Summary of findings 1. Belimumab 10 mg/kg compared to placebo for systemic lupus erythematosus.
| Belimumab 10 mg/kg compared to placebo for systemic lupus erythematosus | ||||||
| Patient or population: people with active systemic lupus erythematosus (but not active nephritis or active central nervous system involvement) Setting: multicenter, international studies Intervention: belimumab 10 mg/kg (alone or in combination with other immunosuppressive drugs or another biologic) Comparison: placebo | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect (95% CI) | No of Participants (studies) | Certainty of the evidence (GRADE) | Comments | |
| Assumed risk | Corresponding risk | |||||
| Placebo | Belimumab 10 mg/kg | |||||
| Reduction of at least 4 points in SELENA‐SLEDAI at 52 weeks SELENA‐SLEDAI score, a validated marker of SLE disease activity (range 0 to 105; higher score = worse disease activity) Follow‐up: mean 52 weeks |
394 per 1000 | 524 per 1000 (480 to 571) | RR 1.33 (1.22 to 1.45) | 2666 (4 RCTs) | ⊕⊕⊕⊕ high | NNTB: 8 (95% CI 6 to 11) Absolute risk difference: 13% better (95% CI 8% to 17%) Relative percentage change: 33% better (95% CI 22% to 45%) |
| Change in HRQOL, on SF‐36 PCS score at 52 weeks Improvement in SF‐36 PCS score from baseline (range: 0 to 100); population mean 50; higher score = better HRQOL; MCID ~2.5 to 5 points) Follow‐up: mean 52 weeks |
The mean change in HRQOL on SF‐36 PCS score at 52 weeks in the control groups ranged from a 1.4 to 2.84 point improvement | The mean change in HRQOL on SF‐36 PCS score at 52 weeks in the intervention groups was 1.60 higher (0.30 lower to 2.90 higher) | MD 1.60 (0.30 to 2.90) | 801 (2 RCTs) | ⊕⊕⊕⊝ moderatea | Absolute risk difference: 1.6% higher (95% CI 0.3% to 2.9%) Relative percentage change: 3.2% higher (95% CI 0.6% to 5.8%) |
| Reduction of glucocorticoid dose by at least 50% Follow‐up: 52 weeks |
194 per 1000 | 309 per 1000 (227 to 417) |
RR 1.59 (1.17 to 2.15) | 537 (2 RCTs) | ⊕⊕⊕⊕ high | NNTB: 9 (95% CI 5 to 28) Absolute risk difference: 11% better (95% CI 4% to 18%) Relative percentage change: 59% better (95% CI 17% to 115%) |
| Participants with one or more serious adverse events Follow‐up: mean 52 to 76 weeks |
167 per 1000 | 145 per 1000 (114 to 185) | RR 0.87 (0.68 to 1.11) | 2890 (5 RCTs) | ⊕⊕⊝⊝ lowa,b | Absolute risk difference: 2% less (95% CI ‐6% to 2%) Relative percentage change: 13% more (95% CI ‐32% to 11%) |
| Participants with one or more serious infections Follow‐up: mean 52 to 76 weeks |
42 per 1000 | 42 per 1000 (28 to 65) | RR 1.01 (0.66 to 1.54) | 2185 (4 RCTs) | ⊕⊕⊕⊝ moderatea | Absolute risk difference: 0% (95% CI ‐1% to 1%) Relative percentage change: 1% fewer (95% CI ‐34% to 54%) |
| Withdrawals due to adverse events Follow‐up: mean 52 to 76 weeks | 79 per 1000 | 65 per 1000 (50 to 85) | RR 0.82 (0.63 to 1.07) | 2890 (5 studies) | ⊕⊕⊕⊝ moderatea | Absolute risk difference: 1% fewer (95% CI ‐3% to 1%) Relative percentage change: 18% fewer (95% CI ‐37% to 7%) |
| Number of participants who died during the study Follow‐up: mean 52 to 76 weeks |
5 per 1000 | 6 per 1000 (2 to 16) | Peto OR 1.15 (0.41 to 3.25) | 2917 (6 studies) | ⊕⊕⊝⊝ lowa,c | Absolute risk difference: 0% (95% CI ‐1% to 1%) Relative percentage change: 15% more (95% CI ‐59% to 221%) |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; HRQOL: health‐related quality of life; MCID: minimal clinically important difference; MD: mean difference; NNTB: number needed to treat for an additional beneficial outcome; OR: odds ratio; PCS: Physical Component Score; RCT: randomized controlled trial; RR: risk ratio; SELENA‐SLEDAI: Safety of Estrogen in Lupus National Assessment (SELENA) ‐ Systemic Lupus Erythematosus Disease Activity Index (SLEDAI); SF‐36: 36‐item short‐form; | ||||||
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GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect | ||||||
aDowngraded one level due to imprecision. The 95% confidence interval includes both no effect and appreciable benefit/harm exceeding a minimal clinically important difference. bDowngraded one level due to inconsistency, I2 = 48% cDowngraded one level due to imprecision. The total number of events was small (n = 15).