Epratuzumab improved systemic lupus erythematosus disease activity among patients with associated Sjögren's syndrome, an effect not seen among patients without an associated diagnosis of Sjögren's syndrome.
The study was a post-hoc analysis of two identical phase 3, randomized, placebo-controlled, double-blind, multicenter trials —EMBODY 1 and 2 — which evaluated the efficacy and safety of epratuzumab for moderate to severe systemic lupus erythematosus (SLE). According to the researchers, the trials found no statistically significant difference in response rates at week 48 between epratuzumab- and placebo-treated patients. However, the researchers reported changes in immunological parameters among epratuzumab-treated patients, including a reduction of peripheral B cells.
“A subset of SLE patients enrolled into the EMBODY trial were diagnosed with [associated Sjögren's syndrome], according to their medical history,” Jacques-Eric Gottenberg, MD, PhD, of Strasbourg University Hospital, in France, and colleagues wrote. “Since B cells have been implicated in the pathogenesis of [Sjögren’s syndrome] and epratuzumab has shown efficacy in a small open trial of primary [Sjögren’s syndrome] patients, the objective of this post-hoc analysis was to determine whether epratuzumab demonstrated a different clinical efficacy profile in SLE patients with an associated diagnosis of [Sjögren’s syndrome].”
The researchers compared the efficacy and safety of epratuzumab between patients with SLE and associated Sjögren’s syndrome and those with SLE without Sjögren’s syndrome. Among the 1,584 patients randomized in the two trials, 133 were positive for anti-Sjögren's-syndrome-related antigen-a and had been diagnosed with associated Sjögren’s syndrome. The remaining 1,375 patients did not have associated Sjögren’s syndrome, of whom 918 had been randomly selected to receive epratuzumab. The researchers evaluated patients using the British Isles Lupus Assessment Group (BILAG) Index and the BILAG-Based Composite Lupus Assessment (BICLA), as well as biologic markers such as B cells, immunoglobulin G, immunoglobulin M and immunoglobulin A.
According to the researchers, a greater proportion of patients with associated Sjögren’s syndrome who received epratuzumab reported a BICLA response as well as a reduction in BILAG score from baseline. In addition, B-cell reduction occurred faster in patients with associated Sjögren’s syndrome. B-cell sensitivity to epratuzumab was lower for patients with associated Sjögren’s syndrome, compared with the combined population of the two trials. The researchers recorded no difference in the frequency of adverse events between patients who received placebo and those treated with epratuzumab.
“Patients with SLE and [associated Sjögren’s syndrome] treated with epratuzumab showed improvements in SLE disease activity compared with placebo, which was not observed in patients without [associated Sjögren’s syndrome],” Gottenberg and colleagues wrote. “B-cell numbers, [immunoglobulin M] and [anti-Sjögren's-syndrome-related antigen-a] levels were consistently reduced in all patient populations receiving epratuzumab; however, B-cell reduction was faster in the [associated Sjögren’s syndrome] patient population. These data suggest that epratuzumab may have clinical benefits in certain subsets of SLE patients and so stratification of SLE patients may be appropriate.” – by Jason Laday
Disclosure: The researchers report funding from UCB Pharma.