Summary

• The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
• Data on the use of STELARA in adult patients with acute severe ulcerative colitis (ASUC) are summarized below.^1-7

CLINICAL DATA

Prospective Study

Vitali et al (2023)¹ conducted a single-center, prospective study to evaluate the long-term efficacy and safety of a combination therapy which included cyclosporin induction and STELARA maintenance in 11 patients with ASUC.

Study Design/Methods

• This study included adult patients with steroid-refractory ASUC who received overlapping sequential therapy with cyclosporin induction and STELARA maintenance therapy between August 2019 and August 2021.
• Patients with ASUC were defined by the Truelove-Witts criteria and were refractory to intravenous (IV) corticosteroid therapy at the recommended dosage (IV hydrocortisone 100 mg 4 times a day or IV prednisolone 100 mg) for a minimum of 3 consecutive days.
• Patients with cytomegalovirus (CMV) superinfection and those with infectious colitis were excluded from the study.
• Patients were administered continuous IV cyclosporin treatment (2 mg/kg) after failed steroid therapy, and cyclosporin treatment responders were switched to oral cyclosporin therapy after 5 days.
  • Cyclosporin therapy was then continued for a maximum of 6 months.
  • After commencement of successful IV cyclosporin induction therapy, IV STELARA therapy (6 mg/kg) was initiated at a mean (range) of 3.2 (1-8) weeks.
  • Subcutaneous (SC) STELARA 90 mg was administered every 6 to 8 weeks as maintenance therapy.
• Patients were followed up for 12 months and assessed at each visit for STELARA administration.
• Primary endpoints included:
  • Clinical response, defined as a decrease from baseline in the partial Mayo score by ≥30% and ≥3 points, with a decrease in the rectal bleeding subscore of ≥1 from baseline
  • Clinical remission, defined as the Mayo rectal bleeding subscore of 0, stool frequency subscore of 0 or 1 with at least 1 point decrease from baseline and a Mayo endoscopy subscore of 0 or 1
• Secondary endpoints included:
  • Endoscopic remission, defined as a Mayo endoscopic subscore of ≤1
  • Histological remission, defined as a Nancy index of ≤2 without neutrophils in the epithelium and lamina propria
  • Symptomatic remission, defined as no rectal bleeding (Mayo rectal bleeding subscore of 0) and normal-to-near-normal stool frequency (Mayo stool frequency subscore of 0 or 1)
  • Steroid-free clinical remission, defined as an absence of steroid use for 2 weeks prior to assessment
  • Biochemical remission (C-reactive protein [CRP] <5 mg/L) assessed at weeks 8, 16, and 52
• Additional response parameters included intestinal ultrasound response, defined as a decrease in the bowel wall thickness evaluated by bowel wall thickness during the follow-up period.

Results

• In total, 11 patients with steroid-refractory ASUC were included in the study.
• Baseline data are presented in Table: Baseline Demographics and Clinical Characteristics of Patients With Steroid-Refractory ASUC.

• The primary and secondary endpoints and other outcomes through week 52 are presented in Table: Clinical Outcomes Assessed Through Week 52 and Rectal Bleeding, Stool Frequency, and Combination of Rectal Bleeding and Stool Frequency Score Through Week 52

• Intestinal ultrasound was performed in all patients at baseline prior to initiation of cyclosporin therapy, except 2 patients with isolated proctitis.
  • The maximum mean bowel wall thickness at baseline, week 8, 16, 24, 52 was 5.5 mm, 4.5 mm, 4.0 mm, 3.3 mm and 3.6 mm, respectively.
• Two patients underwent colectomy after 3 and 6 months (mean [range], 4.5 months [3-6]).
• STELARA was discontinued in 3 patients (after 2 months in 1 patient and after 3 months in 2 patients) due to ineffectiveness and a need to change the ongoing therapy.
• Adverse events (AEs), paresthesia, myalgia, headache, nausea, and hair loss, were reported in 5 of 11 (45%) patients. All observed events were attributed to cyclosporin treatment and cyclosporin dose reduction was necessary in all five patients.

Naganuma et al (2023)^2,8 evaluated the short-term efficacy and safety of advanced therapies (including STELARA) in hospitalized patients with ASUC through a multicenter, observational cohort study.

