Patient adherence has gained increased recognition because of its critical impact on treatment outcomes. Patients’ failure to follow the recommendations of healthcare providers limits the ability to achieve therapeutic goals.1 Additionally, non-adherence contributes to morbidity and mortality and raises healthcare expenditure. Since poor patient adherence is a widespread issue in all areas of medicine, there is a growing interest among healthcare providers to better understand, predict and, ultimately, enhance patient adherence.
Adherence is a challenging behavior to measure. Different methods have been utilized to assess medication adherence, including patient self-reports, physician estimates, records regarding prescription refills, pill counts, serologic drug concentrations and electronic monitoring.2 Overall, electronic monitoring seems to be the most reliable and accurate way to assess adherence. Indirect methods such as self-reports and pill counts are associated with overestimates of adherence.3 The Medication Electronic Monitoring System (MEMS) is an electronic system that quantitatively documents patients’ use of their medicines. The system uses specially designed medication caps that contain a concealed microprocessor that records each date and time a patient opens his or her medication. Furthermore, MEMS provides data regarding adherence across the treatment period, such as whether patients actually begin using the newly prescribed medication at the time it is prescribed, as well as if patients use medication persistently throughout the treatment period. This information cannot be obtained via monitoring pill counts, which can be easily flushed before the return visit.
Why Treatment Adherence is Low in Acne Patients
A positive correlation between poor medication adherence and treatment outcomes in patients with chronic cutaneous disease is becoming more apparent.4 Many skin diseases are chronic and require prolonged treatment to achieve and maintain improvement. In such instances, adherence to medical therapy is often difficult to sustain. Patients may forget to take their medication and/or use too little or too much. These issues regarding long-term therapy are especially true in regard to patients with acne vulgaris, a chronic inflammatory condition involving the pilosebaceous unit. In addition to requiring longstanding treatment to achieve and maintain results, acne patients are often prescribed topical medications. Although topical medications are considered the first-line treatment for acne, topical agents are also associated with lower rates of adherence compared to oral medications. Many patients find topical medications to be unpleasant, messy and time-consuming, thereby reducing adherence to proper application.
Achieving good adherence in patients with acne can also be difficult due to the main age group affected by the disease: teenagers.3,5 Poor adherence among adolescents with acne has been objectively demonstrated in clinical studies. For instance, in an open-label, prospective clinical trial, patients 13 to 18 years of age with mild to moderate acne were instructed to apply topical 5% benzoyl peroxide gel nightly for 6 weeks.6 Medication adherence was objectively assessed using Medication Event Monitoring System caps (MEMS; Aardex Corp, Fremont, CA). During the 6-week study, mean adherence rates ranged from 14% to 79%. Adherence rapidly declined over the study period, from 82% of the patients applying the medication on day 1 compared to only 45% on day 43 (P<0.001). This study demonstrates how difficult it is to get patients, particularly adolescents, to adhere to treatment, even during a short 6-week time period.
One might expect adolescents to be motivated to use their medications, since acne can be a burden physically, cosmetically and psychologically.7 Likewise, many believe that the more severe the disease, the more determined patients will be to adhere to medical regimens. However, studies have not demonstrated a consistent link between variables such as disease severity and patients’ self-image and adherence. In an open-label, evaluator-blind randomized pilot study, the impact of self-image on medication adherence was examined in adolescent patients with mild to moderate acne.8 Overall, there was no association between overall adherence to acne treatment and self-image (P=0.96). Similarly, in a separate observational study, patient adherence to topical acne treatment was negatively correlated with the severity of facial acne (P=0.047).9
The Use of Reminders to Increase Adherence
Reminders are one extensively studied strategy for enhancing adherence. They can provide recurrent cues, encouragement or motivation for patients to adhere to medical recommendations. Different reminder systems have been investigated to determine whether a particular intervention is more effective for increasing adherence. In an open-label, randomized pilot study, adolescent patients with moderate to severe acne were randomized to one of four groups: (1) control group, which did not receive a reminder; (2) frequent office visits (weeks 1, 2, 4, 6, 8 and 12); (3) daily phone call reminders to the patient; and (4) daily phone call to the patients’ parents to prompt them to remind their child to use the medication.10 All patients were provided with adapalene gel 0.1%, which they were instructed to apply once daily for 12 weeks. Adherence was assessed using MEMS caps.
A significant difference in adherence was seen among the four study groups (P<0.05). Patients in the frequent office visits group exhibited the highest median adherence (82%), followed by the control group (59%), daily phone call reminders to the patient (48%) and parental reminders (36%). Interestingly, daily phone calls did not have a positive impact on patient adherence. It is possible that phone calls are not the ideal reminder system, as more people rely on other forms of electronic reminders, such as automatic e-mails, text messages and smart phone calendar/reminder applications. Another possibility is that repeated phone calls, text messages or beeper systems may be perceived as intrusive rather than helpful. Another major finding from this study was the significant negative effect that parental reminders had on adherence. Adolescents may perceive parental reminders as a form of “nagging” and trigger oppositional defiant behavior.
