Adherence, satisfaction and preferences for treatment in patients with psoriasis in the European Union: a systematic review of the literature

Introduction

Psoriasis is a common chronic inflammatory disease of the skin and joints that is typically characterized by erythematous papules and plaques.^1–3 Estimates of the worldwide prevalence of psoriasis range from 1% to 3%^4–6 and it affects ~2% of the population in Europe.^7,8 The disease can present at any age, but the mean age of onset for the first presentation of psoriasis ranges from 15 to 20 years, with a second peak occurring at 55–60 years.⁹ Although psoriasis is not a life-threatening disease, it has a negative effect on patients’ health-related quality of life (HRQoL), similar to that of other major medical conditions.^9–12

The severity of disease is related to the extension of the cutaneous manifestations and is defined by the Psoriasis Area and Severity Index (PASI) or as a percentage of the total body surface area (BSA).¹³ The majority of psoriasis patients suffer from mild disease (PASI ≤10), which can often be managed with topical agents, while phototherapy or systemic therapies are usually used for patients with moderate-to-severe psoriasis (PASI >10). In the last decade, significant advances in the management and treatment of psoriasis have been made with the introduction of biologic agents,^14,15 which have shown greater clinical benefit than traditional systemic therapies.^16–22

With more than 90% of psoriasis patients having a chronic condition, adherence to treatment is crucial for successful disease management and reduction in clinical severity.²³ However, it is estimated that nearly 40% of patients with psoriasis do not use medication as prescribed.^4,24,25 In addition to non-adherence, psoriasis is consistently associated with treatment dissatisfaction.^3,26–28 As satisfaction is closely associated with patient preferences and compliance with treatment,²⁹ taking patients’ opinions about available treatment options into consideration may be crucial to improving satisfaction and adherence, thereby increasing the effectiveness of the treatment and HRQoL.

The introduction of biologic therapies over the past 10 years has further increased the therapeutic options for moderate-to-severe psoriasis. Although all of these biologic agents are highly effective and show a favorable risk–benefit profile, differences in efficacy, rapidity of action and sustainability do exist. This makes the decision-making process regarding the most suitable therapeutic strategy more complex for both patients and physicians, underlining the need to elucidate patients’ treatment preferences. This review aims to examine and describe the current literature on patient preferences, satisfaction and adherence to treatment for psoriasis in the European Union (EU).

Methods

We performed a systematic review of the literature on adherence to treatment, satisfaction with therapy, patient preferences for treatment and HRQoL in psoriatic patients in the EU. In order to obtain an accurate insight into how novel treatment options (available in European countries since 2005) have influenced patient-reported outcomes (PROs), studies from January 1, 2009 to December 31, 2014 were included. International (Medline/pubMed, cochrane Ligrary, ISI Web of knowledge [ISI WOK], SCOPUS) and Spanish electronic databases (Medicina en Español [MEDES], Índice Bibliográfico Español en Ciencias de la Salud [IBECS]) and Google Scholar were used to search the literature. The English and Spanish search terms used are summarized in Table S1.

Original articles, reviews and systematic reviews in English or Spanish that evaluated treatment adherence and satisfaction, patient preferences for treatment and HRQoL in psoriatic patients from a European perspective were included in the review. Publications about all of the treatments available for psoriasis (topical, systemic and biologic agents) were included. On the other hand, studies conducted in non-EU countries, original letters to the editor, editorials, experts’ opinions, case studies, congress proceedings, studies with mixed populations including patients with psoriasis (with or without psoriatic arthritis) and patients with psoriatic arthritis alone or studies related to specific treatments were excluded. The selection of publications was performed by two independent researchers and discrepancies were resolved by consensus.

