S.L. Klijn, J.M.P.A van den Reek, G. van de Wetering, A. van der Kolk, E.M.G.J. de Jong, W. Kievit

1. Biologic treatment sequences for plaque psoriasis:a cost-utility analysis based on 10 years of Dutch real-world evidence from BioCAPTURE S.L. Klijn, J.M.P.A van den Reek, G. van de Wetering, A. van der Kolk,E.M.G.J. de Jong, W. Kievit British Journal of Dermatology. DOI: 10.1111/bjd.16247

2. Introduction What’s already known? • Treatment with biologics may be indicated for patients with moderate to severe plaque psoriasis, butcomparative evidence on cost‑effectiveness is limited • Ustekinumab has a favourable cost-utility compared toetanercept as demonstrated by data from the ACCEPT trial;the comparison to adalimumab is less clear

3. Objective Evaluate the cost-effectiveness of different biologic treatment sequences for psoriasis based on real-world evidence

4. Methods: real-world evidence • Data on more than 500 treatment episodes for psoriasis were sourced from BioCAPTURE • BioCAPTURE is a Dutch registry containing daily practice data on the effectiveness of biologics in patients with severe plaque psoriasis • The dataset comprised patients treated at the Radboud University Medical Centre, covering the period between 2005 and 2015

5. Methods: costs and utilities • Quality of life data were based on the EQ-5D-3L • Unit costs were retrieved from sources recommended by guidelines of the Dutch National Health Care Institute • Adverse events were included in the analyses if they were reported at an incidence rate of 0.1 or higher per 100 patient years for any of the biologics • Data from BioCapture, along with data sourced from scientific literature, were entered into a model that was specifically built for this purpose

6. Methods: model structure • The model simulates the use of available biologics in different orders E.g. starting with adalimumab, followed by ustekinumab and etanercept • These treatment sequences are simulated for 10,000 patients over a period of10 years

7. Results • Initiating a treatment sequence with adalimumab or ustekinumab was associated with the highest utility for patients • Treatment sequences initiating with ustekinumab were associated with the lowest cost Ada, adalimumab; Eta, etanercept; QALY, quality-adjusted life year; Seq, sequence; Ust, ustekinumab

8. Scenario analysis: introduction of etanercept biosimilars • Introduction of etanercept biosimilars reduced the total cost estimates of all sequences compared with the main analysis • The Eta-Ust-Ada sequence, which was one of the more expensive treatment sequences in the main analysis, was expected to incur the lowest total cost in this scenario Ada, adalimumab; Eta, etanercept; QALY, quality-adjusted life year; Seq, sequence; Ust, ustekinumab

9. Discussion • A major strength of this study is the use of real-world data, thoughit can be questioned how representative this sample is of the average psoriasis patient outside of an academic hospital • The study outcomes are based on a modelling approach, instead of direct observations • Due to uncertainty in the analysis (95% credible intervals of the model outcomes were partly overlapping), no strong preference can be given to either the Ada-Ust-Eta or the Ust-Ada-Eta sequence

10. Conclusions • Adalimumab or ustekinumab can best be used as the first biologic to start a treatment sequence; starting with etanercept seems less optimal from a health-economic perspective • As the sequence order of biologics influences both costs and health effects of psoriasis treatment, adopting a long-term perspective at the start of treatment is of importance • Clinicians evaluate a wide range of factors, such as an individual patient’s history and patient preference, to inform treatment decisions; this analysis can provide a valuable context for these decisions

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