Summary

• Please refer to the local labeling for relevant information on STELARA.
• STELARA was evaluated in 3 randomized, double-blind, placebo-controlled phase 3 clinical studies in adult patients with moderately to severely active Crohn’s disease (CD) (Crohn’s Disease Activity Index [CDAI] score of 220 to 450). There were two 8-week intravenous (IV) induction studies (UNITI 1 and UNITI 2), followed by a 44-week subcutaneous (SC) randomized withdrawal maintenance study (IM-UNITI), representing 52 weeks of therapy.¹ STELARA was also evaluated in the long-term extension (LTE) of the IM-UNITI maintenance study through 5 years of therapy, and the results through 3 years² and 5 years^3,4 are reported below. Additionally, results from analyses of corticosteroid-free remission through 1 year and patient reported symptom improvements during induction therapy are summarized below.^5,6
• A post-hoc analysis of pooled data from GALAXI-1 (a phase 2b trial which studied the efficacy of guselkumab in patients with moderately to severely active Crohn's disease) and IM-UNTI assessed the impact of endoscopic response at maintenance on long-term outcomes.^7,8

CLINICAL TRIALS

UNITI Trial Program

The efficacy and safety of STELARA was evaluated in 3 randomized, double-blind, placebocontrolled phase 3 clinical studies in adult patients (≥18 years of age) with moderately to severely active CD (CDAI score of 220 to 450). There were two 8-week IV induction studies (UNITI 1 and UNITI 2), followed by a 44-week SC randomized withdrawal maintenance study (IM-UNITI), representing 52 weeks of therapy.¹ All patients (randomized and non-randomized) who completed the efficacy and safety assessment at week 44 of the IM-UNITI maintenance study were eligible to participate in the IM-UNITI extension (up to 4 years) and continued to receive the same treatment as they were receiving at week 44 of the IM-UNITI maintenance study (no dose adjustment occurred in the LTE).^{1, 3}

In the UNITI program, baseline and disease characteristics were similar among the treatment groups. Patients were allowed to have stable doses of immunosuppressants, mesalamine, antibiotics, or oral glucocorticoids (≤40 mg prednisone daily or ≤9 mg budesonide daily) or a combination of these. In patients who had a response to induction treatment and who were receiving glucocorticoids, tapering was initiated at week 0 of the IM-UNITI trial.¹

UNITI-1 and UNITI-2 Intravenous Induction Studies

UNITI-1 was a phase 3, randomized, double-blind, placebo-controlled, multicenter study was conducted to evaluate the efficacy and safety of 2 STELARA IV induction regimens in adult patients with moderately to severely active CD (CDAI 220-450) who failed or were intolerant to 1 or more tumor necrosis factor (TNF) blockers.^1,9,10

UNITI-2 was a phase 3, randomized, double-blind, placebo-controlled, multicenter study was conducted to evaluate the efficacy and safety of 2 STELARA IV induction regimens in adult patients with moderately to severely active CD who had failed or were intolerant to oral steroid and/or immunosuppressive therapy (ie, azathioprine, mercaptopurine, or methotrexate), but were not refractory to TNF blocker therapy. Patients were allowed to have previously received ≥1 TNF blocker but couldn’t have been intolerant to the TNF blocker(s) and had not met the criteria for primary or secondary nonresponse to the treatment.^1,11,12

Study Design/Methods

• In both studies, at week 0, patients were randomized in a 1:1:1 ratio to receive a single dose of IV placebo, or IV STELARA 130 mg, or weight-based tiered IV STELARA dosing approximating 6 mg/kg (260 mg [weight ≤55kg], 390 mg [weight >55kg and ≤85kg], 520 mg [weight >85kg]).^1,9-12
• Primary endpoint: clinical response at week 6 (defined as a reduction from baseline in CDAI score of ≥100 points or a CDAI score of <150).
• Major secondary endpoints: clinical response and clinical remission (defined as CDAI <150) at week 8, and 70-point CDAI response at weeks 3 and 6.
• Other prespecified secondary endpoints included: clinical response at week 3; clinical remission at weeks 3 and 6; decrease from baseline in CDAI score of at least 70 points at week 8; change in CDAI score, change in C-reactive protein (CRP) level, and normalization of CRP level (<3.0 mg/L) at weeks 3, 6, and 8; and change in fecal calprotectin level and normalization of fecal calprotectin level (≤250 or ≤100 mg/kg) at week 6.
• Of note, secondary endpoints (ie, all endpoints except for the primary and major secondary endpoints) were not adjusted for multiplicity. Statements of significance for these secondary endpoints are based on nominal P values and should be interpreted cautiously.
• At week 8, eligible patients were transitioned to the maintenance study (IM-UNITI) and those who did not enter the maintenance study had a safety follow-up through week 20.

