Tacrolimus bests pimecrolimus for treatment of AD, study says

Kona, Hawaii - Tacrolimus ointment is superior to pimecrolimus cream in treating atopic dermatitis, according to recent trial data reported by Alan Fleischer, M.D., during the 28^th Annual Hawaii Dermatology Seminar here. Both calcineurin inhibitors have identical modes of action and identical metabolism, and bind to the same FKBP receptor. "But pimecrolimus has one-third the binding affinity of tacrolimus," he says.

Tacrolimus is indicated for moderate to severe atopic dermatitis, and comparative studies have show it is at least as effective as a mid-potencytopical corticosteroid in these patients. In similar comparisons, pimecrolimus appears less effective than midpotency corticosteroids, says Dr. Fleischer, professor and chair, department of dermatology, Wake Forest University School of Medicine, Winston-Salem, N.C.

"Corticosteroids are excellent drugs for atopic dermatitis, but they can begin to cause atrophy relatively quickly," he says. For example, the United Kingdom National Health

There is also evidence that concomitant administration of tacrolimus and a corticosteroid is more effective and associated with fewer side effects in atopic patients. In a 21-day study, 57 patients were randomized to apply 0.1 percent clocortolone pivalate cream, 0.1 percent tacrolimus ointment, or both to affected areas. The combination treatment was significantly better in improving total dermatologic score, excoriation, induration, erythema, oozing and crusting and lichenification. In addition, transient pruritis and burning and stinging were significantly reduced from baseline in patients using the combination compared to either monotherapy.

While it is apparent that combination, sequential or monotherapy including a calcineurin inhibitor is beneficial for atopic dermatitis, there have been no previous direct comparison trials using tacrolimus and pimecrolimus to determine the relative efficacy of each agent in the same patient population, Dr. Fleischer says.

Tacrolimus vs. pimecrolimus trial

A multicenter, randomized trial evaluated 193 patients ages 2 to 16 years who applied either 0.1 percent tacrolimus or 1.0 percent pimecrolimus for six weeks or until one week after their atopic dermatitis cleared. Patients in each treatment group had similar baseline characteristics.

"The goal was not to obtain significant improvement. The goal was to have patients clear or almost clear," says Dr. Fleischer.

The primary endpoint was the Investigators Global AD Assessment, and scores of clear or almost clear were seen in 3.2 percent of tacrolimus patients and 4.0 percent of pimecrolimus patients after one week, in 18.1 percent or tacrolimus and 10.1 percent of pimecrolimus at three weeks, and 38.3 percent of tacrolimus and 20.2 percent of pimecrolimus patients after six weeks. Eczema Area and Severity Index and Body Surface Area scores were also more significantly reduced among tacrolimus patients compared to those using pimecrolimus.

Burning and stinging were more prevalent among pimecrolimus users, and twice as many pimecrolimus patients as tacrolimus patients withdrew from the study due to either lack of efficacy or adverse effects. "Adverse events were worse with pimecrolimus, and this is not suprising because it is a less-effective drug which does not repair the skin barrier as readily, so it penetrates the skin, causing burning and stinging," Dr. Fleischer says.

Increased itching was also more common in the pimecrolimus group. The cutaneous side effect differences between treatment groups did not reach statistical significance, however.

Patient preference Dr. Fleischer notes that calcineurin inhibitors should be considered for other conditions requiring long-term treatment, including alopecia areata, chronic cutaneous lupus and vitiligo; for psoriasis, combined with vitamin D analogs, with or without corticosteroids; for hand eczema, with or without corticosteroids; and for seborrheic dermatitis with an antifungal.

While tacrolimus is more effective, some patients may not accept use of an ointment on certain areas such as the scalp, or at certain times of the day. Therefore, pimecrolimus is an equally safe option and may increase compliance in patients preferring a cream. Additionally, patients can use pimecrolimus cream in the morning and reserve tacrolimus ointment for night use, if desired, Dr. Fleischer says.