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This information is intended for US healthcare professionals to access current scientific information about J&J Innovative Medicine products. It is prepared by Medical Information and is not intended for promotional purposes, nor to provide medical advice.

STELARA® (ustekinumab)

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STELARA - Use in Adult Patients with Immune Checkpoint Inhibitor-Induced Colitis

Last Updated: 01/02/2025

SUMMARY

The company cannot recommend any practices, procedures, usage, or dosing that deviates from the approved labeling.
A retrospective study, several case reports, and a case series describing the use of STELARA in adult patients with immune checkpoint inhibitor (ICI)-induced colitis are summarized below.¹^-⁵

CLINICAL DATA

Retrospective Study

Thomas et al (2023)¹ conducted a 2-center, retrospective study to evaluate the efficacy of STELARA in treating ICI-mediated colitis (IMC) refractory to steroids, infliximab (IFX), and/or vedolizumab (VDZ).

Study Design/Methods

Patients who received STELARA for IMC refractory to steroids, IFX, and/or VDZ, and had clinical or endoscopic follow-up were included.
Endoscopic findings were categorized as ulcerative inflammation, nonulcerative inflammation, or normal appearance.
Clinical remission was defined as sustained resolution of diarrhea (graded per Common Terminology Criteria for Adverse Events [CTCAE] version 5) to grade 1 or lower.
Endoscopic remission was defined as Mayo endoscopic subscore of 0 or 1.

Results

A total of 19 patients were included, with the majority receiving programmed cell death protein-ligand 1 (PD-L1) ICI monotherapy (n=10) for stage IV cancer.
Sixteen patients experienced CTCAE grade 3-4 diarrhea, with 14 requiring hospitalization for IMC.
Twelve patients were refractory to IFX and 18 to VDZ, with 11 failing both treatments.
Endoscopic findings revealed that 8 patients showed high-risk features of ulcerative colonic inflammation, indicating a poor prognosis.
Clinical remission was achieved in 13 patients on STELARA treatment, with 12 receiving >1 dose.
Mean ± standard error of the mean (SEM) fecal calprotectin levels significantly decreased from 629.8±101.5 µg/mg to 92.0±21.7 µg/mg after STELARA treatment (P=0.0004).
Among the 11 patients with endoscopic follow-up, 64% achieved mucosal healing.
Endoscopic remission was achieved by 5 patients at the last follow-up.
No significant differences were observed between STELARA responders and nonresponders in terms of clinical/endoscopic findings of IMC or prior exposure to immunosuppression. See Table: Select Characteristics of STELARA Responders and Nonresponders.

Select Characteristics of STELARA Responders and Nonresponders¹

Characteristics	Responders (n=13)	Nonresponders (n=6)	P-Value
Median days from IMC to STELARA (IQR)	389 (287-583)	345.5 (161.25-757.75)	0.898
Peak calprotectin prior to STELARA, mean±SEM	627.8±119	635.8±223.6	0.976
Drop in calprotectin after treatment, mean±SEM	563±140.4	635±161.3	0.758
Colitis (grade ≥2), n (%)	8 (61.5)	5 (83.3)	0.605
Diarrhea (grade ≥2), n (%)	10 (76.9)	6 (100)	0.517
Endoscopic findings, n (%)
Normal	3 (23.2)	2 (33.3)	1.000
Nonulcerative	5 (38.4)	1 (16.7)
Ulcerative	5 (38.4)	3 (50)
Median days of steroid treatment (IQR)	34 (20-57.5)	48.5 (33-62.5)	0.412
Previous biologic treatment, n (%)
Single biologic agent	7 (53.8)	1 (16.7)	0.177
Two biologic agents	6 (46.2)	5 (83.3)	0.177
Abbreviations: IMC; immune checkpoint inhibitor-mediated colitis; IQR, interquartile range; SEM, standard error of the mean.

One patient developed severe sinus congestion/infection due to STELARA which resolved after treatment with antibiotics. STELARA was discontinued.

