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

Abstract

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.

Safety and tolerability of adalimumab for the treatment of psoriasis: a review summarizing 15 years of real-life experience

“…In spite of this evidence for effectiveness and the favourable safety profile, the overall performance of adalimumab in children seems to be inferior to etanercept and ustekinumab. 79,81 Elderly patients are another distinct population requiring specific attention. A retrospective study in 89 patients aged at least 65 years treated with anti-TNF-α agents 82 found PASI50 in 82% of the patients receiving adalimumab at week 156.…”

A systematic review and classification of information-sharing methods

“…common effects) where all data points inform a single parameter independently of whether the evidence is direct or indirect. Examples include pooling RTEs across time-points [32], (sub-)populations [14,35], or interventions of the same treatment class [30,32,39,45], as well as pooling between-trial heterogeneity parameters [45,100,102,103] or meta-regression slopes [36,99,101].…”

“…We also identified the most common synthesis challenges addressed by the included papers. Amongst papers sharing information across populations, 3 [14,33,34] developed models to accommodate simultaneous synthesis of adult and paediatric evidence, 1 [35] described models that allowed informationsharing between patients subgroups, and 2 [36,37] provided model extensions for baseline risk adjustment. Amongst papers sharing information across interventions, 7 [38][39][40][41][42][43][44] simultaneously synthesised multiple dosages of the same treatment, 7 [32,35,40,[44][45][46][47] shared information across interventions that fall under the same 'class', and 5 [30,45,[48][49][50]] dealt with complex interventions (i.e.…”

Classifying information-sharing methods: a citation-mining systematic review

“…We also identified the most common synthesis challenges addressed by the included papers. Amongst papers sharing information across populations, 3 [14,33,34] developed models to accommodate simultaneous synthesis of adult and paediatric evidence, 1 [35] described models that allowed informationsharing between patients subgroups, and 2 [36,37] provided model extensions for baseline risk adjustment. Amongst papers sharing information across interventions, 7 [38][39][40][41][42][43][44] simultaneously synthesised multiple dosages of the same treatment, 7 [32,35,40,[44][45][46][47] shared across interventions that fall under the same 'class', and 5 [30,45,[48][49][50] dealt with complex interventions (i.e.…”

“…common effects) where all data points inform a single parameter independently of whether the evidence is direct or indirect. Examples include pooling RTEs across time-points [32] or (sub-)populations [14,35] as well as pooling between-trial heterogeneity parameters [92] or meta-regression slopes [91].…”