Summary of findings 2. Active drug (etanercept or belimumab) with standard therapy compared to standard therapy with placebo for adults with GPA ANCA‐associated vasculitis.
| Active drug (etanercept or belimumab) with standard therapy compared to standard therapy with placebo for adults with GPA ANCA‐associated vasculitis | ||||||
| Patient or population: adults (age 18 years and older) with GPA ANCA‐associated vasculitis or microscopic polyangiitis (only a subset of patients in one study, i.e. 7.7% of total population and not analysed separately) Setting: clinical centres in etanercept study and not reported in belimumab study Intervention: active drug (etanercept: 25 mg twice a week for a median of 25 months or belimumab: 10 mg/kg on days 0, 14, 28 and every 28 days thereafter until 12 months after the last participant was randomised) with standard therapy Comparison: standard therapy with placebo | ||||||
| Outcomes | Relative effect (95% CI) | Anticipated absolute effects* (95% CI) | Certainty of the evidence (GRADE) | What happens | ||
| With standard therapy and placebo | With active drug (etanercept or belimumab) with standard therapy | Difference | ||||
| Mortality
Number of participants: 285
(2 RCTs) WGET 2005 follow‐up: 27 months; BREVAS 2018 follow‐up: approximately up to 4 years |
Peto OR 2.45 (0.55 to 10.97) | 1.4% | 3.4% (0.8 to 15.3) | 2.0% more (0.6 fewer to 13.9 more) | ⊕⊕⊝⊝ LOW 1 | Five deaths was reported in active drug (etanercept or belimumab) with standard therapy group and two deaths in standard therapy with placebo group. Low‐certainty evidence suggests that active drug (etanercept or belimumab) added to standard therapy when compared with standard therapy does not increase/reduce mortality. |
| Remission (number of patients with remission)
assessed with: BVAS/WG = 0 WGET 2005 follow‐up: 27 months Number of participants: 180 (1 RCT) |
RR 0.97 (0.89 to 1.07) | 92.3% | 89.5% (82.2 to 98.8) | 2.8% fewer (10.2 fewer to 6.5 more) | ⊕⊕⊝⊝ LOW 2, 3 | Low‐certainty evidence suggests that active drug (etanercept or belimumab) added to standard therapy when compared with standard therapy with placebo may have little or no effect on remission. However, any effect is likely to be small. |
| Durable remission assessed with: BVAS/WG = 0 for ≥ 6 months follow‐up: 27 months Number of participants: 174 (1 RCT) | RR 0.93 (0.77 to 1.11) | 75.3% | 70.0% (58 to 83.6) | 5.3% fewer (17.3 fewer to 8.3 more) | ⊕⊕⊝⊝ LOW 1 | Low‐certainty evidence suggests that etanercept added to standard therapy when compared with standard therapy and placebo may have little or no effect on durable remission. |
| Major relapse
assessed with: BVAS (experiencing at least 1 major BVAS item) follow‐up: year 2 week 28 Number of participants: 105 (1 RCT) |
RR 2.94 (0.12 to 70.67) | 0.0% | 0.0% (0 to 0) | 0.0% fewer (0 fewer to 0 fewer) | ⊕⊕⊝⊝ LOW 1 | Low‐certainty evidence suggests that belimumab added to standard therapy when compared with standard therapy and placebo does not increase/reduce major relapse. |
| Disease flare assessed with: BVAS/WG ‐ increase of at least one point in scale follow‐up: 27 months Number of participants: 180 (1 RCT) | RR 0.98 (0.76 to 1.27) | 57.1% | 56.0% (43.4 to 72.6) | 1.1% fewer (13.7 fewer to 15.4 more) | ⊕⊕⊕⊝ MODERATE 3 | Etanercept added to standard therapy when compared with standard therapy with placebo probably does not reduce disease flare. |
| Any adverse event follow‐up: approximately up to 4 years Number of participants: 105 (1 RCT) |
RR 1.12 (0.97 to 1.29) |
82.7% | 92.5% (2.5 to 24) |
9.9% more (2,5 fewer to 24 more) |
⊕⊕⊝⊝ LOW1 | The low‐certainty evidence suggests that belimumab added to standard therapy when compared with standard therapy with placebo may result in little or no difference in any AE. |
| Any severe or serious AE (grade 3, 4 or 5)
assessed with: the National Cancer Institute Toxicity Grading Scale WGET 2005 follow‐up: 27 months; BREVAS 2018 follow‐up: approximately up to 4 years Number of participants: 285 (2 RCTs) |
RR 1.00 (0.80 to 1.27) | 47.6% | 47.6% (38 to 60.4) | 0.0% fewer (9.5 fewer to 12.8 more) | ⊕⊕⊝⊝ LOW 2, 3 | The low certainty evidence suggests that active drug (etanercept or belimumab) added to standard therapy when compared with standard therapy with placebo may result in little or no difference in severe or serious AE (grade 3, 4 or 5). |
| Any withdrawals due to AE
assessed with the National Cancer Institute Toxicity Grading Scale WGET 2005 follow‐up: 27 months; BREVAS 2018 follow‐up: approximately up to 4 years Number of participants: 285 (2 RCTs) |
RR 2.66 (1.07 to 6.59) | 4.2% | 11.2% (4.5 to 27.7) | 7.0% more (0.3 more to 23.5 more) | ⊕⊕⊝⊝ LOW 2, 3 | The low‐certainty evidence suggests that active drug (etanercept or belimumab) added to standard therapy when compared with standard therapy with placebo results in a slight increase in any withdrawals due to AE. NNTH 15, 95% CI 8 to 100 |
| *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/WG: Birmingham Vasculitis Activity Score for Wegener's Granulomatosis; GPA: 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: optimal information size (OIS) not achieved; low number of events; confidence intervals very wide or indicating both harm and benefit
2Downgraded by one level due to high risk of selective outcome reporting bias in both studies
3Downgraded by one level for imprecision: OIS criteria are met, but the CIs are very wide; or OIS not achieved, and confidence interval indicates both harm and benefit
AE ‐ adverse event
ANCA – antineutrophil cytoplasmic antibody
BREVAS ‐ Belimumab in Remission of VASculitis
BVAS – Birmingham Vasculitis Activity Score
BVAS/WG – Birmingham Vasculitis Activity Score for granulomatosis with polyangiitis
GPA – granulomatosis with polyangiitis
NNTH ‐ number needed to treat for an additional harmful effect
OR ‐ odds ratio
RCT ‐ randomized controlled trial
RR ‐ relative risk
WGET ‐ Wegener's Granulomatosis Etanercept Trial