“Patient-centered treatment” for mild-to-moderate psoriasis

Summary

People with mild-to-moderate psoriasis have an impaired health-related quality of life. Surprisingly, on one hand, at least one-third of these patients are not seeing a physician during episodes of at least 1 year on and average. On the other hand, some patients are seen by the GP and simultaneously by several dermatologists. In this review, we will try to understand this discrepancy between unmet need and medical consumption by reviewing evidence-based data on topical treatments as well as patient reported outcomes and aspects of adherence.

In a recent study in patients treated by general practitioners (GPs) in the United Kingdom, awareness of psoriasis, diagnosis, and the options for treatments were low for GPs and their patients. Indeed, it is also our impression that continuous long-term control of mild-to-moderate psoriasis by the GP’s is not adequate in all patients, which they have referred to us. In particular, the limitations of chronic exposure to (super)potent corticosteroids, treatment adherence, and the expectations of the patients have to be reconciled in this respect. In order to provide a high-quality management of patients with mild-to-moderate psoriasis, a “patient centered approach” is proposed. This model is based on the following considerations:

1. The step-wise approach in treatment selection.

2. Monitoring adherence factors and patient reported outcome measures in a virtual environment.

3. A virtual treatment environment and a liaison between echelons of care. The present review provides the rationale and propositions for a tentative program using ICT solutions and face-to-face contacts for a patient centered treatment model. Ultimately we will suggest the “patient-centered approach”, a combination of a virtual treatment environment and face-to-face consultations to improve quality and cost effectiveness of care for patients with mild-to-moderate psoriasis.

Introduction

In a recent large-scale study in the general population of Northern America and Europe (139 948 households), a large unmet medical need was apparent in the subpopulation of patients suffering from psoriasis (1). The average delay between the onset of symptoms and the diagnosis was as much as 2 years. Fifty percent of patients with an involvement of at least four palm-sized lesions indicated that psoriasis had a major impact on psycho-emotional aspects of life (DLQI>5). Forty-five percent of patients with psoriasis had not seen a physician during the previous year. Between 37 and 41% of patients with mild-to-moderate psoriasis had no treatment at all. Although a spectrum of treatments is available for these patients and although the impact on quality of life is substantial, under-treatment of psoriasis appears to be the reality.

About two-third of world’s population of psoriasis patients has a form of mild-to-moderate psoriasis. The mainstream of treatment in these patients is a topical treatment. Vitamin D and corticosteroids are the most frequently used first-line topical treatments; dithranol and tar are classical treatments which may be helpful if first line treatments are not providing satisfactorily control. Topical calcineurin inhibitors are indicated in some patients with flexural and facial psoriasis, although an official registration for this indication has not been obtained. In case of insufficient response (or when topicals alone are not practical due to the extent of the disease), phototherapy, systemic treatments including biologics are indicated. How do we actually make our treatment selection? How do we manage the long-term care in these patients?

Guidelines have been developed based on the best available evidence for efficacy and safety with expert opinions where evidence is insufficient. Indeed, the classical approach to develop guidelines starts from the best evidence available and secondary, the expert opinions on treatments with limited evidence. In real clinical practice of the treatment of psoriasis, multiple factors are relevant to treatment selection and treatment success. It was reported already by Nast et al. (2) that the practical applicability of current guidelines available for psoriasis is disappointing. The general practitioner (GP), dermatologist in a general hospital, and dermatologist in academic centers treat patients with mild-to-moderate psoriasis.

The aim of the review is to understand this discrepancy for the population of patients with mild-to-moderate disease, which is the vast majority of psoriasis patients. Furthermore, we have suggestions how to provide a different approach to care for these patients, which may enlarge the accessibility to treatments and to improve the quality of care at lower costs.

We addressed the following questions regarding the topical treatment of psoriasis, which is by far the most popular treatment in the vast majority of patients:

1. How do we decide in practice on the treatment selection: what are the critical factors in real clinical practice, which guide a decision?

2. What evidence is available from clinical studies on these aspects?

3. How can we optimize the quality and efficiency of care by collaborative programs?

Factors involved in treatment selection in real clinical practice; the views of the dermatologist?

