SUMMARY  

• The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
• Please refer to the local labeling for relevant information regarding the use of STELARA in patients with a history of malignancy.
• STELARA has not been studied in patients with a history of malignancy.¹
• Data from published literature regarding the occurrence of malignancies in patients with a history of malignancy treated with STELARA are summarized below.^1-11

CLINICAL DATA in cROHN’S dISEASE or uLCERATIVE COLITIS

Prospective Study

Axelrad et al (2023)² prospectively investigated whether patients with inflammatory bowel disease (IBD) and a history of malignancy who were subsequently exposed to immunosuppressive IBD therapies had an increased risk of developing new or recurrent malignancy through the SAPPHIRE registry.

• The primary outcome was the occurrence of recurrent or new malignancy stratified by immunosuppression exposure.
• A total of 306 patients with IBD and an index malignancy were included in this study.
• The average age of diagnosis for IBD and index malignancy was 34±16.9 and 51.9±14.6 years, respectively.
• Index malignancies included:
  • Gastrointestinal (n=32, 10%)
  • Hematologic (n=23, 8%)
  • Dermatologic (n=99, 32%)
  • Solid (n=140, 46%)
• The mean (standard deviation [SD]) follow-up duration was 3.4±1.4 years.
• During follow-up, 44 (14%) patients developed 53 subsequent malignancies (25 new, 28 recurrent), including:
  • Gastrointestinal (n=5, 9%)
  • Hematologic (n=1, 2%)
  • Dermatologic (n=25, 47%)
  • Other solid (n=18, 34%)
• Following diagnosis of index malignancies, 58 (19%) patients were exposed to STELARA while 8 (3%) were exposed prior to the diagnosis of malignancy.
  • New or recurrent malignancies were reported in 14 patients exposed to STELARA (11.6 per 100 person-years [PY]; 95% confidence interval [CI], 6.4-19.5; relative risk [RR], 1.75; 95% CI, 0.70-4.58).

Retrospective Studies

Holmer et al (2023)³ conducted a retrospective, multicenter, cohort study comparing the safety of tumor necrosis factor alpha (TNFα) antagonists vs non-tumor necrosis factor (TNF) biologics in patients with IBD and active malignancy or recent prior malignancy.

• The primary exposure was treatment with TNFα antagonists (infliximab, adalimumab, certolizumab pegol, golimumab). The comparator group received non-TNF biologics (vedolizumab, STELARA). Immunomodulator (IMM) monotherapy was included as an alternative comparator to anchor the results against prior studies.
• Cohort A included 125 patients (STELARA, n=9) with active malignancy undergoing therapy or under observation for stable active malignancy, treated with biologics or IMM for IBD started before or after cancer diagnosis.
  • The mean age at cohort entry was 54±15 years.
  • Among the 9 STELARA-treated patients with active malignancy, 2 experienced progression:
    • One patient with colon adenocarcinoma and one patient with breast cancer (invasive ductal adenocarcinoma). Both patients received STELARA prior to cancer development.
• Cohort B included 170 patients (STELARA, n=15) with a recent history of malignancy, confirmed as cancer-free and not undergoing active treatment for malignancy, within 5 years prior to initiating biologics or IMM for IBD.
  • The mean age at cohort entry was 53±15 years.
  • Among the 15 STELARA-treated patients with recent prior malignancy, 2 experienced recurrence during STELARA therapy:
    • One patient had an index malignancy of the colon, with subsequent metastatic colon cancer.
    • The other patient had both index and subsequent recurrent melanoma.

Shani et al (2023)⁴ conducted a retrospective, observational cohort study to review malignancy outcomes in patients with IBD who had a prior or current malignancy before starting treatment for IBD, including STELARA.

• The primary outcome of this study was to identify the relapse of a previously diagnosed malignancy or the development of a secondary malignancy.
  • The relapse of malignancy was defined as documented evidence for recurrence after a confirmed recovery.
  • A new malignancy in patients with a history of previous malignancy was defined as any subsequent incidence of a new primary tumor.
• Eighty-six patients who were diagnosed with IBD after cancer or had cancer at IBD treatment initiation were included in this analysis. Of these 86 patients, 10 had a confirmed second malignancy and 20 had a confirmed recurrent malignancy.
• For the occurrence of a second or recurrent malignancy in patients receiving STELARA, see Table: Patients Receiving STELARA with Secondary or Recurrent Malignancy.

