Calcineurin inhibitors demonstrate versatility

March 1, 2005

Aruba — Along with improved safety over topical steroids, calcineurin inhibitors appear to offer relief for a variety of skin conditions including pruritus and psoriasis, especially in sensitive areas, according to Joseph F. Fowler, Jr., M.D., clinical professor, University of Louisville"s Division of Dermatology.

Aruba - Along with improved safety over topical steroids, calcineurin inhibitors appear to offer relief for a variety of skin conditions including pruritus and psoriasis, especially in sensitive areas, according to Joseph F. Fowler, Jr., M.D., clinical professor, University of Louisville's Division of Dermatology.

In the latter area, a recent study shows pimecrolimus (Elidel, Novartis) provides fairly rapid relief. The study includes more than 170 children ages 2 to 17. Half of the children were given pimecrolimus twice daily for seven days while the other half received a placebo.

"Within about three days of initiating treatment there was a significant difference between the pimecrolimus and the vehicle as far as improvement in itching. And that continued throughout the course of the study (US08 - data on file, Novartis, Inc.)," Dr. Fowler says.

European psoriasis study With respect to psoriasis, a small European study suggests oral doses of 40 mg or 60 mg daily may be effective. In particular, researchers tested these doses on a total of eight patients and found they achieved 60 percent and 75 percent improvement in Psoriasis Area and Severity Index (PASI) scores, respectively (Rappersberger K et al. J Invest Dermatol. 2002;119(4):876-87.).

The study, furthermore, found no significant changes in blood pressure between the two groups, nor any difference in blood lymphocyte subpopulations as measured by flow cytometry.

"It was a very small, limited study," Dr. Fowler observes. "So its findings will need to be confirmed with much larger studies."

Treating sensitive areas Both pimecrolimus and tacrolimus (Protopic, Fujisawa) have been shown to be very useful for treating psoriasis in sensitive skin areas such as the face and groin. One placebo-controlled, blinded study of tacrolimus 0.1 percent for psoriasis involving 167 adults with facial or intertriginous psoriasis found that after eight weeks' treatment, 65 percent of patients in the tacrolimus group achieved clear or almost clear status, versus 31 percent in the vehicle group (p<0.001; Lebwohl et al. J Am Acad Dermatol. 2004;51(5):723-30.).

By the same token, a blinded, vehicle-controlled study of pimecrolimus involving 57 patients with moderate to severe intertriginous psoriasis showed that after eight weeks, 71 percent of patients in the pimecrolimus group were clear or almost clear versus 21 percent in the vehicle group (p<0.001; Gribetz C. et al. J Am Acad Dermatol. 2004;51(5):731-738.).

"These drugs are very suitable for long-term use," Dr. Fowler adds. "That's where their strength lies, because if they have none of the potential side effects that topical steroids can have, both pimecrolimus and tacrolimus are safer in the long term."

Elidel Nevertheless, Elidel contains about 5 percent propylene glycol, which sometimes can cause allergic reactions when applied to the skin. To examine whether this would be the case, Dr. Fowler and his colleagues conducted a soon-to-be-published study involving patients whom they knew from previous studies were allergic to the chemical. After patch testing with small amounts of the cream, patients applied Elidel cream twice daily to the inside of their elbows for one week.

"We wanted to see if there was enough propylene glycol in Elidel cream to cause those people to have a skin reaction. Out of 20 that we tested, only three had a reaction, and all those were very mild, such as slight itching and redness. It showed that even if you think a person is allergic to propylene glycol, it's probably safe to use Elidel most of the time. We didn't expect too many people to have a problem with it, and this confirms that expectation, although it might be somewhat surprising to the general dermatologist who doesn't do as much with skin allergies," he says.