Case Reports and Case Series

Additional data are available through case reports/case series. See Table: Summary of the Use of STELARA in Patients with Immune Checkpoint Inhibitor-Induced Colitis.

Summary of the Use of STELARA in Patients with Immune Checkpoint Inhibitor-Induced Colitis²^-⁵

Author and Year	Patient Characteristics	Case Description
Case Reports
Del Nogal and Patel (2022)²	A 74-year-old male with a history of hypertension, hyperlipidemia, PsA, achalasia requiring multiple dilations, and stage IV anaplastic thyroid carcinoma, who presented to the ED after his ninth pembrolizumab infusion. The patient experienced abdominal pain, 10 bowel movements per day with blood and mucus, urgency, and a 20-pound weight loss in 2 months. He also had a history of Clostridium difficile infection treated with oral vancomycin. Esophagogastroduodenoscopy and colonoscopy were normal 2 years prior.	Laboratory findings revealed leukopenia (3.94x10³/µL), thrombocytopenia (143x10³/µL), and elevated fecal calprotectin levels (>2000 µg/mg). PCR for C. difficile and toxin was negative. Abdominal and pelvic CT scan showed diffuse proctocolitis, while sigmoidoscopic findings revealed diffuse severe inflammation marked by congestion (edema), erythema, friability, mucus, and pseudomembranes. Pathological findings confirmed severely active chronic colitis, leading to initiation of IV methylprednisolone 1-2 mg/kg/day and discontinuation of pembrolizumab due to severe colitis (CTCAE grade 4). Colon biopsies obtained during sigmoidoscopy revealed cytomegalovirus inclusion bodies, and serum testing revealed low-grade viremia, leading to treatment with ganciclovir. Due to the severity of colitis and inadequate response to steroids, IV IFX infusion and hydrocortisone enemas twice daily were initiated, followed by VDZ treatment with minimal improvement. Due to consistent inflammation upon repeat colonoscopies and persistent symptoms, he was started on STELARA IV followed by 90 mg SC and resumed steroid treatment. Clinical improvement of fecal urgency and frequency was observed along with a significant reduction in fecal calprotectin from >1000 to 314 µg/g after 8 weeks and further to 135 µg/g after 6 months. Colonoscopy after 6 months of STELARA treatment revealed a significant improvement in colitis, with only mildly erythematous mucosa in the descending and sigmoid colon and the presence of nonbleeding internal and external hemorrhoids. Resection of 7 polyps (<1 cm in size) in the sigmoid colon revealed mild chronic active colitis and inflammatory pseudopolyps with ulceration. The patient remained in clinical remission with a maintenance dose of 45 mg every 12 weeks.
Fernández-Gordón Sánchez et al (2022)³	A 56-year-old female with stage IV large cell lung cancer treated with pembrolizumab who developed diarrhea (>6 stools/day), requiring hospitalization.	Laboratory tests showed high fecal calprotectin level (2355 μg/g), negative coproculture, proctosigmoiditis on colonoscopy, and biopsy was consistent with IMC. The patient’s condition improved after initiating IV methylprednisolone. To taper high prednisone doses, immunosuppressive therapies like IFX, mycophenolate, or VDZ were considered. Due to hepatotoxicity risks with these drugs, since the patient also had cholestatic liver injury induced by pembrolizumab, STELARA 390 mg IV was initiated, followed by 90 mg SC 8 weeks later. Ursodexicolic acid (15 mg/kg daily) was added for cholestatic liver injury. The patient experienced normalization of the hepatic function along with improvement of colitis with clinical, radiological, and histological remission.