Study Design/Methods

• Patients with ASUC were defined by following Truelove-Witts criteria: ≥6 bloody bowel movements per day with ≥1 markers of systemic toxicity, including heart rate >90 beats/minute, body temperature >37.8°C, hemoglobin (Hb) level <10.5 g/dL, and/or erythrocyte sedimentation rate (ESR) >30 mm/hour. In cases where ESR data could not be measured, CRP >3 mg/dL was used.
• Patients received corticosteroids, apheresis, tacrolimus, infliximab, adalimumab, golimumab, tofacitinib, vedolizumab, STELARA, or cyclosporin A as the first treatment after hospitalization and were monitored until day 28 or colectomy. Any treatment change or addition within 28 days was recorded as a second treatment.
• The type of each treatment after admission and Patient-Reported Outcome 2 (PRO2) were collected at days 0, 3, 7, and 14 of treatment.
  • PRO2 was defined as the sum of all Mayo Endoscopic Subscores (MES) for daily diarrhea and rectal bleeding.
• The primary endpoint was clinical remission (PRO2 <2 without blood in stool) at days 7 and 14 for patients treated with corticosteroids, first and second advanced therapy. Patients requiring alternative treatments or colectomy were considered not in clinical remission.
• The main secondary endpoints were clinical improvement (decrease of ≥50% in PRO2) at days 7 and 14 and the proportion of patients requiring colectomy within 28 days.

Results

• Among the 221 patients included in the study, 120 received corticosteroids and 101 received advanced therapy as first-line treatment. Of these 101 patients, 13 received STELARA.
• The proportion of advanced therapies received by 101 patients included⁸:
• At baseline, disease severity indicators, such as pancolitis (P=0.529), daily diarrhea frequency (P=0.135), body temperature (P=0.281), PRO2 (P=0.149), MES (P=0.351), CRP (P=0.207), Hb (P=0.380), ESR (P=0.873), and serum albumin (P=0.299), were comparable between the corticosteroid and advanced therapy groups. However, the advanced therapy group had significantly higher proportions of patients with steroid-dependent disease (P=0.046), clinical recurrence ≥2 times within the recent 12 months (P=0.002), use of oral steroids at entry (P<0.001), and use of thiopurine at entry (P<0.001) compared with the corticosteroid group.
• PRO2 data on days 0, 3, 7, and 14 among 13 patients with ASUC who received STELARA as first-line treatment is presented in Table: PRO2 in Patients with ASUC Receiving STELARA as the First-Line Treatment.

• Of the 25 patients who received a second advanced therapy, 6 received STELARA. The clinical characteristics and short-term outcomes of these patients are summarized in Table: Clinical Characteristics and Short-term Outcomes in Patients Receiving STELARA as the Second Advanced Therapy.

• A total of 71 AEs were reported in patients with ASUC (first-line treatment, n=53; second-line treatment, n=18).
• Infections were observed in 39 cases (CMV reactivation, n=21; Clostridioides difficile infection, n=9; catheter-related bloodstream infection, n=7; sepsis, herpes simplex infection, and acne, n=1 each).

Retrospective Study

Veyrard et al (2022)³ evaluated the efficacy and safety of bridging therapy with calcineurin inhibitors to STELARA in patients with ASUC refractory to IV steroids through a retrospective study.

Study Design/Methods

• Patients with ASUC (defined by Truelove-Witts criteria) who were refractory to IV steroids (0.8-1 mg/kg; defined by a Lichtiger score of ≥10), were included in the study at the time of treatment initiation.
• All patients received cyclosporine or tacrolimus followed within 60 days by STELARA.
  • Cyclosporine was administered at a dose of 2 mg/kg/day IV (target blood level, 150-250 ng/mL) and tacrolimus, at a dose of 0.05 mg/kg IV. STELARA was administered at a dose of 6 mg/kg IV infusion followed by 90 mg SC every 8 weeks (q8w).
  • After 7 days of IV cyclosporine or tacrolimus, clinical responders were transitioned to oral therapy, targeting the same blood levels. Three months after initiation, calcineurin or tacrolimus was withdrawn from therapy.
• Outcomes included clinical response, clinical remission, and biochemical remission (6 months after treatment initiation), colectomy-free survival, and survival without discontinuation of STELARA.
  • Clinical response was defined as a reduction of ≥3 points in the partial Mayo score, with at least a ≥30% decrease, and a reduction of ≥1 point in the bleeding subscore, with a subscore of 0 or 1, compared with baseline.
  • Clinical remission was defined as a partial Mayo score of <3, with all the subscores <1.
  • Biochemical remission was defined as a CRP level of <5 mg/L.

