Psoriasis is a chronic, immunological and systemic disease with an estimated prevalence of about 2-3 percent. Psoriasis is associated with the joint disease psoriasis arthropathy. There are several treatments options available for psoriasis and patients with moderate to severe psoriasis generally need systemic agents. In 2004 biologics were introduced for patients with moderate to severe psoriasis in Sweden. The overall objective of this thesis was to assess the relationship between Health Related Quality of Life (HRQOL) and clinical outcome measures in psoriasis patients, to analyse the effectiveness of biologics in psoriasis in everyday clinical practice and to explore how costs of the psoriasis population changed after the introduction of biologics in Sweden. Methods: Research was based on national administrative registers and PsoReg, the Swedish registry for systemic treatment of psoriasis. In a cross-sectional study (paper I) the three outcome measures: the generic HRQOL measure EQ-5D, the dermatology specific HRQOL measure the Dermatology Life Quality Index (DLQI) and the clinical measure of skin involvement, Psoriasis Area and Severity Index (PASI), were analysed by demographic characteristics. The generic EQ-5D among psoriasis patients was compared to previously published values for the general population in Sweden. Relationships between measures were examined with correlation tests and regression analysis. A longitudinal study included patients registered in PsoReg who switched to a biologic agent for the first time during registration (paper II). The three outcomes EQ-5D, DLQI, and PASI were analysed before and after switch in the overall patient group and in subgroups. The relative effectiveness of continuing with the standard care of conventional treatment compared to switching from standard care to biologics was analysed in patients with moderate to severe psoriasis (paper III). Patients in PsoReg were matched with propensity scores and average treatment effects were estimated. The estimated outcomes were the change of EQ-5D, DLQI, and PASI. Patients were identified in national registers at the National Board of Health and Welfare when analysing costs; either by a registration of a psoriasis diagnosis in the national patients register and/or by a registration in the prescribed drugs register of a topical treatment with calcipotriol, a substance which has the indication psoriasis only (paper IV). Direct costs included patients’ visits in specialist health care and prescribed drugs used for psoriasis treatment, retrieved from the national patients register and the prescribed drugs register, respectively. Indirect costs included productivity loss in terms of sick leave and disability pension, which estimated as excess costs compared to controls. Controls were selected from the normal population and matched on sex, age and municipality. Productivity loss was estimated based on data from the Longitudinal integration database for health insurance and labour market studies at Statistics Sweden. Results: Patients with moderate to severe psoriasis had significantly lower HRQOL in EQ-5D than the general population (paper I). Women rated their HRQOL lower than men, even though men had more severe clinical skin involvement than women. (paper I). The generic measure EQ-5D and the dermatology-specific DLQI had moderate correlations whereas EQ-5D had low correlation with the clinical measure PASI (paper I). Patients who switched to a biologic agent during registration in PsoReg had significant improvements in all outcomes (paper II). Patients who fulfilled the criteria for moderate to severe psoriasis had the highest benefits of the biologic agents (paper II). The matched conventionally and biologically treated patients with moderate to severe psoriasis were essentially equal in important observable variables (paper III). The subgroup of patients not responding to conventional treatment had high potential benefits of biologic agents (paper III). Individuals with psoriasis had sick leave and disability pension to a larger extent than their matched controls (paper IV). Direct costs increased, whereas the indirect costs of productivity loss decreased between 2006 and 2009 (paper IV). Conclusion: Psoriasis is associated both with direct costs and indirect costs, and it has a negative impact on patients’ HRQOL. When evaluating psoriasis treatments and making decisions about treatment guidelines, both generic, dermatology-specific HRQOL measures, and clinical measures are necessary; as they answer to different needs. Although dependent on data quality, generalisability, and current pricing, results suggest that conventional treatments are suitable as first line and biologic agents as second line treatment. Results indicate that the different types of systemic treatments are not allocated optimally among patients with psoriasis in Swedish clinical practice.

Background: Psoriasis is a heterogeneous disease with several clinical manifestations; the symptoms are characterized by redness, scaliness and thickness of the skin. There are several treatment options available for psoriasis and patients with moderate to severe psoriasis generally need systemic agents. In 2004 biologics were introduced for patients with moderate to severe psoriasis in Sweden. Methods: The Swedish Health Care Registers and the Swedish registry for systemic treatment of psoriasis PsoReg, were used to; estimate the incidence of psoriasis cases in the Swedish specialist care, to examine the treatment allocation and important factors related to the initiation of especially biologic treatment. Results: On average 9000 new psoriasis patients entered specialist care in Sweden each year under study, corresponding to an incidence of 98 patients per 100,000 person-years. In the treatment allocation analysis of the incident psoriasis cases in the Swedish specialist care Patients living in a Metropolitan Area and with a University degree were more likely to initiate a biologic treatment. By analysing biologic-naïve patients enrolled in PsoReg, PASI (the physician’s assessment of the psoriasis severity) and Psoriasis Arthropathy were shown to be two important factors associated with the initiation of biologic treatment while sex was not. Furthermore, it was also shown that the decision to initiate biological treatment was more strongly associated with PASI than with DLQI (the patients’ assessment of the disease impact Quality of Life). Conclusion: These studies indicate that there are inequalities in the assignments of systemic psoriasis treatments (especially in biologic treatment). Since the allocation of treatments should not depend on sex, education or residency in a Metropolitan Area but rather the need of care, it is important that future studies continue analysing possible factors that could influence the initiation of treatment in clinical practice.

