STELARA®
(ustekinumab)
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STELARA® (ustekinumab)
Medical Information
Retreatment of Ulcerative Colitis with STELARA After a Drug-Free Interval
Last Updated: 12/06/2024
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 on dosage and administration for STELARA.
- The efficacy, pharmacokinetic, safety, and immunogenicity data for patients who had at least a year of STELARA treatment interruption during the phase 3 clinical trial program in ulcerative colitis (UC; UNIFI) are summarized below. These patients were in clinical response to STELARA intravenous (IV) induction, randomized to placebo at maintenance baseline, and dose adjusted from subcutaneous (SC) placebo to STELARA 90 mg SC every 8 weeks (q8w) during the long-term extension (LTE).1
CLINICAL DATA
Overall Study Design/Methods
- The safety and efficacy of STELARA were evaluated in adult patients with moderate-to-severe UC in a phase 3, randomized, double-blind, placebo-controlled, multicenter clinical program (UNIFI). The program consisted of an 8-week IV induction study and a 44-week SC maintenance study.
2 - Patients were required to have had an inadequate response to or unacceptable side effects from tumor necrosis factor blockers, vedolizumab, or conventional (ie, nonbiologic) therapy.2
- During the induction phase (8 weeks in duration), patients were randomized 1:1:1 at week 0 (baseline) to receive a single IV induction dose of STELARA 130 mg or a dose approximating STELARA 6 mg/kg (260 mg [weight ≤55 kg], 390 mg [weight >55 kg and ≤85 kg], or 520 mg [weight >85 kg]) or placebo.2
- During the maintenance phase (44 weeks in duration), patients who demonstrated a clinical response at week 8 to a single dose of STELARA IV induction were randomized 1:1:1 to receive STELARA 90 mg SC q8w, STELARA 90 mg SC every 12 weeks (q12w), or placebo SC.2
- The UNIFI LTE study started after the 44-week UNIFI maintenance study.3
- During the LTE, patients were to continue to receive the same treatment regimen at the end of the maintenance study (either placebo, STELARA 90 mg SC q12w, or STELARA 90 mg SC q8w), with the first dose in the LTE being administered at week 48.3
- Patients who were assigned to placebo SC during the maintenance study were discontinued after study unblinding, which occurred after the analysis of maintenance study data.3
- From week 56 onward in the LTE, based on the clinical judgment of the investigator, 1 dose adjustment at any time was allowed:3
- Patients in the placebo SC arm could receive STELARA 90 mg SC q8w.
- Patients in the STELARA 90 mg SC q12w arm could receive STELARA 90 mg SC q8w.
- Patients in the STELARA 90 mg SC q8w arm could continue on STELARA
90 mg SC q8w (sham dose adjustment).
- Patients who were dose adjusted from placebo SC to STELARA 90 mg SC q8w during the LTE were those who had at least a year of STELARA treatment interruption. Specifically, these patients were in clinical response to STELARA IV induction, randomized to placebo at maintenance baseline, and treated during the LTE.3
Results
Efficacy
Symptomatic Remission
- Among the patients who were in clinical response to STELARA IV induction, randomized to placebo SC at maintenance baseline, and treated during the LTE, a total of 42 patients had a dose adjustment to STELARA 90 mg SC q8w during the LTE and had data available at least 16 weeks after dose adjustment.1
- Among the patients in the placebo SC→STELARA 90 mg SC q8w group who had data available at least 16 weeks after dose adjustment, 40.5% (17 of 42 patients) were in symptomatic remission (defined as a Mayo stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0) at the time of dose adjustment, and 71.4% (30 of 42 patients) were in symptomatic remission at the first visit at least 16 weeks after dose adjustment.1
