3 adherence in the treatment of psoriasis

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Original Paper

Dermatology 2011;222:363374 DOI: 10.1159/000329026

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

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

Introduction

With a prevalence of 23% [13] in western industrial countries, psoriasis vulgaris is an important chronic, re-current skin disease which is now categorized as a sys-temic 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 comor-bidity, such as arthritis, depression, cardiovascular andmetabolic diseases or chronic inflammatory auto-im-mune diseases [710] . Accordingly, psoriasis patients are at an increased risk for the development of atherosclerosis and cardiovascular morbidity [11] and in most casesmay 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 pa-tients perspective, psoriasis represents a huge burden be-cause 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 suf-fering 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 doc-tor with reference to the individual needs of the patient

Key Words Psoriasis outcome Medication adherence Treatment compliance Quality of life

Abstract Background: Medication adherence and compliance are es-sential for disease management and can significantly im-prove outcomes and quality of patient care. The literature suggests that up to 40% of patients do not use their medica-tion as intended. Objective: To elucidate current knowledge on adherence/compliance in psoriasis. In particular, meth-ods of adherence/compliance evaluation and influencing factors were to be identified. Methods: Systematic literature review based on a protocol-rooted search in online data-bases, followed by a structured critical appraisal and con-secutive descriptive report. Results: Thirty-five original pub-lications on adherence/compliance in psoriasis were iden-tified, addressing the extent and quality of adherence/compliance in topical, systemic and UV treatments. Esti-mates of compliance varied considerably between 27 and 97%. Age, sex, psychosocial, disease-specific and treatment-specific factors were identified as predictors of adherence/compliance. Conclusion: A better understanding of the de-terminants of adherence can improve the outcomes of pso-riasis treatment and lead to higher patient satisfaction and quality of care. Copyright 2011 S. Karger AG, Basel

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

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, Basel10188665/11/22240363$38.00/0

Accessible online at:www.karger.com/drm

dedeyusufHighlight

Augustin /Holland /Dartsch /Langenbruch /Radtke

Dermatology 2011;222:363374 364

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-deter-mination and competence of the informed and auton-omous patient. The World Health Organization recog-nizes adherence in chronic diseases such as psoriasis as one of the most important factors contributing to effi-cient therapy [24] . Thus, poor adherence and subsequent-ly 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. Conse-quently, any intervention which leads to improved adher-ence 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 re-search 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 adher-ence in psoriasis patients within different therapeutic procedures; (3) characterize factors influencing adher-ence on the basis of a systematic literature search.

Methods

Methodology of Adherence Evaluation In the first step, publications on the methodology of assess-

ments for adherence were identified from the literature by a PubMed research using the following terms: Adherence OR Com-pliance AND (measurement OR evaluation OR assessment) AND (methodology OR methods).

Adherence and Compliance in Psoriasis In the second step, systematic literature searches were per-

formed 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 Adher-ence). In order to specifically identify publications on adherence in systemic therapy, the following search terms were used: [(Fu-mar * OR Methotrexate OR Cyclosporine OR Acitretin * OR In-fliximab 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-

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 mea-sure 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 clin-ical and health care studies involved primarily question-ing of the patient by means of various questionnaires or self-reporting by the patient. Major results can be sum-marized 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 ques-tionnaires. A particular advantage of written documen-tation by the patient is that it offers the possibility of anonymous data acquisition, which increases the proba-bility 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 con-cordance with the more objective methods described be-low [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 theoreti-

cal number of days a prescription should last and the ac-tual frequency with which prescriptions are redeemed. Differences between this parameter and the actual adher-ence arise when a patient visits several pharmacies or re-deems 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 Medica-tion Event Monitoring System (MEMS) [32] and tends

Adherence in the Treatment of Psoriasis Dermatology 2011;222:363374 365

less to overestimation of adherence than direct question-ing [33] .

Counting/Weighing of Unused Medication Counting (in the case of separable forms of presenta-

tion) or weighing unused medication returned after the end of treatment is a way of measuring adherence which is independent of information from the patient. Overes-timation 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 measure-ments, can be important and lead to an estimation of ad-herence.

