Ustekinumab for the Treatment of Moderate-to-severe Plaque Psoriasis in Paediatric Patients (≥ 6 to < 12 Years of Age)

Efficacy, Safety, Pharmacokinetic and Biomarker Results From the Open-label Cadmus Jr Study

S. Philipp; A. Menter; A.F. Nikkels; K. Barber; I. Landells; L.F. Eichenfield; M. Song; B. Randazzo; S. Li; M.-C. Hsu; Y. Zhu; S. DePrimo; A.S. Paller

Disclosures

The British Journal of Dermatology. 2020;183(4):664-672. 

In This Article

Abstract and Introduction

Abstract

Background: Limited options are available for treatment of paediatric psoriasis.

Objectives: To evaluate the efficacy and safety of ustekinumab in paediatric patients with psoriasis (≥ 6 to < 12 years of age).

Methods: CADMUS Jr, a phase III, open-label, single-arm, multicentre study, evaluated ustekinumab in paediatric patients with moderate-to-severe plaque psoriasis. Patients received weight-based dosing of ustekinumab (< 60 kg: 0·75 mg kg−1; ≥ 60 to ≤ 100 kg: 45 mg; > 100 kg: 90 mg) administered by subcutaneous injection at weeks 0 and 4, then every 12 weeks through week 40. Study endpoints (all at week 12) included the proportions of patients achieving a Physician's Global Assessment score of cleared/minimal (PGA 0/1) and ≥ 75%/90% improvement in Psoriasis Area and Severity Index (PASI 75/90), and change in Children's Dermatology Life Quality Index (CDLQI). Serum ustekinumab concentrations, antidrug antibodies and cytokine levels were measured through week 52. Safety was evaluated through week 56.

Results: In total, 44 patients (median age 9·5 years) received at least one dose of ustekinumab. Three patients discontinued the study agent through week 40. At week 12, 77% of patients achieved PGA 0/1, 84% achieved PASI 75 and 64% achieved PASI 90 response. The mean change in CDLQI was −6·3. Trough serum ustekinumab concentrations reached steady state at weeks 28–52. The incidence of antidrug antibodies was 10% (n = 4). Mean serum concentrations of interleukin-17A/F and interleukin-22 were significantly reduced at weeks 12 and 52. Overall, 34 patients (77%) had at least one adverse event and three (7%) had a serious adverse event.

Conclusions: Ustekinumab effectively treated moderate-to-severe psoriasis in paediatric patients, and no new safety concerns were identified.

Introduction

Psoriasis is a chronic, immune-mediated, inflammatory skin disease that affects 2–3% of the world's population.[1] Approximately 35% of adults with psoriasis report signs and symptoms before the age of 20 years.[2] Childhood psoriasis represents a significant burden of disease, with a prevalence of 0·2–2·5% reported across studies.[3–5] Beyond the skin manifestations, juvenile psoriasis has been associated with increased rates of hyperlipidaemia, obesity, hypertension, diabetes mellitus, arthritis and Crohn disease.[4]

Relative to adult psoriasis, there is a paucity of clinical data and fewer approved treatment options for psoriasis in children. The biologic agents that are currently available to treat paediatric psoriasis in Europe include two tumour necrosis factor inhibitors (etanercept and adalimumab, in children ≥ 4 years of age) and an interleukin (IL)-12/23 inhibitor (ustekinumab, in children ≥ 12 years of age). All three biologics are administered subcutaneously; however, the frequency of maintenance dosing varies (i.e. weekly for etanercept, every other week for adalimumab, and every 12 weeks for ustekinumab).[6–8]

Ustekinumab has been shown to be effective for the treatment of moderate-to-severe plaque psoriasis, with a favourable safety profile in adults (age ≥ 18 years) and adolescents (age ≥ 12 to < 18 years) based on the PHOENIX and CADMUS trials, respectively,[8–10] and has been approved for the treatment of moderate-to-severe psoriasis in adults and adolescents in multiple countries.[11] Here we report the results of the CADMUS Jr trial, which was the first study to evaluate the efficacy, safety and pharmacokinetic (PK) profiles of ustekinumab, as well as biomarker assessments before and after ustekinumab treatment, in younger paediatric patients (≥ 6 to < 12 years of age) with moderate-to-severe psoriasis.

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