Results

Efficacy: UNITI-1

• A total of 741 patients were randomized.^1,10
• Among patients enrolled, approximately 50% had previously failed ≥2 TNF blockers due to the following: primary non-response per protocol criteria: 29.1%, secondary nonresponse per protocol criteria: 69.4%, unacceptable side effects: 36.4%.
• Clinical response at week 6 (primary endpoint) was significantly higher in the STELARAtreated patients than in the placebo group. This was observed in 33.7% of the STELARA ~6 mg/kg group and in 34.3% of the STELARA 130 mg group vs 21.5% in the placebo group (P=0.003 and P=0.002, respectively).
• Details regarding major and other secondary endpoints are described in Table: Secondary Endpoints: Clinical Response at Weeks 3 and 8; Clinical Remission at Weeks 3, 6, and 8; 70-point CDAI Response at Weeks 3, 6, and 8 in UNITI-1.^1,13

Efficacy: UNITI-2

• A total of 628 patients were randomized. A total of 68.6% of patients had never received TNF blockers.^1,11
• Clinical response at week 6 (primary endpoint) was significantly higher in the STELARAtreated patients than in the placebo group. This was observed in 55.5% of the STELARA ~6 mg/kg group and in 51.7% of the STELARA 130 mg group vs 28.7% in the placebo group (P<0.001 for both comparisons).
• Details regarding major and other secondary endpoints are described in Table: Secondary Endpoints: Clinical Response at Weeks 3 and 8; Clinical Remission at Weeks 3, 6, and 8; 70-point CDAI Response at Weeks 3, 6, and 8 in UNITI-2.^1,13

Safety: UNITI-1

• The proportions of patients with adverse events (AEs) and serious AEs through week 8 in the STELARA 130 mg (n=246), STELARA ~6 mg/kg (n=249), and placebo group (n=245) were reported as 64.6% and 4.9%, 65.9% and 7.2%, 64.9% and 6.1%, respectively.
• Infections and serious infections through week 8 occurred in 23.2% and 1.2%, and 25.7% and 2.8%, and 23.7% and 1.2% of patients in the in the STELARA 130 mg, STELARA ~6 mg/kg, and placebo groups, respectively.
• AEs associated with infusions (events occurring within 1 hour after infusion) through week 8 occurred in 4.5%, 3.6%, and 2.0% of patients in the STELARA 130 mg, STELARA ~6 mg/kg, and placebo groups, respectively.
• In the STELARA ~6 mg/kg group, one patient who had a preexisting monoclonal gammopathy, and did not continue to the IM-UNITI trial, was diagnosed with multiple myeloma after the 20-week safety follow-up period.
• One opportunistic infection (listeria meningitis) was reported in the STELARA ~6 mg/kg group in a patient who was taking 30 mg of prednisone per day.

Safety: UNITI-2

• The proportions of patients with AEs and serious AEs through week 8 in the STELARA 130 mg (n=212), STELARA ~6 mg/kg (n=207), and placebo group (n=208) were reported as 50.0% and 4.7%, 55.6% and 2.9%, 54.3% and 5.8%, respectively.
• Infections and serious infections through week 8 occurred in 14.6% and 1.4%, and 21.7% and 0.5%, and 23.1% and 1.4% of patients in the in the STELARA 130 mg, STELARA ~6 mg/kg, and placebo groups, respectively.
• AEs associated with infusions (events occurring within 1 hour after infusion) through week 8 occurred in 2.4%, 1.4%, and 2.9% of patients in the STELARA 130 mg, STELARA ~6 mg/kg, and placebo groups, respectively.
• One patient in the placebo group developed basal-cell carcinoma.
• A nonserious case of esophageal candidiasis was reported in a patient in the placebo group who was taking 40 mg of prednisone per day and methotrexate.