The methodological quality of the studies was assessed by assigning a level of evidence and recommendation based on criteria developed by the Centre for Evidence-Based Medicine (CEBM).³⁰

Results

A total of 1,769 titles were identified, of which 587 (33.2%) were duplicates and therefore excluded. The other 1,182 (66.8%) were excluded because they did not provide any relevant information. After full-text reading and application of the inclusion/exclusion criteria, 46 of the remaining 133 publications were included in the review (Figure 1). Twenty-seven (58.7%) articles were related to HRQoL, seven (15.2%) evaluated treatment satisfaction, five (10.9%) examined treatment preferences, four (8.7%) explored treatment adherence and three (6.5%) described cumulative life course impairment (CLCI). Results related to HRQoL (n=27) and CLCI articles (n=3) have been published elsewhere.³¹

Figure 1 PRISMA diagram of systematic review process. Abbreviations: PRISMA, preferred reporting items for systematic reviews and meta-analyses; EU, European Union; PROs, patient reported outcomes; P, psoriasis; PsA, psoriatic arthritis; HRQoL, health related quality of life; CLCI, cumulative life course impairment.

The present article examines and describes the 16 studies, published in the EU between January 1, 2009 and December 31, 2014, that were selected and which related to psoriasis patients’ preferences for treatment, adherence and satisfaction.

Characteristics of selected studies

These 16 studies included the following designs: 4 conjoint analyses, 2 reviews, 1 systematic review, 4 prospective studies, 3 cross-sectional studies and 1 retrospective study. Nearly half were conducted in Germany (n=7), two in the UK, two in Spain, two in the Netherlands, one in Italy and two were multicenter studies across different European countries. The level of evidence in the majority of the studies (n=12) was grade 2c and their CEBM recommendation was grade B, which indicates moderate evidence.

Treatment adherence in patients with psoriasis

Of the 16 studies, 4 (25%) examined adherence to medical therapies. Three of them were reviews, which evaluated rates and determinants of adherence, while the fourth article selected was a Delphi consensus study conducted in Spain.

The systematic review undertaken by Thorneloe et al³² consistently reported low rates of treatment adherence, regardless of the type of treatment, disease severity or type of adherence measurement used (Table 1). Even though there were inconsistent findings with regard to the predictive factors of adherence, studies investigating the role of psychological factors revealed that increased psychological distress and low patient satisfaction with care or therapy were associated with lower levels of adherence. In line with these results, Bewley and Page²⁴ confirmed that rates of adherence to topical medications were low, with 39%–73% of psoriasis patients not using medications as prescribed and revealed that effectiveness and the characteristics of the treatment (cosmetic acceptability) were the main contributors for increasing adherence to psoriasis medication. Moreover, they identified that prescribing therapy in line with patient preferences or improving patient education may result in increased adherence. Similarly, Zschocke et al³³ established that the reasons for non-adherence to treatment amongst psoriasis patients revolve mainly around treatment vehicle, patient–physician relationship or patient motivation. These authors propose that given that the barriers to medication adherence are complex and varied, solutions to improve adherence should be multifaceted and allow tailoring according to each patient’s individual needs.

Table 1 Adherence rates Note: Data from Thorneloe et al.32

Finally, the Delphi study conducted by Puig et al³⁴ with a panel of experts from the Psoriasis Group of the Spanish Academy of Dermatology and Venereology reached a consensus that in order to improve adherence to topical treatment, it was necessary 1) to improve communication between patients and health care staff, 2) to provide written instructions and 3) to simplify treatment with easy-to-use and pleasant products that were preferably applied only once a day. In addition, the panelists agreed that treatment satisfaction increased adherence and tended to improve the HRQoL of psoriasis patients, highlighting the relationship between treatment satisfaction and treatment adherence.

Taken together, these studies draw attention to the low rates of adherence to psoriasis treatments and highlight the importance of involving patients in treatment decision-making, in order to improve their adherence to treatment.

Treatment satisfaction in patients with psoriasis

The following section summarizes seven articles related to treatment satisfaction of patients with psoriasis and to variations depending on type of treatment, demography and clinical factors. Five articles used study-specific questionnaires, while the other two studies assessed patient’s satisfaction using the Treatment Satisfaction Questionnaire for Medication (TSQM) (Table 2).

Table 2 Characteristics of treatment satisfaction studies reviewed Abbreviations: PASI, Psoriasis Area and Severity Index; PROs, patient-reported outcomes; TSQM, Treatment Satisfaction Questionnaire for Medication; SSWTPQ, Spanish Satisfaction with Treatment of Psoriasis Questionnaire; NS, not specified; HRQoL, health-related quality of life; SD, standard deviation.

