New data from an open-label extension ( SL0008 ) of the EMBLEM phase 2b study evaluating the long-term effects of Epratuzumab treatment in adult patients with moderate-to-severe systemic lupus erythematosus ( SLE ) were presented. The primary outcome of the open-label extension was to assess the safety of Epratuzumab in patients with SLE.

Relative to the 12 week, double-blind, placebo-controlled EMBLEM study, data from the open-label, long-term extension identified no new safety or tolerability signals. In addition, relative to EMBLEM baseline values, secondary outcome data indicated that the efficacy of Epratuzumab as measured by reduction in disease activity was maintained over two years. Secondary outcome data also indicated that relative to EMBLEM baseline values, treatment over two years with Epratuzumab was associated with decreases in corticosteroid use in patients receiving greater than 7.5 mg/day.

Epratuzumab is an investigational medicine and the first CD-22/B-Cell receptor ( BCR ) targeted monoclonal antibody to be evaluated in clinical studies for the treatment of systemic lupus erythematosus.

EMBLEM was designed to identify a suitable dosing regimen for Epratuzumab. A total of 227 patients with moderate-to-severe systemic lupus erythematosus received either: placebo, Epratuzumab cumulative dose of 200 mg ( 100 mg every other week ), 800 mg ( 400 mg every other week ), 2400 mg ( 600 mg weekly ), 2400 mg ( 1200 mg every other week ) or 3600 mg ( 1800 mg every other week ).
In the open-label extension 203 patients from any arm of the EMBELM study received 1200 mg Epratuzumab at weeks 0 and 2 of 12-week cycles.

Exposure to Epratuzumab was a median 845 days over a median 10 treatment cycles. Adverse events caused discontinuation in 29 ( 14.3% ) patients. The most common serious adverse reactions were SLE flare ( 3.4% ), lupus nephritis ( 2% ) and symptomatic cholelithiasis ( 1.5% ).
The most common infections/infestations were urinary tract infection ( 24.6% ) and upper respiratory tract infection ( 23.2% ). There were no opportunistic infections and no patterns of specific serious or severe infections.

Evaluation of long-term efficacy of Epratuzumab as measured by reduction in disease activity in patients with moderate-to-severe SLE

Secondary outcome measures in SL0008 included efficacy as measured by reduction in disease activity, and assessed by: British Isles Lupus Assessment Group ( BILAG ) improvement, SLE disease activity index ( SLEDAI ) score, Physician Global Assessment ( PGA ) score and combined treatment response defined as BILAG improvement without worsening, no SLEDAI worsening and no PGA worsening, relative to EMBLEM baseline.
The median BILAG total score was 25.0 at EMBLEM baseline and 9.0 at week 108. The score was 14.0 at SL0008 screening. Median SLEDAI score was 12.0 at EMBLEM baseline and 4.0 at week 108. The score was 10.0 at SL0008 screening. The median PGA score was 50.0 at EMBLEM baseline and 17.5 at week 108 with a score of 31.0 at SL0008 screening.
The proportion of patients achieving the combined treatment response was 32.5% at SL0008 screening ( n=203 ) and 60.3% at week 108 ( n=116 ).

Effect of corticosteroid use of long-term Epratuzumab treatment in patients with moderate-to-severe SLE

Corticosteroid doses were monitored throughout SL0008 and was a secondary outcome measure. Median corticosteroid dose at EMBLEM baseline and SL0008 screening was 10.0 mg/day. At week 116, this was 5 mg/day ( n=112 ). Data indicated that treatment over two years with Epratuzumab was associated with decreases in corticosteroid use in patients receiving greater than 7.5 mg/day with a corresponding increase in the proportion of patients receiving lower doses or no longer receiving corticosteroids.
The proportion of patients requiring 7.5-20 mg/day and greater than 20 mg/day decreased ( 49.8% and 10.8% at baseline and 33.9% and 8.0% respectively, at week 116 ) and the proportion of patients receiving greater than 0–7.5mg/day or no longer receiving corticosteroids increased ( 33.5% and 5.9% at baseline and 45.5% and 12.5% respectively, at week 116 ).

Assessment of immunological parameters to long-term Epratuzumab treatment

Secondary outcome measures in SL0008 also assessed the long-term effect of Epratuzumab treatment on B-cells and other immunological parameters.
Median absolute B-cell count decreased by 50% at week 112, compared to EMBLEM baseline. CD22 expression on B-cells remained low relative to EMBLEM baseline throughout SL0008. No consistent trends were seen in median T cell counts, which remained similar to EMBLEM™ baseline at week 112 and no consistent trends were observed for IgG or IgA which remained within normal levels. IgM levels decreased slightly ( -0.21 g/L by week 112 ).
At week 48, there was little correlation between BILAG improvement rate and B-cell levels. The moderate reduction in B-cell counts and the lack of correlation supports B-cell modulation rather than depletion as a mode of action for Epratuzumab.


Systemic lupus erythematosus or lupus, is a complex, systemic, autoimmune disease that affects many different organ systems, including the skin, joints, lungs, kidneys and blood. Disease activity and rate of progression of organ system damage is highly variable. Systemic lupus erythematosus affects from 20 to 70 people per 100,000 population, and is rare in childhood. It is 10 times more common in women than men.

Source: European League Against Rheumatism ( EULAR ) Congress, 2013

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