Amin and Wang (2021)⁴	A 68-year-old female with a history of stage IV small cell lung cancer, after chemoradiation, presented with CTCAE grade 3 diarrhea after 1 year of atezolizumab treatment.	Colonoscopy revealed normal mucosa with chronic active colitis. The patient’s diarrhea initially improved after steroid treatment, allowing resumption of atezolizumab. However, 9 months later, her diarrhea worsened, and repeat colonoscopy showed inflammation with severe chronic active colitis and ulceration. The patient was then started on steroids followed by VDZ infusion, and atezolizumab was discontinued. However, after a single dose, the patient experienced sinus congestion, leg swelling, and joint pain. STELARA was administered due to worsening symptoms and uncontrolled colitis; however, it led to similar adverse effects and STELARA was therefore discontinued. During this period, there was significant clinical and endoscopic improvement in diarrhea. A new metastasis was found after being off of atezolizumab for 3.5 months, which required surgical resection and resumption of ICI treatment. Due to her prior adverse effects with STELARA and vedolizumab, the patient was started on FMT which was well tolerated. She restarted atezolizumab and was reported to be diarrhea-free for 16 weeks with minimal inflammation per repeat colonoscopy.
Thomas et al (2021)⁵	Case 1: A 56-year-old male with stage III right axillary malignant melanoma who had undergone surgical resection, adjuvant radiation, and nivolumab therapy and then developed CTCAE grade 3 diarrhea.	The patient was discontinued from nivolumab therapy due to grade 3 diarrhea. Colonoscopy and biopsy revealed lymphocytic colitis. Clinical remission was achieved after 3 VDZ infusions; however, colitis relapsed and did not respond to glucocorticoids or additional VDZ. Subsequently, the patient was started on STELARA treatment. After receiving induction and 3 maintenance doses, the patient achieved clinical remission from IMC and was cancer-free.
Thomas et al (2021)⁵	Case 2: A 61-year-old female with stage IV left midback melanoma and subsequent metastases to the lungs, breast, and peritoneum was managed with ipilimumab, resulting in CTCAE grade 3 diarrhea.	Immunotherapy was discontinued due to immune-mediated hepatitis. Colonoscopy with biopsy revealed histologic inflammation. Clinical remission was achieved after treatment with VDZ and glucocorticoids. Upon resuming ipilimumab therapy, IMC recurred and did not respond to glucocorticoids, IFX, or VDZ. Subsequently, treatment with STELARA was initiated, resulting in clinical, endoscopic, and histologic remission. The patient completed all cycles of immunotherapy and the cancer remained stable.
Abbreviations: CT, computed tomography; CTCAE, Common Terminology Criteria for Adverse Events; ED, emergency department; FMT, fecal microbiota transplant; ICI, immune checkpoint inhibitor; IFX, infliximab; IMC, immune-mediated colitis; IV, intravenous; PCR, polymerase chain reaction; PD-1, programmed cell death protein 1; PsA, psoriatic arthritis; q4w, every 4 weeks; q8w, every 8 weeks; SC, subcutaneous; TNF, tumor necrosis factor; VDZ, vedolizumab.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 15 April 2024.

References

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1	Shirwaikar Thomas A, Lee SE, Shatila M, et al. IL12/23 blockade for refractory immune-mediated colitis: 2-center experience. Am J Gastroenterol. 2023;118(9):1679-1683.
2	Del Nogal GP, Patel N. Refractory checkpoint inhibitor colitis responsive to ustekinumab. ACG Case Rep J. 2022;9(12):e00946.
3	Fernández-Gordón Sánchez FM, Gómez-Domínguez E, Paredes Ruiz D, et al. Ustekinumab for corticodependent immune-mediated colitis by pembrolizumab, an alternative for patients with concomitant liver injury. Rev Esp Enferm Dig. 2022;114(6):356-357.
4	Amin R, Wang Y. Sustained remission of fecal transplant-treated colitis after immune checkpoint inhibitor resumption [abstract]. Am J Gastroenterol. 2021;116:S774-S775. Abstract S1746.
5	Thomas AS, Ma W, Wang Y. Ustekinumab for refractory colitis associated with immune checkpoint inhibitors. N Engl J Med. 2021;384(6):581-583.