Table 2.
NMA of efficacy outcomes (clinical response, clinical remission, endoscopic improvement) in bio-naive populationsj.
| Phase | Treatment | Clinical response | Clinical remission | Endoscopic improvement | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| OR (vs PBO) | Absolute rate | SUCRA | OR (vs PBO) | Absolute rate | SUCRA | OR (vs PBO) | Absolute rate | SUCRA | ||
| Induction (6–10 weeks post-baseline) | Upadacitinib 45 mg QD | 6.9i | 79% (68%–87%) | 99% | 9.6i | 50% (25%–77%) | 97% | 6.9i | 69% (54%–81%) | 99% |
| Ustekinumab 6 mg/kga | 3.6i | 67% (50%–80%) | 74% | 2.0 | 18% (6%–41%) | 37% | 1.9i | 38% (24%–54%) | 39% | |
| Infliximab 5 mgb | 3.4i | 65% (53%–76%) | 71% | 3.9i | 29% (15%–48%) | 74% | 3.0i | 50% (39%–60%) | 74% | |
| Infliximab 10 mgb | 3.4i | 65% (51%–77%) | 70% | 3.2i | 25% (12%–45%) | 61% | 3.1i | 50% (38%–61%) | 74% | |
| Filgotinib 200 mg QD | 3.4i | 65% (47%–79%) | 69% | 2.3 | 20% (8%–42%) | 44% | 2.0i | 39% (26%–56%) | 45% | |
| Tofacitinib 10 mg BIDc | 3.1i | 63% (49%–76%) | 63% | 2.3i | 19% (8%–41%) | 42% | 2.1i | 40% (27%–56%) | 46% | |
| Filgotinib 100 mg QD | 2.5i | 58% (40%–74%) | 41% | 1.5 | 13% (5%–32%) | 19% | 1.4 | 31% (19%–47%) | 19% | |
| Adalimumab 160/80 mgd | 2.2i | 55% (41%–67%) | 30% | 1.8 | 16% (7%–31%) | 27% | 1.6i | 34% (25%–44%) | 26% | |
| Vedolizumab 300 mgb | 2.1i | 54% (39%–69%) | 30% | 3.3i | 26% (11%–51%) | 62% | 2.5i | 45% (31%–60%) | 60% | |
| Ozanimod 0.92 mge | 2.1i | 54% (37%–69%) | 29% | 4.1i | 30% (12%–59%) | 73% | 3.6i | 54% (37%–70%) | 81% | |
| Golimumab 200/100 mgf | 1.9i | 52% (36%–68%) | 24% | 3.2i | 25% (10%–51%) | 61% | 1.8i | 37% (25%–51%) | 36% | |
| PBO | 1.0 | 36% (27%–46%) | 0% | 1.0 | 9% (5%–17%) | 3% | 1.0 | 24% (20%–29%) | 2% | |
| Maintenancek (42–54 weeks post-induction response) | Upadacitinib 30 mg QD | 10.4i | 85% (58%–96%) | 96% | 4.2i | 52% (20%–82%) | 72% | 7.2i | 70% (37%–90%) | 86% |
| Tofacitinib 10 mg BIDc | 5.6i | 76% (45%–92%) | 82% | 6.6i | 63% (29%–88%) | 87% | 6.7i | 69% (36%–89%) | 84% | |
| Vedolizumab 300 mg Q8W | 4.7i | 73% (42%–91%) | 76% | 3.5i | 47% (22%–74%) | 65% | 4.1i | 58% (28%–82%) | 64% | |
| Upadacitinib 15 mg QD | 4.6i | 72% (39%–91%) | 73% | 3.0 | 43% (15%–77%) | 57% | 3.7i | 55% (23%–83%) | 57% | |
| Tofacitinib 5 mg BIDc | 4.0i | 69% (37%–89%) | 67% | 5.9i | 60% (27%–86%) | 84% | 4.8i | 61% (29%–86%) | 69% | |
| Filgotinib 200 mg QD | 3.5i | 66% (34%–88%) | 60% | 4.9i | 56% (24%–84%) | 79% | 4.3i | 58% (27%–84%) | 65% | |
| Vedolizumab 300 mg Q4W | 3.4i | 65% (33%–88%) | 59% | 3.9i | 50% (20%–79%) | 69% | 4.6i | 60% (28%–85%) | 68% | |
| Ustekinumab 90 mg Q8W | 3.1i | 64% (31%–88%) | 55% | 2.2 | 36% (12%–69%) | 42% | 2.5 | 45% (18%–76%) | 39% | |
| Ustekinumab 90 mg Q12W | 3.0i | 63% (30%–87%) | 54% | 1.9 | 33% (11%–66%) | 36% | 2.2 | 42% (16%–73%) | 31% | |
