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 phase 3 clinical trial program of STELARA in the treatment of ulcerative colitis (UC) did not evaluate dose escalation during maintenance therapy with 90 mg subcutaneous (SC) every 8 weeks (eg, higher doses or more frequent dosing).¹
• Retrospective cohort studies and a case report describing dose optimization during STELARA maintenance therapy in UC are summarized below.^2-5

CLINICAL DATA

Retrospective Studies

Lim et al (2023)² conducted a retrospective cohort study to evaluate STELARA dose intensification and effectiveness of reinduction during dose intensification in patients with Crohn’s disease (CD) and UC.

Study Design/Methods

• Patients with inflammatory bowel disease (IBD) from a prospectively maintained IBD registry who received STELARA were included.
• Treatment endpoints were corticosteroid-free clinical remission (CFCR), biochemical remission, and endoscopic healing by week 52.

Results

• A total of 63 patients who received STELARA for IBD were included.
• Of the 11 patients with UC, 8 received STELARA dose intensification to every 4 weeks (q4w) or every 6 weeks (q6w).
• Data specific to patients with UC who required dose intensification are not reported in this abstract.
• The median duration of STELARA treatment was 108 weeks (interquartile range [IQR], 44.7-185.9) and the median time to STELARA dose intensification was 31.1 weeks (IQR, 17.8-65.7).
• Overall, 14 out of 42 CD/UC (33%) patients achieved the treatment endpoints after dose escalation to q4w or q6w.
• Of the 14 patients who underwent dose escalation, re-induction of STELARA was given to 13 patients (3 with UC); of these patients, 4 achieved treatment endpoints but this was not statistically significant.
• At week 52, 26 patients did not achieve treatment endpoints, of whom 8 continued with STELARA dose intensification while 11 were switched to other biologics.

Dalal et al (2023)³ conducted a retrospective cohort study to evaluate the clinical and endoscopic outcomes up to 2 years after STELARA dose intensification to q4w or q6w in adult patients with UC or CD. Results specific to UC are described below.

Study Design/Methods

• Electronic records were manually reviewed.
• The primary endpoint was CFCR at 24±2 months (CFCR, defined as a Harvey-Bradshaw Index [HBI] of <5 or Simple Clinical Colitis Activity Index [SCCAI] of ≤2 [or per provider global assessment if scores were not documented]) and no oral or intravenous (IV) corticosteroid use within 30 days preceding assessment.
• The secondary endpoint was CFCR at 12±2 months.
• Additionally, endoscopic response and remission were also assessed. Endoscopic response was defined as a reduction in the Mayo endoscopic subscore for UC by ≥1 point or per endoscopist assessment when compared with the most recent pre-intensification assessment. Endoscopic remission was defined as a Mayo endoscopic subscore of ≤1 or per endoscopist assessment.

Results

• Of the 40 patients with UC who underwent STELARA dose intensification, 26 (65.0%) received q4w dosing and 14 (35.0%) received q6w dosing.
• The median time to dose intensification from induction was 157 days (IQR, 88-279).
• At 24 months, among 15 patients with sufficient documentation, 6 (40.0%) achieved CFCR.
• At 12 months, among 40 patients with sufficient documentation, 21 (52.5%) achieved CFCR.
• Among 6 patients who were in CFCR at 12 months and had sufficient documentation at 24 months, 5 (83.3%) maintained CFCR at 24 months.
• Among 22 patients with available data, 13 (59.1%) achieved endoscopic response at a median of 314 days (IQR, 194-449) after STELARA dose intensification.
  • Twelve (54.5%) patients achieved endoscopic remission.
• During follow-up, bowel resection surgery occurred in 1 (2.5%) patient.
• Twelve (30.0%) patients discontinued STELARA, and the most common reason was loss of response (100%). Adverse events (AEs) did not lead to treatment discontinuation in any patient.

Dalal et al (2022)⁴ conducted a multicenter, retrospective cohort study in adult patients with UC to determine predictors and outcomes of dose optimization with STELARA in UC over a 4-year period.

Study Design/Methods

• Adults with UC initiating STELARA at 2 centers in the United States were included.
• Data was analyzed by reviewing electronic health records and disease activity was assessed using the partial Mayo score or the SCCAI.
  • Partial Mayo score combines point totals for stool frequency (0-3 points), rectal bleeding (0-3 points), and physician global assessment (0-3 points).
  • SCCAI combines point totals for daytime bowel frequency (0-3 points), nighttime bowel frequency (0-2 points), urgency of defecation (0-3 points), blood in stool (0-3 points), general well-being (0-4 points), and extracolonic manifestations (1 point per manifestation).
• The primary endpoint was CFCR defined as an SCCAI/Mayo score <3 points (remission) and no oral/IV corticosteroid use for ≥4 weeks at evaluation 12-16 weeks after dose intensification.
• Secondary endpoints included clinical response (defined as a reduction in SCCAI/Mayo score by ≥3 points from baseline) at 12-16 weeks and time-to-intensification.
• Dose intensification was defined as reducing the dosing interval to q4w or q6w.

Results

• Of the 108 patients with UC initiating STELARA, 91.7% and 39.8% had prior anti-tumor necrosis factor (anti-TNF) and >2 prior biologic exposures, respectively. Additionally, 57.4% of patients were taking oral corticosteroids.
  • Among these patients, 39.6% (40/101 with SCCAI/Mayo data) achieved remission 12-16 weeks after induction.
• Intensification was required in 42.6% (46/108) of patients after a median of 95 days (IQR, 65-208 days) most commonly due to a lack of/minimal response to induction (22/46) or a loss of response (20/46):
  • Of these patients, 33 and 13 patients required intensification to q4w and q6w, respectively.
• For patients with SCCAI/Mayo data, 55% (22/40) and 67.5% (27/40) of patients achieved CFCR and clinical response, respectively, at 12-16 weeks after intensification.
  • Drug discontinuation/colectomy occurred in 30% (12/40) of patients within 16 weeks after intensification.
    • Of these 12 patients, no/minimal response to induction and a loss of response occurred in 10 and 2 patients, respectively.
• Improvement in endoscopic inflammation and fecal calprotectin was reported in 56.3% (9/16 with pre-intensification/postintensification data) of patients.
• Hospitalization related to inflammatory bowel disease and AEs (urinary tract infection and Clostridium difficile infection) occurred in 10% (4/40) and 5% (2/40) of patients, respectively, after a median follow-up of 230 days after intensification.
• A multivariable analysis showed that bowel frequency (hazard ratio [HR], 1.1; 95% confidence interval [CI], 1.02-1.2) and >2 previous biologic exposures (HR, 2.5; 95% CI, 1.1-5.8) were associated with time-to-intensification, whereas no/minimal response to induction was inversely associated with remission after intensification (odds ratio, 0.2; 95% CI, 0.04-0.7).

Case Report

Chateau and Peyrin-Biroulet (2020)⁵ reported the case of a 46-year-old male with left-sided UC who was dose optimized with STELARA 90 mg SC every 3 weeks.

• Treatment history included 3 anti-TNF therapies in combination with azathioprine or methotrexate, etrolizumab, and vedolizumab.
• STELARA therapy was initiated with an induction infusion of 520 mg followed by 90 mg SC every 8 weeks.
• Due to persistent symptoms, the dosing interval was reduced to q4w and later optimized to every 3 weeks with an incomplete response to therapy.
• There were no AEs within the 6 months of treatment and a significant improvement of digestive symptoms was reported.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 30 April 2024.