Summary

• Please refer to local labeling for relevant information regarding the occurrence of infections with STELARA.
• A pooled analysis of cumulative safety data, including infections and serious infections, for the treatment of STELARA in adults up to 5 years across indications was performed. The rate of infections per 100 patient-years (PY) of follow-up was 89.58 vs 110.40 in STELARA-treated patients vs placebo, respectively.¹
• A pooled analysis of opportunistic infections (OI) and tuberculosis (TB) for the treatment of STELARA in adults up to 5 years across indications was performed. OI (including TB) occurred in 18 patients with Crohn’s disease (CD) or ulcerative colitis (UC) and 1 patient with psoriasis (PsO). The rate of OI per 100 PY of follow-up was 0.10 in STELARA-treated patients vs 0.40 in placebo-treated patients through 5 years.²
• Additionally, data on the occurrence of infections from relevant clinical trials in adult patients (≥18 years old) with plaque PsO,^3-13 pediatric (≥6 to <12) or adolescent patients (≥12 to <18) with PsO,^14,15 adult patients with active psoriatic arthritis (PsA),^16-19 adult patients with CD^20-22 or UC,^23-26 and integrated data in patients with CD and UC^27-29 are summarized.

POOLED SAFETY ANALYSIS ACROSS ALL APPROVED INDICATIONS

Long et al (2022)¹ analyzed pooled safety data of STELARA from 13 phase 2/3 studies (through up to 5 years in CD and psoriatic diseases, 2 years in UC, and 1 year in PsA).

• All patients who received ≥1 dose of STELARA were included in this analysis.
• Safety outcomes are presented as events per 100 PY of follow-up and 95% confidence intervals (CI).
• There were 2501 patients treated with placebo with 1244 PY of follow-up and 6710 patients treated with STELARA with 13,807 PY of follow-up.
• In the pooled analysis, the most frequent infectious adverse events (AEs) in STELARA vs placebo groups were:
  • Nasopharyngitis (20.87 vs 20.83)
  • Upper respiratory tract infections (14.53 vs 13.51)
• The most frequently reported serious infections in STELARA vs placebo groups were:
  • Anal abscess (0.17 vs 0.72)
  • Pneumonia (0.14 vs 0.32)
  • Cellulitis (0.11 vs 0.16)
• For infections and serious infections in all approved indications, see Table: Infections and Serious Infections in Patients Receiving STELARA vs Placebo.

Loftus et al (2022)² reported OI from pooled long-term safety data of 13 phase 2/3 studies through 5 years of CD and PsO, 2 years of UC, and 1 year of PsA.

• OI, including active TB, were identified through sponsor clinical review guided by consensus recommendations. Concomitant corticosteroids/immunomodulators were permitted in CD, UC, and PsO studies.
• Herpes zoster ([HZ] including disseminated OI or non-disseminated) was evaluated separately and identified by Medical Dictionary for Regulatory Activities (MedDRA) preferred terms for “varicella” or “zoster” and indicated as infection per the investigator.
• Safety outcomes were presented as events per 100 PY of follow-up.
• There was 19 reported OI, including active TB, in STELARA-treated patients through 5 years:
  • 18 OIs occurred in patients with CD or UC, 1 OI occurred in a patient with PsO.
• There was 16 reported OI, excluding active TB, in STELARA-treated patients through 5 years (1 patient with PsO, 6 patients with UC, and 9 patients with CD).
  • Fourteen of these patients were receiving concomitant medications.
  • The most common OI were esophageal candidiasis (STELARA, n=3; placebo, n=2) and cytomegalovirus (CMV) colitis (STELARA, n=3; placebo, n=1), all patients were receiving confounding concomitant medications.
    • Of the 3 patients treated with STELARA who contracted CMV colitis, they were also receiving concomitant steroids.
  • Other OI included disseminated histoplasmosis (STELARA, n=1), cryptosporidiosis infection (STELARA, n=1), meningitis listeria (STELARA, n=1), disseminated HZ (STELARA, n=1), pneumonia legionella (STELARA, n=1), ophthalmic herpes simplex and oral herpes simplex (STELARA, n=1), listeriosis (STELARA, n=1).
• For the rate of OI, including HZ and active TB in all approved indications, see Table: Opportunistic Infections in Patients Treated with STELARA vs Placebo.

