Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement

The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.


Rituximab Therapy Induces Durable Remissions in Hispanic and African American Patients with Refractory Systemic Lupus Erythematosus (SLE)

Karpouzas1,  George A., Gogia1,  Maneesh, Moran1,  Rosalinda C., Hahn2,  Bevra H.

Harbor-UCLA Medical Center, Torrance, CA
David Geffen School of Medicine at UCLA, Los Angeles, CA

Purpose:

Autoreactive B cells produce pathogenic autoantibodies (Ab) that deposit in tissues and cause injury in patients (pts) with SLE. While combinations of antimalarials, corticosteroids and immunosuppressives may control disease activity in most pts, about 10% suffer recalcitrant disease. Rituximab is a chimeric monoclonal Ab that eliminates B cells through binding of CD20 surface antigen. We evaluated the ability of Rituximab (RTX) to induce sustained remission in minority pts with refractory SLE.

Methods:

We studied 35 pts with refractory SLE between 1/1/06 and 6/30/08. Subjects were given 4 weekly infusions of RTX monotherapy at 375mg/m2. All had regular follow-up in a single academic center. Disease activity was measured with SLEDAI-2k every 3 months. Responses were reported in quarterly intervals and analyzed with paired t-tests.

Results:

Thirty five pts received 1 cycle and 7 received a 2nd cycle within 9±2.4 months (mo) after the 1st infusion. Depletion of CD19+ cells was observed in all (p<0.001-table). Baseline SLEDAI-2k was 8.5±0.8, significantly decreased in the 1st quarter (4.4±0.5, p<0.0001), and remained so to the end of the observation period. This was associated with a significant increase in serum complements. Sixteen pts with arthritis were followed over 15.2±5.1 mo: 75% had initial complete resolution, and 56% had sustained response (SR>=6 mo). Time to SR was 3.6±1.9 mo and SR lasted 13.2±1.3 mo. Primary and 2dary efficacy failures were seen in 19% and 25% of pts respectively. All (100%) achieved 2dary SR within 3.6± 1.3 mo of rechallenge. Among 13 pts with nephritis and baseline proteinuria of 4.5±1.5 g/24h followed over 11.5±5.7 mo, 92.3% had >50% improvement within 5±3.7 mo, and 53.8% achieved SR with proteinuria <500 mg/24 h within 6.8±3.7 mo.

Table 1. Patient Characteristics

Total n35        
Hispanic/AA/A23/11/1        
Females (%)80        
Age (yrs, M±SD)41±12        
Duration (yrs)5.5±3.4        
n-criteria @ Dx4.7±0.9        
n-prednisone (%)31 89)        
Pred dose (mg)28±20        
n-DMARD2.1±0.6        
CD19+ before194±46        
CD19+ after29±9*        
Quarters (mo)012345678
SLEDAI-2k (M±SEM)8.5±0.84.4±0.5*4±0.5*3.6±0.6*3±0.6*2.2±0.4*2.9±0.9*3±1.3m3.3±0.7
SLEDAI-2k<=4%)2063667383948275100
4<SLEDAI-2k<=10 %)5434312713618250
SLEDAI-2k>10 (%)2633040000
Arthritis-remission07556808692100100100
Proteinuria (gr/24h)4.5±1.51.6±0.6m0.6±0.2†1±0.5m0.6±0.3m0.6±0.20.6±0.30.14 
C3 (mg/dl)89±6103±7†105±5†107±7*100±6†118±7*121±12†107±13114±11
C4 (mg/dl)14±218±2*19±2m18±2†16±2m19±2†17±2m15±216±1
Log10 a-dsDNA0.6±0.20.5±0.20.8±0.20.5±0.10.3±0.2m0.3±0.20.2±0.10.3±0.30.4±0.4
* <0.001,†<0.01, m<0.05

Conclusion:

In this open study, RTX therapy induced global durable responses in the majority of our cohort of Hispanic and AA pts with refractory SLE, and should, therefore, be considered as a therapeutic alternative in that context.

To cite this abstract, please use the following information:
Karpouzas, George A., Gogia, Maneesh, Moran, Rosalinda C., Hahn, Bevra H.; Rituximab Therapy Induces Durable Remissions in Hispanic and African American Patients with Refractory Systemic Lupus Erythematosus (SLE) [abstract]. Arthritis Rheum 2009;60 Suppl 10 :274
DOI: 10.1002/art.25357

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