Original Paper

Dermatology 2011;222:363374 DOI: 10.1159/000329026

Received: January 19, 2011 Accepted after revision: April 18, 2011 Published online: July 13, 2011

Adherence in the Treatment of Psoriasis: A Systematic Review

M.Augustin a B.Holland a,b D.Dartsch b A.Langenbruch a M.A.Radtke a

German Centre for Health Services Research in Dermatology, Institute for Health Services Research in Dermatology and Nursing, and b Institute for Pharmacy, University of Hamburg, Hamburg, Germany

Key Words Psoriasis outcome Medication adherence Treatment compliance Quality of life

Introduction

Abstract Background: Medication adherence and compliance are essential for disease management and can significantly improve outcomes and quality of patient care. The literature suggests that up to 40% of patients do not use their medication as intended. Objective: To elucidate current knowledge on adherence/compliance in psoriasis. In particular, methods of adherence/compliance evaluation and influencing factors were to be identified. Methods: Systematic literature review based on a protocol-rooted search in online databases, followed by a structured critical appraisal and consecutive descriptive report. Results: Thirty-five original publications on adherence/compliance in psoriasis were identified, addressing the extent and quality of adherence/ compliance in topical, systemic and UV treatments. Estimates of compliance varied considerably between 27 and 97%. Age, sex, psychosocial, disease-specific and treatmentspecific factors were identified as predictors of adherence/ compliance. Conclusion: A better understanding of the determinants of adherence can improve the outcomes of psoriasis treatment and lead to higher patient satisfaction and Copyright 2011 S. Karger AG, Basel quality of care.

With a prevalence of 23% [13] in western industrial countries, psoriasis vulgaris is an important chronic, recurrent skin disease which is now categorized as a systemic inflammatory reaction [4, 5]. The incidence and disease burden of psoriasis result in a high need for care [6]. There is also a demand for the treatment of comorbidity, such as arthritis, depression, cardiovascular and metabolic diseases or chronic inflammatory auto-immune diseases [710]. Accordingly, psoriasis patients are at an increased risk for the development of atherosclerosis and cardiovascular morbidity [11] and in most cases may require early drug treatment. The high consecutive costs which increase with the severity of the disease constitute the great socio-economic relevance of psoriasis from a health-political perspective [1215]. From the patients perspective, psoriasis represents a huge burden because of the marked decrease in quality of life, the often refractory course and also the considerable side effects of therapy [1620]. Motivation to follow the instructions for treatment can be poor particularly in patients who have been suffering for many years, the consequence being a reduction in compliance and adherence [21]. Patient behaviour which leads to following the doctors instructions is called compliance [22]. By contrast, adherence means sticking to the therapeutic goals set mutually by patient and doctor with reference to the individual needs of the patient
PD Dr. Marc Alexander Radtke, Competenzzentrum Versorgungsforschung in der Dermatologie, Institut fr Versorgungsforschung in der Dermatologie und bei Pflegeberufen, Universittsklinikum Hamburg-Eppendorf Martinistrasse 52 , DE20246 Hamburg (Germany) Tel. +49 40 74105 5428, E-Mail m.radtke@uke.de

2011 S. Karger AG, Basel 10188665/11/22240363$38.00/0 Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Accessible online at: www.karger.com/drm

and any factors which make it difficult for the patient to achieve these goals [23]. The need for this construct arose from the fact that consideration only of compliance fails to take due account of the perspective, right of self-determination and competence of the informed and autonomous patient. The World Health Organization recognizes adherence in chronic diseases such as psoriasis as one of the most important factors contributing to efficient therapy [24]. Thus, poor adherence and subsequently suboptimum therapeutic results can lead to increased costs due to additional office visits and treatments as well as a negative impact on work and productivity. Consequently, any intervention which leads to improved adherence is beneficial. An objective and valid measurement of the two parameters compliance and adherence is difficult because they are both modes of patient behaviour which, in most cases, are difficult to objectify. An approximation can, however, be achieved by the use of established research methods. The aims of the present paper were to (1) identify and assess suitable methods for the evaluation of adherence in psoriasis patients; (2) determine the extent of adherence in psoriasis patients within different therapeutic procedures; (3) characterize factors influencing adherence on the basis of a systematic literature search.

ence in the therapy of psoriasis or other dermatological diseases as a main criterion; (2) factors influencing compliance as a main criterion; (3) a description of the particular methods used to measure compliance; (4) influencing factors with indirect effects on compliance as a main conclusion of the publication; (5) up-to-date information on the management of psoriasis.

Results

Methodology of Adherence Evaluation The methodology for determining compliance in clinical and health care studies involved primarily questioning of the patient by means of various questionnaires or self-reporting by the patient. Major results can be summarized as follows below. Self-Reporting In the procedure of patient questioning, compliance is documented either during an interview by the physician or by the patient himself on previously compiled questionnaires. A particular advantage of written documentation by the patient is that it offers the possibility of anonymous data acquisition, which increases the probability of obtaining truthful answers [25]. The questions can be adapted to each individual study and formulated openly or provided with possible responses. Because the quality of results is greatly dependent on the wording of the questions [26], validated instruments such as the Mirosky Scale [27] and the Medication Adherence Report Scale [28, 29] are preferable to non-validated methods. Direct questioning by interview tends to show low concordance with the more objective methods described below [30] and, consequently, can be recommended for the determination of adherence only with reservations. In conclusion, there is no gold standard of self-reporting techniques for adherence evaluation. Pharmacy Records of Drug Consumption These data are based on a comparison of the theoretical number of days a prescription should last and the actual frequency with which prescriptions are redeemed. Differences between this parameter and the actual adherence arise when a patient visits several pharmacies or redeems his prescription but does not take the medication. Moreover, this method does not provide any indication of the regularity of use [31]. The adherence determined in this way nevertheless showed acceptable correlation with the cumulative adherence determined with the Medication Event Monitoring System (MEMS) [32] and tends
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Methods
Methodology of Adherence Evaluation In the first step, publications on the methodology of assessments for adherence were identified from the literature by a PubMed research using the following terms: Adherence OR Compliance AND (measurement OR evaluation OR assessment) AND (methodology OR methods). Adherence and Compliance in Psoriasis In the second step, systematic literature searches were performed in the databases PubMed and Cochrane library in May 2010. The first search was conducted in PubMed with the search terms (Psoriasis AND Compliance) and (Psoriasis AND Adherence). In order to specifically identify publications on adherence in systemic therapy, the following search terms were used: [(Fumar* OR Methotrexate OR Cyclosporine OR Acitretin* OR Infliximab OR Etanercept OR Adalimumab) AND (compliance OR adherence) AND psoriasis] in the title or abstract. The Cochrane search included the search terms (Psoriasis AND/OR Adherence AND/OR Compliance). In addition, further publications that had not shown up in the databank searches were selected from the bibliographies of the publications identified in the PubMed search. The searches covered all languages and dates of publication. The abstracts had to meet the following criteria for inclusion of the publication in the later evaluation: (1) compliance or adher-

