Table 4.
NMA of safety outcomes (all AEs, discontinuation due to AEs, serious AEs, serious infections) in overall populationsh.
| Phase | Treatment | All AEs | Discontinuation due to AEs | Serious AEs | Serious Infections | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| OR (vs PBO) | Absolute rate | SUCRA | OR (vs PBO) | Absolute rate | SUCRA | OR (vs PBO) | Absolute rate | SUCRA | OR vs PBO) | Absolute rate | SUCRA | ||
| Induction (6–10 weeks post-baseline) | Golimumab 200/100 mga | 0.7 | 43% (30%–57%) | 87.8% | 0.3 | 1.1% (0.0%–11.1%) | 77.2% | 0.4 | 2.7% (0.9%–7.5%) | 79.1% | 0.2 | 0.2% (0.0%–1.5% | 82.6% |
| Vedolizumab 300 mgd | 0.7 | 45% (35%–57%) | 80.2% | 0.7 | 2.9% (0.7%–10.2%) | 52.0% | 0.6 | 3.9% (1.5%–9.8%) | 59.8% | 0.3 | 0.4% (0.0%–2.0% | 68.9% | |
| Ozanimod 0.92 mgb | 0.7 | 45% (33%–60%) | 77.4% | 1.0 | 4.4% (1.2%–14.8%) | 31.0% | 1.3 | 7.8% (2.7%-22.2%) | 18.0% | 0.8 | 0.9% (0.2%–4.1% | 37.8% | |
| Filgotinib 100 mg QD | 0.9 | 49% (37%–60%) | 65.3% | 0.7 | 3.0% (1.0%–8.9%) | 52.0% | 1.1 | 6.7% (2.6%-16.5%) | 22.9% | 0.9 | 1.0% (0.2%–4.1% | 32.7% | |
| Adalimumab 160/80 mgc | 0.9 | 51% (41%–61%) | 51.6% | 0.9 | 3.6% (1.7%–8.0%) | 40.9% | 0.6 | 3.8% (1.8%–7.9%) | 61.7% | 0.9 | 1.0% (0.2%–3.5% | 32.4% | |
| Filgotinib 200 mg QD | 1.0 | 52% (40%–64%) | 44.5% | 0.9 | 3.8% (1.3%–11.1%) | 36.6% | 0.9 | 5.8% (2.2%–14.7%) | 33.0% | 0.5 | 0.5% (0.1%–2.5% | 59.6% | |
| Ustekinumab 6 mg/kge | 1.0 | 52% (40%–64%) | 44.1% | NA | NA | NA | 0.5 | 3.0% (1.1%–8.1%) | 74.1% | 0.2 | 0.2% (0.0%–1.6% | 80.9% | |
| PBO | 1.0 | 53% (45%–60%) | 39.5% | 1.0 | 4.2% (2.8%–6.2%) | 28.8% | 1.0 | 6.2% (3.8%–10.0%) | 23.2% | 1.0 | 1.1% (0.5%–2.5% | 22.9% | |
| Tofacitinib 10 mg BID | 1.0 | 54% (43%–64%) | 33.4% | 1.0 | 4.1% (1.6%–11.1%) | 33.6% | 0.6 | 4.0% (1.7%–9.5%) | 57.2% | 0.6 | 0.7% (0.2%–2.6% | 47.9% | |
| Upadacitinib 45 mg QD | 1.1 | 56% (45%–66%) | 22.3% | 0.2g | 1.1% (0.4%–2.8%) | 90.1% | 0.5 | 3.5% (1.4%–8.4%) | 66.9% | 0.9 | 0.9% (0.2%–3.4% | 33.2% | |
| Infliximab 5 mgd | 2.3 | 72% (48%–87%) | 4.0% | 0.6 | 2.5% (0.6%–10.1%) | 58.0% | 0.7 | 4.2% (1.3%–12.1%) | 54.1% | 0.5 | 0.6% (0.0%–5.0% | 51.2% | |
| Maintenancei (40–54 weeks post–induction response) | Ustekinumab 90 mg Q12W | 0.6 | 53% (30%–76%) | 90.4% | 0.4 | 3.2% (1.0%–9.8%) | 67.4% | 0.7 | 6.7% (2.3%–6.7%) | 57.3% | 1.5 | 2.9% (0.7%–13.4%) | 29.9% |
| Tofacitinib 5 mg BID | 0.9 | 62% (38%–81%) | 73.0% | 0.4 | 3.3% (1.2%–8.9%) | 67.6% | 0.8 | 6.8% (2.2%–6.8%) | 56.1% | 1.0 | 1.9% (0.2%–17.5%) | 45.7% | |
| Vedolizumab 300 mg Q4W | 0.9 | 63% (37%–83%) | 69.6% | 0.3 | 2.6% (0.7%–8.5%) | 75.1% | 0.6 | 5.6% (1.9%–5.6%) | 67.7% | 0.5 | 0.9% (0.1%–5.7%) | 67.2% | |
| Filgotinib 100 mg QD | 0.9 | 63% (39%–82%) | 69.1% | 1.9 | 13.1% (3.7%–37.7%) | 11.8% | 1.2 | 10.5% (3.0%–10.5%) | 32.1% | 1.8 | 3.4% (0.4%–27.4%) | 29.3% | |
| Ustekinumab 90 mg Q8W | 0.9 | 64% (39%–83%) | 66.9% | 0.2g | 1.7% (0.4%–5.8%) | 88.5% | 0.9 | 7.6% (2.7%–7.6%) | 48.9% | 0.7 | 1.3% (0.2%–7.5%) | 57.3% | |
| PBO | 1.0 | 66% (50%–79%) | 63.8% | 1.0 | 7.4% (4.5%–11.7%) | 29.1% | 1.0 | 8.7% (6.0%–8.7%) | 37.7% | 1.0 | 1.9% (1.2%–3.1%) | 44.3% | |
