OBJECTIVES: Improvements in health-related quality of life (HRQoL) with epratuzumab (a monoclonal antibody targeting CD22) have been reported in patients with systemic lupus erythematosus (SLE) in the ALLEVIATE trials from Week 12 to 4 years. In the EMBLEM™ dose-ranging, phase IIb, randomized controlled trial in SLE, epratuzumab resulted in clinically-relevant improvements in disease activity.  We report HRQoL data from EMBLEM™ and its open-label extension (OLE). METHODS: In EMBLEM™, patients with moderate-to-severe  SLE (≥1 BILAG 2004 A or ≥2 Bs) were randomized to placebo (PBO) or epratuzumab (cumulative dose [cd] 200, 800, 2400 or 3600mg divided every other week, or 600mg every week), plus standard of care (SOC). Patients who completed 12 weeks or discontinued due to lack of efficacy after ≥8 weeks were eligible for OLE (1200mg epratuzumab at Weeks 0,2 of 12-week cycles). HRQoL was assessed using Short Form-36 (SF-36) v2.0. Data are reported to the end of EMBLEM™ and OLE Weeks 48 and 108. Mean changes and % patients reporting improvements ≥minimum clinically important differences (MCID) (increases from baseline ≥5.0-points in domain and ≥2.5-points in physical and mental component scores [PCS and MCS]) are presented. RESULTS: Mean PCS and MCS scores across all groups increased from baseline through EMBLEM™ Week 12, with greater increases in the PBO group. Longer epratuzumab treatment during OLE resulted in clinically meaningful changes in HRQoL vs EMBLEM™ baseline. Mean PCS/MCS scores were 34.2/36.1, 38.7/40.0, 40.1/41.6 and 40.5/40.9 at EMBLEM™ baseline, OLE screening, Week 48 and Week 108, respectively. At OLE Week 108 70.8% and 59.3% of patients reported improvements ≥MCID in PCS and MCS scores.  CONCLUSIONS: No differences in improvements in HRQoL were observed with epratuzumab during EMBLEM™, potentially due to short term treatment, small sample sizes and active SOC therapy.  Sustained improvements were observed in the EMBLEM™ OLE, consistent with those in the ALLEVIATE RCTs.