Schaarschmidt et al³⁵ revealed the high impact of the type of treatment on satisfaction scores. Participants receiving biologicals (TSQM: 323.3) and traditional systemic treatments (TSQM: 288.0) were more satisfied than those receiving phototherapy (TSQM: 260.6) or topical agents (TSQM: 266.8; P<0.001). These authors also observed that high disease-related HRQoL impairment, as measured by the Dermatology Life Quality Index (DLQI), and psoriatic arthritis were associated with decreased treatment satisfaction. In line with these results, van Cranenburgh et al³⁶ indicated that, overall, patients with psoriasis were moderately satisfied with their current treatment, with patients receiving biologic treatments being the most satisfied, compared to other groups (total satisfaction score [range from 5= not satisfied to 25= very satisfied]: topical [16.5], phototherapy [18.3], systemic [19.5], biologics [0.9]). These authors identified age (t[1182] =2.9; P=0.004) and disease severity (t[1882] =−18.6; P<0.001) as predictive factors of satisfaction. Similarly, Ragnarson Tennvall et al³⁷ described the highest treatment satisfaction, that is, 8.2 (scale of 0 not at all satisfied to 10 very satisfied) in patients who had been treated with biological drugs for 12 months, followed by patients who received systemic treatment for less than 12 months (6.5) and patients receiving topical treatment (5.7). Van den Reek et al³⁸ confirmed the high satisfaction rates achieved with biologic treatment, with statistically significant (P<0.05) improvements in the “efficacy”, “convenience” and “global satisfaction” domains of TSQM after 3 and 6 months initiation of biologic therapy.

Two studies assessed the relationship between psoriasis severity (PASI) and satisfaction. Schäfer et al³⁹ showed that, while most patients who achieved PASI 75 (92.3%) indicated that their expectations with the treatment were met, this applied to only half (53.1%) of patients with PASI 50 and to 36.4% of patients with lower clinical treatment success (PASI <50). In relation to satisfaction with the condition of their skin after therapy, 84.6% of patients who achieved PASI 75 were completely or predominantly satisfied; this proportion was reduced to 43.7% and 36.4% in the PASI 50 and PASI <50 groups, respectively. Christophers et al⁴⁰ observed that the percent of PASI reduction in patients with severe psoriasis who received biologic therapy was significantly greater than in patients who received topical therapy, phototherapy or traditional systemic therapy (79% vs 55%, 47%, 69%, P<0.001). Thus, a reduction in PASI contributed to an increase in treatment satisfaction. More patients receiving biologic therapy were satisfied (highly or completely) with their current treatment than patients receiving any other therapy (59% patients receiving biologic therapy vs 50% patients receiving traditional systemic therapy vs 34% patients receiving phototherapy vs 45% patients receiving topical agents only; P<0.001).

In line with these results, in a study published by Ribera et al,⁴¹ with the aim of developing a satisfaction questionnaire (Spanish Satisfaction with Treatment of Psoriasis Questionnaire) and assess its validity, reliability and sensitivity to change, patients with severe psoriasis scored higher [(0= highest satisfaction; 48= highest dissatisfaction), 27; SD: 2.6] than patients with moderate psoriasis (22.6; SD: 9.5). These authors described a weak correlation between reduction in PASI score during a 12-month study period and improvement in satisfaction.

In summary, satisfaction studies indicated that patients receiving biologic therapy were more satisfied and their satisfaction was correlated to improvements in clinical features (mainly measured by PASI score).

