Paediatric Plaque Psoriasis Research Articles

AVT04: An Ustekinumab Biosimilar.

AVT04 (Uzpruvo®) is a biosimilar of the reference anti-interleukin (IL)-12 and IL-23 monoclonal antibody ustekinumab. It is approved in the EU for plaque psoriasis, paediatric plaque psoriasis, psoriatic arthritis and Crohn's disease as per the reference product. AVT04 has similar physicochemical characteristics to those of reference ustekinumab, and the pharmacokinetic similarity of the agents has been shown in healthy volunteers and patients with moderate to severe chronic plaque psoriasis. AVT04 demonstrated clinical efficacy similar to that of reference ustekinumab in patients with moderate to severe chronic plaque psoriasis, and was generally well tolerated in this population. The tolerability, safety and immunogenicity profiles of AVT04 were similar to those of reference ustekinumab, and switching from reference ustekinumab to AVT04 had no impact on efficacy, safety or immunogenicity. The role of reference ustekinumab in the management of inflammatory diseases is well established and AVT04 provides an effective biosimilar alternative for patients requiring ustekinumab therapy.

32264 Long-term efficacy and safety of ixekizumab in a phase III, randomized, double-blind, placebo-controlled study in pediatric patients with moderate-to-severe plaque psoriasis (IXORA-PEDS) up to 108 weeks

Background: About 1% of children and adolescents worldwide are affected by plaque psoriasis (PsO)[1]. We report the long-term efficacy and safety of ixekizumab (IXE), a high-affinity monoclonal antibody that selectively targets interleukin 17A[1], for moderate-to-severe pediatric PsO from a randomized, double-blind Phase 3 study (IXORA-PEDS [NCT03073200]) up to 108 weeks.

Real-world experience with ustekinumab for the treatment of plaque psoriasis in pediatric patients: A retrospective, single-center chart review

Our understanding of the efficacy and safety of ustekinumab for the treatment of pediatric plaque psoriasis is limited to two phase 3 clinical trials.1,2 To evaluate the real-world experience of this biologic in children and adolescents, we conducted a retrospective chart review at a community dermatology practice in Calgary, Canada.

Several approved biologic agents are now available to treat paediatric plaque psoriasis

Several approved biologic agents are now available to treat paediatric plaque psoriasis

Secukinumab: A Review in Moderate to Severe Pediatric Plaque Psoriasis.

Subcutaneous secukinumab (Cosentyx®) is a recombinant, fully human, immunoglobulin (Ig) G1κ monoclonal antibody targeted against interleukin (IL)-17A, a proinflammatory cytokine involved in the pathogenesis of psoriasis. Secukinumab is approved in the EU and the USA for the treatment of moderate to severe plaque psoriasis in pediatric patients aged ≥ 6 years. In pivotal phase III trials in pediatric patients aged 6 to < 18 years, both low (75–150 mg) and high (75–300 mg) doses of secukinumab were significantly better than placebo and numerically better than etanercept at week 12 in terms of the proportion of patients achieving ≥ 75% improvement from baseline in Psoriasis Area and Severity Index and significantly better than placebo and etanercept in terms of the proportion of patients achieving an Investigator’s Global Assessment score of 0 or 1. The clinical efficacy of secukinumab observed during the first 12 weeks of treatment was maintained over the longer term. Treatment with secukinumab improved health-related quality of life and was generally well tolerated. In conclusion, secukinumab represents a valuable new addition to the limited treatment options available for children and adolescents with moderate to severe plaque psoriasis.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40272-021-00476-w.

A cross-sectional study of ethnoracial representation in pediatric plaque psoriasis clinical trials

To the Editor: Ethnoracial data on the prevalence of pediatric psoriasis demonstrates a diverse population of affected patients, with 1 study showing a prevalence of 6 African Americans, 16 Hispanic Whites, 20 Asian or Pacific Islanders, and 29 non-Hispanic Whites per 10,000 children.1 Additionally, skin distribution, associated symptoms, and family history of psoriasis demonstrate variability between different racial and ethnic pediatric groups.2 However, even though differences in prevalence and presentation exist between ethnoracial groups, a cross-sectional study of adult phase III clinical trials of plaque psoriasis demonstrated a significant underrepresentation of non-White participants.

