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

Cutis. 2016 October;98(4):269-275

Stephen Tyring, MD, PhD

James A. Solomon, MD, PhD

Gerald Staedtler, MSc

Jason P. Lott, MD, MSHP, MHS

Richard Nkulikiyinka, MD

Kaweh Shakery, MD

Patient-reported treatment outcomes are important for evaluating the impact of drug therapies on patient experience. A randomized, double-blind, vehicle-controlled, parallel-group, multicenter, phase 3 study was conducted in 961 participants to assess patient perception of efficacy, utility, and effect on quality of life (QOL) of an azelaic acid (AzA) 15% foam formulation for the treatment of papulopustular rosacea (PPR). Secondary end points included patient-reported global assessment of treatment response, global assessment of tolerability, and opinion on cosmetic acceptability and practicability of product use. Quality of life assessments included the Dermatology Quality of Life Index (DLQI) and Rosacea Quality of Life Index (RosaQOL). Self-reported global assessment of treatment response favored AzA foam over vehicle foam (P<.001), with 57.2% of the AzA foam group reporting excellent or good improvement versus 44.7% in the vehicle foam group. Tolerability was rated excellent or good in 67.8% of the AzA foam group versus 78.2% of the vehicle foam group. Mean overall DLQI scores at end of treatment (EoT) were improved (P=.018) in favor of the AzA foam group compared with the vehicle foam group. Both treatment groups showed improvements in RosaQOL. Treatment with AzA foam was associated with improved QOL and meaningful reductions in the patient-perceived burden of PPR, which correlates with earlier reported primary end points of this study and supports the inclusion of patient perspectives in studies evaluating the effects of topical dermatologic treatments.

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Practice Points

Patient perceptions of treatment are an important consideration in developing topical therapeutic strategies for papulopustular rosacea.
A novel hydrophilic foam formulation of azelaic acid (AzA) provided substantial benefits in patient-reported measures of treatment response and quality of life.
Patients reported high levels of satisfaction with the usability, tolerability, and practicability of AzA foam.
The positive treatment experience described by patients parallels investigator-reported measures of clinical efficacy reported elsewhere.

References

Cardwell LA, Farhangian ME, Alinia H, et al. Psychological disorders associated with rosacea: analysis of unscripted comments. J Dermatol Surg. 2015;19:99-103.
Moustafa F, Lewallen RS, Feldman SR. The psychological impact of rosacea and the influence of current management options. J Am Acad Dermatol. 2014;71:973-980.
Wilkin J, Dahl M, Detmar M, et al. Standard classification of rosacea: report of the National Rosacea Society Expert Committee on the Classification and Staging of Rosacea. J Am Acad Dermatol. 2002;46:584-587.
Yamasaki K, Gallo RL. The molecular pathology of rosacea. J Dermatol Sci. 2009;55:77-81.
Del Rosso JQ. Advances in understanding and managing rosacea: part 1: connecting the dots between pathophysiological mechanisms and common clinical features of rosacea with emphasis on vascular changes and facial erythema. J Clin Aesthet Dermatol. 2012;5:16-25.
Bohm D, Schwanitz P, Stock Gissendanner S, et al. Symptom severity and psychological sequelae in rosacea: results of a survey. Psychol Health Med. 2014;19:586-591.
Elewski BE, Draelos Z, Dreno B, et al. Rosacea—global diversity and optimized outcome: proposed international consensus from the Rosacea International Expert Group. J Eur Acad Dermatol Venereol. 2011;25:188-200.
Dirschka T, Micali G, Papadopoulos L, et al. Perceptions on the psychological impact of facial erythema associated with rosacea: results of international survey [published online May 29, 2015]. Dermatol Ther (Heidelb). 2015;5:117-127.
Abram K, Silm H, Maaroos HI, et al. Subjective disease perception and symptoms of depression in relation to healthcare-seeking behaviour in patients with rosacea. Acta Derm Venereol. 2009;89:488-491.
Stein L. Clinical studies of a new vehicle formulation for topical corticosteroids in the treatment of psoriasis. J Am Acad Dermatol. 2005;53(1, suppl 1):S39-S49.
Yentzer BA, Camacho FT, Young T, et al. Good adherence and early efficacy using desonide hydrogel for atopic dermatitis: results from a program addressing patient compliance. J Drugs Dermatol. 2010;9:324-329.
Finacea (azelaic acid) foam 15% [package insert]. Whippany, NJ: Bayer Pharmaceuticals; 2015.
Draelos ZD, Elewski BE, Harper JC, et al. A phase 3 randomized, double-blind, vehicle-controlled trial of azelaic acid foam 15% in the treatment of papulopustular rosacea. Cutis. 2015;96:54-61.
Solomon JA, Tyring S, Staedtler G, et al. Investigator-reported efficacy of azelaic acid foam 15% in patients with papulopustular rosacea: secondary efficacy outcomes from a randomized, controlled, double-blind, phase 3 trial. Cutis. 2016;98:187-194.
Nicholson K, Abramova L, Chren MM, et al. A pilot quality-of-life instrument for acne rosacea. J Am Acad Dermatol. 2007;57:213-221.
Herdman M, Gudex C, Lloyd A, et al. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res. 2011;20:1727-1736.
Basra MK, Salek MS, Camilleri L, et al. Determining the minimal clinically important difference and responsiveness of the Dermatology Life Quality Index (DLQI): further data. Dermatology. 2015;230:27-33.
Bergstrom KG, Arambula K, Kimball AB. Medication formulation affects quality of life: a randomized single-blind study of clobetasol propionate foam 0.05% compared with a combined program of clobetasol cream 0.05% and solution 0.05% for the treatment of psoriasis. Cutis. 2003;72:407-411.

