Introduction

Psoriasis vulgaris is a chronic, non-infectious inflammatory disease, and with a prevalence of 2–3 % one of the most frequent chronic skin diseases worldwide [9, 25, 58, 61].

Moreover, it is associated with numerous comorbidities such as cardiovascular and metabolic diseases as well as chronic immune diseases like rheumatism, chronic bowel disease, and Crohn’s disease. Thus, psoriasis is connected with a high disease burden, in particular marked reductions of patient’s quality of life.

Treatment of psoriasis consists of topical agents, UV treatment, traditional systemic treatments, and since 2003 also of biologics. Costs, especially for systemic treatments including biologics can be overwhelming to patients and the health care system [4].

Chronic diseases, which often require a lifelong treatment, cause significant follow-up costs and, therefore, have a high relevance concerning health economic aspects. While treatment costs as a monetary term are relatively easy to determine, different types to evaluate the benefit of a therapy exist. So far, the most often cited measurements to determine the benefit considering economic objectives are clinical outcomes like the Psoriasis Area and Severity Index (PASI) and cost outcomes, for example reduced follow-up costs [9].

In case of comparing the costs and benefits of treatment options, a cost-effectiveness analysis will be conducted. In cost-effectiveness analyses, outcomes are measured in program-specific units such as clinical parameters like the severity of disease or health outcomes like quality of life, cases cured, and days absent averted. When measuring quality of life in terms of a person’s health, factors to consider are for example pain level, mobility, and general mood. In case of combining outcome parameters of a treatment into a single aggregated summary outcome, the comparison with costs refers to a cost-utility analysis. There are different methods available to generate outcomes of a treatment in benefit units, for example the concept of quality-adjusted life-years (QALYs) [20]. A QALY gives an idea, how many extra months or years of life with a reasonable health-related quality a patient might gain as a result of treatment. Thereby, quality of life can range from 0 (worst possible health) to 1 (the best possible health). With the consideration of costs, cost–utility analyses present the cost of using a treatment to provide a year of the best quality of life available. Cost–utility analyses as kind of cost-effectiveness analyses using the QALYs to measure the effectiveness are expressed as cost per QALY [20, 34, 46].

Focusing on the costs of a cost-effectiveness/-utility analysis, costs are basically differentiated into direct and indirect ones. Direct costs include all resource consumptions that are associated with the medical treatment (e.g., costs of pharmaceuticals) as well as all resources that are used as a consequence of the treatment or disease, known as direct non-medical costs (e.g., for transportation, for household help, or for the educational system). Indirect costs generate all other costs caused indirectly through the treatment or the disease, including in particular disability days [25].

The variety of benefits and costs, economic analysis methods, and modeling techniques (e.g. decision tree, Markov model) indicate a wide range of different health economic evaluation studies. Many aspects have to be considered in planning a health economic study. Hence, there are several guidelines available [20, 37, 47, 64].

In the course of the chronic skin disease psoriasis, where a variety of interventions is available, a strong growth of health economic studies comparing treatment costs and benefits can be noticed. With the help of a systematic literature search, the researchers aimed to identify health economic evaluations of psoriasis treatments. Of particular interest were the following research questions:

  1. 1.

    Which health economic studies on costs and benefits of psoriasis treatment have been published?

  2. 2.

    Which analytical methods were used?

  3. 3.

    Which outcomes were analyzed?

  4. 4.

    Which models can be identified (decision tree, Markov model, or discrete event simulation)?

  5. 5.

    Which treatments were investigated?

  6. 6.

    What gaps exist in health economic studies of psoriasis care?

Materials and methods

Literature search

A literature search using Medline database (via PubMed and Ovid) and Cochrane Library was performed to identify the current situation of available health economic studies, evaluating treatment interventions for psoriasis patients and the respectively used benefit parameters and costs as well as modeling techniques. Search alerts were generated and reviewed for articles published until the 20 January 2016.

For example, the search algorithm in PubMed Medline was as follows:

  • (psoriasis) AND (“cost effectiveness” OR “cost effective” OR “health economic” OR “pharmacoeconomics” OR “pharmacoeconomic” OR “cost benefit” OR “cost utility”).

The literature search was limited to articles in English and German languages.

