Summary

• STELARA is a selective immunosuppressant. Immunosuppressive agents have the potential to increase the risk of malignancy. Some patients who received STELARA in clinical studies developed cutaneous and noncutaneous malignancies.¹
• STELARA has not been studied in patients with a history of malignancy. Caution should be exercised when considering the use of STELARA in patients with a history of malignancy or when considering continuing treatment in patients who develop a malignancy.¹
• All patients, in particular those greater than 60 years of age, patients with a medical history of prolonged immunosuppressant therapy or those with a history of psoralen plus ultraviolet A (PUVA) treatment, should be monitored for the appearance of nonmelanoma skin cancer (NMSC).¹
• A pooled analysis of long-term safety data for the treatment of STELARA in adults up to 5 years across indications (Crohn’s disease [CD], ulcerative colitis [UC], psoriasis, and psoriatic arthritis [PsA]) was performed. The incidence of NMSC and other malignancies for STELARA vs placebo for pooled indications were 0.70 vs 0.96 and 0.53 vs 0.32 per 100 patient-years (PY) of followup, respectively.²
• In adult patients with psoriasis, the cumulative safety experience with up to 5 years of treatment across phase 2 and phase 2 was reported (representing 8998 PY of follow-up), the rate of malignancies other than NMSC per 100 PY was 0.60 (0.45-0.78) for the combined group (STELARA 45 mg and 90 mg).³
• The risk of malignancy was evaluated using a nested case-control analyses in patients with psoriasis in the Psoriasis Longitudinal Assessment and Registry (PSOLAR).⁴
• In a pooled safety analysis from one phase 2 and two phase 3 studies (PSUMMIT I and PSUMMIT II), including adult patients with PsA exposed to STELARA for up to 2 years, the rates of malignancies other than NMSC per 100 PY were 0.00 for placebo, 0.39 for STELARA 45 mg, 0.00 for STELARA 90 mg, and 0.21 for STELARA combined groups.⁵
• In a phase 3 multicenter, randomized, double-blind, placebo-controlled study of 110 adolescent patients age 12 to 17 years with moderate to severe plaque psoriasis, there were no malignancies reported through week 60.⁶
• In a phase 3, multicenter, open-label, single-arm study of 44 pediatric patients age 6 to 11 years with moderate to severe plaque psoriasis, there were no malignancies reported through week 56.⁷
• An integrated safety analysis of data from phase 2/3 and phase 3b studies in CD and UC showed that through up to 1 year of treatment, the rate of malignancies excluding NMSC (events per 100 PY) was 0.34 in STELARA-treated bio-naïve patients and 0.44 in placebo-treated bio-naïve patients. Through up to 5 years of treatment, the rate of malignancies excluding NMSC (events per 100 PY) was 0.46 in STELARA-treated bio-naïve patients and 0.27 in placebo-treated bio-naïve patients.⁸
• A pooled analysis of long-term safety of STELARA treatment among biologic failure patients up to 5 years in CD and 2 years in UC was performed. The event rates of malignancies excluding NMSC (events per 100 PY) for STELARA vs placebo were 0.51 vs 0.42.⁹
• A pooled long-term safety analysis of data from phase 2/3 studies in CD and UC showed that through up to 1 year of treatment, the rate of malignancies excluding NMSC (events per 100 PY) for STELARA vs placebo was 0.40 vs 0.17.¹⁰
• A pooled safety analysis through 5 years of treatment in CD and 4 years in UC showed that, the rate of malignancies excluding NMSC (events per 100 PY) through up to 5 years was 0.39 and 0.32 for STELARA and placebo, respectively.¹¹
• The risk of malignancy in patients with inflammatory bowel disease (IBD; CD and UC) and a history of cancer subsequently exposed to immunosuppressive IBD therapies was evaluated using data from a registry.¹²

Pooled Safety Analysis Across All Approved Indications

Long et al (2022)² reported malignancies from pooled long-term safety data of 13 phase 2/3 studies (5 years in CD and psoriasis, 2 years in UC, and 1 year in PsA).

