SUMMARY

• The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
• A prospective and several retrospective studies evaluated the use of STELARA for the treatment of pouchitis.^1-7
• Additionally, case reports have described the use of STELARA for the treatment of pouchitis.^8-10

CLINICAL DATA

Prospective Study

Outtier et al (2024)¹ evaluated the efficacy and safety of STELARA in adult patients with chronic pouchitis through a prospective, open-label study.

Study Design/Methods

• Adult patients (≥18 years) with ulcerative colitis (UC) who had undergone proctocolectomy and ileal pouch-anal anastomosis (IPAA) at least 1 year before screening and met one of the following criteria:
  • Relapsing pouchitis (≥3 episodes within 1 year before screening, each treated with ≥2 weeks of antibiotic therapy)
  • Pouchitis refractory to ≥4 weeks of maintenance antibiotic therapy or refractory to anti-tumor necrosis factor (TNF) or vedolizumab therapy for ≥12 weeks
• Pouchitis was defined by a Modified Pouchitis Disease Activity Index (mPDAI) score of ≥5 and a minimum endoscopic subscore of 2 (outside the staple or suture line).
• During the induction phase, patients received a single weight-based infusion of STELARA (~6 mg/kg) followed by maintenance subcutaneous (SC) injections of STELARA (90 mg) every 8 weeks (q8w).
• Ciprofloxacin was used as bridging therapy for the first 4 weeks, and a need for antibiotics thereafter was regarded as treatment failure (nonresponder imputation).
• No antibiotic therapy was allowed from week 4 until week 16.
• The Pouchitis Disease Activity Index (PDAI, 0-18; higher scores indicate greater severity) and mPDAI (PDAI without the histologic subscore, 0-12; higher scores indicate greater severity) were assessed at baseline and at weeks 16 and 48.
• Fecal calprotectin (FCP) was evaluated at baseline and at weeks 16 and 48.
• C-reactive protein (CRP) level was evaluated at all visits during the induction and maintenance periods.
• The primary endpoint was the proportion of patients achieving steroid-free remission (defined as mPDAI of <5 and reduction of ≥2 points from baseline) at week 16.
• Secondary endpoints were:
  • Steroid-free remission at week 48, clinical response (≥2 points reduction from baseline in mPDAI) at week 16 and 48, changes in mPDAI, and mPDAI clinical and endoscopic subscores
  • CRP and FCP levels and quality of life (measured using the EuroQoL-5 dimension-5 level [EQ-5D-5L] questionnaire) compared with baseline

Results

• A total of 22 patients with a median age of 42.2 (interquartile range [IQR], 32.2-52.3) years were included in the study.
• Of these, 21 (95%) patients remained in the study until week 16, and 14 (64%) patients remained in the study until week 48.
• All patients who discontinued STELARA did so due to a lack of efficacy, except for 1 patient who withdrew consent for practical reasons.
• During the maintenance phase, 4 patients experienced flares requiring antibiotic treatment. One patient required 2 antibiotic courses, whereas the other 3 patients required 1 antibiotic course.
• Previous treatments for pouchitis included topical or systemic 5-aminosalicylic acid (n=6), topical or systemic steroids (n=17), immunomodulators (n=8), anti-TNF agents (n=9), vedolizumab (n=7), and tofacitinib (n=1).

Efficacy - Primary and Secondary Endpoints

• At week 16, 27.3% and 54.5% of patients achieved steroid-free remission and response, respectively.
• Changes in the mPDAI score, PDAI score, and CRP and FCP levels are described in Table: mPDAI Scores, PDAI Scores, CRP Levels, and FCP Levels at Week 16 vs Baseline.

• At week 48, 36.4% and 54.5% of patients achieved steroid-free remission and response, respectively.
• Changes in the mPDAI score, PDAI score, and CRP and FCP levels are described in Table: mPDAI Scores, PDAI Scores, CRP Levels, and FCP Levels at Week 48 vs Baseline.

Quality of Life

• The EQ-5D-5L usual activities score improved significantly by week 48 (P=0.0071), but the mobility score worsened significantly by week 16 (P=0.036).
• The visual analog scale of health increased from 57.5 (IQR, 41.3-70) at baseline to 60 (IQR, 55-77) at week 16 and 71.5 (IQR, 68.5-79.5) at week 48 (P<0.0001).

Safety

• New safety signals were not observed during the study.
• Overall, 3 serious adverse events (AEs), including hospitalization for subobstruction, worsening pouchitis, and choledocholithiasis, were reported but not considered to be related to STELARA.

