Summary

• The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
• Please refer to local labeling for relevant information on dosage and administration of STELARA.
• Phase 3 studies compared the efficacy and safety of 2 different doses of STELARA and investigated dosing interval adjustment from every 12 weeks (q12w) to every 8 weeks (q8w) for nonresponders or partial responders (intensified dosing).^1,2
• Additional analyses of these phase 3 studies assessed longer-term efficacy and safety.^3-6

CLINICAL DATA

PHOENIX 1

Leonardi et al (2008)¹ conducted the 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 study, a phase 3, double-blind, placebo-controlled, multicenter trial evaluating the efficacy and safety of STELARA in 766 adult patients with moderate to severe plaque psoriasis (PsO).

Study Design/Methods

• Adult patients with a diagnosis of plaque PsO for ≥6 months who were candidates for phototherapy or systemic therapy, and had a baseline Psoriasis Area and Severity Index (PASI) score ≥12, and ≥10% of their body surface area (BSA) involved were eligible for enrollment.
• Patients with non-plaque forms of PsO were ineligible.
• Eligible patients were randomized in equal proportions to 1 of 3 treatment groups:
  • STELARA 45 mg subcutaneous (SC) at weeks 0 and 4, and q12w.
  • STELARA 90 mg SC at weeks 0 and 4, and q12w.
  • Placebo at weeks 0 and 4, with half of the patients randomized to cross over to STELARA 45 mg and the other half to STELARA 90 mg at week 12.
• The primary endpoint was the proportion of patients achieving an at least 75% improvement in PASI (PASI 75) response at week 12.
• Major secondary endpoints included the proportion of patients with a Physician's Global Assessment (PGA) score of “cleared” or “minimal” at week 12 and the time to loss of PASI 75 response in the patients receiving STELARA maintenance therapy compared with patients withdrawn from treatment at week 40 (randomized withdrawal phase).

Poulin et al (2011)³ and Kimball et al (2012)⁴ described results related to dosing interval reduction through year 3 in the PHOENIX 1 trial.

• At week 28, 23% (n=86) of patients in the STELARA 45 mg group and 16% (n=60) of patients in the STELARA 90 mg group were partial responders (at least 50% improvement in PASI [PASI 50] to <75) and had their dosing interval reduced from q12w to q8w.³
• Overall, 79.8% (601/753) of STELARA-treated patients remained in the study through year 3, including 78.6% (297/378) in the 45 mg group and 81.1% (304/375) in the 90 mg group.⁴
  • Among partial responders adjusted to q8w dosing, a substantial proportion achieved PASI 75 response by week 52 (45 mg, 51.7%; 90 mg, 42.3%); with stable and continuous q8w dosing, PASI 75 response was generally maintained (45 mg, 50.9%) or improved (90 mg, 52.0%) through year 3.
  • Among partial responders, rates and patterns of adverse events (AEs) and infections adjusted for length of follow-up were generally similar before and after dosing adjustment, suggesting no increased risk with STELARA q8w dosing.

Kimball et al (2013)⁵ evaluated the efficacy and safety of STELARA through 5 years in the PHOENIX 1 trial. This analysis included 766 patients. Of the 753 patients who received at least 1 dose of STELARA, 68.7% (517/753) received STELARA through the last scheduled year 5 dose (at or before week 244) in the PHOENIX 1 trial.

Results

Efficacy: Partial Responders Adjusted to q8w Dosing at Week 28 or 40

• PASI 75 response rate through week 244 was 57.6% in the 45 mg group and 55.1% in the 90 mg group.
• At least 90% improvement in PASI (PASI 90) response rate at week 244 was 27.2% in the 45 mg group and 27.5% in the 90 mg group.

Safety

• STELARA was generally well tolerated without evidence of cumulative toxicity with increased duration of exposure through 5 years in 3104 patient-years (PY) of follow-up; the average duration of follow-up was 214 weeks in the combined group.
• Rates of AEs per 100 PY (all rates reported are per 100 PY) for the 45 mg and 90 mg groups, respectively, were 220.92 and 209.05; the rate in the combined group was 214.94.
• Through year 5, rates of serious AEs were 5.26 and 5.43 in the 45 mg and 90 mg groups, respectively; the rate in the combined group was 5.35.

PHOENIX 2

Papp et al (2008)² conducted the PHOENIX 2 study, which was a phase 3, multicenter, double-blind, placebo-controlled trial evaluating the efficacy and safety of STELARA in 1230 adult patients with moderate to severe plaque PsO.

Study Design/Methods

• Adult patients with a diagnosis of plaque PsO for ≥6 months who were candidates for phototherapy or systemic therapy, had a baseline PASI score ≥12, and had ≥10% of their BSA involved were eligible for enrollment.
• Patients with non-plaque forms of PsO were ineligible.
• The trial was divided into 3 phases: placebo-controlled phase (weeks 0-12), placebo crossover and active treatment phase (weeks 12-28), and a randomized dose intensification phase (weeks 28-52).
• At baseline, eligible patients were randomized in a 1:1:1 ratio to 1 of 3 treatment groups as in PHOENIX 1.
  • STELARA 45 mg SC at weeks 0 and 4, and q12w.
  • STELARA 90 mg SC at weeks 0 and 4, and q12w.
  • Placebo at weeks 0 and 4, with half of the patients randomized to STELARA 45 mg and the other half to STELARA 90 mg at weeks 12 and 16, and q12w thereafter.
• The primary endpoint was the proportion of patients who achieved a PASI 75 response at week 12.
• Major secondary endpoints included the proportion of patients with a PGA score of “cleared” or “minimal” at week 12 and the number of visits with PASI 75 response between weeks 40 and 52 in the group receiving STELARA q8w compared with the group receiving STELARA q12w.

