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January 2016, Vol 4, No 1 - Inside Drug Update
Loretta Fala

Rosacea, a chronic, noncontagious dermatitis of the facial skin, affects approximately 16 million people in the United States.1,2 Furthermore, millions of additional people may be in temporary remission from rosacea.2 The increasing prevalence of rosacea in the past decade is a trend that may coincide with the aging of the US population.3

Characterized by red patches, flushing, and tiny visible blood vessels, rosacea frequently develops into inflammatory lesions that manifest as papules (raised spots), pustules (red and yellow pimples), and spidery red veins.1,4 The areas of the face that are often affected by rosacea are the nose, cheeks, forehead, and chin. Approximately 50% of the patients with rosacea also experience eye problems, such as dryness or irritated, swollen eyelids.5 In some cases, these ocular symptoms may precede the skin symptoms.5 In rare cases, rosacea can lead to rhinophyma, a thickening of the skin on the nose, which is more common in men than in women.5

The exact cause of rosacea is unknown.4 Rosacea may flare up and recede over the course of many years.4 Unlike acne, which is caused by too much sebum in the skin, rosacea is believed to be caused by 1 or more factors involving the nervous system, the immune system, blood vessels, genetics, or the environment.4,6 Another potential cause of rosacea is the presence of microbes and Demodex mites on the skin.6

Rosacea generally affects people aged ≥30 years, and is more common in fair-skinned individuals and in women.5-9 Patients often report burning and stinging of the skin, skin irritation, and/or facial edema.8 Despite its signs and symptoms, rosacea is often underrecognized.6 According to a survey of 1459 patients with rosacea conducted by the National Rosacea Society (NRS), 47% of patients were not familiar with rosacea before their diagnosis, and 95% said they knew little or nothing about the signs and symptoms of this condition.6 A survey of 502 women with rosacea demonstrated that 54% waited ≥7 months after symptom onset before seeking medical assistance, and that the mean time from symptom onset to diagnosis of rosacea was 12.9 months (median, 6 months).9

Aside from its physical manifestations, rosacea has a substantial impact on patients’ emotional well-being and quality of life.6,8 In surveys conducted by the NRS, 90% of patients with rosacea reported that the effect on their physical appearance diminished their self-esteem and confidence, and 41% of patients avoided public contact or social events because of their appearance.6

Left untreated, rosacea may worsen with time and may lead to facial disfigurement, serious ocular complications, and physical and emotional distress.3 Although there is no cure for rosacea, treatment and lifestyle changes can help control and reduce its signs and symptoms.5

Rosacea may progress from mild to moderate to severe at varying rates; therefore, early diagnosis and treatment are impor­tant.7 The initial management of rosacea includes the avoidance of factors that exacerbate the condition, including sun exposure, excessive heat or cold, stress, strenuous exercise, spicy foods, hot beverages, alcohol, and irritating skin care products.3,5

The treatment of papulopustular lesions generally includes skin care, protection from the sun, and topical therapy; for some patients, depending on the severity of symptoms, an oral treatment may be prescribed (ie, an antibiotic with anti-inflammatory effects, such as doxycycline).5,10 In some cases, a combination of oral and topical treatments may be prescribed. FDA-approved topical treatments include azelaic acid gel, brimonidine topical gel, ivermectin cream, and metronidazole (gel, emulsion, cream, and lotion).11 A new formulation (delivery vehicle) for azelaic acid became available in July 2015.12,13

Azelaic Acid Foam: A New Treatment Option for Rosacea

On July 31, 2015, azelaic acid foam 15% (Finacea Foam; Bayer HealthCare Pharmaceuticals), a saturated dicarboxylic acid,12 received FDA ap­proval as a topical treatment for the inflammatory papules and pustules of mild-to-moderate rosacea.13 Azelaic acid cream 20% (Azelex; Allergan) was approved by the FDA in 1995 for the treatment of mild-to-moderate inflammatory acne vulgaris.14,15 In late 2002, azelaic acid gel 15% (Finacea gel) was approved by the FDA for the topical treatment of inflammatory papules and pustules of mild-to-moderate rosacea.16,17