Retrospective Studies

Uchitel et al (2024)² conducted a retrospective cohort study that evaluated the efficacy of different treatments, including STELARA and the Crohn's disease exclusion diet (CDED), for managing chronic pouchitis. Results specific to STELARA are summarized below.

• Demographic, clinical, endoscopic, histologic, and laboratory values of adult patients with UC who developed chronic pouchitis after an IPAA surgery and were treated with biologics or CDED, were collected at baseline and at weeks 12, 26, and 52 of treatment.
• Response was assessed by mPDAI and defined as a reduction of ≥2 points from baseline.
• Of the 51 patients included in the study, 7 were treated with STELARA and had a mean (±standard deviation) age of 45.1±15.7 years.
• Chronic pouchitis was reported in 2 (28.6%) patients.
• Two of 7 (28.6%) patients received antibiotics during induction therapy.
• The median (IQR) mPDAI at baseline was 6 (5-10).
  • At week 52, the mPDAI response rate for STELARA was 60%.

Park et al (2022)³ conducted a retrospective, multicenter cohort study that evaluated the efficacy and safety of STELARA vs vedolizumab in adult patients with Crohn’s disease of the pouch (CDoP). Results specific to the STELARA arm are summarized below.

• The primary outcome was clinical response at 3 or 6 months.
• The secondary outcomes were clinical remission, endoscopic response, histologic response, pouch failure or surgery, and AEs.
• Among the 101 patients included in the analysis, 60 were treated with STELARA.
• Forty-seven (78%) patients had a history of biologic exposure.
• Clinical response at 3 and 6 months was achieved in 65% and 68% of patients, respectively.
• Clinical remission at 3 and 6 months was achieved in 33% and 33% of patients, respectively.
• Endoscopic response and remission were achieved in 35% and 12% of patients, respectively. Histologic response and remission were achieved in 44% and 6% of patients, respectively.
• Inflammatory bowel disease-related hospitalization was reported in 61.6% of patients, and pouch failure or surgery was reported in 11% of patients.
• AEs reported among STELARA-treated patients included arthralgia (n=1), hair loss (n=1), syncope (n=1), and upper respiratory infection (n=1).

Dalal et al (2021)⁴ assessed the outcomes of standard and intensified dosing (every 4 weeks [q4w] or every 6 weeks) of STELARA in adults with CDoP who underwent total proctocolectomy (TPC) with IPAA.

• The primary outcome was clinical response determined by the patient’s healthcare provider 8-16 weeks after STELARA induction.
• There were 46 patients who initiated STELARA for chronic antibiotic-refractory pouchitis (CARP) (n=6), cuffitis (n=4), or CDoP (n=36).
• Pouch-associated fistulae were present in 14/46 patients (pouch-perianal fistulae, n=12 and pouch-vaginal fistulae, n=2).
• Clinical response was achieved in 37 (80.4%) patients.
• Of the 46 patients who initiated STELARA, 23 (50%) underwent dose intensification after a median of 223 days and 14 (63.6%) achieved clinical response 8-16 weeks after dose intensification (1 patient was lost to follow-up).
  • Improvement in the extent/severity of pouch inflammation was seen in 7/10 (70%) patients with available endoscopic data following a median of 234 days from dose intensification.
• Improvement in fistula drainage and/or pain 8-16 weeks after induction was reported in 8/14 (57.1%) patients with pouch-associated fistulae.
• Improvement in fistula drainage was reported in 3/4 (75%) of patients with persistent symptoms who proceeded to dose intensification and had available follow-up data 8-16 weeks after dose intensification.
• One AE, acneiform reaction, led to the discontinuation 807 days after dose intensification. No infectious complications were reported.

Ollech et al (2019)⁵ evaluated the efficacy and safety of STELARA for the treatment of CARP.

