PMC

Key safety events per 100 patient-years of exposure during the first, second, and third year of ustekinumab maintenance therapy. AE, adverse events; CI, confidence interval; IV, intravenous; LTE, long-term extension; NMSC, nonmelanoma skin cancer; q8w, every 8 weeks; q12w, every 12 weeks; SC, subcutaneous.a. Number of AEs per 100 patient-years of follow-up and 95% confidence interval [rates by each year of follow-up] in the pooled ustekinumab ulcerative colitis safety cohort. Confidence intervals based on an exact method assuming that the observed number of events follows a Poisson distribution.
b. Infection as assessed by the investigator.
c. All ustekinumab [first year] includes: 1] patients who received ustekinumab SC [q8w or q12w] in this maintenance study; 2] patients who were in clinical response to ustekinumab IV induction dosing and received placebo SC on entry into this maintenance study; and 3] data from Week 0 to Week 8 for patients who were in clinical response to ustekinumab IV induction dosing and were randomised to placebo SC on entry into this maintenance study.
d. All ustekinumab-treated in the LTE [second year] includes: 1] data from Week 44 through Week 96 for patients who were in clinical response to ustekinumab IV induction dosing and were randomised to ustekinumab 90 mg SC q12w on entry into the maintenance study; 2] patients who were in clinical response to ustekinumab IV induction dosing and were randomised to receive ustekinumab 90 mg SC q8w on entry into the maintenance study, with data from Week 44 through Week 96; 3] patients who were in clinical response to ustekinumab IV induction dosing, randomised to receive placebo SC on entry into the maintenance study, and had a dose adjustment prior to Week 96 to ustekinumab 90 mg SC q8w, with data from the time of dose adjustment onward; and 4] patients who were not in clinical response to ustekinumab at induction Week 8 but were in clinical response at induction Week 16 after an SC administration of ustekinumab at induction Week 8 and received ustekinumab 90 mg SC q8w on entry into the maintenance study with data from Week 44 through Week 96.
e. All ustekinumab in the LTE [third year] includes: 1] data from Week 96 through Week 156 for patients who were in clinical response to ustekinumab IV induction dosing and were randomised to ustekinumab 90 mg SC q12w on entry into the maintenance study; 2] patients who were in clinical response to ustekinumab IV induction dosing and were randomised to receive ustekinumab 90 mg SC q8w on entry into the maintenance study, with data from Week 96 through Week 156; 3] patients who were in clinical response to ustekinumab IV induction dosing, randomised to receive placebo SC on entry into the maintenance study, and had a dose adjustment at or after Week 96 to ustekinumab 90 mg SC q8w, with data from the time of dose adjustment onward; and 4] patients who were not in clinical response to ustekinumab at induction Week 8 but were in clinical response at induction Week 16 after an SC administration of ustekinumab at induction Week 8 and received ustekinumab 90 mg SC q8w on entry into the maintenance study with data from Week 96 through Week 156.

All adverse events (A) and key safety events (B) during ustekinumab exposure^{, ,, ,}
†. Number of treatment-emergent adverse events per 100 patient-years of follow-up and 95% confidence interval (rates by each year of follow-up) in the pooled ustekinumab ulcerative colitis safety cohort. Confidence intervals based on an exact method assuming that the observed number of events follows a Poisson distribution.
‡. Infection as assessed by the investigator.
§. Placebo (First Year) includes 1) Patients who were in clinical response to ustekinumab IV induction dosing and were randomized to placebo SC on entry into this maintenance study and were followed after Week 8; and 2) Patients who were in clinical response to placebo IV induction dosing and received placebo SC on entry into this maintenance study. Only includes data from Week 8 onward for patients who were in clinical response to ustekinumab IV induction dosing and were randomized to placebo SC on entry into this maintenance study.
¶. All Ustekinumab (First Year) includes 1) patients who received ustekinumab SC (q8w or q12w) in this maintenance study; and 2) patients who were in clinical response to ustekinumab IV induction dosing and received placebo SC on entry into this maintenance study; 2)data from Week 0 to Week 8 for patients who were in clinical response to ustekinumab IV induction dosing and were randomized to placebo SC on entry into this maintenance study.
††. All Ustekinumab-treated in the LTE (Second Year) includes: 1) Patients who were in clinical response to ustekinumab IV induction dosing and were randomized to receive ustekinumab 90 mg SC q12w or q8w on entry into the maintenance study, with data from Week 44 through Week 96; 2) Patients who were in clinical response to ustekinumab IV induction dosing, randomized to receive placebo SC on entry into the maintenance study, and had a dose adjustment to ustekinumab 90 mg SC q8w, with data from the time of dose adjustment onward; 3) Patients who were not in clinical response to ustekinumab at I-8 but were in clinical response at I-16 after a SC administration of ustekinumab at I-8 and received ustekinumab 90 mg SC q8w on entry into the maintenance study with data from Week 44 through Week 96.
Key: CI, confidence interval; IV, intravenous; NMSC, nonmelanoma skin cancer; q8w, every 8 weeks; 12w, every 12 weeks; SC, subcutaneous

A, Among patients exposed to ustekinumab and having had a severe cardiovascular event (SCE), ustekinumab initiation was screened during 2 periods prior to SCE. The number of ustekinumab initiations during the risk period was compared with the number of ustekinumab initiations during the reference period, leading to assessment of the odds ratio (OR) of the case-crossover analysis. B, Time trends in the general prescribing pattern for ustekinumab between 2010 and 2016. Because the number of ustekinumab initiations was not constant over time, time controls were introduced in the model. The OR among time controls estimates how much the case-crossover analysis is associated with the time trends in the prescription of ustekinumab over time. The final OR of the case-time-control estimates the association between the initiation of ustekinumab and SCE (ie, the OR of the case-crossover analysis), adjusted for time trends (estimated among time controls). M-6 indicates the 6th month before the index date; and M-12, the 12th month before the index date.

OR indicates odds ratio.
^aLow risk if fewer than 2 cardiovascular risk factors and no history of SCE; high risk if more than 2 cardiovascular risk factors or a history of SCE.
^bExposure: ustekinumab initiation; event: hospitalized in intensive care unit with acute coronary syndrome and stroke; 6-month periods.
^cExposure: ustekinumab initiation, reinitiation (after 6 months without ustekinumab prescription), and dose increases; event: hospitalized in intensive care unit with acute coronary syndrome and stroke; 6-month periods.
^dExposure: ustekinumab initiation; event: acute coronary syndrome, stroke, and unstable angina; 6-month periods.