| Golimumab 100 mg Q4Wg | 2.7i | 60% (31%–84%) | 47% | 2.9i | 43% (19%–74%) | 57% | 2.9i | 49% (24%–77%) | 47% | |
| Infliximab 10 mg/kg Q8Wh | 2.5 | 58% (25%–85%) | 44% | 1.5 | 27% (8%–63%) | 26% | NA | NA | NA | |
| Golimumab 50 mg Q4Wg | 2.2i | 55% (26%–82%) | 36% | 2.3 | 37% (14%–69%) | 44% | 2.4i | 44% (19%–74%) | 35% | |
| Infliximab 5 mg/kg Q8Wh | 2.1 | 54% (22%–83%) | 35% | 1.4 | 26% (8%–62%) | 24% | NA | NA | NA | |
| Ozanimod 0.92 mg QDe | 1.8 | 50% (22%–78%) | 26% | 2.5 | 38% (14%–70%) | 47% | 2.3 | 43% (18%–73%) | 33% | |
| Filgotinib 100 mg QD | 1.6 | 47% (19%–77%) | 22% | 1.9 | 33% (11%–67%) | 36% | 1.6 | 35% (12%–67%) | 19% | |
| Adalimumab 40 mg Q2Wh | 1.3 | 42% (15%–74%) | 15% | 1.2 | 23% (7%–55%) | 17% | NA | NA | NA | |
| PBO | 1.0 | 36% (16%–61%) | 4% | 1.0 | 20% (9%–39%) | 8% | 1.0 | 25% (12%–44%) | 2% | |
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: AM, adapted Mayo score; 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; RBS, rectal bleeding score; RE, random effects model; REA, RE model adjusted for baseline/PBO risk; SC, subcutaneous; SFS, stool frequency score; SUCRA, surface under the cumulative ranking curve.
aIV dose based on body weight (~6 mg/kg) at week 0.
bIV doses at week 0, 2, and 6 for induction.
cTofacitinib studies (OCTAVE 1, OCTAVE 2, and OCTAVE Sustain) additionally required RBS = 0 for clinical remission and for maintenance, bio-naive was defined as non-bio-failure.
dSC 160 mg at week 0 and 80 mg at week 2, then 40 mg Q2W.
eOral 0.23 mg QD for 4 days, 0.46 mg QD for 3 days, then 0.92 mg QD starting on day 8. Ozanimod study (TRUE NORTH) used AM to define clinical response (decrease in AM ≥2% and ≥35% from baseline, and a decrease in RBS ≥1 or an absolute RBS ≤1) and remission (SFS ≤1- and ≥1-point decrease from baseline, RBS = 0, and endoscopic subscore ≤1).
fSC 200 mg at week 0 and 100 mg at week 2.
gGolimumab study PURSUIT-J reported maintenance clinical remission and response as sustained over 2 post-induction timepoints, while study PURSUIT-M reported maintenance clinical response and endoscopic improvement as sustained over 2 post-induction timepoints.
hMaintenance outcomes for infliximab and adalimumab from the treat-through studies ACT-1 and ULTRA-2, respectively, were imputed to mimic re-randomized responder design outcomes.
iDenotes statistical significance (OR 95% CrI excludes 1). 95% CrIs can be found in Appendices 8 and 9.
jResults (medians with 95% CrI as applicable) displayed for ‘best-fitting’ model per fit statistics (REA for induction clinical response, RE for all other outcomes) and ordered in descending (best to worst rank) SUCRA values for clinical response.
kOutcomes of maintenance treatment among induction responders.