SUMMARY

• The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
• An analysis evaluating the impact of prior surgical history on the efficacy of STELARA among a subgroup of patients in the UNITI pivotal clinical program was conducted and the results are summarized below.¹
• Additionally, published data from prospective studies, retrospective studies, and registries relevant to this topic are described below.^2-11

CLINICAL DATA

Phase 3 Studies: UNITI-1, UNITI-2, and IM-UNITI

Hanauer et al (2018)¹ conducted a subgroup analysis of the phase 3 UNITI-1, -2, and IM-UNITI studies to evaluate the impact of prior surgical history on the efficacy of STELARA in patients with Crohn’s disease (CD).

Methods

• Subgroups of patients were analyzed based on prior CD-related intra-abdominal surgeries (0, ≥1, or ≥2 surgeries), specific previous surgeries (prior fistula surgery or colectomy), and the presence of current or prior fistula at baseline.

Results

• In UNITI-1 and -2, 50.5% and 33.5% of patients, with or without a history of anti-tumor necrosis factor (TNF) therapy failure, had prior CD-related surgeries at baseline, respectively.
• In the STELARA and placebo groups, the overall rates of clinical response and remission decreased with an increase in the number of prior surgeries. Clinical remission and response rates by the number of prior surgeries at baseline are described in Table: Clinical Remission and Response Rates for UNITI-1, UNITI-2, and IM-UNITI by the Number of Prior Surgeries at Baseline.
• Clinical remission and response rates by specific previous surgeries at baseline are described in Table: Clinical Remission and Response Rates for UNITI-1, UNITI-2, and IM-UNITI by Prior Colectomy, Perianal Surgery, or Prior or Current Fistula at Baseline.

• Where there were sufficient patients to evaluate, among patients with specific previous surgeries enrolled in UNITI-1 and -2, the overall rates of clinical response and remission were higher in the STELARA group compared with the placebo group.

Prospective Studies

Allez et al (2023)² conducted a prospective, multicenter, observational cohort study comparing STELARA and adalimumab in patients with postoperative CD.

Methods

• Patients with CD who had been exposed to at least one biologic and who received STELARA or adalimumab after surgery were included in the study.
• The primary endpoint was endoscopic recurrence within a year following surgery, as defined by Rutgeerts score ≥ i2.
• A propensity score based analysis using overlap weights was used to account for the imbalance in pre-treatment confounders between STELARA and adalimumab groups.

Results

• A total of 123 patients were enrolled in the cohort, of whom 60 received STELARA and 63 received adalimumab postoperatively.
• Of the 60 patients who received STELARA, 15 (25.0%) had prior surgeries and 29 (48.3%) had been exposed to > 1 biologic.
• Endoscopic recurrence (Rutgeerts ≥ i2) rates were 58.3% and 47.6% in STELARA and adalimumab groups, respectively (P=not significant [NS]). Rates of severe lesions (Rutgeerts i3-i4) were similar between groups, 11.7% for STELARA and 14.3% for adalimumab.
• For the weighted population, there was no significant difference in rates of endoscopic recurrence (STELARA vs adalimumab: odds ratio [OR]=1.92 [95% confidence interval (CI): 0.83-4.43]) or rates of severe recurrence (STELARA vs adalimumab: OR=0.85 [95% CI: 0.23-3.05]).

Ahmed et al (2021)³ conducted a study evaluating the efficacy of biologics, including STELARA, in patients with postoperative CD.

Methods

• Patients with postoperative CD receiving their first postoperative biologic were included in the study.
• The primary outcome was the comparison of deep remission (DR) rates between antiTNF therapy and STELARA ≤12 months after the treatment. DR was defined as achieving both clinical and objective remissions.
  • Clinical remission was defined as Harvey-Bradshaw Index (HBI) <5, Crohn’s Disease Patient-Reported Outcomes 2-item (CD-PRO-2) <8, or remission stated.
  • Objective remission was defined as endoscopic (Simple Endoscopic Score for Crohn’s Disease [SES-CD] <3, Rutgeerts score ≤i2a, or absence of ulcers) or biochemical (fecal calprotectin [FCP] <150 μg/g or C-reactive protein [CRP] <1 mg/dL) remission, if endoscopy was unavailable.