Rosacea is a chronic inflammatory disorder that may negatively impact patients’ quality of life (QOL).^1,2 Papulopustular rosacea (PPR) is characterized by centrofacial inflammatory lesions and erythema as well as burning and stinging secondary to skin barrier dysfunction.^3-5 Increasing rosacea severity is associated with greater rates of anxiety and depression and lower QOL⁶ as well as low self-esteem and feelings of embarrassment.^7,8 Accordingly, assessing patient perceptions of rosacea treatments is necessary for understanding its impact on patient health.^6,9

The Rosacea International Expert Group has emphasized the need to incorporate patient assessments of disease severity and QOL when developing therapeutic strategies for rosacea.⁷ Ease of use, sensory experience, and patient preference also are important dimensions in the evaluation of topical medications, as attributes of specific formulations may affect usability, adherence, and efficacy.^10,11

An azelaic acid (AzA) 15% foam formulation, which was approved by the US Food and Drug Administration in 2015, was developed to deliver AzA in a vehicle designed to improve treatment experience in patients with mild to moderate PPR.¹² Results from a clinical trial demonstrated superiority of AzA foam to vehicle foam for primary end points that included therapeutic success rate and change in inflammatory lesion count.^13,14 Secondary end points assessed in the current analysis included patient perception of product usability, efficacy, and effect on QOL. These patient-reported outcome (PRO) results are reported here.

Methods

Study Design

The design of this phase 3 multicenter, randomized, double-blind, vehicle-controlled, parallel-group clinical trial was described in more detail in an earlier report.¹³ This study was approved by all appropriate institutional review boards. Eligible participants were 18 years and older with moderate or severe PPR, 12 to 50 inflammatory lesions, and persistent erythema with or without telangiectasia. Exclusion criteria included known nonresponse to AzA, current or prior use (within 6 weeks of randomization) of noninvestigational products to treat rosacea, and presence of other dermatoses that could interfere with rosacea evaluation.

Participants were randomized into the AzA foam or vehicle group (1:1 ratio). The study medication (0.5 g) or vehicle foam was applied twice daily to the entire face until the end of treatment (EoT) at 12 weeks. Efficacy and safety parameters were evaluated at baseline and at 4, 8, and 12 weeks of treatment, and at a follow-up visit 4 weeks after EoT (week 16).

Results for the coprimary efficacy end points—therapeutic success rate according to investigator global assessment and nominal change in inflammatory lesion count—were previously reported,¹³ as well as secondary efficacy outcomes including change in inflammatory lesion count, therapeutic response rate, and change in erythema rating.¹⁴

Patient-Reported Secondary Efficacy Outcomes

The secondary PRO end points were patient-reported global assessment of treatment response (rated as excellent, good, fair, none, or worse), global assessment of tolerability (rated as excellent, good, acceptable despite minor irritation, less acceptable due to continuous irritation, not acceptable, or no opinion), and opinion on cosmetic acceptability and practicability of product use in areas adjacent to the hairline (rated as very good, good, satisfactory, poor, or no opinion).

Additionally, QOL was measured by 3 validated standardized PRO tools, including the Rosacea Quality of Life Index (RosaQOL),¹⁵ the EuroQOL 5-dimension 5-level questionnaire (EQ-5D-5L),¹⁶ and the Dermatology Life Quality Index (DLQI). The RosaQOL is a rosacea-specific instrument assessing 3 constructs: (1) symptom, (2) emotion, and (3) function. The EQ-5D-5L questionnaire measures overall health status and comprises 5 constructs: (1) mobility, (2) self-care, (3) usual activities, (4) pain/discomfort, and (5) anxiety/depression. The DLQI is a general, dermatology-oriented instrument categorized into 6 constructs: (1) symptoms and feelings, (2) daily activities, (3) leisure, (4) work and school, (5) personal relationships, and (6) treatment.