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PubMed
Psoriasis and compliance 184 Psoriasis and adherence 114

Cochrane
Psoriasis and adherence and compliance 55 Overlap with PubMed 31 Title irrel. 10

298 Title irrel. 217 Abstracts 81

24

Abstracts 14

Studies not meeting inclusion criteria 60 Studies meeting inclusion criteria 35

Fig. 1. Methodology of the literature

search.

less to overestimation of adherence than direct questioning [33]. Counting/Weighing of Unused Medication Counting (in the case of separable forms of presentation) or weighing unused medication returned after the end of treatment is a way of measuring adherence which is independent of information from the patient. Overestimation of the actual adherence is however possible even with this method if intentionally or unintentionally the patient does not return all the unused medication [26]. Clinicochemical Parameters In the case of systemic therapy, the determination of clinicochemical parameters, e.g. blood level measurements, can be important and lead to an estimation of adherence. Electronic Measuring Systems (MEMS Cap) The MEMS consists of a standard bottle with a screw cap housing a microprocessor. The time, date and time elapsed since the bottle was last opened is recorded every time the cap is unscrewed. Provided the pharmaceutical formulation is suitable, the bottles can be used not only for solid and liquid, but also for semisolid presentation forms [34]. This monitoring system tends to furnish lower adherence values than the patient interview [35, 36] or
Adherence in the Treatment of Psoriasis

the determination of medication usage [32] and, consequently, is often regarded as todays reference standard despite the costs and limited usage.

Adherence and Compliance in Psoriasis The search term combination (Psoriasis AND Compliance) produced 184 hits in PubMed, while the combination (Psoriasis AND Adherence) achieved 114 hits. Of these, 81 abstracts were viewed in addition to 14 abstracts from the Cochrane search, which produced 55 hits, 31 of which overlapped with the results of the PubMed search. In total, 35 publications were chosen for this literature study on the basis of the inclusion criteria (fig.1). The main topic in 8 studies was compliance in psoriasis treatment, while 4 studies examined the influencing factors and 15 the concomitant circumstances which, in turn, affect compliance. Studies with the Primary Criterion Compliance or Adherence In an anonymous questionnaire survey of 120 patients at a specialized psoriasis clinic in Great Britain in 1999, 61% of the patients with psoriasis said that they were always compliant, while the other 39% ticked sometimes or never [37]. Another similar survey in the USA in 2006 involving 53 patients under topical corticosteroid treatDermatology 2011;222:363374

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ment had a comparable compliance rate, with 40% nonadherent patients [38]. Higher compliance values were reported in a study conducted in Turkey in 2008 in which 103 outpatients were surveyed at the end of 8 weeks of treatment. The questionnaire employed elicited data on the doses used, the relationship of which to the doses prescribed (= 100%) allowed a mean medication adherence score of 75% to be calculated [39]. In contrast, 73% of 1,281 active members of several psoriasis patient organizations in France, the UK, Belgium, Germany and the Netherlands stated in a patient questionnaire to determine compliance in their psoriasis treatment that they had not adhered strictly to the instructions in the last 3 days and over the previous weekend [40]. The results of objectively measured and subjectively reported compliance can differ substantially from each other, as a study with 201 outpatients conducted in Great Britain in 2004 has shown: the mean medication adherence measured objectively by counting or weighing the unused medication was 60.6%, while the patients had an adherence score of 92.0% in the questionnaire survey [41]. A comparison of the data of a MEMS cap with the corresponding patient diaries in 2003 showed a discrepancy of the same magnitude for patients in the USA: the mean compliance was 67% according to the diaries and 92% according to the MEMS [35]. Another MEMS assessment conducted in 2004 in a US clinical study of 29 patients showed a mean adherence of 55% a figure similar to that obtained from determination of unused medication or the use of anonymous questionnaires. The continuous data recording also showed that adherence in the case of the twice daily application of salicylic acid gel was significantly higher on the days close to office visits (82 days) than on the other days of the 8-week observation period [42]. When the correlation between adherence and the therapeutic result was examined in 24 patients of the same study, it was found that a decrease in adherence of 10% was associated with a deterioration of the psoriasis of 1 point on a 9-point scale [43]. A further study conducted in the USA examined adherence in 27 patients under combined therapy consisting of acitretin and UV phototherapy which was to be performed at home. Tablet ingestion was determined with a MEMS cap, irradiation with data loggers for the UV lamps. Over the 12-week observation period, acitretin ingestion decreased continuously from around 94 to 54%, while adherence to phototherapy remained constant [44]. A survey performed in 2006 also showed that adherence is greater under therapy with biologicals than under other psoriasis treatments [45].
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While the aim of most studies is to determine medication adherence, that of a study conducted in Denmark in 2008 was primary adherence, i.e. 322 outpatients of a dermatology clinic were followed up to determine how many redeemed their prescription. The survey was made possible by an electronic register so far established only in Denmark. Almost 45% of psoriasis patients failed to redeem their prescriptions a percentage for primary adherence much lower than in patients with some other skin diseases [46]. Table 1 provides an overview of the measuring methods used in the individual studies together with an assessment of the results by the authors of the individual publications. Sociodemographic Factors with an Influence on Compliance The main sociodemographic factors examined to date are sex, age and marital status. A study by Zaghloul and Goodfield [41] found that adherence was higher in the women, the study of primary adherence by Storm et al. [46] showed that it was higher in the men, while Gokdemir et al. [39] were unable to establish any association between sex and adherence. With regard to age, Storm et al. [46] and Richards et al. [37] both reported that older patients tended to be more compliant than younger ones. Zaghloul and Goodfield [41] and Gokdemir et al. [39] disagreed as regards the influence of marital status, employment and smoking habits. In the study by Zaghloul and Goodfield, adherence was higher in married, employed and non-smoking patients, while Gokdemir et al. found higher adherence in single patients and no influence on adherence for employment and smoking habits. Gokdemir et al. also observed a positive association between higher educational level and adherence, and Zaghloul and Goodfield reported a negative association between increased alcohol consumption and adherence. An overview of these findings is presented in table2. Treatment-Specific Factors Influencing Compliance Evaluation of the patient questionnaires completed by 1,281 members of several psoriasis patient organizations in Europe shows that the main reasons for non-compliance were low efficacy, poor cosmetic properties, timeconsuming use and the occurrence of side effects [40]. The results of a questionnaire survey of 567 patients provide information about the preferred forms of presentation. Distinct differences were found in the satisfaction with the mode of administration injectable agents were preferred to oral and oral to topical treatments. Moreover, satisfaction increased with the length of treatment in
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Table 1. Studies of topical and systemic psoriasis therapy with the primary criterion compliance or adherence
First author, Method year Richards [37], 1999 Topical, systemic, photo- or combined therapy; anonymous patient questioning; subdivision into compliers (always compliant) and non-compliers (sometimes or never compliant) Topical or oral therapy; determination of medication adherence from theoretical and actual use by weighing/counting unused medication (objective method) and patient interview for comparison purposes (subjective method) Topical therapy; MEMS cap; on salicylic acid gel in contralateral comparison salicylic acid gel + tacrolimus ointment versus salicylic acid gel + base ] indirect adherence measurement for tacrolimus ointment Topical therapy; patient diary versus MEMS with salicylic acid gel versus weighing of unused medication Perspective/ rater Patient Compliance 61% Authors conclusions None