• One case of HZ was disseminated and counted as an OI:
  • A 53-year-old patient with PsO treated with STELARA reported left-sided flank pain 1 day prior to the first dose of STELARA. Four days later, the patient was diagnosed with disseminated cutaneous HZ based on the presence of 19 cutaneous vesicles outside the primary dermatome which resolved with treatment.

CLINICAL DATA - PsO

The safety and efficacy of STELARA in adult patients diagnosed with moderate to severe plaque PsO were evaluated in 3 (1 phase 2 and 2 phase 3) randomized, double-blind, placebo-controlled studies.^3-5

Cumulative Safety Experience: Results from PsO Clinical Trials

2007 Safety Analysis

The cumulative safety experience of STELARA was analyzed across phase 2 and phase 3 (PHOENIX [A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial Evaluating the Efficacy and Safety of CNTO 1275 in the Treatment of Subjects with Moderate to Severe Plaque-type Psoriasis Followed by Long-term Extension] 1 and PHOENIX 2) plaque PsO clinical trials with up to 76 weeks of treatment (referred to as the 2007 Safety Analysis). The 2007 Safety Analysis included 2266 adult patients treated with 2251 PY of follow-up, including 1970 exposed for up to 6 months, 1285 exposed for up to 1 year, and 373 exposed for up to 18 months.⁶

In the 2007 Safety Analysis, the rates of serious infections were 1.08 per 100 PY, 1.05 per 100 PY, and 1.07 per 100 PY for STELARA 45 mg, STELARA 90 mg, and STELARA-combined groups, respectively.⁶

2009 Safety Analysis

In addition, serious infections across phase 2 and phase 3 (PHOENIX 1, PHOENIX 2, and ACCEPT [Active Comparator (CNTO 1275/Enbrel) Psoriasis Trial]) plaque PsO clinical trials were analyzed with up to 152 weeks of treatment (referred to as the 2009 Safety Analysis). The 2009 Safety Analysis included 3117 adult patients with 4782 PY of follow-up, including 2414 exposed for up to 6 months, 1852 exposed for up to 1 year, 1694 exposed for up to 18 months, 1247 exposed for up to 2 years, 611 exposed for up to 2.5 years, and 157 exposed for up to 3 years.⁶

In the 2009 Safety Analysis, the rates for STELARA 45 mg, STELARA 90 mg, and STELARA combined groups were 0.82 per 100 PY, 1.50 per 100 PY, and 1.19 per 100 PY, respectively; however, through 3 years, the rates of overall infections, treated infections, and infections requiring antibiotics were not different between the STELARA 45 mg and 90 mg groups.⁶

Through 3 years, infections were reported in 67.3% of patients in the combined STELARA treatment group. Infections occurring in ≥5.0% of STELARA-treated patients through 3 years included nasopharyngitis, upper respiratory tract infection, influenza, sinusitis, bronchitis, and gastroenteritis. The rates of overall infections per 100 PY were 134.7, 91.1, and 77.0 in years 1, 2, and 3 in the combined STELARA treatment group, respectively. The rate of overall infections pooled over all 3 years was 112.4.⁷

Through 3 years, serious infections were observed in 1.6% of patients in the combined STELARA treatment group. Serious infections occurring in >0.1% of STELARA-treated patients through 3 years included cellulitis, pneumonia, and gastrointestinal (GI) disorders. Serious infection rates during the controlled period per 100 PY were 1.70 for placebo patients compared with 0.49, 1.97, and 1.23 for STELARA 45 mg, 90 mg, and the combined groups, respectively. The rates of serious infections per 100 PY in the combined STELARA treatment group were 1.41, 1.00, and 0.78 in years 1, 2, and 3, respectively. The rate of serious infections pooled across all 3 years was 1.19.⁷

Additionally, through 3 years, the rate of serious infections in the combined STELARA treatment group (1.19, 95% CI, 0.90-1.54) was consistent with the rate expected in the general PsO population from the MarketScan Database (1.51, 95% CI, 1.18-1.90).⁷

