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 regarding the use of STELARA in patients undergoing surgery.
• Data regarding postoperative outcomes in patients receiving STELARA who underwent surgery from a prospective study and retrospective studies are summarized below.^1–12

CLINICAL DATA

Prospective Study

Kumar et al (2021)¹ evaluated the relationship between preoperative serum ustekinumab levels and 30-day postoperative outcomes among patients with Crohn’s disease (CD) or ulcerative colitis (UC) undergoing abdominal surgery.

• Serum ustekinumab levels were collected the day of abdominal surgery and patients were divided into 2 groups: undetectable (<0.9 µg/mL) and detectable ustekinumab levels (≥0.9 µg/mL).
• Of the 36 patients included, 31 had CD and 4 had UC. The median age of the cohort was 38.
• Baseline characteristics were similar across both groups, however, median preoperative hematocrit (40 vs 35; P=0.02) and albumin (4 vs 3.6; P=0.02) were significantly higher in patients with detectable ustekinumab level group.
• Ustekinumab levels were detectable in 25 (69%) patients with a median concentration of 6.4 µg/mL (range, 0.9-25 µg/mL) and undetectable in 11 (31%) patients.
• There were no significant differences between the undetectable and detectable level groups regarding postoperative morbidity (27% vs 28%, P=0.72), 30-day readmission rate (18% vs 8%, P=0.57), postoperative ileus (18% vs 8%, P=0.57), or wound infection (9% vs 4%, P=0.52).
• Median postoperative length of stay was 4 days vs 2 days in the undetectable vs detectable group, respectively, (P=0.06).
• No reports of death or anastomotic leak in either group.

Retrospective Studies

Fumery et al (2023)² assessed the risk of post-operative complications in patients with CD exposed to biologics, including STELARA through a retrospective, multicenter, cohort study.

• All patients with intestinal resection for CD were included.
• The risk of post-operative complications (≤30 days) in patients exposed to biologics was compared to those who were not exposed by logistic progression and propensity-score matched analysis which was adjusted for confounding factors.
• Among the 1201 patients included, 76 (6.3%), 491 (41%), and 57 (4.7%) were exposed to STELARA, anti-tumor necrosis factors (TNFs), or vedolizumab within 6 months of surgery, respectively.  
• The rates of overall complications are below:
  • Patients not exposed to biologics: 26.1%
  • Exposed to STELARA: 34.7%
  • Exposed to anti-TNFs: 25.1%
  • Exposed to vedolizumab: 29.8%
• The risks of intra-abdominal infectious complications are below:
  • Patients not exposed to biologics: 13.5%
  • Exposed to STELARA: 13.3%
  • Exposed to anti-TNFs: 11.1%
  • Exposed to vedolizumab: 8.8%
• Exposure to STELARA (odds ratio [OR], 1.17 [0.39-3.51]) anti-TNFs (OR, 0.80 [0.51-1.24]), and vedolizumab (OR, 1.28 [0.32-5.17]) within 3 months of surgery were not significantly associated with the risk of intra-abdominal infectious complications. Similar results were observed in patients exposed to these treatments in the month prior to surgery.

Aziz et al (2022)³ conducted a retrospective study to evaluate the surgical outcomes in patients with CD who underwent ileocolonic resection and had preoperative biologic therapy, including STELARA.

• The primary outcome was any intra-abdominal septic complication at 30 days (defined as anastomotic leak, peritonitis secondary to infection requiring reoperation, or intra-abdominal abscess). These outcomes were determined by the presence of clinical signs and radiological evidence. Secondary outcomes included overall 30-day complications based on the Clavien-Dindo classification.
• There were 274 patients identified: 52 (19%) were receiving STELARA, 113 (41.2%) were receiving anti-TNFs, and 19 (7%) were receiving vedolizumab. For postoperative outcomes among these patients, see Table: Postoperative Outcomes.

Uchino et al (2022)⁴ evaluated the association between preoperative treatment with biologics and surgical morbidity in patients with CD who underwent intestinal resection.