It is born out of clinical practice that a plethora of factors are involved in treatment selection besides the medical guidelines. The physical and emotional impact of the disease, the benefits and risk of various treatments, patient education, patient preference, and the achievability to reach the treatment goals in real clinical practice are all important for the decision of which treatment will be selected. It is of eminent importance that psoriasis is a chronic disease and that these factors may change during the follow up of the individual patient, changing the treatment context. In this section, we strive to provide an overview of these factors based on the experience in our hospitals.

1. The previous history of the patient: Every patient has his/her own previous history, which is of eminent importance to estimate disease severity and responsiveness to treatments.

• The previous history starts with disease management by the GP. GPs with a special interest in psoriasis may have instructed the patient adequately with respect to the course of the disease, triggering factors and have prescribed several courses of topical treatments, which all are adequate. On the other hand, some GPs have great difficulty with diagnosis of inflammatory skin diseases and refer the patient immediately to the dermatologist; these patients may be virtually treatment-naive. The variability between general practitioners with respect to criteria for referral is a crucial factor to be reconciled by the dermatologist.

• Patients who are not responsive to a vitamin D and class 2–3 corticosteroids are different from patients with adequate response to these treatments and should be stratified in a different disease class.

1. The efficacy and side effects of the treatments: In real clinical practice, a PASI score at the time for primary outcome in itself is not the whole story. A fast onset of robust improvement is extremely important for optimal treatment adherence. However, short-term maximal improvement is not good enough; sustained improvement is what patients with a chronic condition need.

• The percentages of body surface area involved with psoriasis may in some patients be an important outcome, whereas in another patient other aspects, such as itch or visibility, may be the key.

• Which outcome criteria are relevant? The PASI does not capture patients’ perceptions. Patient reported outcomes related to health-related quality of life and subjective sensations such as itch may be more important.

• The presentation at consultation may predict the response to treatments, such as the state of exacerbation and localizations of the lesions.

1. Treatment adherence: Adherence is the degree to which patients use medication as prescribed by their physician. Poor adherence can be caused by, among other things:

• Frustration with efficacy and inconveniences of the treatments.

• Unclear instructions and fear of side effects.

• How easy is it to carry out the treatment schedules in the individual setting of the individual patient? Indeed, multiple topical treatments with sequential combinations or different topical treatments for the various localizations may represent a serious compliance problem for some patients.

• Treatment costs may be substantial for a chronic disease such as psoriasis and for some patients represent a serious limitation.

1. The perspective of the patient: What is it that the patient really wants to achieve? What is the motivation of the patient to cope with the discomfort of the treatments? Can the patient understand the information on psoriasis and treatment to the extent that he/she can translate this into adherence to treatment instructions?

• Some patients want the diagnosis to be confirmed and get some information on the disease, whereas others want to be for 100% clear forever. Some patients want to get rid of their psoriasis on visible areas only. Other patients want to be without itch and do not mind to have some psoriatic plaques.

To guide the treatment in real clinical practice, the dermatologist focuses on the relevant parameters out of a host of factors in the individual patient at the very moment of consultation, anticipating an optimal treatment following the consultation. This is the personalized approach in the treatment of psoriasis, which is provided by the dermatologist. The first question is what evidence is available on the actual validity of these factors for treatment outcome. We will now address the question to what extend such evidence is available regarding the above-mentioned factors related to the topical treatment of psoriasis.

What evidence is available for the decisions we take in real clinical practice?

The previous history of the patients

Patients are seen first by the general practitioner (GP). Recently a survey was conducted under members of psoriasis patient organization. Patients indicated that psoriasis was diagnosed correctly by the GP at 75% of first consultations (3). In total, 68% of the patients had been referred to a dermatology center. About 30% of these referrals were at the request of the patient. About 54% of the patients were not given adequate information by the GP’s and despite the fact that half of the patients experienced emotional distress; only 13% of these patients had received professional support. In another study, qualitative semi-structured interviews were conducted with a diverse sample of 29 people with psoriasis and 14 GPs. These interviews revealed that GP’s need to improve their knowledge and skills in assessment and management of psoriasis (4).