Additional Safety Analysis through 3 Years

Leonardi et al (2010)⁸ evaluated the impact of STELARA on the rates, duration, and severity of infections in PHOENIX 1 and 2 patients through 3 years and whether the half-life of STELARA affects the outcome of infections. Through week 12, serious infection rates (0.5%, 0.0%, and 0.5%), overall infections (22.6%, 25.3%, and 23.1%), infections requiring treatment (7.8%, 6.2%, and 8.3%), and discontinuation of treatment due to infections (0.2%, 0.0%, and 0.5%) were similar in the placebo, STELARA 45 mg, and 90 mg groups, respectively. Through week 12, rates of infection were generally comparable at different time points during the dosing interval for the placebo, STELARA 45 mg, and 90 mg groups (weeks 0-4: 12.3%, 12.7%, 11.7%; weeks 4-8: 7.1%, 7.7%, 6.6%; weeks 8-12: 5.9%, 8.8%, 7.6%). The median time to infection after the last injection occurred in the middle of the dosing interval for every-12-week dosing and was not dose dependent. Through week 12, overall infections severity was similar, with the majority of infections considered mild between the placebo and STELARA-treated groups. Through week 12, the median duration of overall infections was similar between the placebo and STELARA-treated groups: 11 days (range, 6.0-16.0) for placebo; 9.5 days (range, 6.0-15.0) for STELARA 45 mg; and 9 days (range, 6.0-15.0) for STELARA 90 mg. Through 3 years, no clear impact of STELARA on the frequency, severity, or duration of infections requiring treatment over time was identified.

2010 Safety Analysis

Reich et al (2011, 2012)^9,10 evaluated the cumulative safety experience of STELARA in adult patients with up to 4 years of treatment across phase 2 and phase 3 (PHOENIX 1, PHOENIX 2, and ACCEPT) PsO clinical trials (referred to as the 2010 Safety Analysis). The 2010 Safety Analysis included 3117 patients with 6791 PY of follow-up, including 2414 exposed for up to 6 months, 1852 exposed for up to 1 year, 1694 exposed for up to 18 months, 1650 exposed for up to 2 years, 1129 exposed for up to 3 years, and 619 patients from the PHOENIX 2 study exposed for at least 4 years.

STELARA dose adjustment from 45 mg to 90 mg occurred for 194 subjects in PHOENIX 2, and pooled results were based on the dose received at the time the event occurred. The analyses were adjusted for follow-up and expressed as rates per 100 PY of follow-up with 95% CIs.^9,10

In the 2010 Safety Analysis, the numbers of events of serious infection per 100 PY with 95% CIs were 0.80 (0.51-1.21), 1.32 (0.99-1.73), and 1.10 (0.87-1.38) for 45 mg, 90 mg, and combined groups, respectively.^9,10

2011 Safety Analysis

Papp et al (2013)¹¹ analyzed the cumulative safety experience of STELARA in adult patients with up to 5 years of treatment across phase 2 (n=301/320) and phase 3 (PHOENIX 1 [n=753/766], PHOENIX 2 [n=1212/1230], and ACCEPT [n=851/903]) PsO clinical trials (referred to as the 2011 Safety Analysis).

The 2011 Safety Analysis included 3117 patients receiving at least 1 dose of STELARA with 8998 PY of follow-up, including 1855 exposed up to 1 year, 1653 exposed up to 2 years, 1569 exposed up to 3 years, 1482 exposed up to 4 years, 1435 exposed up to 4.5 years, and 838 exposed up to 5 years.¹¹

Infections per 100 PY follow-up with 95% CIs were reported at a rate of 89.8 (86.82-92.90), 84.1 (81.67-86.66), and 86.5 (84.61-88.47) in the 45 mg, 90 mg, and combined groups, respectively. The numbers of infections requiring treatment per 100 PY follow-up with 95% CIs were reported at a rate of 28.97 (27.27-30.74), 27.58 (26.18-29.04), and 28.16 (27.08-29.28) in the 45 mg, 90 mg, and combined groups, respectively. The numbers of serious infections per 100 PY follow-up with 95% CIs were reported at a rate of 0.98 (0.69-1.35), 1.19 (0.91-1.52), and 1.10 (0.89-1.34) in the 45 mg, 90 mg, and combined groups, respectively.¹¹