Results

Efficacy

• At week 28, 22.7% of patients in the STELARA 45 mg group and 15.8% of patients in the STELARA 90 mg group were partial responders.
• Dosing intensification did not result in greater efficacy compared with q12w dosing among all the rerandomized partial responders, as assessed by the number of visits between weeks 40 and 52 where a PASI 75 response was achieved (mean, 1.75 visits and 1.56 visits in the q8w and q12w groups, respectively; P=0.468).
• Unlike the response to STELARA 45 mg intensified dosing, STELARA 90 mg dosing intensification resulted in a greater number of visits with PASI 75 response in partial responders (mean, 2.63 vs 1.58 visits; P=0.014) and a higher PASI 75 response rate (68.8% vs 33.3% in patients with q8w vs q12w dosing).

Safety

• During the dosing intensification period, AEs were seen in more patients receiving q8w dosing than those receiving q12w dosing; serious AEs were seen in more patients receiving q12w dosing than in those receiving q8w dosing.
• There was no dose response seen in the rates of AEs, serious AEs, or AEs leading to treatment discontinuation by the end of week 52. In STELARA-treated patients, the most common serious AEs included infections and cardiac disorders.

Langley et al (2014)⁶ evaluated the safety and efficacy of STELARA through 5 years in the PHOENIX 2 trial.

Study Design/Methods

• PASI and PGA were used to evaluate treatment response through week 244. Safety endpoints were monitored through week 264.
• The overall study population included all patients who received at least 1 dose of STELARA.
• Early adjusters were patients who were partial responders (PASI 50 to <PASI 75) at week 28 or week 40 who had their dosing intervals adjusted from q12w to q8w.
• Late adjusters included patients who received their original STELARA dose and dose interval through week 52, but had their dosing regimen adjusted during the long-term extension (at the discretion of the investigator).
  • Patients receiving STELARA 45 mg q12w could have their treatment regimen adjusted to 45 mg q8w, then to 90 mg q8w.
  • Patients receiving STELARA 45 mg q8w could receive a single dose adjustment to 90 mg q8w.
  • Patients receiving STELARA 90 mg q12w could receive a single dose interval adjustment to 90 mg q8w.
• Nonadjusters were patients who received their original randomized STELARA dose q12w with no adjustment to dose or dose interval.

Results

• This analysis included 1212 patients who received at least 1 dose of STELARA in the PHOENIX 2 trial. Of these, 849 (70%) completed study treatment at year 5.
• Of patients continuing treatment past week 28, 20% (223/1112) were early adjusters, 31% (345/1112) were late adjusters, and 48.9% (544/1112) were nonadjusters.

Efficacy at Week 244

Overall Population

• PASI 75 response rates: STELARA 45 mg, 76.5%; STELARA 90 mg, 78.6%.
• PASI 90 response rates: STELARA 45 mg, 50.0%; STELARA 90 mg, 55.5%.
• One hundred percent improvement in PASI (PASI 100) response rates: STELARA 45 mg, 28.1%; STELARA 90 mg, 31.3%.
• PGA 0/1: STELARA 45 mg, 54.0%; STELARA 90 mg, 58.6%.

Early Adjusters

• STELARA 45 mg: At week 52, the proportion of early adjusters achieving PASI 75 did not significantly differ between those receiving STELARA 45 mg q8w vs those receiving STELARA 45 mg q12w (34.9% vs 31.3%; P=0.718).
• STELARA 90 mg: At week 52, the proportion of early adjusters achieving PASI 75 was greater in patients receiving STELARA 90 mg q8w vs q12w (68.8% vs 33.3%; P=0.004).
• During the long-term extension (through week 244) the proportion of early adjusters receiving STELARA 45 mg who achieved a PASI 75 increased and approached that of the STELARA 90 mg group (64.2% and 67.9%).

Late Adjusters at 144 Weeks of Follow-up

Originally randomized to STELARA 45 mg:

• PASI 75: 57.1% of nonresponders and 88.6% of partial responders.
• PASI 90: 56.4% of PASI 75 to <PASI 90 responders.
• PASI 100: 31.6% of PASI 90 to <PASI 100 responders.

Originally randomized to STELARA 90 mg:

• PASI 75: 44.4% of nonresponders and 77.8% of partial responders.
• PASI 90: 52.9% of PASI 75 to <PASI 90 responders.
• PASI 100: 18.2% of PASI 90 to <PASI 100 responders.

Nonadjusters

• At week 28, 95% of nonadjusters had achieved a PASI 75. Most retained response through week 244 (PASI 75, 91.3%; PASI 90, 74.2%).

Safety Through Week 264

• Cumulative rates of AEs and serious AEs were generally comparable between patients receiving STELARA 45 and 90 mg in the overall population and between nonadjusters and adjusters.
• There were no cases of active tuberculosis or infections of interest (atypical mycobacterial, systemic fungal, or Salmonella).
• The most common serious infections included diverticulitis (n=7), cellulitis (n=5), and cholecystitis (n=3).
• There were no reported cases of anaphylaxis or serum sickness-like reactions.

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 4 June 2024. Data presented are from phase 3 clinical trials.