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 low-er adherence values than the patient interview [35, 36] or

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

Adherence and Compliance in Psoriasis

The search term combination (Psoriasis AND Com-pliance) produced 184 hits in PubMed, while the combi-nation (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 psoria-sis 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 al-ways compliant, while the other 39% ticked sometimes or never [37] . Another similar survey in the USA in 2006 involving 53 patients under topical corticosteroid treat-

Psoriasis and compliance

184

Psoriasis and adherence

114

298

Studies meeting inclusion criteria 35

Title irrel. 217

24

Abstracts 81

Psoriasis and adherence and compliance

55

Overlap with PubMed

31

Abstracts 14

Title irrel. 10

Studies not meeting inclusion criteria 60

PubMed Cochrane

Fig. 1. Methodology of the literature search.


Dermatology 2011;222:363374 366

ment had a comparable compliance rate, with 40% non-adherent patients [38] . Higher compliance values were re-ported 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 pre-scribed (= 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 organi-zations in France, the UK, Belgium, Germany and the Netherlands stated in a patient questionnaire to deter-mine 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 adher-ence 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 discrep-ancy 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 assess-ment conducted in 2004 in a US clinical study of 29 pa-tients showed a mean adherence of 55% a figure similar to that obtained from determination of unused medica-tion or the use of anonymous questionnaires. The con-tinuous data recording also showed that adherence inthe case of the twice daily application of salicylic acid gel was significantly higher on the days close to office visits ( 8 2 days) than on the other days of the 8-week observa-tion period [42] . When the correlation between adher-ence and the therapeutic result was examined in 24 pa-tients 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 de-creased continuously from around 94 to 54%, while ad-herence to phototherapy remained constant [44] . A sur-vey performed in 2006 also showed that adherence is greater under therapy with biologicals than under other psoriasis treatments [45] .

While the aim of most studies is to determine medica-tion adherence, that of a study conducted in Denmark in 2008 was primary adherence, i.e. 322 outpatients of a der-matology clinic were followed up to determine how many redeemed their prescription. The survey was made pos-sible by an electronic register so far established only in Denmark. Almost 45% of psoriasis patients failed to re-deem their prescriptions a percentage for primary ad-herence much lower than in patients with some other skin diseases [46] . Table1 provides an overview of the measuring methods used in the individual studies to-gether 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 Gok-demir 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] dis-agreed as regards the influence of marital status, employ-ment 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. Gok-demir 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 over-view 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-compli-ance were low efficacy, poor cosmetic properties, time-consuming 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 pre-ferred to oral and oral to topical treatments. Moreover, satisfaction increased with the length of treatment in


Table 1. Studies of topical and systemic psoriasis therapy with the primary criterion compliance or adherence

First author, year

Method Perspective/rater

Compliance Authors conclusions

Richards[37], 1999

Topical, systemic, photo- or combined therapy;anonymous patient questioning; subdivision into compliers (always compliant) and non-compliers (sometimes or never compliant)

Patient 61% None

Zaghloul [41], 2004

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)

InvestigatorPatient

61%92%

The resultant Medication Adherence Score furnishes objective data; theresult a percentage is preferred tothe subdivision into compliers and non-compliers based on a cut-off limit

Carroll[36], 2004

Topical therapy; MEMS cap; on salicylic acid gelin contralateral comparison salicylic acid gel + tacrolimus ointment versus salicylic acid gel + base ] indirect adherence measurement for tacrolimus ointment

Investigator 60% Suitable method for objective determination of adherence, as the patients were not informed about the nature of the adherence measurement

Carroll [36], 2004

Topical therapy; patient diary versus MEMS with salicylic acid gel versus weighing of unused medication

Investigator

Patient

From 85 to 51% (after 8 weeks)90%

Only the MEMS is a suitable measuring method, but not diaries or weighing of unused medication because of extreme variability of the results

Balkrishnan [35], 2003

Topical therapy; patient diary versus MEMS with salicylic acid gel

PatientInvestigator

92%67%

Electronic determination is more reliable than questioning

Four[40], 2005

Topical or combined therapy; patient questionnaire; compliance defined as strict adherence to instructions in the last 3 days and on the previous weekend

Patient 27% 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

Brown [38], 2006

Topical cortisone therapy; anonymous patient questionnaire (inclusion criterion: at least1 cortisone therapy in the previous 12 months)

Patient 60% This type of data generation poses the risk of memory errors or gaps; however, the results agree with those of other adherence studies

Storm[46], 2008

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)