Results

• Among the 10 patients included in the study, 9 had prior exposure to infliximab and 8, to vedolizumab with a median disease duration of 7 years (interquartile range [IQR], 3-8.7).
• The median follow-up duration was 9 months (IQR, 5-11).
• At baseline, the median partial Mayo score was 8 (IQR, 8-9), and the median CRP level was 17.5 mg/L (IQR, 4.1-38.8).
• Three patients were steroid-dependent prior to hospitalization.
• Nine (90%) patients received cyclosporine and 1 (10%) received tacrolimus.
  • Within the first week, 6 (60%) patients were transitioned to oral therapy, and 4 (40%) continued to receive IV therapy.
  • Within 2 months of treatment initiation, all patients discontinued the calcineurin inhibitor.
    • The median duration between STELARA initiation and calcineurin inhibitor withdrawal was 45 days (IQR, 45-60).
    • The median duration between the initiation of calcineurin inhibitor and STELARA was 22 days (range, 6-60).
    • Two (20%) patients were initiated on STELARA therapy within 7 days following admission.
• At 6 months, compared with baseline, the median partial Mayo score reduced significantly (P=0.005) from 10.6 to 1.0, and the median CRP levels reduced significantly (P=0.02) from 17.5 mg/L (IQR, 4.1-38.8) to 2.3 mg/L (IQR, 1.7-3.2).
  • No patients underwent colectomy.
  • One patient did not achieve clinical response and remission, and 1 continued to be on steroids at 6 months.
• With a median follow-up duration of 9 months (IQR, 5-11), 1 patient withdrew STELARA due to treatment failure; 2 patients required STELARA dose optimization after 3 months due to persistent symptoms, despite achieving clinical response.
• One case of alopecia not leading to treatment discontinuation was reported.

Case Series

Hooper et al (2020)⁷ assessed the efficacy of STELARA induction therapy in 4 patients with steroid-refractory severe inflammatory bowel disease, including 3 patients with steroid-refractory severe ulcerative colitis (UC), through a single-center, retrospective case series.

• All 3 patients with steroid-refractory severe UC received IV corticosteroids on admission.
• Patient 1:
  • History of extensive UC for 9 years
  • Previously failed infliximab and adalimumab and was on vedolizumab at the time of admission
  • Inpatient computed tomography (CT) enterography revealed extensive colitis with terminal ileitis.
  • On day 8 of hospitalization, IV STELARA was administered.
• Patient 2:
  • History of pan-UC for 1 year
  • Was treated with infliximab failure at the time of admission
  • CT scan and colonoscopy revealed pancolitis and terminal ileitis.
  • On day 3 of hospitalization, rescue therapy with infliximab 10 mg/kg was unsuccessful.
  • On day 9, IV STELARA therapy was administered.
• Patient 3:
  • Past medical history of psoriasis; developed extensive UC 1 month after initiating treatment with secukinumab for psoriasis
  • CT scan revealed multifocal enteritis and colitis, partial small bowel obstruction, and a 3 cm intra-abdominal abscess that was treated with percutaneous drainage and IV antibiotics.
  • On day 14 of hospitalization, IV STELARA was administered due to active enterocolitis despite IV corticosteroids and sepsis control.
• All 3 patients achieved clinical response or remission with STELARA and IV corticosteroids and were discharged a mean of 4.75 days (range, 2-9) after STELARA infusion.
• After initiating STELARA, CRP levels initially increased in all 3 patients and then decreased to a mean±standard deviation of 21.1±2.9 mg/L.
• AEs included deep vein thrombosis in the first patient and self-limited nausea and vomiting in the third patient. No patient discontinued STELARA during follow-up.

Case Reports

Affendi et al (2022)⁴ reported the efficacy of STELARA in a 75-year-old male patient with ASUC.

• The patient presented with complaints of bloody diarrhea (6 times/day), severe lethargy, and fever (38.2°C). He was diagnosed with UC 3 weeks prior, and treatment with mesalazine 3 g/day was initiated. The patient had multiple underlying comorbidities, including ischemic heart disease, congestive heart failure, diabetes mellitus, and chronic obstructive pulmonary disease (COPD).
• Abdominal CT scan and unprepared left-flexi sigmoidoscopy findings, including severe inflammation and deep ulceration, were consistent with ASUC.
• Treatment with IV hydrocortisone 100 mg 4 times a day was initiated. On day 5, the patient showed a good clinical response, and the CRP level reduced from 144 mg/L before treatment to 19 mg/L.
• On day 8, transitioning to oral prednisolone therapy led to worsening of diarrhea (10 times/day), and CRP level increased to 70.89 mg/L. IV steroids were initiated again; however, adequate response was not achieved, and the patient’s diabetes was uncontrolled.
• Since the patient was a high-risk surgical candidate, surgery was ruled out. Due to the patient’s COPD, infliximab and cyclosporine were not initiated. Therefore, STELARA therapy was initiated at a loading dose of 390 mg IV at week 0 followed by 90 mg SC at weeks 2 and 6 and then q8w.
• The patient demonstrated good clinical response to STELARA, with complete mucosal healing with pseudopolyps and scar formation at week 24, as revealed by repeat colonoscopy.

