TABLE 3.
Treatment Through 1 Year: Patients with Safety Events Per 100 Patient-Years of Follow-Upa
| Ulcerative Colitis | Crohn’s Disease | Inflammatory Bowel Disease | ||||
|---|---|---|---|---|---|---|
| Placebo | Ustekinumab | Placebo | Ustekinumab | Placebo | Ustekinumab | |
| Patients Treated | 446 | 825 | 943 | 1749 | 1389 | 2574 |
| Average follow-up (weeks) | 29.14 | 39.53 | 19.11 | 32.89 | 22.33 | 35.02 |
| Patient-years of follow-up | 250 | 627 | 347 | 1106 | 596 | 1733 |
| Key safety events, Rate (N) | ||||||
| Adverse events | 121.65 (304) | 95.03 (596) | 197.97 (686) | 131.52 (1455) | 165.99 (990) | 118.32 (2051) |
| 95% CI | (108.36, 136.12) | (87.55, 102.97) | (183.43, 213.36) | (124.85, 138.46) | (155.81, 176.67) | (113.25, 123.55) |
| Serious adverse events | 18.41 (46) | 12.91 (81) | 34.05 (118) | 25.94 (287) | 27.50 (164) | 21.23 (368) |
| 95% CI | (13.48, 24.55) | (10.26, 16.05) | (28.19, 40.78) | (23.03, 29.12) | (23.45, 32.04) | (19.12, 23.51) |
| Infectionsb | 59.23 (148) | 49.75 (312) | 95.52 (331) | 72.59 (803) | 80.31 (479) | 64.32 (1115) |
| 95% CI | (50.07, 69.57) | (44.38, 55.58) | (85.51, 106.39) | (67.65, 77.78) | (73.28, 87.84) | (60.60, 68.21) |
| Serious infections | 4.00 (10) | 3.19 (20) | 6.64 (23) | 6.06 (67) | 5.53 (33) | 5.02 (87) |
| 95% CI | (1.92, 7.36) | (1.95, 4.92) | (4.21, 9.96) | (4.69, 7.69) | (3.81, 7.77) | (4.02, 6.19) |
| Serious MACEc | 0.80 (2) | 0.16 (1) | 0.00 (0) | 0.09 (1) | 0.34 (2) | 0.12 (2) |
| 95% CI | (0.10, 2.89) | (0.00, 0.89) | (0.00, 0.86) | (0.00, 0.50) | (0.04, 1.21) | (0.01, 0.42) |
| Discontinuation due to adverse event | 13.21 (33) | 4.15 (26) | 13.56 (47) | 9.76 (108) | 13.41 (80) | 7.73 (134) |
| 95% CI | (9.09, 18.55) | (2.71, 6.07) | (9.97, 18.04) | (8.01, 11.79) | (10.64, 16.69) | (6.48, 9.16) |
| Death | 0.00 (0) | 0.32 (2) | 0.00 (0) | 0.00 (0) | 0.00 (0) | 0.12 (2) |
| 95% CI | (0.00, 1.20) | (0.04, 1.15) | (0.00, 0.86) | (0.00, 0.27) | (0.00, 0.50) | (0.01, 0.42) |
| Malignancies (excluding NMSC) | 0.40 (1) | 0.64 (4) | 0.00 (0) | 0.27 (3) | 0.17 (1) | 0.40 (7) |
| 95 % CI | (0.01, 2.23) | (0.17, 1.63) | (0.00, 0.86) | (0.06, 0.79) | (0.00, 0.93) | (0.16, 0.83) |
| Infections of Interest, Rate (N) | ||||||
| Clostridium difficile infectiond | 2.00 (5) | 0.64 (4) | 2.31 (8) | 1.08 (12) | 2.18 (13) | 0.92 (16) |
| Herpes Zostere | 1.20 (3) | 1.12 (7) | 1.44 (5) | 0.99 (11) | 1.34 (8) | 1.04 (18) |
| GI-related abscessesf | 0.80 (2) | 0.16 (1) | 8.37 (29) | 4.61 (51) | 5.20 (31) | 3.00 (52) |
| 95% CI | (0.10, 2.89) | (0.00, 0.89) | (5.60, 12.02) | (3.43, 6.06) | (3.53, 7.38) | (2.24, 3.93) |
