Treating Papulopustular Rosacea With Oral Sarecycline

Patients with rosacea report having lowered self-esteem and self-confidence due to the condition’s persistent and visible redness.¹ Effective treatment can mean a world of difference for these patients. When clear or almost clear skin is achieved, 83% of patients reported improved psychological well-being, 73% reported improved social lives, and 63% reported  reported improvement in their occupational well-being.¹ While new therapies are advancing the treatment of rosacea, dermatologists continue to explore novel ways of addressing the multiple phenotypes of the disease.

James Q. Del Rosso, DO, FAOCD, FAAD, is a board-certified dermatologist at Thomas Dermatology and research director/principal investigator of JDR Dermatology Research in Las Vegas, NV. He also serves as senior vice president of clinical research and strategic development at Advanced Dermatology and Cosmetic Surgery in Maitland, FL.

Dr Del Rosso founded the Scientific Panel for Antibiotic Use in Dermatology in 2005, with three meetings and multiple scientific publications authored under his direction that help to educate and guide clinicians on optimal antibiotic use in dermatology. He shared his insights on sarecycline, a newer tetracycline, for papulopustular rosacea in reference to the study “Oral Sarecycline for Treatment of Papulopustular Rosacea: Results of a Pilot Study of Effectiveness and Safety.”²

Sarecycline is an oral tetracycline agent approved by the FDA for the treatment of patients 9 years of age and older with moderate to severe acne vulgaris. It is administered once daily using weight-based dosing with or without food. Although not approved for rosacea, Dr Del Rosso and a group of coinvestigators sought to evaluate the effectiveness of sarecycline in patients with papulopustular rosacea.

Other than a specifically formulated modified-release doxycycline 40-mg capsule taken once daily, oral tetracyclines that have been used to treat rosacea, such as doxycycline and minocycline, are not approved for rosacea treatment. Compared with doxycycline and minocycline, sarecycline offers the advantage of being a narrow-spectrum tetracycline in terms of antibiotic activity based on microbiologic studies. In addition, large-scale pivotal trials of sarecycline used to treat acne demonstrated a low rate of tetracycline-associated side effects, such as vertigo, gastrointestinal reactions, photosensitivity, and vaginal yeast infections. These relative differences noted with sarecycline prompted interest in evaluating its use for rosacea, especially when presenting with papulopustular lesions.

moderate to severe papulopustular facial rosacea including a range of 15 to 50 papules and pustules along with facial erythema. Other treatments that could affect rosacea were excluded using established wash-out periods prior to study entry. Skin care, such as cosmetic use, also was controlled and stable throughout the study. Women using oral contraceptives had to remain on a stable product and dose.

“We wanted to control any other variables that can influence the effectiveness or the lack of effectiveness, or impact on any side effects. We wanted to look at just what that oral sarecycline was able to achieve in adults with papulopustular rosacea,” stated Dr Del Rosso.

There were 97 patients who finished this pilot study, randomized in a 3:1 ratio and investigator-blinded fashion to receive either sarecycline (n=72) or a multivitamin tablet once daily. All patients were encouraged to avoid any known triggers of rosacea throughout the study, and patients were seen at weeks 4, 8, and 12. The primary evaluation for efficacy was whether they became completely clear or almost clear based on the Investigator Global Assessment. Lesion counts of papules and pustules were also completed at every study visit. To be considered a success in the study, the patients had to be rated as clear or almost clear at week 12.

The results showed that at week 12, 75% of patients treated with sarecycline achieved clear or almost clear compared with 16% of those receiving a multivitamin tablet. These results were statistically significant as well as numerically significant based on changes in papulopustular lesion counts. Tolerability and safety proved to favorable in both study groups.

It is important to recognize that there are multiple pathophysiologic factors that collectively cause the facial erythema of rosacea. With papulopustular rosacea, which occurs during a flare, there is perilesional erythema that is directly associated with the papules and pustules. Treatment with topical agents such as metronidazole, azelaic acid, or ivermectin or with an oral tetracycline agent (eg, sarecycline) reduces the papules and pustules and the perilesional erythema caused by these lesions.

The pilot clinical study² demonstrated that sarecycline was effective and safe in reducing papulopustular lesions and the erythema associated with these lesions. Once a papulopustular rosacea flare resolves with any effective treatment, the diffuse background erythema that is present on the central face is due to the fixed dilation of superficial blood vessels. This redness is referred to as persistent facial erythema (PFE). The PFE presentation of rosacea can be treated with a topical α-agonist and/or physical modalities such as vascular lasers and intense pulse light.

Another advantage of sarecycline, as compared to antibiotic doses of doxycycline and minocycline, is that sarecycline is a narrow-spectrum tetracycline agent. Unlike doxycycline and minocycline, which exhibit broad-spectrum antibiotic activity, sarecycline has negligible antibiotic effects against gram-negative and several anaerobic bacteria. Therefore, it produces less antibiotic selection pressure against commensal bacteria, especially those commonly present in the gastrointestinal tract microbiome. Importantly, a reduction in causing antibiotic resistance is a clinically relevant consideration when prescribing antibiotic therapy.

“It was a natural extension to evaluate oral sarecycline in rosacea, especially since sarecycline has some potential advantages over the other tetracyclines that are broad spectrum antibiotics,” said Dr Del Rosso. “We've had doxycycline and minocycline for years, and they work for papulopustular rosacea, but there are differences with sarecycline that are important to consider.”

Even with the potential of oral sarecycline for resolving papules and pustules, rosacea requires the dermatologist to look at the entire phenotypic presentation. “With regard to the management of papulopustular rosacea, we need to recognize that when we're looking at a patient that presents to us with papulopustular rosacea, some of the visible manifestations that they have are not necessarily going to go away completely,” said Dr Del Rosso. “The papules and pustules and the perilesional redness they cause are going to go away, but even with therapies that effectively reduce papulopustular lesions, the patient is still going to be left with some background redness. That background redness is from the persistently dilated facial blood vessels and the therapy for papulopustular rosacea is not addressing that component of the disease, at least in the short term.

“You have to make sure patients understand that you can get them significantly better, but to treat all the visible signs of rosacea, treatment will require a combination of different therapies. Maybe it will be enough in some patients that most of the redness will be gone with the resolution of papules and pustules, and they may be happy with that. If they are still concerned about the persistent background redness, there are other treatments that can be used to treat that component of the disease.”

Dr Del Rosso shared another pearl for dermatologists approaching rosacea: “Controlling the skin care in all these patients is extremely important. Very fundamental to rosacea, regardless of anything else we recommend, is the right skin care,” he explained. If the patient is using harsh skin care products, their rosacea is likely to worsen due to irritation.

“Patients need gentle skin care products that are good for moisturization, because rosacea is a condition where their skin tends to be sensitive. It is easy to lose moisture through increased transepidermal water loss. With proper moisture content, your skin functions normally and keeps its healthier appearance. The skin inflammation caused by utilizing the wrong skin care and from the rosacea itself tends to cause loss of skin moisture. You want to make sure that skin care optimizes the level of moisture in their skin.

“Regardless of anything else we are doing,” said Dr Del Rosso, “educating patients on proper skin care is crucial to the success of rosacea management.”