SUMMARY

• Please refer to the local labeling for relevant information on the use of STELARA in the geriatric population.
• Data regarding STELARA treatment in elderly patients with Crohn’s disease (CD) or ulcerative colitis (UC) are reported below.^1-15

COMPANY CORE DATA SHEET

STELARA Clinical Information

Dosage and Administration

Special Populations - Elderly

Of the 6710 patients exposed to STELARA, a total of 353 were 65 years or older (58 patients with CD and 43 patients with UC). No major age-related differences in clearance or volume of distribution were observed in clinical studies. Although no overall differences in safety or efficacy were observed between older and younger patients in clinical studies in approved indications, the number of patients aged 65 and over is not sufficient to determine whether they respond differently from younger patients.¹

STELARA Pharmacological Properties

Pharmacokinetic Properties

Special Populations - Elderly (65 Years of Age and Older)

No specific studies have been conducted in elderly patients.¹

CLINICAL DATA

Pooled Analysis of Phase 2/3 Studies

Ghosh et al (2021)² evaluated the safety of STELARA in elderly patients (age ≥60 years) compared with non-elderly patients (age <60 years) with inflammatory bowel disease (IBD; CD and UC), psoriatic diseases (psoriasis [PsO] and psoriatic arthritis [PsA]), using the STELARA 2020 pooled safety data across approved indications.

Study Design/Methods

• Data from patients who received ≥1 dose of STELARA in 13 phase 2/3 studies (6 in CD/UC and 7 in PsO/PsA) were pooled.
• Concurrent administration of immunomodulators and corticosteroids were permitted for CD, UC, and PsA but not for PsO.
• Safety outcomes, including serious adverse events (SAEs) and serious infections, were reported as events per 100 patient-years (PY) of follow-up.

Results

• There were 856 elderly patients and 6326 non-elderly patients for all approved indications, of whom 245 and 2701, respectively, were in the IBD group.
• Baseline demographics between elderly and non-elderly patients were generally similar.
• The mean age of diagnosis for elderly and non-elderly patients was 51.5 and 27.4 years, respectively.
• Concomitant immunomodulator and corticosteroid use occurred in 19 (7.8%) elderly and 283 (10.5%) non-elderly patients.
• Overall rates for adverse events (AEs) and infections were generally similar between the STELARA and placebo groups in IBD, psoriatic diseases, and all approved indications pooled within each age group (elderly or non-elderly). See Table: Rates of AEs and Infections in Elderly and Non-elderly Patients.
• SAEs and serious infections in elderly patients are summarized in Table: SAEs and Serious Infections in Elderly Patients.

• When comparing malignancy in elderly patients with that in the Surveillance, Epidemiology, and End Results (SEER) database, all standardized incidence ratios for the STELARA group were approximately 1, indicating no increased risk of malignancy with STELARA treatment. See Table: Observed vs Expected Malignancies in Elderly Patients Compared with SEER.

Prospective Study

Bozon et al (2023)³ compared the risk of infection in elderly patients (age ≥65 years) with IBD treated with STELARA or vedolizumab versus (vs) anti-tumor necrosis factor (TNF) therapy in a prospective, multicenter, real-life observational study from six French tertiary hospitals.

• A total of 94 elderly patients received either STELARA (n=31) or vedolizumab (n=63) and 113 elderly patients received anti-TNF therapy.
• The primary outcome was the occurrence of any type of infection during the 1-year follow-up.
• The median duration of follow-up was 11 (interquartile range [IQR] 8-13) months and the median age of patients at inclusion was 71 (IQR 68-75) years.
• For occurrence of infection in the cohort of elderly patients with IBD, see Table: Rates of Infections in Elderly Patients (age ≥65 years) with IBD.

