Evaluation of psoriasis patients’ attitudes toward benefit–risk and therapeutic trade-offs in their choice of treatments

Introduction

Psoriasis is a chronic, inflammatory disease that manifests as red, scaly plaques varying in size and symptom burden.1,2 Quality of life can be adversely affected, with both physical and psychological well-being severely affected.1,3,4 Patient self-management can be challenging, with significant comorbidities such as arthritis, metabolic syndrome, atheromatous vascular disease, diabetes, obesity, and psychosocial impairment often complicating treatment outcomes.5–7 As no cure exists, treatment is aimed at working with the patient to maximize skin clearance while minimizing risk.8–10 A dialog is usually established between the clinician and the patient to explore the patient’s expectations and the range of treatment options available that suit the patient’s lifestyle and attitude compared to the therapeutic benefit–risk.2,11

Treatment options have expanded significantly in recent years, with conventional systemic oral therapies such as methotrexate and a range of effective injectable biologic options, including antitumor necrosis factor-α, anti-interleukin 12/23, and anti-interleukin 17 agents, now available to patients with moderate-to-severe psoriasis who are not benefiting from topical treatments or phototherapy.2,7,9 However, biologic therapy may come with a higher risk of serious infection than other therapeutic options,12 and one study found that biologic treatments are often initiated late in the treatment pathway, with a mean duration from psoriasis diagnosis to the first biologic of 22.1 years.13

Both the National Institute for Health and Care Excellence (NICE)2 and the American Academy of Dermatology11 have placed increased emphasis on patient-centric care and patients’ preferences. Guidance from the latter, in particular, has moved away from systematic sequencing in favor of immediate treatment plans based on individual patient needs, placing a specific emphasis on patient education and input.11 Using the various available patient-reported outcomes measurement tools for psoriasis,14,15 there has been a shift to improve the understanding of patients’ preferences and to incorporate these into the prescribing decision to improve overall therapeutic effectiveness in real-world clinical practice, especially as studies have shown considerable patient dissatisfaction with current treatment options, and a gulf has developed between patient expectations and the care they receive.1,16,17

The aim of this discrete choice experiment (DCE) was to capture the preferences of patients with moderate-to-severe psoriasis regarding different aspects of their treatment, including mode and frequency of administration, adverse event risks, and therapeutic benefit. The impact of prior treatment history and health-related quality-of-life (HRQL) status on these preferences was also evaluated. This information can help different decision makers with health technology assessment, shared decision making, and benefit–risk assessment.

Methods

Results

Discussion

This prospective study was designed to determine the relative value individuals diagnosed with moderate-to-severe psoriasis place on attributes of treatment for the disease. The results revealed the importance of minimizing the extent of lesions, but also the views of participants regarding the long-term risks of side effects, such as melanoma or NMSC, tuberculosis, and serious infections. The survey also assessed the importance of issues related to the convenience of taking medication either orally or by injection. These attributes represent different issues that need to be considered when making treatment choices. The preference weights from the study show how important these issues are for a sample of individuals with psoriasis in the UK.

This research builds on the previous studies reporting patients’ preferences for the treatment of psoriasis.24–27 In a recent DCE conducted in German patients with moderate-to-severe psoriasis, Kromer et al25 found that the safety of biologics was the most important attribute, followed by efficacy, but preferences varied with sociodemographic characteristics and working status. These results were consistent with an earlier report by Seston et al27 who found that attributes such as adverse effects, time to improvement, and relapse time frames influence treatment choices of individuals with psoriasis. Although Seston et al found a preference for minimizing the risk of adverse events, Schaarschmidt et al, in a 2011 study,26 reported that patients were willing to trade an increased risk of adverse events for better therapeutic outcomes. Unlike our study, neither study considered the previous treatment history of patients and how this might impact decision making. Schaarschmidt et al26 concluded that incorporating patients’ preferences into the prescribing decision may facilitate increased adherence and lead to better treatment outcomes, a view shared by Umar et al28 whose systemic review concluded that using patients’ preferences in decision making would likely improve both patient satisfaction and treatment outcomes.

In this study, participants showed a strong preference for avoiding treatments with serious long-term toxicities, such as melanoma or NMSC and serious infections, and for avoiding injectable therapies, especially if they had not previously used biologic therapies. These stated patient preferences may, in part, explain the protracted period of >22 years between diagnosis and initiation on biologic treatment reported by Fonia et al13 in UK clinical practice. Other factors that may affect this delay include the current reimbursement criteria in terms of disease severity and the prerequisite of the number of treatments patients must have failed before being eligible for biologic therapies in the UK.2,29 A delay in referral from primary to secondary care, general challenges in access to specialist dermatology services throughout the UK, and the high cost of biologic treatment may also play a part.

Participants who reported that their psoriasis had a very large impact on their quality of life (DLQI score >10; n=126, 43.1%) had a higher likelihood of accepting treatment-related toxicities in relation to risk of serious infection and were less reluctant to receive injections. Overall, participants with no prior experience with biologic therapies were more averse to the risks of treatment toxicities compared with people with biologic experience. A trend was also observed for the biologic-experienced group to be more willing to accept injection treatments. This suggests that previous experience with biologic therapies or experiencing a very large effect on HRQL (DLQI score >10) may affect patients’ treatment preferences by reducing aversion to injections and increasing acceptance of adverse events and reduced efficacy. These two subgroups also stated preferences that appeared to place less differentiation between the hypothetical treatment options included in the DCE and less extreme preferences for all attributes considered. The similarities between the treatment preferences seen in participants with a DLQI score >10 and biologic-experienced participants can be expected because the majority of biologic-experienced patients (60%) also reported a DLQI score >10. Such an overlap is not surprising, given that the criteria for receiving biologic therapy in the UK include having a DLQI score >10. Moreover, the experience of failing on or switching between multiple therapies, including biologics, may affect patients’ expectations of future treatment, increasing their willingness to accept treatments with different modes of administration, such as injections, and altering their benefit–risk tolerances. This may apply particularly to participants in the current DCE who reported both biologic experience and a DLQI score >10. These factors in combination may be an indicator of being treatment refractory due to lack of efficacy or due to toxicities, thus leaving them few treatment options to consider in real life and therefore reducing their concerns about trying hypothetical treatments with less-favorable profiles.