IM-UNITI Subcutaneous Maintenance Study

A phase 3, randomized, double-blind, placebo-controlled, multicenter study was conducted to evaluate the efficacy and safety of 2 maintenance SC regimens of STELARA in patients with moderately to severely active CD who responded to IV treatment with STELARA in the UNITI-1 and UNITI-2 studies.^1,14,15

Study Design/Methods

• Patients who were in clinical response at week 8 to IV STELARA during the UNITI-1 or UNITI-2 induction study (n=397, primary population) were randomly assigned in a 1:1:1 ratio to receive (through week 40) placebo SC (n=133), or STELARA 90 mg SC every 8 weeks (q8w), (n=132), or STELARA 90 mg SC every 12 weeks (q12w), (n=132).^1,14,15
• A total of 884 patients were in the non-randomized population.^1,14,15
• Patients who received placebo or SC STELARA 90 mg SC q12w and met criteria of loss of response (defined as a CDAI score ≥220 and an increase from their baseline CDAI score of ≥100 points) between weeks 8 and 32 underwent dose adjustment and were allowed to cross over to receive STELARA 90 mg SC q8w. Patients who were already receiving STELARA 90 mg SC q8w continued to receive that regimen after loss of response.
• Patients who responded to placebo during the UNITI-1 or UNITI-2 study continued to receive SC placebo during the IM-UNITI study (part of the non-randomized population).
• Patients who were not in clinical response to IV placebo or STELARA in the UNITI-1 or UNITI-2 study were given both IV and SC study agent at the first visit of this maintenance study (week 0; part of the non-randomized population).
  • Patients previously receiving IV placebo were given STELARA 130 mg IV at week 0 (and SC placebo), and patients previously receiving IV STELARA were given 90 mg STELARA SC at week 0 (and IV placebo).
• Primary endpoint: clinical remission at week 44 (CDAI score <150).
• Major secondary endpoints: clinical response at week 44 (decrease in CDAI score of ≥100 points from week 0 of induction or clinical remission), maintenance of remission at week 44 among patients in remission at week 0 of the maintenance trial, glucocorticoidfree remission at week 44, and clinical remission at week 44 among those who previously failed or were intolerant to TNF blockers (ie, UNITI-1 population).
• Other prespecified secondary endpoints included: clinical remission at week 44 in the subgroup of patients in whom conventional therapy failed (UNITI-2 population), change in CDAI score through week 44, change in CRP level through week 44, and change in fecal calprotectin level at week 44.
• Of note, secondary endpoints (ie, all endpoints except for the primary and major secondary endpoints) were not adjusted for multiplicity. Statements of significance for these secondary endpoints are based on nominal P values and should be interpreted cautiously.

Results

Efficacy

Clinical Response and Remission

• Clinical remission at week 44 (primary endpoint) was observed in 53.1% and 48.8% of patients in the STELARA 90 mg SC q8w (n=128) and STELARA 90 mg SC q12w (n=129) groups, respectively, compared to 35.9% of patients in the placebo group (n=131; P=0.005 and P=0.040, respectively).^1,14
• Details regarding major and other secondary endpoints are described in Table: Secondary Endpoints: Clinical Response and Remission at Week 44 in the IM-UNITI Maintenance Trial.

Safety

• The proportions of patients in the primary population (randomized) with AEs and serious AEs through week 44 in the STELARA 90 mg q8w (n=131), STELARA 90 mg q12w (n=132), and placebo groups (n=133) were reported as 81.7% and 9.9%, 80.3% and 12.1%, 83.5% and 15.0%, respectively.
• Infections and serious infections through week 44 occurred in 48.1% and 2.3%, and 46.2% and 5.3%, and 49.6% and 2.3% of patients in the STELARA 90 mg q8w, STELARA 90 mg q12w, and placebo groups, respectively.
• AEs associated with injection site reactions through week 44 occurred in 6.9%, 2.3%, and 0.8% of patients in the STELARA 90 mg q8w, STELARA 90 mg q12w, and placebo groups, respectively.
• In the primary population, there were 2 malignancies reported (1 basal cell carcinoma in each of the placebo and STELARA 90 mg SC q8w groups).
• A nonserious case of esophageal candidiasis was reported in a patient who was not in the primary IM-UNITI population and who was receiving STELARA 90 mg SC q8w (pantoprazole and infliximab were prescribed within the prior 2 weeks).
• One report of active pulmonary tuberculosis occurred approximately 10 months after an induction dose of STELARA 130 mg in a patient assigned to receive placebo in the IMUNITI trial.
• In a patient who had received a single dose of STELARA 90 mg SC at week 0 of the IMUNITI trial, a nonfatal stroke resulting from a ruptured cerebral aneurysm was reported.
• Through 1 year of treatment, there were no deaths or cases of reversible posterior leukoencephalopathy.