Patient preferences for therapies in psoriasis

Five publications examined patient preferences for treatment; four of them described the results of a conjoint analysis based on a discrete choice experiment that aimed to analyze the preferences of individuals with moderate or severe psoriasis for outcome and process attributes^42–45 (Table 3). In a study published by Schaarschmidt et al,⁴² the attribute regarded as most important was treatment location (where the treatment takes place) (relative importance score [RIS]: 26.76), followed by probability of benefit (RIS: 23.77) and method of delivery (RIS: 23.49). The RISs for all process attributes were higher than for adverse effect (AE)-related attributes, indicating that participants were willing to trade an increased risk of AEs for increased probability and magnitude of therapeutic benefit. Age, disease severity (PASI score) and household income were the only factors that affected preferences. Older participants (≥65 years) found the probability of benefit less important than younger participants (P=0.005); patients with intermediate incomes (€1,000–€2,000 per month) granted less importance to treatment delivery method compared with patients with lower income; patients with higher PASI score considered the probability of benefit as less important (P=0.02) but the frequency of treatment more important compared with participants with a lower PASI score (P=0.04). Schaarschmidt et al⁴³ described the impact of treatment experience (satisfaction with current treatment, number of prior visits, disease duration, number of preceding therapies and currently prescribed treatment modalities) on treatment preferences. With regard to disease and treatment duration, participants with longer disease duration attached greater importance to the duration of benefit (β=0.206, P=0.018), whereas participants on oral therapy were more concerned about magnitude of benefit by trend (β=0.218, P=0.058). Participants receiving injectable therapy not only set higher value to probability of benefit (RIS =32.80 vs 21.89, P=0.025) but also to treatment location (RIS =44.74 vs 23.03, P=0.011), delivery method and treatment frequency (RIS =31.24 vs 16.89, P=0.005) and duration (RIS =32.54 vs 16.57, P=0.003) compared to others.⁴³ These results suggest that treatment preferences change over the course of time and with treatment experience. Participants on injectable therapy attached great importance to the effectiveness and convenience of treatment and were highly satisfied with it. As reported by Umar et al,⁴⁴ prolonged treatments in the inpatient setting (Mean Preference Score [MPS]: −13.48) and those with a lower probability of benefit (MPS: −12.28) were the least preferred while treatments with a high probability of benefit (MPS: 10.51) were most preferred. Patients were more concerned about improvement of their skin condition than about the reversibility or the severity of treatment side effects. Using data from the conjoint analysis, Umar et al⁴⁵ published a prospective cohort study which assessed the extent to which matching physicians’ treatment recommendations to patients’ treatment preferences was associated with improvement in treatment. The results of the study suggested that a closer match between physicians’ recommendations and patients’ preferences was associated with greater improvement in treatment satisfaction over time in each of the four subscales: effectiveness (β=0.53, P<0.001), side effects (β=0.25, P=0.009), convenience (β=0.78, P<0.001) and global satisfaction (β=0.49, P<0.001).

Table 3 Characteristics of preferences related studies reviewed Abbreviations: PASI, Psoriasis Area and Severity Index; SD, standard deviation; AE, adverse event; UV, ultraviolet; TSQM, Treatment Satisfaction Questionnaire for Medication; NHS, national health system.

Finally, Torbica et al⁴⁶ conducted a discrete choice experiment on 244 Italian psoriatic patients. Overall, patients preferred the subcutaneous or intravenous route of administration (vs oral administration) and treatments that took less time to show improvement, ensured a longer time free of symptoms, involved a lesser reduction in life expectancy and had lower costs. In general, older patients placed significantly greater importance on reduced life expectancy, whereas time free of symptoms was less important to them than to patients under 60 years of age. Patients with high DLQI scores placed higher value on time free of symptoms than those with lower DLQI scores.

Data from these studies offer a focus on patients’ preferences for psoriasis treatment and suggest that when making decisions about treatment, the heterogeneity of patient’s expectations and preferences should be considered in order to identify individualized treatments that would aid in optimizing patient satisfaction and well-being, as well as overall treatment effectiveness.

Discussion

Despite the heterogeneity of the articles selected in terms of patients, treatment and methodology features, the information obtained from the studies included in this review provides an assessment of the challenge of non-adherence in psoriasis, together with an identification of patients’ preferences and levels of satisfaction regarding the medications currently approved for the treatment of psoriasis in the EU.

According to the results reported, adherence rates in patients with psoriasis were generally low and were influenced by multiple factors, such as the characteristics of patients and the treatments, treatment effectiveness, patient–physician relationship or patient motivation. However, findings were inconsistent with regard to predictive factors of adherence.

