Medical Adherence to Acne Therapy: A Systematic Review

Stephanie Snyder; Ian Crandell; Scott A. Davis; Steven R. Feldman

Am J Clin Dermatol. 2014;15(2):87-94.

Abstract and Introduction

Abstract

Background: Poor adherence of acne patients to treatment may equate to poor clinical efficacy, increased healthcare costs, and unnecessary treatments. Authors have investigated risk factors for poor medical adherence and how to improve this difficult problem in the context of acne.

Objective: This systematic review aims to describe what methods have been used to measure adherence, what is known about acne patients' adherence to treatment, and the factors affecting adherence.

Methods: A MEDLINE search was performed for randomized controlled trials published between 1978 and June 2013, focusing on patient adherence to prescribed acne medications. A test for equality of proportions was performed on studies of similar design to collectively analyze adherence to oral versus topical medication. The self-reported adherence data collected from these clinical trials were then compared with adherence data from a pharmacy database study.

Results: Studies varied in modalities of data collection, but the majority utilized subjective methods. Topical therapies were more often studied than oral. The overall oral adherence rate, as calculated by a test of equality of proportions, was 76.3 %, while the overall topical adherence rate was 75.8 % (p = 0.927). The occurrence of side effects and young age were cited as the top reasons for poor adherence, followed by forgetfulness.

Limitations: The MEDLINE search resulted in a limited sample of adherence studies. In addition, there is currently no standardized or fully validated method of measurement, allowing for variability in what was considered 'adherent'. Lastly, data collected via subjective methods cannot guarantee reliable results.

Conclusions: Overall, the values reflected a population adherent to both topical and oral medications, with no significant difference in adherence between the two. However, the methodologies used by many of the studies were weak, and the findings are not consistent with results of more objective measures of adherence. The leading factors that contribute to poor adherence may be reduced with enhanced patient consultation, reminder systems, and education.

Introduction

Poor adherence is a common cause for treatment failure in treatable diseases such as acne. Numerous studies have examined this relationship, along with the reasons why patients tend to not adhere to their acne medications and methods that may improve their adherence. Poor adherence can include failure to obtain the medication, 'drug holidays', early discontinuation, or simply misunderstanding how the medication is supposed to be used. Insufficient adherence leads to the addition of unnecessary acne treatments, patient frustration and dissatisfaction, and increase in medical expense. It is estimated that only about 50 % of patients actually adhere properly to the therapeutic regimen defined by their dermatologist.^[1,2]

In a meta-analysis performed by McDonald et al.,^[3] as many as 17 studies showed a statistically significant relationship between medication adherence and improved efficacy. Hence, for a medication to work properly, it must be taken regularly and correctly, and a better understanding of this relationship is crucial to improving therapeutic success rates. First, examining the methods used to measure such relationships must be analyzed so that the differences between methodologies and the data collected from these studies can be taken into account. Then, the reasons behind poor adherence can be examined, so that, ultimately, strategies for enhancing adherence can be devised. The purpose of this study is to examine patient adherence to prescribed acne medications, compare available adherence data, and investigate the factors that affect adherence.

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Abstract and Introduction
Methods
Results
Discussion
References