UNITI Trials: Symptom Improvement Results Within the First Week from UNITI-1, Serum CRP, Fecal Calprotectin, Immunogenicity

Symptom Improvement Results Within the First Week from UNITI-1

• A post hoc analysis of UNITI-1 data was conducted to evaluate symptom improvement within the first week of the STELARA IV induction dose. Patient CDAI diary daily data (day -7 to +14) for the 3 patient-reported CDAI components (stool frequency [SF], abdominal pain [AP], and general well-being [WB]) were analyzed.¹⁶
• A comparison in the mean change from baseline in CDAI (over the 7-day period) between STELARA 6 mg/kg IV (n=184) and STELARA 130 mg IV (n=188) vs placebo (n=191) was made for the followings: SF+AP (1:1 weighted), SF+AP (CDAI weighted), and percentage of patients with ≥50-point improvement in CDAI based solely on SF+AP.
• Within the first 2 weeks, STELARA IV induced significant improvement in all 3 components, with AP first significantly better than placebo on day 2 for both STELARA doses, and consistently significantly better than placebo beginning on day 6 for STELARA 6 mg/kg IV and day 8 for STELARA 130 mg IV.
• For both STELARA IV doses, mean improvement in SF was first significantly better than placebo on day 7, while this occurred on day 8 for WB.
• For both STELARA IV doses, week 1 and 2 SF+AP with CDAI weighting was significantly improved compared to placebo at day 7 and day 14. Also, SF+AP added with equal 1:1 weight was significantly improved for both STELARA IV doses at day 14 and for STELARA 130 mg IV on day 7. See Table: UNITI-1: Mean Change in SF and AP from CDAI for further information.

Serum CRP

• In the induction trials, STELARA 130 mg IV and ~6 mg/kg IV were associated with greater reductions in and normalization of serum CRP levels than placebo (nominally significant differences as early as week 3 and through week 8). The P values of these comparisons vs placebo were considered nominally significant, since the endpoint was not among the type I error-controlled endpoints.¹
• Median CRP levels for patients in the STELARA 90 mg SC q8w and SC q12w group remained generally unchanged at week 44, while the levels for patients in the placebo group increased over time, with a noticeable separation from the STELARA groups beginning at week 12.

Fecal Calprotectin

• In the induction trials, STELARA 130 mg IV and ~6 mg/kg IV were associated with greater reductions from baseline in fecal calprotectin levels than placebo at week 6. For both comparisons of the STELARA groups vs placebo the P values was nominally significant, since the endpoint is not among the type I error-controlled endpoints.
• At week 44, the proportions of patients with fecal calprotectin concentrations ≤250 mg/kg were higher in the STELARA 90 mg SC q8w and STELARA 90 mg SC q12w groups compared with the placebo group (30.1% and 27.5% vs 10.8%, respectively). The difference was nominally significant, since the endpoint was not among the Type 1 errorcontrolled endpoints.^1,13

Immunogenicity

• Two patients who had received STELARA 130 mg IV tested positive for antidrug antibodies, and both had neutralizing antibodies. In IM-UNITI, the incidence of antidrug antibodies at week 44 was 2.3% (n=27 of 1154 patients).

IM-UNITI Study LTE

LTE - 3 Years

Hanauer et al (2020)² evaluated the long-term efficacy and safety of STELARA through 3 years in the LTE of the IM-UNITI maintenance study.

• The LTE is for up to 4 years (after the 44-week IM-UNITI study) and efficacy results through week 152 and safety results through week 156 were reported.
• There were 3 types of analyses conducted: 1) all randomized patients in maintenance, regardless of whether they entered the LTE (intent-to-treat [ITT] analysis of randomized patients from week 0 of IM-UNITI); 2) patients who entered the LTE (randomized patients and all patients); 3) observed cases with inclusion only of randomized patients who entered the LTE and who had data at a designated visit.
• A total of 567 STELARA-treated patients from the IM-UNITI study (237 from the randomized primary population) entered the LTE continuing the same treatment as they were on during the IM-UNITI maintenance study without any subsequent dose adjustment. After study unblinding, placebo-treated patients discontinued treatment. As described above in the IM-UNITI Study Design/Methods, a one-time dose adjustment to 90 mg q8w is allowed for randomized patients who met loss of response criteria from weeks 8-32 of the IM-UNITI maintenance study.
• Of the 567 patients in the LTE, 29.6% discontinued treatment prior to week 156.

