Rosacea is a chronic inflammatory skin disorder that primarily affects the convexities of the central face.1,2 It is most prevalent among fair-skinned individuals of Northern and Western European descent,3 and in women.4 In the United States, rosacea is estimated to affect more than 15 million people.5,6 Rosacea has been classified into 4 main subtypes, including erythematotelangiectatic, papulopustular, phymatous, and ocular, and treatments often occur in sequence or in combination.7,8
Although nonpharmacologic and behavioral interventions are generally recommended to all patients with rosacea,8,9 topical treatments, such as metronidazole or azelaic acid, are typically the first-line therapies that patients with mild-to-moderate rosacea receive.9 Other first-line therapies for rosacea may include oral tetracyclines and macrolides.9
Several clinical trials have demonstrated the superior efficacy of metronidazole and azelaic acid compared with placebo in reducing inflammatory skin lesions and the severity of erythema in patients with papulopustular rosacea.10-15 However, after the application of topical treatments, a greater incidence of skin discomfort (eg, burning, itching, and stinging sensations) was reported compared with placebo.10-14
Given that skin discomfort may drive treatment choices, affect clinical outcomes, and impair the patient’s quality of life (QOL), it is important to understand the extent to which treatment side effects affect patient preferences and satisfaction to optimize therapeutic strategies. Although some surveys have assessed patient experience with rosacea or its treatment,16-18 to our knowledge, no study has tried to assess which characteristics of topical rosacea treatments drive patient satisfaction and QOL.
Accordingly, this survey-based study aimed to identify key patient concerns and preferences regarding rosacea treatments, as well as to examine treatment characteristics associated with patient satisfaction and QOL.
Reliant Medical Group (RMG), the largest privately held and physician-run multispecialty group practice in Massachusetts, provided the study data. RMG is a nonprofit, 501(c)(3) organization and includes a research group with the ability to conduct patient surveys. Its database includes electronic medical records (EMRs) of patients enrolled in several commercial insurance plans, as well as Medicare and Medicaid. Among them, 122,000 patients are enrolled in the Fallon Community Health Plan, a health insurance plan that was started by RMG.
RMG is an integrated healthcare delivery system for these patients; as such, RMG can provide patients’ linked EMR and claims data at the patient level. Eligible patients were identified between January 1, 2010, and January 1, 2015, and a sample of these patients was sent a survey. The survey data were deidentified, and all patients who participated in the survey provided informed consent. The study was reviewed and approved by the RMG Institutional Review Board.
The patient selection criteria are presented in the Figure. Patients were required to have at least 1 medical record with a diagnosis code for rosacea (International Classification of Diseases, Ninth Revision code 695.3); have 1 prescription for a topical rosacea treatment, including azelaic acid (gel or cream), brimonidine tartrate, or metronidazole (cream, emulsion, gel, or lotion); be aged ≥18 years at the index date (defined as the study data cut-off date of January 1, 2015, or the end of insurance coverage, whichever occurred first); have 6 months of data history before the index date; and have interacted with RMG (eg, visited or refilled a prescription) in the 3 months preceding January 1, 2015.
In December 2015, RMG mailed the survey to 900 patients selected from those who met the selection criteria and received 1 or more of the 3 most common treatments—metronidazole gel, metronidazole cream, and azelaic acid gel—among the topical rosacea treatments assessed. The completed surveys were returned between December 2015 and March 2016.
Because the minimum sample size for survey studies as recommended by the International Society for Pharmacoeconomics and Outcomes Research is 200 patients, the survey was sent to 900 patients, assuming a return rate of 20% to 30%. All users of metronidazole cream and azelaic acid gel were sent the survey, because of the small number of such patients, whereas a random sample of metronidazole gel users were sent the survey until a total of 200 patients had returned the survey.
This study used a one-time cross-sectional survey design. Patient eligibility criteria, demographics, and clinical characteristics were extracted from the EMR and claims data. The patient survey comprised 36 questions and was divided into a background section (self-reported data on rosacea type and current treatment) and 3 questionnaires: the Rosacea Treatment Preference Questionnaire (RTPQ; available at www.AHDBonline.com), the Treatment Satisfaction with Medicines Questionnaire (SATMED-Q), and the Dermatology Life Quality Index (DLQI), as detailed below.