Zaghloul [41], 2004

Investigator Patient

61% 92%

The resultant Medication Adherence Score furnishes objective data; the result a percentage is preferred to the subdivision into compliers and non-compliers based on a cut-off limit Suitable method for objective determination of adherence, as the patients were not informed about the nature of the adherence measurement Only the MEMS is a suitable measuring method, but not diaries or weighing of unused medication because of extreme variability of the results Electronic determination is more reliable than questioning The compliance determined is lower than in other studies because of different definition and measuring instruments; errors or bias are inevitable with this kind of data generation This type of data generation poses the risk of memory errors or gaps; however, the results agree with those of other adherence studies Method for the objective determination of primary adherence (once in Denmark) Adherence rates are often overestimated when as in this case they are based on patients reports

Carroll [36], 2004

Investigator

60%

Carroll [36], 2004

Investigator Patient Patient Investigator

From 85 to 51% (after 8 weeks) 90% 92% 67% 27%

Balkrishnan Topical therapy; patient diary versus MEMS with [35], 2003 salicylic acid gel Four [40], 2005

Topical or combined therapy; patient questionnaire; Patient compliance defined as strict adherence to instructions in the last 3 days and on the previous weekend Topical cortisone therapy; anonymous patient questionnaire (inclusion criterion: at least 1 cortisone therapy in the previous 12 months) A new (not further described) therapy for the patient; electronic register: 4 weeks after the visit, check on whether the prescription was redeemed (primary adherence) Oral, topical, photo- or combined therapy; patient questionnaires: daily record of drug use (actual consumption) and determination of the adherence score by established method from theoretical and actual consumption Oral and phototherapy; MEMS cap (acitretin), data loggers (UV lamps) Systemic therapy; drug consumption data from the pharmacy for patients for whom biologicals (inter alia) were prescribed Topical, photo(chemo)- or systemic therapy; patient questionnaires, sent to subscribers to Psoriasis (magazine of the Dutch Psoriasis Patient Organization) Patient

Brown [38], 2006

60%

Storm [46], 2008

Investigator

55%

Gokdemir [39], 2008

Patient

75%

Yentzer [44], 2008 Bhosle [45], 2006 Van de Kerkhof [47], 2000

Investigator

From 94 to 54% after 12 weeks (acitretin) 66% (biologicals) and 36% (other) Compliance relating to frequency of use: 51% (topical therapy); 90% photo(chemo)therapy; 97% systemic therapy

Both methods determine adherence objectively; the loggers are validated for recording UV irradiation The adherence scores are higher for biologicals than for other psoriasis therapies Selection bias possible by contact made via Psoriasis subscription ] overestimation of compliance possible because of greater interest in or worry about the disease

Investigator

Patient

Adherence in the Treatment of Psoriasis

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Table 2. Sociodemographic factors influencing compliance/adherence

First author, year

Construct

Influencing factors female sex age f d d living alone (vs. in partnership) f d employed d 0 nicotine (N), alcohol (A) A: f, N: f N: 0

Zaghloul [41], 2004 Storm [46], 2008 Gokdemir [39], 2008 Richards [37], 1999

compliance primary adherence adherence compliance

d 0

d = Higher compliance/adherence; f = lower compliance/adherence; 0 = no effect.