Shaffer et al (2021)⁵ reported the use of cyclosporine plus STELARA in 2 patients with ASUC.

Case 1

• A 21-year-old male patient diagnosed with extensive UC in 2016 was hospitalized for ASUC in 2019. Flexible sigmoidoscopy revealed severe colitis.
• The patient did not respond to 3-day therapy with IV steroids. Cyclosporine 3 mg/kg IV (target level, 300-400 ng/mL) was initiated, and by day 4 of therapy, the patient experienced rapid response into clinical remission.
• On day 4, a loading dose of STELARA 390 mg IV was administered, and the patient was discharged on oral prednisone, oral cyclosporine, and antibiotic prophylaxis for Pneumocystis jirovecii pneumonia.
• At week 2, tapering of prednisone was initiated, and at week 8, cyclosporine was discontinued.
• Four months after discharge, the patient was on maintenance therapy of STELARA SC and continued to be in stable clinical remission with a CRP level of <5 mg/L (compared with 22 mg/L at baseline) and a fecal calprotectin (FCP) level of 242 µg/g.
• The patient did not experience any AEs.

Case 2

• A 20-year-old female patient who was diagnosed with pancolitis in 2018 developed ASUC and Clostridioides difficile infection.
• Flexible sigmoidoscopy revealed severe colitis.
• The patient did not respond to 3-day therapy with IV steroids. IV cyclosporine was initiated, and the patient showed clinical response.
• Vedolizumab was initiated on the day of discharge and the patient received 3 loading doses; however, she did not maintain remission (FCP level, 1150 µg/g). Vedolizumab maintenance therapy was not administered, and oral cyclosporine therapy and antibiotic prophylaxis for Pneumocystis jirovecii pneumonia was continued.
• Eleven weeks after initiation of cyclosporine therapy and 5 weeks after the last vedolizumab dose, STELARA 260 mg IV was administered, and the patient experienced improvement within 2 weeks.
• Six weeks after STELARA therapy initiation, FCP level was 380 µg/g.
• Cyclosporine was discontinued, and the patient was clinically stable after receiving STELARA SC maintenance therapy for 4 months.
• The patient did not experience any AEs.

Ganzleben et al (2020)⁶ reported the use of combination therapy of cyclosporine and STELARA in a 33-year-old male patient with ASUC.

• The patient who was diagnosed with left-sided UC at the age of 25 years presented with abdominal pain, recurrent fever, and increased stool frequency (14-16 times/day) with blood in most of the stools.
• Prior to admission, the patient did not improve with high-dose IV prednisolone (100 mg/day).
• Sigmoidoscopy revealed severe endoscopic inflammation (endoscopic Mayo score, 3) with spontaneous bleeding and extended superficial mucosal ulcerations. Histology findings indicated severe inflammation (Geboes score, 5).
• Cyclosporine therapy was initiated at a dose of 2 mg/kg/day IV (day 0) and the patient showed clinical response.
• On day 6 of cyclosporine therapy, STELARA 390 mg IV was administered.
• At the time of discharge, cyclosporine trough level was 251 µg/L (target serum trough level during oral cyclosporine therapy, 250-300 ng/mL), and CRP level was 26 mg/L (vs 64 mg/L at the time of presentation).
• At day 62, the patient presented at outpatient for follow-up:
  • Partial Mayo score: 0 vs 8 at baseline
  • Endoscopic findings: mild mucosal inflammation (endoscopic Mayo score, 1) with mucosal erythema and decreased vascular pattern
  • Histologic findings: mild inflammation (Geboes score, 3)
  • FCP and CRP levels: within normal range
  • Ustekinumab level: 6.47 µg/mL
• STELARA 90 mg SC was administered. On day 83, oral cyclosporine was discontinued.
• After day 139, the patient continued to be in clinical remission and endoscopic remission, with no signs of active inflammation. Histologic findings indicated mild inflammation (Geboes score, 2). FCP level was 58 µg/mL; CRP level was within normal range. Ustekinumab drug level was 3.52 µg/mL. STELARA maintenance therapy was continued at the same dose.
• On day 195, the patient remained in clinical remission, and FCP and CRP levels were within normal range.
• No treatment-related AEs were reported with STELARA.

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 06 December 2024.