Summary

• Prior to initiating therapy with STELARA, patients should receive all age-appropriate immunizations as recommended by current immunization guidelines.¹
• Patients being treated with STELARA should not receive live vaccines.¹
• Bacillus Calmette-Guerin (BCG) vaccines should not be given during treatment with STELARA or for 1 year prior to initiating treatment or 1 year following discontinuation of treatment.¹
• Caution is advised when administering live vaccines to household contacts of patients receiving STELARA because of the potential risk for shedding from the household contact and transmission to patient.¹
• Nonlive vaccinations received during a course of STELARA may not elicit an immune response sufficient to prevent disease.¹
• Studies were conducted to evaluate patients receiving STELARA and vaccine response.^2-5

PRODUCT LABELING

WARNINGS AND PRECAUTIONS

Theoretical Risk for Vulnerability to Particular Infections

Individuals genetically deficient in interleukin (IL)-12/IL-23 are particularly vulnerable to disseminated infections from mycobacteria (including nontuberculous, environmental mycobacteria), salmonella (including nontyphi strains), and BCG vaccinations. Serious infections and fatal outcomes have been reported in such patients.¹

It is not known whether patients with pharmacologic blockade of IL-12/IL-23 from treatment with STELARA may be susceptible to these types of infections. Appropriate diagnostic testing should be considered, eg, tissue culture, stool culture, as dictated by clinical circumstances.¹

Immunizations

Prior to initiating therapy with STELARA, patients should receive all age-appropriate immunizations as recommended by current immunization guidelines. Patients being treated with STELARA should not receive live vaccines. BCG vaccines should not be given during treatment with STELARA or for 1 year prior to initiating treatment or 1 year following discontinuation of treatment. Caution is advised when administering live vaccines to household contacts of patients receiving STELARA because of the potential risk for shedding from the household contact and transmission to patient.¹

Nonlive vaccinations received during a course of STELARA may not elicit an immune response sufficient to prevent disease.¹

CLINICAL DATA

IL-12/23 Pathway Inhibition on Immunocompetency (Psoriasis)

Brodmerkel et al (2010)² reported the effects of IL-12/23 pathway inhibition on immunocompetency in an evaluation of data from a phase 1 study of adult patients with moderate to severe plaque psoriasis (PsO). In this study, 18 patients received a single dose of intravenous STELARA 0.09 mg/kg (n=4), 0.27 mg/kg (n=4), 0.9 mg/kg (n=5), or 4.5 mg/kg (n=5).

• Patients who had not had pneumococcal vaccination within the past 5 years were inoculated with a 23-valent pneumococcal vaccine at 72 hours after receiving STELARA. Immune titers were measured 1 month after inoculation.
• If at least 6 of the 12 serotypes doubled in titer after pneumococcal vaccination, a patient was considered to have had a positive response. A patient was considered to have had a negative response if 5 or fewer titers doubled.
• If the prevaccination titer for a particular serotype was greater than half the upper level of quantification, the response was considered indeterminate. In addition, a patient's antibody response was considered to be indeterminate if there were less than 6 positive responses, or with 6 or more positive and indeterminate serotype responses. The results are presented in Table: Summary of Antibody Response to Pneumococcal Vaccination in Patients with Moderate to Severe PsO Following IV Treatment with STELARA.

Nonmemory B-cell Antibody Response and Memory T-cell Antibody Response (PsO)

Brodmerkel et al (2010)² evaluated the ability of adult patients with moderate to severe plaque PsO to have a nonmemory B-cell antibody response and a memory T-cell antibody response after a single dose of subcutaneous (SC) STELARA 0.27 mg/kg (n=5), 0.675 mg/kg (n=4), 1.35 mg/kg (n=4), 2.7 mg/kg (n=4), or placebo (n=4) in a phase 1 study.

• In order to evaluate the ability of a patient to generate a nonmemory B-cell antibody response, patients who had not received a pneumococcal vaccine within the prior 5 years were inoculated with a 23-valent pneumococcal vaccine 3 days after receiving STELARA. Postimmunization antipneumococcal antibody concentrations were determined 25 days after the inoculation.
• Patients were considered to have had a normal antibody response to the polyvalent pneumococcal vaccine if there was at least a 2-fold increase in antibody levels from baseline in at least 6 of the 12 serotypes. The results are presented in Table: Summary of Antibody Response to Pneumococcal Vaccination in Patients with Moderate to Severe PsO Following SC Treatment with STELARA.