Table 1. Summary of data from 14 studies on acne medication adherence
Study; year; country	Samplesize	Oral adherence rate	Topical adherence rate	Measurement methods used	Adherence factors examined
Miyachi et al. [4]; 2011; Japan	428	7 %, 14 % combination oral	52 %, 49 % combination topical	Self/dermatologist questionnaires, ECOB questionnaire	Age, onset age, parental acne, DLQI, PCP, other guidance, scarring, improvement in acne
Dréno et al. [2]; 2010; Sweden, Denmark, France, Norway, Spain, Hong Kong, India, Philippines, Singapore, Brazil, Chile, Columbia, Mexico, Venezuela, Canada, USA	3,339	54 % ISO; 46 % combination oral and topical	60 %, 56 % combination oral and topical	Self/dermatologist questionnaire, ECOB questionnaire	Age, occurrence of side effects, improvement in acne, previous systemic therapy, patient education, PCP, DLQI, acne severity, use of cosmetics
Mufleh et al. [10]; 1999; UK	20	89.9 % ± 11.5 (pill count method); 93.2 % ± 7.6 (interview method)	Not examined	Pill count method, compliance assessment questionnaire	Acne disability (acne disability index), acne severity (Leeds Grading Technique), duration of treatment, alcohol intake, level of education, living alone
Pawin et al. [5]; 2009; France	246	96 % had good adherence; combined oral and topical: 81 % had good adherence to one or both; 59 % had poor adherence	54 % had good adherence; 46 % had poor adherence	Self/dermatologist questionnaire	Treatment modality
Tan et al. [6]; 2009; Canada	152	Not examined	24 % rated as 100 % adherent to therapy; 49 % rated as 75–99 % adherent to therapy; 26 % rated as <75 % adherent to therapy	Questionnaire after 2 months of therapy	Age, gender, duration of acne, education level, third-party drug plan coverage, smoking history, recreational drug use, ingestion of alcohol, and number of prescribed topicals, facial acne severity, QoL score
Eichenfield et al. [7]; 2008; USA	544	Not examined	94.5, 93.5, 94.5 % at weeks 3, 6, and 12, respectively, for patients using 0.04 % tretinoin gel. 94.7, 96.5, 94.6 %, respectively, for patients using 0.1 % tretinoin gel	Questionnaire
Zaghloul et al. [11]; 2005; UK	403	ISO therapy 71.4 %	Topicals and oral medication other than ISO 35.2 %	The pill count/weight method	Gender, marital status, age, employment status, treatment distribution, first-time and multitime ISO treatment, paying for prescription, smoking, alcohol consumption, acne severity, DLQI
Flanders and McNamara [12]; 1984; USA		49 % overall average		Self-assessment questionnaire	Acne severity and initial health beliefs
Jones-Caballero et al. [8]; 2008; Spain	1,628	Not examined	57.4 % reported 'everyday' use; 38.8 % reported 'almost everyday' use; 3.5 % reported 'sometimes'; 0.4 % reported 'almost never'	Self-reported adherence to treatment in which a researcher asked patients how often they had been using the treatment, using a 4-item scale (every day, almost every day, sometimes or almost never)	Gender, QoL, age, employment, lack of time, forgetting, boring treatment, side effects
Baker et al. [9]; 2001; USA	2,545	Not examined	47 % of subjects reported applying medication daily; 45 % applied it almost daily	Self-assessment questionnaire
Marrazi et al. [13]; 2002; England	188	Not examined	89 % of ISO/erythromycin group and 70 % of benzoyl peroxide/erythromycin group were 76–100 % compliant at each assessment time	Patient diary cards; the study nurse/pharmacist noted on the case report forms whether or not the patients had applied the medication according to the protocol (yes/no)
Cunliffe et al. [14]; 2005; UK	246	Not examined	Mean adherence rate among patients using clindamycin/zinc gel once daily: 98 %; mean adherence rate using clindamycin/zinc gel twice daily: 92 %; mean adherence using clindamycin gel twice daily: 92 %	Patient diaries	Dosing frequency
Cook-Bolden, [15] The MORE trial; 2006; USA	1,979	Not examined	Adapalene only at 12 weeks (self reports): 88.3 %; add-on study arms at 12 weeks (self reports): 87 % adapalene only at 12 weeks (prescription refills): 80.3 %; addon study arms at 12 weeks (prescription refills): 80.4 %	Self reports and prescription refills	Time elapsed since last appointment
Yentzer et al. [16]; 2009; USA	11	Not examined	82 % adherent on day 1; 45 % at 6 weeks	Electronic medication event monitoring system	Time elapsed since last appointment
Tan et al. [17]; 2013; USA	24,438	Antibiotics: 4.04 %; retinoids (ISO): 57.28 %; contraceptives: 48.99 %; glucocorticoids: 1.64 %	Antibiotics: 3.89 %; retinoids: 2.29 %; glucocorticoids: 1.98 %	MPR^a	Age, comorbidity, gender, number of drug refills, and no. of drug class used

DLQI Dermatology Life Quality Index, ECOB Elaboration d'un outil d'evaluation de l'observance des traitements Medicamenteux (Development of a tool for assessment of compliance with drug treatment), ISO isotretinoin, MPR medication possession ratio, PCP prior consultation, QoL quality of life
^aRatio of the number of days for which medication was dispensed divided by the number of days for which medication was needed (as determined by days between medication fills

Table 2. Assessment of risk factors for non-adherence
	Miyachi et al. [4]	Dréno et al. [2]	Mufleh et al. [10]	Tan et al. [6]	Zaghloul et al. [11]	Jones-Caballero et al. [8]	Tan et al. [17]
Treatment dissatisfaction	X	X
DLQI high score	X				X
Use of OTC medication	X
Experience of side effect	X	X		X		X
Previous systemic treatment		X
Young age		X			X	X	X
Poor improvement		X		X
Poor knowledge of treatment
Low education level			X
Living alone/single			X		X
Forgetfulness				X	X	X
Males					X	X
Unemployed					X	X
Self-pay for prescriptions					X
Frustration					X
Too busy					X	X
Other comorbidity							X