In addition to treatment adherence, this review investigated current knowledge regarding patient preferences and satisfaction with available treatment options for psoriasis. The results highlight that patients receiving biologic treatment were consistently more satisfied compared to those receiving traditional systemic therapies, while patients receiving topical therapies were the least satisfied. Moreover, the positive association between clinical treatment success and satisfaction suggested that the use of effective drugs that provide greater reduction in disease severity (PASI score) may contribute to higher rates of satisfaction.

Several studies conducted outside the EU support these results. Overall satisfaction scores, as measured by the TSQM, obtained in a cross-sectional study of 1,182 moderate-to-severe psoriasis patients conducted by Callis Duffin et al⁴⁷ in the US, were highest for patients receiving biologic monotherapies, biologic combinations or phototherapy (83.3), while scores were lowest for those receiving topical therapies only (66.7). Significant correlations were found between overall survival and both PASI (ρ=−0.36, P<0.001) and DLQI (ρ=−0.47, P<0.001). Similarly, Finch et al⁴⁸ reported that levels of satisfaction with phototherapy and systemic treatments were high; conversely, there were higher levels of dissatisfaction with topical treatments.

Regarding patients’ preferences, psoriasis patients attach greater importance to process attributes (treatment location, method of delivery, frequency, duration and cost) than to outcome attributes (probability, magnitude or duration of benefit and AE probability, reversibility or severity) when selecting treatment. Although the probability of benefit was also highly considered, psoriasis patients appear to be willing to accept treatment-related AEs if the process characteristics of psoriasis treatment provide a better fit with their personal and professional life. Treatment preferences may change over time and with treatment experience. Recently, in a study conducted by Kromer et al,⁴⁹ the most important attributes in relation to biologic agents for patients with moderate-to severe psoriasis were safety (probability of severe AE) and efficacy (probability of 90% improvement). With regard to efficacy, although a 75% improvement in PASI score (PASI 75) is generally considered the gold standard of treatment efficacy in the clinical setting in patients with psoriasis,⁵⁰ when the advances obtained with biologic therapy are considered, PASI 90 may represent the best meaningful clinical response, particularly in patients with very severe psoriasis.⁵¹

Additionally, these authors have revealed that preferences vary with sociodemographic characteristics and working status. Of note, men were more concerned about the probability of symptom improvement than women, and women attached greater value to treatment frequency than men. Older participants judged the probability of improvement less important than younger patients but they worried more about severe side effects. Finally, patients with a full-time job gave more value to time until response, treatment location and treatment frequency than non-working patients.⁴⁹

In line with these data, a review that aimed to examine the published evidence regarding patient preferences and satisfaction in rheumatoid arthritis,⁵² process attributes, such as vehicle, and treatment location attributes were also very important for patients with rheumatoid arthritis. In addition, when given a choice among various therapeutic options, these patients chose a biologic or combination therapy that included a biologic agent.

The overall results suggested that incorporating patient preferences into treatment decision-making may contribute to improve treatment satisfaction, adherence and thus, clinical outcome.

Possible limitations of this review included the small number of papers retrieved. This may be due to the exclusion of studies published before the introduction of biologic treatments. In addition, there may be relevant papers in languages other than English or Spanish or that are indexed in databases other than those searched, which we did not identify. Nevertheless, as all the studies included European populations, this review reflects the disease characteristics of homogeneous populations in industrialized countries.

Finally, it is important to point out that, although there were differences between study designs, populations, outcome parameters and the treatments compared among the publications included, the information with regard to adherence and PROs in psoriasis that was obtained from our comprehensive search was very robust and valuable in terms of facilitating shared decision-making during the clinical encounter.

Conclusion

The results of this review support the conclusion that adherence rates in patients with psoriasis are suboptimal, highlight the need to improve treatment compliance and add satisfaction with treatment to enhance the HRQoL for patients with psoriasis. To this end, a better understanding of the factors that motivate and discourage patient participation in treatment is necessary. Patient preferences should be taken into account in the treatment decision-making process in order to improve patients’ clinical outcomes by ensuring satisfaction and adherence.

Disclosure

The study was sponsored by Novartis Farmacéutica S.A. The authors report no other conflicts of interest in this work.

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Supplementary material

Table S1 Search terms and research strategies used in international and Spanish databases