The 2011 Safety Analysis is the final summary from the STELARA PsO clinical development program. The long-term safety profile of STELARA remained stable over time, and is consistent with the previous reports after 3 and 4 years of follow-up.^10,12,13

CLINICAL DATA - Pediatric PsO

Landells et al (2015)¹⁴ reported results from CADMUS, a phase 3, multicenter, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of STELARA in 110 adolescent patients, age 12 to 17 years with moderate to severe plaque PsO. Infections were reported in 22.2% (8/36) of patients receiving the approved dose of STELARA and 37.8% (14/37) of patients receiving placebo through week 12. Through week 60, infections were reported in 67.3% (74/110) of the combined STELARA group. Two serious infections (pyelonephritis and ear infection) were reported through week 60.

Philipp et al (2020)¹⁵ reported results from CADMUS Jr, a phase 3, open-label, single-arm, multicenter study evaluating 44 pediatric patients (≥6 to <12 years of age) with moderate to severe plaque PsO receiving weight-based STELARA dosing through 56 weeks. Infections were reported in 65.9% (29/44) of patients, of which 27.3% (12/44) received antimicrobial treatment. Three most commonly reported AEs were nasopharyngitis (25% [11/44]), pharyngitis (13.6% [6/44]), and upper respiratory tract infection (13.6% [6/44]) through week 56. Serious infections were reported in 2% (1/44) of patients. One of 3 serious AEs reported through week 56 was infectious mononucleosis, which was not considered to be related to the study treatment by the investigator. No cases of TB or OI were reported through week 56.

CLINICAL DATA - PsA

McInnes et al (2013)^16,17 reported results from PSUMMIT I (A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Ustekinumab, a Fully Human Anti-IL-12/23p40 Monoclonal Antibody, Administered Subcutaneously, in Subjects with Active Psoriatic Arthritis), a phase 3, multicenter, double-blind, placebo-controlled study to assess the efficacy and safety of STELARA in reducing signs and symptoms of active PsA in adult patients.

Results

• The average duration of follow-up through week 52 was 29.75, 50.41, and 50.21 weeks for the placebo-to-STELARA 45 mg, STELARA 45 mg, and STELARA 90 mg groups, respectively.
• Through week 16, the most common AEs in patients receiving STELARA included nasopharyngitis in 19 (4.6%) patients and upper respiratory tract infection in 14 (3.4%) patients.
• No serious infections were reported through week 24.
• After week 24, cholecystitis was reported in 2 patients (1 receiving placebo/STELARA 45 mg, and 1 receiving STELARA 45 mg).
• Salpingitis was reported in 1 patient in the 45 mg group, erysipelas was reported in 1 patient in the 90 mg group, and pharyngolaryngeal abscess was reported in 1 patient in the 90 mg group.
• Through week 52, no OI, including TB, were reported.
• The average duration of follow-up through week 108 was 91.9 weeks for the combined STELARA treatment groups.
• Serious infections occurred at a rate of 1.23 per 100 PY of follow-up through week 108.

Ritchlin et al (2014)¹⁸ evaluated the efficacy and safety of STELARA in PSUMMIT II (A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Ustekinumab, a Fully Human Anti-IL-12/23p40 Monoclonal Antibody, Administered Subcutaneously, in Subjects with Active Psoriatic Arthritis Including Those Previously Treated with Biologic AntiTNFα Agent[s]), a phase 3, multicenter, double-blind, placebo-controlled study in adult patients with active PsA with and without previous anti-tumor necrosis factor (TNF) agent experience.

Results

• Through week 16, investigator-reported infections occurred in 27.1% and 24% of patients treated with STELARA and placebo, respectively.
• Through week 16, serious infections were reported in 1 placebo patient and no STELARA-treated patients.
• Through week 60, there were 2 serious infections occurring in 2 patients in the STELARA 90 mg group (rate of 0.74 per 100 PY of follow-up). One patient experienced septic shock and severe dehydration with Candida present in the stool. A second patient experienced bacteremia (methicillin sensitive Staphylococcus aureus) attributed to a psoriatic plaque infection.
• There were no cases of TB reported.