| Anal, rectal, and perirectal | 0.80 (2) | 0.16 (1) | 7.21(25) | 2.98 (33) | 4.53 (27) | 1.96 (34) |
| 95% CI | (0.10, 2.89) | (0.00, 0.89) | (4.67, 10.65) | (2.05, 4.19) | (2.98, 6.59) | (1.36, 2.74) |
| Abdominal and intestinal | 0.00 (0) | 0.00 (0) | 0.87 (3) | 0.45 (5) | 0.50 (3) | 0.29 (5) |
| 95% CI | (0.00, 1.20) | (0.00, 0.48) | (0.18, 2.53) | (0.15, 1.05) | (0.10, 1.47) | (0.09, 0.67) |
| Abscess, Other | 0.00 (0) | 0.00 (0) | 0.29 (1) | 1.18 (13) | 0.17 (1) | 0.75 (13) |
| 95% CI | (0.00, 1.20) | (0.00, 0.48) | (0.01, 1.61) | (0.63, 2.01) | (0.00, 0.93) | (0.40, 1.28) |
| ≥10 Adverse events occurring in any treatment group | ||||||
| Nasopharyngitis | 17.21 | 17.86 | 15.58 | 18.26 | 16.26 | 18.11 |
| Upper respiratory tract infection | 6.00 | 6.70 | 15.30 | 14.01 | 11.40 | 11.36 |
| Nausea | 5.60 | 5.74 | 18.76 | 15.46 | 13.25 | 11.94 |
| Crohn’s disease | 0.00 | 0.00 | 37.81 | 23.59 | 21.96 | 15.06 |
| Abdominal pain | 6.00 | 5.10 | 20.78 | 15.19 | 14.59 | 11.54 |
| Diarrhea | 1.20 | 3.51 | 10.10 | 5.88 | 6.37 | 5.02 |
| ≥10 Adverse events occurring in any treatment group | ||||||
| Vomiting | 2.40 | 2.55 | 10.10 | 9.85 | 6.87 | 7.21 |
| Ulcerative Colitis | 36.82 | 15.15 | 0.00 | 0.00 | 15.43 | 5.48 |
| Arthralgia | 9.20 | 8.45 | 22.51 | 21.15 | 16.93 | 16.56 |
| Headache | 9.20 | 11.00 | 21.64 | 19.62 | 16.43 | 16.50 |
| Fatigue | 4.80 | 4.46 | 10.10 | 8.23 | 7.88 | 6.86 |
| Pyrexia | 6.80 | 3.99 | 17.03 | 12.29 | 12.74 | 9.29 |
| Anemia | 11.20 | 7.81 | 7.21 | 4.07 | 8.89 | 5.42 |
Abbreviations: CI, confidence interval; NMSC, non-melanoma skin cancer.
aUlcerative Colitis: CNTO1275UCO3001; Crohn’s disease: C0379T07 (only placebo-controlled IV population), C0743T26, CNTO1275CRD3001 and CNTO1275CRD3002.
bInfection as assessed by the investigator.
cMajor adverse cardiovasulcar events (MACE) events in Crohn’s disease studies were externally adjudicated, and in ulcerative colitis, studies were identified through clinical review by the sponsor.
d Clostridium difficile included all preferred terms in the higher-level term of clostridial infections.
eHerpes zoster included preferred terms in the higher-level term of herpes viral infections that also contain the words zoster or varicella.
fGI abscesses include all preferred terms included in the following categories: anal, rectal, and perirectal: anal abscess, rectal abscess, perirectal abscess; abdominal and intestinal: abdominal abscess, abscess intestinal; abscess, other: groin abscess, vaginal abscess, stoma site abscess, vulval abscess, pelvic abscess, perineal abscess, genital abscess.