Trial opens door to topical-only psoriasis therapy: COBRA enrolled nearly 2,500 patients.

WAIKOLOA, HAWAII -- Clobetasol propionate spray 0.05% resulted in dramatic clinical improvement with a low rate of adverse events and excellent acceptance in patients with moderate to severe generalized psoriasis in the largest community-based trial ever conducted in psoriasis.

Results of the 2,488-patient Clobex Spray Community-Based Research Assessment (COBRA) trial advance psoriasis therapy to the threshold of a breakthrough era, said Dr. John Koo at the annual Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation. For patients with moderate to severe generalized disease, there is now the prospect of entirely topical short-term and maintenance therapy that's practical and offers absolute systemic safety.

"I'm glad that we have the biologics and that things are becoming safer with methotrexate and cyclosporine, but at the same time many of us don't really want to have to think about demyelinating diseases, tuberculosis, cancer, lymphoma, hemolytic anemia, vaccination issues, and so forth," said Dr. Koo, who is professor and vice chairman of the department of dermatology and director of the psoriasis treatment center at the University of California, San Francisco.

COBRA was an open-label study conducted at 455 U.S. sites. Participants received clobetasol propionate spray 0.05% (Clobex) twice daily for 4 weeks. The efficacy evaluation involved 1,254 patients with moderate to severe plaque psoriasis treated with clobetasol spray as monotherapy and 731 others with more treatment-resistant disease who received it as add-on therapy. Participants had a 14-year mean duration of psoriasis. Dr. Koo drew particular attention to the mean 11% body surface area involvement at baseline.

COBRA included 183 of the evaluable 1,254 patients who received clobetasol spray as add-on therapy because they did not respond adequately to a biologic agent. The other common ongoing treatments alone or in various combinations were topical calcipotriene, non-class-1 topical steroids, and oral antipsoriatic agents.

"Physicians don't usually think about using topical medications for patients with more than 10% body surface area affected. Anything more than 10% qualifies for inclusion in biologic studies. But this is a spray. Patients can cover a large area very quickly," the dermatologist noted.

The COBRA trial did not utilize the familiar Psoriasis Area and Severity Index (PASI) scores widely reported in randomized clinical trials. Since COBRA was conducted in real-world clinical practice settings, Dr. Koo and the rest of the steering committee felt PASI determinations would be too time consuming for busy private-practice dermatologists.

COBRA instead relied upon two alternative measures of effectiveness. Treatment success on a target plaque severity measure was defined as clearing, near clearing, or at least a 2-point improvement on a 6-point severity scale. This was achieved at week 2 in 60% of those on clobetasol monotherapy and in 59% who received the superpotent topical steroid spray as add-on therapy. After 4 weeks, the success rate was 80% in both populations.

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On the target plaque severity scale, success rates at week 4 for clobetasol spray as add-on therapy were 76%-84%.

The other outcome measure was physician global assessment of improvement. Success required a rating of clear or almost clear on whole body assessment. This was achieved in 30% of the monotherapy group and 27% of the add-on treatment group at week 2, and in 69% of monotherapy and 62% of add-on therapy patients at week 4.

Seventy-five percent of participants were reported by their physicians as being very satisfied with their treatment at week 4, while another 19% were somewhat satisfied. Ninety-five percent of patients completed the study.

Among the 2,242 patients included in the safety analysis, one-quarter to one-third experienced treatment-related erythema, stinging/burning, dryness, or peeling/scaling, but these side effects were rated severe in less than 1% of cases.

Dr. Koo stressed that twice-daily clobetasol spray is approved for up to 1 month at a time and can safely be repeated after a month off. Pathologic suppression of the hypothalamic-pituitary-adrenal (H-P-A) axis becomes an issue only with longer daily treatment.

Month-on/month-off daily clobetasol spray repeated indefinitely appears to avoid problems with H-P-A axis suppression while essentially eliminating the need for systemic therapy. For the isolated plaques that don't clear with the superpotent steroid spray or that flare during the month-long holiday, one promising option is targeted supraerythemogenic 308-nm UVB laser phototherapy, which will become a lot more practical later this year when Photo Medex releases a new machine with twice the power of its current XTRAC Ultra excimer laser, according to Dr. Koo.

Dr. Koo is on the scientific advisory board of Galderma, which sponsored the COBRA trial. He is also a consultant to PhotoMedex, Abbot, Amgen, Biogen, Bristol-Myers Squibb, Centacor, Connetics, Eisai, Fujisawa, Genentech, Novartis, Serono, Teikoku, Valeant, and Warner-Chilcott.

SDEF and this news organization are wholly owned subsidiaries of Elsevier.

BY BRUCE JANCIN

Denver Bureau Patients Successfully Treated With Clobetasol Propionate Spray for Psoriasis

Add-on therapy Monotherapy

(n = 731) (n = 1,254) Week 2 59% 60% Week 4 80% 80% Note: Based on a target plaque severity measure on a 6-point scale. Source: Dr. Koo Note: Table made from bar graph.