Gary Goldenberg, MD, Assistant Clinical Professor of Dermatology at the Icahn School of Medicine at Mount Sinai, New York, NY, commented, “According to recent studies, Finacea foam can help with papules, pustules and redness of rosacea. This is good news for patients with this chronic condition.”18

Dosing and Administration

Azelaic acid foam 15% is a white to off-white emulsion containing 0.15 g of azelaic acid for the topical treatment of rosacea on affected skin.12 The drug is supplied in a pressurized 50-g aluminum can.12

A thin layer of the foam is applied topically twice daily (morning and evening) to the entire facial area (cheeks, chin, forehead, and nose). After the foam has dried, cosmetics may be applied. Azelaic acid foam should be used continuously for 12 weeks. If no improvement is observed after 12 weeks of treatment, the patient’s condition should be reassessed.12

Azelaic acid foam is not for oral, ophthalmic, or intravaginal use.12

Mechanism of Action

Azelaic acid foam contains 15% azelaic acid, a naturally occurring saturated dicarboxylic acid. The exact mechanisms by which azelaic acid interferes with the pathogenic events in rosacea are not known.12

Clinical Studies

The efficacy and safety of azelaic acid foam were evaluated in 2 randomized, double-blind, vehicle-controlled, 12-week studies involving a total of 1362 patients with inflamma­tory papules and pustules.8,10,12 The patients were randomly assigned to the active treatment (N = 681) or to vehicle only (N = 681), and the age range was 19 to 92 years (mean age, 50.6 years). Azelaic acid foam or vehicle foam was applied topically twice daily for 12 weeks. Patients were instructed to avoid food and beverages that may provoke erythema, flushing, or blushing (eg, spicy foods, alcoholic beverages) and to avoid using any product that may irritate the skin (soap, astringents, alcohol-containing cleansers, or abrasives/peeling agents) throughout the study.12

The 2 primary efficacy end points in these studies were (1) the change in inflammatory lesion count from baseline and (2) the success of the treatment, defined as a score of “clear” or “minimal,” with a reduction from baseline of at least 2 points on a 5-point Investigator’s Global Assessment (IGA) scale. The IGA assessment definitions are listed in Table 1.12

Table 1

The primary efficacy results for these studies are shown in Table 2. In study 1, azelaic acid foam was superior to the vehicle alone in reducing the number of inflammatory papules and pustules and in demonstrating success based on IGA scores (P <.001 for both comparisons).10,12 Similarly, study 2 showed that azelaic acid foam was superior to the vehicle alone in decreasing the number of inflammatory lesions (P <.001) and in achieving success (P = .017).8,12

Table 2

According to Draelos and colleagues (of the research team for both studies), the gel formulation of azelaic acid was developed to achieve a treatment that can be applied and spread easily and dries rapidly.19 In study 2, the investigators concluded, “The treatment success demonstrated in the current study also is likely due in part to the inherent characteristics of foams (eg, ease of application and spread, more rapid drying time, reduced density), which often are preferred by patients over other vehicles such as gels or creams.”8 The investigators also suggested that patient preference for a particular formulation may help improve treatment adherence.8

Adverse Events

Adverse reactions that occurred in ≥0.5% of the 1362 patients who participated in the 2 studies are shown in Table 3.12 Hypopigmentation, as well as irritation of the eye and mucous membranes, also were reported.12

Table 3

Azelaic acid foam has no contraindications.

Warnings and Precautions

Skin reactions
Isolated cases of hypopigmentation were reported after the use of azelaic acid. Patients with a dark complexion should be monitored for early signs of hyperpigmentation, because azelaic acid has not been studied adequately in these patients.12

Irritation of the eye and mucous membranes
Azelaic acid has caused irritation of the eyes. Therefore, contact with the eye, mouth, and mucous membranes should be avoided. If azelaic acid foam comes in contact with the eyes, they should be washed well with water, and a physician should be consulted if irritation persists.12

Flammability
The propellant in azelaic acid foam is flammable. Patients should be instructed to avoid fire, flame, and smoking during and immediately after application. The containers should not be punctured, incinerated, exposed to heat, or stored at tem­peratures above 120°F (49°C).12

Use in Specific Populations and Conditions

Pregnancy
Adequate studies of this drug have not been conducted in pregnant women. Therefore, it should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus.12