comparison to a treatment time of less than 2 months [48]. Treatment satisfaction is, in turn, associated with better adherence, as demonstrated in a study with 103 outpatients. On the other hand, this study failed to find any association between adherence and the type of therapy [39]. Among 120 anonymously questioned patients of a specialized psoriasis clinic, compliance was poorer in those who felt more impaired by the treatment [37]. In keeping with this, psoriasis patients from 4 centres in the USA expressed a wish for fast-acting treatments. A study with 201 outpatients showed a significantly higher adherence when the treatment was used for the first time and only once daily, and a lower adherence on occurrence of adverse drug effects [41]. The results of an anonymous questionnaire survey of 53 patients under topical corticoid therapy showed that the main reasons for non-adherence were dissatisfaction with the efficacy, inconvenient or unpleasant treatment and fear of adverse drug effects. The actual occurrence of side effects, on the other hand, had as little influence on adherence as did the proposed frequency of use of the medication [38]. Although a clinical study with 27 patients under combined therapy with acitretin and narrow-band UVB phototherapy showed a marked decrease in adherence for acitretin over time, this could not be attributed to side effects. The frequency of use of the phototherapy remained almost constant over the 12-week observation period an indication that the necessary expenditure of time did not negatively affect adherence [44]. Biologicals, which have now been available in psoriasis therapy for several years, display better efficacy than the previously available options [49]. Although there are no studies of the correlation between efficacy and adherence which directly compare biologicals with classical forms of therapy, the higher adherence under therapy with biologicals suggests that good efficacy has a positive effect on adherence (table3).
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Disease-Specific Factors Influencing Compliance A distinct correlation between compliance and disease-specific factors was demonstrated in a study with 201 outpatients. Compliance was reduced in lesions of the face and in severe disease, i.e. more than 3 disturbing lesions [41]. An anonymous questionnaire study of 120 patients under treatment in a specialized psoriasis clinic produced similar results: patients who were not compliant displayed significantly greater severity (by self-assessment) and were more impaired by the disease [37]. Another questionnaire study of 567 patients to determine satisfaction with their medication showed a negative correlation of the severity of the disease and patient satisfaction [48] with lower treatment satisfaction being associated with lower adherence [39]. The factors which affect the severity of psoriasis were determined in a questionnaire study of 317 outpatients: Significant associations were found between the factors which affect the severity of psoriasis and itching, burning, painful skin, arthritis, psoriatic arthritis and joint pain [50] (table4). Psychosocial Factors Influencing Compliance In keeping with the significance of interactions between psoriasis and the patients mental state, many studies have devoted themselves to researching psychosocial determinants of both the disease and treatment compliance. Table5 presents an overview of the findings generated in this connection. The documentation of health-related quality of life was prompted by, among other things, the fact that a poor quality of life has a negative effect on adherence. Zaghloul and Goodfield [41], for instance, found an inversely proportional relationship between the Dermatology Life Quality Index and adherence. Resignation on the part of the patients can likewise have negative effects on adherence [39]. As the reason for
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Table 3. Therapy-specific factors influencing compliance/adherence

First author, year

Construct

Influencing factors topical therapy (vs. systemic) satisfaction d d d d f d side effects f f f f (expected) 0 (occurred) 0 (reported) therapy effort (time) f f f f 0

Four [40], 2005 Atkinson [48], 2004 Gokdemir [39], 2008 Richards [37], 1999 Zaghloul [41], 2004 Brown [38], 2006 Yentzer [44], 2008 Bhosle [45], 2006

compliance adherence adherence compliance compliance adherence adherence adherence

f 0

d = Higher compliance/adherence; f = lower compliance/adherence; 0 = no effect.

their non-adherence, around 22% of such patients reported that they had had enough. Depression is a major comorbidity of psoriasis (1062%) which is accompanied by a distinct deterioration of the care indicators of psoriasis (number of days ill or unable to work, office visits). Suicidal thoughts are reported with significantly greater frequency than in other dermatological diseases. The occurrence of depression correlates negatively with adherence [52]. After it had been demonstrated that a poor quality of life, depression and resignation on the part of the patient had a negative effect on compliance, various studies were designed in which the psychosocial characteristics were also placed in relation to the milieu. One study with 22 hospitalized psoriasis patients addressed the question of whether their psychosocial characteristics differed from those of healthy adults and whether they could be influenced positively by special rehabilitation measures. The strength of the wish of psoriasis patients for social contact, differentiation and self-assertion was significantly below average in comparison with a normal sample. After just 3 weeks of rehabilitation, however, increased interest in social contact was observed as well as a distinct reduction in the PASI [53]. In agreement with the above findings, a study with 58 psoriasis patients and their partners has shown that the patients suffer significantly more from anxiety, depression and worry [54]. Because this is often kept hidden from their partners, however, the latter underestimate the psychological burden and this, in turn, has a negative effect on the patients well-being and, secondarily, on their adherence to therapy. Interviews of psoriasis patients from 4 centres in the USA have also shown that they wish for greater acknowlAdherence in the Treatment of Psoriasis

Table 4. Disease-specific factors influencing compliance/adher-

ence First author, year Construct Influencing factors facial lesions severity Zaghloul [41], 2004 Richards [37], 1999 Atkinson [48], 2004 compliance compliance adherence f f f f

d = Higher compliance/adherence; f = lower compliance/ adherence.

edgement of the psychological distress caused by their illness [55]. The improvement of the psoriasis symptoms alone did not automatically improve the patients mental state, as was discovered in another study: at the end of a successful course of PUVA therapy, the 72 psoriasis patients felt less restricted and stressed as a result of being asymptomatic, but the disease-related distress, anxiety, depression and worry, their attitude to and ability to cope with the disease remained unchanged [56]. Denial of the disease can help some patients to cope and must also be taken into account as a potential factor for non-adherence [51]. It was against this background that a questionnaire survey of the acceptance of their disease was conducted in 100 hospitalized patients. It was found that gender, age, duration and severity of the disease (self-assessment) and a family history of psoriasis had no effect on the acceptance. In contrast, optimism, absence of a why me? atDermatology 2011;222:363374

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Table 5. Psychosocial factors influencing compliance/adherence

First author, year

Construct

Influencing factors general quality of life resignation depression denial positive attitude to the drug

Zaghloul [41], 2004 Gokdemir [39], 2008 Richards [52], 2006 Awadalla [51], 2007 Horne [28], 1999

compliance adherence adherence adherence adherence

d = Higher compliance/adherence; f = lower compliance/adherence.