In the guideline on psoriasis by the Dutch Council for General Practitioners (NHG), a stepwise treatment paradigm and treatment goals were defined in very general terms. https://www.nhg.org/standaarden/volledig/nhg-standaard-psoriasis. Such guidelines may explain in part the large variability between GP’s with respect to their referral policy. Some GP’s refer the patient after having prescribed the full spectrum of topical treatments, whereas other colleagues refer a patient with psoriasis at first consultation.

Also, the request of the patient is important in this respect, and requests for referral may vary from patient to patient. Some patients urge a referral to a dermatologist immediately, although they have minimal psoriasis, whereas others prefer the GP as the doctor “just around the corner”. It implies that individual patients, seen by the dermatologist for the first time, may be very different and all require an individualized approach.

The responses to previous treatments are of importance to define disease severity from a therapeutic point of view. Indeed, non-responders to topical treatments are eligible for phototherapy or systemic therapy and represent a more severe disease as compared to the patients responding well to topical treatments. Within the patients treated with topical treatments there is substantial inter-subject variability with respect to responsiveness to the various treatments. In the Salford Psoriasis Index (SPI), the response to previous treatment has been incorporated as a major parameter (5).

The efficacy and side effects of the treatments

Topical treatment with vitamin D analogues and corticosteroids is the mainstream treatment for patients with mild-to-moderate psoriasis (6). Mono-therapy with the vitamin D analogues calcipotriol (twice daily 50 μg/g), calcitriol (twice daily 3 mg/g) or tacalcitol (once daily 4 μg/g) is effective in the treatment of psoriasis. After 4 weeks, the patients have reached a meaningful improvement with a maximum efficacy reached after 8–12 weeks treatment. On an average, a 50% reduction of the various severity scores have been reported for the vitamin D analogues. Although further improvement was not seen in clinical trials beyond 12 weeks of treatment, no signs of tachyphylaxis were noticed. Provided that the quantities of the vitamin D preparations per week do not exceed the maximally allowed quantities (100 g per week for calcipotriol and 200 g for calcitriol), no signs or symptoms of hyper-calcemia have been reported. Long-term sustained efficacy has been shown for up to 52 weeks (7–11).

Augustin et al. (6) reported remission rates between 40 and 60% of the patients treated with topical corticosteroids. The side effects of long-term treatment with potent and super-potent topical corticosteroids are well known: suppression of hypothalamic–pituitary axis, Cushing syndrome, atrophy of the skin, perioral dermatitis, tachyphylaxis, – resulting from decreased adherence by the patients or from decreased biologic response to prolonged treatment – and rebound of psoriatic lesions. Long-term continuous treatment with corticosteroids as mono-therapy in psoriasis has been evaluated in some small studies of up to 6 months. Hypothalamic–pituitary axis suppression was reported in up to 41% of patients treated with desoxymethasone cream but not with betamethasone 17-valerate (12). In a study on the intermittent use of topical betamethasone-dipropionate, no signs of atrophy or systemic suppression of adrenal glands were shown (13). However, the rather heterogeneous picture of the actual corticosteroid side effects in psoriatics treated with topical corticosteroids has to be regarded with caution. The maximum duration of treatment is only a few months up to 6 months, a range of different potencies of corticosteroids does exist, localizations may be very different and the area of involvement may differ, the application frequency varies from sparse intermittent use up to continuous twice-daily use. Penetration enhancers and occlusion may have been used. Therefore, the long-term safety studies on topical corticosteroids are difficult to interpret, and a realistic impression on the actual frequency of potential side effects of corticosteroids are not available. Guidelines are clear on the use of super-potent topical corticosteroids: they are not approved for continuous long-term use beyond 2–4 weeks (14). For potent corticosteroids continuous long-term use beyond 8 weeks is not regarded as safe.