Investigator 55% Method for the objective determination of primary adherence (once in Denmark)

Gokdemir [39], 2008

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

Patient 75% Adherence rates are often overestimated when as in this case they are based on patients reports

Yentzer[44], 2008

Oral and phototherapy; MEMS cap (acitretin),data loggers (UV lamps)

Investigator From 94 to 54% after12 weeks (acitretin)

Both methods determine adherence objectively; the loggers are validated for recording UV irradiation

Bhosle[45], 2006

Systemic therapy; drug consumption data from the pharmacy for patients for whom biologicals (inter alia) were prescribed

Investigator 66% (biologicals) and36% (other)

The adherence scores are higher for biologicals than for other psoriasis therapies

Van deKerkhof [47], 2000

Topical, photo(chemo)- or systemic therapy;patient questionnaires, sent to subscribers to Psoriasis (magazine of the Dutch Psoriasis Patient Organization)

Patient Compliance relating to frequency of use: 51% (topical therapy); 90% photo(chemo)therapy;97% systemic therapy

Selection bias possible by contactmade via Psoriasis subscription ] overestimation of compliance possible because of greater interest in or worry about the disease


Dermatology 2011;222:363374 368

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 outpa-tients. On the other hand, this study failed to find any as-sociation between adherence and the type of therapy [39] .

Among 120 anonymously questioned patients of a spe-cialized 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 ad-verse drug effects [41] . The results of an anonymous ques-tionnaire 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 com-bined therapy with acitretin and narrow-band UVB pho-totherapy showed a marked decrease in adherence for acitretin over time, this could not be attributed to side ef-fects. 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 op-tions [49] . Although there are no studies of the correla-tion between efficacy and adherence which directly com-pare biologicals with classical forms of therapy, the high-er adherence under therapy with biologicals suggests that good efficacy has a positive effect on adherence ( table3 ).

Disease-Specific Factors Influencing Compliance A distinct correlation between compliance and dis-

ease-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 le-sions [41] . An anonymous questionnaire study of 120 pa-tients under treatment in a specialized psoriasis clinic produced similar results: patients who were not compli-ant displayed significantly greater severity (by self-as-sessment) and were more impaired by the disease [37] . Another questionnaire study of 567 patients to determine satisfaction with their medication showed a negative cor-relation of the severity of the disease and patient satisfac-tion [48] with lower treatment satisfaction being associ-ated 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, burn-ing, painful skin, arthritis, psoriatic arthritis and joint pain [50] ( table4 ).

Psychosocial Factors Influencing Compliance In keeping with the significance of interactions be-

tween psoriasis and the patients mental state, many stud-ies have devoted themselves to researching psychosocial determinants of both the disease and treatment compli-ance. Table5 presents an overview of the findings gener-ated in this connection. The documentation of health-re-lated 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

Table 2. Sociodemographic factors influencing compliance/adherence

First author, year Construct I nfluencing factors

female s ex

age living alone (vs.in partnership)

employed nicotine (N),alcohol (A)

Zaghloul [41], 2004 compliance d f f d A: f, N: fStorm [46], 2008 primary adherence dGokdemir [39], 2008 adherence 0 d 0 N: 0Richards [37], 1999 compliance d

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


their non-adherence, around 22% of such patients report-ed that they had had enough. Depression is a major co-morbidity 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). Sui-cidal thoughts are reported with significantly greater fre-quency than in other dermatological diseases. The occur-rence 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 pa-tient 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 signifi-cantly below average in comparison with a normal sam-ple. After just 3 weeks of rehabilitation, however, in-creased 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 signifi-cantly more from anxiety, depression and worry [54] . Be-cause this is often kept hidden from their partners, how-ever, 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 thera-py. Interviews of psoriasis patients from 4 centres in the USA have also shown that they wish for greater acknowl-

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 dis-ease 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, dura-tion and severity of the disease (self-assessment) and a family history of psoriasis had no effect on the accep-tance. In contrast, optimism, absence of a why me? at-

Table 3. Therapy-specific factors influencing compliance/adherence


topical therapy(vs. s ystemic)

satisfaction side effects therapy effort(time)

Four [40], 2005 compliance d f fAtkinson [48], 2004 adherence f dGokdemir [39], 2008 adherence 0 dRichards [37], 1999 compliance f fZaghloul [41], 2004 compliance f fBrown [38], 2006 adherence d f (expected)