Results

Efficacy

ITT Analysis of Randomized Patients from Week 0 of Maintenance

• In an ITT analysis of randomized patients from maintenance (weeks 0-152) who responded to STELARA during induction, 38.0% of 129 patients in the STELARA 90 mg SC q12w group and 43.0% of 128 patients in the STELARA 90 mg SC q8w group were in remission at week 152.

Randomized Patients Entering LTE

• For further efficacy results in randomized patients who entered the LTE, see Table: IM-UNITI Efficacy Assessments at Week 152 Among Randomized Patients Who Entered LTE.

All Treated Patients Entering LTE

• Among all STELARA-treated patients (randomized and non-randomized entering the LTE), remission rates at week 152 for the STELARA 90 mg SC q12w and STELARA 90 mg SC q8w groups were 56.3% (of 213 patients) and 55.1% (of 354 patients), respectively.

Observed Case Analysis of Randomized Patients Entering LTE

• In the observed case analysis of randomized patients who entered the LTE, remission rates at week 152 for the STELARA 90 mg SC q12w and STELARA 90 mg SC q8w groups were 74.3% (n=70) and 82.6% (n=69), respectively.

Safety

• From weeks 0-156, safety events (per 100 patient-years) were similar among all STELARA-treated patients compared to placebo, including overall AEs, serious AEs, and serious infections.
• See Table: Summary of Key Safety Findings from Week 0 through Week 156 Among All Patients Who Entered the LTE for safety results reported through week 156.

• From week 44 through week 156, safety events (per 100 patient-years) were similar among all STELARA-treated patients (1061.6 patient-years of follow-up) compared to placebo, including AEs (325.26 vs 358.80), serious AEs (19.40 vs 23.11), and serious infections (4.14 vs 4.62).
• Six deaths were reported from week 44 through week 156. From weeks 96-156, 3 deaths (end stage renal disease, acute myocardial infarction, septic shock) were reported.
• A total of 4 solid and hematological malignancies (testicular seminoma, adenocarcinoma of the small intestine, chronic myeloid leukemia, and papillary thyroid cancer) were reported.
• Through 3 years, 7 patients had nonmelanoma skin cancer (NMSC; 4 basal cell carcinomas and 3 squamous cell carcinomas).
• A case of tuberculosis was reported (resolved with treatment) in the LTE but not during the third year.

Immunogenicity

• Through week 156, antibodies to STELARA occurred in 4.6% (11/237) of all randomized STELARA-treated patients.

LTE - 5 Years

Sandborn et al (2022)³ evaluated the long-term efficacy and safety of STELARA through 5 years in the LTE of the IM-UNITI maintenance study.

• Of the 397 patients who were randomized in the IM-UNITI trial, 298 patients entered the LTE.
• Among patients randomized to STELARA maintenance therapy and entered the LTE, 52.3% (124/237) of these patients completed dosing through 5 years.
• The most common reasons for discontinuation were AEs, lack of efficacy, and withdrawal of consent, as described in Table: Randomized Patients Who Discontinued Study Agent During the LTE (through Week 252).

Results

Efficacy

• Among all patients originally randomized in the maintenance study (ITT analysis), 28.7% and 34.4% of patients in the STELARA 90 mg SC q12w group and STELARA 90 mg SC q8w group were in clinical remission at week 252, respectively.
• Results through 5 years among randomized patients are summarized in Table: Efficacy Assessments at Week 252 Among Randomized Patients.

Safety

• Safety events (per 100 patient-years of follow-up) were generally similar among all STELARA-treated patients entering the LTE compared with placebo from week 0 through week 252.
• See Table: Summary of Key Safety Findings from Week 0 through Week 252 Among All Patients Who Entered the LTE and Table: Summary of Key Safety Findings from Week 0 through Week 252 Among Randomized Patients Who Entered the LTE for safety results reported through week 252.