Results

• Overall, 186 patients were included, of whom 67 received STELARA, 101 received antiTNF therapy, and 18 received vedolizumab. Of the 67 patients who received STELARA, 53 and 22 patients had prior exposure to anti-TNF therapy and prior surgery, respectively.
• DR was higher in patients who received anti-TNF therapy vs STELARA in the total population (DR, 45% vs 22%; P=0.007).
  • Clinical remission rates were 63% vs 43%; P=0.028.
  • Objective remission rates were 72% vs 53%; P=0.027.

Retrospective Studies

Hosomi et al (2024)⁴ conducted a retrospective study to evaluate the effectiveness of STELARA in preventing postoperative CD recurrence in patients with CD who underwent surgery.

Methods

• To evaluate the effectiveness of STELARA vs continued TNF inhibitor (TNFi) in preventing postoperative CD recurrence in patients with CD who underwent surgery due to primary or secondary nonresponse to TNFi therapy.
• Among patients who required bowel-resection surgery during TNFi therapy, 15 switched to STELARA (STELARA switch group) and 40 continued TNFi therapy after surgery (TNFi continuation group).
• Endoscopic recurrence was defined as the presence of an anastomotic ulcer or anastomotic stenosis at the first colonoscopy at least 3 months after surgery.
• Clinical relapse was defined as hospitalization, surgery, or treatment change due to the exacerbation of CD.

Results

• The median age (range) and duration of disease in the STELARA switch group and TNFi continuation group, respectively were:
  • 34.7 years (17.2-49.6) vs 36.6 years (19.0-77.6)
  • 16.2 years (2.0-27.9) vs 7.75 years (0.9-35.5)
• The cumulative 2-year maintenance rate was 60% and 79.9% in STELARA switch group and TNFi continuation group, respectively (no statistical difference between 2 groups, P=0.432).
• A follow-up endoscopy was performed in the STELARA switch group (n=14) and TNFi continuation group (n=36).
  • Anastomotic recurrence was observed in 8 and 14 patients in the STELARA switch group and TNFi continuation group, respectively (no statistical difference between 2 groups, P=0.343).

Macaluso et al (2023)⁵ conducted a retrospective, multicenter study to evaluate the effectiveness of STELARA for the treatment of endoscopic postoperative recurrence (ePOR) post ileocolic resection in adult patients with CD from the cohort of Sicilian Network for Inflammatory Bowel Diseases (SN-IBD).

Methods

• Adult patients with ePOR (Rutgeerts score ≥i2) 6-12 months after ileocolic resection who were initiated on STELARA within 1-month from the baseline post-op colonoscopy (without the use of other biological agents) and a post-treatment colonoscopy ≥ 8 months after STELARA initiation were included.
• The primary outcome was endoscopic success, defined as at least 1-point reduction of Rutgeerts score when conducted at least 8 months after STELARA initiation.
• The secondary outcome was clinical success at the end of follow-up, defined as persistence on STELARA and in absence of one of the following for clinical failure:
  • Mild clinical relapse (HBI 5-7)
  • Clinically relevant relapse (HBI>7)
  • Need of new intestinal resection

Results

• Overall, 44 patients initiated on STELARA were included with a mean follow-up of 17.8±8.4 months.
• Post-treatment colonoscopy was performed after a mean of 14.5±5.5 months following initiation of STELARA and endoscopic success was reported in 22 (50%) patients.
• In addition, of the patients with ePOR at baseline, 12 (27.3%) patients achieved a Rutgeerts score i0 or i1 at post-treatment colonoscopy.
• At the end of follow-up, all 22 patients with endoscopic success continued treatment with STELARA. 19 (86.4%) of 22 patients had CRP values below the upper limit of normal.
• Clinical failure occurred in 12 (27.3%) patients due to: mild disease activity (n=5), clinically relevant disease activity (n=3), and intestinal resection (n=4). None of these patients achieved endoscopic success at post-treatment colonoscopy.
  • 6 patients discontinued STELARA at the end of follow-up and the remaining 6 patients continued STELARA due to lack of alternative medical option.
• No adverse events were reported.

Chaparro et al (2022)⁶ conducted a retrospective, multicenter, noninterventional study to evaluate the durability of STELARA treatment and reasons for STELARA discontinuation in a real-world setting in patients with CD (SUSTAIN study).