The RTPQ is an open-ended, author-developed questionnaire that inquires about patients’ treatment-related concerns and side effects, the importance and tolerability of these concerns and side effects, and their likelihood of switching to a hypothetical rosacea treatment that did not cause any burning, stinging, or itching sensations to the skin. The SATMED-Q is a validated, multidimensional generic questionnaire designed for use in patients with any chronic disease treated with medicines.19 The questions cover topics such as treatment satisfaction, side effects, treatment efficacy, convenience, and impact on everyday life.19 The DLQI is a validated, dermatology-specific questionnaire that measures the effect of skin diseases on a patient’s health-related QOL (eg, effect on everyday activities) during the previous week.20-22
Patients were provided with 1 copy of the full 36-question survey and 2 copies of an abbreviated version in the event that they were using multiple topical rosacea treatments.
The baseline demographic and clinical characteristics assessed included the patients’ age at the index date, sex, insurance type, Charlson comorbidity index score,23 rosacea-relevant comorbidities and complications, rosacea treatment–related side effects, as well as self-reported rosacea subtype and symptom severity.
The patients’ self-reported concerns and side effects, and their associated importance and tolerability regarding their current topical rosacea treatments in the past 4 weeks, were extracted from the RTPQ. Responses to the open-ended questions were grouped into thematic categories (eg, concerns about treatment efficacy) by 2 of the study investigators.
Within the same RTPQ, the patients were asked to rate the importance of a list of prespecified treatment-related concerns, which encompassed issues related to efficacy, cost, texture, side effects, and the frequency of application. Furthermore, patients listed and rated 5 concerns that they would consider when deciding whether to switch to a new topical rosacea treatment; they also rated (as not at all, a little bit, somewhat, quite a bit, or very much) the likelihood of switching to a hypothetical rosacea treatment that did not cause any burning, stinging, or itching sensations.
The numerical scores or categorical responses (eg, very much vs somewhat) to questions on the RTPQ indicated the importance or tolerability of different aspects of a topical rosacea treatment (eg, cost or side effects). The numerical scores were rated on a 0 to 10 scale, with 0 meaning no importance and 10 extreme importance, or with regard to side effects, 0 meaning tolerable (ie, no pain/discomfort) and 10 intolerable (ie, unbearable pain/discomfort).
Using the SATMED-Q, treatment satisfaction was scored on a standardized 100-point scale, with 0 being not satisfied at all and 100 being completely satisfied. Subscores were also calculated on each of its 6 domains, including side effects, effectiveness, convenience, impact, medical care, and satisfaction, for which a higher score represents a greater endorsement of that domain.19
Using the DLQI, QOL related to rosacea was scored on a 30-point scale, with 0 indicating no impact and 30, a great impact.20,24
The scores of the top 5 prespecified concerns were used to assess the association between patient concerns about treatment and SATMED-Q–measured treatment satisfaction and DLQI-measured QOL.
The baseline demographic and clinical characteristics were assessed for the overall survey responders who were at the time receiving a treatment for rosacea and were stratified by the specific treatments (according to their reporting). A similar analysis of the survey responders and nonresponders was conducted to determine the potential differences between the 2 cohorts.
Treatment concerns as reported in the RTPQ, treatment satisfaction as reported in the SATMED-Q, and QOL as reported in the DLQI were assessed based on the overall survey responders’ responses who reported to be using a treatment, and were stratified by rosacea treatments.
The means and standard deviations were used for continuous variables, whereas frequencies and percentages were used for categorical variables. Univariate and multivariate linear regressions were performed to assess the association between the patients’ concerns and treatment satisfaction and QOL. Multivariate regressions controlled for the baseline characteristics that were significantly (P ≤.05) associated with SATMED-Q and DLQI scores and included age at index date and the severity of symptoms.
Of the 900 patients who were sent the survey, 216 (24%) patients returned a total of 230 surveys: a total of 13 patients were receiving multiple rosacea treatments and thus returned multiple surveys.
Characteristics of Survey Responders
The characteristics of the patients who did and did not return the survey were largely similar; however, compared with survey responders, nonresponders were slightly older (mean age, 57.6 vs 59.8 years, respectively) and were more likely to have used gel- or cream-based rosacea treatments (8.3% vs 12.9%, respectively).
Of the 230 returned surveys, 215 (93.4%) reported current use of a rosacea treatment, with the most common treatments being metronidazole gel (52.0%), metronidazole cream (35.2%), and azelaic acid gel (7.2%). Of the 215 surveys from current users, 213 were contributed by unique patients.