• Of the 4 patients receiving STELARA with a recurrent malignancy:
  • Nonmelanoma skin cancer (NMSC) occurred in 3 patients (odds ratio [OR], 5.00; 95% CI, 0.91-24; P-value=0.047).
  • Melanoma occurred in 1 patient (OR, 4.11; 95% CI, 0.18-47.3; P-value=not significant).

Davies et al (2022)⁵ reviewed the safety and efficacy of STELARA in patients with IBD through a retrospective chart review.

• Of 120 patients, 98, 17, and 5 patients had Crohn’s disease (CD), ulcerative colitis (UC), and IBD-unspecified (IBD-U), respectively. Median follow-up was 13.9 months (interquartile range [IQR], 3-20.5).
• The median age at STELARA initiation was 35.5 (16–81) years, and 10% (14/120) were >60 years of age at time of starting STELARA.
• Eight (7%) patients had a prior malignancy:
  • NMSC (n=4)
  • Solid organ (n=2)
  • Melanoma (n=1)
  • Hematological (n=1)
• Of the 8 patients with a prior malignancy, 5 patients were >60 years of age with a median of 10 years (IQR, 5-11) since remission. No episodes of recurrence were reported.
• One patient developed malignancy post-STELARA treatment.
• Adverse events were reported in 7 patients (5.8%). Serious adverse events were reported in 6 (5%) patients, including 4 patients (<60 years of age) who required hospitalization for intravenous antibiotics vs 1 patient (>60 years of age) (P=0.57).

Hasan et al (2022)⁶ retrospectively evaluated the risk of new or recurrent malignancy in patients with IBD and a history of malignancy subsequently treated with STELARA, vedolizumab, or anti-TNF agents.

• A control sample (n=181) was randomly selected from 3714 patients with IBD who did not receive treatment with anti-TNF agents, vedolizumab, or STELARA after an index diagnosis of malignancy.
• Random selection of controls was conducted within 4 subgroups and randomly matched to the pooled treatment groups by gender and type of IBD.
• Of 160 patients receiving biologics after an index malignancy, 34 were exposed to vedolizumab, 99 to anti-TNF agents, and 27 to STELARA.
• Of the 27 STELARA-treated patients after an index malignancy, 23 (85%) had CD and 4 (15%) had UC.
  • The median age of STELARA patients at IBD and index malignancy diagnoses were 38±17 and 49±14 years, respectively.
  • The median total duration of exposure to STELARA was 1.7 PY.
• Of the 181 patients in the control group, 117 (65%) and 64 (35%) patients had CD and UC, respectively.
  • The median age of patients at IBD and index malignancy diagnoses were 42±18 and 60±13 years, respectively.
• Index malignancies in patients receiving STELARA included:
  • Gastrointestinal (4%)
  • Hematologic (7%)
  • Dermatologic (37%)
  • Other solid (52%)
• Index malignancies in the control group included:
  • Gastrointestinal (12%)
  • Hematologic (9%)
  • Dermatologic (20%)
  • Other solid (60%)
• For new or recurrent malignancy in STELARA vs the control group, see Table: Characteristics of New or Recurrent Malignancy in Patients Receiving STELARA vs Control.

• After adjusting for age at malignancy diagnosis and premalignancy antimetabolite therapy:
  • No significant increases in risk of incident malignancy were found based on treatment with STELARA vs control (HR, 0.88; 95% CI, 0.25-3.03; P=0.833).
  • The risk of incident malignancy was not significantly associated with new or recurrent malignancy in patients who received STELARA vs anti-TNF agents (HR, 5.23; 95% CI, 0.96-28.41; P=0.06).

Hong et al (2022)⁷ performed a retrospective cohort study to identify the risk of subsequent malignancy in patients with IBD receiving biologics, including STELARA, with a history of malignancy.