titude, less fixation on (negative) emotions and objectively severer disease (according to PASI) had a positive effect [57]. A study of 324 patients with different diseases has shown how the attitudes of the patients to their medication affect adherence. The results show that adherence was affected negatively when reservations about, for example, dependency on or late sequelae of drug use outweighed the assessment of the need to take the medication. A positive attitude to medication, on the other hand, resulted in a measurable improvement of adherence [28] (table5). Compliance: Comparison of Topical versus Systemic Therapy Compliance with topical therapy is influenced by specific factors which do not appear in systemic therapy. They include the cosmetic and galenic properties (very greasy, desiccating or sticky vehicles), the smell of the preparation and the time required for its application. Moreover, the efficacy of topical medication is often inferior to that of the systemic agents, and even with effective topical therapy only 40% of patients would respond very well, while 40% would experience partial improvement and 20% would not respond at all to the treatment [58]. Consistent with this is the finding that the generally inadequate adherence in the treatment of psoriasis is even worse under topical therapy [44] and many patients do not even redeem their prescriptions for topical preparations [46]. The dissatisfaction was also highlighted in an anonymous questionnaire survey of 52 patients: 40% of the participants were non-adherent and applied the topical cortisone preparation either less or more frequently than prescribed [38]. Even less motivated were 1,281 members of European psoriasis patient organizations, 73% of whom reported that they were non-compliant as
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regards their topical psoriasis treatment. The reasons given for the non-compliance were poor efficacy, poor cosmetic properties, too time-consuming use and the occurrence of side effects [40]. Contrary results were reported in just one study with 201 outpatients, in which adherence in the case of topical or combined therapy was significantly higher than with oral therapy [41]. In summary, it can be concluded that apart from those associated with the mode of administration there appear to be no factors which are by themselves relevant to adherence in the case of systemic therapy, but that the majority of influencing factors shown to be significant for adherence are independent of the mode of administration.

Discussion

The present investigation was conducted in order to elucidate the current knowledge on adherence and compliance in psoriasis. In particular, the methods of evaluation, the extent of (non-)adherence in psoriasis and the determinants were to be identified. Moreover, a clear-cut definition of compliance, adherence and concordance was to be established. With respect to a definition, compliance, adherence and concordance describe the degree to which a patient correctly follows medical advice [59]. In particular, compliance refers to a behaviour of following the physicians instructions whereas adherence and concordance imply informed patient consent and a cooperative decision between patient and doctor which is then followed. Since most of the publications found concern compliance and adherence, these two terms are used in this article. It needs to be mentioned that the perception of these expressions also depends on cultural and social factors [60].
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In the first search, evaluation methods of adherence and compliance were retrieved from studies. It resulted that there are various techniques which can be applied. For ethical reasons however, adherence research cannot be performed without patient consent. The resulting observer effect cannot be avoided. In the psoriasis studies, compliance rates varied between 27 and 92%. As the authors of the publications remarked critically, the subjective methods employed to determine compliance show deviations of varying magnitude from the methods regarded as objective, e.g. electronic measurement. When measuring methods depend on patient reports, it must be borne in mind that compliance might be overestimated. This applies in particular to studies in which the data are not generated anonymously, since the patients might not want to risk straining the relationship with their physician, disappointing him or suffering potential disadvantages in their further treatment. In patient interviews in particular, there is a high probability that the patients will misrepresent their compliance as being more in line with the presumed expectations of their therapist. This could explain the high compliance rate of 92% found in a study in which this procedure was used. The compliance rate of 75% found in another study also exceeds expectations and is probably attributable to data generation in the form of daily documentation, i.e. a kind of patient diary. Thus, where data are not acquired anonymously, it must be considered with all methods of patient questioning (even using the Mirosky Scale, Medication Adherence Report Scale or patient diaries) that compliance will be overestimated. In an indirect comparison, anonymous questionnaire surveys led to results similar to those obtained by determining unused medication or from the use of MEMS. Primary packages with integrated microprocessors permit accurate recording of the frequency and time of medication, the intervals between use and any increase in use at certain times of the day; consequently, the method is considered to be more meaningful than patient questioning (interviews or questionnaires), patient diaries, tablet counts or serum level measurements (as these document only the momentary situation) [61]. However, one factor which could affect the accuracy of the MEMS data is the knowledge or lack of knowledge about its use, since non-adherent patients could trigger the counting process without subsequently using the medication. The lowest compliance (27%) was reported in a study by Four et al. [40]. It must however be noted here that the construct compliance was very tightly defined, namely as strict adherence to the instructions in the preAdherence in the Treatment of Psoriasis

vious 3 days and the last weekend. Moreover, the patient population consisted of members of psoriasis patient organizations, who possibly practise highly autonomous disease or treatment management and who also tend to display higher disease severity. For instance, 74% of the patients self-assessed their psoriasis as at least moderately severe, which as other studies have shown might likewise have had a negative effect on compliance [37, 41, 48]. When these aspects are considered, a compliance of 5060% should be expected for psoriasis patients, a rate which is in general agreement with the adherence rates determined in an earlier overview for patients with skin diseases under topical therapy [24]. In view of the importance of adherence for the success of therapy, several studies have addressed major predictors of adherence. In particular, those factors which can be controlled in the treatment process were considered. In many cases, adherence can be influenced by the choice of therapy and drug application. Preferences by the patient should be considered. Even if not all studies came to the same results, it is still clear that low efficacy, poor cosmetic properties (of topical therapy), a too time-consuming or burdensome treatment and the occurrence of side effects all have a negative effect on adherence [37, 38, 40, 41]. It is remarkable that time needed for treatment was the major predictor of quality of life impairment in psoriasis [6]. On the other hand, adherence is better when (a) the drug is administered for the first time, (b) it is to be used only once per day and (c) a rapid onset of effect is observed [41, 55]. Disease-specific factors are not accessible to any external influence apart from effective therapy. Although it might be assumed that patients with severe disease would be more disposed to adhere to the instructions for treatment, the opposite is true both for psoriasis patients and for dermatological patients in general [62, 63]. Both patients and physicians complained of a deficit of information about psoriasis and the management of its treatment and called for better education of the patients in the interests of adherence [38, 55, 64, 65]. Young and Oppenheimer [66] have demonstrated that fear of side effects is less in patients who have been fully informed about the probability of the occurrence of side effects than in those given inadequate information and that, in turn, less fear of side effects is positively associated with adherence. Similarly, patient training as advocated by Fortune et al. [67], Bonnekoh et al. [68] and Werfel et al. [69] also has a positive effect. The emotional condition of patients has a significant influence on adherence and, in psoriasis patients, differs from that of healthy persons in that the wish
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371