Kavanaugh et al (2014)¹⁹ described results of a pooled safety analysis from 1 phase 2, and 2 phase 3 studies (PSUMMIT I and PSUMMIT II) including adult patients exposed to STELARA for up to 2 years. The rates of serious infections per 100 PY were 0.69 for placebo, 0.52 for STELARA 45 mg, 2.06 for STELARA 90 mg, and 1.21 for the STELARA combined groups.

CLINICAL DATA - CD

The safety of STELARA was assessed in adult patients with moderately to severely active CD in 3 randomized, double-blind, placebo-controlled, parallel-group, multicenter, phase 3 clinical studies. There were two 8-week intravenous (IV) induction studies (UNITI-1 and UNITI-2) followed by a 44-week subcutaneous (SC) randomized withdrawal maintenance study (IM-UNITI) representing 52 weeks of therapy.²⁰

In both induction studies, at week 0, patients were randomized in a 1:1:1 ratio to receive a single dose of IV placebo, or IV STELARA 130 mg, or weight-based tiered IV STELARA dosing approximating 6 mg/kg. In UNITI-1, a total of 741 patients were randomized and in UNITI-2, a total of 628 patients were randomized.²¹

• During UNITI-1 through week 8, infections were reported in 23.2%, 25.7%, and 23.7% and serious infections were reported in 1.2%, 2.8%, and 1.2% of patients in the STELARA 130 mg, STELARA ~6 mg/kg, and placebo groups, respectively.
• During UNITI-2 through week 8, infections were reported in 14.6%, 21.7%, and 23.1% and serious infections were reported in 1.4%, 0.5%, and 1.4% of patients in the STELARA 130 mg, STELARA ~6 mg/kg, and placebo groups, respectively.

Patients who were in clinical response at week 8 to IV STELARA during the UNITI-1 or UNITI-2 induction study (n=397, primary population) were randomly assigned in a 1:1:1 ratio to receive (through week 40) placebo SC (n=133), or STELARA 90 mg SC every 8 weeks (q8w) (n=132), or STELARA 90 mg SC every 12 weeks (q12w) (n=132).²¹

• Through week 44, infections were reported in 48.1%, 46.2%, and 49.6% and serious infections were reported in 2.3%, 5.3%, and 2.3% of patients in the STELARA 90 mg q8w, STELARA 90 mg q12w, and placebo groups, respectively.

Long-Term Extension through 3 Years

Following the induction and maintenance studies, eligible patients entered a long-term extension (LTE) after completing week 44 of the IM-UNITI study. During the LTE, STELARA-treated patients continued to receive the same treatment they were receiving at week 44 of the IM-UNITI maintenance study. Placebo-treated patients discontinued after study unblinding which was after IM-UNITI week 44 analyses. The safety analysis for the LTE (data accrued through 3 years) included 567 patients in the combined STELARA group with 1544.8 PY of follow-up and 151 patients in the placebo group with 301.9 PY of follow-up.²⁰

• Among all patients entering the LTE, the incidence of infections from week 0 through week 156 was 107.59 (95% CI, 102.48-112.89) per 100 PY follow-up in the combined STELARA group and 100.36 (95% CI, 89.38-112.32) per 100 PY follow-up in the placebo group.
• Among all patients entering the LTE, the incidence of serious infections from week 0 though week 156 was 4.21 (95% CI, 3.25-5.36) per 100 PY follow-up in the combined STELARA group and 3.97 (95% CI, 2.05-6.94) per 100 PY follow-up in the placebo group.
• Serious infections occurring in 2 or more STELARA-treated patients included: anal abscess, 1.4%; pneumonia, 0.7%; cellulitis, 0.4%; gastroenteritis, 0.4%; perirectal abscess, 0.4%; pyelonephritis, 0.4%; and sepsis, 0.4%.
• Other serious infections of interest occurred in 2 patients receiving placebo which included CMV colitis and liver abscess.
• One case of TB was completely resolved with therapy.