The clinical efficacy of a two-compound formulation of calcipotriol and betamethasone dipropionate was compared and contrasted with the single compound formulations of calcipotriol and betamethasone and the formulation without active components (15). All preparations were applied twice daily. The mean percentage reduction in PASI from baseline to end of treatment was 73.2% in the combination group (n = 301), 48.8% in the calcipotriol group (n = 308), 63.1% in the betamethasone dipropionate group (n = 312), and 28.8% in the new vehicle group (n = 107) (p < 0.001). The new vehicle with the combination showed greater efficacy with a more rapid onset of action compared to the mono-therapies.

Three schedules of the two-compound formulation of calcipotriol 50 μg/g and betamethasone 0.5 mg/g were investigated in a 52-week prospective double-blind randomized study (n = 634) (16,17): (i) the two compound formulation used as needed (combination group), (ii) the two compound formulation alternating every 4 weeks between the two-compound formulation and calcipotriol mono-therapy (alternating group), (iii) a 4-week induction therapy with the fixed two-compound-formulation followed by calcipotriol 50 μg/g monotherapy (monotherapy group). In the combination group, satisfactory response was observed in 84% of patients as compared with 75% in the alternating group and 70% in the monotherapy group (16). With regard to efficacy, the authors concluded a trend in favor of a long-term use of the fixed combination. Adverse effects related to chronic corticosteroid use occurred in 4.4% of patients in the combination group as compared with 2.8% in the alternating and 2.9% in the mono-therapy group (17).

Remaining topical therapies, which are not used as first-line treatment, include dithranol, coal tar, calcineurin inhibitors, and the retinoid tazarotene. The evidence for efficacy and safety has been provided in a recent systematic literature search (18). Dithranol and coal tar treatment are not used as first-line treatments anymore. The efficacy of these treatments is considerable; however, staining, stinging, and skin irritation are serious limitations for a routine treatment. These treatments are largely restricted to specialized day care centers and for those situations in which first-line treatments were not effective or were contraindicated. Calcineurin inhibitors are used for facial and flexural psoriasis as second line treatment.

Evidence-based data on efficacy and safety of topical treatments have important limitations. So far, we are not aware of the modification of the long-term course of the disease by topical treatments. The questions remain unanswered whether our treatments have a significant impact on the natural course of the disease, yielding into long-lasting improvement of the disease or whether it is just a temporarily reduction of the signs and symptoms of the disease. Anyhow, it is important to treat our patients to reach a certain degree of improvement to improve quality of life and to optimize the emotional and social development.

Although the information on the improvement by these topical treatments is available with respect to PASI score and quality of life parameters, evidence-based data on the effect on BSA and itch are limited. Furthermore, our information is limited on efficacy and safety in subpopulations of patients, for example, stable versus unstable disease and some localizations such as palms and soles, face, flexures, and genital area. There are at the moment no validated scores with fixed cut-off values to define the population of patients who are eligible for topical versus systemic therapy.

In children with psoriasis, the above-mentioned schedules can be used. Van Geel et al. (19) described a daily clinical practice schedule of four applications of the two-compound formulation per week, resulting in a significant improvement of psoriasis. Children had been treated during a median time of 35.0 weeks (range 1.0–176.0). At week 12, mean PASI decreased 15.4% (from 5.2 to 4.4), BSA barely changed, and median CDLQI decreased significantly from 5.5 to 4.0 (19). However, in children, we have to be reluctant to use super-potent corticosteroids and penetration enhancers in combination with potent corticosteroids during prolonged periods of time.

Adherence to treatments

Adherence of the patients to the proposed instructions is far below expectation during topical treatment. 95% of patients are under dose treatment. In one study, 35% of the expected individual dosages were used (20). Adherence to treatment comprises a host of factors that involve various more or less complex interactions involving the patients in his/her social context, the disease, the treatment characteristics and outcomes. 40% of patients reported that they did not use recommended treatment as directed by their doctor. The International Psoriasis Council has created a model to capture these aspects (21). This model comprises the following elements:

1. The physician patient interaction: A strong relationship between physician and patient is key for treatment adherence, comprising trust, motivation, and information.

2. Patient characteristics: These comprise age, gender, ethnicity, genetic propensities, level of education, forgetfulness, willingness to invest time, energy, and money.

