Belimumab with Background Mycophenolate Shows Potential in Early, Diffuse Systemic Sclerosis

New York, NY—November 16, 2016

Systemic sclerosis (SSc) has the highest rates of morbidity and mortality of all rheumatic diseases. Patients suffering from this often debilitating, multi-system condition typically face a lifetime of symptom management with limited treatment options.

However, investigators from Hospital for Special Surgery and Weill Cornell Medical College in New York City have found potential efficacy using a medication currently approved to treat lupus. In a small randomized, placebo-controlled pilot trial, the human monoclonal antibody drug belimumab was found to be safe and possibly effective in treating SSc.

The findings – the first to assess the feasibility of belimumab therapy in SSc – were presented today at the American College of Rheumatology Annual Meeting in Washington, DC.

In the study, 20 patients with early, diffuse SSc of three years of duration or less were randomized to receive either intravenous lupus belimumab (Benlysta®), dosed at 10mg per kilogram of body weight, or a placebo. Both groups were administered background therapy with mycophenolate mofetil (CellCept®), dosed at 1000mg given orally twice a day.

The primary goal of this pilot study was to assess the safety and tolerability of the treatment as indicated by the number of adverse and serious adverse events, while also determining its potential efficacy based on a measure called the Modified Rodnan Skin Score (MRSS) after one year.

After randomization, one patient in each group was withdrawn from the study due to disease progression. In the remaining patients, no significant differences in the rates of adverse events were seen between groups; and although three serious adverse events were reported, they all occurred in the placebo group and were deemed unrelated to the study.

Though not reaching statistical significance, seven out of nine of the study subjects treated with belimumab saw at least a 20% improvement in their MRSS score, compared with just three out of nine in the placebo group.

"Our study was underpowered to show a definitive treatment effect of belimumab," says lead author Jessica K. Gordon, MD, rheumatologist at HSS. "However it was done so we could get an initial sense of whether or not this medication is safe in systemic sclerosis patients – which it appears to be – and also whether there might be findings suggesting efficacy."

As Dr. Gordon explains, abnormal activity in a form of white blood cells called B-cells is thought to play a role in SSc. A similar mechanism is involved in lupus, for which belimumab is an approved treatment.

"There are similarities in the immunologic alterations in SLE and SSc, so this is a reasonable consideration. Additionally, other approaches to inhibiting B-cell function have suggested benefit in SSc as well," says Robert Spiera, MD, senior author of the paper and rheumatologist at HSS.

A related study conducted by Drs. Gordon and Spiera and colleagues in collaboration with a team from Dartmouth – which will be presented as a poster at the ACR meeting - looked at gene expression profiles in skin biopises from the same  two patient groups.

They found that in patients in the belimumab group whose skin scores improved, there were decreases in the expression of certain genes associated with B-cell signaling; this was not the case in the placebo group and appears to reflect a pharmacologic effect of the medication.

"There are no FDA-approved treatments for scleroderma and these patients can suffer for many, many years," admits Dr. Gordon. "But these findings lay the foundation for larger and more definitive studies in this complex patient group."