Long-term Extension through 5 Years

The safety analysis for the LTE (data accrued through 5 years) included 567 patients in the combined STELARA group with 2267.6 PY of follow-up and 151 patients in the placebo group with 305.5 PY of follow-up.²²

• For infections data among patients entering the LTE, see Table: Incidence of Infections from Week 0 through Final Safety Visit.
• The rates of treatment-emergent serious infections (per 100 PY) from week 44 through week 252 for the combined STELARA, STELARA 90 mg SC q12w, STELARA 90 mg SC q8w, and placebo groups were 3.19, 4.00, 2.70, and 4.53, respectively.³⁰
• In the combined STELARA group, rate of serious infections (per 100 PY) included:³⁰
  • Serious infections and infestations: 2.91
    • Anal abscess: 0.62
    • Pneumonia: 0.22
    • Cellulitis, diverticulitis, gastroenteritis: 0.17 (each)
    • Abdominal abscess, perirectal abscess, pyelonephritis, sepsis, cholecystitis: 0.11 (each)

CLINICAL DATA - UC

The safety of STELARA was evaluated in 2 randomized, double-blind, placebo-controlled clinical studies in adult patients with moderately to severely active UC (UNIFI phase 3 clinical program). There was an 8-week IV induction study followed by a 44-week SC randomized withdrawal maintenance study for a total of 52 weeks of therapy.²¹

During the UNIFI induction study (8 weeks in duration), patients were randomized 1:1:1 at week 0 (baseline) to receive a single IV induction dose of STELARA 130 mg or a dose approximating STELARA 6 mg/kg (~6 mg/kg) or placebo. A total of 961 patients were randomized to treatment in the primary analysis population (STELARA 130 mg IV, n=320; STELARA ~6 mg/kg IV, n=322; placebo IV, n=319).²³

• Among the randomized patients through the final safety visit in the induction trial, infections were reported in 15.4% (49/319), 15.9% (51/321), and 15.9% (51/320) and serious infections were reported in 1.6% (5/319), 0.6% (2/321), and 0.3% (1/320) of patients in the placebo IV, STELARA 130 mg IV, and STELARA ~6 mg/kg IV groups, respectively.

Patients who demonstrated a clinical response at week 8 to a single dose of STELARA IV induction, and patients who did not have a response to IV induction placebo and who then received a dose of STELARA ~6 mg/kg IV at week 8 and had a response at week 16, entered the 44-week maintenance trial (n=523) and were randomized 1:1:1 to receive STELARA 90 mg SC q8w (n=176), STELARA 90 mg SC q12w (n=172), or SC placebo (n=175). These patients comprised the randomized maintenance population (primary analysis population).²³

• Among the randomized patients through week 44 of the maintenance trial, infections were reported in 46.3% (81/175), 33.7% (58/172), and 48.9% (86/176) and serious infections were reported in 2.3% (4/175), 3.5% (6/172), and 1.7% (3/176) of patients in the placebo SC, STELARA 90 mg SC q12w, and STELARA 90 mg SC q8w groups, respectively.

Long-term Extension through 2 Years

Patients who completed the UNIFI maintenance study were eligible to enter the LTE and those randomized to STELARA treatment during the maintenance study continued to receive the same treatment as they were receiving at week 44 of UNIFI maintenance. Patients who were assigned to placebo SC during UNIFI maintenance discontinued the study after unblinding, which occurred after analysis of the UNIFI maintenance study data. The safety analysis from week 44 through week 96 for the LTE included 454 patients in the combined STELARA group and 188 patients in the placebo group.²⁴

• The incidence of infections from week 44 through week 96 was 46.9% in the combined STELARA group and 32.4% in the placebo group.
• The incidence of serious infections from week 44 through week 96 was 2.2% in the combined STELARA group and 1.6% in the placebo group.