Methods

• Adults with active CD who received ≥1 initial dose of intravenous (IV) STELARA ≥6 months prior to the start of the study were included.
• The primary outcome was the STELARA retention rate (defined as the proportion of patients maintained under STELARA treatment at a certain timepoint) from the start of STELARA treatment (the first STELARA dose received by the patient) to the last recorded dose.
• Select secondary outcomes were evaluation of the short-term effectiveness of STELARA at 8 and 16 weeks, proportion of patients who underwent dose escalation or intensification during the follow-up period, and response to dose adjustments.
• Stepwise multivariate analysis using the Cox regression model was used to investigate factors potentially associated with STELARA discontinuation. A logistic regression model was used to evaluate variables associated with the likelihood of achieving remission after STELARA induction.

Results

• Overall, 463 patients were included in the study, of whom 96.5% had prior exposure to biologic therapy and 60.7% had previous surgery for CD, including abdominal (47.1%) and perianal (22.9%) surgeries.
• After a median follow-up of 15.5 months, 356 patients (76.9%; 95% CI, 72.8-80.7) were still receiving STELARA and 107 (23.1%) had discontinued the treatment; the incidence of STELARA discontinuation was 18.4% per patient-year of follow-up.
  • In the multivariate analysis, previous intestinal surgery was associated with a higher risk of STELARA discontinuation (hazard ratio [HR], 2.14; 95% CI, 1.47-3.18).
• At week 16, 56.1% and 70.2% of patients achieved clinical remission and response, respectively.
  • In the multivariate analysis, previous abdominal surgery and all previous surgeries were associated with a lower probability of achieving clinical remission (OR, 0.6; 95% CI, 0.4-0.9) and response (OR, 0.7; 95% CI, 0.4-1.0) at week 16, respectively.
• Among patients with previous surgery for CD, no difference was observed between those who did not receive and those who received dose escalation or intensification (217 of 342 [63.5%] and 64 of 121 [52.9%], respectively; P=0.051).

Yanai et al (2022)⁷ conducted a retrospective, multicenter study comparing the effectiveness of STELARA and vedolizumab with that of anti-TNF therapy in preventing ePOR after curative ileocecal resection (ICR) in adults with CD.

Methods

• Patients with CD who were >17 years old, underwent ICR, started prophylaxis ≤6 months after surgery, and underwent an ileocolonoscopy ≥4 months after prophylaxis were included in the study.
• ePOR (Rutgeerts score ≥i2 or colonic-segmental-SES-CD ≥6) was assessed at 12, 24, and 36 months after surgery.
• Multivariate logistic regression was used to assess the risk factors for ePOR, and inverse probability of treatment weighting (IPTW) was performed to compare the effectiveness between agents.

Results

• Overall, 297 patients were included, of whom 224 received anti-TNF therapy, 39 received vedolizumab, and 34 received STELARA for the prevention of postoperative recurrence.
• At 12 months, the ePOR rates for STELARA, vedolizumab, anti-TNF therapy were 61.8%, 33%, and 40.2%, respectively. At 24 months, the rates were 72.4%, 44.4%, and 46.5%. At 36 months, the rates were 62.5%, 44.0%, and 47.9%.
• After controlling for the disparities between groups using the IPTW method, the risk of ePOR at 12 months was comparable between patients receiving anti-TNF therapy vs vedolizumab or anti-TNF therapy vs STELARA; however, the risk of ePOR at 12 months was higher with STELARA vs vedolizumab (OR, 3.75; 95% CI, 1.33-10.6; P=0.012).

Buisson et al (2021)⁸ conducted a retrospective, multicenter study comparing the effectiveness of STELARA vs azathioprine in preventing ePOR in patients with CD.

Methods

• Adult patients with CD who had undergone surgical resection for ileal, ileocolonic, or colonic CD with ileocolonic anastomosis were included. All macroscopic lesions had to be removed during the surgery, and the anastomosis had to be reachable by ileocolonoscopy.
• Patients with prior exposure to STELARA before the surgery were included.
• Patients were excluded if they started STELARA >90 days after intestinal resection or following stoma closure or they presented with persistent macroscopic lesions after surgery.
• Propensity score analyses with IPTW were applied to compare the 2 groups.
• The primary endpoint was ePOR (Rutgeerts score ≥i2) at 6 months after intestinal resection or following stoma closure.
• The secondary endpoints were alternative definitions of ePOR using Rutgeerts score ≥i2b (i2b‐ePOR) and Rutgeerts score ≥i3 (severe ePOR) as cutoff values.