Study Designs/Methods

• A total of 6710 patients (IBD, n=2575; psoriatic indications, n=4135) were exposed to ≥1 dose of STELARA with 13,807 PY of exposure.
• The incidence per 100 PY and corresponding 95% confidence intervals (CIs) by malignancy type are presented in Table: Type of Malignancy: Incidence per 100 PY of Follow-up.

• The majority of NMSCs were reported in patients with psoriatic indications, with comparable event rates between the STELARA and placebo groups.
• The ratio of basal cell carcinoma (BCC): squamous cell carcinoma (SCC) events in the STELARA group was approximately 4:1.
• The most frequently reported malignancies other than NMSC were prostate, melanoma, colorectal, and breast.
• Overall, lymphoma was reported in 2 patients with psoriasis in the STELARA group. One patient with cutaneous T-cell lymphoma, incorrectly diagnosed as psoriasis and was determined to have been present prior to study entrance. The other patient possibly had Hodgkin lymphoma based on autopsy findings in a patient who died from traumatic bowel perforation.
• The standardized incidence ratio (SIR) of observed patients with non-NMSC events compared to expected, based on Surveillance, Epidemiology and End Results (SEER) rates was 0.96 (95% CI, 0.75-1.22), indicating no increased risk of malignancy with STELARA treatment.

CLINICAL DATA IN PLAQUE PSORIASIS

Cumulative Safety Experience: Results from Psoriasis Clinical Trials

2007 Safety Analysis

Gordon et al (2009)¹³ analyzed the cumulative safety experience of STELARA 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) psoriasis clinical trials with up to 76 weeks of treatment (referred to as the 2007 Safety Analysis).

Study Design/Methods

• The 2007 Safety Analysis included 2266 adult patients treated with 2251 PY of follow-up, including 1970 exposed for at least 6 months, 1285 exposed for at least 1 year, and 373 exposed for at least 18 months.

Results

• The rates of NMSC per 100 PY were 0.63, 0.97, and 0.80 for the STELARA 45 mg, STELARA 90 mg, and STELARA combined groups, respectively.
• The rates of malignancies other than NMSC per 100 PY were 0.63, 0.09, and 0.36 for the STELARA 45 mg, STELARA 90 mg, and STELARA combined groups, respectively.

2009 Safety Analysis

Gordon et al (2009, 2012)^13,14 analyzed occurrence of malignancies across phase 2 and phase 3 (PHOENIX 1, PHOENIX 2, and ACCEPT [Active Comparator (CNTO 1275/Enbrel) Psoriasis Trial]) psoriasis clinical trials in adult patients with up to 152 weeks of treatment (referred to as the 2009 Safety Analysis). Papp et al (2010)¹⁵ compared the rates of malignancies from these trials to rates expected in the United States (US) population.

Study Design/Methods

• The 2009 Safety Analysis included 3117 adult patients with 4782 PY of follow-up, including 2414 exposed for at least 6 months, 1852 exposed for at least 1 year, 1694 exposed for at least 18 months, 1247 exposed for at least 2 years, 611 exposed for at least 2.5 years, and 157 exposed for at least 3 years.
• During each of the 3 years, safety data were evaluated on an annualized basis. The first year included data for ≤48 weeks from phase 2 and phase 3 (PHOENIX 1, PHOENIX 2, and ACCEPT) psoriasis clinical trials, the second year included data for 48 weeks to 96 weeks from PHOENIX 1 and PHOENIX 2, and the third year included data for >96 weeks from PHOENIX 1.

