Beyond Psoriasis: Novel Uses for Biologic Response Modifiers in Pediatric Dermatology

Dermatologists have witnessed the increasing availability of novel biologic response modifiers for the treatment of inflammatory and autoimmune diseases in recent years. The most common dermatologic indication for the use of biologic response modifiers in adults is psoriasis, but the U.S. Food and Drug Administration has not approved any of these agents for use in any dermatologic disease in children with the exception of omalizumab, and as such, use in this population is considered off‐label. In this review, we focus on the use of these agents in children to treat inflammatory skin diseases other than psoriasis, including atopic dermatitis, hidradenitis suppurativa, pemphigus vulgaris, bullous pemphigoid, and toxic epidermal necrolysis, with an emphasis on the use of etanercept, infliximab, rituximab, omalizumab, and ustekinumab. By highlighting novel uses of these agents, particularly for the treatment of dermatologic conditions for which optimal therapies are yet to be established, we hope to raise awareness of the potential use of this class of medications to treat inflammatory skin diseases in children.     

Psoriasis:Biologic treatment and liver disease

Patients with moderate or severe psoriasis have a high prevalence of chronic liver disease. Chronic liver disease in these patients is related to metabolic syndrome, alcohol abuse or viral infections. Therefore,treatment of these patients is challenging. Classic systemic treatments may be contraindicated because of their immunosuppressive and hepatotoxic potential.First-line therapy in this setting is generally ultraviolet B phototherapy combined with topical treatment, but its feasibility and efficacy are sometimes limited. The therapeutic options are further restricted by concomitant psoriatic arthritis. Biologic treatments have shown to be effective in psoriasis and psoriatic arthritis, and they are largely devoid of liver toxicity. Anti-tumor necrosis factor-alpha(TNF-α) treatments have proven to be effective and safe in patients with chronic hepatitis C virus(HCV) infections and other non-infectious chronic liver disorders, including alcoholic and non-alcoholic liver diseases. However, in chronic hepatitis B virus(HBV), anti-TNF-α treatments carry a high risk of HBV reactivation. Anti-interleukin-12/23 treatments are also effective in patients with psoriasis, but data regarding their safety in chronic hepatitis infections are still limited. Safety reports in patients with psoriasis and chronic HCV infection are contradictory, and in chronic HBVevidence indicate a potential risk of viral reactivation. Moreover, concerns remain about the long-term safety of both TNF-α antagonists and ustekinumab. Non-viral liver diseases such as alcoholic and non-alcoholic liver diseases are more prevalent in patients with psoriasis than in the general population. TNF-α antagonists have also been prescribed in these patients. Although data are still scarce in this setting, results suggest a favorable profile in patients with psoriasis and non-alcoholic liver diseases. We review the literature regarding all these aspects.     

Managing Pediatric Patients with Psoriasis

Childhood-onset psoriasis affects approximately one-third of the psoriatic population. Among many potential treatments of childhood psoriasis, biological agents are emerging as a valuable option in the management of this disease. InEurope, etanercept has recently been approved for children aged 8 years and over. Data froma well-designed clinical trial indicate that in children, etanercept effectively reduces psoriasis symptoms, with beneficial effects evident as early as 4 weeks after the initiation of treatment. Etanercept iswell tolerated; adverse effects are typically mild to moderate in severity. Early data from other biological agents are promising.     

银屑病的生物治疗新进展

银屑病是一种CD4+T淋巴细胞介导的自身免疫紊乱性疾病,生物制剂以阻断不同的免疫环节为靶点,治疗中重度银屑病疗效显著。阿法西普、依那西普、英利昔单抗、阿达木单抗及Ustekinumab是获得美国食品与药品管理局(Food and Drug Administration,FDA)批准应用的五种生物制剂,对其临床疗效、不良反应及应用前景进行了阐述。     

Integrating Biologic Agents into Management of Moderate-to-Severe Psoriasis: A Consensus of the Canadian Psoriasis Expert Panel