- Among the patients who were not in symptomatic remission at the time of dose adjustment and had data available at least 16 weeks after dose adjustment in the placebo SC→STELARA 90 mg SC q8w group, 64.0% (16 of 25 patients) were in symptomatic remission at the first visit at least 16 weeks after dose adjustment.1
Partial Mayo Remission
- Among the patients in the placebo SC→STELARA 90 mg SC q8w group who had data available at least 16 weeks after dose adjustment, 40.5% (17 of 42 patients) were in partial Mayo remission (defined as a partial Mayo score ≤2) at the time of dose adjustment, and 76.2% (32 of 42 patients) were in partial Mayo remission at the first visit at least 16 weeks after dose adjustment.1
- Among the patients who were not in partial Mayo remission at the time of dose adjustment and had data available at least 16 weeks after dose adjustment in the placebo SC→STELARA 90 mg SC q8w group, 80.0% (20 of 25 patients) were in partial Mayo remission at the first visit at least 16 weeks after dose adjustment.1
Inflammatory Biomarkers
- Among patents in the placebo SC→STELARA 90 mg SC q8w group who had data available at least 16 weeks after dose adjustment, the median inflammatory biomarker concentrations at the time of dose adjustment and at the first visit at least 16 weeks after dose adjustment, respectively, were as follows:1
- C-reactive protein: 3.6 mg/L, 2.0 mg/L
- Fecal lactoferrin: 128.9 µg/g, 28.3 µg/g
- Fecal calprotectin: 1016.5 mg/kg, 355.0 mg/kg
Pharmacokinetics
- Serum ustekinumab concentrations increased following dose adjustment from placebo to STELARA 90 mg SC q8w. Specifically, the median serum ustekinumab concentration increased from 0.0 µg/mL at week 44 to 4.70 µg/mL and 3.64 µg/mL at week 68 and week 92, respectively.1
Safety
- Overall, the safety profile for randomized patients was consistent with that observed among all treated patients.1
- Among the limited number of patients who had a dose adjustment to STELARA
90 mg SC q8w, the safety profile was generally consistent with that observed in patients randomized in maintenance to STELARA 90 mg SC q8w (with safety data from week 44 through week 96 or up to the time of dose adjustment).1 - See Table: Safety Results from Week 44 through Week 96: Randomized Patients in Maintenance Who Were Treated in the LTE for safety results.
| STELARA | All STELARA | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Placebo SCa | 90 mg SC q12w | 90 mg SC q8w | ||||||||
| Placebo SCb | Placebo SC→ STELARA 90 mg SC q8wc | 90 mg SC q12wb | 90 mg SC q12w→ 90 mg SC q8wc | Combined (as randomized) | 90 mg SC q8wb | 90 mg SC q8w→ 90 mg SC q8wc | Combined (as randomized) | |||
| Analysis set: randomized patients in maintenance who were treated in the LTE | 115 | 53 | 141 | 40 | 141 | 143 | 37 | 143 | 337 | |
| Average duration of follow-up (weeks) | 32.4 | 31.2 | 44.5 | 22.7 | 50.9 | 44.2 | 29.2 | 51.7 | 48.2 | |
| Patients who died | 0 | 1 (1.9%)d | 0 | 0 | 0 | 0 | 0 | 0 | 1 (0.3%) | |
| Patients with 1 or more | ||||||||||
| 76 (66.1%) | 37 (69.8%) | 95 (67.4%) | 20 (50.0%) | 99 (70.2%) | 97 (67.8%) | 19 (51.4%) | 102 (71.3%) | 238 (70.6%) | ||
| Serious AEs | 5 (4.3%) | 2 (3.8%) | 7 (5.0%) | 5 (12.5%) | 12 (8.5%) | 6 (4.2%) | 1 (2.7%) | 7 (4.9%) | 21 (6.2%) | |
| Infectionse | 39 (33.9%) | 24 (45.3%) | 61 (43.3%) | 12 (30.0%) | 69 (48.9%) | 58 (40.6%) | 15 (40.5%) | 69 (48.3%) | 162 (48.1%) | |
| Serious infectionse | 1 (0.9%) | 1 (1.9%) | 4 (2.8%) | 1 (2.5%) | 5 (3.5%) | 2 (1.4%) | 0 | 2 (1.4%) | 8 (2.4%) | |
| AEs leading to the discontinuation of study agent | 3 (2.6%) | 3 (5.7%) | 6 (4.3%) | 3 (7.5%) | 9 (6.4%) | 2 (1.4%) | 0 | 2 (1.4%) | 14 (4.2%) | |
