Psoriasis Maintenance Therapy with Nonsteroidal Agents Evaluated

BOCHUM, Germany, Sept. 18 -- For patients with intertriginous psoriasis, maintenance therapy with the topical drugs Elidel (pimecrolimus) or Dovonex (calcipotriol) may be as effective as topical corticosteroids with less risk of side effects, a study here suggested.

However, topical corticosteroids such as betamethasone should remain the treatment of choice for acute intertriginous psoriasis, said Alexander Kreuter, M.D., of the Ruhr University.

Betamethasone was significantly more effective than Elidel or Dovonex at reducing intertriginous psoriasis symptoms during short-term (four week) treatment, Dr. Kreuter and colleagues said in the September issue of Archives of Dermatology.

However, after 70 days of treatment, there was no significant difference in symptom scores among intertriginous psoriasis patients treated with Elidel, Dovonex, or betamethasone, the researchers said.

Because long-term use of topical corticosteroids like betamethasone are associated with side effects such as skin atrophy, irreversible striae, or adrenocortical suppression, the investigators reasoned that maintenance therapy with "less potent" agents such as Elidel and Dovonex might be safer.

Dovonex is an analogue of vitamin D₃. Elidel is a calcineurin inhibitor, which inhibits cytokine production in mast cells and T-lymphocytes. Previous studies have suggested both drugs are effective for treating intertriginous psoriasis, but none has directly compared them with corticosteroids in this setting, the investigators said.

The study included 80 adults with intertriginous psoriasis. They were randomized to treatment with one of the three drugs as well as a placebo group which received an emollient cream containing no active drug. Concentrations of the drugs were 1% for Elidel, 0.005% for Dovonex, and 0.1% for betamethasone.

Dr. Kreuter's study was supported by Novartis, maker of Elidel. Elidel is approved for atopic dermatitis as second-line therapy but is investigational for psoriasis.

After four weeks of treatment, betamethasone reduced psoriasis symptom scores by 84% (P<.001). In comparison, Elidel reduced symptoms by nearly 40% (P=.001) and Dovonex by about 62% (P<.001). In this phase of treatment, betamethasone was "clearly more effective," the authors said.

One a side note, the placebo emollient cream reduced symptoms by 21% (P=.008). The borderline effectiveness of the placebo "may not be explained by a placebo effect alone but underline the known beneficial effects of emollients in the treatment of psoriasis through increased hydration of the stratum corneum and keratolytic effects," the authors said.

From four weeks of treatment through the end of the 70-day study period, symptoms increased in all four study arms, though they remained significantly below baseline. By day 70, there was no longer a significant difference among the four groups, the authors said.

In the betamethasone group, the symptom score increased from 2.94 at week four to 9.65 at day 70. Over the same time period, symptom scores increased from 11.45 to 12.75 in the Elidel group, from 9.68 to 17.63 in the Dovonex group, and from 13.84 to 14.63 in the placebo group.

The study confirmed that corticosteroids are still the most effective topical approach for psoriasis, the authors said.

"However, their use in long-term management, particularly for the treatment of intertriginous areas, which are more prone to steroid adverse effects, is limited," they added.

"To combine the rapid anti-inflammatory effects of a topical corticosteroid with the favorable long-term effects and safety profile of pimecrolimus or calcipotriol, short-term application of topical corticosteroids for acute disease followed by maintenance treatment with one of these agents seems to be a reasonable approach in the treatment of intertriginous psoriasis," they concluded.

No serious events occurred during the study. However, five patients (25%) in Elidel reported an increase in itching and burning shortly after application. The effect lasted for two weeks. Two patients in the Dovonex group reported an increase in erythema, warmth, and irritation which also resolved after two weeks.

On Jan. 19, 2006, the FDA issued a warning about Elidel. Animal studies and post-marketing surveillance indicate the drug might be linked to cases of cancer, particularly lymphoma, and particularly in young children, the FDA said.

Elidel should not be used in children younger than two, the FDA cautioned. It should be used only as a second-line agent, and then "only for short periods of time, not continuously," the agency advised in a statement. The drug is approved for treating atopic dermatitis, not psoriasis.