0 (occurred)f

Yentzer [44], 2008 adherence 0 (reported) 0Bhosle [45], 2006 adherence f d

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

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


fa cial lesions severity

Zaghloul [41], 2004 compliance f fRichards [37], 1999 compliance fAtkinson [48], 2004 adherence f

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


Dermatology 2011;222:363374 370

titude, less fixation on (negative) emotions and objective-ly 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 medica-tion affect adherence. The results show that adherence was affected negatively when reservations about, for ex-ample, dependency on or late sequelae of drug use out-weighed the assessment of the need to take the medica-tion. 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 spe-

cific 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 in-ferior to that of the systemic agents, and even with effec-tive topical therapy only 40% of patients would respond very well, while 40% would experience partial improve-ment 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 prepara-tions [46] . The dissatisfaction was also highlighted in an anonymous questionnaire survey of 52 patients: 40% of the participants were non-adherent and applied the topi-cal 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

regards their topical psoriasis treatment. The reasons giv-en for the non-compliance were poor efficacy, poor cos-metic properties, too time-consuming use and the occur-rence of side effects [40] . Contrary results were reported in just one study with 201 outpatients, in which adher-ence in the case of topical or combined therapy was sig-nificantly higher than with oral therapy [41] . In summa-ry, 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 in-fluencing 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 com-pliance in psoriasis. In particular, the methods of evalu-ation, 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, com-pliance refers to a behaviour of following the physicians instructions whereas adherence and concordance imply informed patient consent and a cooperative decision be-tween 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 ex-pressions also depends on cultural and social factors [60] .

Table 5. Psychosocial factors influencing compliance/adherence


general qualityof life

resignation depression denial positive attitudeto the drug

Zaghloul [41], 2004 compliance dGokdemir [39], 2008 adherence fRichards [52], 2006 adherence fAwadalla [51], 2007 adherence fHorne [28], 1999 adherence d

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


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 ob-server effect cannot be avoided.

In the psoriasis studies, compliance rates varied be-tween 27 and 92%. As the authors of the publications re-marked critically, the subjective methods employed to determine compliance show deviations of varying mag-nitude from the methods regarded as objective, e.g. elec-tronic measurement. When measuring methods depend on patient reports, it must be borne in mind that compli-ance might be overestimated. This applies in particular to studies in which the data are not generated anony-mously, since the patients might not want to risk strain-ing 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 ex-pectations 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 proba-bly 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 sur-veys led to results similar to those obtained by determin-ing 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 ques-tioning (interviews or questionnaires), patient diaries, tablet counts or serum level measurements (as these doc-ument 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 pre-

vious 3 days and the last weekend. Moreover, the patient population consisted of members of psoriasis patient or-ganizations, 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 moderate-ly 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 predic-tors 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 pa-tient should be considered. Even if not all studies came to the same results, it is still clear that low efficacy, poor cos-metic properties (of topical therapy), a too time-consum-ing 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 pso-riasis [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 ef-fects 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 pa-tients, differs from that of healthy persons in that the wish


Dermatology 2011;222:363374 372

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 adher-ence 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. consid-ered 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 psycho-logical 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, lettersor phone calls providing comprehensive information about the therapy, demonstrating correct use of the med-ication and choosing the treatment most suited to the pa-tient 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 medica-tion as instructed, for example because of the occurrence of side effects or because of his own benefit-risk estima-tion. 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.

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 particu-lar worries of the patient in the benefit-risk assessment, they have so far not been included in any of the question-ing procedures [71] .

Conclusion

The evaluation of the studies included in this paper suggests that only around 5060% of patients are compli-ant 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-eco-nomic 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 pa-tients risk depends on such levels of non-adherence. For instance, the cost impact and the patient risk are low

Physician prescribes

Treatment decision

Patient gets drug

Patient goes home

Drug in use

Patient refuses no

No drug pick-up no

Drug gets lost yes

low

mod.

mod.

Costs Patient risk

No use of drug yes mod.

Irregular use yes yes

Regular drug use Fig. 2. The non-adherence pathway of psoriasis treatment: impact on costs and patient risk.

Colo

r ver

sion

ava

ilabl

e on

line


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 prop-erly.

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 treat-ments 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 psy-

chological state. A collaborative model of management which is im-

perative for the optimal management of psoriasis.

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