New York- Results from a 12-month, open-label extension study highlight the efficacy and safety of the fixed triple-combination cream containing hydrocortisone 4 percent, tretinoin 0.05 percent and fluocinolone acetonide 0.01 percent (Tri-Luma Cream, Galderma) as a modality for the long-term management of melasma, says Helen M. Torok, M.D.
New York - Results from a 12-month, open-label extension study highlight the efficacy and safety of the fixed triple-combination cream containing hydrocortisone 4 percent, tretinoin 0.05 percent and fluocinolone acetonide 0.01 percent (Tri-Luma Cream, Galderma) as a modality for the long-term management of melasma, says Helen M. Torok, M.D.
In a poster presented at the American Academy of Dermatology's Academy '04 here, Dr. Torok, a private practitioner in Medina, Ohio, and one of the study investigators, presented outcomes from an intention-to-treat analysis that included 569 patients who used the triple-combination cream intermittently or continuously for up to 12 months. All of the patients had participated in an eight-week, randomized, double-blind study during which they had been assigned to treatment with the triple-combination cream (n=142) or one of three control groups using preparations containing only two of the active ingredients (n=427).
The subjects who continued in the open-label study included both individuals whose melasma had improved to clear or mild at the completion of the randomized study and who then restarted treatment with the triple combination cream as needed, and patients whose melasma was still moderate or severe and who continued once daily treatment until they improved satisfactorily or were judged to be nonresponders. All patients were counseled on sun avoidance and to routinely use an SPF 30 broad-spectrum sunscreen.
In addition, the efficacy analyses indicated that from both the investigators' and patients' perspective, the triple-combination cream was beneficial in improving melasma that had not previously responded to treatment as well as effective in treating recurrent disease.
"Melasma is a chronic, recurring disease that can be challenging to treat and difficult to maintain clearance. The pivotal trial results showed this triple-combination depigmenting product was a significant advance in providing a convenient, safe and effective treatment for clearing or significantly reducing melasma over eight weeks," says Dr. Torok. "The analyses from this open-label extension demonstrate it can be used for longer intervals to increase the effectiveness on an as-needed basis with the same excellent safety profile as seen during eight weeks of use."
The 569 patients who received medication during the open-label extension study were nearly all females (98 percent), and were mostly Caucasian (66 percent) with skin phototypes I to III (79 percent).Mean cumulative exposure to the fixed-combination cream was 204 days; among patients who had received the triple-combination cream during the eight-week randomized study, total mean cumulative exposure was 256 days. There were 389 patients who completed the first six months of the open-label study and 327 who were seen at 12 months. The fixed triple-combination cream was used for >180 days by 330 patients and by >360 days by 92 patients.
The study withdrawal rate was slightly higher among patients who originally were treated with a dual combination versus the triple fixed-combination - 46 percent versus 40 percent. However, only 2 percent of patients withdrew from the study because of treatment failure.
As in the eight-week study, desquamation and erythema were the most common side effects, each being reported by about one-third of the patients. Other local reactions, including burning, dryness, inflammation, pigmentation, itching and rash, each occurred at rates 10 percent.
Sixty percent of patients experienced some side effect, although those events were generally minor. The frequency of application-site adverse events increased slightly with increasing duration of exposure, but the types and severity of adverse events did not change over the course of the study.
"Erythema and scaling occur with the use of hydroquinone and tretinoin as monotherapy, and so it is not surprising to see that they were the most common side effects with the triple-combination cream. Importantly, however, despite the prolonged period of use, very few patients developed skin changes that might be corticosteroid-related, or discontinued treatment because of an adverse event," Dr. Torok says.
Mild skin atrophy occurred in two patients, and one of those cases resolved. Other putative corticosteroid-induced side effects included rosacea (one patient) and mild telangiectasia (23 patients). At the end of follow-up, the telangiectasia had also improved in 15 patients, and only two individuals withdrew from study participation because of the vascular changes.
Disclosure: Dr. Torok is a consultant to Galderma.