Selected Developments in Biotechnology Law and the Biotechnology Industry

Selected Developments in Biotechnology Law and the Biotechnology Industry

The Use of TNFα Inhibitors in Treating Pediatric Skin Disorders.

Tumor necrosis factor alpha (TNF) inhibitors have had a significant impact in medicine since the approval of the first drug of its class by the US FDA in 1998. New clinical data and indications have emerged for TNF inhibitors in recent years. Currently, four TNF inhibitors have been approved by the US FDA for dermatology, two of which include US FDA-approved pediatric use. In particular, growing evidence supports the use of etanercept and adalimumab as attractive therapies for pediatric psoriasis. Data for use of etanercept in treating toxic epidermal necrolysis and either etanercept or infliximab for Kawasaki disease is expanding. In addition, there have been clinical reports on the use of TNF inhibitors to treat a variety of other pediatric dermatologic conditions. To help clinicians keep pace with the new data provided by many pediatric dermatology studies involving TNF inhibitors, this review provides an overview of the use of TNF inhibitors in the treatment of pediatric plaque psoriasis, hidradenitis suppurativa, atopic dermatitis, pyoderma gangrenosum, toxic epidermal necrolysis, and Kawasaki disease. For TNF inhibitors with little data in the pediatric population, data on adult use is discussed. Furthermore, the review summarizes available clinical data on efficacy, safety, and tolerability of agents currently available.

Pharmacokinetics and safety of apremilast in pediatric patients with moderate to severe plaque psoriasis: Results from a phase 2 open-label study

Nooral systemic treatments are approved for pediatric patients with psoriasis. To evaluate the pharmacokinetics and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in pediatric patients with psoriasis. This phase 2, multicenter, open-label study enrolled pediatric patients with moderate to severe plaque psoriasis. Patients received apremilast twice daily without titration for 2weeks (group 1 [age, 12-17years; weight, ≥35kg]: apremilast 20 or 30mg; group 2 [age, 6-11years; weight, ≥15kg]: apremilast 20mg), followed by a 48-week extension. Primary endpoints were pharmacokinetics and safety. Other endpoints were taste/acceptability and change from baseline in score on the Psoriasis Area and Severity Index. A total of 42 enrolled patients (21 adolescents [age, 12-17years] and 21 children [age, 6-11years]) received apremilast. Pharmacokinetics modeling and noncompartmental analyses showed that weight-based dosing with apremilast 20mg twice daily in children or apremilast 20 or 30mg twice daily in adolescents provides exposure (area under the concentration-time curve from time 0 to 12hours after the dose) that is comparable to that achieved with apremilast 30mg twice daily in adults. The safety profile was generally similar to that in adults. Most study participants liked the taste of the tablet. Improvements from baseline in mean Psoriasis Area and Severity Index score were 68% for adolescents (overall) and 79% for children. No children weighing less than 20kg were enrolled. This first-time-in-children phase 2 study supports weight-based apremilast dosing for futurephase 3 studies of pediatric plaque psoriasis.

SB5: An Adalimumab Biosimilar.

