Table 3.
NMA of efficacy outcomes (clinical response, clinical remission, endoscopic improvement) in bio-exposed populationsh.
| 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 | 13.6g | 79% (60%–90%) | 99% | 9.8g | 18% (6%–45%) | 97% | 15.1g | 61% (33%–85%) | 99% |
| Filgotinib 200 mg QD | 5.4g | 59% (35%–80%) | 80% | 3.3g | 7% (2%–21%) | 47% | 2.6g | 21% (8%–47%) | 61% | |
| Tofacitinib 10 mg BIDa | 3.8g | 51% (30%–72%) | 66% | 5.2g | 10% (3%–29%) | 72% | 4.8g | 33% (14%–62%) | 80% | |
| Ustekinumab 6 mg/kgb | 3.6g | 49% (26%–72%) | 62% | 5.9g | 12% (3%–35%) | 77% | 3.7g | 28% (11%–56%) | 72% | |
| Ozanimod 0.92 mgc | 2.6g | 42% (19%–69%) | 47% | 3.5g | 7% (2%–23%) | 50% | 1.5 | 14% (4%–39%) | 37% | |
| Filgotinib 100 mg QD | 2.6g | 42% (21%–66%) | 46% | 1.9 | 4% (1%–14%) | 21% | 1.8 | 16% (6%–39%) | 43% | |
| Vedolizumab 300 mgd | 1.6 | 30% (14%–53%) | 24% | 3.2g | 7% (2%–20%) | 45% | 1.2 | 11% (4%–26%) | 25% | |
| Adalimumab 160/80 mge | 1.4 | 28% (12%–53%) | 21% | 2.7 | 6% (1%–19%) | 38% | 1.1 | 10% (4%–26%) | 20% | |
| PBO | 1.0 | 21% (12%–34%) | 4% | 1.0 | 2% (1%–6%) | 2% | 1.0 | 9% (5%–18%) | 12% | |
| Maintenancei (42–54 weeks post–induction response) | Upadacitinib 30 mg QD | 12.1g | 78% (54%–91%) | 93% | 19.4g | 66% (35%–90%) | 93% | 14.6g | 70% (42%–90%) | 93% |
| Tofacitinib 10 mg BIDa | 8.7g | 71% (47%–88%) | 84% | 4.7g | 32% (14%–59%) | 55% | 4.8g | 44% (21%–71%) | 62% | |
| Upadacitinib 15 mg QD | 7.4g | 68% (42%–86%) | 76% | 15.4g | 61% (30%–87%) | 87% | 9.5g | 61% (32%–85%) | 81% | |
| Filgotinib 200 mg QD | 5.1g | 59% (34%–80%) | 63% | 4.4g | 31% (11%–64%) | 52% | 2.8g | 31% (13%–60%) | 41% | |
| Tofacitinib 5 mg BID | 4.8g | 58% (33%–80%) | 59% | 2.6 | 21% (8%–45%) | 30% | 3.1g | 33% (14%–61%) | 43% | |
| Vedolizumab 300 mg Q8Wd | 4.3g | 55% (30%–79%) | 55% | 8.2g | 45% (21%–75%) | 74% | 7.1g | 53% (26%–80%) | 73% | |
| Ozanimod 0.92 mg QDc | 3.8g | 52% (28%–76%) | 49% | 3.8g | 28% (11%–58%) | 46% | 2.8g | 31% (13%–59%) | 41% | |
| Vedolizumab 300 mg Q4W | 3.8g | 52% (24%–79%) | 48% | 8.0g | 45% (17%–78%) | 72% | 9.6g | 61% (29%–87%) | 82% | |
| Ustekinumab 90 mg Q8W | 3.0g | 46% (24%–69%) | 37% | 3.2g | 24% (10%–48%) | 39% | 2.8g | 31% (14%–57%) | 41% | |
| Adalimumab 40 mg Q2Wf | 2.9 | 45% (18%–77%) | 37% | 2.7 | 21% (5%–62%) | 34% | NA | NA | NA | |
| Filgotinib 100 mg QD | 2.3 | 40% (19%–66%) | 27% | 3.8g | 28% (9%–61%) | 45% | 2.1 | 25% (9%–54%) | 29% | |
| Ustekinumab 90 mg Q12W | 2.0 | 37% (18%–61%) | 21% | 1.9 | 16% (6%–36%) | 20% | 1.2 | 16% (6%–36%) | 11% | |
| PBO | 1.0 | 22% (15%–31%) | 1% | 1.0 | 9% (6%–14%) | 2% | 1.0 | 14% (9%–22%) | 5% | |
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; SC, subcutaneous; SFS, stool frequency score; SUCRA, surface under the cumulative ranking curve.
aTofacitinib studies (OCTAVE 1, OCTAVE 2, and OCTAVE Sustain) additionally required RBS=0 for clinical remission and for maintenance, bio-exposed was defined as bio-failed.
bIV dose based on body weight (~6 mg/kg) at week 0. Ustekinumab study (UNIFI) defined bio-exposed as bio-failed for clinical remission and endoscopic improvement.
cOral 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).
dIV doses at weeks 0, 2, and 6 for induction. Vedolizumab study (GEMINI) defined bio-exposed as bio-failed.
eSC 160 mg at week 0 and 80 mg at week 2, then 40 mg Q2W.
fMaintenance outcomes for adalimumab from the treat-through study ULTRA-2 were imputed to mimic re-randomized responder design outcomes.
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 (RE for all outcomes) and ordered in descending (best to worst rank) SUCRA values for clinical response.
iOutcomes of maintenance treatment among induction responders.