• Pulmonary tract infection was the most common AE in the STELARA or vedolizumab group (10%) while digestive tract infection was most common in patients treated with anti-TNF (8%).
• The rates of infection-related hospitalizations between the anti-TNF and STELARA or vedolizumab groups were similar, (7% vs 64%, respectively). However, the rate was higher in patients>75 years when compared with younger patients (P=0.049).
• A total of 32% of patients experienced a significant IBD flare in the
  STELARA or vedolizumab treatment group compared to 37% patients in the anti-TNF group during the follow-up period.
• For the secondary outcomes including IBD-related hospitalizations, and changes in therapy, see Table: Secondary Outcomes in Patients Receiving Anti-TNFs vs STELARA or Vedolizumab.

Retrospective Cohort Studies

Gebeyehu et al (2024)⁴ compared the safety and effectiveness of STELARA vs anti-TNF agents in elderly patients (age >60 years) with CD in a retrospective, multicenter, cohort study.

• Elderly patients, identified from a locally maintained IBD biologics database, who were treated with STELARA or an anti-TNF agent at the time of therapy commencement were included.
• Patients were treated with a standard induction therapy for each of the respective agents and received a maintenance dose of STELARA (8- or 12-weekly), infliximab, and adalimumab after the completion of induction therapy.
• The Harvey-Bradshaw index (HBI) was calculated at initiation and months 2, 4, and 6 after therapy initiation. Clinical remission was defined as an HBI of <5, and clinical response was defined as a reduction of ≥3 points in the HBI from baseline.
• Outcomes:
  • The primary outcome was the occurrence of serious infections, defined as those patients who required hospitalization.
  • Effectiveness was primarily assessed through clinical remission and response rates.
  • The association of clinical variables with serious infections and clinical remission rates was also assessed.
• Multiple logistic regression model analyses and propensity score-matched analyses using inverse probability of treatment weighting (IPTW) were performed to reduce the effects of treatment selection bias and confounding factors.
• The 6-month discontinuation-free survival and serious infection-free survival were evaluated using Cox regression analysis (P<0.05 was considered significant).
• A total of 83 patients were treated with STELARA, and 124 patients were treated with anti-TNF agents.
• The proportion of patients receiving concomitant steroids at baseline was higher among STELARA-treated patients compared with anti-TNF-treated patients (37% vs 7.3%, P<0.001)
• The overall serious infection rate was 52.3 per 1000 PY and 65.9 per 1000 PY in STELARA-treated and anti-TNF-treated patients, respectively.
• For serious and nonserious infections by 6 months, see Table: Infections in STELARA vs Anti-TNF Groups by 6 Months.

• None of the patients who developed serious infections were on systemic steroids within 4 weeks of developing the infections.
• Results of the IPTW-adjusted analyses for TP, steroid-free TP, clinical response and remission rates and incidence of serious infections at 6 months in the STELARA vs anti-TNF group are presented in Table: Summary of Efficacy and Safety Outcomes After IPTW.

• A significant reduction in the HBI from baseline through 6 months was observed in both treatment groups.
• One patient from the STELARA group (colectomy) and no patients from the anti-TNF group underwent intestinal resection for treatment failure during follow-up.
• Univariate analysis showed that the HBI at initiation was associated with the clinical remission rate at 6 months (P=0.003); however, multivariate analysis showed no association with the clinical remission rate at 6 months (P=0.079).
• Reasons for treatment discontinuation by 6 months in both treatment groups are presented in Table: Treatment Discontinuation by 6 Months.

Suárez Ferrer et al (2024)⁵ evaluated the efficacy and safety of STELARA and other biologics in elderly patients (age ≥65 years) with IBD in a retrospective, multicenter study from 45 Spanish hospitals from the Spanish Working Group on Crohn’s Disease and Ulcerative Colitis (GETECCU).

• Elderly patients with confirmed IBD (including UC, CD, or indeterminate colitis) receiving biologics including STELARA between February 2006 and February 2020 were included.
• After induction therapy (around 12 weeks of treatment):
  • Clinical response (defined as remission, response without remission, or no response by physician criteria) and biochemical response (C-reactive protein [CRP] and fecal calprotectin levels [FCP]) were evaluated.
• After 52 weeks of treatment:
  • Clinical response (clinical remission, partial response without remission or no response by physician criteria) was evaluated.
• Of the 1090 patients included in this study, 157 (14.5%) received STELARA.
• Efficacy at weeks 12-14 and 52 are presented in Table: Efficacy at Week 12-14 and at Week 52.