In addition, the analyses indicated that people with better HRQL (DLQI score ≤10) placed more value on treatments that reduce the extent of BSA affected by psoriasis. Similar effects have been seen previously in other chronic diseases.30–32 It is possible that people who value treatments more highly are more likely to be adherent and therefore experience less disease burden.30 Longitudinal research is needed to explore these effects in more detail. These methods may be able to provide fresh insights into what drives good outcomes in psoriasis.

The regulatory environment is also becoming increasingly accepting of evidence on patients’ treatment preferences during their decision-making processes. Indeed, the 2012 US Food and Drug Administration guidelines from the Center for Devices and Radiological Health on benefit–risk analysis clearly state the importance of considering patients’ preferred treatment when approving medical devices to market.33 The Food and Drug Administration is also using patient feedback and preference DCE evidence to help to facilitate the development and use of patient-centric weight-loss devices for obese patients, a move away from its previous “one-size-fits-all” approach.34,35 In Belgium, DCE studies have been used to consider the importance of decision criteria among citizens with reference to reimbursement,36 whereas the US Centers for Medicare and Medicaid Services uses patient experience surveys to link Medicare payments to health care quality via its Hospital Value-Based Purchasing program.37 This has become an area of research for health technology assessment reimbursement agencies such as NICE in the UK, which has previously consulted on the use of multiple criterion decision analysis in their decision-making framework.38 A recent collaboration between Myeloma UK and NICE to examine how patients’ treatment preferences can be quantitatively captured and incorporated alongside other data in decision modeling as part of the Health Technology Assessment program underscores the growing interest in understanding the impact and role of patients’ treatment preferences in the decision-making process in the UK.39

Some limitations of this study should be considered. Patient self-reporting of psoriasis diagnosis and severity means there is potential room for error across patient comparisons. To best quantify the results, the number of attributes included in the survey needed to be finite. As a result, there may be other attributes that patients with moderate-to-severe psoriasis find important when choosing a treatment, but which we were not able to include. This is a constraint of the methodology. The pretest interviews supported the choice of attributes.

The choice survey is intended to simulate decisions in clinical practice, but of course it does not have the clinical or emotional consequences of actual decisions. Differences can arise between stated and actual choices. The results indicate the importance of different issues for patients, but this limitation should be considered when interpreting them. In addition, levels associated with each attribute may not reflect marketed therapies for psoriasis based on the available data. However, the dosing schedules for the injectable treatments reflected the most widely used biologic therapies for psoriasis in the UK at the time of this study.40 The subgroup analyses were univariate and need to be interpreted cautiously. They were exploratory and descriptive in nature, which may have limitations. However, they can go some way to help us understand heterogeneity in the preference data.

To avoid well-known cognitive problems with evaluating small probabilities, we defined the risk exposure as the chance of each of three serious side effects over 10 years. The actual risk of serious infection may not be linear over time, but exploring preferences for potential nonlinearities in risk exposure was beyond the scope of this study.

The population recruited in this study appeared to be representative of the general psoriasis population in the UK in terms of age, sex, and disease severity.41,42 A comparison of participants’ demographics from this study shows some similarities with patients included in a prospective registry study in the UK and Ireland evaluating patients treated with biologic therapy.40 However, some notable differences included a shorter mean disease duration (12.6 vs 19.0 years) and a lower mean DLQI score (10.5 vs 18.0) in this study. It is possible that the method for recruitment resulted in some selection bias, as most participants in the DCE had moderate disease. However, population-based studies of psoriasis using electronic medical records from the Health Improvement Network, which are representative of the general population in the UK, have reported that a higher proportion of psoriasis patients have moderate (~35%, BSA: 3%–10%) compared with severe (~13%, BSA >10%) disease,41,42 which is similar to the patient population recruited for our DCE. The study did not seek to correlate preferences for treatment attributes in patients with difficult-to-treat manifestations, such as nail, scalp, or palmoplantar psoriasis.

Conclusions

This study shows the importance of patients’ preferences toward the attributes of various potential treatment profiles for psoriasis and provides some insight into the extent to which people balance efficacy against risks of side effects and toxicities and even convenience issues. As regulators and reimbursement bodies begin to tangibly recognize the importance of patients’ preferences, it will be important for health care professionals to be aware and communicate benefit–risk information to patients. The data from this study could be used to help communicate how patients feel about the benefits and risks of treatments for psoriasis and promote shared care in treatment decision making. In addition, analyses were able to demonstrate how the preferences varied within the study sample. Preferences varied in terms of disease impact on HRQL and also in terms of whether people had received biologic therapy previously. The results show how experience with biologic therapy can reduce patients’ concerns about injection-based therapy. Many factors influence the quality of patient outcomes in chronic diseases. This type of research can complement clinical trial data by providing insight into the relative weight of efficacy, tolerability, and other factors for patients with psoriasis.