Efficacy of Epratuzumab, an Anti-CD22 Monoclonal IgG Antibody, in Systemic Lupus Erythematosus Patients With Associated Sjögren's Syndrome: Post Hoc Analyses From the EMBODY Trials

Abstract

Objective: EMBODY 1 (ClinicalTrials.gov identifier: NCT01262365) and EMBODY 2 (ClinicalTrials.gov identifier: NCT01261793) investigated the efficacy and safety of epratuzumab, a CD22-targeted humanized monoclonal IgG antibody, in patients with systemic lupus erythematosus (SLE). The studies showed no significant difference from placebo in primary or secondary clinical outcome measures but did demonstrate B cell-specific immunologic activity. The aim of this post hoc analysis was to determine whether epratuzumab had a different clinical efficacy profile in SLE patients with versus those without an associated diagnosis of Sjögren's syndrome (SS).

Methods: The efficacy and safety of epratuzumab were compared between 2 patient subpopulations randomized in EMBODY 1 and 2: SLE patients with and those without a diagnosis of associated SS. British Isles Lupus Assessment Group (BILAG) total score, BILAG-based Combined Lupus Assessment (BICLA) clinical response to treatment, biologic markers (including B cells, IgG, IgM, and IgA), and safety were assessed.

Results: A total of 1,584 patients were randomized in the EMBODY 1 and EMBODY 2 trials; 113 patients were anti-SSA positive and had a diagnosis of associated SS, and 1,375 patients (86.8%) had no diagnosis of associated SS (918 patients were randomized to receive epratuzumab and 457 to receive placebo). For patients with associated SS, but not those without associated SS, a higher proportion of patients receiving epratuzumab achieved a BICLA response and a reduction from baseline in BILAG total score. B cell reduction was faster in patients with associated SS. The sensitivity of B cells to epratuzumab as measured by the mean concentration producing 50% of the maximum B cell count depletion was lower for patients with associated SS (9.5 μg/ml) versus the total EMBODY population (87.1 μg/ml). No difference in the frequency of adverse events in those receiving placebo was reported.

Conclusion: Patients with SLE and associated SS treated with epratuzumab showed improvement in SLE disease activity, which was associated with bioactivity, such as decreases in B cell number and IgM level.

Figure 1

A–D, British Isles Lupus Assessment Group (BILAG)–based Combined Lupus Assessment (BICLA) response rate (A), change in total BILAG score from baseline (B), change in physician's global assessment (PGA) from baseline (C), and change in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) from baseline (D) in SLE patients without associated Sjögren's syndrome (SS; non‐aSjS patients) receiving placebo or epratuzumab (Emab). E–H, BICLA response rate (E), change in total BILAG score from baseline (F), change in PGA from baseline (G), and change in SLEDAI from baseline (H) in SLE patients with associated SS receiving placebo or epratuzumab. Analyses were conducted using the full analysis set. Values are the median percent change from baseline. For total BILAG score, PGA, and SLEDAI, statistical testing was conducted only at weeks 24 and 48. Nonresponder imputation was used for the BICLA response. The last observation carried forward method was used to impute missing values for the total BILAG score, PGA, and SLEDAI. Light asterisk = P < 0.05 for epratuzumab 1,200 mg every other week (QOW) versus placebo; dark asterisk = P < 0.05 for epratuzumab 600 mg every week (QW) versus placebo.

Figure 2

A and B, Percentage change from baseline in CD19+ cells from patients with systemic lupus erythematosus (SLE) without associated Sjögren's syndrome (SS; non‐aSjS patients) (A) and patients with SLE with associated SS (B) receiving placebo or epratuzumab (Emab). C, Pharmacokinetics/pharmacodynamics modeling of B cell reduction following intravenous epratuzumab. Dotted lines represent the 5th, 25th, 75th, and 95th percentiles, respectively, of the observed epratuzumab average steady‐state plasma drug concentration during multiple‐dose administration; broken line represents the 50th percentile. The shaded area shows the 95% confidence interval based on 500 bootstrap sampling with replacement available for all the “All data” model only. QOW = every other week; QW = every week. Color figure can be viewed in the online issue, which is available at http://onlinelibrary.wiley.com/doi/10.1002/art.40425/abstract.

Figure 3

A and B, Median percent change from baseline in IgM (A) and IgG (B) serum concentrations in patients with systemic lupus erythematosus (SLE) without associated Sjögren's syndrome (SS; non‐aSjS) receiving placebo or epratuzumab (Emab). C and D, Median percent change from baseline in IgM (C) and IgG (D) serum concentrations in patients with SLE with associated SS receiving placebo or epratuzumab. Analyses were conducted using the full analysis set and observed data. Values are the median (25th–75th percentile) percent change from baseline. QOW = every other week; QW = every week. Color figure can be viewed in the online issue, which is available at http://onlinelibrary.wiley.com/doi/10.1002/art.40425/abstract.

Figure 4

A and B, Mean change from baseline in anti‐SSA (A) and anti‐SSB (B) in patients with systemic lupus erythematosus (SLE) without associated Sjögren's syndrome (SS; non‐aSjS) receiving placebo or epratuzumab (Emab). C and D, Mean change from baseline in anti‐SSA (C) and anti‐SSB (D) in patients with SLE with associated SS receiving placebo or epratuzumab. Analyses were conducted using the full analysis set and observed data. Values are the mean (95% confidence interval) change from baseline. QOW = every other week; QW = every week. Color figure can be viewed in the online issue, which is available at http://onlinelibrary.wiley.com/doi/10.1002/art.40425/abstract.