Original Research

Patient-Reported Outcomes of Azelaic Acid Foam 15% for Patients With Papulopustular Rosacea: Secondary Efficacy Results From a Randomized, Controlled, Double-blind, Phase 3 Trial

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References

Results

Of the 961 participants included in the study, 483 were randomized to receive AzA foam and 478 were randomized to receive vehicle foam. The mean age was 51.5 years, and the majority of participants were female (73.0%) and white (95.5%)(Table). At baseline, 834 (86.8%) participants had moderate PPR and 127 (13.2%) had severe PPR. The mean inflammatory lesion count (SD) was 21.4 (8.9). No significant differences in baseline characteristics were observed between treatment groups.

Patient-reported global assessment of treatment response differed between treatment groups at EoT (P<.001)(Figure 1). Higher ratings of treatment response were reported among the AzA foam group (excellent, 17.2%; good, 40.0%) versus vehicle foam (excellent, 9.7%; good, 35.0%). The number of participants reporting no treatment response was 13.1% in the AzA foam group, with 1.8% reporting worsening of their condition, while 19.4% of participants in the vehicle foam group reported no response, with 6.3% reporting worsening of their condition (Figure 1).

Figure 1. Patient-reported global assessment of treatment response at end of treatment. AzA indicates azelaic acid. P value derived from Wilcoxon rank sum test comparing distribution of ratings between AzA foam versus vehicle foam groups (P<.001). The sum of excellent, good, and fair responses was 85.1% (AzA foam) and 74.3% (vehicle foam). Note that the total sample does not equal 961 because of missing data for these outcomes.


Tolerability was rated excellent or good in 67.8% of the AzA foam group versus 78.2% of the vehicle foam group (Figure 2A). Approximately 38.4% of the AzA foam group versus 38.2% of the vehicle foam group rated treatment tolerability as excellent, while 93.5% of the AzA foam group rated tolerability as acceptable, good, or excellent compared with 89.5% of the vehicle foam group. Only 1.4% of participants in the AzA foam group indicated that treatment was not acceptable due to irritation. In addition, a greater proportion of the AzA foam group reported cosmetic acceptability as very good versus the vehicle foam group (40.5% vs 28.7%)(Figure 2B), with two-thirds reporting cosmetic acceptability as very good or good. Practicability of product use in areas adjacent to the hairline was rated very good by substantial proportions of both the AzA foam and vehicle foam groups (42.8% vs 35.9%)(Figure 2C).

Figure 2. Global assessment of tolerability at end of treatment (EoT)(A). Opinion on cosmetic acceptability at EoT (B). Opinion on practicability of product use in areas adjacent to hairline at EoT (C). AzA indicates azelaic acid. For global assessment of tolerability, acceptable indicates acceptable despite minor irritation; less acceptable, less acceptable due to continuous irritation. Note that the total sample does not equal 961 because of missing data for these outcomes.


At baseline, average disease burden was moderate according to mean overall DLQI scores (SD) for the AzA foam (5.4 [4.8]) and vehicle foam (5.4 [4.9]) groups. Mean overall DLQI scores improved at EoT, with greater improvement occurring in the AzA foam group (2.6 vs 2.1; P=.018)(Figure 3). A larger proportion of participants in the AzA foam group versus the vehicle foam group also achieved a 5-point or more improvement in overall DLQI score (24.6% vs 19.0%; P=.047). Changes in specific DLQI subscore components were either balanced or in favor of the AzA foam group, including daily activities (0.5 vs 0.4; P=.019), symptoms and feelings (1.2 vs 1.0; P=.069), and leisure (0.5 vs 0.4; P=.012). Specific DLQI items with differences in scores between treatment groups from baseline included the following questions: Over the last week, how embarrassed or self-conscious have you been because of your skin? (P<.001); Over the last week, how much has your skin interfered with you going shopping or looking after your home or garden? (P=.005); Over the last week, how much has your skin affected any social or leisure activities? (P=.040); Over the last week, how much has your skin created problems with your partner or any of your close friends or relatives? (P=.001). Differences between treatment groups favored the AzA foam group for each of these items.

Figure 3. Reduction in mean Dermatology Life Quality Index (DLQI) scores from baseline to end of treatment. AzA indicates azelaic acid. P values derived from Wilcoxon rank sum test. For personal relationships and work/school, AzA foam (n=435); vehicle foam (n=431). For symptoms/feelings and daily activities, AzA foam (n=435); vehicle foam (n=430). For leisure, AzA foam (n=435); vehicle foam (n=429). Component score responses do not include missing data.


Participants in the AzA foam and vehicle foam groups also showed improvement in RosaQOL scores at EoT (6.8 vs 6.4; P=.67), while EQ-5D-5L scores changed minimally from baseline (0.006 vs 0.007; P=.50).

Safety

The incidence of drug-related adverse events (AEs) was greater in the AzA foam group versus the vehicle foam group (7.7% vs 4.8%). Drug-related AEs occurring in 1% of the AzA foam group were application-site pain including tenderness, stinging, and burning (3.5% for AzA foam vs 1.3% for vehicle foam); application-site pruritus (1.4% vs 0.4%); and application-site dryness (1.0% vs 0.6%). One drug-related AE of severe intensity—application-site dermatitis—occurred in the vehicle foam group; all other drug-related AEs were mild or moderate.14 More detailed safety results are described in a previous report.13

Comment

The PRO outcome data reported here are consistent with previously reported statistically significant improvements in investigator-assessed primary end points for the treatment of PPR with AzA foam.13,14 The data demonstrate that AzA foam benefits both clinical and patient-oriented dimensions of rosacea disease burden and suggest an association between positive treatment response and improved QOL.

Specifically, patient evaluation of treatment response to AzA foam was highly favorable, with 57.2% reporting excellent or good response and 85.1% reporting positive response overall. Recognizing the relapsing-remitting course of PPR, only 1.8% of the AzA foam group experienced worsening of disease at EoT.

The DLQI and RosaQOL instruments revealed notable improvements in QOL from baseline for both treatment groups. Although no significant differences in RosaQOL scores were observed between groups at EoT, significant differences in DLQI scores were detected. Almost one-quarter of participants in the AzA foam group achieved at least a 5-point improvement in DLQI score, exceeding the 4-point threshold for clinically meaningful change.17 Although little change in EQ-5D-5L scores was observed at EoT for both groups with no between-group differences, this finding is not unexpected, as this instrument assesses QOL dimensions such as loss of function, mobility, and ability to wash or dress, which are unlikely to be compromised in most rosacea patients.

Our results also underscore the importance of vehicle in the treatment of compromised skin. Studies of topical treatments for other dermatoses suggest that vehicle properties may reduce disease severity and improve QOL independent of active ingredients.10,18 For example, ease of application, minimal residue, and less time spent in application may explain the superiority of foam to other vehicles in the treatment of psoriasis.18 Our data demonstrating high cosmetic favorability of AzA foam are consistent with these prior observations. Increased tolerability of foam formulations also may affect response to treatment, in part by supporting adherence.18 Most participants receiving AzA foam described tolerability as excellent or good, and the discontinuation rate was low (1.2% of participants in the AzA foam group left the study due to AEs) in the setting of near-complete dosage administration (97% of expected doses applied).13

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