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Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: A randomised, placebo-controlled, phase III trial
The Lancet - Early Online Publication, 02/08/2011
Clinical Article
Navarra SV et al. – The efficacy and safety of the fully human monoclonal antibody belimumab (BLyS-specific inhibitor) was assessed in patients with active systemic lupus erythematosus.Elimumab has the potential to be the first targeted biological treatment that is approved specifically for systemic lupus erythematosus, providing a new option for the management of this important prototypic autoimmune disease.
Methods- Patients (aged ≥18 years) who were seropositive with scores of at least 6 on the Safety of Estrogens in Lupus Erythematosus National Assessment—Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) were enrolled in a multicentre phase 3 study, which was done in Latin America, Asia-Pacific, and eastern Europe
- Patients randomly assigned by use of central interactive voice response system in 1:1:1 ratio to belimumab 1 mg/kg or 10 mg/kg, or placebo by intravenous infusion in 1 h on days 0, 14, and 28, and then every 28 days until 48 weeks, with standard of care
- Patients, investigators, study coordinators, and sponsors masked to treatment assignment
- Primary efficacy endpoint was improvement in the Systemic Lupus Erythematosus Responder Index (SRI) at week 52 (reduction ≥4 points in SELENA-SLEDAI score; no new British Isles Lupus Assessment Group [BILAG] A organ domain score and no more than 1 new B organ domain score; and no worsening [<0·3 increase] in Physician's Global Assessment [PGA] score) versus baseline
- Method of analysis by modified intention to treat
- 867 patients were randomly assigned to belimumab 1 mg/kg (n=289) or 10 mg/kg (n=290), or placebo (n=288)
- 865 were treated and analysed in the belimumab (1 mg/kg, n=288; 10 mg/kg, n=290) and placebo groups (n=287)
- Significantly higher SRI rates were noted with belimumab 1 mg/kg (148 [51%], OR 1·55 [95% CI 1·10—2·19]; p=0·0129) and 10 mg/kg (167 [58%], 1·83 [1·30—2·59]; p=0·0006) than with placebo (125 [44%]) at week 52
- More patients had their SELENA-SLEDAI score reduced by at least 4 points during 52 weeks with belimumab 1 mg/kg (153 [53%], 1·51 [1·07—2·14]; p=0·0189) and 10 mg/kg (169 [58%], 1·71 [1·21—2·41]; p=0·0024) than with placebo (132 [46%])
- More patients given belimumab 1 mg/kg (226 [78%], 1·38 [0·93—2·04]; p=0·1064) and 10 mg/kg (236 [81%], 1·62 [1·09—2·42]; p=0·0181) had no new BILAG A or no more than 1 new B flare than did those in placebo group (210 [73%])
- No worsening in PGA score noted in more patients with belimumab 1 mg/kg (227 [79%], 1·68 [1·15—2·47]; p=0·0078) and 10 mg/kg (231 [80%], 1·74 [1·18—2·55]; p=0·0048) than with placebo (199 [69%])
- Rates of adverse events similar in groups given belimumab 1 mg/kg and 10 mg/kg, and placebo: serious infection reported in 22 (8%), 13 (4%), and 17 (6%) patients, respectively, and severe or serious hypersensitivity reactions on an infusion day reported in 2 (<1%), 2 (<1%), and no patients, respectively
- No malignant diseases reported