Statistical Analyses

Patient-reported outcomes were analyzed in an exploratory manner and evaluated at EoT relative to baseline. Self-reported global assessment of treatment response and change in RosaQOL, EQ-5D-5L, and DLQI scores between AzA foam and vehicle foam groups were evaluated using the Wilcoxon rank sum test. Categorical change in the number of participants achieving an increase of 5 or more points in overall DLQI score was evaluated using a χ² test.

Safety

Safety was analyzed for all randomized patients who were dispensed any study medication. All analyses were performed using SAS version 9.2.

References

Cardwell LA, Farhangian ME, Alinia H, et al. Psychological disorders associated with rosacea: analysis of unscripted comments. J Dermatol Surg. 2015;19:99-103.
Moustafa F, Lewallen RS, Feldman SR. The psychological impact of rosacea and the influence of current management options. J Am Acad Dermatol. 2014;71:973-980.
Wilkin J, Dahl M, Detmar M, et al. Standard classification of rosacea: report of the National Rosacea Society Expert Committee on the Classification and Staging of Rosacea. J Am Acad Dermatol. 2002;46:584-587.
Yamasaki K, Gallo RL. The molecular pathology of rosacea. J Dermatol Sci. 2009;55:77-81.
Del Rosso JQ. Advances in understanding and managing rosacea: part 1: connecting the dots between pathophysiological mechanisms and common clinical features of rosacea with emphasis on vascular changes and facial erythema. J Clin Aesthet Dermatol. 2012;5:16-25.
Bohm D, Schwanitz P, Stock Gissendanner S, et al. Symptom severity and psychological sequelae in rosacea: results of a survey. Psychol Health Med. 2014;19:586-591.
Elewski BE, Draelos Z, Dreno B, et al. Rosacea—global diversity and optimized outcome: proposed international consensus from the Rosacea International Expert Group. J Eur Acad Dermatol Venereol. 2011;25:188-200.
Dirschka T, Micali G, Papadopoulos L, et al. Perceptions on the psychological impact of facial erythema associated with rosacea: results of international survey [published online May 29, 2015]. Dermatol Ther (Heidelb). 2015;5:117-127.
Abram K, Silm H, Maaroos HI, et al. Subjective disease perception and symptoms of depression in relation to healthcare-seeking behaviour in patients with rosacea. Acta Derm Venereol. 2009;89:488-491.
Stein L. Clinical studies of a new vehicle formulation for topical corticosteroids in the treatment of psoriasis. J Am Acad Dermatol. 2005;53(1, suppl 1):S39-S49.
Yentzer BA, Camacho FT, Young T, et al. Good adherence and early efficacy using desonide hydrogel for atopic dermatitis: results from a program addressing patient compliance. J Drugs Dermatol. 2010;9:324-329.
Finacea (azelaic acid) foam 15% [package insert]. Whippany, NJ: Bayer Pharmaceuticals; 2015.
Draelos ZD, Elewski BE, Harper JC, et al. A phase 3 randomized, double-blind, vehicle-controlled trial of azelaic acid foam 15% in the treatment of papulopustular rosacea. Cutis. 2015;96:54-61.
Solomon JA, Tyring S, Staedtler G, et al. Investigator-reported efficacy of azelaic acid foam 15% in patients with papulopustular rosacea: secondary efficacy outcomes from a randomized, controlled, double-blind, phase 3 trial. Cutis. 2016;98:187-194.
Nicholson K, Abramova L, Chren MM, et al. A pilot quality-of-life instrument for acne rosacea. J Am Acad Dermatol. 2007;57:213-221.
Herdman M, Gudex C, Lloyd A, et al. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res. 2011;20:1727-1736.
Basra MK, Salek MS, Camilleri L, et al. Determining the minimal clinically important difference and responsiveness of the Dermatology Life Quality Index (DLQI): further data. Dermatology. 2015;230:27-33.
Bergstrom KG, Arambula K, Kimball AB. Medication formulation affects quality of life: a randomized single-blind study of clobetasol propionate foam 0.05% compared with a combined program of clobetasol cream 0.05% and solution 0.05% for the treatment of psoriasis. Cutis. 2003;72:407-411.

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

References

Methods

Pages

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