Results

• Overall, 32 and 31 patients were included in the STELARA and azathioprine groups, of whom 49.6% and 45.5% had undergone prior bowel resection and 31.4% and 29.9% received >2 biologics before surgery, respectively, after IPTW.
• A higher proportion of patients in the STELARA vs azathioprine group were exposed to STELARA prior to surgery (34.4% vs 9.7%; P=0.018)
• The rate of ePOR (Rutgeerts score ≥i2) was significantly lower in the STELARA vs azathioprine group before adjustment (31.2% vs 58.1%; P=0.032) and after IPTW (28.0% vs 54.5%; P=0.029).
• A significant difference was not observed in the STELARA vs azathioprine group in the rate of ePOR (Rutgeerts score ≥i2b; before adjustment: 21.9% vs 41.9%; P=0.091; after IPTW: 20.8% vs 42.5%; P=0.066) and severe ePOR (Rutgeerts score ≥i3; before adjustment: 18.8% vs 25.8%; P=0.50; after IPTW: 16.9% vs 27.9%; P=0.24).
• No adverse events (AEs) were observed in patients treated with STELARA.

Tursi et al (2021)⁹ reported the use of STELARA in patients with POR (postoperative recurrence) of CD who were previously refractory to biologics.

• Adult patients with CD who had active disease, defined as HBI ≥5 and Rutgeerts score ≥2, were included.
• Clinical remission was defined as HBI ≤4, and mucosal healing was defined as Rutgeerts score <2.
• Overall, 15 patients were included, of whom 10 had prior exposure to anti-TNF therapy, 5 had prior exposure to anti-TNF therapy and vedolizumab.
• Clinical remission was achieved in 12 patients at a median of 6 months (IQR, 6-12).
• Mucosal healing was achieved in 11 patients who had colonoscopy during follow-up, and all 11 patients achieved steroid-free remission.
• Steroid-free response and remission were achieved in 13 and 12 patients, respectively.
• One mild AE of hypertension was reported without the need to discontinue STELARA.

Alric et al (2019)¹⁰ conducted a retrospective, observational cohort study to evaluate the efficacy and safety of STELARA vs vedolizumab in patients with CD who were refractory or intolerant to anti-TNF therapy from 5 IBD centers.

• A propensity score with IPTW was calculated to compare the variables between the STELARA and vedolizumab groups.
• Overall, 239 patients were included in the study, of whom 107 received STELARA and 132 received vedolizumab. A total of 50 (46.7%) and 55 (41.7%) patients who received STELARA and vedolizumab, respectively, had prior abdominal CD-related surgery.
• Subgroup analyses showed that STELARA was associated with a higher rate of clinical remission in patients with a history of CD-related surgery (OR, 3.26; 95% CI, 1.40-7.61) compared with vedolizumab.
• Overall, 21 (19.6%) AEs were reported in the STELARA group. Treatment was stopped in 1 (0.9%) patient in the STELARA group due to intolerance.
• No deaths were reported during follow-up.

Registry

Mañosa et al (2022)¹¹ conducted a study using data from the ENEIDA registry (a prospectively maintained database of the Spanish working group in IBD [Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU)]) to evaluate the efficacy of STELARA in preventing ePOR in patients with CD.

Methods

• Patients with CD who were prescribed STELARA for primary prevention of POR within the first 3 months after ileocecal or ileocolonic resection with anastomosis were included.
• The rates of endoscopic, clinical, or surgical POR in the first 18 months were evaluated. ePOR was defined as Rutgeerts score >i1 and significant ePOR as >i2.

Results

• Overall, 40 patients treated with STELARA were included in the study. A total of 25% of patients received concomitant immunosuppressants and 32% received a 3-month course of metronidazole after surgery.
• STELARA was initiated at a median of 31 days (IQR, 22-61) after the index surgery.
• Prior to the index surgery, 55% of patients were exposed to STELARA.
• The median follow-up time for STELARA was 17 months (IQR, 11-21).
• 17% (7 patients) developed clinical POR during the follow-up with a cumulative probability of having clinical POR of 32% at 12 months.
• 70% (28 patients) underwent endoscopic assessment within 18 months after surgery.
• Of the patients who underwent endoscopic assessment, 42% (17 patients) developed ePOR and 21% (6 patients) developed significant ePOR within 18 months after surgery.
  • STELARA dosing regimen was escalated to 90 mg every 4 weeks due to clinical POR (n=7), ePOR (n=2), persistently increased faecal calprotectin levels (n=1), and perianal disease (n=1).
• 15% (6 patients) discontinued STELARA due to endoscopic and clinical POR. One patient underwent intestinal resection.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 22 August 2024.