Background/Purpose: The EMBODY 1 (SL0009; NCT01262365) and EMBODY 2 (SL0010; NCT01261793) phase 3 studies investigated the efficacy and safety of epratuzumab (Emab; Immunomedics Inc), a CD22-targeted monoclonal IgG1 antibody, in patients (pts) with systemic lupus erythematosus (SLE).¹ The studies showed no significant difference from placebo (PBO) in any of the primary/secondary outcome measures, although B cell-specific immunological activity and a favourable safety profile were demonstrated. An analysis of the subset of pts with secondary Sjögren’s syndrome (sSjS) is of special interest due to the pathogenic role of B cells in primary SjS.

Methods: In EMBODY 1 & 2, adult pts with moderately to severely active SLE were randomized to PBO or 1 of 2 dosing regimens of Emab (both received a cumulative dose of 2400 mg Emab delivered over the first 4 weeks [wks] of each of four 12-wk treatment cycles), with the primary endpoint measured at Wk 48.¹ This post-hoc analysis included pts with an additional diagnosis of sSjS who were SS-A positive at baseline. Biological markers (B cells, IgG/IgM, SS-A), primary/secondary outcome measures of SLE disease activity (BICLA, BILAG, PhGA) and overall safety were assessed.¹ For BICLA, missing data were imputed using modified non-responder imputation with p values calculated using logistic regression with factors for treatment, pooled region and baseline disease status. For BILAG and PhGA missing values were imputed using last observation carried forward and p values calculated using ANCOVA adjusted for baseline, region and baseline disease severity.

Results: Across both studies, 170 (11%) SLE pts had sSjS in their medical history; of these, 112 pts (40 PBO, 72 Emab) were SS-A positive at baseline and were included in this analysis. Demographics/disease characteristics did not differ between groups (Table A). A higher proportion of Emab pts achieved a BICLA response at Wks 24 and 48 compared with PBO (Table B). Similarly, reductions from baseline in BILAG total score were numerically greater for Emab than PBO pts at both time points. PhGA did not differ significantly between the two groups; both PBO and Emab pts showed improvements from baseline. During treatment, B cells, IgM, and SS-A decreased in Emab but not PBO pts (Figure, and data not shown); no substantial changes were observed in other parameters including IgG, rheumatoid factor, SS-B. Emab appeared safe and well-tolerated with no difference in the frequency of adverse events from PBO.

Conclusion: In this post-hoc analysis, pts with SLE and sSjS treated with Emab showed improvements in SLE disease activity compared to PBO, with decreases in B cells and B cell-related biomarkers (IgM and SS-A). Further evaluation in a larger SjS population, using SjS-specific outcome measures, is necessary to assess the clinical relevance of the data. References: 1. Clowse MEB, Arthritis Rheumatol. 2015;67

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/epratuzumab-treatment-of-patients-with-systemic-lupus-erythematosus-and-secondary-sjogrens-syndrome-an-exploratory-analysis-of-phase-3-studies/