Results

• In the 2009 Safety Analysis, the rates of NMSC per 100 PY were 0.64, 0.77, and 0.71 for the STELARA 45 mg, STELARA 90 mg, and STELARA combined groups, respectively.
• The rates of malignancies other than NMSC per 100 PY were 0.69, 0.46, and 0.57 for the STELARA 45 mg, STELARA 90 mg, and STELARA combined groups, respectively.
• The rates of NMSC per 100 PY were 0.80 and 1.06 for STELARA 45 mg and 90 mg, respectively, for year 1. For year 2, the rates were 0.27 and 0.59 for STELARA 45 mg and 90 mg, respectively, and 0.96 for STELARA 45 mg and 0.00 for STELARA 90 mg for year 3.
• There were 34 STELARA-treated patients who developed NMSC (28 patients had BCC and 9 patients had SCC). The ratio of BCC:SCC was 3.1:1, which was consistent with the ratio reported in immunocompetent patients in the general population.
• The rates of malignancies other than NMSC per 100 PY were 0.44 and 0.35 for STELARA 45 mg and 90 mg, respectively, for year 1. The rates were 1.21 for STELARA 45 mg and 0.82 for STELARA 90 mg for year 2, and 0.32 for STELARA 45 mg and 0.00 for STELARA 90 mg for year 3.
• There were 27 malignancies other than NMSC reported in STELARA-treated patients. Among these malignancies, those that were reported include these types of cancer: prostate (n=9), breast (n=3), colorectal (n=2), renal (n=2), head and neck (n=2), melanoma (n=3), and lymphoma (n=1).
• Through 3 years, the rate of malignancies other than NMSC in the combined STELARA treatment group was consistent with the rate expected in the general US population from the National Institutes of Health SEER database (SIR, 1.05 [95% CI, 0.69-1.53]).

2010 Safety Analysis

Reich et al (2011, 2012)^16,17evaluated 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) psoriasis clinical trials (referred to as the 2010 Safety Analysis). Papp et al (2012)¹⁸ compared the rates of malignancies from these trials to rates expected in the US population.

Study Design/Methods

• The 2010 Safety Analysis included 3117 adult patients with 6791 PY of follow-up, including 2414 exposed up to 6 months, 1852 exposed up to 1 year, 1694 exposed up to 18 months, 1650 exposed up to 2 years, 1129 exposed up to 3 years, and 619 patients from the PHOENIX 2 study exposed up to 4 years.
• STELARA dose adjustment from 45 mg to 90 mg occurred for 194 patients 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.
• During each of the 4 years, data were evaluated on an annualized basis. The first year included data for patients receiving ≤48 weeks of treatment, the second year included data for patients receiving 48 weeks to 96 weeks of treatment, the third year included data for patients receiving >96 weeks to 144 weeks of treatment, and the fourth year included data for patients receiving >144 weeks of treatment.

Results

• In the 2010 Safety Analysis, the cumulative rates of NMSC per 100 PY with 95% CIs were 0.70 (0.43-1.09) for 45 mg, 0.53 (0.33-0.82) for 90 mg, and 0.61 (0.43-0.82) (1.3% of STELARA-treated patients) for the combined group.
• The rates of malignancies other than NMSC per 100 PY were 0.63 (0.37-1.00) for 45 mg, 0.61 (0.39-0.91) for 90 mg, and 0.62 (0.45-0.84) (1.3% of STELARA-treated patients) for the combined group.
• The most frequently observed malignancies other than NMSC during the clinical trials were: prostate, colorectal, melanoma in situ, and breast.
• Through the 2010 analysis, the rates of other malignancies were consistent with the expected incidences in the general US population, using the SEER database (2009) adjusted for age, gender, and race.
• The SIRs with 95% CIs for malignancies other than NMSC were 1.12 (0.66-1.76) for 45 mg, 1.01 (0.64-1.52) for 90 mg, and 1.06 (0.76-1.43) for the combined group.
• The rates by year of NMSC per 100 PY with 95% CIs for the STELARA 45 mg, 90 mg, and combined group, are described in Table: Rates by Year of NMSC per 100 PY with 95% CIs for the STELARA 45 mg, 90 mg, and Combined Groups.

• The rates by year of malignancies other than NMSC per 100 PY with 95% CIs for STELARA 45 mg, 90 mg, and combined group, are described in Table: Rates by Year of Malignancies Other Than NMSC per 100 PY with 95% CIs for the STELARA 45 mg, 90 mg, and Combined Groups.

• Rates of NMSC and other malignancies have remained stable compared with earlier analyses without an apparent dose effect.

2011 Safety Analysis

Papp et al (2013)³ 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]) psoriasis clinical trials (referred to as the 2011 Safety Analysis).

Study Designs/Methods

• The 2011 Safety Analysis included 3117 adult 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.