• A retrospective single-center study included patients with UC who had undergone a TPC with IPAA and subsequently developed CARP.
• Patients received a single STELARA 90 mg intravenous (IV) loading dose infusion followed by 90 mg injections q8w.
• Patients with Crohn’s disease (CD) of the pouch or pre- or postoperative diagnosis of CD were excluded.
• Patients were classified as having CARP when pouch inflammation was confirmed on pouchoscopy, and patients had over 4 weeks of pouch symptoms (eg, increased stool frequency, urgency, tenesmus, and fecal seepage, despite standard courses [>1 month] of antibiotic treatment).
• Patients were included in the study if they had a minimum follow-up time of 3 months.
• Twenty-four patients were included in the analysis.
• Previous treatment for pouchitis included antibiotics (ciprofloxacin or metronidazole) in all patients, biologics other than STELARA in 12 patients (50%), and immunomodulators in 6 patients (25%).
• The median follow-up duration was 12.9 (IQR, 7.9-16) months. Over the follow-up time period, 5 patients discontinued STELARA, 2 patients had a pouch excision, and 3 patients were switched to other treatments.
• Thirteen patients had pouchoscopies available after STELARA was initiated.
  • In these patients, the median endoscopic subscore of PDAI decreased from 5 (IQR, 4-6) to 4 (IQR, 2-5) post-treatment (P=0.016).
  • Nine of these 13 patients (69%) had an ulcerated surface area >10% before STELARA treatment; after treatment with STELARA, 4 patients (31%) had an ulcerated surface area of >10%. No patient achieved a PDAI endoscopic subscore of 0 (complete endoscopic normalization of the pouch).
  • For the group of 8 patients who had previously received treatment for pouchitis with immunomodulatory and biologic drugs before treatment with STELARA and for whom follow-up endoscopic data was available, the endoscopic subscore of the PDAI decreased from a median of 6 to a median of 4. Four of these patients had an ulcerated surface area of >10% before STELARA treatment, while 1 patient still had an ulcerated surface area of >10% after STELARA treatment.
• Twelve patients (50%) had a significant clinical response based on the physician’s clinic note. Also, the median number of bowel movements within 24 hours decreased from 8 (IQR, 5-12) to 6 (IQR, 5-8) (P=0.002).

Weaver et al (2019)⁶ evaluated the efficacy of STELARA in patients with CDoP and chronic pouchitis.

• A retrospective multicenter study evaluating the efficacy of STELARA as a treatment for CDoP and chronic pouchitis (chronic antibiotic-dependent pouchitis [CADP] or CARP) was conducted.
• Patients were included in the cohort if they had received prior therapy with STELARA for treatment of CDoP or chronic pouchitis for ≥3 months and were ≥18 years of age.
• Patients with a history of TPC with IPAA as a treatment for UC were eligible; however, patients who had an existing diagnosis of CD prior to undergoing colectomy with IPAA, and patients who had undergone pouch excision or had a diverting ileostomy before STELARA therapy were excluded.
• The primary outcomes of the study were clinical response and clinical remission at 6 months based on physician assessment.
  • Clinical remission was defined as a return to baseline symptoms with reported normal, nonbloody bowel movements, without pain or urgency, increased nocturnal bowel movements, and the absence of a fistula (if a fistula was previously present).
  • Clinical response was defined as any improvement in symptoms after initiating STELARA, including a decrease in bowel movements, pain, or fistula drainage.
• A total of 56 patients (47 with CDoP and 9 with chronic pouchitis, noted as CADP) were included in the study.
• Colectomy with IPAA was performed for severe or refractory UC in 53/56 (95%) patients. A total of 41 (73%) patients had previously been treated with either anti-TNF therapy, vedolizumab, or both after IPAA.
• At the time of primary outcome analysis, 36 patients with CDoP and 6 patients with chronic pouchitis had completed 6 months of therapy.
  • Of these 6 patients with chronic pouchitis, 5 (83%) were in clinical response at 6 months. No patients were in clinical remission.
  • Among the 5 responders, 3 (60%) were able to stop all antibiotic therapy.
  • No patients with chronic pouchitis stopped therapy or experienced a relapse of disease.
• Of the 9 patients with chronic pouchitis, 8 (88%) showed clinical response at 3 months. No patients were in clinical remission.
• Four patients with chronic pouchitis reached the 12-month mark of evaluation in the study. Of these patients, 1 (25%) was in clinical remission and 3 (75%) were in clinical response.

Tsistrakis et al (2018)⁷ reported the use of STELARA for the treatment of refractory inflammatory conditions of the ileal pouch including pouchitis.

• A retrospective chart review of adult patients with prior IPAA receiving STELARA was conducted.
• A total of 4 patients were identified and all previously had refractory UC before proctocolectomy with IPAA.
• All previously had failed ≥1 anti-TNF treatment and 1 patient failed anti-integrin therapy.
• Two patients had a history of fistulizing disease and 1 had prior stricturing disease.
• In all patients, pouch inflammation was seen and 3 out of 4 patients had inflow limb involvement. Pouch disease was categorized as either pouchitis or CDoP.
• Three of the 4 patients achieved clinical response at ≥6 weeks post treatment initiation.
• No patients achieved clinical remission in this analysis.
• Of the 3 patients who underwent endoscopy post treatment, 2 achieved endoscopic response and remission.