The demographics and clinical characteristics of survey responders who reported currently using a treatment are presented in Table 1. Female patients represented 78.7% of the responders. Erythematotelangiectatic and papulopustular rosacea were reported by 80.3% and 60.7% of responders, respectively. Moderate-to-severe rosacea was reported by approximately 19.6% of responders and was more common among patients who used azelaic acid gel.
A total of 125 survey responders reported concerns related to the treatment they were receiving at that time and their side effects (Table 2). The most common concerns were treatment efficacy (64.8%), dryness (18.4%), unspecified side effects (9.6%), burning (8.8%), and application technique (eg, ease of use or confusion about what other treatments it could be used with; 8.0%). Dryness (17.6%), redness or disease worsening (10.4%), burning (6.4%), and itching (5.6%) were the most common side effects associated with the current treatment that the patients were receiving. Overall, 79.5% of metronidazole cream users reported they had no side effects, representing the highest percentage among the treatment groups reporting no side effects.
The most common concerns related to switching treatment were efficacy (63.2%), unspecified side effects (45.6%), cost (38.4%), application technique (23.2%), and dryness (14.4%). Among the RTPQ’s list of prespecified concerns, in order of importance, were efficacy (9.1), soreness (7.6), itching (7.5), burning (7.4), dryness (7.3), and cost (7.3). The likelihood of switching treatment was relatively high (very much, 30.4%; quite a bit, 16.8%; somewhat, 26.4%). Approximately 25% to 50% of patients reported that they would be very likely to switch medications across the 3 treatment groups.
Treatment Satisfaction and Quality of Life
Of the 230 returned surveys, 121 respondents fully completed the SATMED-Q and 120 DLQI–related questions (Table 3). Among the completed SATMED-Qs, the overall mean score was 56.5, reflecting neutrality toward treatment. Among the individual SATMED-Q domains, undesirable side effects had a low mean score (2.8), indicating little interference with the patient’s life, and convenience of use had a high mean score (84.5), suggesting acceptable convenience. Nonetheless, treatment effectiveness had a mean score of 56.1, indicating only a moderate perceived effectiveness, and this was particularly low (27.4) for other treatments.
The mean DLQI ranged from 2.4 in the metronidazole cream group to 4.0 in the azelaic acid gel group, reflecting the small effect of rosacea across these groups.
Association Between Treatment-Related Concerns and Treatment Satisfaction/QOL
The results from linear regressions illustrate the association between concerns related to treatment characteristics and treatment satisfaction and QOL (Table 4).
Efficacy, soreness, itching, burning, and dryness were used to assess the association between patient concerns and the SATMED-Q–measured treatment satisfaction and DLQI-measured QOL. Only efficacy was significantly (P = .006) associated with the SATMED-Q score, with a 1-unit increase in the efficacy importance score associated with a small decrease of 2.08 points in the SATMED-Q score. After adjusting for age at the index date and the severity of symptoms, this association was no longer significant (P = .056). Nevertheless, trends toward significance were observed for all the treatment characteristics. After adjustment, only dryness was significantly associated with the DLQI score; specifically, the DLQI score increased by 0.15 points (P = .025) for every 1-point increase in the dryness importance score.
This survey-based study served to characterize patients with rosacea, assess their concerns and satisfaction with currently available topical treatments for rosacea, and evaluate patients’ QOL. The results show that most patients were older females; had been prescribed metronidazole gel, metronidazole cream, or azelaic acid gel; and reported having no to mild symptoms of rosacea.
Among patients currently using topical treatments for rosacea, the most frequently reported treatment-related concerns that were deemed the most important were efficacy, dryness, unspecified side effects, burning, application technique, soreness, itching, and cost. In terms of concerns related to treatment-related side effects, the most frequently reported were dryness, redness or worsening of rosacea, burning, itching, and unspecified side effects.
Overall, the patients deemed the tolerability of side effects to be moderate, and the majority of patients were somewhat to very much likely to switch treatment if they were presented with a hypothetical topical treatment that would not cause burning, stinging, or itching. The minority of patients who indicated that they would not switch may be more willing to tolerate the side effects. Taken together, these results underscore the extent to which patients are concerned about their current treatments.