Introduktion: Psoriasis är en kronisk inflammatorisk systemsjukdom som drabbar främst hud och leder.  På grund av mycket snabbt tillväxt av hudceller ger psoriasis utslag på huden.  En av de vanligaste typerna av psoriasis är plack-psoriasis som kännetecknas av större än 0,5 cm i diameter runda fjällande hudutslag som kliar. Mekanismen som ligger bakom plack-psoriasis medieras med hjälp av T-celler och dendritiska celler som är en viktig del av immunsystemet. Stimulering av dessa immunceller leder till frisättning av följande proinflammatoriska cytokiner såsom IL-17, IFN-γ, TNF samt IL-22. Dessa cytokiner utövar sin effekt på keratinocyter genom att öka psoriatisk inflammation. Flera biologiska läkemedel utvecklas nu för behandling av plack-psoriasis. I detta arbete har fokus lagts på två av dem, sekukinumab som är en IL-17A hämmare och ustekinumab, som är en IL-12 och IL-23 hämmare. Syfte: Syftet med arbetet är att undersöka effektivitet av sekukinumab vid behandling av plack-psoriasis. Vidare undersöks även hur behandling av plack-psoriasis med sekukinumab skiljer sig från behandling med ustekinumab gällande minskning av plack-psoriasis. Metod: Detta arbete är en litteraturstudie som inkluderar fem vetenskapliga artiklar som baserades på randomiserade kontrollerade studier som sponsrades av läkemedelsföretag.  Resultat: Resultatet av de fem studier visar att behandling med hjälp av sekukinumab 300 mg och 150 mg var mer effektiv än behandling med ustekinumab 45/90 mg, enligt PASI 75, PASI 90 och PASI 100. Diskussion: Alla fem studierna var dubbel-blinda randomiserade kontrollerade studier vilket leder till säkra och tillförlitliga resultat. Däremot var samtliga studier sponsrade av läkemedelsföretag vilket kan leda till att positiv effekt beskrivs i större utsträckning för att kunna sälja sin produkt.  Slutsats: Sekukinumab 300 mg och 150 mg är signifikant mer effektiv än placebo och signifikant mer effektiv än ustekinumab 45/90 mg vid behandling av medelsvår och svår plack-psoriasis. / Introduction: Psoriasis is a chronic inflammatory systemic disease that mainly affects the skin and joints. Due to the very rapid growth of skin cells, psoriasis causes rashes on the skin. One of the most common types of psoriasis is plaque psoriasis which is characterized by larger than 0.5 cm in diameter round scaly skin rash that itches. The mechanism behind plaque psoriasis is mediated by T cells and dendritic cells, which are an important part of the immune system. Stimulation of these immune cells leads to the release of the following proinflammatory cytokines such as IL-17, IFN-γ, TNF and IL-22. These cytokines exert their effect on keratinocytes by increasing psoriatic inflammation.  Several biological drugs are now being developed for the treatment of plaque psoriasis. In this study, the focus has been on two of them, secukinumab which is an IL-17A inhibitor and ustekinumab, which is an IL-12 and IL-23 inhibitor. Purpose: The purpose of this study is to investigate the efficacy of secukinumab in the treatment of plaque psoriasis. Furthermore, it is also investigated if the treatment of plaque psoriasis with secukinumab differs from treatment with ustekinumab regarding reduction of plaque psoriasis. Method: This work is a literature study that includes five scientific articles based on randomized controlled trials sponsored by pharmaceutical companies.  Results: The results of the five studies show that treatment with secukinumab 300 mg and 150 mg was more effective than treatment with ustekinumab 45/90 mg, according to PASI 75, PASI 90 and PASI 100. Discussion: All five studies were double-blind randomized controlled trials leading to safe and reliable results. On the other hand, all studies were sponsored by pharmaceutical companies, which may lead to a positive effect being described to a greater extent in order to be able to sell their product. Conclusion: Secukinumab 300 mg and 150 mg are significantly more effective than placebo and significantly more effective than ustekinumab 45/90 mg in the treatment of moderate to severe plaque psoriasis.

Background: Chronic plaque-type psoriasis is a major dermatosis, but a significant question is still unanswered: What defines severity in chronic plaque-type psoriasis? While objective assessments like the Psoriasis Area and Severity Index (PASI) have frequently been used in clinical trials, quality of life (QOL) questionnaires are currently becoming more and more popular. Objective: This article summarizes the most important objective and subjective measurements of severity in psoriasis. For every dermatologist it is critically important to distinguish between severe psoriasis and psoriasis that severely affects QOL. Even if the PASI also has disadvantages, it is the most adequate instrument available to evaluate severity in plaque-type psoriasis. Result: We provide reasons why PASI >12 defines severe, PASI 7–12 moderate and PASI <7 mild chronic plaque-type psoriasis. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Background: Chronic plaque-type psoriasis is a major dermatosis, but a significant question is still unanswered: What defines severity in chronic plaque-type psoriasis? While objective assessments like the Psoriasis Area and Severity Index (PASI) have frequently been used in clinical trials, quality of life (QOL) questionnaires are currently becoming more and more popular. Objective: This article summarizes the most important objective and subjective measurements of severity in psoriasis. For every dermatologist it is critically important to distinguish between severe psoriasis and psoriasis that severely affects QOL. Even if the PASI also has disadvantages, it is the most adequate instrument available to evaluate severity in plaque-type psoriasis. Result: We provide reasons why PASI >12 defines severe, PASI 7–12 moderate and PASI <7 mild chronic plaque-type psoriasis. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.