Table 8.
Exposure-adjusted incidence rates of GI adverse events in the overall safety population
| Adverse event | UC |
CD |
UC and CD |
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Placebo n=149* |
Vedolizumab n=1107† |
Placebo n=355‡ |
Vedolizumab n=1723§ |
Placebo n=504¶ |
Vedolizumab n=2830** |
|||||||
| No. of patients with event | No. of patients with event/100 PY (95% CI) | No. of patients with event | No. of patients with event/100 PY (95% CI) | No. of patients with event | No. of patients with event/100 PY (95% CI) | No. of patients with event | No. of patients with event/100 PY (95% CI) | No. of patients with event | No. of patients with event/100 PY (95% CI) | No. of patients with event | No. of patients with event/100 PY (95% CI) | |
| Any GI AE | 54 | 86.2 (61.5 to 110.9) | 592 | 43.3 (39.2 to 47.5) | 126 | 133.2 (107.0 to 159.4) | 1090 | 75.3 (69.6 to 81.1) | 180 | 114.5 (95.8 to 133.1) | 1682 | 59.8 (56.2 to 63.4) |
| Fistula†† | 0 | 0 | 0 | 0 | 13 | 10.0 (4.5 to 15.5) | 121 | 4.6 (3.8 to 5.5) | 13 | 6.2 (2.8 to 9.5) | 121 | 2.6 (2.1 to 3.0) |
| Stenosis | 1 | 1.2 (0.0 to 3.7) | 10 | 0.5 (0.2 to 0.8) | 5 | 3.8 (0.5 to 7.1) | 102 | 3.8 (3.1 to 4.6) | 6 | 2.8 (0.6 to 5.1) | 112 | 2.4 (1.9 to 2.8) |
| Duodenal and small intestinal stenosis and obstruction‡‡ | 1 | 1.2 (0.0 to 3.7) | 5 | 0.2 (0.0 to 0.5) | 3 | 2.3 (0.0 to 4.8) | 33 | 1.2 (0.8 to 1.6) | 4 | 1.9 (0.0 to 3.7) | 38 | 0.8 (0.5 to 1.0) |
| Ileal stenosis and obstruction§§ | 0 | 0.0 (0.0 to 3.7) | 3 | 0.1 (0.0 to 0.3) | 1 | 0.8 (0.0 to 2.2) | 32 | 1.2 (0.8 to 1.6) | 1 | 0.5 (0.0 to 1.4) | 35 | 0.7 (0.5 to 1.0) |
| Stenosis and obstruction, other¶¶ | 0 | 0.0 (0.0 to 3.7) | 1 | <0.1 (0.0 to 0.1) | 1 | 0.8 (0.0 to 2.2) | 29 | 1.1 (0.7 to 1.5) | 1 | 0.5 (0.0 to 1.4) | 30 | 0.6 (0.4 to 0.9) |
| Colonic and rectal stenosis and obstruction*** | 0 | 0.0 (0.0 to 3.7) | 1 | <0.1 (0.0 to 0.1) | 0 | 0.0 (0.0 to 2.3) | 14 | 0.5 (0.2 to 0.8) | 0 | 0 (0.0 to 1.4) | 15 | 0.3 (0.2 to 0.5) |
| Anal stenosis and obstruction††† | 0 | 0 | 0 | 0 | 0 | 0.0 (0.0 to 2.3) | 2 | 0.1 (0.0 to 0.2) | 0 | 0 (0.0 to 1.4) | 2 | <0.1 (0.0 to 0.1) |
| Pancreatitis‡‡‡ | 1 | 1.2 (0.0 to 3.7) | 2 | 0.1 (0.0 to 0.2) | 0 | 0.0 (0.0 to 2.3) | 10 | 0.4 (0.1 to 0.6) | 1 | 0.5 (0.0 to 1.4) | 12 | 0.3 (0.1 to 0.4) |
| Any serious GI AE | 12 | 15.3 (6.5 to 24.2) | 149 | 7.4 (6.2 to 8.6) | 30 | 24.0 (15.2 to 32.8) | 389 | 15.4 (13.8 to 17.0) | 42 | 20.7 (14.3 to 27.1) | 538 | 11.8 (10.8 to 12.9) |
| Fistula†† | 0 | 0 | 0 | 0 | 2 | 1.5 (0.0 to 3.6) | 21 | 0.8 (0.4 to 1.1) | 2 | 0.9 (0.0 to 2.2) | 21 | 0.4 (0.3 to 0.6) |
