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.
• Phase 3 clinical trials for STELARA in Crohn’s disease (CD) did not evaluate intravenous (IV) maintenance dosing.¹
• Retrospective studies and a case series describing the use of STELARA IV infusion during maintenance therapy in CD are summarized below.^2-7

clinical data

Retrospective Studies

Win et al (2023)² conducted a retrospective study to evaluate the effectiveness of STELARA IV vs STELARA subcutaneous (SC) as maintenance therapy in adult patients with inflammatory bowel disease (IBD).

• A total of 51 patients (CD, 88%; ulcerative colitis [UC], 8%; indeterminate colitis, 4%) were included. Of the 43 patients who received STELARA SC maintenance treatment, 8 switched to STELARA IV maintenance treatment due to lack of response.
• When comparing STELARA IV vs STELARA SC as maintenance therapy, 40% vs 42% of patients showed improvement (confirmed via endoscopy or imaging) and 20% vs 25% of patients showed significant progression, respectively.
• Hospital admission rates during treatment, mean C-reactive protein (CRP) levels, and mean fecal calprotectin (FCP) levels among patients receiving STELARA IV vs SC as maintenance therapy are presented in Table: Recorded Characteristics Among Patients Receiving STELARA IV vs SC as Maintenance Therapy.

Argüelles-Arias et al (2023)³ conducted an observational, retrospective study evaluating the effectiveness and safety of STELARA IV maintenance therapy in patients with IBD who had a partial response or complete loss of response to STELARA SC maintenance therapy.

• A total of 23 patients with IBD (CD, 82.6% [n=19]; UC, 17.4% [n=4]) who received STELARA IV maintenance therapy for ≥12 weeks (with ≥3 doses) were included.
• The primary endpoint was clinical remission at week 12, defined as either a Harvey-Bradshaw Index (HBI) of ≤4 for CD or a partial Mayo score (pMS) of ≤2 for UC.
• The secondary endpoints were a reduction in disease activity (FCP and CRP) and clinical response (defined as a decrease of ≥3 points in HBI for CD and of ≥3 points and 30% in pMS for UC, from baseline).
• Before STELARA IV maintenance treatment was initiated, 13% and 56.5% of patients received STELARA 90 mg SC every 6 weeks (q6w) and every 4 weeks (q4w), respectively.
• After a median duration of 14.7 months on SC maintenance treatment, patients were escalated to STELARA IV maintenance treatment.
  • A total of 78.3% (n=18) of patients were escalated to 130 mg IV q4w, 13% (n=3) to 260 mg IV q4w, 4.3% (n=1) to 130 mg IV q6w, and 4.3% (n=1) to 130 mg IV every 8 weeks.
• Median duration of follow-up was 9.3 months (interquartile range [IQR], 4.4-13.6).
• Overall, clinical remission and response were achieved by 43.5% (n=10) and 82.6% (n=19) of patients, respectively, after 12 weeks of STELARA IV maintenance therapy.
• Among the 19 patients with CD, median HBI at baseline was 10 (IQR, 8-12) and was reduced to 4 (IQR, 4-7) after 12 weeks of STELARA IV maintenance therapy (P<0.001).
  • Among these 19 patients with CD, 10 achieved clinical remission after 12 weeks of STELARA IV maintenance therapy.
• Median FCP levels decreased from baseline to 12 weeks (1198.7 µg/g [IQR, 638.5-3688.8] vs 520.5 µg/g [IQR, 276.0-1389.5]; P=0.005).
• Median serum CRP levels decreased from baseline to 12 weeks (7.9 mg/L [IQR, 5.0-13.3] vs 3.9 mg/L [IQR, 0.9-9.0]; P=0.004).
• Median ustekinumab trough levels before STELARA IV maintenance were 3.02 µg/mL (IQR, 0.7-5.8), which increased to 11.45 µg/mL (IQR, 7.2-19.9) after STELARA IV maintenance (P<0.001).
• At the end of follow-up, all patients maintained IV maintenance treatment.
• No adverse events (AEs) were reported during the study.