Treatment decision Patient refuses Physician prescribes No drug pick-up Patient gets drug Drug gets lost Patient goes home No use of drug Drug in use Irregular use

Costs no

Patient risk low

no

mod.

yes

mod.

yes

mod.

yes

yes

Fig. 2. The non-adherence pathway of

Regular drug use

psoriasis treatment: impact on costs and patient risk.

of the former for social contact and self-assertion is less pronounced, and patients suffer to a significantly greater extent from anxiety, depression and worry. The influence of depression, anxiety, worry, resignation, denial of the disease and a low (disease-related) quality of life on adherence has been demonstrated in several studies [39, 41, 51, 52, 56, 70]. In contrast, a positive attitude towards the drug prescribed and acceptance of the disease promote patient adherence to therapy [28, 57]. A distinction is made between deliberate, i.e. considered and intentional, and unintentional non-adherence [52]. The latter results from forgetfulness on the part of the patients, from a cognitive or organizational inability to follow the instructions for treatment or from psychological problems which make it difficult or impossible for the patient to use the medication. It should be possible to influence all these factors by reminders notes, letters or phone calls providing comprehensive information about the therapy, demonstrating correct use of the medication and choosing the treatment most suited to the patient and his lifestyle the positive therapeutic results attainable justify the time and effort expended. In the case of deliberate non-adherence, on the other hand, the patient takes a conscious decision not to use the medication as instructed, for example because of the occurrence of side effects or because of his own benefit-risk estimation. Where the decision is based on false assumptions, it will be necessary to educate and convince the patient; if the reasons for the deliberate non-compliance are well founded, then the therapeutic strategy must be changed.
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A practical means to improve adherence is to ask the patient specifically about his preferred therapy. A study which elicited preferences with regard to therapy found that 44% of the patients would prefer systemic therapy, 26% creams, 17% ointments and 3% a phototherapy as well as an effective therapy which is safe in the long term [37]. Although there has been speculation about more specific aspects such as preferred forms of presentation in systemic therapy, preferred frequency of use and particular worries of the patient in the benefit-risk assessment, they have so far not been included in any of the questioning procedures [71].

Conclusion

The evaluation of the studies included in this paper suggests that only around 5060% of patients are compliant or adherent in the therapy of psoriasis. In practice, i.e. outside of studies, this percentage could be even lower. Measures to improve adherence are, therefore, urgently required in order to optimize the results of therapy both in the interests of the patients and from a pharmaco-economic perspective. When systematically trying to improve adherence, it may be helpful to reflect the potential steps of patient management where non-adherence may occur (fig. 2). The impact of non-adherence on costs and on the patients risk depends on such levels of non-adherence. For instance, the cost impact and the patient risk are low
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when a prescription is not redeemed in the pharmacy. However, there will be an increased risk and high cost impact when the drug is obtained and not used properly. This paper suggests that the following factors might be a suitable starting point for both topical and systemic therapy: Choice of the simplest possible therapy suited to the patients personal lifestyle, only recommending treatments that are effective in circumstances when they are required with lower levels of side effect or fewer concerns for long-term use. Inclusion of the patient in the therapy decisions.

Simplifying dosage regimen by selecting a different drug or using a sustained-release preparation that needs fewer doses during the day. Attainment of a good physician-patient relationship. Communication of comprehensible instructions for the use of medication. Provision of comprehensive information to the patient about potential risks. Regular follow-up examinations. Measures to put or maintain the patient in a good psychological state. A collaborative model of management which is imperative for the optimal management of psoriasis.

