0.05). Analysis showed no significant correlation between plasma biomarkers and clinical scores. Adverse events were experienced by 33.3% of subjects (n = 6) and were primarily mild or moderate in severity. CONCLUSIONS: Nemolizumab PK and safety profiles in adolescents with moderate to severe AD are consistent with previous nemolizumab studies in adults. PK/PD models demonstrate similar exposure-response profiles in 12- to 17-year-old adolescents and adults for three clinical endpoints (EASI, IGA, and PP-NRS). Nemolizumab treatment reversed AD-related pro-inflammatory biomarkers in skin, indicating that the neuroimmune cytokine IL-31 is an important mediator of multiple pathways in AD. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov NCT03921411.

American Academy of Dermatology Guidelines: Awareness of comorbidities associated with atopic dermatitis in adults.

BACKGROUND: Studies found associations between atopic dermatitis (AD) and various comorbidities. OBJECTIVE: To appraise evidence of the association between AD and comorbidities among adults. METHODS: Our multidisciplinary work group conducted a systematic review of the association between AD and selected comorbidities. We applied the Grading of Recommendations, Assessment, Development, and Evaluation for prognosis approach for assessing the certainty of the evidence, providing statements of association based on the available evidence. RESULTS: Analysis of the evidence resulted in 32 statements. Clear evidence of the association of AD in adults and select allergic, atopic, immune-mediated mental health and bone health conditions and skin infections was identified. There is some evidence supporting an association between AD and substance use, attention deficit hyperactivity disorder, and elements of metabolic syndrome. Evidence suggests a small association with various cardiovascular conditions. The association between AD in adults and autism spectrum disorders, myocardial infarction, stroke, and metabolic syndrome is inconclusive. LIMITATIONS: This analysis is based on the best available evidence at the time it was conducted. This guideline does not make recommendations for screening or management of comorbidities in adults with AD. CONCLUSIONS: Clinicians should be aware of comorbidities associated with AD. Further research is needed to determine whether screening or management of comorbidities is beneficial for adults with AD.

Efficacy and Safety of Abrocitinib in Combination With Topical Therapy in Adolescents With Moderate-to-Severe Atopic Dermatitis: The JADE TEEN Randomized Clinical Trial.

Importance: Dupilumab subcutaneous injection is approved for treating moderate-to-severe atopic dermatitis (AD) in adolescents, but there has been too little research on an efficacious systemic oral treatment with a favorable benefit-risk profile for adolescents with moderate-to-severe AD. Objective: To investigate the efficacy and safety of oral abrocitinib plus topical therapy in adolescents with moderate-to-severe AD. Design, Setting, and Participants: The phase 3, randomized, double-blind, placebo-controlled study JADE TEEN was conducted in countries of the Asia-Pacific region, Europe, and North America in patients aged 12 to 17 years with moderate-to-severe AD and an inadequate response to 4 consecutive weeks or longer of topical medication or a need for systemic therapy for AD. The study was conducted between February 18, 2019, and April 8, 2020. The data were analyzed after study completion. Interventions: Patients were randomly assigned 1:1:1 to receive once-daily oral abrocitinib, 200 mg or 100 mg, or placebo for 12 weeks in combination with topical therapy. Main Outcomes and Measures: Coprimary end points were achievement of an Investigator's Global Assessment (IGA) response of clear (0) or almost clear (1) with improvement of 2 or more grades from baseline (IGA 0/1) and 75% or greater improvement from baseline in Eczema Area and Severity Index (EASI-75) response at week 12. Key secondary end points included 4-point or greater improvement in Peak Pruritus Numerical Rating Scale (PP-NRS4) at week 12. Adverse events (AEs) were monitored. Results: This study included 285 adolescents with moderate-to-severe AD (145 boys [50.9%] and 140 girls [49.1%]), of whom 160 (56.1%) were White and 94 (33.0%) were Asian; the median age was 15 years (interquartile range 13-17 years). Substantially more patients treated with abrocitinib (200 mg or 100 mg) vs placebo achieved an IGA response of 0/1 (46.2%; 41.6% vs 24.5%; P < .05 for both), EASI-75 (72.0%; 68.5% vs 41.5%; P < .05 for both), and PP-NRS4 (55.4%; 52.6% vs 29.8%; P < .01 for 200 mg vs placebo) at week 12. Adverse events were reported for 59 (62.8%), 54 (56.8%), and 50 (52.1%) patients in the 200 mg, 100 mg, and placebo groups, respectively; nausea was more common with abrocitinib, 200 mg (17 [18.1%]) and 100 mg (7 [7.4%]). Herpes-related AEs were infrequent; 1 (1.1%), 0, and 2 (2.1%) patients had serious AEs. Conclusions and Relevance: This randomized clinical trial found that oral abrocitinib combined with topical therapy was significantly more effective than placebo with topical therapy in adolescents with moderate-to-severe AD, with an acceptable safety profile. Trial Registration: ClinicalTrials.gov identifier: NCT03796676.

Paradoxical Psoriasis in Children Receiving Anti-TNFα Treatment for Inflammatory/autoimmune Disease.

Tumor necrosis factor alpha inhibitors (TNFi) are widely used in children with autoimmune and autoinflammatory conditions. Although TNFi are approved to treat psoriasis, they have also been shown to paradoxically induce psoriasiform lesions. In this review, we aim to focus on the clinical presentation and management of paradoxical psoriasis after exposure to TNFi in children with juvenile idiopathic arthritis (JIA), inflammatory bowel disease (IBD), or chronic nonbacterial osteomyelitis (CNO). A narrative review of the literature was performed given the limited number of publications on this topic. Children with IBD, CNO, and JIA have a higher risk of developing psoriasis at baseline, which increases after TNFi use in those with JIA and IBD. Risk factors for paradoxical psoriasis remain incompletely defined, and patients with IBD and/or CNO develop paradoxical psoriasis more commonly than those with JIA. Sex, race, and family history were not significantly associated with paradoxical psoriasis. The most commonly implicated TNFi include infliximab and adalimumab. Paradoxical psoriasis occurs in a similar distribution on the body to isolated psoriatic lesions and is morphologically indistinguishable. In many instances, topical therapies are effective in treating psoriasis and children can continue on TNFi for their primary disease. If lesions are severe or unacceptable to patients, TNFi may be switched or discontinued. Further research is needed to better characterize risk factors and understand the mechanism of disease pathogenesis. Pediatric health care providers who prescribe TNFi should counsel families regarding the risk of paradoxical psoriasis prior to starting the medication and monitor for new cutaneous eruptions.