Table 3.
Key safety events/100 PYs of follow-up during the initial placebo-controlled portions and through year 1 of psoriasis, PsA, and CD studies
| Placebo-controlled periods | ||||||||
|---|---|---|---|---|---|---|---|---|
| Psoriasis (0–12 weeks)a | PsA (0–16 weeks)a | CD (0–8 weeks)a | All patients | |||||
| Placebo | Ustekinumab | Placebo | Ustekinumab | Placebo | Ustekinumab | Placebo | Ustekinumab | |
| Number of patients treated | 732 | 1582 | 379 | 692 | 624 | 1362 | 1735 | 3636 |
| Mean weeks of follow-up | 12.57 | 13.37 | 15.14 | 15.70 | 8.15 | 8.16 | 11.54 | 11.86 |
| Mean number of administrationsb | 2.21 | 2.12 | 2.29 | 2.20 | 1.00 | 1.00 | 1.79 | 1.72 |
| D/C study drug due to AEs [n (%)] | 17 (2.3) | 24 (1.5) | 15 (4.0) | 8 (1.2) | 27 (4.3) | 26 (1.9) | 59 (3.4) | 58 (1.6) |
| PYs of follow-up | 177 | 407 | 110 | 209 | 98 | 214 | 385 | 829 |
| Event rate/100 PYs | ||||||||
| AEs | 415.5 | 511.3 | 352.4 | 382.4 | 1040.4 | 959.4 | 556.1 | 594.3 |
| 95% CIc | 386.0–446.7 | 489.5–533.7 | 318.3–389.3 | 356.4–409.9 | 977.5–1106.4 | 918.3–1001.9 | 532.8–580.1 | 577.9–611.2 |
| SAEs | 6.8 | 7.9 | 12.7 | 6.2 | 50.1 | 42.6 | 19.5 | 16.4 |
| 95% CIc | 3.5–11.9 | 5.4–11.1 | 6.9–21.3 | 3.3–10.6 | 37.1–66.3 | 34.3–52.3 | 15.3–24.4 | 13.8–19.4 |
| Infectionsd | 122.1 | 141.4 | 112.3 | 100.5 | 187.2 | 168.4 | 135.8 | 138.1 |
| 95% CIc | 106.4–139.5 | 130.1–153.5 | 93.4–134.0 | 87.4–115.1 | 161.1–216.4 | 151.5–186.7 | 124.4–148.0 | 130.2–146.3 |
| Serious infectionsd | 1.6 | 1.2 | 0.9 | 0.0 | 7.2 | 10.3 | 2.9 | 3.3 |
| 95% CIc | 0.4–5.0 | 0.4–2.9 | 0.0–5.1 | 0.0–1.4 | 2.9–14.8 | 6.5–15.6 | 1.4–5.1 | 2.2–4.7 |
| Adjudicated serious MACE | 0.0 | 1.2 | 0.9 | 0.0 | 0.0 | 0.0 | 0.3 | 0.6 |
| 95% CIc | 0.0–1.7 | 0.4–2.9 | 0.0–5.1 | 0.0–1.4 | 0.0–3.1 | 0.0–1.4 | 0.0–1.5 | 0.2–1.4 |
| Deaths | 0.0 | 0.3 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.1 |
| 95% CIc | 0.0–1.7 | 0.0–1.4 | 0.0–2.7 | 0.0–1.4 | 0.0–3.1 | 0.0–1.4 | 0.0–0.8 | 0.0–0.7 |
| Malignancies (excluding NMSC) |
0.6 | 0.3 | 0.0 | 0.0 | 0.0 | 0.0 | 0.3 | 0.1 |
| 95% CIc | 0.0–3.2 | 0.0–1.4 | 0.0–2.7 | 0.0–1.4 | 0.0–3.1 | 0.0–1.4 | 0.0–1.5 | 0.0–0.7 |
| Through approximately year 1e | ||||||||
|---|---|---|---|---|---|---|---|---|
| Psoriasis | PsA | CD | All patients | |||||
| Placebof | Ustekinumabg | Placeboh | Ustekinumabi | Placeboj | Ustekinumabk | Placebo | Ustekinumab | |
| Number of patients treated | 733 | 3117 | 379 | 1018 | 943 | 1749 | 2055 | 5884 |
| Mean weeks of follow-up | 12.93 | 42.80 | 19.90 | 43.40 | 19.12 | 32.89 | 17.05 | 39.96 |
| Mean weeks of treatment | 4.90 | 26.49 | 11.96 | 27.66 | 9.87 | 18.80 l | 8.41 | 24.41 |
| D/C study drug due AEs [n (%)] | 17 (2.3) | 86 (2.8) | 22 (5.8) | 31 (3.0) | (4.8) | 108 (6.2) | 84 (4.1) | 225 (3.8) |
| PYs of follow-up | 182 | 2,566 | 145 | 850 | 347 | 1,106 | 674 | 4,521 |
| Event rate/100 PYs | ||||||||
| AEs | 414.8 | 390.6 | 343.4 | 254.2 | 712.2 | 641.6 | 552.4 | 426.4 |
| 95% CIc | 385.8–445.5 | 383.0–398.3 | 313.9–374.9 | 243.6–265.2 | 684.3–740.8 | 626.8–656.7 | 534.8–570.4 | 420.4–432.5 |