References
1 Schaefer I, Rustenbach SJ, Zimmer L, Augustin M: Prevalence of skin diseases in a cohort of 48,665 employees in Germany. Dermatology 2008;217:169172. 2 Schfer I, Rustenbach SJ, Radtke M, Augustin J, Glaeske G, Augustin M: Epidemiology of psoriasis in Germany analysis of secondary health insurance data. Gesundheitswesen 2011;73:308313. 3 Neimann AL, Porter SB, Gelfand JM: Epidemiology of psoriasis. Expert Rev Dermatol 2006;1:6375. 4 Augustin M, Reich K, Reich C, Purwins S, Jeff Rustenbach S, Schfer I, Radtke M: Quality of psoriasis care in Germany results of the national study PsoHealth 2007. J Dtsch Dermatol Ges 2008; 6:640645. 5 Augustin M, Krger K, Radtke MA, Schwippl I, Reich K: Disease severity, quality of life and health care in plaque-type psoriasis: a multicenter cross-sectional study in Germany. Dermatology 2008; 216:366372. 6 Blome C, Simianer S, Purwins S, Laass A, Rustenbach SJ, Schaefer I, Radtke M, Augustin M: Time needed for treatment is the major predictor of quality of life in psoriasis. Dermatology 2010; 221:154159. 7 Reich K, Krger K, Mssner R, Augustin M: Epidemiology and clinical pattern of psoriatic arthritis in Germany: a prospective interdisciplinary epidemiological study of 1,511 patients with plaque-type psoriasis. Br J Dermatol 2009; 160:10401047. 8 Radtke MA, Reich K, Blome C, Rustenbach S, Augustin M: Prevalence and clinical features of psoriatic arthritis and joint complaints in 2,009 patients with psoriasis: results of a German national survey. J Eur Acad Dermatol Venereol 2009; 23:683691. 9 Augustin M, Reich K, Glaeske G, Schaefer I, Radtke M: Co-morbidity and age-related prevalence of psoriasis: analysis of health insurance data in Germany. Acta Derm Venereol 2010;90:147151. 10 Augustin M, Glaeske G, Radtke MA, Christophers E, Reich K, Schfer I: Epidemiology and comorbidity of psoriasis in children. Br J Dermatol 2010; 162:633636. Boehncke WH, Sterry W: Psoriasis a systemic inflammatory disorder: clinic, pathogenesis and therapeutic perspectives. J Dtsch Dermatol Ges 2009;7:948952. Sohn S, Schffski O, Prinz J, Reich K, Schubert E, Waldorf K, Augustin M: Cost of moderate to severe plaque psoriasis in Germany: a multicenter cost-of-illness study. Dermatology 2006; 212:137144. Berger K, Ehlken B, Kugland B, Augustin M: Cost-of-illness in patients with moderate and severe chronic psoriasis vulgaris in Germany. J Dtsch Dermatol Ges 2005; 3: 511 518. Schffski O, Augustin M, Prinz J, Rauner K, Schubert E, Sohn S, Reich K: Costs and quality of life in patients with moderate to severe plaque-type psoriasis in Germany: a multicenter study. J Dtsch Dermatol Ges 2007; 5: 209219. Kimball AB, Guerin A, Tsaneva M, Yu AP, Wu EQ, Gupta SR, Bao Y, Mulani PM: Economic burden of comorbidities in patients with psoriasis is substantial. J Eur Acad Dermatol Venereol 2011; 25:157163. Krueger G, Koo J, Lebwohl M, Menter A, Stern RS, Rolstad T: The impact of psoriasis on quality of life: results of a 1998 National Psoriasis Foundation patient-membership survey. Arch Dermatol 2001; 137:280284. Zachariae R, Zachariae H, Blomqvist K, Davidsson S, Molin L, Mork C, Sigurgeirsson B: Quality of life in 6,497 Nordic patients with psoriasis. Br J Dermatol 2002; 146: 1006 1016. Schmid-Ott G, Knsebeck HW, Jger B, Sittig U, Hofste N, Ott R, Malewski P, Lambrecht F: Significance of the stigmatization experience of psoriasis patients: a 1-year follow-up of the illness and its psychological consequences in men and women. Acta Derm Venereol 2005; 85:2732. Dubertret L, Mrowietz U, Ranki A, van de Kerkhof PC, Chimenti S, Lotti T, Schfer G, EUROPSO Patient Survey Group: European patient perspectives on the impact of psoriasis: the EUROPSO Patient Survey. Br J Dermatol 2006;155:729736. Kurd SK, Troxel AB, Crits-Cristoph P, Gelfand JM: The risk of depression, anxiety, and suicidality in patients with psoriasis: a population-based cohort study. Arch Dermatol 2010;146:891895. Augustin M, Reich K, Radtke MA: Lebensqualitt, Compliance und Empowerment bei Psoriasis, ed 1. Bremen, Uni-Med, 2007, p 64. World Health Organization: Adherence to long term therapy: evidence for action. http://www.who.int/chronic_conditions/ adherencereport/en/2003 (accessed January 8, 2009). Osterberg L, Blaschke T: Adherence to medication. N Engl J Med 2005;353:487497. Serup J, Lindblad AK, Maroti M, Kjellgren KI, Niklasson E, Ring L, Ahlner J: To follow or not to follow dermatological treatment a review of the literature. Acta Derm Venereol 2006;86:193197. Castelo-Branco C, Palacios S, Ferrer-Barriendos J, Alberich X, Cervantes Study Group: Do patients lie? An open interview vs a blind questionnaire on sexuality. J Sex Med 2010;7:873880. Farmer KC: Methods for measuring and monitoring medication regimen adherence in clinical trials and clinical practice. Clin Ther 1999;21:10741090. Mirosky DE, Green LW, Levine DM: Concurrent and predictive validity of a self-reported measure of medication adherence. Med Care 1986;24:6774. Horne R, Weinman J: Patients beliefs about prescribed medicines and their role in adherence to treatment in chronic physical illness. J Psychosom Res 1999;47:555567. Thompson K, Kulkarni J, Sergejew AA: Reliability and validity of a new Medication Adherence Rating Scale (MARS) for the psychoses. Schizophr Res 2000;42:241247.

11

20

12

21

13

22

14

23 24

15

25

16

26

17

27

18

28

29

19

Adherence in the Treatment of Psoriasis

Dermatology 2011;222:363374

373

30 Garber MC, Nau DP, Erickson SR, Aikens JE, Lawrence JB: The concordance of self-report with other measures of medication adherence: a summary of the literature. Med Care 2004;42:649652. 31 Rudd P, Marshall G: Resolving problems of measuring compliance with medication monitors. J Compliance Health Care 1987; 2: 2335. 32 Choo PW, Rand CS, Inui TS, Lee ML, Cain E, Cordeiro-Breault M, Canning C, Platt R: Validation of patient reports, automated pharmacy records, and pill counts with electronic monitoring of adherence to antihypertensive therapy. Med Care 1999; 37: 846 857. 33 Guenette L, Moisan J, Preville M, Boyer R: Measures of adherence based on self-report exhibited poor agreement with those based on pharmacy records. J Clin Epidemiol 2005; 58:924933. 34 Hodari KT, Nanton JR, Carroll CL, Feldman SR, Balkrishnan R: Adherence in dermatology: a review of the last 20 years. J Dermatolog Treat 2006;17:136142. 35 Balkrishnan R, Carroll CL, Camacho FT, Feldman SR: Electronic monitoring of medication adherence in skin disease: results of a pilot study. J Am Acad Dermatol 2003; 49: 651654. 36 Carroll CL, Feldman SR, Camacho FT, Manuel JC, Balkrishnan R: Adherence to topical therapy decreases during the course of an 8-week psoriasis clinical trial: commonly used methods of measuring adherence to topical therapy overestimate actual use. J Am Acad Dermatol 2004;51:212216. 37 Richards HL, Fortune DG, OSullivan TM, Main CJ, Griffiths CE: Patients with psoriasis and their compliance with medication. J Am Acad Dermatol 1999;41:581583. 38 Brown KK, Rehmus WE, Kimball AB: Determining the relative importance of patient motivations for non-adherence to topical corticosteroid therapy in psoriasis. J Am Acad Dermatol 2006;55:607613. 39 Gokdemir G, Ari S, Koslu A: Adherence to treatment in patients with psoriasis vulgaris: Turkish experience. J Eur Acad Dermatol Venereol 2008;22:330335. 40 Four S, Adjadj L, Pawin H: How patients experience psoriasis: results from a European survey. J Eur Acad Dermatol Venereol 2005;19:26. 41 Zaghloul SS, Goodfield MJ: Objective assessment of compliance with psoriasis treatment. Arch Dermatol 2004; 140:408414. 42 Feldman SR, Camacho FT, Krejci-Manwaring J, Carroll CL, Balkrishnan R: Adherence to topical therapy increases around the time of office visits. J Am Acad Dermatol 2007;57:8183. 43 Carroll CL, Feldman SR, Camacho FT, Balkrishnan R: Better medication adherence results in greater improvement in severity of psoriasis. Br J Dermatol 2004; 151:895897.