Background Approximately 2% of people worldwide have psoriasis, with as many as 1 million people with psoriasis in Canada alone.1,2 The severity of psoriasis ranges from mild to severe. It can lead to substantial morbidity and psychological stress and have a profound negative impact on patient quality of life.3,4 Although available therapies reduce therapies reduce the extent and severity of the disease and improve quality of life,3 reports have indicated a patient preference for more aggressive therapy and a dissatisfaction with the effectiveness of current treatment options.5Objective A Canadian Expert Panel, comprising Canadian dermatologists, convened in Toronto on 27 February 2004 to reach a consensus on unmet needs of patients treated with current therapies and how to include the pending biologic agents in and improve the current treatment algorithm for moderate-to-severe psoriasis. Current treatment recommendations suggest a stepwise strategy starting with topical agents followed by phototherapy and then systemic agents.3,6,7 The Panel evaluated the appropriate positioning of the biologic agents, once approved by Health Canada, for the treatment of moderate-to-severe psoriasis.Methods The Panel reviewed available evidence and quality of these data on current therapies and from randomized, controlled clinical trials.8–14 Subsequently, consensus was achieved by small-group workshops followed by plenary discussion.Results The Panel determined that biologic agents are an important addition to therapies currently available for moderate-to-severe psoriasis and proposed an alternative treatment algorithm to the current step wise paradigm.Conclusion The Panel recommended a new treatment algorithm for moderate-to-severe psoriasis whereby all appropriate treatment options, including biologic agents, are considered together and patients’ specific characteristics and needs are taken into account when selecting the most appropriate treatment option.

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SommaireAntècèdents Près de 2 % de la population mondiale est atteinte de psoriasis, dont un million de personnes au Canada.1,2 Le psoriasis peut varier de bénin à grave. Cette affection entraîne arfois une morbidité accrue et une détresse psychologique en plus d’avoir un impact négatif profond’sur la qualité de vie du patient.3,4 Bien que les traitements disponibles réduisent I’étendue et la gravité de la maladie et améliorent la qualité de vie,3 les rapports ont dénoté une préférence pour les traitements plus agressifs et une insatisfaction à I’égard de I’efficacite des options de traitement actuelles.5Objectif Un panel d’experts canadiens, formé de dermatologues, s’est réuni á Toronto le 27 février 2004 en vue d’atteindre un consensus sur les besoins non comblés des patients traités au moyen des thérapies actuelles, ainsi que d’évaluer les façons d’inclure les agents biologiques et d’améliorer les algorithmes de traitement du psoriasis modéré à grave. Actuellement, les traitements recommandés sont axés sur une stratégic par étapes, débutant avec des agents topiques, suivis d’une phototherapie et enfin des agents systémiques.3,6,7 panel a évalué le positionnement approprié des agents biologiques, une fois approuvés par Santé Canada, dans le traitement du psoriasis modéré à grave.Méthodes Le panel a passé en revue les rapports disponibles et la qualite des données relativement à ces thérapies ainsi que ceux des essais cliniques randomisés.8–14 Par la suite, un consensus a été atteint au moyen de petits ateliers de travail suivis d’une discussion plénière.Résultats Le panel a déterminé que les agents biologiques étaient un important ajout aux options thérapeutiques offertes actuellement dans le traitement du psoriasis modéré à grave et a proposé un algorithme de traitement en replacement à I’algorithme par étapes actuel.Conclusion Le panel a recommandé un nouvel algorithme de traitement pour le psoriasis modéré à grave, où on considère toutes les options thérapeutiques, y compris les agents biologiques, dans leur ensemble et on tient compte des caractéristiques et des besoins specifiques de chaque patient dans le choix de I’option adéquate.

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The Canadian Expert Panel meeting was supported by an educational grant from Serono Canada Inc. The opinions expressed are those of the authors and not of Serono. All participants have been involved in clinical trials involving at least one of the therapeutic agents discussed.

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At the time of the Canadian Expert Panel meeting, biologic agents such as alefacept, efalizumab, etanercept, and infliximab were not approved in Canada for the treatment of psoriasis. Upon final submission of this article, alefacept had just received approval for the treatment of psoriasis.     

Diagnosis and Treatment of Pediatric Psoriasis: Current and Future

Psoriasis is a common yet complex inflammatory dermatosis that may be seen in infants, children, and adolescents. The clinical presentation and course may be quite variable, and while patients with mild disease are often easily managed, those with recalcitrant or more severe disease often present a therapeutic dilemma given the number of therapies available and the relative lack of data on the efficacy and safety of use of these therapies in children. This review presents the reader with an overview of the current understanding of the pathophysiology, diagnosis, and treatment of pediatric psoriasis, with an emphasis on the available data in the literature that pertains to the use in children of currently available topical and systemic therapies, including topical corticosteroids, vitamin D analogs, phototherapy, systemic immunosuppressive medications, and biologic agents.     

