Lupus is not believed to arise from a single pathogenesis mechanism, and multiple factors—including high placebo response, presence of the disease in different parts of the body and prescribing excessive corticosteroids or immunosuppressive drugs—may further challenge the clinical trial pathway for SLE.7
Significant Improvements
Dr. Gottenberg tells The Rheumatologist that his group analyzed subgroups of SLE patients that could respond to epratuzumab, taking advantage of the variety of research data, including assessment of antibodies, in the EMBODY database. The team identified 113 patients (13% of the EMBODY SLE population) whose medical history included a diagnosis of Sjögren’s and who were positive for the anti-SS-A/Ro extractable nuclear antigen, linked to both SLE and SLE associated with Sjögren’s.
Their analysis found a higher proportion of SLE patients with Sjögren’s who received epratuzumab responded to treatment according to the BILAG-Based Composite Lupus Assessment (BICLA) of disease activity, which draws on the British Isles Lupus Assessment Group disease activity index.8 Results also included a 30–40% reduction in the number of B cells in the blood. “For the first time, a significant improvement was observed for a subset of SLE patients treated with epratuzumab,” he says, emphasizing this study was a post-hoc analysis. “This is an interesting result, pointing to a general strategy of treating lupus or Sjögren’s syndrome by targeting B cells,” he says.
“There is a need to confirm the results via randomized controlled trials,” Dr. Gottenberg says. He is unaware of any trials underway to examine the effectiveness of epratuzumab.
A recent summary of seven clinical trials investigating the efficacy and safety of epratuzumab in SLE underscores opportunities for subgroups, such as Sjögren’s patients, as well as the need for further research to explore other potential subgroups that might respond.9 Another open trial study of epratuzumab in primary Sjögren’s produced similar effects—including a 30% reduction in B cell count and clinical improvements in disease, although it only involved 16 patients.10
The data suggest that epratuzumab may have clinical benefits in certain subsets of SLE patients, pointing to the importance of patient stratification for research in this area. “We may find other subgroups of lupus patients where targeting B cells may be useful,” Dr. Gottenberg said. Small and preliminary studies targeting different subgroups could show positive results whereas big lupus trials with mixed patient populations tend to produce negative results and disappointment. There may also be implications for primary Sjögren’s, as well.
The key message for rheumatologists, Dr. Gottenberg says, is that B cells remain a relevant target in autoimmune diseases.