SB5 (Imraldi®) is a biosimilar of the reference anti-TNF monoclonal antibody adalimumab. It is approved for use in the following indications for which reference adalimumab is approved: rheumatoid arthritis (RA), juvenile idiopathic arthritis [polyarticular juvenile idiopathic arthritis (pJIA) and enthesitis-related arthritis (ERA)], axial spondyloarthritis [ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA)], psoriatic arthritis (PsA), psoriasis, pediatric plaque psoriasis, hidradenitis suppurativa (HS), Crohn's disease, pediatric Crohn's disease, ulcerative colitis (UC), and non-infectious uveitis. SB5 has similar physicochemical and pharmacodynamic properties to those of reference adalimumab, and the pharmacokinetic similarity of these agents has been shown in healthy volunteers and patients with RA. SB5 demonstrated clinical efficacy considered equivalent to that of reference adalimumab in patients with RA, and was generally well tolerated in this population. The safety and tolerability profile of SB5 was similar to that of reference adalimumab, as was the immunogenicity profile. Switching from reference adalimumab to SB5 had no impact in terms of efficacy, safety or immunogenicity. The role of reference adalimumab in the management of RA, pJIA, ERA, AS, nr-axSpA, PsA, psoriasis, pediatric plaque psoriasis, HS, Crohn's disease, UC and non-infectious uveitis is well established and SB5 provides an effective biosimilar alternative for patients requiring adalimumab therapy.

Risk of malignancy associated with paediatric use of tumour necrosis factor inhibitors

ObjectiveTo determine whether tumour necrosis factor inhibitor (TNFi) use is associated with an increased rate of incident malignancy compared with no TNFi use in the treatment of juvenile idiopathic arthritis...

SB4 (Benepali®; an etanercept biosimilar): a profile of its use

SB4 [Benepali® (EU); Brenzys™ (Australia, Canada, Korea)] is an etanercept biosimilar approved for all indications for which reference etanercept is approved, including rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, axial spondyloarthritis, plaque psoriasis and paediatric plaque psoriasis. In a phase 3 trial in patients with moderate to severe rheumatoid arthritis receiving methotrexate, the efficacy of subcutaneous SB4 was equivalent to that of reference etanercept, and both agents had a similar tolerability profile, except for a higher incidence of injection-site reactions with reference etanercept. In patients switched from reference etanercept to SB4, there was no loss of efficacy or an increase in adverse events or immunogenicity. Switching to treatment with SB4, using a well-designed communication strategy, may potentially result in cost savings for healthcare budgets, thereby improving patient access to treatment.

GP2015: An Etanercept Biosimilar.

GP2015 is the second biosimilar of the reference p75 TNF receptor-Fc fusion protein etanercept. It is approved for use in all indications for which reference etanercept is approved, including rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, plaque psoriasis and paediatric plaque psoriasis. GP2015 has similar physiochemical and pharmacodynamic properties to those of reference etanercept, and the pharmacokinetic biosimilarity of the agents has been shown in healthy volunteers. GP2015 demonstrated clinical efficacy equivalent to that of reference etanercept in patients with moderate-to-severe plaque psoriasis; the tolerability, safety and immunogenicity profiles of the two agents were also generally similar. Switching between GP2015 and reference etanercept had no impact on clinical efficacy, tolerability or immunogenicity. The role of reference etanercept in the management of inflammatory autoimmune conditions is well established and GP2015 provides an effective biosimilar alternative for patients requiring etanercept therapy.

Biologics and Pediatric Generalized Pustular Psoriasis: An Emerging Therapeutic Trend.

Generalized pustular psoriasis (GPP) is a rare form of childhood psoriasis, often requiring systemic therapy, which is challenging as there is a paucity of randomized controlled trials and standardized guidelines. Biologic agents have been used in adults and in pediatric plaque psoriasis, but evidence regarding their efficacy in pediatric GPP has slowly become available. The objective of this study is to summarize and compare the efficacy and safety of biologic agents, such as etanercept, infliximab, and adalimumab, in the treatment of pediatric GPP. A PubMed literature review was conducted and 12 studies met the inclusion criteria for analysis. After reviewing the efficacy of these drugs in pediatric GPP patients and their safety in the use of other pediatric conditions, etanercept was identified as a possible first-line biologic agent for pediatric psoriasis, including GPP, followed by infliximab and adalimumab. In conclusion, several case reports have documented the successful use of biologic agents in refractory cases of pediatric GPP, but clinical trials are needed to gain a better understanding of the efficacy and side effect profile in this population.