Long-term Extension through 3 Years

The safety analysis of data from maintenance week 0 through week 156 for the LTE included 457 patients in the combined STELARA group with 1236.4 PY of follow-up and 188 patients in the placebo group with 304.0 PY of follow-up.²⁵

• For the occurrence of infections from week 0 through 156 in patients who were treated in the LTE, see Table: Incidence of Infections from Week 0 through Week 156.
• Nasopharyngitis and upper respiratory tract infection were among the most frequently reported (≥5 events per 100 PY of follow-up) AE in the combined STELARA group through week 156.
• A case of potential OI was reported in 1 patient in the STELARA 90 mg SC q8w group who received concomitant 6-mercaptopurine and experienced concurrent serious AEs of neutropenic sepsis and oral herpes simplex infection between weeks 96 and 156.
  • The patient recovered after reduction in the dose of 6-mercaptopurine and did not discontinue STELARA treatment.

Long-term Extension through 4 Years

Safety was evaluated through week 220 for all 588 patients treated in the LTE, including randomized and nonrandomized patients. Total PY of follow-up for patients receiving STELARA vs placebo was 1647.4 and 301.7, respectively.²⁶

• Serious infections per 100 PY of follow-up in patients receiving STELARA vs placebo was 2.00 vs 3.31, respectively.
• Through week 220, among patients receiving STELARA, 1 case of CMV was reported.

CLINICAL DATA - INTEGRATED SAFETY ANALYSIS OF CD AND UC STUDIES

Pooled Safety Analysis in IBD through 5 Years in CD and 4 Years in UC

Ghosh et al (2024)²⁷ evaluated the cumulative safety of STELARA from 6 phase 2/3 studies in CD and UC (5 CD studies and 1 UC study) through 5 years in patients with CD and 4 years in patients with UC.

• Concomitant immunomodulators and corticosteroids were permitted.
• All patients receiving ≥1 dose of STELARA were included in the analysis.
• A total of 2575 patients received STELARA and 1389 received placebo. The total PY of follow-up was 4826 for STELARA and 943 for placebo.
• Safety outcomes were reported as the number of events per 100 PY of follow-up or the number of patients per 100 PY when indicated.
• The most frequently reported infections (rate ≥2), with similar rates in the STELARA and placebo groups, were nasopharyngitis, upper respiratory tract infections, sinusitis, urinary tract infection, influenza, gastroenteritis, bronchitis, and oral herpes.
• The most frequently reported serious infections were anal abscess, pneumonia, cellulitis, abdominal abscess, Clostridium difficile colitis, postoperative abscess, rectal abscess, liver abscess, viral pneumonia, and gastroenteritis.
• For rates of infections and serious infections, see Table: Rate of Infections and Serious Infections in Patients Treated with STELARA vs Placebo.

Rate of Infections and Serious Infections in Patients Treated with STELARA vs Placebo

• For pooled data in CD and UC, the rates for C. difficile, HZ, and GI-related abscesses were no higher in the STELARA group compared to placebo.
• A total of 20 patients had OI in IBD, including 15 STELARA-treated patients and 5 placebo-treated patients.
  • Overall rates of OI were 0.31 and 0.53 for STELARA and placebo groups, respectively.
  • The most frequently reported OI were esophageal candidiasis and CMV.
  • Through up to 5 years of follow-up, 16 of the 17 patients with OIs (excluding TB) were receiving concomitant immunosuppressants, including corticosteroids.
  • Active TB cases were reported in 1 (0.02 per 100 PYs) patient in the STELARA group and 2 (0.21 per 100 PYs) patients in the placebo group.
    • The one patient in the STELARA group was a 45-year-old South African patient with CD who received STELARA q8w during the long-term extension phase and was also receiving concomitant steroids. The patient was asymptomatic and had a positive QuantiFERON-TB Gold test along with positive bronchial brushings for Mycobacterium tuberculosis infection.
    • In the placebo group, one case of active TB was reported in a 32-year-old Hungarian patient with CD 10 months after the last STELARA dose (the patient was also receiving concomitant steroids).
    • Another case of pulmonary TB was reported in a 52-year-old Korean patient with UC who received placebo and never received STELARA in the 1-year maintenance period.
• There was no difference in the risk of serious infections compared to placebo (Hazard ratio [95% CI]: 0.928 [0.646-1.334]).
• No significant predictors of serious infection were observed among the variables assessed for patients in the STELARA group, either for CD or UC (P<0.05).