Study identification

Criteria for selecting the available research were: disease state is psoriasis, and the study is a health economic analysis, comparing costs as well as benefits of at least two interventions. Thus, analyses of one treatment only as well as cost-of-illness studies and cost-minimization analyses, in which no differences in the effectiveness of interventions are assumed, were excluded. In addition, only full texts, which were available for the authors, were considered. Pure abstracts based on a congress presentation were excluded. Finally, the researchers were only interested in original research articles. Thus, review papers were only included if synthesized data were generated.

Study inclusion was determined at two levels. At the first level, articles resulted from the literature search were screened on the basis of their title and abstract. At the second level, when fulfilling the inclusion criteria, full texts were reviewed to identify the applied method of the health economic study, the treatment options being compared, the kind of costs and outcome parameters as well as the modeling technique. Further characteristics of studies, which have been summarized, were the year of publication and the study setting.

Results

The search with PubMed Medline, Ovid Medline, and Cochrane Library combining “psoriasis” with terms of health economic analyses like “cost effectiveness” and “health economic” resulted in 318 articles without duplicates. Thereof 60 health economic analyses in psoriasis management were identified (see Tables 1 and 2). In total, 258 articles were excluded for not being an health economic study comparing costs and effectiveness of different treatment interventions or disease state other than psoriasis (Fig. 1). The 60 health economic analyses were from countries in Europe (32 including 13 times UK setting), North America (24), Asia (5), and from Brazil (1). A few studies were conducted in a multiple setting.

Fig. 1
figure 1

Search flow showing literature search results

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In addition to the extraction of publication year and country, included articles were compared with each other concerning their treatment comparisons, modeling method, and used costs and effectiveness parameters.

The analyses varied in type of treatment, see Figs. 2 and 3. The most considered systemic treatments were the biological agents etanercept (36), adalimumab (27), and infliximab (26) followed by ustekinumab (17) and phototherapy (incl. UV-B, PUVA/psoralen combined with UV-A) (14). Comparisons including topical treatments mostly focused on vitamin D treatment (14), corticosteroids (13), and coal tar products (6) followed by dithranol (5) and tazarotene (4). Some comparisons of systematic treatments with “basal” or “non-systemic” treatments contained no specific information about the topical treatment.

Fig. 2
figure 2

Distribution of compared topical treatments considered in included articles

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Fig. 3
figure 3

Distribution of compared systemic treatments considered in included articles

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In addition, the timeline (Fig. 4) shows an overview of the number of topical, UV, and traditional systemic treatments as well as biologics analyzed in cost-effectiveness studies over the years. While the number of UV treatments, topical treatments, and traditional systemic treatments over the years ranges from 0 to 14, the number of biologics considered in health economic studies increases from 3 (2003) to 45 (2015).

Fig. 4
figure 4

Overview of the number of topical, UV, and traditional systemic treatments as well as biologics analyzed in cost-effectiveness studies over the years

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A further comparison of included studies shows the distribution of comprised costs and effectiveness parameters in the respective cost-effectiveness and cost-utility analyses (Table 3). If there is a health economic study available, which includes a cost-effectiveness analysis as well as a cost-utility analysis, effectiveness parameters like PASI and DLQI (Dermatology Life Quality Index) were counted in the first row (cost-effectiveness), whereas utility parameters to measure QALYs are shown in the second row (cost-utility). Additionally in this case, modeling type and kind of costs were in a double reporting.

According to Table 3, most health economic analyses in psoriasis management are cost-effectiveness evaluations (45). The clinical parameter PASI is the most often used outcome to compare the costs with the effectiveness of a treatment (33 times in cost-effectiveness analyses). In most articles, the primary outcome was the proportion of patients achieving a 75 % reduction in the PASI score (so-called “PASI 75”). To include the patient-reported health-related quality of life, 5 cost-effectiveness studies used the DLQI. Further effectiveness parameters were disease-free days (DFD) (4), also reported as disease controlled days (DCD), and in 2 cost-effectiveness studies treatment free days (TFD). In the presence of cost-utility studies, the effectiveness is compared with costs in terms of QALYs. The latter were mostly measured by EuroQol five dimensions questionnaire (12), which was partly generated with the help of PASI or DLQI values. For example, a familiar research article to get QALYs with the help of DLQI is the publication of Currie and Conway [17].

Concerning the cost parameters, indirect costs are considered in 9 articles of 60 included hits. The majority of identified health economic studies is focusing on the direct medical and non-medical costs without consideration of productivity losses. As a result, data concerning productivity losses are rarely available in health economic analyses of psoriasis management.