Treating pediatric plaque psoriasis: challenges and solutions.

Psoriasis is a T-lymphocyte-mediated chronic inflammatory disorder involving the skin and joints. Nearly 3.5% of the population has been diagnosed to have psoriasis. In a dermatology department, almost one-third of psoriasis patients are in the pediatric age group. With an annual prevalence of up to 0.71%, childhood psoriasis can now be regarded as a frequently seen chronic inflammatory skin disorder having a significant impact on the quality of life. Based on the age of onset, psoriasis in children can be broadly classified as infantile psoriasis that can be mostly self-limited, psoriasis having an early onset, which needs specific treatment, and psoriasis that is associated with arthritis. Treating a child with psoriasis is a challenge, considering the physical development, body metabolism, rate of cutaneous absorption, and metabolism of drugs, which are quite different from those of the adults. The long duration of sun exposure for the rest of their life makes it more demanding while considering phototherapy in children. Long-term treatment of psoriasis, with phototherapy or drugs, needs critical evaluation in children. Hence, a thorough understanding of the disease in all its aspects will certainly help manage childhood psoriasis better. Timely diagnosis and adequate management not only arrest progression but also minimize the psychological burden caused by the disease, averting disfiguring states and evolution into a metabolic syndrome.

Effectiveness and safety of cyclosporine in pediatric plaque psoriasis: A multicentric retrospective analysis

Background: Cyclosporine (CysA) is effective for psoriasis in adult patients but little data exist about its efficacy and safety in childhood and adolescence psoriasis. Objectives: To assess the effectiveness and safety of CysA for childhood and adolescence psoriasis. Methods: Retrospective analysis of a group of children and adolescents (age < 17 years) with plaque psoriasis treated with CysA at several Italian dermatology clinics. Results: Our study population consisted of 38 patients. The median age at the start of treatment was 12.3 years. Therapy duration varied from one to 36 months. The median maintenance dosage per day was 3.2 mg/kg (range 2–5 mg/kg). Fifteen patients (39,4%) achieved a complete clearance or a good improvement of their psoriasis defined by an improvement from baseline of ≥75% in the psoriasis area and severity index (PASI) at week 16. Eight patients (21.05%) discontinued the treatment due to laboratory anomalies or adverse events. Serious events were not recorded. Conclusions: In this case series, CysA was effective and well-tolerated treatment in a significant quote of children. CysA, when carefully monitored, may represent a therapeutic alternative to the currently used systemic immunosuppressive agents for severe childhood psoriasis.

Humira indicated for paediatric plaque psoriasis

Humira indicated for paediatric plaque psoriasis

Genotype-phenotype correlations in a prospective cohort study of paediatric plaque psoriasis: lack of correlation between HLA-C*06 and family history of psoriasis.

This study aims to investigate associations between observed clinical parameters and known genetic risk factors of psoriasis in a well-defined prospective cohort of paediatric patients with plaque psoriasis (n = 151). Significant associations were found for paediatric-onset psoriasis with ERAP1 (p = 0.002), IL23R (p = 0.01), LCE3C_LCE3B-del (p = 0.00049) and HLA-C*06 (p = 3.15 × 10(-30)). Psoriasis severity was associated with the single nucleotide polymorphisms tagging IFIH1 and ERAP1 (p < 0.05). An onset before 10 years of age was associated with IL12B (p = 0.02). Nail psoriasis was more often seen in HLA-C*06-negative patients (p = 0.008). Remarkably, family history is clearly not associated with HLA-C*06 in this specific group. The large proportion of patients with a positive family history in HLA-C*06 negative patients (and the lack of correlation between the two) indicates that other genes, either alone or interaction between two or more genes, may have significant effects on heritability.

Etanercept: 'clinically meaningful' benefit in paediatric plaque psoriasis

Etanercept: 'clinically meaningful' benefit in paediatric plaque psoriasis