• Preoperative biologic treatment included the use of therapy within 4 or 12 weeks prior to surgery.
• Postoperative complications (grade ≥3 per Clavien-Dindo classification system, including bowel obstruction and infectious complications [pneumonia, urinary tract infection, or bloodstream infection], surgical site infections [SSIs], and venous thrombi) and SSIs that occurred within 30 days after surgery were evaluated.
• A total of 305 patients who underwent intestinal resection for CD were included.
• The proportion of patients on preoperative biologic treatment within 4 or 12 weeks prior to surgery are presented in Table: Preoperative Biologic Treatment Within 4 or 12 Weeks Before Surgery.

• The results of univariate analysis for the association of preoperative biologic treatment with total complications are shown in Table: Association Between the Use of Preoperative Biologics Within 4 or 12 Weeks Before Surgery and Total Complications.
• The use of STELARA within 4 or 12 weeks prior to surgery was not significantly associated with postoperative complications (P=0.82 and P=0.70, respectively).

García et al (2021)⁵ investigated if preoperative treatment with anti-TNF agents, STELARA, or vedolizumab in inflammatory bowel disease (IBD) patients increase the risk of complications after intra-abdominal surgery.

• Postoperative complications were defined as those occurring 30 days postsurgery (including superficial wound infection, intra-abdominal infection, urinary tract infection, bacteremia, respiratory infection, fever >38°C of unknown origin, anastomosis leak, mechanical obstruction, postoperative ileus, bleeding, thrombosis, fistula, or evisceration).
• To evaluate the risk of postoperative complications, patients who received biologics within the last 12 weeks prior to surgery (exposed) vs those who did not (nonexposed) were compared.
• Of the 1535 surgeries in 1370 patients, 711 (46.3%) and 824 (53.7%) patients made up the exposed and nonexposed cohort, respectively.
• Of the 711 patients in the exposed cohort, 69 received STELARA, 58 received vedolizumab, and 584 received anti-TNFs.
• Results of the univariate analysis of the association between preoperative biologic therapy and postsurgical complications are summarized in Table: Effect of Preoperative Biologic Therapy on Postoperative Complications and Infections.

• Biologic therapy was not associated with an increased risk of postoperative complications (odds ratio [OR], 1.24; 95% confidence interval [CI], 0.97-1.58) but with an increased risk of postoperative infections (OR, 1.50; 95% CI, 1.03-2.17).
  • No specific treatment was associated with postsurgical complications or infections.

Shah et al (2021)⁶ evaluated the association between preoperative biologic therapy and postoperative complications in adult patients with CD undergoing ileocecal resection (ICR).

• Preoperative biologic exposure defined as exposure to anti-TNF agents, vedolizumab or STELARA within 12 weeks.
• The primary endpoint was the 90-day rate of intra-abdominal septic complications (IASC) defined as intra-abdominal abscess or leak.
• Overall, 815 patients who underwent ICR were included, and the median age of surgery was 36.
• Of the 815 patients, 21 (2.6%) received STELARA within 12 weeks of surgery.
• There was no significant difference in overall IASC rates in patients treated with STELARA (4.8%), vedolizumab (18.8%), anti-TNF agents (14.6%) or no biologic (10.6%), P=0.17.
• The rate of intra-abdominal abscesses was significantly higher in patients exposed to biologics (vedolizumab, 18.8%; anti-TNF agents, 12.5%; STELARA, 4.8%), vs patients not exposed, 7.7%, P=0.04.
• Using a multivariable logistic regression model, STELARA was not significantly associated with IASC (OR 0.33 [95% CI, 0.01-9.30], P=0.52).
• For other 90-day outcomes among biologic groups, please see Table: 90-Day Outcomes Among Preoperative Biologic Groups.

• Due to high rates of diverting ostomy in vedolizumab and STELARA groups, surgical outcomes were compared. There were no significant differences reported in the rate of IASC and other postoperative surgical outcomes in patients with an anastomosis without ostomy between STELARA and vedolizumab vs no biologic group.