3. Disease characteristics: Extent and distributions of lesions, health-related quality of life and disease impact.

4. Treatment characteristics: Efficacy, safety, side effects, costs, convenience, and complexity.

• These factors all are key elements required to optimize in order to enhance efficacy of a treatment. In the review by Feldman et al. (22), several suggestions have been highlighted to improve patient adherence. Patient education is a major opportunity to address several of the above-mentioned adherence factors. Instruction modules can either be given by specialized nurses or via e-learning modules. More frequent visits and interactions with the doctor also may increase adherence (23).

• Based on a systematic literature review, qualitative patient focus interviews and expert group’s input, a new 51 point questionnaire was developed to assess adherence risk factors in topical therapy (24).

1. The perspective of the patient: In routine daily practice, the benefit from the patient perspective is of utmost importance. Patient relevant benefit only can be assessed reliably by the patient in view of the discrepancies between the patient and the physicians’ perspective (25). Treatment goals should largely be set by the expectation of the patients. In a recent study, the Dermatology Life Quality Index (DLQI) scores were assessed during prescription of topical medication, and the scores were compared between patients with clear versus almost clear skin. In terms of DLQI, totally cleared skin has a substantial value as compared with almost cleared skin (26).

Several patient-reported outcomes have been validated for psoriasis. The patient defined benefit can be measured by a validated instrument: the Patient Benefit Index (PBI) (27). This instrument is based on a standardized list of questions which the patient has to answer. The PBI covers a broad range of outcomes. During treatment, the same questions are addressed and the improvement is designated as the PBI.

How can we optimize the quality and efficiency of care by collaborative programs?

1. The step wise approach.

2. Monitoring adherence factors and patient reported outcome measures.

3. A virtual environment with a liaison between echelons of care.

The step wise approach

Clearing therapy

Before starting the treatment, the responses to previous treatments are crucial information to select the future treatment.

In the management of psoriasis with topical treatments, it is important to define the clearing period up to clearing or maximally 8 weeks In some patients calcipotriol or calcitriol monotherapy may be adequate and in case of irritation a mild corticosteroid will subside irritation. A clearing phase of 8 weeks is often needed if this schedule is selected. In case the patient has to reach the optimal result faster, the two compound formulation may be prescribed once daily for 4 weeks and an additional 4 weeks if needed. This treatment can be empowered by prescribing clobetasol propionate on weekend days.

Maintenance phase

The question arises to what extent topical treatment should be “on demand” or be structured according to a clear schedule? The “on demand schedule” leaves the decision to start and discontinue a treatment course to the patient. Compared to “on-demand” treatment with calcipotriol/betamethasone dipropionate gel a structured twice-weekly applications of this two compound product was more effective and associated with a lower rate of relapse in a comparative real practice study (28). Considering a group of psoriatic patients, an intermittent schedule of the two compound products twice weekly was a better maintenance treatment as compared to an on demand schedule.

To individualize treatment of psoriasis, it is important to select a schedule which is adequate in the individual patient. Although some patients benefit from a highly flexible schedule, other patients need tight control with clear instructions. Five maintenance schedules can be proposed after clearing (Table 1).

Table 1. Maintenance schedules for patients with mild-to-moderate psoriasis.

Maintenance schedule 1: No maintenance treatment at all may be adequate if the patient has a short previous history of psoriasis or in patients with guttate psoriasis. In particular in those patients with triggering factors which have been resolved, such as focal infections, medications or stress, no maintenance therapy may be preferred.

Maintenance schedule 2: Calcipotriol ointment or cream or calcitriol mono-therapy as maintenance once-twice daily is the first-line maintenance treatment. In case the patient has mild disease, treatment episodes with a vitamin D may be sufficient to control the disease. In case of irritation a mild corticosteroid can be added.

Maintenance schedule 3: Calcipotriol monotherapy once-twice daily on week-days and the two compound product of calcipotriol and betamethasone ointment or gel on weekend-days uses both compound in its optimal efficacy/safety ratio. In those patients where calcipotriol maintenance provides insufficient control this intermittent schedule may be very helpful.

Maintenance schedule 4: Courses of 4 weeks of daily applications of calcipotriol/betamethasone ointment or gel are indicated in case of a relapse of psoriasis.

