Summary

• Data from observational studies, retrospective studies, and a registry-based study in patients with ulcerative colitis (UC) are summarized below.^1-18

CLINICAL DATA

Observational Studies

Iborra et al (2023)¹ evaluated the short- and long-term effectiveness and safety of STELARA in an open-label cohort of Spanish patients with active UC who were refractory to multiple lines of treatment (conventional and/or advanced therapies).

Study Design/Methods

• Adult patients who received at least 1 STELARA intravenous (IV) infusion (6 mg/kg) were included.
• Symptomatic response was evaluated using the partial Mayo (pMayo) score (including Mayo stool frequency and Mayo rectal bleeding subscores) and objective response using C-reactive protein (CRP) and fecal calprotectin (FC) levels.
• Disease activity was assessed at weeks 8, 16, 24, and 52 and at months 18 and 24 when data was available.
  • Clinical remission was defined as a pMayo score of ≤2, including a combined rectal bleeding and stool frequency subscore of ≤1.
  • Clinical response was defined as a decrease in the pMayo score of ≥3 and ≥30% from baseline, with either a decrease in rectal bleeding subscore of ≥1 or an absolute rectal bleeding subscore of 0 or 1.
  • Corticosteroid-free remission (CSFR) was defined as achieving clinical remission with the complete withdrawal of systemic corticosteroids.
  • FC and CRP levels were considered normalized when they were <250 µg/g and <5 mg/L, respectively.
  • Endoscopy findings were graded per the Mayo endoscopic subscore as normal, mild, moderate, or severe. Endoscopic improvement was defined as a Mayo endoscopic subscore of 0 or 1, encompassing both endoscopic remission (Mayo endoscopic score [MES] 0) and mildly active disease (MES 1).

Results

Patient Characteristics

• A total of 108 patients with UC who received the first weight-based IV dose of STELARA 6 mg/kg were included in the study.
  • Of these patients, only 2 (1.9%) were not exposed to any biologic or novel small molecules.
  • Prior treatment history included: anti-tumor necrosis factor (TNF)-α agent in 26 (24.1%) patients; vedolizumab (VDZ) in 3 (2.8%); anti-TNF-α and tofacitinib in 5 (4.6%); anti-TNF-α and VDZ in 45 (41.7%); anti-TNF-α, VDZ, and tofacitinib/upadacitinib in 26 (24%); and VDZ and tofacitinib in 1 (0.9%) patients.
• The median follow-up duration was 57.7 weeks.

Efficacy

• At weeks 8, 16, 24, and 52, clinical remission was achieved in 59%, 56.5%, 57%, and 69% of patients and clinical response was observed in 43%, 52%, 54%, and 57%, respectively.
  • Long-term clinical remission was maintained in 28/43 (65%) and 20/25 (80%) patients who achieved remission at 18 and 24 months, respectively.
• Of the 24 patients who received immunomodulators at baseline, 9 discontinued them.
• Among the 44 patients on corticosteroids at baseline, 34 (77%) discontinued them within a median of 11.6 weeks (interquartile range [IQR], 7-25) and 13 (29.5%) achieved CSFR at week 16.
• At weeks 8, 16, 24, and 52, CRP levels were normalized in 77%, 82%, 80%, and 76.5% of patients, whereas FC levels were normalized in 40%, 38%, 41%, and 51%, respectively.
• Long-term CRP and FC normalizations were observed in 72.5% and 61% of patients at 18 months and 70% and 58% at 24 months, respectively.
  • Normalization of FC levels was positively associated with secondary vs primary failure to previous anti-TNF therapy (P=0.014), whereas normalization of CRP levels was associated with a lower number of previous biologic treatments (P=0.025).
• Among the 29 patients who underwent endoscopy during follow-up (a median of 38.5 weeks), endoscopic improvement was observed in 15 (52%) patients, with endoscopic remission in 8 (28%).
• Among the 17 patients who had an endoscopy at the start and during follow-up, endoscopic improvement was noted in 9 (53%) patients after a median treatment duration of 53 weeks (IQR, 31-61).

Safety

• Overall, 20 (18.5%) patients required hospitalization during treatment, with 8 hospitalized at the beginning of treatment due to severe flare, and 10 (9.3%) required colectomy.
• Through the last follow-up, 5 adverse events (AEs) occurred in 5 (4.6%) patients.
  • Treatment was not interrupted due to minor AEs (asthenia, arthralgia, and C. difficile infection).
  • Two serious adverse events (SAEs) (relapsed uveitis and venous thromboembolism [VTE]) were reported, which led to STELARA treatment discontinuation.
• STELARA was discontinued in 23 (21%) patients (due to primary failure, n=9; loss of response, n=4; AEs, n=2; partial response with subsequent colectomy, n=8).