• Of 390 patients with IBD and a history of malignancy, 14 patients were receiving STELARA (CD, n=10; UC, n=2; IBD-U, n=2) and 267 patients did not receive immunosuppressive therapy following malignancy diagnosis.
• The mean age at IBD diagnosis was 46.8±18.4 and 44.9±17.6 years for patients receiving STELARA vs no immunosuppressive therapy, respectively.
• The mean age at prior malignancy diagnosis was 53.7±15.7 and 57.3±15.7 years for patients receiving STELARA and no immunosuppressive therapy, respectively.
• Prior malignancies in patients receiving no immunosuppressive therapy included:
  • Gastrointestinal (n=42, 16%)
  • Hematologic (n=9, 3%).
  • Dermatologic (n=46, 17%).
  • Solid (n=170, 64%).
• Prior malignancies in patients receiving STELARA included:
  • Gastrointestinal (n=2, 14%).
  • Hematologic (n=3, 21%).
  • Dermatologic (n=1, 7%).
  • Solid (n=8, 57%).
• Through follow-up, 79/390 (20%) patients developed subsequent malignancy with no significant difference in the time to subsequent malignancy between groups (P=0.50). For malignancy outcomes in patients receiving STELARA vs no immunosuppression, see Table: Subsequent Malignancy Outcomes in Patients Receiving STELARA vs No Immunosuppression.

• Through a multivariable Cox model adjusting for IBD type, age at index malignancy, smoking status, Penn classification of recurrence risk, malignancy stage, time from malignancy to treatment initiation and duration of exposure, STELARA was not significantly associated with subsequent malignancy development (adjusted HR [aHR], 0.96; 95% CI, 0.17-5.41).
• After excluding nonmelanoma skin malignancy, there was no significant increased risk of subsequent malignancy between groups (P=0.59), and the adjusted risk for subsequent malignancy remained similar for STELARA (aHR, 0.57; 95% CI, 0.03-11.50).
• In patients who initiated biologics within 5 years of a malignancy diagnosis, there was no significant differences in subsequent malignancy risk with STELARA (aHR, 1.31;
  95% CI, 0.23-7.53).

Dolby et al (2020)⁸ retrospectively reviewed the safety and efficacy of STELARA in
259 patients with CD.

• The mean disease duration was 11.78 years, and most patients had ileocolonic disease (n=137).
• There was 1 death from a pre-existing primary malignant melanoma, 3 cases of newly diagnosed malignancies (1 small bowel adenocarcinoma, 1 breast cancer, and 1 hepatocellular carcinoma), and 2 recurrences of previous known malignancies (1 basal cell carcinoma of the skin and 1 bladder transitional cell carcinoma).

AGA - Clinical Practice Updates

The American Gastroenterological Association (AGA) published the Institute Clinical Practice Update (CPU) Commentary on management of IBD in patient with malignancy. The document discusses the risks associated with different malignancies in patients with IBD and the impact of available medical therapies (including STELARA) on malignancy risk⁹:

• Current evidence does not show an increased risk of malignancy in IBD patients treated with STELARA, although, long-term data are lacking.
• Additionally, there are no data on the cancer risk in patients who receive combined biologic and small molecule therapies.

clinical data in psoriasis

Retrospective Study

Battista et al (2024)¹⁰ evaluated the efficacy and safety of biologics, including STELARA, in a case series among patients with psoriasis (PsO) who had a preexisting or newly diagnosed malignancy.

• A total of 20 patients between 36 to 75 years of age were included in the study.
• Fifteen patients (75%) were diagnosed with malignancy prior to initiating biologic therapy, while the remaining 4 patients (20%) developed malignancy during biologic therapy.
• The mean duration from cancer diagnosis to initiation of biologic therapy was 3.8±3 years.
• Reported malignancies in 2 STELARA-treated patients included esophagus and chronic lymphatic leukemia.
• Additionally, there was one patient who reported breast cancer while taking certolizumab. This patient also received multiple biologics in the past, including adalimumab, etanercept, ustekinumab and certolizumab.
• In 5 cases, biologic treatment was temporarily discontinued after the diagnosis of malignancy due to safety concerns and resumed following oncologist approval. Two patients resumed the same biologic treatments (certolizumab and STELARA) that were previously discontinued.
• Of the 20 patients, only 1 patient, a 65-year-old male diagnosed with esophageal cancer being treated with STELARA who experienced cancer progression and was scheduled to restart chemotherapy (at the time of this report).

Valenti et al (2022)¹¹ assessed the efficacy and safety of biologic agents in 16 patients with severe plaque PsO and a history of malignancy in the past 10 years through a retrospective, single center study.

• Of the 16 patients included in this analysis, 4 patients received STELARA. Reported malignancies in 3 out of 4 STELARA-treated patients included breast, uterus, and non-Hodgkin’s lymphoma.
• During the study period through 96 weeks, no malignancy reactivation or new malignancy was reported.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, DERWENT^® (and/or other resources, including internal/external databases) was conducted on 16 September 2024.