Tuesday, September 30, 2008

SLE: From the Clinic to New Treatments

Here's a layman's interpretation of an SLE presentation given at the 2008 European League Against Rheumatism (EULAR) Conference in Paris. The presentation concentrated on two major themes, one of which was B-cell-directed therapies in SLE. Here are just two of the drugs highlighted in the session:

1) Epratuzumab (drug name LymphoCide) - "shows promise for the treatment of SLE."

How it works:

Epratuzumab is a monoclonal antibody directed against CD22, a molecule present on the surface of B-cells, which are a type of White Blood Cell (WBC) responsible for protecting the body against infections. It binds to cells that express the CD22 molecule on their surface and results in cell death. It is now being tested in a number of worldwide trials in the treatment of lymphomas, leukemias and some immune diseases, such as lupus, or other diseases that involve abnormal B-cells.

LymphoCide is a humanized monoclonal antibody and is less likely to cause allergic reactions when compared with other monoclonal antibodies, including Rituximab that contains very small amounts of protein sequences from mice.

Test Results:

Patients in both epratuzumab groups had greater reductions in disease activity from weeks 4 through 48, compared with those receiving placebo. Overall efficacy was most consistent in the epratuzumab 360-mg/m2 group. Epratuzumab-treated patients used less corticosteroid than placebo-treated patients over 24 weeks. All very good news!

2) Mycophenolate (drug name Cellcept) - "results in improvement of lupus disease activity"

How it works:

Mycophenolatae belongs to a class of medications known as immunosuppressives. This medication was used originally in the management of patients with organ transplants, but is now recommended in the treatment of some autoimmune diseases. It targets an enzyme in the body called inosine monophosphate dehydrogenase that is important for the formation of DNA in cells. By interfering with DNA, the medication impairs function of immune system cells that become overactive in autoimmune diseases such as lupus. It's also been used to treat people with rheumatoid arthritis, vasculitis, inflammatory bowel disease such as Crohn's disease, and some other kidney or skin disorders.

Test Results:

In a 24-week phase 2 trial of 140 patients with active lupus nephritis, induction therapy with oral mycophenolate mofetil was superior to monthly intravenous cyclophosphamide. (CYC, used to treat various types of cancer, is a chemotherapy drug that works by slowing or stopping cell growth.) All patients received oral prednisone at doses of up to 60 mg/ day.

104 of 185 patients responded to MMF, compared to 98 of 185 patients who responded to intravenous CYC. Some patients also achieved remission of lupus nephritis disease activity: 54 of 182 patients treated with MMF, compared to 45 of 181 patients treated with intravenous CYC. Both drugs resulted in improvement of lupus disease activity, and future results of this trial should be most interesting.

Conclusion:

Clinical experience with B-cell-directed therapies in SLE continues to be encouraging and suggests that subsets of patients with SLE may respond to this treatment approach. However, clinical trials reported to date have been either of inadequate design (open-label, uncontrolled, or with an inadequate primary efficacy endpoint) or flawed by interruptions in medication supply to determine therapeutic efficacy adequately. Additional randomized, double-blind, placebo-controlled clinical trials of B-cell-directed therapies are needed to confirm the clinical utility of this approach to treating SLE.

Medscape 9/25/08, Jonathan Kay, MD, FACP, FACR Disclosures

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