Lightner et al (2019)⁷ conducted a retrospective chart review of adults with CD who underwent abdominal surgery from 2017 to 2018 to evaluate the impact of STELARA on postoperative outcomes.

• Patients were included if they were exposed to STELARA 12 weeks prior to a major abdominal surgery. A control group of patients with CD who also underwent abdominal surgery without exposure to biologics 12 weeks prior were also included.
• The primary outcome was 90-day rates of postoperative intra-abdominal sepsis. Secondary outcomes included 90-day superficial surgical site infections (sSSI), overall infectious complications, unplanned hospital readmissions.
• Of the 334 patients, 57 were exposed to STELARA and 277 were in the control group (no exposure to a biologic).
  • A greater proportion of STELARA treated patients were receiving immunomodulators at the time of surgery (35.1% vs 15.9%).
• Intra-abdominal sepsis occurred in 22 patients; of these patients, 14% were exposed to STELARA and 5% were in the control group.
  • Based on a multivariable logistic regression analysis, STELARA was significantly associated with intra-abdominal sepsis (OR, 2.93; 95% CI, 1.16-7.40; P=0.02).
• sSSIs occurred in 42 (13%) patients: (12% were exposed to STELARA and 13% were in the control group).
  • The use of immunomodulators preoperatively were significantly associated with sSSIs (OR, 2.60, 95% CI, 1.25-5.40; P=0.11) based on a multivariable logistic regression analysis.
• There were 81 (24%) patients with infectious complications (35% of these patients exposed to STELARA, 22% in the control group).
  • Based on a multivariable logistic regression analysis, immunomodulators and duration of disease remained significantly associated with infectious complications (OR, 2.01; 95% CI, 1.08-3.76; P=0.03); (OR, 1.02, 95% CI 1.00-1.05; P=0.03), respectively.
• Unplanned hospital readmission within 90 days of surgery occurred in 70 patients (20 patients in the STELARA group, 50 patients in the control group).
  • Exposure to STELARA and corticosteroid were significantly associated with readmission on a multivariable analysis¹³:
    • Exposure to STELARA, (OR, 2.13; 95% CI 1.09-4.17; P=0.03)
    • Corticosteroids, (OR, 1.82; 95% CI 1.03-3.24; P=0.04)
• There are several points described in the discussion section of the study by the authors which include: a greater proportion of STELARA treated patients (35.1%) were on concurrent immunomodulator therapy; the inability to account for nutritional status, and overall disease severity of these patients.

D’Andrea et al (2020)⁸ compared 30-day postoperative outcomes in adult patients with CD undergoing bowel resection with preoperative exposure to STELARA, vedolizumab, and anti-TNF agents.

• Biologic exposure was defined as exposure within 60 days of a major abdominal surgery.
• Postoperative complications including SSIs, ileus, and anastomotic leak were compared at 30 days.
• Of 415 patients, 74 were exposed to STELARA, 30 to vedolizumab, 152 to anti-TNF agent, and 159 to no biologic treatment.
• There were no significant differences in the rate of 30-day postoperative SSIs, ileus, anastomotic leak, readmission and reoperation.

Novello et al (2019)⁹ assessed postoperative complications after colorectal surgical surgery in patients with IBD receiving STELARA and vedolizumab.

• Patients were stratified based on biologic treatment within 12 weeks of surgery.
• The primary endpoint was overall morbidity within 30 days postcolorectal surgery.
• STELARA-treated patients were matched to vedolizumab-treated patients based on gender, age ±5 years, date of operation ±3 years, and the type of surgery to perform conditional logistic regression analyses of the matched pairs.
• Of 103 patients with CD included, 73 were receiving vedolizumab and 30 were receiving STELARA.
• For postoperative outcomes, please see Table: Postoperative Outcomes in Patients Receiving Vedolizumab or STELARA.

