E DI TO R IA L
BJD
British Journal of Dermatology
Allocation of biologics: health economics and clinical decision making in plaque psoriasis
DOI: 10.1111/bjd.16504 Linked Article: Klijn et al. Br J Dermatol 2018; 178:1181– 1189. Over the last decade biological treatments for plaque psoriasis have become increasingly popular due to their efficacy and safety.1 However, these treatments are also associated with substantially increased treatment costs. Due to the finite resources available to healthcare services, it is imperative that available funds are used in the most cost-effective and efficient manner possible. Evidence-based practice utilizes evidence of effectiveness and cost-effectiveness to guide service provision, and thus when implemented correctly can enable commissioners and clinicians to prioritize treatments based on potential patient benefits and health service expenditure. Health economics is becoming increasingly influential in dermatology commissioning and funding decisions.2 Health economists examine the relationship between the cost of health care and the associated patient benefits, using methods of economic evaluation to identify the incremental costs and benefits of competing interventions. In the U.K., the average annual cost for treating a patient with plaque psoriasis using a biological treatment is more than £10 000.3 Although biologics cost more than conventional therapeutics (such as methotrexate), overall they offer increased patient benefits and reduced side-effects, particularly when conventional therapeutics are unsuitable. Almost onethird of patients discontinue methotrexate treatment due to side-effects, therefore alternative treatments are essential.4 In practice, the treatment of psoriasis using biologics can be convoluted, as patients may need to try more than one biological agent before either finding a drug that works for them or resorting to nonbiological supportive care when biological treatment fails. The failure of one biologic does not predict the efficacy of another, thus clinicians must be prepared to change treatment promptly if clinical goals are not being met.5 Rates of diminishing response to treatment are relatively high for these drugs; between 10% and 25% of patients experience loss of efficacy of biologics.6 Each failed biological treatment causes substantial and potentially avoidable expenditure. National Institute for Health and Care Excellence guidance in the U.K. supports the prescribing of secondary biologics as an alternative to best supportive care, but there is less clear guidance on the order in which these drugs should be prescribed. It is therefore imperative to establish firstly when clinicians should change from conventional to biological therapy, © 2018 British Association of Dermatologists
and secondly the order in which different biologics should be prescribed. Such decisions must be based on good-quality evidence from a range of sources. For instance, head-to-head trial-based comparisons of cost-effectiveness and efficacy are important to guide practice, but these should also be supplemented with evaluations of real-world data, as demonstrated by Klijn et al. in the Dutch BioCAPTURE study.7 In the BioCAPTURE study the estimated cost and effect differences among six consecutive lines of biological treatments (with etanercept, adalimumab and ustekinumab) over a 10-year time horizon were marginal and remained without statistical significance in this analysis. Indeed, the maximum differences in costs (€141 962–148 442) and associated quality-adjusted life-years (QALYs) (779–803) were both < 5% (46% and 31%, respectively). Although a seemingly small maximum gain of 024 QALYs may constitute over 35 additional months of health for the average patient with psoriasis (as outlined by the authors of the analysis), this has to be seen in the context of a lifelong chronic disease with the burden of skin symptoms lasting over decades. Notably, the clinicians in the BioCAPTURE group may have chosen wisely and/or intuitively the treatment sequences that met health economic goals. Further research is needed to prioritize biological treatments definitively using a range of criteria, including cost-effectiveness, efficacy, tolerability, patient demographics and others. Diverse methods of analysis, including sensitivity analysis and statistical modelling, should be used to examine the probability of a given biological treatment being effective and costeffective in a specific clinical situation or patient group. In the future, personalized medicine using genetic markers including HLA-C*06 allele status8 and/or the presence of certain singlenucleotide polymorphisms of the IL17RA gene,9 or variants involved in nuclear factor-jB, tumour necrosis factor (TNF)-a and pattern recognition,10 may be able to predict a priori a differential clinical outcome to treatment with TNF antagonists vs. ustekinumab or other biologics. Recent data have shown that approximately one-third of patients with psoriasis do not respond to a specific treatment and require a change.11 The employment of predictive approaches may help to avoid the ‘trial and error’ policy10 that often takes place and results in periods of suboptimal treatment for the patient and increased treatment costs. Clinical outcomes are important (such as the Psoriasis Area and Severity Index); however, plaque psoriasis affects many aspects of patients’ health and well-being, thus adopting a focus solely on clinical outcomes and costs may underestimate the impact of these treatments. Treatment decisions ultimately
British Journal of Dermatology (2018) 178, pp997–998
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fall to the clinician, who must also factor in patient history and preference.7 Polistena et al.12 found that adopting a societal perspective (taking account of additional costs and benefits associated with lost productivity, caregiver assistance and health-related quality of life) reduced the estimated cost per QALY for biological treatments by 35%. Furthermore, they found that nonmedical and indirect costs decreased by almost 72% after biological treatment. What is clear is that in the evaluation of biologics (as well as other antipsoriatic drugs), a range of data are required from diverse sources, including clinical trials, patient-reported outcomes, economic evaluations, real-world data and statistical models.