44 Yentzer BA, Yelverton CB, Pearce DJ, Camacho FT, Makhzoumi Z, Clark A, Boles A, Fleischer AB Jr, Balkrishnan R, Feldman SR: Adherence to acitretin and home narrowband ultraviolet B phototherapy in patients with psoriasis. J Am Acad Dermatol 2008;59: 577581. 45 Bhosle MJ, Feldman SR, Camacho FT, Timothy Whitmire J, Nahata MC, Balkrishnan R: Medication adherence and health care costs associated with biologics in Medicaid-enrolled patients with psoriasis. J Dermatolog Treat 2006;17:294301. 46 Storm A, Andersen SE, Benfeldt E, Serup J: One in 3 prescriptions are never redeemed: primary non-adherence in an outpatient clinic. J Am Acad Dermatol 2008;59:2733. 47 Van de Kerkhof PCM, de Hoop D, de Korte J, Cobelens SA, Kuipers MV: Patient compliance and disease management in the treatment of psoriasis in the Netherlands. Dermatology 2000;200:292298. 48 Atkinson MJ, Sinha A, Hass SL, Colman SS, Kumar RN, Brod M, Rowland CR: Validation of a general measure of treatment satisfaction, the Treatment Satisfaction Questionnaire for Medication (TSQM), using a national panel study of chronic disease. Health Qual Life Outcomes 2004;26:212. 49 Kircik LH, Del Rosso JQ: Anti-TNF agents for the treatment of psoriasis. J Drugs Dermatol 2009;8:546559. 50 Fleischer AB, Feldman SR, Rapp SR, Reboussin DM, Exum ML, Clark AR, Rajashekhar V: Disease severity measures in a population of psoriasis patients: the symptoms of psoriasis correlate with self-administered psoriasis area severity index scores. J Invest Dermatol 1996;107:2629. 51 Awadalla FC, Yentzer B, Balkrishnan S, Feldman SR: A role for denial in poor adherence to psoriasis treatment. J Dermatolog Treat 2007;18:324325. 52 Richards HL, Fortune DG, Griffiths CE: Adherence to treatment in patients with psoriasis. J Eur Acad Dermatol 2006;20:370379. 53 Bahmer JA, Petermann F, Kuhl J: Psychosocial factors in psoriasis: a pilot study. Hautarzt 2007;58:959965. 54 Richards HL, Fortune DG, Chong SL, Mason DL, Sweeney SK, Main CJ, Griffiths CE: Divergent beliefs about psoriasis are associated with increased psychological distress. J Invest Dermatol 2004; 123:4956. 55 Uhlenhake EE, Kurkowski D, Feldman SR: Conversations on psoriasis what patients want and what physicians can provide: a qualitative look at patients and physician expectations. J Dermatolog Treat 2010;21:612. 56 Fortune DG, Richards HL, Kirby B, McElhone K, Main CJ, Griffiths CE: Successful treatment of psoriasis improves psoriasisspecific but not more general aspects of patients well-being. Br J Dermatol 2004; 151: 12191226.

57 Zalewska A, Miniszewska J, Chodkiewicz J, Narbutt J: Acceptance of chronic illness in psoriasis vulgaris patients. J Eur Acad Dermatol Venereol 2007; 21:235242. 58 Chu T: Better patient compliance in psoriasis. Practitioner 2000;244:238242. 59 Marinker M, Shaw J: Not to be taken as directed. BMJ 2003;326:348349. 60 Larsen J, Stovring H, Kragstrup J, Hansen DG: Can differences in medical drug compliance between European countries be explained by social factors: analyses based on data from the European Social Survey, round 2. BMC Public Health 2009;9:145. 61 Koehler AM, Maibach HI: Electronic monitoring in medication adherence measurement: implications for dermatology. Am J Clin Dermatol 2001; 2:712. 62 Renzi C, Picardi A, Abeni D, Agostini E, Baliva G, Pasquini P, Puddu P, Braga M: Association of dissatisfaction with care and psychiatric morbidity with poor treatment compliance. Arch Dermatol 2002;138:337342. 63 Renzi C, Abeni D, Picardi A, Agostini E, Melchi CF, Pasquini P, Puddu P, Braga M: Factors associated with patient satisfaction with care among dermatological outpatients. Br J Dermatol 2001; 145:617623. 64 Kinney MA, Feldman SR: Whats new in the management of psoriasis? G Ital Dermatol Venereol 2009;144:103117. 65 Laine C, Davidoff F, Lewis CE, Nelson EC, Nelson E, Kessler RC, Delbanco TL: Important elements of outpatient care: a comparison of patients and physicians opinions. Ann Intern Med 1996;125:640645. 66 Young SD, Oppenheimer DM: Different methods of presenting risk information and their influence on medication compliance intentions: results of three studies. Clin Ther 2006;28:129139. 67 Fortune DG, Richards HL, Griffiths CE, Main CJ: Targeting cognitive-behaviour therapy to patients implicit model of psoriasis: results from a patient preference controlled trial. Br J Clin Psychol 2004; 43: 65 82. 68 Bonnekoh B, Schmid-Ott, Herold S, SayeghJodehl S, Dierkes J, Gollnick H: Interdisciplinary training program for adults with psoriasis: six months follow-up. Hautarzt 2006;57:917922. 69 Werfel T, Breitbart E, Kleinheinz A, Gieler U, Schmid-Ott G: The educational program for the management of psoriasis vulgaris according to the rules of the Task Force on Dermatological Prevention: current status. Hautarzt 2006;57:913916. 70 Rapp SR, Feldman SR, Exum L, Fleischer AB, Reboussin DM: Psoriasis causes as much disability as other major medical diseases. J Am Acad Dermatol 1999;41:401407. 71 Nelson AA, Pearce DJ, Fleischer AB, Balkrishnan R, Feldman SR: New treatments for psoriasis: which biologic is best? J Dermatolog Treat 2006;17:96107.

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