Nursing mothers
It is not known whether aze­laic acid is secreted in human breast milk. The importance of the drug to the mother should be considered in decisions to discontinue nursing or to discontinue the drug.12

Pediatric use
The safety and effectiveness of azelaic acid foam in children aged <18 years have not been established.12

Geriatric use
In clinical studies of azelaic acid foam, 18.8% of all patients were aged ≥65 years (7.2% were aged ≥75 years).12 No overall differences in safety or effectiveness were observed between these and younger patients; however, greater sensitivity of some elderly individuals cannot be ruled out.12

Conclusion

With the recent FDA approval of azelaic acid foam 15%, another topical treatment option became available for patients with mild-to-moderate inflammatory papulopustular rosacea.

In 2 large 12-week clinical trials of patients with mild-to-moderate rosacea, the success rate (per IGA criteria) with azelaic acid foam was significantly higher than with the vehicle alone, and the reduction from baseline in inflammatory lesion count was significantly greater.

For some patients, azelaic acid foam may be easier to apply and spread than other formulations, and the drying time is rapid.




References

  1. US National Library of Medicine. Rosacea. www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0024824/. Accessed October 19, 2015.
  2. Drake L. Rosacea now estimated to affect at least 16 million Americans. Rosacea Rev. Winter 2010. www.rosacea.org/rr/2010/winter/article_1.php. Accessed October 20, 2015.
  3. Blount BW, Pelletier AL. Rosacea: a common, yet commonly overlooked, condition. Am Fam Physician. 2002;66:435-440.
  4. National Library of Medicine. Rosacea: overview. Updated August 14, 2014. www.ncbi.nlm.nih.gov/pubmedhealth/PMH0072660/. Accessed October 19, 2015.
  5. Mayo Clinic. Diseases and conditions: rosacea. Updated August 17, 2013. www.mayoclinic.org/diseases-conditions/rosacea/basics/definition/con-20014478. Accessed October 19, 2015.
  6. Drake L. Rosacea awareness month focuses on potential causes. Rosacea Rev. Spring 2015. www.rosacea.org/rr/2015/spring/article_1.php. Accessed October 21, 2015.
  7. National Rosacea Society. All about rosacea. www.rosacea.org/patients/allaboutrosacea.php. Accessed October 22, 2015.
  8. Draelos ZD, Elewski B, Staedtler G, Havlickova B. Azelaic acid foam 15% in the treatment of papulopustular rosacea: a randomized, double-blind, vehicle-controlled study. Cutis. 2013;92:306-317.
  9. Luftman DB. Best practices in: psychosocial impact of rosacea. Dermatol News. www.edermatologynews.com/view-pdf.html?file=uploads/media/BP_PsychImpactRosacea_01. Accessed October 21, 2015.
  10. Del Rosso JQ, Thiboutot D, Gallo R, et al. Consensus recommendations from the American Acne & Rosacea Society on the management of rosacea, part 5: a guide on the management of rosacea. Cutis. 2014;93:134-138.
  11. Center Watch. FDA approved drugs by medical condition: rosacea. www.centerwatch.com/drug-information/fda-approved-drugs/medical-conditions/R#. Accessed October 22, 2015.
  12. Finacea (azelaic acid) Foam, 15% [prescribing information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc; July 2015.
  13. FDA OKs azelaic acid (Finacea) [foam] for papulopustular rosacea [press release]. Medscape Medical News. July 31, 2015. www.medscape.com/viewarticle/848933. Accessed October 20, 2015.
  14. US Food and Drug Administration. Drug details: Azelex. www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Overview&DrugName=AZELEX. Accessed October 21, 2015.
  15. Azelex (azelaic acid cream) 20% [prescribing information]. Irvine, CA: Allergan, Inc; September 2015.
  16. US Food and Drug Administration. Drug details: Finacea.www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Overview&DrugName=FINACEA. Accessed October 21, 2015.
  17. Finacea (azelaic acid) Gel, 15% [prescribing information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc; April 2015.
  18. FDA approves new rosacea treatment: Finacea Foam. Press release; August 3, 2015. Drugs.com. www.drugs.com/news/fda-approves-new-rosacea-finacea-foam-57766.html. Accessed October 21, 2015.
  19. 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.
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