Results

• In the 2011 Safety Analysis, the cumulative rates of NMSC per 100 PY with 95% CIs were 0.64 (0.41-0.95) for 45 mg, 0.44 (0.28-0.66) for 90 mg, and 0.52 (0.39-0.70) for the combined group.
  • Over time, NMSC rates varied year-to-year with no increasing trend.
  • Of the 47 patients with NMSC (including 3 patients reporting both SCC and BCC), 40 had BCC and 10 had SCC (BCC:SCC ratio of 4:1).
• The rates of malignancies other than NMSC per 100 PY were 0.59 (0.37-0.89) for 45 mg, 0.61 (0.42-0.87) for 90 mg, and 0.60 (0.45-0.78) for the combined group.
  • Over time, there was year-to-year variability, but no increasing trend was evident.
• Through year 5 of follow-up, 54 STELARA-treated patients reported malignancies other than NMSC. Among these malignancies, those that were reported include these types of cancer: prostate (n=14), melanoma (n=6), colorectal (n=5), breast (n=4), renal (n=3), head and neck (n=3), bladder (n=2), leukemia (n=2), lymphoma (n=2), myeloma (n=2), pancreatic (n=2), adenocarcinoma, unknown primary (n=1), cervical (n=1), endometrial (n=1), esophageal (n=1), lung (n=1), ovarian (n=1), SCC, unknown primary (n=1), testicular (n=1), thyroid (n=1).
  • Of the 2 cases of lymphoma, 1 patient reported preexisting cutaneous T-cell lymphoma prior to study entry and there was also 1 possible case of Hodgkin disease based on autopsy findings in a patient who died from traumatic bowel perforation.
• Through the 2011 analysis, the rates of other malignancies were consistent with the expected incidences in the general US population, using the SEER database adjusted for age, gender, and race. The SIRs of malignancies other than NMSC with 95% CIs were 0.99 (0.62-1.50) for 45 mg, 0.98 (0.66-1.39) for 90 mg, and 0.98 (0.74-1.29) for the combined group.

The 2011 Safety Analysis is the final summary from the STELARA psoriasis 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.^14,17,19

PSOLAR REGISTRY

PSOLAR is a long-term, prospective, observational cohort of adult patients with moderate to severe plaque psoriasis who were receiving or candidates to receive systemic treatment (including phototherapy) across Europe and North/South America. Information on patient demographics, disease activity and severity, comorbidities, and psoriasis medication use is collected every 6 months with a planned follow-up for each patient of at least 8 years from registry enrollment. Potential confounding variables tested for inclusion in the model included but was not limited to, the use of other study medications, including the odds ratio (OR) for STELARA which was adjusted for methotrexate and anti-tumor necrosis factor (TNF) use.⁴

• There were 12,090 registry participants (48,870 PY) in this analysis with a registry cutoff date of August 23, 2015. A total of 252 PSOLAR participants met eligibility criteria for malignancy cases and were matched to 1008 controls (4:1). The mean age for malignancy cases excluding NMSC was 59.9 years (standard deviation, ±10.9 years) and 137 (54.4%) malignancy cases excluding NMSC occurred in male participants.⁴
• Individually, there was no increased risk of malignancy with STELARA for each of the 5 most common malignancies in PSOLAR (breast cancer [n=40], prostate cancer [n=36], lung cancer [n=29], melanoma [n=28], and lymphoma [n=14]).⁴
• No overall increased risk for malignancy for any duration of treatment was seen for STELARA when compared to no STELARA treatment:⁴
  • OR 0.66 (95% CI, 0.14-3.07) for >0 months to <3 months; 1.12, (95% CI, 0.63-2.01) for ≥3 months to <12 months; and 0.98, (95% CI, 0.63-1.53) for ≥12 months.
• ORs of incident malignancies associated with monotherapy of STELARA can be found in Table: Odds Ratios of Incident Malignancies Associated with Monotherapy of STELARA.

CLINICAL DATA IN PsA

McInnes et al (2013)²⁰ 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 108 was 91.9 weeks for the combined STELARA treatment groups.
• Malignancies occurred at a rate of 0.38 per 100 PY of follow-up through week 108.

Ritchlin et al (2014)²¹ 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 Anti-TNFα Agent[s]), a phase 3, multicenter, double-blind, placebo-controlled study in patients with active PsA with and without previous TNF agent experience.