| Duodenal and small intestinal stenosis and obstruction‡‡ | 1 | 1.2 (0.0 to 3.7) | 5 | 0.2 (0.0 to 0.5) | 1 | 0.8 (0.0 to 2.2) | 24 | 0.9 (0.5 to 1.2) | 2 | 0.9 (0.0 to 2.2) | 29 | 0.6 (0.4 to 0.8) |
| Ileal stenosis and obstruction§§ | 0 | 0.0 (0.0 to 3.7) | 3 | 0.1 (0.0 to 0.3) | 0 | 0.0 (0.0 to 2.3) | 23 | 0.8 (0.5 to 1.2) | 0 | 0 (0.0 to 1.4) | 26 | 0.5 (0.3 to 0.8) |
| Stenosis and obstruction, other¶¶ | 0 | 0.0 (0.0 to 3.7) | 1 | <0.1 (0.0 to 0.1) | 1 | 0.8 (0.0 to 2.2) | 16 | 0.6 (0.3 to 0.9) | 1 | 0.5 (0.0 to 1.4) | 17 | 0.4 (0.2 to 0.5) |
| Colonic and rectal stenosis and obstruction*** | 0 | 0 | 0 | 0 | 0 | 0.0 (0.0 to 2.3) | 5 | 0.2 (0.0 to 0.3) | 0 | 0 (0.0 to 1.4) | 5 | 0.1 (0.0 to 0.2) |
Exposure-adjusted incidence rates for each AE were calculated by dividing the number of patients experiencing the event by the total PYs, multiplied by 100. PYs were calculated as the sum of each patient's contribution, calculated from the days of exposure (ie, AE onset date minus the date of first dose plus 1 day). For each AE, the PYs were truncated after a patient experienced the AE and each AE was counted only once per patient. Patients who were randomised to placebo and then rolled over into an open-label study could contribute to events in either the placebo or vedolizumab group depending on when they experienced the AE. PYs were calculated accordingly for placebo or vedolizumab for each AE. When the number of events=0, the 95% CI was calculated based on rule of 3 (ie, (0, 3/total PYs)×100).
*Includes patients from GEMINI 1.
‡Includes patients from GEMINI 2 and GEMINI 3.
§Includes patients from studies C13004, GEMINI 2, GEMINI 3 and GEMINI LTS.
¶Includes patients from GEMINI 1, GEMINI 2 and GEMINI 3.
**Includes patients from all six studies.
††Includes MedDRA PTs: anal fistula, colonic fistula, enterocolonic fistula, enterocutaneous fistula, enterovesical fistula, female genital tract fistula, fistula, ileal fistula, perineal fistula, postprocedural fistula, rectourethral fistula, vaginal fistula.
‡‡Includes MedDRA PTs: duodenal stenosis, small intestinal obstruction, small intestinal stenosis.
§§Includes MedDRA PTs: ileal stenosis, ileus, subileus.
¶¶Includes MedDRA PTs: intestinal obstruction, intestinal stenosis.
***Includes MedDRA PTs: colonic obstruction, colonic stenosis, rectal stenosis.
†††Includes MedDRA PTs: anal stenosis.
‡‡‡Includes MedDRA PTs: pancreatitis, pancreatitis acute, pancreatitis chronic.
AE, adverse event; CD, Crohn's disease; GI, gastrointestinal; LTS, long-term safety; MedDRA, Medical Dictionary for Regulatory Activities; PT, preferred term; PY, person-years; UC, ulcerative colitis.