The Importance of Patient Education
In addition to implementing reminder systems and other modalities to enhance patient adherence, patient education remains a major factor that impacts adherence. For instance, encouraging patients to participate in the decision-making process regarding the management of their disease is important for improving adherence.11 However, in order for patients to be involved in the decision-making process, they need to have a good understanding of their disease and the different treatment options. It is also critical that healthcare providers educate patients about the expected outcomes of treatment, how long it typically takes to achieve improvement and how acne management requires long-term therapy. The reason this information is critical is that patient dissatisfaction is one of the leading reasons for poor adherence to topical acne treatment. Dissatisfaction is often related to patients having unrealistic expectations regarding treatment outcomes, as many patients anticipate their acne will rapidly improve with use of the prescribed medication. Similarly, many patients think they can discontinue medication once they have achieved improvement or clearance of their acne.
Another important aspect of patient education is providing instructions regarding proper use of topical acne medications. Many topical acne products can cause skin irritation, especially if too much medication is applied. Patients may decrease their use of the medication or completely discontinue therapy due to side effects. As a result, healthcare providers need to educate patients on proper use of the medication, potential side effects and ways to prevent or minimize the severity of such side effects.
Simplify Treatment Regimens
Acne regimens often involve concomitant use of other topical and/or oral agents. Although combination therapy for acne is more efficacious than monotherapy, such regimens complicate treatment and contribute to poor adherence. Therefore, simplifying treatment regimens is one means to improve patient adherence. This can be achieved by reducing the doses per day and by decreasing the number of medications prescribed. Combination formulations, such as clindamycin 1.2% + tretinoin 0.025% gel (Ziana), adapalene 0.1% + benzoyl peroxide 2.5% gel (Epiduo) and clindamycin 1% + benzoyl peroxide 5% gel (Duac), have a potential advantage in improving adherence by keeping daily application of medications to a minimum. A single topical formulation with multiple active ingredients is much easier to use and less time-consuming to apply when compared to multiple individual products.
The positive impact of combined formulations on patient adherence has been demonstrated in clinical studies. In an investigator-blinded, randomized controlled clinical trial, 26 patients with mild to moderate acne were randomized to receive either concomitant therapy with generic topical clindamycin 1% gel (C gel) + generic topical tretinoin 0.025% cream (T cream) or a formulation consisting of clinidamycin phosphate 1.2% with tretinoin 0.025% gel (Combo gel).10 Adherence was measured using MEMS caps. Mean adherence over the 12-week study period was 88% in the Combo gel group and 61% in the C gel + T cream group. Although patients in the Combo gel group exhibited a greater reduction in acne lesions compared to subjects in the C gel + T cream group, the findings were not statistically significant. While it may seem intuitive, larger clinical trials are needed to scientifically demonstrate that combination agents are ultimately more efficacious for acne over time.
Looking for New Ways to Improve Adherence
Healthcare providers are experimenting with different methods to improve patient adherence to physician-prescribed medications. Previous studies have shown patients have a tendency to increase the use of their medication around the time of their office visits.12,13 This phenomenon is known as “white coat compliance.” However, increasing the frequency of follow-up appointments for relatively stable conditions requires significant financial investment and manpower.
Internet-based surveys and smartphone applications have recently been implemented as a novel method for improving patient adherence. In an investigator-blinded, randomized, prospective study, 20 male and female patients ages 13 to 18 with mild to moderate acne were prescribed topical benzoyl peroxide 5% gel on a daily basis for 12 weeks. Patients were randomized 1:1 to a control group or to an Internet-based survey group. Patients in the Internet survey group received a weekly e-mail with a link to a survey. Patients were asked questions regarding the severity of their acne, their perceived efficacy of the treatment and side effects. Medication adherence was assessed objectively using medication event monitoring system caps, which contain electronic monitors that recorded the time and date patients opened their medication containers. Over the 12-week study period, median adherence was 74% for the Internet survey group versus 32% for the control group (P<0.01). Although patients’ use of medication declines with time, as demonstrated by rapid reduction in the mean adherence of the control group (P=0.02), patients in the Internet survey group did not exhibit a statistically significant change in adherence over the 12-week study period (P=0.10). The findings from this small pilot study suggest that Internet-based systems of communication may serve as a potential method to enhance patient adherence.
Interestingly, other electronic “reminders” have not been as efficacious for improving medication adherence in adolescent patients with acne. It is possible that patients in the Internet survey group perceived the survey like a virtual office visit, thus driving adherence through a type of online “white coat compliance” mechanism.
When attempting to implement different strategies to improve patient adherence, the major goals include improving patients’ understanding, recall and motivation.14 While certain interventions such as reminder systems potentially target each of these factors, other strategies such as patient education or reward systems may only target one variable. Evidence suggests that combining adherence-modifying strategies, such as reminders plus additional interventions, results in a greater overall effect than any intervention alone.15-17 It may be that Internet and smartphone based interventions can accomplish this by not just reminding a patient to take a pill or apply a cream, but also provide education as well as much-needed motivation for our acne patients.
Drs. Gustafson and Yentzer are with the Center for Dermatology Research and the department of dermatology at Wake Forest University School of Medicine in Winston-Salem, NC.
Disclosure: The Center for Dermatology Research is supported by an educational grant from Galderma Laboratories, L.P.