Hermida Pérez et al (2023)⁴ conducted a retrospective study evaluating the efficacy and safety of STELARA IV maintenance therapy as a rescue strategy in patients with CD.

• A total of 12 adult patients with CD who were nonresponders or had a loss of response to standard therapy with STELARA and received ≥2 consecutive STELARA IV doses as a rescue strategy were included.
• Clinical remission was defined as an HBI score of <5 without steroids.
• Clinical response was defined as a ≥2-point decrease in HBI.
• Overall, 75% of patients started STELARA IV maintenance therapy, after previous SC treatment, at doses of 390 mg (50%), 260 mg (42%), and 130 mg (8%).
• The initial infusion interval was 8, 6, and 4 weeks in 67%, 8%, and 25% of patients, respectively, which was shortened in 25% of patients.
• Mean follow-up duration was 117.1 weeks, and mean therapy survival duration was 105.9 weeks.
• Summary of clinical response and remission and median basal FCP and CRP levels through 52 weeks of STELARA IV maintenance therapy are presented in Table: Efficacy of STELARA IV Maintenance Therapy through 52 Weeks.

• After 52 weeks of STELARA IV maintenance therapy, 17% of patients were de-escalated to STELARA SC therapy.
• No severe AEs were reported, and 25% of patients had mild AEs that did not require hospital admission or therapy withdrawal.

Garcia-Alvarado et al (2022)⁵ conducted a retrospective study to evaluate the effectiveness of STELARA IV administered at regular intervals (usually, every 4-6 weeks) in patients with CD or UC who had insufficient efficacy or loss of response to STELARA 90 mg SC every 4-6 weeks.

• Data were collected from patients with active CD (n=73) or UC (n=6) defined by HBI or pMS >4 points and/or persistent biomarker elevation (calprotectin >250 μg/g) and/or endoscopic or radiological evidence of disease activity.
• FCP levels before and after initiating STELARA IV were available for 44 patients, and ustekinumab trough levels were available for 48 patients.
• Before STELARA IV was initiated, 31.6% of patients received STELARA 90 mg SC q6w, and 68.4% of patients received STELARA 90 mg SC q4w.
• Three patients were biologic-naïve and 41.8% had received ≥1 biologic.
• Mean follow-up period after the first STELARA IV dose administration was 13.22 months (IQR, 2-37).
• After 12 weeks of the first STELARA IV dose, 43% of patients achieved clinical remission (HBI <5 or pMS 2). At the end of the follow-up, 59.5% of patients achieved clinical remission.
• FCP levels decreased significantly from baseline to 12 months (612.6 mg/kg vs 384.1 mg/kg; P=0.0002) and at the end of the follow-up (222 mg/kg; P=0.0048).
• Ustekinumab levels at the beginning of STELARA IV administration were 2.6 µg/mL (IQR, 0.13-11.69) and significantly increased from baseline (weeks 12-16, 9.09 μg/mL; after 1 year, 10.7 µg/mL; P<0.001 for both).
• At the end of the follow-up, 81% of the patients maintained therapy.

Hashmi et al (2022)⁶ evaluated the safety and effectiveness of STELARA reinduction and IV maintenance therapy in patients with refractory CD at a single-center Veteran Affairs medical center.

• A total of 4 patients with refractory CD were included. Each patient received STELARA IV induction.
• All patients had loss of response or inadequate response (objectively measured via CRP, FCP, endoscopy, and radiography) upon transitioning to STELARA SC maintenance therapy. Ustekinumab trough levels remained subtherapeutic (<4.5 µg/dL) with ongoing active disease despite dose optimization to q4w.
• These patients were then switched to weight-based STELARA IV maintenance dosing q4w, and disease activity was reassessed after 3 months.
  • All patients achieved endoscopic and/or radiographic remission with therapeutic drug troughs (not reported).
  • No AEs were reported during the study.