• In order to evaluate the ability of a patient to generate a memory T-cell antibody response, patients who had not received a tetanus vaccine within the prior 10 years received a tetanus toxoid vaccine 3 days after receiving STELARA.
• Tetanus titers were evaluated 25 days after inoculation. A positive humoral recall response to the tetanus toxoid was considered to be a titer that increased by at least
  4-fold from baseline. The results are presented in Table: Summary of Antibody Response to Tetanus Toxoid in Patients with Moderate to Severe PsO Following SC Treatment with STELARA.

Nonmemory B-cell Antibody Response and Memory T-cell Antibody Response (Multiple Sclerosis)

Brodmerkel et al (2010)² studied the ability of adult patients with relapsing forms of multiple sclerosis to have a nonmemory B-cell antibody response and a memory T-cell antibody response after receiving SC STELARA 0.27 mg/kg (n=4), 0.675 mg/kg (n=4), 1.35 mg/kg (n=4), 2.7 mg/kg (n=4) or placebo (n=4) in a phase 1, multicenter, randomized, double-blind, placebo-controlled, escalating dose study.

• Pneumococcal vaccination and tetanus toxoid response were measured in the same manner as described in the previous phase 1 SC STELARA study in patients with moderate to severe PsO.
• Antibody responses to pneumococcal vaccination are described in Table: Summary of Antibody Response to Pneumococcal Vaccination in Patients with Multiple Sclerosis Following SC Treatment with STELARA.

• Antibody responses to tetanus toxoid vaccination are presented in Table: Summary of Antibody Response to Tetanus Toxoid in Patients with Multiple Sclerosis Following SC Treatment with STELARA.

Long-term STELARA Therapy (PsO)

Brodmerkel et al (2013)³ evaluated the effects of long-term STELARA therapy (≥3 years) on tetanus toxoid (T-cell-dependent) and pneumococcus (T-cell-independent) vaccine response in adult patients with moderate to severe plaque PsO in a multicenter, nonrandomized, open-label, controlled trial.

Study Design/Methods

• Two patient groups were included in the study:
  • Group 1 (n=60) included a subset of patients who were enrolled in the long-term extension of PHOENIX 2 (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)⁶ and were being treated with STELARA 90 mg (n=45) or STELARA 45 mg (n=15) at a dosing frequency of either every 8 weeks or every 12 weeks, and who had a history of moderate to severe chronic plaque PsO. Average exposure to STELARA prior to vaccination was 196.8 weeks (approximately 3.8 years).
  • Group 2 (control group [n=56]) included an external control cohort of patients who were currently not receiving systemic therapies for their moderate to severe chronic plaque PsO.
  • All randomized patients enrolled in the PHOENIX 2 trial were not receiving background immunosuppressive therapy at study entry.
• Patients treated with STELARA received their vaccinations 4 weeks prior to a regularly scheduled STELARA dose and all patients were followed for safety and vaccine responses for 4 weeks following vaccination.
• Patients were excluded from this substudy if they had received a tetanus-containing vaccine within 5 years, had ever been vaccinated with a pneumococcal vaccine, or had received another biologic within the previous 3 months (other than STELARA for the PHOENIX 2 patients) or any systemic therapy for PsO within 4 weeks of the scheduled vaccination.
• All patients were vaccinated with both TdaP or ADACEL^® (tetanus, diphtheria, and acellular pertussis) and PNEUMOVAX^® 23 (polyvalent pneumococcus) vaccines.
• Serum was collected prevaccination and 4 weeks postvaccination in order to measure antibody response.
• Baseline demographics and disease characteristics were similar between the 2 groups.
• The mean age at the time of vaccination was 49.5 years and 51.1 years for the control group and the STELARA group, respectively.

Results

Tetanus Vaccine Response

• Prevaccination and postvaccination samples were available for 59/60 (98.3%) patients in the STELARA group and 54/56 (96.4%) patients in the control group.
• From prevaccination to postvaccination, patients in the control group experienced a 9.5-fold increase (0.48 to 4.60 IU/mL) in antitetanus immunoglobulin G (IgG) antibodies compared to an 11.7-fold increase (0.38 to 4.40 IU/mL) in the STELARA group.
• Response was defined as ≥4 fold increase in antitetanus IgG antibodies from prevaccination to postvaccination.
• In the control group, 77.8% of patients achieved response as compared to 84.7% of patients in the STELARA group.
• A protective antibody level was defined as a tetanus antibody concentration of ≥0.5 IU/mL. The percentage of patients that did not have a prevaccination protective antibody titer was 44.4% in the control group (n=24) and 55.9% in the STELARA group (n=33). Of these patients, the percentage that achieved response postvaccination was similar among the control group (100%) and the STELARA group (97%). Of those who had a prevaccination protective antibody titer in the control group (n=30) and the STELARA group (n=26), 60% and 69.2% of patients achieved response, respectively.