• The clinical remission rate after 52 weeks of treatment with STELARA was 50.5% for patients with CD and 60% for patients with UC.
• AEs related to STELARA included tumors in 10 patients (6.4%), discontinuation of biologics following tumor diagnosis in 4 patients (40%), and infections in 22 patients (14.1%). Additionally, 1 patient (0.6%) reported SAEs associated with STELARA.

Holvoet et al (2024)⁶ evaluated the effectiveness and safety of STELARA and vedolizumab in elderly (≥60 years) and non-elderly (<60 years) patients with IBD in a retrospective, multicenter, cohort study from centers in Belgium and Spain.

• The primary outcome was the corticosteroid-free remission at 1 year.
• Secondary outcomes included corticosteroid-free remission at 6 months, endoscopic remission at 1 year, and overall safety.
• Clinical and endoscopic remission were evaluated at 6 months, 1 year, and 2 years.
• Corticosteroid-free remission was defined as the presence of clinical remission at the time of evaluation without the use of corticosteroids.
• A total of 911 patients were treated with STELARA (n=327) or vedolizumab (n=584).
  • In elderly patients, 60 and 111 were treated with STELARA and vedolizumab, respectively.
• The efficacy and safety outcomes were observed for elderly patients and presented in Table: Efficacy and Safety Outcomes for STELARA Vs Vedolizumab in Elderly Patients

Garg et al (2023)⁷ evaluated the efficacy and safety of STELARA and vedolizumab in elderly patients (age ≥65 years) with CD at the Cleveland Clinic health system.

• Elderly patients with CD were included retrospectively if they received at least one infusion of STELARA or vedolizumab and had at least one clinical or endoscopic follow-up after first infusion.
• Efficacy outcomes measured included clinical response or remission, steroid-free response/ remission, and mucosal healing.
• Safety outcomes included infusion/injection site reactions, infections, and SAEs.
• Overall, 78 elderly patients were included in the study, STELARA (n=39) and vedolizumab (n=39).
• The mean overall follow-up was 16.1±17.4 months in STELARA and 25.5±18.1 months in vedolizumab treatment groups.  
• For efficacy outcomes of STELARA and vedolizumab, see Table: Outcomes of STELARA and Vedolizumab in Elderly Patients with Crohn’s Disease

• There were no differences between STELARA and vedolizumab groups in dose escalation 17.9% (7/39) vs 10.0% (3/30), infusion or injection reactions n=1, 2.6% for each group.
• Two patients (5.2%) receiving STELARA and 1 (2.6%) patient receiving vedolizumab developed infectious complications.
  • STELARA: recurrent cystitis and Mycobacterium avium-intracellulare infection.
  • Vedolizumab: recurrent upper respiratory infections.

Gebeyehu et al (2023)⁸ compared the safety and effectiveness of STELARA vs anti-TNF agents in elderly patients (age ≥60 years) with CD through a retrospective, multicenter, cohort study.

• Outcomes were reported as time to development of any infection, TP, and clinical response rates.
• Confounders were adjusted using propensity score matched analysis weighted by the IPTW.
• Factors associated with infections and TP were analyzed using a logistic regression analysis.
• A total of 83 patients were treated with STELARA and 124 patients with anti-TNF agents. More STELARA-treated patients were on concomitant steroids at baseline (37% vs 7.3%, P<0.001).
• Infection-free survival at 12 months was similar between patients treated with STELARA and patients treated with anti-TNF agents (hazard ratio 0.79, 95% confidence interval [CI] 0.58-1.07, P=NS).
• Serious infection rate was 7.55 per 100 PY and 5.3 per 100 PY for STELARA-treated and anti-TNF-treated patients, respectively (P=NS).
• There was no difference in TP between treatment groups at 6 months (odds ratio [OR] 1.23, 95% CI 0.37-4.10, P=NS) and 12 months (OR 1.07, 95% CI 0.45-2.55, P=NS).
• A significant reduction in HBI from baseline was observed in both treatment groups (P<0.001).

