Avoiding atrophy: Triple combination cream unlikely to impact skin

Dallas - Long-term use of a triple-combination cream for melasma (fluocinolone acetonide, hydroquinone, tretinoin; TriLuma, Galderma) is effective and unlikely to cause skin atrophy, according to a recent study.

In the 24-week study, however, the majority of patients were unable to decrease to a lower maintenance dose after 12 or more weeks of daily use without relapsing.

Based on clinical examinations, "We know that the triple combination cream does not seem to cause atrophy of the skin over a period of up to a year," says Amit G. Pandya, M.D., professor of dermatology, University of Texas Southwestern Medical Center, Dallas, and a study co-author.

However, dermatologists don't know if the product causes skin atrophy that can be detected histologically, he says.

"Sometimes, the skin looks normal, but when one looks at it under the microscope, there's atrophy," Dr. Pandya tells Dermatology Times.

Clinical study

To confirm histologically that the cream doesn't cause atrophy - and to determine the optimum maintenance regimen for patients with melasma - researchers enrolled 70 patients ages 18 to 65 years with moderate-to-severe melasma. Nearly three-quarters were Hispanic, with Fitzpatrick skin type IV.

Patients applied the cream once daily for at least 12 weeks, continuing this regimen until an investigator assessed their skin as clear or almost clear.

Upon reaching this milestone, patients transitioned to a maintenance phase, in which they applied the cream twice weekly. However, they resumed daily treatment if an investigator determined that they had relapsed to mild or worse disease. Patients who never reached clear or almost clear status continued daily dosing for the entire 24-week study period.

For histologic assessments, investigators took 2 mm punch biopsies (one each from an involved area and a nearby uninvolved area) at baseline, week 12 and week 24.

Analysis

Jag Bhawan, M.D. &38212 a dermatopathologist blinded to which samples came from patients on daily or maintenance dosing - used standardized histologic analysis to determine dermal and epidermal thickness. He also evaluated telangiectasias histologically by assessing the number of blood vessels in involved versus uninvolved areas at baseline and at the two follow-up visits.

Ultimately, investigators excluded eight patients who did not meet evaluation criteria from their calculations.

Of the remaining 62, Dr. Bhawan says, "Thirty had to stay on daily treatment through all 24 weeks of therapy (Group A)." Conversely, he says eight patients went to maintenance therapy after week 12 and remained relapse-free with twice-weekly dosing (Group B). The remaining 24 patients (Group C) were able to go on to maintenance dosing, but relapsed and returned to daily dosing.

"There was no evidence of atrophy for any patient at any point during the study," Dr. Pandya says.

More specifically, mean epidermal thickness reported in all patients at each visit was between 0.05 mm and 0.061 mm, and no significant changes occurred. Likewise, doctors reported that mean dermal thickness in all patients at each visit measured between 1.816 mm and 1.962 mm, also with no significant changes.

"And we saw a decrease in the amount of melanin in the treated skin, which is to be expected," Dr. Pandya says.

’Unique’ evaluations

In this regard, he says researchers' efficacy evaluations were unique in that they compared pigmentation levels between the skin with melasma and adjacent normal skin.

"This is a new way of looking at improvement of pigmentation," he says.

In previous studies, Dr. Pandya says researchers compared dark spots post-treatment to how they had looked pretreatment, "but we believe it's better to evaluate the adjacent normal skin, as well, because the patient wants the skin to look normal. By looking at the difference between the diseased and normal skin, we're able to tell how close we came to success," he says.

Measurements

Using a Mexameter (Courage & Khazaka) for pigment analysis, furthermore, provided objective measurements, he says.

When measured with this device, all members of all three groups experienced improvement in pigmentation, Dr. Pandya says.

"They also all showed improvement when we measured using subjective evaluations - the melasma area severity index (MASI) score and global improvement scores," he says.

By all measures used, he says, "The patients' melasma improved by well over 50 percent."

Histopathologic analysis showed a significant increase in mean number of blood vessels after 24 weeks of treatment in Groups A (34.5 to 50.1 per mm², P2, P= 0.005).

Study strengths, weaknesses

The study's strengths include the use of biopsies to assess atrophy, the use of treatment times up to six months, and the inclusion of patients with moderate to severe disease exclusively, Dr. Pandya says.

As for potential weaknesses, "One could say that if we went to 12 months of treatment, perhaps we could have seen some atrophy. But that's not very likely, given that after six months, we saw no atrophy at all," he says.

Dr. Pandya says he looks forward to the development of even more effective treatments for melasma.

"We're also hoping that a combination of treatments, using perhaps topical agents, chemical peels, lasers and other devices, will be found to be more effective in the future, so we can find the optimal combination therapy," he says. DT

Disclosure: Dr. Pandya is a consultant for Galderma, which funded the study.