Pneumococcal Vaccine Response

• Patient response was defined as a ≥2-fold increase in antibody level from prevaccination to postvaccination for ≥7 of 14 serotypes. In the control group and STELARA group, 92.6% and 96.6% of patients achieved response, respectively.
• The proportion of patients achieving ≥4-fold increase in antibody levels to all 14 pneumococcal serotypes was comparable between the control and STELARA groups, except for serotypes 3 and 4, in which the STELARA group had higher response rates (>20% higher) than the control group.
• An elevated prevaccination antibody titer was defined as ≥1.6 μg/mL for ≥7 of 14 pneumococcal antigens. In patients without an elevated prevaccination titer, 93.6% (n=47) and 96.5% (n=57) of patients in the control group and the STELARA group achieved a response, respectively. In patients with an elevated prevaccination antibody titer, 85.7% (n=7) and 100% (n=2) of patients in the control group and in the STELARA group achieved response, respectively.

Safety

• No adverse events (AEs) leading to serious AEs, deaths, or treatment discontinuation were reported.
• AEs were reported in 26.7% of patients in the STELARA group and 8.9% of patients in the control group.
• AEs reported higher in the STELARA group were primarily related to injection-site reactions to the vaccinations (3.3% for tetanus and 8.3% for pneumococcal). These reactions were mild in intensity and subsequently resolved.

Antibody and Cellular Immune Responses to Influenza Vaccination (Crohn’s Disease)

Doornekamp et al (2020)⁴ assessed antibody and cellular immune responses to an inactivated trivalent influenza vaccine (TIV; 2018-2019 season) in adult patients with Crohn’s disease (CD) treated with STELARA compared with those treated with adalimumab and with healthy controls in a single-center, prospective study.

Study Design/Methods

• This prospective study enrolled adult patients with CD between September 2018 and November 2018 who were treated with STELARA (n=15) or adalimumab (n=12) and who wished to be vaccinated with the inactivated TIV. Healthcare workers who received the TIV for occupational reasons were included as healthy controls (n=20) after age and sex matching to the CD cohort.
• An STELARA dose of 90 mg injected every 8 or 12 weeks and an adalimumab dose of 40 mg injected every 2 weeks were considered to be standard doses; doses injected more frequently were considered to be escalated doses.
  • In the STELARA group, 1 patient was injected every 7 weeks and 1 patient every 6 weeks; in the adalimumab group, 2 patients were injected weekly, 2 patients every 10 days, and 1 patient every 4 weeks.
• The 2018-2019 inactivated TIV formulation, administered via intramuscular injection in the deltoid, contained 15 mcg of hemagglutinin antigen of each of the following influenza virus strains: A/Michigan/45/2015 (H1N1)pdm09-like virus, A/Singapore/INFIMH-16-0019/2016 (H3N2)-like virus, and B/Colorado/06/2017-like virus (B/Victoria/2/87 lineage).
• Blood sampling was performed at baseline (prior to TIV administration) and at 1, 3, and 9 months after vaccination.
• Antibody response was assessed by the following outcomes: seroprotection rate (defined as the proportion of patients with antibody titers >40 in each group), seroconversion rate (defined as the proportion of patients with ≥4-fold increases in antibody levels postvaccination compared with prevaccination levels), and geometric mean titers (GMTs) per time point.
• Cellular response was measured by the proliferation of influenza-specific total cluster of differentiation 3-positive (CD3+), CD4+, and CD8+ T-cells.
• Baseline characteristics were comparable across the 3 groups; however, the median (interquartile range [IQR]) duration of adalimumab treatment was significantly longer than that of STELARA treatment (32 [15-82] vs 13 [5-19] months; P=0.022).
• The mean of the median ages in each group was 39 years (IQR, 29-50 years) and 57% of the study population was female.
• Three patients in the STELARA group used immunomodulators compared with 2 patients in the adalimumab group.
• Montreal classification, use of concomitant medications, and influenza vaccination history were not significantly different between the 3 groups.
• In order to prevent finding significances due to multiple testing, a comparison between 2 groups was performed only if the comparison between the 3 groups showed a P value of <0.10.

