New and emerging therapies

San Francisco

- While all doctors face the challenge of wanting to be on the cutting edge, it’s important to think about evidence-based support for therapies, says Joseph L. Jorizzo, M.D., professor and founding chairman, department of dermatology, Wake Forest University School of Medicine, Winston-Salem, N.C.

Dr. Jorizzo gave selected examples of new and emerging therapies for autoimmune and connective tissue diseases Sunday at the 67th Annual Meeting of the American Academy of Dermatology here.

Patients often have the expectation that doctors are going to solve all of their problems quickly, he says, but doctors need to discipline themselves and use therapeutic ladders of appropriate treatments, depending on the severity of the disease.

"Once you get into systemic disease, you’re more likely to have double-blind, placebo-controlled studies," he says.

Experimental therapies for systemic lupus erythematosus, Dr. Jorizzo says, include interferon, UVA-1 (340 to 400 nm), bone marrow transplantation, autologous stem cell transplantation, extracorporeal immunomodulation, monoclonal antibodies and gene therapy.

Patients with dermatomyositis should be treated differently than patients with lupus, he says, with options that include systemic corticosteroids, low-dose methotrexate, azathioprine and IVIG. After two years, the majority of patients are on no systemic therapy, he says.

With non-ulcerative vasculitis, he says, "just spots on the ankle probably don’t require corticosteroids," but ulcerative lesions "are a much more significant problem." More severe diseases can require treatment with prednisone, azathioprine, cyclophosphamide, mycophenolate mofetil, chlorambucil, cyclosporine, TNF-alpha inhibitors, leflunomide or rituximab.

Other therapies include interferon and ribavarin, extracorporeal immunomodulation, high-dose IV immunoglobulin, and experimental therapies using recombinant cytokines, growth factors and thrombolytics.

Experimental therapies for scleroderma include thalidomide derivatives, TNF-alpha inhibitors, IVIG and targeted biological therapies, he says.

The cost of selected newer therapies, such as interferons, topical calcineurin inhibitors, bioengineered immunomodulators and immune globulin, for some conditions can range "from expensive to really expensive," Dr. Jorizzo notes.

Among interferon’s side effects, "Flu-like symptoms are huge," he says, and depression frequently occurs. Still, "The No. 1 side effect is probably the cost."

Tacrolimus and pimecrolimus are useful topically for the treatment of inflammatory dermatoses, "but the problem is, you have to deliver the drug to the site of the pathology," Dr. Jorizzo says. Some "interesting" off-label uses include the treatment of oral and genital lichen planus, he says.

A handful of recent reports of progressive multifocal leukoencephalopathy have been linked to the use of Raptiva (Genentech), he notes. The drug now carries a boxed warning label. DT