Maintenance schedule 5: Courses of super-potent corticosteroids, corticosteroids under occlusion or in combination with a penetration enhancer should be given in patients with recalcitrant hyperkeratotic lesions. Either daily applications during 2 weeks or intermittent treatments (2–3 times per week) can be selected.

From a safety perspective, it is important to avoid the use of super-potent corticosteroids as daily treatment for more that 2 weeks and to avoid unrestricted daily use of potent corticosteroids, also if incorporated in the combination product calcipotriol betamethasone dipropionate. Continuous daily treatment with this two-compound formulation should not be more than 4 weeks and can be repeated only under supervision of the prescriber. Treatment with the two-compound formulation beyond 8 weeks has to be an intermittent treatment with applications on 3–5 d of the week.

Monitoring adherence factors and patient-reported outcome measures

A structured monitoring of adherence factors and patient-reported outcomes are important in several respects. It will help the professional guidance of the individual patient. From the adherence and the actual outcome together, the physician will have all relevant information to tune the treatment to optimal success. To improve quality of a health care unit, it is important to measure key outcomes. From the monitoring of adherence factors and outcomes, a performance driven quality system can be implemented.

The question arises, who has to do all the work of reporting all the parameters in the system. In a patient-centered approach, the patient him or herself should get the information into the system. In this way, the patient gets ownership of a major part of his patient file and leadership over his/her disease and his/her treatment.

In the above-mentioned paragraphs, the topical therapy adherence questionnaire (24) and the patient benefit index (27) are validated instruments for the topical treatment of psoriasis and could be used to monitor disease-related quality of life over years.

A virtual environment with liaison between echelons of care

At present, care for patients with mild-to-moderate disease is provided by three echelons: the GP, the dermatologist in general hospital, and the dermatologist in academic center. However, it should be realized that most patients do not get any care. The organizations of primary care physicians have their own guidelines, and dermatologists have their guidelines. Referral of patients is an unstructured process and largely results from the fact that a patient is not satisfied with a treatment result. As has been illustrated in this overview, the selection of treatments is a complex process which depends on many factors and is difficult to be explained in a simple decision tree. It is of major importance to harmonize guidelines for psoriasis between the echelons and to organize modules for continuing medical education in a region for the specialties involved in a care program.

In the model of “patient centered approach”, the factors relevant for treatment guidance are captured in a uniform format and recorded in the virtual treatment environment. The patient has ownership of this system and takes care that all patient reported data have been entered in the system. The lead physician is responsible that all medical information is available in the system. The patient is treated by the GP or dermatologist in general or academic hospital. Referral from GP to dermatologist in general hospital or academic hospital is made, based on the actual need for referral on a case-to-case situation. As there are so many reasons for referral, it is not possible to make an absolute criterion based on “complexity”. As a rule, patients have to be referred back to the regional hospital or GP if the expertise of the dermatologist is less important for the patient compared to the generalistic approach of the GP.

The virtual environment in the patient-centered approach is coupled with special modules, comprising teaching modules, feedback modules on the quality of care, and specialized modules such a coping with the disease and focused modules of psychotherapy via e-health.

Conclusion

The ultimate goal is to provide cost-effective personalized treatment for patients with mild-to-moderate psoriasis: a health care issue of major societal significance, comprising at least 1% of world’s population. The gap between gross under-treatment on one hand and insufficient care/or the reverse, medical over-consumption, on the other hand, has to be bridged by a well controlled system. A patient-centered approach is the proposition with a “virtual consultation environment” and a cost-effective intervention by the leading physician, either the GP, dermatologist in general hospital, or dermatologist at academic center for face-to-face consultation. Easy access consultation by the other echelons and an easy transition of the lead physicianship. Cost effectiveness will result from the virtual consultation environment, resulting in a reduction of the number of times needed for face-to-face consultations. Unnecessary duplication or triplication of time and energy will be avoided and a consistent plan for virtual and face-to-face consultations will be the future reality. The referral between echelons will come entirely natural as a result of the decision of the lead-physician together with the patient and should not be governed by short vision financial incentives.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.