Mínguez Sabater et al (2022)² evaluated the effectiveness and safety of STELARA in patients with UC up to 1 year through an observational study.

Study Design/Methods

• Patients received weight-based STELARA infusion (~6 mg/kg) at week 0 and then 90 mg subcutaneously (SC) at week 8, followed by 90 mg SC every 8 weeks (q8w) or every 12 weeks (q12w) for maintenance, with a follow-up at 1 year.

Results

• All patients (N=23) included in the study had prior exposure to biologics.
  • Of these patients, 52% had prior exposure to ≥2 anti-TNF agents, 65% to VDZ, and 30% to Janus kinase (JAK) inhibitors.
• At baseline, the median pMayo score was 5 (IQR, 3-7), median CRP was 8.1 mg/L (IQR, 4.1-29.7), and median FC was 2276 µg/g (IQR, 1641-3569).
• Clinical remission, defined as a pMayo score of ≤2, was achieved in 61%, 58%, 56%, and 79% of patients after 8, 16, 24, and 52 weeks, respectively.
• Normalized CRP levels (<5 mg/L) were achieved in 76%, 93%, and 80% of patients after 8, 24, and 52 weeks, respectively.
• Normalized FC levels (<150 µg/g) were achieved in 35%, 31%, and 40% of patients after 8, 24, and 52 weeks, respectively.
• Among the 6 patients who underwent endoscopy before and after STELARA treatment, 5 had a Mayo endoscopy subscore of ≤1.
• Treatment persistence rate at 6 and 12 months was 83% and 79%, respectively.
• The standard dose of STELARA was maintained in 12 (52%) patients, and the dose was adjusted in 13 (56%) patients (reinduction and dose escalation).
• During follow-up, 2 AEs were reported (1 hospitalization and 1 colectomy).

Retrospective Studies

Fumery et al (2024)³ evaluated the effectiveness of STELARA vs VDZ in patients with UC.

Study Design/Methods

• Adult patients (age ≥18 years) with symptomatic UC (pMayo score >2) and prior exposure to at least 1 anti-TNF agent (eg, infliximab, adalimumab, or golimumab) were included in the study.
• Patients received STELARA weight-based IV induction dose (6 mg/kg), followed by SC maintenance therapy of 90 mg q8w or q12w. STELARA dose intensification to 90 mg every 4 weeks (q4w) or q8w was permitted for patients with an insufficient response or a loss of response. VDZ induction consisted of an IV infusion of 300 mg at weeks 0, 2, and 6, with an optional additional infusion administered at week 10 per the physician's judgment. The maintenance interval for VDZ was determined by the physician (either q4w or q8w). No patients received SC VDZ injections during the study.
• The primary endpoint was CSFR at week 16, defined as a pMayo score of ≤2.
• Secondary endpoints included endoscopic remission (defined as a combination of CSFR and an endoscopic Mayo score of ≤1) and histological remission (defined as a combination of CSFR, an endoscopic Mayo score of ≤1, and a Nancy index of ≤1) at week 16.

Results

Efficacy

• A total of 316 patients were included in the study (STELARA, n=142; VDZ, n=151).
• The median (IQR) disease duration was significantly higher in the STELARA group than in the VDZ group (9.3 [3-12] vs 7.2 [2-9] years; P=0.003). A significantly higher proportion of patients in the STELARA group than that in the VDZ group had prior exposure to more than 2 biologics (46.4% vs 6%; P<0.0001), including primary failure with least 1 biologic (58.8% vs 41.7%; P=0.002), and prior exposure to tofacitinib (26.7% vs 3.3%; P<0.001). Among patients treated with STELARA, 69.7% had previously been exposed to VDZ.
• The CSFR rate for STELARA at week 16 was 45.1% (n=64/142). At week 16, 8 (5.6%) patients required colectomy.
• In univariate analysis, female sex (P=0.046), failure with ≥3 biologics (P=0.016), and primary failure with at least 1 biologic/small-molecule therapy (P=0.017) were associated with a reduced CSFR rate at week 16 for STELARA. In multivariable analysis, primary failure with at least 1 biologic/small-molecule therapy (odds ratio [OR], 0.31; 95% CI, 0.11-0.82; P=0.018) was significantly associated with a reduced CSFR rate at week 16 for STELARA.
• No significant differences in the pMayo score (P=0.71) and CRP level at baseline (P=0.14) were observed between patients treated with STELARA and those treated with VDZ.
• After inverse probability of treatment weighting (IPTW) adjustment, there was no difference observed between STELARA and VDZ with regard to CSFR using propensity score analyses, see Table: Steroid-Free Clinical Remission at Week 16.