Pooled Safety Analysis in CD and UC: Bio-naïve and Bio-failure Subgroups

Danese et al (2022)²⁸ conducted an integrated safety analysis incorporating data from phase 2/3 and phase 3b studies in CD and UC for bio-naïve patients (up to 5 years in CD and up to 2 years in UC).

• Bio-naïve was defined as patients who were never treated with biologics. Concomitant immunomodulators and corticosteroids were permitted.
• Infections and serious infections are presented as event rates per 100 PY of follow-up.
• Through up to 1 year, the median duration of follow-up for STELARA and placebo was 39.26 and 27.61 weeks, respectively. The total PY of follow-up was 582 for STELARA and 226 for placebo.
  • The rate of infections (events per 100 PY) for bio-naïve patients in the STELARA group was 90.02 (95% CI, 82.48-98.07) vs 90.85 (95% CI, 78.84-104.18) in the placebo group.
  • The rate of serious infections (events per 100 PY) for bio-naïve patients in the STELARA group was 2.23 (95% CI, 1.19-3.82) vs 2.66 (95% CI, 0.98-5.79) in the placebo group.
• Through up to 5 years, the median duration of follow-up was 101.90 weeks for STELARA and 45.96 weeks for placebo. The total PY of follow-up for STELARA and placebo was 1511 and 376, respectively. There were 771 bio-naïve patients who received STELARA and 425 bio-naïve patients who received placebo.
  • The rate of infections (events per 100 PY) for bio-naïve patients in the STELARA group was 70.76 (95% CI, 66.58-75.13) vs 80.93 (95% CI, 72.08-90.56) in the placebo group.
  • The rate of serious infections (events per 100 PY) for bio-naïve patients in the STELARA group was 2.12 (95% CI, 1.45-2.99) vs 3.19 (95% CI, 1.65-5.58) in the placebo group.

Loftus et al (2022)²⁹ conducted an integrated safety analysis incorporating data from 5 phase 2/3 studies in CD and UC in patients with a history of prior biologic failure (up to 5 years in CD and up to 2 years in UC).

• Infections and serious infections are presented as event rates per 100 PY of follow-up.
• Through up to 1 year, the average duration of follow-up for STELARA and placebo was 32.63 and 19.79 weeks, respectively. The total PY follow-up was 1001 for STELARA and 322 for placebo. A total of 1595 patients received STELARA and 847 received placebo.
  • The rate of infections (events per 100 PY) for patients with a history of biologic failure in the STELARA group was 130.48 (95% CI, 123.50-137.76) vs 146.39 (95% CI, 133.48-160.21) in the placebo group.
  • The rate of serious infections (events per 100 PY) for patients with a history of biologic failure in the STELARA group was 6.69 (95% CI, 5.19-8.50) vs 8.37 (95% CI, 5.52-12.18) in the placebo group.
• Through up to 5 years, the average duration of follow-up for STELARA and placebo was 64.18 and 29.06 weeks, respectively. The total PY follow-up was 1970 for STELARA and 473 for placebo. A total of 1596 patients received STELARA and 847 received placebo.
  • The rate of infections (events per 100 PY) for patients with a history of biologic failure in the STELARA group was 118.95 (95% CI, 114.18-123.87) vs 129.91 (95% CI, 119.84-140.59) in the placebo group.
  • The rate of serious infections (events per 100 PY) for patients with a history of biologic failure in the STELARA group was 5.23 (95% CI, 4.27-6.34) vs 6.97 (95% CI, 4.80-9.79) in the placebo group.
• The most frequently reported infections were nasopharyngitis and upper respiratory tract infection.

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 18 March 2024.

Summarized in this response are relevant data from pivotal clinical trials in the treatment of PsO (adult patients, phase 2 and 3; adolescent patients, phase 3; pediatric patients, phase 3), PsA (adult patients, phase 2 and 3), CD (adult patients, phase 2/3 and phase 3b) and UC (adult patients, phase 3). Additionally, relevant data from pooled analyses of phase 2/3 clinical trials across approved indications are also summarized.