Results

• There were 2 malignancies reported through week 60, a SCC in situ of the skin (uncovered from cleared psoriasis plaque) in a patient treated with STELARA 90 mg, and breast cancer reported in a patient treated with STELARA 45 mg. Both patients had been previously treated with anti-TNF agents.

Kavanaugh et al (2014)⁵ described results of a pooled safety analysis from one phase 2, and two phase 3 studies (PSUMMIT I and PSUMMIT II), including adult patients exposed to STELARA for up to 2 years. The rates of malignancies other than NMSC per 100 PY were 0.00 for placebo, 0.39 for STELARA 45 mg, 0.00 for STELARA 90 mg, and 0.21 for STELARA combined groups. The rates of NMSC per 100 PY were 0.00 for placebo, 0.00 for STELARA 45 mg, 0.64 for STELARA 90 mg, and 0.29 for STELARA combined groups.

Pooled Safety data from phase 2/3 CD and UC studies

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

Ghosh et al (2024)¹¹ evaluated the cumulative safety of STELARA from six phase 2/3 CD and UC studies (5 CD studies and 1 UC study) through 5 and 4 years of treatment, respectively.

Study Design/Methods

• All patients receiving ≥1 dose of STELARA were included in the analysis.
• Concomitant immunomodulators and corticosteroids were permitted.
• The pooled analysis included 2575 and 1389 patients who received STELARA and placebo, respectively. The 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.

Results

• Overall rates of all malignancies including NMSC were similar between the STELARA and placebo groups.
• The rate of malignancies excluding NMSC (per 100 PY) in the STELARA vs placebo group was 0.39 (95% CI, 0.24-0.62) vs 0.32 (95% CI, 0.07-0.93).
• No cases of lymphoma were reported.
• The rate of NMSC (per 100 PY) for the pooled IBD was 0.38 (95% CI, 0.22-0.59) for the STELARA group vs 0.32 (95% CI, 0.07-093) for the placebo group.
• The most frequently reported malignancies (>2 patients; rates [patients with specified events]) in the STELARA vs placebo group were BCC (0.54 [14] vs 0.14 [2]), SCC (0.23 [6] vs 0.14 [2]) and melanoma (0.11 [3] vs 0.07 [1]).
• Excluding NMSC, the other malignancies reported for the combined IBD group (in either the placebo or STELARA group) were melanoma, prostate, renal, rectal, and small intestine.
• Comparing results from pooled long-term safety with SEER, the SIR (95% CI) for malignancies (other than NMSC and cervical cancer in situ) was approximately 1 in the STELARA group for patients with CD and UC and all patients with IBD, indicating no increased risk of malignancy with STELARA treatment, see Figure: Observed Rates of Malignancies Compared with Expected (SEER) and SIR.¹¹

Pooled Safety Analysis in IBD through 1 Year

Sandborn et al (2021)¹⁰ evaluated the cumulative safety of STELARA from six phase 2/3 CD and UC studies through 1 year of treatment.

Study Design/Methods

• The pooled analysis included 2574 patients (phase 3 UC studies, n=825; phase 2/3 CD studies, n=1749) for a total of 1733 PY of follow-up.
• Rates of observed malignancies (events per 100 PY) were compared with data from the SEER database with adjustments for age, sex, and race.

Results

• Rates of observed malignancies and SIR of observed vs expected number of malignancies as per SEER database are summarized in Table: Rates of Malignancies in the Pooled (CD+UC) STELARA vs Placebo Groups.
• The number of malignancy events observed vs the number expected per the SEER database are summarized in Table: Number of Observed Malignancies Compared with the SEER Database.
• Through 1 year of treatment, no cases of lymphoma, 4 cases of BCC, and 3 cases of SCC were reported in the IBD population.
• Most patients with malignancies were previously treated with at least 1 biologic prior to starting STELARA. Additionally, half of the patients only received 2 doses of STELARA (1 IV, 1 SC) and the longest exposure was 3 doses (1 IV, 2 SC).

