Ustekinumab in adolescent patients age 12 to 17 years with moderate-to-severe plaque psoriasis: Results of the randomized phase 3 CADMUS study

Landells, Ian; Marano, Colleen; Hsu, Ming Chun; Li, Shu; Zhu, Yaowei; Eichenfield, Lawrence F.; Hoeger, Peter H.; Menter, Alan; Paller, Amy S.; Taı̈eb, Alain; Philipp, Sandra; Szapary, Philippe; Randazzo, B.

doi:10.1016/j.jaad.2015.07.002

Cited by 192 publications

(203 citation statements)

References 12 publications

(12 reference statements)

Supporting

Mentioning

170

Contrasting

Unclassified

Order By: Relevance

“…adalimumab, [39][40][41][42][43][44][45][46][47]79,80,87 etanercept and ustekinumab [72][73][74][75]81,82,88 ). The RCTs investigated short-term clinical efficacy and AEs.…”

Section: Characteristics Of the Included Studiesmentioning

confidence: 99%

“…Data on safety and efficacy (blinded period) were available from one peer-reviewed journal paper, 72 a conference abstract, 73 regulatory documentation 74 and a CSR provided by the manufacturer. 88 The CADMUS RCT was a double-blind, placebo-controlled study in adolescent participants (aged 12-17 years) who had had a diagnosis of moderate to severe plaque psoriasis for ≥ 6 months, which was conducted at multiple sites in Europe (Belgium, France, Germany, Hungary, Portugal, Russian Federation, Sweden, Ukraine and the UK) and Canada.…”

Section: Efficacy and Safety Of Ustekinumabmentioning

confidence: 99%

“…Three adult studies 106,108,132 have substantially higher placebo response rates (approximately 18-20%) than the other studies. Four studies, including the two trials in children and young people 72 and two in adults, 114,116 have approximately double the average placebo rate.…”

Section: Adjustment For Differences In Placebo Response Rates Across mentioning

confidence: 99%

See 2 more Smart Citations

Adalimumab, etanercept and ustekinumab for treating plaque psoriasis in children and young people: systematic review and economic evaluation

Duarte

Mebrahtu

Gonçalves

et al. 2017

Health Technol Assess

View full text Add to dashboard Cite

Background Psoriasis is a chronic inflammatory disease that predominantly affects the skin. Adalimumab (HUMIRA®, AbbVie, Maidenhead, UK), etanercept (Enbrel®, Pfizer, New York, NY, USA) and ustekinumab (STELARA®, Janssen Biotech, Inc., Titusville, NJ, USA) are the three biological treatments currently licensed for psoriasis in children. Objective To determine the clinical effectiveness and cost-effectiveness of adalimumab, etanercept and ustekinumab within their respective licensed indications for the treatment of plaque psoriasis in children and young people. Data sources Searches of the literature and regulatory sources, contact with European psoriasis registries, company submissions and clinical study reports from manufacturers, and previous National Institute for Health and Care Excellence (NICE) technology appraisal documentation. Review methods Included studies were summarised and subjected to detailed critical appraisal. A network meta-analysis incorporating adult data was developed to connect the effectiveness data in children and young people and populate a de novo decision-analytic model. The model estimated the cost-effectiveness of adalimumab, etanercept and ustekinumab compared with each other and with either methotrexate or best supportive care (BSC), depending on the position of the intervention in the management pathway. Results Of the 2386 non-duplicate records identified, nine studies (one randomised controlled trial for each drug plus six observational studies) were included in the review of clinical effectiveness and safety. Etanercept and ustekinumab resulted in significantly greater improvements in psoriasis symptoms than placebo at 12 weeks’ follow-up. The magnitude and persistence of the effects beyond 12 weeks is less certain. Adalimumab resulted in significantly greater improvements in psoriasis symptoms than methotrexate for some but not all measures at 16 weeks. Quality-of-life benefits were inconsistent across different measures. There was limited evidence of excess short-term adverse events; however, the possibility of rare events cannot be excluded. The majority of the incremental cost-effectiveness ratios for the use of biologics in children and young people exceeded NICE’s usual threshold for cost-effectiveness and were reduced significantly only when combined assumptions that align with those made in the management of psoriasis in adults were adopted. Limitations The clinical evidence base for short- and long-term outcomes was limited in terms of total participant numbers, length of follow-up and the absence of young children. Conclusions The paucity of clinical and economic evidence to inform the cost-effectiveness of biological treatments in children and young people imposed a number of strong assumptions and uncertainties. Health-related quality-of-life (HRQoL) gains associated with treatment and the number of hospitalisations in children and young people are areas of considerable uncertainty. The findings suggest that biological treatments may not be cost-effective for the management of psoriasis in children and young people at a willingness-to-pay threshold of £30,000 per quality-adjusted life-year, unless a number of strong assumptions about HRQoL and the costs of BSC are combined. Registry data on biological treatments would help determine safety, patterns of treatment switching, impact on comorbidities and long-term withdrawal rates. Further research is also needed into the resource use and costs associated with BSC. Adequately powered randomised controlled trials (including comparisons against placebo) could substantially reduce the uncertainty surrounding the effectiveness of biological treatments in biologic-experienced populations of children and young people, particularly in younger children. Such trials should establish the impact of biological therapies on HRQoL in this population, ideally by collecting direct estimates of EuroQol-5 Dimensions for Youth (EQ-5D-Y) utilities. Study registration This study is registered as PROSPERO CRD42016039494. Funding The National Institute for Health Research Health Technology Assessment programme.