• There were no new reports of death after week 156.
• Between weeks 156 and 272, 6 patients reported malignancies (excluding NMSC): intraocular melanoma and renal cell carcinoma in the STELARA 90 SC q12w group, and endometrial adenocarcinoma, lentigo maligna melanoma, lobular breast cancer in situ, and pancreatic carcinoma in the STELARA 90 mg SC q8w group.

Immunogenicity

• Through week 272, antibodies to STELARA occurred in 5.8% of patients (31/532) who received STELARA during induction and maintenance and continued on STELARA in the LTE.

Health-Related Quality of Life (HRQoL)

• Improvements in inflammatory bowel disease questionnaire (IBDQ) and the 36-item short form (SF-36) scores were maintained from maintenance baseline through week 252 in patients treated with STELARA.⁴
  • See Table: Improvements in IBDQ Score through Week 252.
  • The IBDQ is a 32-item questionnaire with 4 dimensions: bowel symptoms, systemic symptoms, emotional function, and social function. The total score ranges from 32 to 224 with a higher score indicating a better quality of life. An IBD score change of ≥16 point indicates a clinically meaningful improvement.
  • The SF-36 includes the mental and physical component summaries. The score for each component ranges from 0 to 100 with a higher score indicating a better quality of life. A score change of ≥5 points in the mental or physical component indicate a clinically meaningful improvement.
• In patients treated with STELARA, clinically meaningful improvements from baseline through week 252 in IBDQ total score were achieved in 40.8% of patients in the STELARA 90 mg q12w group and in 43.2% of patients in the STELARA 90 mg q8w group.
• For the SF-36 physical component, clinically meaningful improvements from baseline through week 252 were observed in 37.5% of patients in the STELARA 90 mg q12w group and in 37.7% of patients in the STELARA 90 mg q8w group. For the SF-36 mental component, clinically meaningful improvements were observed in 33.9% of patients in the STELARA 90 mg q12w group and in 31% of patients in the STELARA 90 mg q8w group.⁴

Analysis of Corticosteroid-Free Remission

Panés et al (2023)⁵ evaluated the rates of corticosteroid-free remission at week 44 and ≥30 and ≥90 days before week 44 among patients who responded to STELARA IV induction and were randomized in the IM-UNITI maintenance study.

• Corticosteroid-free remission was defined as in clinical remission (CDAI score of <150) and not receiving steroids at week 44 of the maintenance study or ≥30 or ≥90 days before week 44 of the maintenance study.
• In the IM-UNITI study, corticosteroid tapering was required after the induction phase (starting at week 8, unless medically inappropriate).
• See Table: Corticosteroid-free Remission at Week 44 or ≥30 or ≥90 Days Before Week 44 in the IM-UNITI Trial.

Post-Hoc Analysis: UNITI Trials- Patient-Reported Symptom Improvement

Symptom Improvement Within the First 2 Weeks after STELARA IV Induction Dose

• A post hoc analysis of UNITI-1 and UNITI-2 was conducted to evaluate patient-reported symptom improvement within the first 2 weeks after STELARA IV induction dose.⁶
• Patients were classified as the followings based on their response to the STELARA treatment:
  • Week 8 responders: Patients who achieved clinical response 8 weeks after the STELARA 6 mg/kg IV induction infusion. These patients were then randomized to receive STELARA 90 mg SC q8w or q12w through week 44.
  • Week 16 responders: Patients who did not achieve clinical response at week 8 following the STELARA 6 mg/kg IV induction infusion, but received STELARA 90 mg SC at week 8, and achieved clinical response at week 16. These patients continued receiving STELARA 90 mg SC q8w through week 44.
  • Week 16 nonresponders: Patients who did not achieve clinical response neither at week 8 or week 16 after receiving the STELARA 6 mg/kg IV induction dose and STELARA 90 mg SC at week 8. These patients were discontinued.
• The mean change from baseline in 3 patient-reported CDAI components (SF, AP, and general WB) through day 14 was compared between STELARA 6 mg/kg IV (n=184) and placebo (n=191) and were evaluated for week 8 responders, week 8 nonresponders and week 16 nonresponders.
• In UNITI-1 and UNITI-2, a significant improvement in general WB compared with placebo was observed on day 1 after STELARA induction and was observed consistently among all patient-reported symptoms by day 10.