• STELARA was more effective than VDZ in achieving endoscopic remission and histo-endoscopic remission based on propensity score analyses.
• For endoscopic remission and histo-endoscopic remission at week 16, see Table: Endoscopic Remission and Histo-Endoscopic Remission at Week 16.

• For treatment discontinuation between STELARA and VDZ using propensity score analyses, see Table: Treatment Discontinuation.

• The likelihood of drug retention was not significantly different between VDZ and STELARA among patients achieving CSFR at week 16 (HR [95%CI], 1.24 [0.48-3.22]; P=0.65). At the end of follow-up, 6 (4.0%) and 8 (5.6%) patients treated with VDZ and STELARA, respectively, required colectomy.

Safety

• For safety outcomes during follow-up, see Table: Safety Events with STELARA and VDZ Treatments.

Tursi et al (2024)⁴ evaluated the safety and effectiveness of STELARA in a real-world, multicenter, retrospective, observational, cohort study of patients with UC who failed treatment with standard or biological therapies or tofacitinib.

Study Design/Methods

• The study included patients with UC aged ≥18 years. During the induction phase, all patients received weight-based IV induction dose: 260 mg for <55 kg, 390 mg for 55-85 kg, and 520 mg for >85 kg. After IV induction, patients received STELARA 90 mg SC q8w as maintenance therapy.
• The primary outcome was clinical remission at weeks 8 and 24.
  • Clinical remission was defined as a pMayo score of ≤1.
• The coprimary outcome was the safety of STELARA.
• Secondary outcomes included: the clinical response at weeks 8 and 24 (defined as a ≥2-point reduction in the pMayo score from baseline), CSFR at weeks 8 and 24, mucosal healing at week 24 (defined as Mayo endoscopic subscore of ≤1), endoscopic response at week 24 (defined as ≥1 point change from baseline in endoscopic score). The surgery rate during follow-up was also recorded. Variations in CRP, FC, and the pMayo score during follow-up were analyzed, including short-term changes between 0 and 8 weeks based on the number of prior biologic therapies. Clinical response during follow-up was also monitored.

Results

Patient Characteristics

• A total of 256 patients were included.
  • The median (IQR) age of the patients was 52 (36-65) years.
  • The median (IQR) disease duration was 9.5 (5-16.75) years.
  • The majority of the patients (n=237; 92.6%) had prior exposure to biologics, with the primary reason for initiating STELARA therapy being a secondary loss of response to previous biologics or small-molecule treatments (n=108; 42.2%). Additionally, most patients had been treated with anti-TNF agents (golimumab, n=20 [7.8%]; adalimumab, n=84 [32.8%]; infliximab, n=161 [62.9%]; VDZ, n=139 [54.3%]; and tofacitinib, n=24 [9.4%]). Previous use of conventional medications included mesalazine (n=254; 99.2%), steroids (n=245; 95.7%), thiopurines (n=81; 31.6%), and methotrexate (n=11; 4.3%).

Efficacy

• For the clinical effectiveness of STELARA at weeks 8 and 24, see Table: Clinical and Endoscopic Outcomes of STELARA.

• Both CRP (P<0.0001) and FC (P<0.0001) decreased significantly in the first 8 weeks from baseline. FC decreased gradually from week 8 to week 12 (P=0.0004) and from week 12 to week 24 (P=0.038), after which it stabilized, with median values remaining within the 200 μg/g threshold for the rest of the follow-up period.
• A significant decrease in endoscopic severity scores was observed over the 24-week follow-up (P=0.000003).
• For clinical remission and clinical response rates as well as mucosal healing and endoscopic outcomes at 8 and 24 weeks per the number of prior biologics, see Table: Clinical Remission, Clinical Response, Mucosal Healing, and Endoscopic Outcomes at Weeks 8 and 24 Per Prior Biologic Exposure.

