Early disease patients were recruited because skin problems may regress in later stages, making it more difficult to assess whether therapy is working, says Dr. Gordon. This approach also addressed a desire to explore possibilities for prevention of disease progression, she says.
In addition to treatment with belimumab, the study design called for patients to receive a background therapy of mycophenolate mofetil, a drug commonly used to treat autoimmune diseases, says Dr. Gordon. In recent years, evidence for the use of mycophenolate in scleroderma has been increasing, suggesting it improves skin disease and stabilizes lung function—although its use is still considered off label, she says.
“We didn’t want to ask [patients] to just take placebo without any background therapy,” because study participants had active disease, explains Dr. Gordon.
After a wash-in period, patients were randomized to receive intravenous doses of 10 mg/kg of belimumab or placebo at two-week intervals for the first three doses and then at four-week intervals up to Week 48. They also continued with twice daily treatments of mycophenolate mofetil at 1,000 mg per dose and returned for final assessment at Week 52.
Most patients were female, which is representative of the condition, and on average had been symptomatic for less than one year. In this study, patients had severe widespread skin involvement, covering the trunk, thighs and upper arms, and a small percentage had significant interstitial lung disease, says Dr. Gordon.
“A significant portion of the patients were positive for the anti-RNA polymerase 3 antibody, which is an autoantibody in systemic sclerosis associated with rapidly progressive and severe skin disease,” notes Dr. Gordon.
Results
Researchers found no significant difference in the number of adverse events between the groups, with 53 in the belimumab group and 56 in the placebo group.
Dr. Gordon says this was the first time these patients had been exposed to belimumab, and the results indicate the safety profile was similar to what is seen in lupus treatment, meaning there were no unexpected adverse events.
“The safety profile was reassuring,” says Dr. Gordon, but she notes that “additional studies are needed to determine if belimumab has a role in the treatment of diffuse scleroderma.”
Among patients in the belimumab group, there was a trend toward greater improvement in skin thickness based on the MRSS, but there was no significant difference in the median score compared with the placebo group, meaning the primary efficacy endpoint was not met. Additionally, patients with improved MRSS in the belimumab group had a significant decline in expression of B cell signaling and profibrotic genes and pathways not seen in the placebo group.
