Comparative efficacy of biological treatments for moderate-to-severe psoriasis: a network meta-analysis adjusting for cross-trial differences in reference arm response

Signorovitch, James; Betts, Keith A.; Yan, Yaohua; LeReun, C; Sundaram, Murali; Wu, Eric Q.; Mulani, Parvez

doi:10.1111/bjd.13437

Cited by 65 publications

(60 citation statements)

References 42 publications

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“…Six NMAs (Bansback et al., 2009, Gomez-Garcia et al., 2017, Lin et al., 2012, Reich et al., 2012, Signorovitch et al., 2015, Woolacott et al., 2006) have been published examining the relative efficacy of biologics for psoriasis. Treatment tolerability is an important consideration for patients, with such concerns directly influencing whether patients adhere to treatment after initiation (Thorneloe et al., 2016).…”

Section: Introductionmentioning

confidence: 99%

Quantitative Evaluation of Biologic Therapy Options for Psoriasis: A Systematic Review and Network Meta-Analysis

Jabbar‐Lopez

Yiu

Ward

et al. 2017

Journal of Investigative Dermatology

116

133

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Multiple biologic treatments are licensed for psoriasis. The lack of head-to-head randomized controlled trials makes choosing between them difficult for patients, clinicians, and guideline developers. To establish their relative efficacy and tolerability, we searched MEDLINE, PubMed, Embase, and Cochrane for randomized controlled trials of licensed biologic treatments for skin psoriasis. We performed a network meta-analysis to identify direct and indirect evidence comparing biologics with one another, methotrexate, or placebo. We combined this with hierarchical cluster analysis to consider multiple outcomes related to efficacy and tolerability in combination for each treatment. Study quality, heterogeneity, and inconsistency were evaluated. Direct comparisons from 41 randomized controlled trials (20,561 participants) were included. All included biologics were efficacious compared with placebo or methotrexate at 3–4 months. Overall, cluster analysis showed adalimumab, secukinumab, and ustekinumab were comparable in terms of high efficacy and tolerability. Ixekizumab and infliximab were differentiated by very high efficacy but poorer tolerability. The lack of longer term controlled data limited our analysis to short-term outcomes. Trial performance may not equate to real-world performance, and so results need to be considered alongside real-world, long-term safety and effectiveness data. These data suggest that it is possible to discriminate between biologics to inform clinical practice and decision making (PROSPERO 2015:CRD42015017538).

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Section: Introductionmentioning

confidence: 99%

Quantitative Evaluation of Biologic Therapy Options for Psoriasis: A Systematic Review and Network Meta-Analysis

Jabbar‐Lopez

Yiu

Ward

et al. 2017

Journal of Investigative Dermatology

116

133

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“…Persistence measured under optimal (standardized) conditions in prescreened, highly motivated patient populations, using tight protocols and independent investigators during clinical trials does not necessarily coincide with the drug survival of therapies prescribed in the real-world settings (10,11). There are studies on the short-term persistence of biological therapies used in psoriasis; however, very limited comparative evidence is available on the long-term persistence of biological therapies used in the real-world settings (12). The objectives of this study were to analyze the characteristics of all psoriasis patients treated with any of the biological therapies currently marketed in Hungary (adalimumab, etanercept, infliximab, ustekinumab), to compare long-term drug survival of such therapies in the real-world settings and also to assess the impact of additional factors, like patient age, gender, biological therapynaïve status or the use of methotrexate (MTX) on drug survival.…”

Section: Introductionmentioning

confidence: 99%

Long-term drug survival and predictor analysis of the whole psoriatic patient population on biological therapy in Hungary

Pogácsás

Borsi

Takács

et al. 2017

Journal of Dermatological Treatment

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Persistence is an important component of therapeutic success, which depends on a variety of factors. Persistence measured under optimal conditions during clinical trials does not necessarily coincide with persistence observed in the real-world settings. The aim of the present study was to compare persistence rate of TNF-alpha inhibitors and interleukin 12/23 inhibitor in all psoriasis patients in Hungary, as well as to analyze the predictors of persistence. Data collected from 1263 patients over a period of 46 months were subjected to a retrospective analysis. Drug survival rate has been calculated according to Kaplan-Meier analysis and Cox regression was used to study the predictors. The overall persistence rate for the four biologicals exceeded 60% after 3 years. The persistence rate of ustekinumab at 3 years was 67.83%, which was superior compared to that of the TNF-alpha inhibitors, where the mean persistence rate was shown to be 50.76% (p < .05). Male patients showed significantly higher persistence than females (HR ¼ .76, p < .05 CI: 0.63, 0.92). Age, therapy-naïve status and use of concomitant MTX did not have significant effect on drug survival. Persistence rate of ustekinumab was significantly higher than that of TNF-alpha inhibitors, and among predictors, only male gender influenced persistence significantly. ARTICLE HISTORY

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“…Lists of excluded trials and reasons for exclusion were also reviewed and relevant trials identified. To supplement this review, the results of a recently published systematic review and NMA, 103 which adjusted for cross-trial differences in the comparative efficacy of biological treatments for moderate to severe psoriasis in adults, were also examined to cross-check that the majority of relevant studies had been identified in the…”

Section: Framework Of Analysis For Informing the Relative Efficacy Ofmentioning

confidence: 99%

“…placebo response) were explored. 103 These models impose a common interaction effect between baseline risk and relative effectiveness that accounts for variation in reference arm response across trials. NMA meta-regression models that explore variability caused by age effects were also implemented.…”

Section: Evidence Synthesis To Inform the Relative Efficacy Of The Inmentioning

confidence: 99%

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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

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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.

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Comparative efficacy of biological treatments for moderate-to-severe psoriasis: a network meta-analysis adjusting for cross-trial differences in reference arm response

Abstract: A model adjusted for reference arm response rates was found to fit clinical trial data significantly better than unadjusted models.

Cited by 65 publications

References 42 publications

Quantitative Evaluation of Biologic Therapy Options for Psoriasis: A Systematic Review and Network Meta-Analysis

Quantitative Evaluation of Biologic Therapy Options for Psoriasis: A Systematic Review and Network Meta-Analysis

Long-term drug survival and predictor analysis of the whole psoriatic patient population on biological therapy in Hungary

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

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