Case Reports

Kayal et al (2021)⁸ reported the case of a 30-year-old male with medically refractory UC who underwent TPC with IPAA and was treated with STELARA for Crohn’s disease-like pouch inflammation (CDLPI).

• Approximately 1 year after IPAA, the patient developed recurring acute pouchitis with symptoms of frequency (>15 bowel movements per day including >3 overnight), urgency, abdominal pain, and joint pain.
• Over the course of 6 months, he became refractory to treatment with antibiotics. A pouchoscopy was performed which revealed patchy erythema, ulcerations involving the afferent limb, and complete loss of vascular pattern in the pouch body.
• Due to the extensive involvement of the afferent limb and antibiotic-refractory nature of the pouchitis, he was diagnosed with CDLPI and initiated STELARA.
• Six months after induction with STELARA, he was admitted due to symptom exacerbation, which was reflected upon a pouchoscopy.
• He was prescribed a prednisone taper and STELARA was optimized to q4w.
• Within 3 months of STELARA dose optimization, he reported resolution of stool frequency, urgency, and abdominal and joint pain.
• A follow-up pouchoscopy 6 months after STELARA dose optimization revealed a normal afferent limb and patchy erythema with no ulcerations.

Peter et al (2018)⁹ described a case of a male patient with chronic refractory pouchitis who received rescue therapy with STELARA.

• A 40-year-old male was diagnosed with UC and was initiated on steroid therapy.
• Chronic active UC developed, and azathioprine was discontinued due to pancreatitis. Treatment with infliximab, adalimumab, and vedolizumab did not achieve remission. Additionally, treatment with leukocyte apheresis did not reduce disease activity.
• Approximately 10 years after diagnosis with UC, a colectomy and IPAA was performed; however, in the further course, stenosis of the anastomosis and refractory pouchitis occurred.
• Induction with STELARA (in combination with prednisolone) was initiated due to: failure of antibiotic treatments and fecal microbiota transplantation, a steroid-dependent course, and the findings of an endoscopy (indicating mucosal erythema, ulcerations, loss of vascular patterns, and granularity of pouch mucosa).
• IV STELARA 390 mg with 50 mg prednisolone was given (week 0) and follow-up occurred q4w.
• Improvement in clinical symptoms were reported at week 4 and frequency of bowel movements decreased from 20 to 8-10 times/day without mucus or blood.
• Significant improvement was demonstrated on a pouchoscopy at week 8 and repeated testing showed normalized serum CRP and FCP.
• Prednisolone dose was reduced to 5 mg/day after 6 months.

Tran-Minh et al (2017)¹⁰ reported 2 cases of chronic pouchitis refractory to immunosuppressants and anti-TNF therapies that were treated with STELARA.

Case 1

• A 22-year-old male with UC underwent IPAA for chronic active disease with transient response to optimized infliximab and methotrexate (MTX) combination therapy and failure to azathioprine and adalimumab.
• Three years postsurgery, the patient presented with recurrent pouchitis that initially responded to switching antibiotics strategy, and chronic symptoms developed which included tenesmus, mild bleeding, severe abdominal pain, and up to 10 liquid stools per day.
• STELARA 90 mg SC injection at weeks 0 and 4, and q8w thereafter was initiated.
• Baseline endoscopy results showed diffuse inflammation in the pouch with multiple superficial ulcers.
• The patient was symptom free at week 4 and in clinical remission with almost complete mucosal healing and normalized CRP at week 12.
• Clinical remission with negative CRP remained after 2 years of maintenance therapy with STELARA.

Case 2

• A 71-year-old female with UC underwent IPAA due to intolerance to thiopurines and failure of MTX, infliximab, and adalimumab.
• Approximately 5 years postsurgery, the patient presented with severe acute pouchitis that responded to antibiotics, prednisone suppository, and oral budesonide.
• After approximately 2 months, her pouchitis relapsed and she developed chronic invalidating watery diarrhea with emergency and she failed several antibiotic and probiotic courses.
• STELARA 90 mg SC injection at weeks 0 and 4, and q8w thereafter was initiated approximately 8 months after relapse.
• Baseline endoscopy results showed multiple superficial and deep ulcers in the pouch.
• At week 12, rapid improvement was seen with 3 formed stools per day and normalized CRP.
• Week 24 endoscopy results showed a subnormal pouch with a single superficial ulcer and sparse erythema.
• Clinical remission with negative CRP remained after 2 years of maintenance therapy 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 13 January 2025.