an systems at baseline. The most common active organ systems at baseline based on SELENA-SLEDAI were mucocutaneous (82% in both studies); immunology (Trial 2: 74%, Trial 3: 85%); and musculoskeletal (Trial 2: 73%, Trial 3: 59%). Less than 16% of patients had some degree of renal activity and less than 7% of patients had activity in the vascular, cardio-respiratory, or CNS systems.
At screening, patients were stratified by disease severity based on their SELENA-SLEDAI score (≤ 9 vs ≥10), proteinuria level (< 2 g/24 hr vs ≥ 2 g/24 hr), and race (African or Indigenous-American descent vs. other), and then randomly assigned to receive BENLYSTA 1 mg/kg, BENLYSTA 10 mg/kg, or placebo in addition to standard of care. The patients were administered study medication intravenously over a 1-hour period on Days 0, 14, 28, and then every 28 days for 48 weeks in Trial 3 and for 72 weeks in Trial 2.
The primary efficacy endpoint was a composite endpoint (SLE Responder Index or SRI) that defined response as meeting each of the following criteria at Week 52 compared with baseline:
•
≥ 4-point reduction in the SELENA-SLEDAI score, and
•
no new British Isles Lupus Assessment Group (BILAG) A organ domain score or 2 new BILAG B organ domain scores, and
•
no worsening (< 0.30-point increase) in Physician’s Global Assessment (PGA) score.
The SRI uses the SELENA-SLEDAI score as an objective measure of reduction in global disease activity; the BILAG index to ensure no significant worsening in any specific organ system; and the PGA to ensure that improvements in disease activity are not accompanied by worsening of the patient’s condition overall.
In both Trials 2 and 3, the proportion of SLE patients achieving an SRI response, as defined for the primary endpoint, was significantly higher in the BENLYSTA 10 mg/kg group than in the placebo group. The effect on the SRI was not consistently significantly different for the BENLYSTA 1 mg/kg group relative to placebo in both trials. The 1 mg/kg dose is not recommended. The trends in comparisons between the treatment groups for the rates of response for the individual components of the endpoint were generally consistent with that of the SRI (Table 3). At Week 76 in Trial 2, the SRI response rate with BENLYSTA 10 mg/kg was not significantly different from that of placebo (39% and 32%, respectively).
Table 3. Clinical Response Rate in Patients with SLE After 52 Weeks of Treatment Trial 2 Trial 3
Patients dropping out of the study early or experiencing certain increases in background medication were considered as failures in these analyses. In both studies, a higher proportion of placebo patients were considered as failures for this reason as compared to the BENLYSTA groups.
The 1 mg/kg dose is not recommended.
Response *
Placebo + Standard of Care (n = 275)
BENLYSTA 1 mg/kg + Standard of Care † (n = 271)
BENLYSTA 10 mg/kg + Standard of Care (n = 273)
Placebo + Standard of Care (n = 287)
BENLYSTA 1 mg/kg + Standard of Care † (n = 288)
BENLYSTA 10 mg/kg + Standard of Care (n = 290)
SLE Responder Index
34%
41% (p = 0.104)
43% (p = 0.021)
44%
51% (p = 0.013)
58% (p < 0.001)
Odds Ratio (95% CI) vs. placebo
1.3 (0.9, 1.9)
1.5 (1.1, 2.2)
1.6 (1.1, 2.2 )
1.8 (1.3, 2.6)
Components of SLE Responder Index
Perc |