Patient Satisfaction with Psoriasis Therapies: An Update and Introduction to Biologic Therapy

Background Psoriasis is a chronic, immune-mediated skin condition that often requires lifelong treatment. Many patients report dissatisfaction with traditional nonbiologic therapies because they are ineffective for their psoriasis, are associated with side effects, or impact negatively on quality of life.Objectives The aim of this article is to review the effect on patient quality of life of traditional nonbiologic psoriasis therapies and to discuss the impact of biologic psoriasis therapies on patient satisfaction.Methods A review of the literature is presented.Results Traditional nonbiologic psoriasis therapies can negatively impact quality of life due to a variety of factors including inconvenience and toxicity. Biologic agents have been developed that target the immunopathogenesis of psoriasis. Based on favorable efficacy and safety results in clinical trials, some of these agents are now approved for clinical use. Evidence suggests that patients receiving biologic therapies experience significant improvements in health-related quality of life.Conclusion Biologic agents offer new hope for patients with psoriasis that their chronic condition can be controlled in a manner that improves their quality of life and may lead to high levels of satisfaction with their treatment.

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SommaireAntécédents Le psoriasis est une affection cutanée chronique et à médiation immunologique qui nécessite souvent un traitement la vie longue. Un grand nombre de patients sont insatisfaits des traitements traditionnels non biologiques en raison de leur inefficacité contre le psoriasis, des effets secondaires ou de leur conséquences négatives sur la qualité de vie.Objectifs L’objectif du présent article est de passer en revue l’effet des traitements traditionnels non biologiques sur la qualité de vie des patients atteints de psoriasis et de discuter l’impact des traitements biologiques sur la satisfaction des patients.Méthodes Une révision des articles et des rapports publiés est présentée.Résultats Les traitements traditionnels non biologiques du psoriasis ont un impact négatif sur la qualité de vie des personnes affectées pour plusieurs raisons, notamment la toxicité et l’incommodité. Des agents biologiques qui s’attaquent à l’immunopathogenèse du psoriasis ont été mis au point. À la suite des résultats favorables quant à leur efficacité et à leur innocuité dans les essais cliniques, certains de ces agents ont été approuvés dans les traitements cliniques. Les symptômes suggèrent que les patients ayant reçu un traitement biologique présentent des améliorations considérables à la qualité de vie reliée à la santé.Conclusion Les agents biologiques offrent aux patients souffrant de psoriasis un nouvel espoir que leur condition chronique pourra être maîtrisée de façon à améliorer leur qualité de vie et qu’ils pourront être grandement satisfaits de leur traitement.

     

Active Tuberculosis in Patients with Psoriasis Receiving Biologic Therapy: A Systematic Review

American Journal of Clinical Dermatology - Biologic therapies pose a risk for opportunistic infections, especially for reactivating latent tuberculosis infection (LTBI). The aim was to describe the...     

Use of Biologic Agents in Combination with Other Therapies for the Treatment of Psoriasis

Psoriasis is a chronic inflammatory skin disorder, which is associated with a significant negative impact on a patient’s quality of life. Traditional therapies for psoriasis are often not able to meet desired treatment goals, and high-dose and/or long-term use is associated with toxicities that can result in end-organ damage. An improved understanding of the involvement of cytokines in the etiology of psoriasis has led to the development of biologic agents targeting tumor necrosis factor (TNF)-α and interleukins (ILs)-12/23. While biologic agents have improved treatment outcomes, they are not effective in all individuals with psoriasis. The combination of biologic agents with traditional therapies may provide improved therapeutic options for patients who inadequately respond to a single drug or when efficacy may be increased with supplementation of another treatment. In addition, combination therapy may reduce safety concerns and cumulative toxicity, as lower doses of individual agents may be efficacious when used together. This article reviews the current evidence available on the efficacy and safety of combining biologic agents with systemic therapies (methotrexate, cyclosporine, or retinoids) or with phototherapy, and the combination of biologic agents themselves. Guidance is provided to help physicians identify situations and the characteristics of patients who would benefit from combination therapy with a biologic agent. Finally, the potential clinical impact of biologic therapies in development (e.g., those targeting IL-17A, IL-17RA, or IL-23 alone) is analyzed.     

