Background/Purpose:

Epratuzumab is a monoclonal antibody targeting CD22. Improvements in health-related quality of life (HRQoL) with epratuzumab in patients with systemic lupus erythematosus (SLE) have been reported in the ALLEVIATE trials from week 12 and sustained to 4 years.^1,2 In the EMBLEM™ study (dose-ranging phase IIb randomized controlled trial [RCT] in SLE), epratuzumab treatment resulted in clinically relevant improvements in SLE disease activity.³  We report HRQoL data from EMBLEM^TM and its open-label extension (OLE) (NCT00660881).

Methods:

In EMBLEM^TM patients with moderate-to-severely active SLE (≥1 BILAG 2004 A or ≥2 Bs) were randomized to 1 of 6 intravenous regimens over 12 weeks added to standard of care (SOC): placebo (PBO) or cumulative dose (cd) epratuzumab (200, 800, 2400 or 3600 mg in equal divided doses using 2 every other week [EOW] infusions or 2400 mg cd as 600 mg every week [QW]). Patients from any EMBLEM^TM arm completing 12 weeks blinded treatment and those who discontinued due to lack of efficacy but completed ≥8 weeks were eligible to enter the OLE where all patients received 1200mg epratuzumab at weeks 0 and 2 of repeating 12-week cycles. Short Form-36 (SF-36) Version 2.0 was used to assess HRQoL. Data are reported to the end of EMBLEM^TM and to weeks 48 and 108 of the OLE (week 108 is last time-point when ≥ 50% of patients reported SF-36 data). Mean changes and % pts 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.  Observed case analyses are presented for the OLE.

Results:

In EMBLEM^TM mean SF-36 PCS, MCS and domain scores across epratuzumab and placebo groups (both receiving background SOC) generally increased over time from baseline through week 12, with greater increases in the PBO group. Longer treatment with epratuzumab during OLE resulted in clinically meaningful changes in HRQoL vs EMBLEM baseline (Table).  At week 108 in the OLE 70.8% and 59.3% of patients reported improvements ≥ MCID in PCS and MCS scores.

Conclusion:

In the 12 week EMBLEM^TM study treatment period no differences in improvements in HRQoL were observed with epratuzumab, which may be attributed to short term treatment, small sample sizes and active background (SOC) therapy.  Nonetheless, over a greater length of time sustained improvements were observed in the EMBLEM^TM OLE, which are consistent with those in the ALLEVIATE RCTs.^1,2

References:

1. Strand V. et al. ACR 2008; 2. Strand V. et al. Rheumatology in Press 3. Wallace DJ. et al. Ann Rheum Dis, Online First 12 January 2013. DOI: 10.1136/annrheumdis-2012-202760.