show abstract

“…adalimumab, [39][40][41][42][43][44][45][46][47]79,80,87 etanercept and ustekinumab [72][73][74][75]81,82,88 ). The RCTs investigated short-term clinical efficacy and AEs.…”

Section: Characteristics Of the Included Studiesmentioning

confidence: 99%

Section: Efficacy and Safety Of Ustekinumabmentioning

confidence: 99%

See 1 more Smart Citation

Adalimumab, etanercept and ustekinumab for treating plaque psoriasis in children and young people: systematic review and economic evaluation

Duarte

Mebrahtu

Gonçalves

et al. 2017

Health Technol Assess

View full text Add to dashboard Cite

show abstract

“…Etanercept, ustekinumab, and adalimumab are approved in Europe for the treatment of severe pediatric psoriasis, whereas only recently (2016) etanercept received FDA approval for this indication . Reports outside the context of clinical trials are scarce …”

Section: Detailed Patient Information Including Demographic Data Dismentioning

confidence: 99%

“…Biologics are effective for severe pediatric psoriasis. Based on clinical trials, the overall safety data seems overlapping with the existing evidence for adults . Most short‐term AEs are mild‐to‐moderate infections, which have not been unequivocally linked to biological treatments since they are common in otherwise healthy children .…”

Section: Detailed Patient Information Including Demographic Data Dismentioning

confidence: 99%

Switching biologics in severe pediatric psoriasis: a retrospective analysis

et al. 2017

View full text Add to dashboard Cite

Pathophysiology, Clinical Presentation, and Treatment of Psoriasis

Armstrong

Read

2020

JAMA

1,284

1,105

View full text Add to dashboard Cite

ImportanceApproximately 125 million people worldwide have psoriasis. Patients with psoriasis experience substantial morbidity and increased rates of inflammatory arthritis, cardiometabolic diseases, and mental health disorders.ObservationsPlaque psoriasis is the most common variant of psoriasis. The most rapid advancements addressing plaque psoriasis have been in its pathogenesis, genetics, comorbidities, and biologic treatments. Plaque psoriasis is associated with a number of comorbidities including psoriatic arthritis, cardiometabolic diseases, and depression. For patients with mild psoriasis, topical agents remain the mainstay of treatment, and they include topical corticosteroids, vitamin D analogues, calcineurin inhibitors, and keratolytics. The American Academy of Dermatology-National Psoriasis Foundation guidelines recommend biologics as an option for first-line treatment of moderate to severe plaque psoriasis because of their efficacy in treating it and acceptable safety profiles. Specifically, inhibitors to tumor necrosis factor α (TNF-α) include etanercept, adalimumab, certolizumab, and infliximab. Other biologics inhibit cytokines such as the p40 subunit of the cytokines IL-12 and IL-13 (ustekinumab), IL-17 (secukinumab, ixekizumab, bimekizumab, and brodalumab), and the p19 subunit of IL-23 (guselkumab, tildrakizumab, risankizumab, and mirikizumab). Biologics that inhibit TNF-α, p40IL-12/23, and IL-17 are also approved for the treatment of psoriatic arthritis. Oral treatments include traditional agents such as methotrexate, acitretin, cyclosporine, and the advanced small molecule apremilast, which is a phosphodiesterase 4 inhibitor. The most commonly prescribed light therapy used to treat plaque psoriasis is narrowband UV-B phototherapy.Conclusions and RelevancePsoriasis is an inflammatory skin disease that is associated with multiple comorbidities and substantially diminishes patients’ quality of life. Topical therapies remain the cornerstone for treating mild psoriasis. Therapeutic advancements for moderate to severe plaque psoriasis include biologics that inhibit TNF-α, p40IL-12/23, IL-17, and p19IL-23, as well as an oral phosphodiesterase 4 inhibitor.

show abstract

Ustekinumab in adolescent patients age 12 to 17 years with moderate-to-severe plaque psoriasis: Results of the randomized phase 3 CADMUS study

Abstract: In this patient population (12-17 years), the standard ustekinumab dose provided response comparable to that in adults with no unexpected AEs through 1 year.

Cited by 192 publications

References 12 publications

Adalimumab, etanercept and ustekinumab for treating plaque psoriasis in children and young people: systematic review and economic evaluation

Adalimumab, etanercept and ustekinumab for treating plaque psoriasis in children and young people: systematic review and economic evaluation

Switching biologics in severe pediatric psoriasis: a retrospective analysis

Pathophysiology, Clinical Presentation, and Treatment of Psoriasis

Contact Info

Product

Resources

About