Pooled Safety Analysis in IBD through 5 Years: Bio-naïve and Bio-failure Subgroups

Danese et al (2022)⁸ 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.
• Through up to 1 year, the median duration of follow-up for placebo and STELARA was 27.61 and 39.26 weeks, respectively. The total PY of follow-up was 226 for placebo and 582 for STELARA.
• Through up to 5 years, the median duration of follow-up was 45.96 weeks for placebo and 101.90 weeks for STELARA. The total PY of follow-up for placebo and STELARA was 376 and 1511, respectively.
• Malignancies (excluding NMSC) are presented as event rates per 100 PY of follow-up.
• Through up to 5 years, there were 425 bio-naïve patients who received placebo and 771 bio-naïve patients who received STELARA.
• Through up to 1 year of treatment, the rate of malignancies excluding NMSC (events per 100 PY) was 0.34 (n=2; [95% CI, 0.04-1.24]) in STELARA-treated bio-naïve patients (n=771) and 0.44 (n=1; [95% CI, 0.01-2.47]) in placebo-treated bio-naïve patients (n=425).
• Through up to 5 years of treatment, the rate of malignancies excluding NMSC (events per 100 PY) was 0.46 (n=7; [95% CI, 0.19-0.95]) in STELARA-treated bio-naïve patients (n=771) and 0.27 (n=1; [95% CI, 0.01-1.48]) in placebo-treated bio-naïve patients (n=425).

Ghosh et al (2022)⁹ conducted an integrated safety analysis incorporating data from five phase 2/3 and phase 3 studies in CD and UC for patients with a history of biologic failure (up to 5 years in CD and 2 years in UC).

Study Design/Methods

• All patients who received ≥1 dose of STELARA and had a history of biologic failure were included in the analysis.

Results

• Among patients with IBD who had a history of biologic failure, 1596 received STELARA, with 1970 PY of follow-up, and 847 received placebo, with 473 PY of follow-up.
• The average duration of follow-up was 64.18 weeks for the STELARA group and 29.06 weeks for the placebo group.
• The rate of malignancies excluding NMSC (events per 100 PY) was 0.51 (95% CI, 0.240.93) in STELARA-treated and 0.42 (95% CI, 0.05-1.53) in placebo-treated patients who had a history of biologic failure.

CLINICAL DATA IN 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 studies. There were two 8-week IV induction studies (UNITI-1 and UNITI-2) followed by a 44 week SC randomized withdrawal maintenance study (IM-UNITI) and a subsequent open-label long-term extension (LTE).^22,23

• The rate of malignancies including NMSC (events per 100 PY), throughout 1 year of treatment in CD clinical studies, was 0.63 (n=1,749; PY 1105 [CI, 0.25-1.30]) in STELARA-treated patients and 0.58 (n=943; PY 346 [CI, 0.07-2.09]) in placebo-treated patients.¹⁰
• Throughout 1 year of treatment in the CD clinical studies, the rate of malignancies excluding NMSC (events per 100 PY) was 0.27 (n=1,749; PY 1106 [CI, 0.06-0.79]) in STELARA-treated patients and 0 (n=943; PY 347 [CI, 0.00-0.86]) in placebo-treated patients.¹⁰

IM-UNITI Study LTE

LTE - 3 Years

Hanauer et al (2020)²⁴ evaluated the long-term efficacy and safety of STELARA through 3 years in the LTE of the IM-UNITI maintenance study.

• The LTE is for up to 4 years (after the 44-week IM-UNITI study) and efficacy results through week 152 and safety results through week 156 were reported.

Results

• A total of 4 solid and hematological malignancies were reported: testicular seminoma, adenocarcinoma of the small intestine, and chronic myeloid leukemia in patients treated with STELARA in the study extension, and papillary thyroid cancer in a patient who remained on placebo throughout the study.
• Through 3 years, 7 patients had NMSC (4 BCC and 3 SCC).

LTE - 5 Years

Sandborn et al (2020)²³ evaluated the long-term efficacy and safety of STELARA through 5 years in the LTE of the IM-UNITI maintenance study.

• Safety data through the final safety visit at week 272 and efficacy data through the final efficacy visit at week 252 were reported.

Results

• Between weeks 156 and 272, 6 patients reported malignancies (excluding NMSC): intraocular melanoma and renal cell carcinoma in the STELARA 90 mg SC q12w group, and endometrial adenocarcinoma, lentigo maligna melanoma, lobular breast cancer in situ, and pancreatic carcinoma in the STELARA 90 mg SC q8w group.

