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Topical, Systemic Therapies Are on the Horizon for Lupus


 

WAIKOLOA, HAWAII — Keep an eye out for two promising novel therapies for cutaneous lupus—one topical, the other systemic—as they currently work their way through the drug developmental pipeline, Dr. David Fiorentino advised.

The topical agent is 0.5% R-salbutamol cream. Salbutamol, a ?2-agonist, is widely prescribed in an inhaled powdered formulation for the treatment of asthma and chronic obstructive pulmonary disease, Dr. Fiorentino said at the annual Hawaii dermatology seminar sponsored by the Skin Disease Education Foundation.

Dermatologists at Copenhagen University Hospital and Astion Pharma believed the drug had therapeutic potential in cutaneous lupus based on its anti-inflammatory effects, its ability to inhibit superoxide generation from stimulated granulocytes, and its inhibition of interleukin-2 and interferon-gamma release by stimulated T cells.

They found that twice-daily topical therapy showed greater efficacy in subcutaneous lupus erythematosus than in treatment-resistant discoid lupus erythematosus in their nine-patient open-label pilot study (Arch. Dermatol. 2007;143:1589-90).

Inhaled salbutamol is associated with mucosal irritation, tachycardia, and tremor.

Two lupus patients developed dermatitis after topical therapy, but there was no tachycardia or tremor despite twice-daily treatment of up to 2,000 cm2.

Topical salbutamol is slated for a phase III clinical trial this year, according to Dr. Fiorentino, a dermatologist at Stanford (Calif.) University.

“It would be really nice to have another topical therapy besides corticosteroids,” he said.

The systemic therapy is efalizumab (Raptiva), which is approved for the treatment of psoriasis.

Efalizumab is a humanized monoclonal antibody directed against the CD11a chain of leukocyte-functioning antigen. It blocks T-cell activation.

A growing body of anecdotal evidence suggests that this biologic is effective for treating discoid and subcutaneous lupus erythematosus refractory to conventional therapies.

Dermatologists at Leeds (England) General Infirmary reported that 12 of 13 patients with discoid lupus showed responses ranging from good to excellent after a mean of less than 6 weeks on efalizumab (Arch. Dermatol. 2007;143:873-7).

Dr. Fiorentino added that he, too, has used efalizumab off label and has found it “incredibly effective” in patients with subacute or discoid lupus.

He disclosed having interests in Genentech Inc.

Both the Skin Disease Education Foundation and RHEUMATOLOGYNEWS are wholly owned subsidiaries of Elsevier.

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