Efficacy through Week 16

• Clinical response and remission rates through week 16 are summarized in Table: Clinical Response and Remission Rates for Patients in UNITI-1 and UNITI-2 through 16 Weeks.

• In the UNITI-2 cohort, 68.9% of patients who received STELARA IV induction infusion were bionaïve and clinical response rates were 56.9% at week 8 and 72.9% at week 16 after administration of blinded STELARA 90 mg SC or placebo at week 8. Corresponding clinical remission rates were 44.4% and 60.4%.

Week 16 Response in Week 8 Nonresponders

• Among week 8 nonresponders, the clinical efficacy was not a reliable predictor of eventual week 16 response after receiving blinded STELARA 90 mg SC dose at week 8. Specifically, among patients who had no improvement or a minor improvement in CDAI score (≤49 points) at week 8, 55.3% (UNITI-1) and 55.5% (UNITI-2) of patient subsequently had a 100-point CDAI improvement at week 16. See Table: UNITI-1 and UNITI-2: Distribution of CDAI Score Changes from Baseline to Week 8 for Week 8 Nonresponders for further information.

• Serum trough concentration of ustekinumab at week 8 and week 16 did not appear meaningfully different between week 8 responders, week 16 responders, and week 16 nonresponders.
• At week 8, the medium serum level of ustekinumab were 6.44 µg/mL (IQR, 3.57-10.06), 6.83 µg/mL (IQR, 3.38-9.93), and 5.84 µg/mL (IQR, 3.12-9.12) for week 8 responders, week 16 responders, and week 16 nonresponders, respectively.
• At week 16, the medium serum level of ustekinumab were 2.80 µg/mL (IQR, 1.19-4.43), 2.63 µg/mL (IQR, 1.17-4.32), and 2.10 µg/mL (IQR, 1.06-3.35) for week 8 responders, week 16 responders, and week 16 nonresponders, respectively.
• During the induction period, the pharmacokinetics of ustekinumab was not reliably predictive of the clinical outcomes. The pharmacokinetics in week 8 nonresponders did not reliably predict the response potential at week 16.

Efficacy through Week 44

• The maintenance efficacy through week 44 was similar for week 8 responders and week 8 nonresponders (those who received blinded STELARA 90 mg SC at week 8, achieved clinical response at week 16 and subsequently continued treatment with STELARA 90 mg SC q8w.). See Table: Clinical Response Through Week 44 Among Week 8 Responders and Non-responders.

Pooled Analysis of GALAXI-1 and IM-UNITI Trials: ER at 1 Year at EOM and Long-term CD Outcomes

Neff-Baro et al (2024)^7,8 conducted a post-hoc analysis evaluating the impact of endoscopic response at 1 year (also known as end of maintenance [EOM]) on long-term outcomes using pooled data from the GALAXI-1 and IM-UNITI trials.

• Endoscopic response at EOM (~48 weeks) and outcomes during the LTE (~96 weeks) were evaluated. Multivariate analyses were conducted and adjusted for the treatment arm during maintenance, clinical remission status at EOM, and endoscopic response at EOM.^7,8 
• Outcomes assessed included clinical response, clinical remission, quality of life (using the IBDQ), and risk of hospitalizations and/or surgeries.^7,8 
• A total of 461 patients (IM-UNITI, n=177; GALAXI-1, n=284) had endoscopy and clinical remission data available at EOM. Regarding LTE outcomes, IBDQ remission data were available for 290 patients and clinical remission and clinical response data were available for 383 patients.^7,8 

Results

• At EOM, endoscopic response was significantly associated with a higher odds for LTE clinical remission and IBDQ remission (odds ratio [OR], 1.91 and 1.99, respectively) and a lower odds for LTE CRP abnormality (OR, 0.46).^7,8 
• A greater proportion of patients without endoscopic response at EOM experienced hospitalizations and/or surgeries than that of patients with endoscopic response at EOM (16% vs 9%). For further information, see Table: Relationship Between EOM Endoscopic Response and LTE Outcomes in Pooled Analysis.

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 21 October 2024.

Summarized in this response are relevant data from the pivotal phase 3 clinical studies in the UNITI trial program (UNITI-1, UNITI-2, and IM-UNITI), LTE of the IMUNITI maintenance study and a post-hoc analysis of pooled data from the GALAXI-1 and IM-UNITI trials.