| Vedolizumab 300 mg Q8W | 1.0 | 67% (45%–83%) | 58.0% | 0.4g | 3.0% (1.1%–7.6%) | 71.7% | 0.7 | 6.7% (3.0%–6.7%) | 57.4% | 0.8 | 1.5% (0.3%–7.0%) | 52.2% | |
| Upadacitinib 15 mg QD | 1.1 | 68% (43%–86%) | 53.3% | 0.3 | 2.4% (0.6%–8.2%) | 77.8% | 0.5 | 4.4% (1.5%–4.4%) | 78.1% | 0.8 | 1.6% (0.3%–6.5%) | 51.6% | |
| Upadacitinib 30 mg QD | 1.2 | 69% (44%–86%) | 49.5% | 0.5 | 4.1% (1.2%–12.3%) | 57.5% | 0.4 | 3.8% (1.2%–3.8%) | 84.1% | 0.6 | 1.2% (0.2%–5.3%) | 61.1% | |
| Filgotinib 200 mg QD | 1.2 | 70% (47%–86%) | 46.5% | 1.1 | 8.2% (2.1%–27.3%) | 29.1% | 1.2 | 10.5% (3.1%–10.5%) | 31.6% | 1.0 | 1.9% (0.2%–18.2%) | 46.6% | |
| Infliximab 5 mg/kg Q8W | 1.2 | 70% (43%–88%) | 45.4% | 0.9 | 6.6% (2.0%–20.1%) | 36.4% | 0.8 | 7.0% (2.7%–7.0%) | 54.9% | 0.6 | 1.1% (0.2%–5.5%) | 63.0% | |
| Tofacitinib 10 mg BID | 1.3 | 71% (47%–87%) | 41.5% | 0.5 | 3.5% (1.3%–9.4%) | 64.4% | 0.8 | 7.5% (2.5%–7.5%) | 49.8% | 0.4 | 0.8% (0.0%–10.8%) | 67.0% | |
| Adalimumab 40 mg Q2Wf | 1.4 | 73% (54%–86%) | 33.5% | 1.3 | 9.5% (3.9%–23.5%) | 19.5% | 1.7 | 14.3% (6.5%–14.3%) | 12.6% | 0.4 | 0.8% (0.0%–10.5%) | 66.5% | |
| Golimumab 50 mg Q4W | 1.6 | 75% (54%–90%) | 27.6% | 0.8 | 5.9% (1.6%–18.6%) | 42.2% | 0.9 | 7.9% (2.7%–7.9%) | 47.2% | 1.8 | 3.4% (0.7%–17.0%) | 27.5% | |
| Infliximab 10 mg/kg Q8W | 1.8 | 77% (51%–92%) | 23.5% | 1.0 | 7.3% (2.2%–21.8%) | 32.0% | 0.9 | 7.9% (3.1%–7.9%) | 46.3% | 1.7 | 3.3% (0.9%–12.5%) | 26.1% | |
| Ozanimod 0.92 mg QD | 1.7 | 76% (55%–89%) | 23.0% | 0.5 | 3.5% (0.6%–15.8%) | 62.5% | 0.6 | 5.7% (2.0%–5.7%) | 65.7% | 0.4 | 0.9% (0.1%–5.4%) | 68.8% | |
| Golimumab 100 mg Q4W | 1.9g | 79% (60%–91%) | 15.5% | 1.5 | 10.4% (3.4%–28.5%) | 17.6% | 1.4 | 11.8% (4.4%–11.8%) | 22.4% | 1.8 | 3.4% (0.6%–17.1%) | 27.1% | |
| Adalimumab 40 mg QW | NA | NA | NA | NA | NA | NA | NA | NA | NA | 0.4 | 0.7% (0.0%–11.4%) | 68.9% | |
Coloring in SUCRA columns is based on SUCRA value; values of 100% are green in color, values of 0% are red in color, intermediates values are colored along the green-to-red gradient. Abbreviations: AE, adverse event; BID, twice daily; CrI, credible interval; IV, intravenous; NA, not available; NMA, network meta-analysis; OR, odds ratio; PBO, placebo; Q#W, every # week; QD, once daily; RE, random effects model; REA, RE model adjusted for baseline/PBO risk; SC, subcutaneous; SUCRA, surface under the cumulative ranking curve.
aSC 200 mg at week 0 and 100 mg at week 2.
bIV dose based on body weight (~6 mg/kg) at week 0.
cSC 160 mg at week 0 and 80 mg at week 2, then 40 mg Q2W.
dIV doses at weeks 0, 2, and 6.
eOral 0.23 mg QD for 4 days, 0.46 mg QD for 3 days, then 0.92 mg QD starting on day 8.
fFor treat-through trials M10-447 and ULTRA-2 for adalimumab, induction numbers were subtracted from the overall numbers to obtain maintenance numbers.
gDenotes statistical significance (OR 95% CrI excludes 1). 95% CrIs can be found in Appendices 8 and 9.
hResults (medians with 95% CrI as applicable) displayed for ‘best-fitting’ model per fit statistics (REA for all AEs; RE for all others) and ordered in descending absolute rates for all AEs. Safety endpoints as defined in trials.
iOutcomes of maintenance treatment among induction responders.