Safety

• AEs occurred in 6 patients (2.34%).
• Two patients experienced a cytomegalovirus (CMV) infection (8-week follow-up, n=1; 24-week follow-up, n=1); furthermore, 1 patient developed itching, 2 patients contracted a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and 1 patient developed cystitis.
• One patient died due to severe coronavirus disease 2019 (COVID-19) pneumonia at 24 weeks.
• Dose optimization was implemented in 5 patients at 12 weeks and 1 patient at 24 weeks.
• Four patients underwent colectomy (n=1, 12 weeks; n=2, 24 weeks; and n=1, 48 weeks).

Alrashed et al (2023)⁵ evaluated the effectiveness of STELARA and VDZ in a real-life cohort of patients with UC and Crohn’s disease who had failed to respond to an anti-TNF agent in a retrospective, observational study (enroll-ex study).

Study Design/Methods

• Patients with moderate to severe UC were defined as those with a clinical Mayo score of 6-12 and an endoscopic subscore of 2-3.
• The primary endpoints were the proportion of patients with mucosal healing, hospitalization, surgery, and steroid courses received at week 52 in those who had prior biologic exposure.
  • In patients with UC, mucosal healing was defined as an endoscopic Mayo score of 0 or 1.
  • The number of patients with surgeries was defined as those who underwent IBD-related surgery ≥6 weeks after initiating VDZ or STELARA.
  • The number of patients with hospitalizations was defined as those hospitalized for ≥6 weeks for IBD-related complications after initiating VDZ or STELARA.

Results

• A total of 77 patients had UC, with a mean age of 33.9 years.
  • Of these patients, 42 (54.5%) and 35 (45.5%) had prior exposure to infliximab and adalimumab, respectively.
  • Among patients who failed prior anti-TNF therapy, 44 (57.1%) received STELARA and 33 (42.8%) received VDZ.
• Among patients who received STELARA and VDZ, 86% and 81% were not hospitalized, 93% and 91% had no surgery, 70% and 51% were in CSFR, and 57% and 53% achieved mucosal healing, respectively.
• Three patients receiving STELARA and 3 receiving VDZ had a colectomy followed by ileal pouch anal anastomosis, respectively.

Buisson et al (2023)⁶ evaluated the effectiveness of STELARA vs tofacitinib in patients with UC who had prior exposure to ≥1 anti-TNF therapy in the TORUS study.

Study Design/Methods

• Adult patients with UC (pMayo score of >2) treated with STELARA or tofacitinib were included.
• The primary endpoint was CSFR (pMayo score ≤2) at week 16. The secondary endpoints were endoscopic remission (CSFR and MES ≤1) and histologic remission (CSFR, MES ≤1, and Nancy index ≤1).

Results

Efficacy

• A total of 289 patients were included (STELARA, n=165; tofacitinib, n=124).
• At week 16, based on the propensity score analysis for STELARA vs tofacitinib, CSFR rate was 35.6% vs 37.8% (P=0.75), endoscopic remission rate was 11.7% vs 17.0% (P=0.47), and histological remission rate was 7.8% vs 4.4% (P=0.32), respectively.
• At week 16, among patients who had failed ≥1 prior biologics, CSFR rate was 25.9% in the STELARA group and 46.3% in the tofacitinib group (P=0.13).
• At week 16, CSFR rates were comparable between the STELARA and tofacitinib groups (41.5% vs 40.6%) for patients with more severe UC (pMayo score of ≥6) and with CRP levels of >30 mg/L (33.0% vs 27.2%).
• Factors associated with the absence of CSFR at week 16 in patients receiving STELARA included male sex (P=0.035), having ≥3 prior biologics (P=0.013), prior use of tofacitinib (P=0.03), and primary failure to ≥1 biologics (P=0.013).

Dalal et al (2024)⁷ assessed the effectiveness of STELARA compared to tofacitinib in adult patients with UC up to 1 year after prior anti-TNF failure in a retrospective cohort study.

Study Design/Methods

• The primary outcome was CSFR at weeks 12 and 52 (±4) after drug initiation. The secondary outcome was drug survival.
  • CSFR was defined as a Simple Clinical Colitis Activity Index (SCCAI) of <2 without the use of oral or IV corticosteroids ≤30 days preceding the clinical assessment.
  • Drug survival was defined as the time to drug discontinuation due to nonresponse, including colectomy for refractory disease, throughout the follow-up period.