Conflicts of interest N.B. has no relevant funding or conflicts of interest to declare. P.W. has received research grants or honoraria for taking part in advisory boards or presenting at meetings and/or travel support from AbbVie, Almirall, Celgene, Eli Lilly, Janssen, LEO Pharma, Merck Sharp & Dohme, Novartis, Sandoz and Pfizer. 1
Centre for Health Economics and Medicines Evaluation, Ardudwy Hall, Bangor University, Gwynedd LL57 2PZ, U.K. 2 Department of Dermatology, Medical University of Graz, Auenbruggerplatz 8, 8036 Graz, Austria E-mails:
[email protected];
[email protected]
N . B R A Y 1 iD P . W O L F 2 iD
References 1 Bray N. Considering the role of health economics in pyoderma gangrenosum and other dermatology research. Br J Dermatol 2017; 177:1475–6.
British Journal of Dermatology (2018) 178, pp997–998
2 Schmitt J, Rosumeck S, Thomaschewski G et al. Efficacy and safety of systemic treatments for moderate-to-severe psoriasis: meta-analysis of randomized controlled trials. Br J Dermatol 2014; 170:274–303. 3 National Institute for Health and Care Excellence. National costing report. Psoriasis: the assessment and management of psoriasis. Available at: https://www.nice.org.uk/guidance/cg153 (last accessed 26 February 2018). 4 Menter A, Korman NJ, Elmets CA et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 6. Guidelines of care for the treatment of psoriasis and psoriatic arthritis: case-based presentations and evidence-based conclusions. J Am Acad Dermatol 2011; 65:137–74. 5 Kerdel F, Zaiac M. An evolution in switching therapy for psoriasis patients who fail to meet treatment goals. Dermatol Ther 2015; 28:390–403. 6 Gniadecki R, Bang B, Bryld LE et al. Comparison of long-term drug survival and safety of biologic agents in patients with psoriasis vulgaris. Br J Dermatol 2015; 172:244–52. 7 Klijn SL, van den Reek JMPA, van de Wetering G et al. Biologic treatment sequences for plaque psoriasis: a cost-utility analysis based on 10 years of Dutch real-world evidence from BioCAPTURE. Br J Dermatol 2018; 178:1181–89. 8 Talamonti M, Galluzzo M, van den Reek JM et al. Role of HLAC*06 in clinical response to ustekinumab: evidence from real-life in a large cohort of European patients. Br J Dermatol 2017; 177:489–96. 9 Batalla A, Coto E, Gomez J et al. IL17RA gene variants and anti-TNF response among psoriasis patients. Pharmacogenomics J 2018; 18:76–80. 10 Loft ND, Skov L, Iversen L et al. Associations between functional polymorphisms and response to biological treatment in Danish patients with psoriasis. Pharmacogenomics J 2017; https://doi.org/10. 1038/tpj.2017.31 11 Nast A, Jacobs A, Rosumeck S, Werner RN. Efficacy and safety of systemic long-term treatments for moderate-to-severe psoriasis: a systematic review and meta-analysis. J Invest Dermatol 2015; 135:2641–8. 12 Polistena B, Calzavara-Pinton P, Altomare G et al. The impact of biologic therapy in chronic plaque psoriasis from a societal perspective: an analysis based on Italian actual clinical practice. J Eur Acad Dermatol Venereol 2015; 29:2411–16.
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