Results

Seroprotection

• Seroprotection rates to the H3N2 strain were 100% in all 3 groups at 1 month postvaccination. At 3 months postvaccination, the rate remained at 100% in the STELARA and healthy control groups and was 81.8% in the adalimumab group (overall P=0.056 [vs STELARA and healthy control groups]).
• Results for seroprotection rates to all virus strains are presented in Table: Seroprotection Rates to Influenza Virus Strains at Baseline and 1 and 3 Months Postvaccination in Patients with Crohn’s Disease and in Healthy Controls.

Seroconversion

• At 3 months postvaccination, seroconversion rates to the H3N2 strain were significantly higher in the STELARA group than in the adalimumab (P=0.015) and healthy control (P=0.035) groups.
• Results for seroconversion rates to all virus strains are presented in Table: Seroconversion Rates to Influenza Virus Strains at 1 and 3 Months Postvaccination in Patients with Crohn’s Disease and in Healthy Controls.

Antibody Titers

• The STELARA group showed comparable postvaccination antibody GMTs to those observed in the healthy control group.
• In the adalimumab group, antibody GMTs were lower than the other 2 groups for all influenza vaccine strains at both 1 month and 3 months postvaccination, except for the H1N1 strain at the 3 months postvaccination; the difference was significant for the B/Victoria strain when comparing the 3 groups (overall P=0.031 and P=0.028 at 1 and 3 months, respectively) and when comparing the STELARA and adalimumab groups (P=0.028 and P=0.009 at 1 and 3 months, respectively).
• Prevaccination antibody GMTs for A/H3N2 were significantly lower in the STELARA group than in the adalimumab and healthy control groups (26 vs 59 vs 163, respectively; overall P=0.013); as a result, postvaccination antibody GMTs were reassessed after correcting for the high titers in the adalimumab and healthy control groups.
  • Postcorrection antibody GMTs for A/H3N2 were significantly higher in the STELARA and healthy control groups than in the adalimumab group at 3 months postvaccination (132 vs 85 vs 35, respectively; overall P=0.041).
  • Postcorrection antibody GMTs for B/Victoria were significantly higher in the STELARA group than in the adalimumab and healthy control groups at both 1 month (53 vs 13 vs 31, respectively; overall P=0.014) and 3 months (42 vs 10 vs 21, respectively; overall P=0.015) postvaccination.

Cellular Immune Response

• There were no significant differences in cellular immune responses when time points and T-cell subsets were compared across the 3 groups; however, one-on-one comparisons showed that CD3+CD8+ T-cell response at 1 month postvaccination was significantly greater in the STELARA group than in the healthy control group (P=0.025).

Recombinant Zoster Vaccine in Patients with Inflammatory Bowel Disease

Khan et al (2022)⁵ conducted a retrospective cohort study to evaluate the efficacy of recombinant zoster vaccine (RZV) in preventing herpes zoster (HZ) infection in patients with inflammatory bowel disease (IBD) and to determine variation in RZV efficacy due to the use of IBD medications, including STELARA.

Study Design/Methods

• Patients aged ≥50 years who were diagnosed with IBD (CD and/or ulcerative colitis) according to International Classification of Diseases, Version 9, Clinical Modification (ICD-9-CM) or International Classification of Diseases, Version 10, Clinical Modification (ICD-10-CM) on or before the study start date (January 3, 2018) were included from the US National Veterans Affairs Healthcare System.
• To adjust for prior exposure to HZ vaccine due to previous recommendations, patients were categorized into 2 age-based cohorts: 50- to 60-year-old and >60-year-old.
• Patients were followed up from the start of the study (January 3, 2018) until the earliest of the following: diagnosis of HZ, end of the study (October 31, 2020), or death.
• The exposure of interest was receipt of RZV. Patients were categorized into 3 groups based on vaccination status: unvaccinated, single-dose vaccinated, and full-dose vaccinated.
• Multivariate Cox regression analyses using non-time-varying (baseline) and time-varying covariates were performed to evaluate the risk of HZ infection in the vaccinated vs unvaccinated group, stratified by IBD medications, including STELARA.

Results

• A total of 7008 and 26,292 patients with IBD were included in the 50- to 60-year-old and >60-year-old cohorts, respectively.
  • 50- to 60-year-old: no dose, n=5995; single-dose, n=358; and 2 doses, n=655
  • >60-year-old: no dose, n=20,554; single-dose, n=1518; and 2 doses, n=4220
• The incidence rate of HZ based on vaccination status and use of STELARA in the 50- to 60-year-old and >60-year-old cohorts is given in the Table: Incidence of HZ Based on RZV Vaccination Status and Use of STELARA.

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 11 January 2025.