Summary of findings 1. Mepolizumab compared to placebo for adults with EGPA ANCA‐associated vasculitis.
| Mepolizumab compared to placebo for adults with EGPA ANCA‐associated vasculitis | ||||||
| Patient or population: adults (age 18 years and older) with EGPA ANCA‐associated vasculitis Setting: clinical centres Intervention: mepolizumab (300 mg; 3 separate injections every 4 weeks) Comparison: placebo | ||||||
| Outcomes | Relative effect (95% CI) | Anticipated absolute effects* (95% CI) | Certainty of the evidence (GRADE) | What happens | ||
| With placebo | With mepolizumab | Difference | ||||
| Mortality follow‐up: 52 weeks Number of participants: 136 (1 RCT) | Peto OR 7.39 (0.15 to 372.38) | 0.0% | 0.0% (0 to 0) | 0.0% fewer (0 fewer to 0 fewer) | ⊕⊕⊝⊝ LOW 1 | During 52 weeks follow‐up, one death was reported in the mepolizumab group and no deaths in placebo group. The low‐certainty evidence suggests that mepolizumab results in little to no difference in mortality. |
| Remission for at least 24 weeks assessed with: BVAS v.3 of 0 (on a scale from 0 to 63) follow‐up: 52 weeks Number of participants: 136 (1 RCT) | RR 9.50 (2.30 to 39.21) | 2.9% | 27.9% (6.8 to 100) | 25.0% more (3.8 more to 112.4 more) | ⊕⊕⊝⊝ LOW 1 | The low‐certainty evidence suggests mepolizumab results in a large increase of the probability of accruing at least 24 weeks of remission over a 52‐week period. NNTB 4, 95% CI 3 to 8 |
| Durable remission within the first 24 weeks sustained until week 52 assessed with: BVAS v.3 of 0 (on a scale from 0 to 63) follow‐up: 52 weeks Number of participants: 136 (1 RCT) | RR 13.00 (1.75 to 96.33) | 1.5% | 19.1% (2.6 to 100) | 17.6% more (1.1 more to 140.2 more) | ⊕⊕⊝⊝ LOW 1 | The low‐certainty evidence suggests that mepolizumab results in a large increase of the probability of durable remission within the first 24 weeks, sustained until week 52. NNTB 6 95% CI 4 to 13 |
| Disease relapse follow‐up: 52 weeks Number of participants: 136 (1 RCT) | RR 0.68 (0.53 to 0.86) | 82.4% | 56.0% (43.6 to 70.8) | 26.4% fewer (38.7 fewer to 11.5 fewer) | ⊕⊕⊕⊝ MODERATE 2 | Mepolizumab probably results in a reduction in disease relapse. NNTB 4, 95% CI 3 to 9 |
| Disease flares | Not measured | |||||
| Any adverse event follow‐up: 52 weeks Number of participants: 136 (1 RCT) | RR 1.03 (0.96 to 1.11) | 94.1% | 96.9% (90.4 to 100) | 2.8% more (3.8 fewer to 10.4 more) | ⊕⊕⊝⊝ LOW 1 | The low‐certainty evidence suggests that mepolizumab does not increase any adverse event. Number of participants reporting similar rates of any AEs in mepolizumab and placebo group (97% vs 94%). |
| Any serious adverse event follow‐up: 52 weeks Number of participants: 136 (1 RCT) | RR 0.67 (0.35 to 1.28) | 26.5% | 17.7% (9.3 to 33.9) | 8.7% fewer (17.2 fewer to 7.4 more) | ⊕⊕⊝⊝ LOW 1 | The low‐certainty evidence suggests that mepolizumab results in little to no difference in any serious adverse event. |
| Any withdrawals due to AEs follow‐up: 52 weeks Number of participants: 136 (1 RCT) | RR 2.00 (0.19 to 21.54) | 1.5% | 2.9% (0.3 to 31.7) | 1.5% more (1.2 fewer to 30.2 more) | ⊕⊕⊝⊝ LOW 1 | The low‐certainty evidence suggests that mepolizumab does not increase any withdrawals due to AEs. The study reported similar number of patients withdrawn from mepolizumab and placebo groups due to AEs. |
| *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). ANCA: anti‐neutrophilic cytoplasmic antibodies; CI: Confidence interval; BVAS: Birmingham Vasculitis Activity Score; EGPA: eosinophilic granulomatosis with polyangiitis; RR: Risk ratio; OR: Odds ratio; | ||||||
| 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 | ||||||
1Downgraded by two levels for imprecision: CIs are wide and the number of events was too low to reliably assess optimal information size (OIS); or OIS not met
2Downgraded by one level for imprecision: the number of events was lower than indicated in GRADE guidance
AE ‐ adverse event
ANCA – antineutrophil cytoplasmic antibody
BVAS – Birmingham Vasculitis Activity Score
EGPA – eosinophilic granulomatosis with polyangiitis
NNTB ‐ number needed to treat for an additional beneficial outcome
OR ‐ odds ratio
RCT ‐ randomized controlled trial
RR ‐ relative risk