| SAEs | 8.8 | 8.8 | 13.8 | 9.3 | 43.8 | 35.4 | 27.9 | 15.4 |
| 95% CIc | 5.0–14.3 | 7.7–10.0 | 8.4–21.3 | 7.4–11.6 | 37.2–51.4 | 31.9–39.0 | 24.1–32.2 | 14.3–16.6 |
| Infectionsd | 120.7 | 137.4 | 102.8 | 78.0 | 145.1 | 134.0 | 129.4 | 125.4 |
| 95% CIc | 105.3–137.8 | 132.9–142.0 | 86.9–120.6 | 72.2–84.2 | 132.7–158.3 | 127.3–141.0 | 120.9–138.3 | 122.2–128.7 |
| Serious infectionsd | 1.6 | 1.4 | 0.7 | 0.9 | 6.9 | 6.4 | 4.2 | 2.5 |
| 95% CIc | 0.3–4.8 | 1.0–1.9 | 0.0–3.8 | 0.4–1.9 | 4.4–10.3 | 5.0–8.1 | 2.8–6.0 | 2.1–3.1 |
| Adjudicated serious MACE | 0.6 | 0.6 | 0.7 | 0.7 | 0.0 | 0.1 | 0.3 | 0.5 |
| 95% CIc | 0.0–3.1 | 0.3–0.9 | 0.0–3.8 | 0.3–1.5 | 0.0–0.9 | 0.0–0.5 | 0.0–1.1 | 0.3–0.7 |
| Deaths | 0.0 | 0.2 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.1 |
| 95% CIc | 0.0–1.6 | 0.1–0.5 | 0.0–2.1 | 0.0–0.4 | 0.0–0.9 | 0.0–0.3 | 0.0–0.4 | 0.0–0.3 |
| Malignancies (excluding NMSC) | 0.6 | 0.4 | 0.0 | 0.1 | 0.0 | 0.4 | 0.2 | 0.4 |
| 95% CIc | 0.0–3.1 | 0.2–0.8 | 0.0–2.1 | 0.0–0.7 | 0.0–0.9 | 0.1–0.9 | 0.0–0.8 | 0.2–0.6 |
AEs adverse events, CD Crohn’s disease, CI confidence interval, D/C discontinuation, IV intravenous, MACE major adverse cardiovascular event, NMSC non-melanoma skin cancer, PsA psoriatic arthritis, PYs patient-years, SAE serious adverse event, SC subcutaneous
aPsoriasis—phase II, PHOENIX-1, PHOENIX-2; PsA—phase II, PSUMMIT-1, PSUMMIT-2; CD—phase IIa (only placebo-controlled IV population), CERTIFI, UNITI-1, UNITI-2
bSC administration in psoriasis and PsA trials; IV administration in CD trials
cCIs based on an exact method assuming the observed number of events follows a Poisson distribution
dInfection as assessed by the investigator
ePsoriasis—phase II, PHOENIX-1, PHOENIX-2, ACCEPT (all through week 52); PsA—phase II (through week 36), PSUMMIT-1 (through week 52), PSUMMIT-2 (through week 60); CD—phase IIa (only placebo-controlled IV population in population 1; through week 28), CERTIFI (through week 36), UNITI-1 and UNITI-2 (through week 8 for patients who entered IM-UNITI; through week 20 for patients who did not enter IM-UNITI), IM-UNITI (through week 44)
fIncludes data up to the time of crossover, and does not include etanercept patients in ACCEPT
gIncludes data from the first ustekinumab dose onward for patients who crossed over from placebo
hIncludes data up to the time of early escape or crossover
iIncludes data from the first ustekinumab dose onward for patients who escaped early or crossed over from placebo
jIncludes data up to the first ustekinumab dose for patients who were initially treated with placebo; includes data on or after 16 weeks from the first (and last) ustekinumab dose for patients who were initially treated with ustekinumab and were then crossed over or re-randomized to placebo
kIncludes data up to 16 weeks from the first ustekinumab dose for patients who were crossed over or re-randomized to placebo
lExcludes periods of placebo treatment among some ustekinumab responders who were re-randomized to placebo at maintenance and subsequently resumed ustekinumab treatment following loss of response