Internalized Stigma in Pediatric Psoriasis: A Comparative Multicenter Study

BackgroundInternalized stigma, adoption of negative attitudes and stereotypes of the society regarding persons'' illness, has not been studied previously in pediatric psoriasis patients.ObjectiveWe aimed to investigate the internalized stigma in pediatric psoriasis patients and to determine differences according to factors affecting internalized stigma compared to adult psoriasis patients.MethodsThis multicenter, cross-sectional, comparative study included 125 pediatric (55 female, 70 male; mean age±standard deviation [SD], 14.59±2.87 years) and 1,235 adult psoriasis patients (577 female, 658 male; mean age±SD, 43.3±13.7 years). Psoriasis Internalized Stigma Scale (PISS), Dermatology Life Quality Index (DLQI), Perceived Health Status (PHS), and the General Health Questionnaire (GHQ)-12 were the scales used in the study.ResultsThe mean PISS was 58.48±14.9 in pediatric group. When PISS subscales of groups were compared, the pediatric group had significantly higher stigma resistance (p=0.01) whereas adult group had higher scores of alienation (p=0.01) and stereotype endorsement (p=0.04). There was a strong correlation between mean values of PISS and DLQI (r=0.423, p=0.001). High internalized stigma scores had no relation to either the severity or localization of disease in pediatric group. However, poor PHS (p=0.007) and low-income levels (p=0.03) in both groups, and body mass index (r=0.181, p=0.04) in the pediatric group were related to high PISS scores.ConclusionInternalized stigma in pediatric patients is as high as adults and is related to poor quality of life, general health, and psychological illnesses. Unlike adults, internalized stigma was mainly determined by psoriasis per se, rather than disease severity or involvement of visible body parts, genitalia or folds.     

[Translated article] Practical Update of the Recommendations Published by the Psoriasis Group of the Spanish Academy of Dermatology and Venereology (GPs) on the Treatment of Psoriasis with Biologic Therapy. Part 1. Concepts and General Management of Psoriasis With Biologic Therapy

Background and objectivesA new, updated AEDV Psoriasis Group (GPs) consensus document on the treatment of moderate to severe psoriasis was needed owing to the approval, in recent years, of a large number of new drugs and changes in the treatment paradigm.MethodologyThe consensus document was developed using the nominal group technique and a scoping review. First, a designated coordinator selected a group of Psoriasis Group members for the panel. The coordinator defined the objectives and key points for the document and, with the help of a documentalist, conducted a scoping review of articles in Medline, Embase, and the Cochrane Library up to January 2021. The review included systematic reviews and meta-analyses as well as clinical trials not included in those studies and high-quality real-world studies. National and international clinical practice guidelines and consensus documents on the management of moderate to severe psoriasis were also reviewed. Based on these reviews, the coordinator drew up a set of proposed recommendations, which were then discussed and modified in a nominal group meeting. After several review processes, including external review by other GPs members, the final document was drafted.ResultsThe present guidelines include general principles for the treatment of patients with moderate to severe psoriasis and also define treatment goals and criteria for the indication of biologic therapy and the selection of initial and subsequent therapies. Practical issues, such as treatment failure and maintenance of response, are also addressed.     

Association of Metabolic Comorbidities with Pediatric Psoriasis: A Systematic Review and Meta-Analysis

BackgroundAn evident relationship has been shown between psoriasis and metabolic comorbidities. However, the results in pediatric psoriasis vary from study to study, and no meta-analysis exists on the association of metabolic comorbidities with pediatric psoriasis.ObjectiveTo evaluate the association between psoriasis and metabolic comorbidities in pediatric patients.MethodsWe searched articles published in PubMed, EMBASE, and Cochrane Library databases from inception to April 30, 2019. All observational studies reporting the prevalence of obesity or metabolic comorbidities in pediatric patients with psoriasis were included.ResultsThe meta-analysis included 16 unique studies meeting the inclusion criteria. The pooled odds ratios in pediatric patients with psoriasis was 2.40 (95% confidence interval [CI], 1.60~3.59) for obesity (13 studies), 2.73 (95% CI, 1.79~4.17) for hypertension (8 studies), 2.01 (95% CI, 1.09~3.73) for diabetes mellitus (8 studies), 1.67 (95% CI, 1.42~1.97) for dyslipidemia (7 studies), and 7.49 (95% CI, 1.86~30.07) for metabolic syndrome (4 studies).ConclusionPediatric patients with psoriasis showed a significantly higher prevalence of obesity, hypertension, diabetes, dyslipidemia, and metabolic syndrome. Adequate monitoring and timely management of metabolic comorbidities should be considered in these patients.