• A paired-analysis of outcomes, using a conditional logistic regression model, found no significant difference among the matched pairs for overall complications, infectious complications, readmission rate, dehydration, enteric leak, intra-abdominal abscess, perineal wound infection, pneumonia, sepsis, organ space SSI, and superficial SSI.

Lightner et al (2018)¹⁰ conducted a retrospective chart review to evaluate the incidence of postoperative infectious complications among patients with CD who received STELARA as compared with those who received anti-TNF therapy within 12 weeks of a major operation.

• Clinical charts of 213 adult patients who received STELARA (study patients; n=44) or anti-TNF therapy (control cohort; n=169) within 12 weeks prior to undergoing abdominal surgery for CD were reviewed.
• Patients were excluded if they did not have 30 days of follow-up after their operation or if their index operation was performed at an outside hospital.
• The primary endpoint was the 30-day postoperative SSI rate, defined as superficial SSI, mucocutaneous separation, deep space SSI (i.e., abdominal or pelvic abscess), or anastomotic leak.
• Secondary outcomes included the incidence of 30-day non-SSI infectious complications (i.e., catheter-associated infections, urinary tract infections, and pneumonia), small bowel obstruction or ileus, 30-day unplanned hospital readmission, and 30-day return to the operating room.
• Univariate and multivariable logistic regression were used to evaluate predictors of SSI among all CD patients as well as within the STELARA group.
• Baseline characteristics were similar between treatment groups with the exception that significantly more patients in the anti-TNF group received combination therapy with an immunomodulator (57%, n=97) as compared with STELARA (37%, n=16).
• The incidence rate of 30-day postoperative SSI in the STELARA and anti-TNF groups were 13% and 20%, respectively (P=0.33). Please see Table: Thirty-Day Postoperative Complications in Patients Undergoing Abdominal Surgery for CD for all endpoint results.
• One 30-day postoperative death was reported in the anti-TNF group (0.6%).

• On univariate analysis of predictors of 30-day postoperative SSI for all CD patients, preoperative serum albumin level (P=0.02) and corticosteroid use (P=0.04) were reported to be significantly different among patients without postoperative SSI (n=173) and those with postoperative SSI (n=40).
• On multivariable analysis, no independent predictors of 30-day postoperative SSI were identified among all patients.
• When comparing patients who had a SSI (14%; n=6) vs those who did not (86%; n=38) within the STELARA-treated cohort, there were no differences in age, sex, smoking history, body mass index, presence of diabetes, corticosteroid use, immunomodulator use, or laboratory values.

Shim et al (2017)¹¹ conducted a retrospective observational cohort study to evaluate the occurrence of postoperative complications in STELARA-treated patients with CD who underwent abdominal surgery between 2009 and 2016. The STELARA cohort (n=20) was compared to randomly selected anti-TNF therapy-treated patients with CD (control group; n=40) who underwent surgery over the same period of time.

• The primary endpoint was occurrence of postoperative complications up to 6 months, stratified by timing (early <30 days vs late complications ≥30 days postoperatively).
• Patients received STELARA or anti-TNF treatment preoperatively for a median 6.5 and 18 months, respectively.
• Median postoperative follow-up was 14.5 months and 39.5 months for the STELARA and anti-TNF therapy group, respectively.
• There was no significant difference in the occurrence of postoperative complications across both cohorts up to 6 months after surgery. Results for postoperative outcomes including complications stratified by time and other details are provided in Table: Select Postoperative Outcomes.

Bakkour et al (2016)¹² conducted a retrospective study to evaluate continuing/stopping biologic therapy in patients with psoriasis and psoriatic arthritis (PsA) undergoing a surgical procedure.

• There were 300 patients with psoriasis and PsA included in this study.
• Of these patients, there were 54 (70%) procedures performed on 28 psoriasis patients and 23 (30%) procedures performed on 14 PsA patients.
• Biologic therapy was stopped prior to the procedure in 20 (26%) cases and continued in 57 (74%) cases.
• STELARA was not stopped in any of the 5 cases where it was used, and no complications were reported in these patients.

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 25 November 2024.