Gebeyehu et al (2023)⁹ compared the safety and effectiveness of STELARA vs vedolizumab in elderly patients (age ≥60 years) with CD through a retrospective, multicenter, cohort study.

• The primary outcome was serious infections requiring hospitalization.
• Treatment effectiveness was evaluated based on TP and steroid-free TP.
• Confounders were adjusted using propensity score matched analysis weighted by the IPTW.
• Factors associated with serious infections and TP were analyzed using a logistic regression analysis.
• The median follow-up time was 12 (IQR 2.75) and 12 (IQR 0) months for STELARA and vedolizumab, respectively. Median treatment duration was 12 (IQR 5) and 12 (IQR 2) months for STELARA and vedolizumab, respectively.
• A total of 83 patients were treated with STELARA and 42 patients with vedolizumab.
• Severe infection was reported in 10% of patients (75.5 per 1000 PY) receiving STELARA treatment and 13.8% of patients (110.6 per 1000 PY) receiving vedolizumab treatment within 12 months of treatment initiation (P=0.698).
• Rates of serious infection at 6 and 12 months were not significantly different between STELARA-treated and vedolizumab-treated patients, according to a propensity score adjusted logistic regression analysis.
  • OR (CI) at 6 months: 1.61 (0.209-12.4); P=NS
  • OR (CI) at 12 months: 1.24 (0.293-5.26); P=NS
• A total of 2 patients in each group developed malignancy following initiation of treatment.
• No infusion reactions or cutaneous lesions were reported. Two patients receiving STELARA developed new onset arthralgia.
• TP rates in the STELARA and vedolizumab groups were 68.1% vs 80.0% at 12 months (P=NS).
• Additionally, there were no significant differences in steroid-free TP and clinical remission rates at 6 and 12 months between STELARA and vedolizumab.

Hahn et al (2022)¹⁰ evaluated the drug sustainability, effectiveness, and safety of biologic therapies in elderly patients (age ≥60 years) with CD or UC.

• Local electronic medical charts were used to retrospectively identify elderly patients  (age≥60 years) with CD or UC who were previously or currently treated with a biologic agent and followed up at the McGill University Health Center Inflammatory Bowel Diseases Center between January 2000 and January 2020.
• Clinical response and remission were assessed using the HBI and Mayo scores, measured at baseline and at 3, 6-9, and 12-18 months of follow-up.
• The primary outcome was drug sustainability and comparative time-dependent safety analysis in elderly patients with IBD who received treatment with different biologic therapies.
• Secondary outcomes were comparisons of rates of clinical remission based on the biologic therapy used.
• Of the 147 elderly patients included in the study, 109 had CD and 38 had UC.
  • Patients received vedolizumab (n=23), adalimumab (n=57), infliximab (n=42), and STELARA (n=25).
• Among the 4 biologic agents, no significant difference was found in the time to treatment discontinuation (P=0.195), time to AE (P=0.158), or time to infections (P=0.973).
• For efficacy outcomes of STELARA therapy at 3, 6-9, and 12-18 months, see Table: Efficacy Outcomes of STELARA Therapy in Elderly Patients with CD or UC.

Kochhar et al (2022)¹¹ assessed the risk of malignancy and opportunistic infections (OIs) in elderly patients (age ≥65 years) with IBD treated with STELARA.

• TriNetX database was used to retrospectively identify elderly patients with IBD and compared the 3-year risk of malignancy and OIs in patients between the age of 18 and 65 years.
• A total of 147 patients on STELARA were identified from 22,242 elderly patients with IBD.
• There was no significant difference in malignancy rates (OR: 0.58, 95% CI; 0.29-1.15) and OI (OR:1.04, 95% CI; 0.50-2.1) when compared to 5-aminosalicylic acid treatment.
• Additionally, STELARA was compared with other medications (anti-TNF agents, vedolizumab, tofacitinib) in the cohort and no difference was seen in the outcomes of malignancy and OI.