Regarding the modeling type, Markov model is the most often applied kind of model. Discrete-event simulation is not yet applied in psoriasis management.

Discussion

Since it is already known that health economic studies are no new field in psoriasis management [9], the objective of the presented systematic review was to identify health economic analyses concerning psoriasis interventions that have been published to date. Until 20 January 2016, 60 health economic studies comparing costs and benefits were found with the help of the presented systematic literature research. Most of them were examined in Europe, particularly 13 in the UK. There, the National Institute for Health and Care Excellence (NICE) examines independently verified evidence on how well a drug works and whether it provides good value for money. This means whether it is cost-effective. With the use of QALYs as a standard and internationally recognized method to compare different treatments and measure their clinical effectiveness, NICE wants to ensure a fair evaluation of the effectiveness [14]. Therefore, it is not surprising that included evaluations from UK in the present systematic review are in most cases cost-effectiveness analyses using QALYs, known as cost-utility analyses.

It can be noted that since the approvals of the first biological agents by the Federal Drug Association (FDA) in 2003, biologics were directly considered in resulted articles (3). This number increased from 3 in 2003 to 45 in 2015. Biologics are known as considerably more expensive than traditional treatments [24, 55]. Due to their high benefit values for a specific group of psoriasis patients, they are now a permanent standard of treatment [45]. In some years, an update of this review will also yield in cost-effectiveness analyses considering additionally biosimilars. Biosimilars are biotechnologically processed drugs whose amino acid sequence is identical to the original biopharmaceutical [57].

This review of current health economic studies is limited by articles in English and German language with specific keywords. Thus, the search may have missed some relevant articles, published in languages other than English or German and not including selected keywords. Moreover, only full and available publications were considered. Abstracts based on a congress presentation or the like were excluded, given the fact that too little information is presented for this systematic review. Despite these limitations, this article gives an informative overview of health economic analyses, which have been conducted for the comparison of psoriasis treatments.

With regard to all 60 articles and the comparison in Table 3, it was noted that there are no standards on methods and outcome measures available. Even if the review shows that PASI was the most often used measurement in cost-effectiveness analyses of psoriasis interventions, no standardized measurement is used to compare patient-reported quality of life. Therefore, QALYs by EQ-5D or SF-36 (Short Form (36) Health Survey) and the DLQI were used mostly. The literature research yielded also health economic studies, in which no quality of life measurement was used (see Tables 1, 2). According to the increasing importance of the patient perspective, such health economic studies are less comparable with evaluations including patient-reported outcomes.

Table 1 Resulted hits of studies exclusively comparing topical treatments
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Table 2 Resulted hits of studies comparing systemic treatments, including comparisons with topical treatments
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Table 3 Distribution of used costs, effectiveness parameters, and model types in all resulted articles (n = 60 publications)
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Concerning the use of costs it was noted that indirect costs are rarely considered in health economic studies of psoriasis treatment. The literature search showed that in only 9 of 60 articles indirect costs were included. However, cost-of-illness studies point out that psoriasis has a high impact on occupational disability [27, 63].

In view of available guidelines [20, 25, 36, 64], a variety of needed content to create a valid health economic evaluation exists. These mostly include details about the study design with objective, methodology, interventions, and target population, the perspective, the validity of data sources, the cost determination as well as the collection of outcome parameters, time horizon, discounting rates, modeling type, sensitivity analyses, and the discussion of outcomes including the presentation of limitations. While focusing on these items, it is possible to assess the quality of an economic analysis. While picking out some articles of the 60 included hits the researchers noted gaps on inter alia data conception, sensitivity analysis, critical discussion of limitations, and inclusion of patient-reported outcomes. Although several articles on topical and systemic agents are published, only a small number of well-conducted health economic studies exists.

In conclusion, the lack of standard on methods and outcome measures leads to a very limited comparability of health economic studies and presents no comfortable basis to examine a meta-analysis of health economic results. Given the setting, compared treatments, and study conditions, different results can be found for medical decision-making. In this context, it should be noted additionally that very heterogeneous requirements by authorities are given. Whereas the NICE requires health outcomes to be expressed in terms of QALYs, the Institute for Quality and Efficiency in Health Care (IQWiG) in Germany refers to the ethical and methodological problems being accompanied by the use of QALYs [36, 49]. The presented systematic review shows the need for nationwide data and interpretation.