Case Series

Masood et al (2023)⁷ conducted a case series to evaluate the efficacy of STELARA IV maintenance therapy in 6 patients with CD who were switched to STELARA IV every 12 weeks (q12w) for maintenance, due to reasons unrelated to treatment effect, after receiving at least 1 IV induction dose. Patients weighing between 55 kg and 85 kg received a 390 mg IV maintenance dose, whereas those weighing above 85 kg received a 520 mg IV maintenance dose.

• Patient 1 was a 69-year-old male (61 kg) with perianal and ileal CD previously treated with mesalamine and infliximab with secondary loss of response.
  • The patient received STELARA SC therapy for 149 weeks and was subsequently switched to STELARA IV maintenance therapy (completed 60 weeks of IV therapy to date).
  • The patient remained in endoscopic and clinical remission while receiving STELARA IV maintenance therapy.
  • After 30 weeks of treatment, the patient experienced diarrheal symptoms, which resolved following 10 days of treatment with rifaximin.
• Patient 2 was a 66-year-old female (89 kg) with CD affecting the ascending colon and ileum. She was previously treated with infliximab without any loss of response but was later switched to certolizumab (which resulted in primary nonresponse) and STELARA to manage enteropathic arthritis.
  • The patient received STELARA SC therapy for 30 weeks and was subsequently switched to 30 weeks of STELARA IV maintenance therapy.
  • The patient has maintained clinical remission while on STELARA IV maintenance therapy but has not undergone follow-up endoscopy at the time of this report.
• Patient 3 was a 74-year-old male (69 kg) with rectal and perianal CD previously treated with mesalamine.
  • The patient received STELARA SC therapy for 145 weeks and was subsequently switched to 56 weeks of STELARA IV maintenance therapy.
  • The patient remained in clinical remission, with a decrease in the HBI score from 3 to 1. Furthermore, endoscopic remission was confirmed on colonoscopy.
• Patient 4 was a 69-year-old female (80 kg) who had undergone partial colectomy with an end-to-side ileocolonic anastomosis. She then developed CD affecting the ileum and ileocolonic anastomosis and had received treatment with mesalamine, prednisone, and budesonide.
  • The patient received STELARA SC therapy for 91 weeks and was subsequently switched to 39 weeks of STELARA IV maintenance therapy.
  • The patient remained in clinical remission, with a decrease in the HBI score from 5 to 0; however, she has not undergone follow-up endoscopy since starting STELARA IV maintenance therapy.
  • At the 22-week follow-up, the STELARA IV dosing was adjusted to every 10 weeks (from q12w) due to reappearance of urgency and diarrhea symptoms at the 10-week mark.
  • Following dose adjustment, the patient has remained in clinical remission with drug levels at 8 µg/mL and over 10 µg/mL at 12 and 22 weeks, respectively.
• Patient 5 was a 70-year-old male (74.8 kg) with CD affecting the ileum and colon following a small bowel and ileocolic resection with an end-to-side ileocolonic anastomosis; he was previously treated with mesalamine.
  • The patient received STELARA SC therapy for 55 weeks and subsequently completed 41 weeks of STELARA IV maintenance therapy.
  • The patient has maintained clinical remission while on STELARA IV maintenance therapy but has not undergone follow-up endoscopy.
• Patient 6 was a 79-year-old male (69.9 kg) with ileal CD previously treated with sulfasalazine.
  • The patient received STELARA SC therapy for 158 weeks and STELARA IV therapy for 38 weeks.
  • The patient has maintained clinical remission but has not undergone follow-up endoscopy.

Details about the patients’ laboratory values and endoscopic and clinical scoring, respectively, are summarized in Table: Laboratory Values Before and After STELARA IV Therapy and Table: Endoscopic and Clinical Scoring Before and After STELARA IV Therapy.

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 16 October 2024.