De Galan et al (2021)¹² conducted an international, multicenter, retrospective study to evaluate the safety of vedolizumab and STELARA in elderly patients (age ≥60 years) with IBD.

• AEs, infectious AEs, and SAEs (hospitalization [both IBD and non-IBD related], malignancy, and death) were assessed.
• Of the 856 patients included in the study, 159 were elderly (vedolizumab, n=99; STELARA, n=60) and 697 were non-elderly (vedolizumab, n=429; STELARA, n=268).
• No differences were observed between elderly patients treated with vedolizumab vs STELARA in the following:
  • Incidence of AEs (37.4% vs 38.3%; P=0.904).
  • Incidence of SAEs (26.3% vs 26.7%; P=0.955).
• The incidence of non-IBD hospitalizations was significantly higher in elderly vs non-elderly patients (11.5% vs 5.8%; P=0.012), as was the incidence of malignancies (2.5% vs 0.6%; P=0.043). There was no difference between elderly patients treated with vedolizumab vs STELARA.

Garg et al (2021)¹³ assessed the safety and efficacy of STELARA in elderly patients (age ≥65 years) with CD.

• A retrospective chart review was performed on adult patients with CD who received STELARA between September 2016 to September 2019. Patients were included in this analysis if they received at least one dose of STELARA and had at least one follow-up after the first infusion.
• Patients were categorized as: elderly (age ≥65 years) and non-elderly (age ≥18 and 65 years).
• Efficacy outcomes included clinical remission or response, steroid-free remission or response, and mucosal healing:
  • Clinical response or remission was assessed using the Physician’s Global Assessment, where response was defined as partial (<50%) or significant (≥50%) reduction in CD-related symptoms; complete clinical remission was defined as complete resolution of CD-related symptoms.
  • Steroid-free remission was defined as in clinical remission and completely off steroids; steroid-free response was defined as achieving partial or significant clinical response along with steroids being tapered below baseline dose.
  • Mucosal healing was defined as absence of ulcers/erosions based on endoscopic assessment.
• Dose escalations were performed when clinically needed and defined as an increase in the frequency of STELARA injections from the standard dosing schedule (every 8 weeks) or reinduction with intravenous STELARA.
• There were 39 elderly patients and 78 non-elderly patients included in this analysis.
• Dose escalation was seen in 17.9% of patients in the elderly group and 25.6% of patients in the non-elderly group.
• The follow-up duration for the elderly and non-elderly was approximately 1.3 years.
• Complete clinical remission was observed in 28.2% and 52.6% of patients in the elderly and non-elderly groups, (P=0.03) respectively.
• Significant response was achieved in 46.2% and 23.1% of patients in the elderly and non-elderly groups, respectively. Partial response was seen in 17.9% and 12.8% of patients in the elderly and non-elderly groups, respectively.
• Of the patients receiving steroids at baseline, 30% of elderly patients achieved steroid-free remission and 50% achieved steroid-free response compared to 54% and 32% of non-elderly patients (P=0.22 for both), respectively.
• Mucosal data was available in 71 patients; on a subsequent endoscopy, there were no significant differences in the rates of mucosal healing for elderly and non-elderly patients, respectively (25.9% vs 29.5%).
• A multivariable analysis adjusting for confounders, age-group, disease duration, steroid use, and concomitant medications (number of biologics, immunomodulators) showed no significant association with clinical remission or steroid-free remission.
• Dose escalation of STELARA was the only factor found to be significantly associated with clinical remission (OR, 0.14; 95% CI, 0.04-0.53; P=0.004).
• There were 5 infusion/injection-site reactions that occurred in the non-elderly and
  1 infusion/injection-site reaction in the elderly. There was no significant difference in the incidence of infusion/injection-site reactions between the 2 groups.
• Infectious complications occurred in 8 patients (2 elderly, 6 non-elderly). In the elderly group, one patient developed recurrent cystitis and one developed Mycobacterium avium-intracellulare infection; no deaths occurred in either group due to infectious complications.