Consistent with the treatment concern and side-effect findings, the results regarding treatment satisfaction and QOL showed that patients were neutral regarding their treatments, and that they considered rosacea to have a small effect on their lives. Moreover, although none of the top 5 prespecified treatment concerns was significantly associated with treatment satisfaction, and only dryness was significantly associated with worsening QOL, the trends toward significance were observed for increasing soreness, itching, and burning in association with worsening QOL.
The finding that patients with rosacea were predominantly older and female is consistent with previous epidemiologic research that has shown that rosacea is more common among individuals aged ≥30 years and women, although the higher prevalence among women may be partly explained by the fact that women seek care for rosacea more often than men.4,25-27 The finding that patients have distinct concerns regarding treatment efficacy and have experienced side effects, including dryness (17.6%), burning, (6.4%) and itching (5.6%), is consistent with findings from previous studies.14 The results from 2 studies of patients with moderate rosacea who used 15% azelaic acid gel found that after 12 weeks, 38% had experienced transient burning, stinging, and/or itching sensations, whereas 11.7% had experienced persistent dryness.14 The persistence of dryness may explain why the current results in our study showed that dryness was the most often reported and important side effect.
A 2015 study of patients with moderate-to-severe rosacea who used metronidazole cream found that after 16 weeks, 15.5%, 12.8%, and 11.4% said they experienced worsening stinging or burning, dryness, and itching, respectively.28 The study’s investigators speculated that those symptoms were a result of severe rosacea,28 which could explain why our study observed lower percentages of stinging/burning and itching. Finally, a recent analysis of an online forum on rosacea showed that questions about efficacy and facial dryness and irritation were the most common.29
The results of our study point to the existence of a number of specific concerns regarding the currently available topical treatments for rosacea. These concerns appear to have repercussions on the QOL of patients with rosacea; the more patients were concerned about their treatment, the more likely they were to report that rosacea had an impact on their QOL. Taken together, these results suggest that, among patients with rosacea, there is an unmet need for new, more tolerable topical treatments. By being effective and having fewer and less severe side effects, such treatments would likely lead to improved patient satisfaction and QOL.
This study had several limitations. First, recall bias might have affected the quality and direction of the results.
Second, although the SATMED-Q and DLQI are validated surveys, the RTPQ is not, and has not been used in any other study to date; however, the RTPQ questions were consistent with the grounded theory qualitative research approach,30 which is a standard research methodology used in the field of psychometrics. In addition, open-ended questions paired with rating scales are adept at deriving a conceptual understanding of patient preferences.
Third, the response rate in our study was relatively low, although comparisons of the baseline demographic and clinical characteristics between responders and nonresponders suggest that they were largely similar. Accordingly, the risk for substantial selection bias was likely minimal. Because the number of patients assessed in this study was small, statistical comparisons between the treatment groups could not be conducted, and the numeric differences should be interpreted with caution.
Finally, patients were recruited from a single center in central Massachusetts, so the study results may not be generalizable to patients with rosacea in other geographic locations or to patients receiving care within other types of clinical and payer environments.
Rosacea treatment–related patient concerns are common and predominantly pertain to the treatment efficacy and side effects, including soreness, itching, burning, and dryness. Patient satisfaction with select current topical treatments was found to be only neutral. The results of this study indicate that the more important that patients rank treatment concerns, the larger the impact on their QOL and the more dissatisfied they are with their treatment. Physicians should therefore strive to determine if patients have concerns with their current treatment, and, when appropriate, they should consider alternative treatments that may mitigate these concerns and improve patient satisfaction.
We are indebted to Cinzia Metallo, PhD, for assistance with medical writing.
Source of Funding
This study was funded by Bayer HealthCare. The funding sponsor had a role in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; the preparation, review, and approval of the manuscript; and the decision to submit the manuscript for publication.
Author Disclosure Statement
Dr Williamson is an employee of Bayer HealthCare; Ms Cheng and Ms McCormick are employees of Analysis Group, a consulting firm that received funding from Bayer HealthCare to conduct this research; Mr Vekeman was an employee of Analysis Group at the time this manuscript was developed.
Dr Williamson is Vice President, US Medical Affairs, Bayer Pharmaceuticals, Whippany, NJ; Ms Cheng is Manager, Analysis Group, Boston, MA; Ms McCormick is Senior Analyst, Analysis Group, Boston, MA; Mr Vekeman is Former Vice President, Analysis Group, Montréal, Québec, Canada.
This study is based on a registered clinical trial #NCT02602470.
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