| All malignancies | 1 (0.9%) | 0 | 1 (0.7%) | 0 | 1 (0.7%) | 0 | 0 | 0 | 1 (0.3%) | |
| Excluding NMSC | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
| NMSC | 1 (0.9%) | 0 | 1 (0.7%) | 0 | 1 (0.7%) | 0 | 0 | 0 | 1 (0.3%) | |
| Abbreviations: AE, adverse event; CMV, cytomegalovirus; IV, intravenous; LTE, long-term extension; NMSC, nonmelanoma skin cancer; q8w, every 8 weeks; q12w, every 12 weeks; SC, subcutaneous; UC, ulcerative colitis. aPatients who were in clinical response to STELARA IV induction dosing and were randomized to placebo SC on entry into the maintenance study. bIncludes data from week 44 through week 96 or up to the time of dose adjustment for patients who had a dose adjustment to STELARA 90 mg SC q8w during the LTE. cIncludes data from the time of dose adjustment for patients who had a dose adjustment to STELARA 90 mg SC q8w (or a sham dose adjustment for the STELARA 90 mg SC q8w group) during the LTE. dThe patient had received 1 dose of STELARA after dose adjustment from placebo; the immediate cause of death was attributed to cardiac arrest and was deemed unrelated to STELARA treatment. Prior to cardiac arrest, the patient with multiple comorbidities reported CMV colitis, worsening UC, and failure to thrive. eInfection as assessed by the investigator. | ||||||||||
Immunogenicity
- The incidence of antibodies to ustekinumab was higher in patients who had a dose adjustment to STELARA 90 mg SC q8w from placebo (13.2%).1
- The incidence of antibodies was higher among patients who were receiving intermittent STELARA therapy (ie, patients who received STELARA during induction, were randomized to placebo in maintenance, and had a dose adjustment to STELARA during the LTE) compared to those who were on continuous STELARA therapy.1
- For the incidence of antibodies to ustekinumab through week 96 among randomized patients, please see Table: Ustekinumab Antibody Status through Week 96: Randomized Patients in Maintenance Who Were Treated in the LTE.
| PBO SCa | STELARA 90 mg SC q12wa | STELARA 90 mg SC q8wa | PBO SC→ STELARA 90 mg SC q8wb | STELARA 90 mg SC q12w→ STELARA 90 mg SC q8wb | STELARA 90 mg SC q8w→ STELARA 90 mg SC q8wb | Total | |
|---|---|---|---|---|---|---|---|
| Randomized patients in maintenance who were treated in the LTE | 62 | 101 | 106 | 53 | 40 | 37 | 399 |
| Through week 96 | |||||||
| Patients with appropriate samplesc | 62 | 101 | 106 | 53 | 40 | 37 | 399 |
| Patients positive for antibodies to UST at any timed,e | 5 (8.1%) | 5 (5.0%) | 5 (4.7%) | 7 (13.2%) | 3 (7.5%) | 2 (5.4%) | 27 (6.8%) |
| Abbreviations: IV, intravenous; LTE, long-term extension; PBO, placebo; q8w, every 8 weeks; q12w, every 12 weeks; SC, subcutaneous; UST, ustekinumab. aPatients who were in clinical response to STELARA IV induction dosing, were randomized to the specified treatment group on entry into the maintenance study, and did not have a dose adjustment during the LTE. bPatients who had a dose adjustment to STELARA 90 mg SC q8w (or with a sham dose adjustment for the STELARA 90 mg SC q8w group) during the LTE. cPatients who had 1 or more samples obtained after their first study agent administration of the induction study through the evaluation visit. dPatients who had at least 1 positive sample at any time after their first study agent administration of the induction study through the evaluation visit. eDenominator is patients with appropriate samples. | |||||||
Literature Search
A literature search of MEDLINE®
References
| 1 | Data on File. Ustekinumab. Clinical Study Report (96-Week) CNTO1275UCO3001. Janssen Research & Development, LLC. EDMS-ERI-205140704; 2020. |
| 2 | |
| 3 |