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After randomization, one patient in each group was withdrawn from the study due to disease progression.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."
About HSS | Hospital for Special Surgery
HSS is the world’s leading academic medical center focused on musculoskeletal health. At its core is Hospital for Special Surgery, nationally ranked No. 1 in orthopedics (for the ninth consecutive year) and No. 3 in rheumatology by U.S.News & World Report (2018-2019). Founded in 1863, the Hospital has one of the lowest infection rates in the country and was the first in New York State to receive Magnet Recognition for Excellence in Nursing Service from the American Nurses Credentialing Center four consecutive times. The global standard total knee replacement was developed at HSS in 1969. An affiliate of Weill Cornell Medical College, HSS has a main campus in New York City and facilities in New Jersey, Connecticut and in the Long Island and Westchester County regions of New York State. In 2017 HSS provided care to 135,000 patients and performed more than 32,000 surgical procedures. People from all 50 U.S. states and 80 countries travelled to receive care at HSS. In addition to patient care, HSS leads the field in research, innovation and education. The HSS Research Institute comprises 20 laboratories and 300 staff members focused on leading the advancement of musculoskeletal health through prevention of degeneration, tissue repair and tissue regeneration. The HSS Global Innovation Institute was formed in 2016 to realize the potential of new drugs, therapeutics and devices. The culture of innovation is accelerating at HSS as 130 new idea submissions were made to the Global Innovation Institute in 2017 (almost 3x the submissions in 2015). The HSS Education Institute is the world’s leading provider of education on the topic on musculoskeletal health, with its online learning platform offering more than 600 courses to more than 21,000 medical professional members worldwide. Through HSS Global Ventures, the institution is collaborating with medical centers and other organizations to advance the quality and value of musculoskeletal care and to make world-class HSS care more widely accessible nationally and internationally.