Treatment Options for Rosacea

Rosacea is a chronic skin condition characterized by transient or persistent erythema of the central face including inflammatory papules or pustules, telangiectasia, or hyperplasia of the connective tissue.¹ At least 14 million people in the United States have rosacea, and the prevalence may be as high as 5%.^1,2 This disease is most common in women (especially during menopause), people with fair skin, and in adults between the ages of 30 and 60.²

Although the pathogenesis of rosacea is not well understood, the innate immune system and cutaneous neurovascular dysregulation may be responsible.³ The cutaneous immune system is comprised of structural (keratinocytes, sebocytes) and immune (mast cells, neutrophils, natural killer cells, dendritic cells) cellular elements.³ Proinflammatory peptides such as cathelicidins and defensins are secreted by keratinocytes in response to injury, UV radiation, and pathogens such as bacteria, viruses, and fungi.³ The distribution of sebaceous glands on the face as well as nerve innervation and vascular composition play a role in the etiology of rosacea.¹ There is also a probable genetic component in the pathogenesis of rosacea.³

There are 4 subtypes of rosacea:^1,2

• Erythematotelangiectatic (Erythema) - Flushing and persistent central facial erythema with or without telangiectasia
• Papulopustular (Papules and Pustules) - Persistent central facial erythema with transient, central facial papules or pustules or both
• Phymatous (Phyma) - Thickening skin, irregular surface nodularities and enlargement; may occur on the nose, chin, forehead, cheeks, or ears
• Ocular - Foreign body sensation in the eye, burning or stinging, dryness, itching, ocular photosensitivity, blurred vision, telangiectasia of the sclera or other parts of the eye, or periorbital edema

Patients frequently report the following triggers as factors that initiate or aggravate symptoms: sun exposure (81%), emotional stress (79%), hot weather (75%), wind (57%), strenuous exercise (56%), and alcohol consumption (52%).¹ Keeping a journal can help patients to identify potential triggers that cause flare-ups.¹

Drug Therapies for Rosacea^1-13

Drug

Dosage Form

FDA Indication for Rosacea

Adverse Event

topical metronidazole (Metrogel, Metrocream, Metrolotion, Noritate, Rosadan)

gel, cream, or lotion

Varies by product -

Metrogel : inflammatory lesions of rosacea.

Metrocream, Metrolotion, Rosadan: inflammatory papules and pustules of rosacea.

Noritate:

inflammatory lesions and erythema of rosacea

Pruritus, stinging, irritation, dryness

oral doxycycline (Oracea)

oral capsule

only inflammatory lesions (papules and pustules) of rosacea

nasopharyngitis, sinusitis, diarrhea, hypertension

azelaic acid (Finacea)

gel

inflammatory papules and pustules of mild to moderate rosacea

Stinging, irritation, burning

brimonidine (Mirvaso)

gel

persistent (non-transient) erythema of rosacea

Pruritus, burning, irritation, dryness, erythema

ivermectin (Soolantra)

cream

inflammatory lesions of rosacea

Burning, skin irritation

oxymetazoline (Rhofade)

cream

persistent facial erythema associated

with rosacea

Irritation, burning, worsening inflammatory lesions of

rosacea

Drug Treatment Recommendations for Each Subtype of Rosacea^3,13

Erythematotelangiectatic (Erythema)

• Topical brimonidine - The effectiveness of topical brimonidine was demonstrated in 2 high-quality studies to be an effective treatment for erythema of rosacea. On day 29 of treatment, a 2-grade improvement on the Clinician Erythema Assessment (CEA) scale was seen in 31.5% of patients in the brimonidine group but only 9.2% of those on vehicle. Brimonidine tartrate was well tolerated during 4 weeks of daily treatment with mild, transient adverse events.
• Topical oxymetazoline - Rhofade cream was recently approved in January 2017. Oxymetazoline is the same chemical ingredient in Afrin nasal spray and Clear Eyes eye drops. Based on the clinical trial information in the prescribing information, a maximum of 18% of patients met the treatment goal in clinical trials.
• Topical metronidazole - Topical metronidazole has been shown in 6 studies to provide statistically and clinically significant improvement in erythema by patient and physician assessment and is more effective than placebo. The rate of adverse events for metronidazole is similar to placebo.
• Topical azelaic acid - azelaic acid has shown limited efficacy in 5 studies for treatment of erythema of rosacea, with decreases in erythema of 44% to 48% compared with 28% to 38% for placebo. Treatment site irritation is common.
• Oral doxycycline - There is evidence showing efficacy of doxycycline for reduction of erythema of rosacea. However, this was based on a study of patients with papulopustular rather than erythematotelangiectatic rosacea. Efficacy for background erythema alone is uncertain. Doxycycline 40 mg (modified release) dosage form and doxycycline 100 mg appear to be equivalent

Papulopustular (Papules and Pustules)

• Topical ivermectin - In 2 large, randomized-controlled trials with a combined total of 1371 patients, ivermectin resulted in statistically significant improvement in patient- and physician-assessed global outcomes and also significant and clinically important reductions in lesions compared with placebo. Ivermectin was associated with fewer adverse events than placebo, with patients reporting less dry skin and itching.
• Topical azelaic acid - In 1 trial, azelaic acid resulted in a greater reduction in papules and pustules than placebo.
• Topical metronidazole - There is moderate-quality evidence that metronidazole leads to reduction in the number of lesions; however, these data were skewed and inadequately reported.
• Oral doxycycline - There is high-quality evidence showing efficacy of doxycycline for treatment of papules and pustules of rosacea. The 40 mg (modified release) and 100 mg doses appear to be equivalent.

Phymatous (Phyma)

• Oral doxycycline - Based on anecdotal evidence, oral doxycycline may be useful for mild phymatous rosacea, particularly if there is an inflammatory component.

Ocular

• Oral doxycycline - Open-label trials of doxycycline 40 mg once daily have reported improvement of ocular rosacea symptoms.

References

1. Oge LK, Muncie, HL, Phillips-Savoy AR. Rosacea: Diagnosis and Treatment. Am Fam Physician. 2015 Aug 1;92(3):187-196.

2. What is rosacea? National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). https://www.niams.nih.gov/health_info/Rosacea/rosacea_ff.asp Accessed January 22, 2017.

3. Asai Y, Tan J, Baibergenova A, et al. Canadian Clinical Practice Guidelines for Rosacea. J Cutan Med Surg. 2016; 20(5):432—445.

4. Metrocream [package insert]. Fort Worth, TX; Galderma Labs, March 2011.

5. Metrogel topical [package insert]. Fort Worth, TX: Galderma Labs; October 2011.

6. Metrolotion topical [package insert]. Fort Worth, TX: Galderma Labs; October 2015.

7. Oracea [package insert]. Fort Worth, TX: Galderma Labs; December 2014.

8. Rosadan [package insert]. Fairfield , NJ: Medimetircks, Inc.; April 2012.

9. Noritate [package insert]. Bridgewater, NJ: Valeant Pharmaceuticals North America LLC; March 2015.

10. Mirvaso [package insert]. Fort Worth, TX: Galderma Labs; October 2015.

11. Finacea [package insert]. Morristown, NJ: Intendis Inc., April 2011.

12. Soolantra [package insert]. Fort Worth, TX: Galderma Labs; February 2016.

13. Rhofade [package insert]. Irvine, CA: Allergan; January 2017.