CLINICAL DATA IN UC

The safety of STELARA was evaluated in two 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 and a subsequent open-label LTE.^25,26

• With up to 1 year of treatment in the UC clinical studies, the rate of malignancies including NMSC (events per 100 PY) was 1.12 (n=825; PY 625 [CI, 0.45-2.31]) in STELARA-treated patients and 0.40 (n=446; PY 250 [CI, 0.01-2.23]) in placebo-treated patients.¹⁰
• Throughout 1 year of treatment in UC clinical studies, the rate of malignancies excluding NMSC (events per 100 PY) was 0.64 (n=825; PY 626 [CI, 0.17-1.64]) in STELARA-treated patients and 0.40 (n=446; PY 250 [CI, 0.01-2.23]) in placebo-treated patients.¹⁰

UNIFI LTE - 2 Years

Panaccione et al (2020)²⁷ reported efficacy outcomes though week 92 and safety outcomes through week 96 for patients who continued SC STELARA maintenance treatment in the UNIFI LTE. The UNIFI LTE analyzes SC STELARA through 220 weeks of maintenance treatment. The LTE study started after the 44-week UNIFI maintenance study.

• No increase was observed in the overall rate of malignancies (excluding NMSC) from week 44 through week 96 in the LTE.
• A summary of malignancies per 100 PY of follow-up from maintenance week 0 through week 96 (patients treated in the LTE) is provided in Table: Malignancies per 100 PY of Follow-up from Maintenance Week 0 through Week 96 (Patients Treated in the LTE).

• From week 44 through week 96 in the LTE, among patients who received STELARA, 3 had NMSCs: 1 patient each who received STELARA 90 mg SC q12w or q8w had BCC, and 1 patient who received STELARA 90 mg SC q8w had concurrent BCC and SCC. Among patients who received placebo, 1 had BCC and 1 had lentigo malignant melanoma. No other malignancies were reported.

UNIFI LTE - 3 Years

Abreu et al (2022)²⁶ reported efficacy outcomes through week 152 and safety outcomes through week 156 for patients who continued STELARA SC maintenance treatment in the UNIFI LTE.

• No increase in the rate of malignancies (excluding NMSC) was observed through 3 years of treatment relative to prior years.
• A summary of malignancies per 100 PY of follow-up from maintenance week 0 through week 156 (patients treated in the LTE) is provided in Table: Malignancies per 100 PY of Follow-up from Maintenance Week 0 through Week 156 (Patients Treated in the LTE).

SAPPHIRE REGISTRY

Safety Of Immunosuppression in a Prospective Cohort of Inflammatory Bowel Disease Patients With A History Of Cancer (SAPPHIRE) is a prospective observational cohort study examining patients with IBD exposed to anti-TNF and/or immunomodulators and a confirmed first cancer (index cancer) within 5 years of enrollment from centers affiliated with the New York Crohn’s and Colitis Organization (NYCCO) since 2017. Patients receiving chemotherapy or radiation at enrollment, a first cancer diagnosed >5 years prior to study entry, or recurrent cancer within the last 5 years were excluded. The primary objective of SAPPHIRE is to evaluate whether patients with IBD and a history of cancer subsequently exposed to immunosuppressive IBD therapies are at a greater risk of new or recurrent cancer compared with those not exposed to immunosuppression.¹²

• A total of 267 patients with IBD and an index cancer were identified, of whom 52 (19%) patients had 87.6 PY of exposure to STELARA following index cancer.
  • New or recurrent cancer was observed in 11/52 (21%) patients.
  • Rate of new or recurrent cancer per 100 PY of exposure was 12.6 (95% CI, 6.3-22.5).

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 plaque psoriasis (phase 2 and 3; adult patients), PsA (phase 2 and 3; adult patients), CD (phase 2/3 and phase 3b; adult patients), UC (phase 2/3; adult patients), pediatric patients 6 to 11 and 12 to 17 years of age with plaque psoriasis (both phase 3) and pooled analyses from pivotal phase 2/3 clinical trials across indications. In addition, relevant data from PSOLAR and SAPPHIRE registries are also included.