EXPERT ANALYSIS FROM ODAC 2017
MIAMI (FRONTLINE MEDICAL NEWS) – Management of rosacea continues to challenge dermatologists and patients alike, although new advances and recent studies shine a light on promising new therapies to target this inflammatory skin condition.
Linda Stein Gold, MD, who directs dermatology clinical trials at the Henry Ford Hospital in Detroit, shared new information about the pathophysiology of rosacea and the controversial associations with cardiovascular disease and addressed the rosacea “genes versus environment” etiology question at the Orlando Dermatology Aesthetic and Clinical Conference.
Effective treatment of rosacea continues to be vexing because “this is abnormality of innate immune system, and the innate immune system is our first line of defense,” Dr. Stein Gold said. “Fortunately, we have some great new and emerging therapies for rosacea.”
The topical vasoconstrictor of cutaneous vasculature, oxymetazoline hydrochloride cream 1%, showed a statistically significant improvement in erythema, compared with vehicle only in people with rosacea in a phase III study, Dr. Stein Gold said. The outcome was strict, requiring both physician and patient assessment of at least a two-point improvement on the Erythema Assessment Scale. Investigators observed responses over 12 hours on the same day. “It’s actually kind of fun to do these studies,” she added. “You get to see what happens with patients across a whole day.”
A long-term analysis showed the efficacy of oxymetazoline “actually increased over the course of 52 weeks,” Dr. Stein Gold said. A total of 43% of participants experienced a two-grade improvement in erythema during this time. The agent was generally well tolerated, with dermatitis, pruritus, and headaches the most common treatment-related adverse events reported. (In January, the Food and Drug Administration approved oxymetazoline cream for the treatment of “persistent facial erythema associated with rosacea in adults.”)
Topical minocycline foam is another treatment showing promise for people with rosacea, showing efficacy and no major side effects, with some mild to moderate irritation, based on phase II study results, Dr. Stein Gold said. It is currently being evaluated in phase III trials, for both acne and rosacea, she added.
Sometimes, a new formulation can make a difference in terms of treatment tolerability, a major consideration for patients with rosacea, Dr. Stein Gold said. Recent evidence suggests azelaic acid foam, 15% (Finacea), approved by the FDA in 2015, provides a well-tolerated option with only 6.2% of patients experiencing any application site pain, compared with 1.5% on vehicle alone, she added.
Cardiovascular comorbidities
“We’ve heard a lot about psoriasis and cardiovascular comorbidities, and we worry that other skin diseases may have similar associations,” Dr. Stein Gold said. New revelations in the pathogenesis of rosacea suggest a comparable association, she added, including findings related to matrix metalloproteinases (MMPs). MMPs have a key role in rosacea, for example, and are also important in the pathogenesis of cardiovascular disease, she noted. Several studies have confirmed this association as well as other links, including to Parkinson’s disease.
Although these studies support associations, more evidence is needed to prove any causal relationship between rosacea and other conditions where inflammation plays a prominent role, she added.
Translating findings into action
Given this emerging evidence, “what are we going to do about it?” Dr. Stein Gold asked attendees at the meeting. Research suggests tetracycline might be protective, she said, because this antibiotic can inhibit MMP activity. In a retrospective cohort study, investigators discovered rosacea patients on tetracycline therapy were at lower risk for developing vascular disease ( J Invest Dermatol. 2014 Aug;134[8]:2267-9 ).
Nature or nurture?
Researchers and clinicians frequently debate the precise etiology of rosacea and whether the underlying causes are primarily genetic versus environmental. Investigators conducted a twin cohort study to find a more concrete answer, specifically looking at identical and fraternal twin pairs to determine how much genetics or environment likely contributes to factors on the National Rosacea Society grading system ( JAMA Dermatol. 2015 Nov;151[11]:1213-9 ).
“The bottom line is it’s really about half and half – about half were associated with genetics, the other half with environment,” Dr. Stein Gold said.
No matter what the etiology, it’s important to diagnose and treat rosacea, Dr. Stein Gold said. Although patients tend to be middle-aged white women, the condition is not limited to this patient population, and “you have to think about it to diagnose it in skin of color,” she added.
Rosacea, which has a high emotional impact, presents an opportunity for dermatologists to improve quality of life, Dr. Stein Gold said. “When people walk around with papules and pustules, [other] people think there is something wrong with them.”
Dr. Stein Gold disclosed that she is a consultant, member of the advisory boards and speaker’s bureaus for, and receives research grants from Galderma, Leo, Novan, Valeant, Novartis, Celgene and Allergan. She is also a consultant, advisory board member, and receives research grants from Dermira and Foamix. She is a consultant to Sol-Gel, Promis, Anacor, and Medimetriks. She is on the advisory board for Promis.