Fiske et al (2021)¹⁴ evaluated the safety and efficacy of STELARA in elderly patients (age ≥60 years) with CD through a retrospective, multicenter cohort study.

• The primary outcome was serious infection requiring hospitalization.
• Efficacy was assessed by serial HBI measurement and TP.
• At baseline, of the 70 patients included in the study, 44 (62.9%) had prior exposure to an anti-TNF agent and 15 (21.4%), to vedolizumab.
• Median treatment duration was 12 months (range, 2-48) with a total of 84 PY.
• Seven patients (10%) had 9 serious infections, of which 1 was life-threatening.
  • Incidence of serious infections was 0.107 per PY. The overall rate of infection was 0.42 per PY.
• Three patients developed a malignancy (non-Hodgkin’s lymphoma, melanoma, and pancreatic cancer).
• Compared with baseline, mean HBI showed improvement at 6 months (baseline, 8.13; 6 months, 4.64; P<0.0001) and at the last follow-up (4.10; P<0.0001).
• The rate of TP was 61.4% (n=43) and 36 (51.4%) were steroid-free.
• Reasons for treatment discontinuations were primary non-response (42%), AEs (32%), secondary loss of response (10%), malignancy (10%), and lack of funding (5%).

ENEIDA Registry

Casas-Deza et al (2023)¹⁵ evaluated the effectiveness and safety of STELARA in elderly patients (age >60 years) with CD through an observational, multicenter study using data from the ENEIDA registry.

The ENEIDA registry is a large prospective Spanish IBD database, promoted by the Spanish Working Group in Crohn’s and Colitis (Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa), initiated in 2007. In 2021, it had data on more than 60,000 patients from 86 centers. The registry includes data on effectiveness and AEs associated with immunomodulators and biological therapies.

• Elderly patients (age >60 years) with CD who had received ≥1 dose of STELARA were identified. For every elderly patient, 2 non-elderly adult controls who initiated STELARA treatment before 60 years of age were randomly selected. These controls were matched by center, treatment history of anti-TNF agents, and smoking status to avoid selection bias.
• Effectiveness was evaluated by clinical response, clinical remission, steroid-free remission, and levels of CRP and fecal calprotectin at weeks 16, 32, and 54.
• Of the 648 patients included in the study, 212 were elderly and 436 were non-elderly adult controls.
• At baseline, concomitant use of immunomodulators or corticosteroids during induction with STELARA were similar between the 2 groups.
  • Intensified previous biologic treatment was used in 55.3% of the elderly and 51.4% of the non-elderly patients.
• At treatment initiation with STELARA, 109 elderly patients and 262 non-elderly adult controls had active disease.
  • Among patients with active disease, both groups were identical in clinical activity at baseline (median HBI score [IQR] in both groups, 8 [6.00-10.0]; P=0.5).
• The effectiveness of STELARA in patients with active disease at treatment initiation is presented in Table: Effectiveness of STELARA in Patients with Clinical Activity at Treatment Initiation.

• In the safety analysis, no significant differences were identified between the 2 groups, except for the occurrence of neoplasm; see Table: Safety Outcomes in Patients Treated with STELARA.

• Neoplasms diagnosed in elderly patients were prostate adenocarcinoma (n=1), urothelial carcinoma (n=1), lung neoplasm (n=1), glioblastoma multiforme (n=1), lymphoma (n=1), high-risk squamous cell tumor (n=1), and colorectal cancer (n=2). In non-elderly patients, glioblastoma multiforme, urothelial carcinoma, and cervical intraepithelial neoplasia were diagnosed.
• Only 1 infusion reaction was reported in the elderly group.
• No death related to AEs was attributed to treatment with STELARA.

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.

Summarized in this response are pooled analyses from phase 2/3 clinical trials across indications, prospective and retrospective studies. In addition, relevant data from the ENEIDA registry are included.