Results

Efficacy

• A total of 166 patients were included (STELARA, n=97; tofacitinib, n=69), with a median follow-up of 88.0 weeks.
• In an unadjusted analysis, when comparing STELARA vs tofacitinib, CSFR was achieved in 31/96 (32%) vs 36/68 (53%) patients (P<0.01) at week 12 and 44/90 (49%) vs 37/66 (56%) patients (P=0.38) at week 52, respectively. However, after the IPTW was performed, there was no significant difference in CSFR between the STELARA and tofacitinib groups at week 12 (OR, 1.65; 95% CI, 0.79-3.41), or at week 52 (OR, 1.14; 95% CI, 0.55-2.34).
• After IPTW, there was no significant difference in drug survival related to nonresponse (adjusted HR, 1.37; 95% CI, 0.78-2.37) between STELARA vs tofacitinib.
• Treatment was discontinued by 38/97 (39%) patients in the STELARA group (nonresponse, 90%; dysplasia, 8%; AEs, 3%) and 30/69 (43%) patients in the tofacitinib group (nonresponse, 83%; dysplasia, 7%; AEs, 3%; insurance coverage, 3%; self-discontinuation, 3%).

Safety

• A total of 10 AEs were reported in 8 patients on STELARA (bronchiolitis obliterans, C. difficile infection, arthralgia [n=2], nausea, rash [n=2], deep vein thrombosis, ruptured appendicitis, and miscarriage).
• A total of 17 AEs were reported in 14 patients on tofacitinib (shingles [n=4], possible miscarriage [n=2], groin abscess, elevated liver enzymes [n=2], deep vein thrombosis [n=2], norovirus infection, lymphopenia, pneumonia, recurrent C. difficile infection, SARS-CoV-2 infection, and heart block).
• Treatment was discontinued by 1 patient in both the STELARA (due to nausea with arthralgia) and tofacitinib (due to elevated liver enzymes) groups because of an AE. No deaths were reported.

Kochhar et al (2023)⁸ evaluated the real-world efficacy of VDZ, STELARA, and tofacitinib as second-line therapies in patients with UC who had prior exposure to a TNF inhibitor in a propensity-matched, retrospective cohort study.

Study Design/Methods

• The primary outcome was the risk of a composite outcome of hospitalization requiring IV steroid use, and colectomy within 2 years, among different second-line biologic or small-molecule therapies.
• The secondary outcomes included the risk of oral steroid use and the proportion of patients with a change in therapy (defined as those requiring therapy with a different mechanism of action from second-line treatment) within 2 years for those initiated on second-line biologic or small-molecule therapies. Additionally, the 2-year risk of composite outcomes, including hospitalization requiring IV steroids and colectomy, were assessed in patients who were switched to VDZ, STELARA, or tofacitinib after exposure to 2 TNF inhibitors.

Results

Efficacy

• A total of 2141 TNF inhibitor-exposed patients were included, of whom 348 (16.2%), 1077 (50.3%), and 716 (33.4%) were switched to tofacitinib, VDZ, and STELARA as second-line therapy, respectively.
• After propensity score matching, there was no difference in the risk of a composite outcome of IV steroid use and colectomy between the STELARA and tofacitinib cohorts (adjusted OR, 1.29; 95% CI, 0.89-1.86). However, the VDZ cohort had a higher risk of a composite outcome of IV steroid use and colectomy vs the STELARA cohort (adjusted OR, 1.67; 95% CI, 1.29-2.16).
  • The tofacitinib cohort showed a higher risk of colectomy (adjusted OR, 2.63; 95% CI, 1.24-5.58) vs the STELARA cohort; however, there was no difference in the risk of oral steroid use between the 2 cohorts (adjusted OR, 1.11; 95% CI, 0.80-1.53).
  • The VDZ cohort showed a higher risk of IV steroid use vs the STELARA cohort (adjusted OR, 1.60; 95% CI, 1.23-2.07); however, there was no difference in the risk of colectomy (adjusted OR, 1.72; 95% CI, 0.78-3.79) and oral steroid use (adjusted OR, 1.14; 95% CI, 0.90-1.44) between the 2 cohorts.
• After propensity score matching, the tofacitinib cohort showed a higher risk of change in therapy vs the STELARA cohort (adjusted OR, 2.38; 95% CI, 1.48-3.92); however, there was no difference between the STELARA and VDZ cohorts (adjusted OR, 1.45; 95% CI, 0.95-2.19).
• Of the 508 (23.7%) patients exposed to 2 TNF inhibitors, 51 (11%) were switched to tofacitinib, 229 (45%) to VDZ, and 228 (44%) to STELARA as second-line therapy.
  • In patients with UC who were exposed to 2 TNF inhibitors, there was no difference in the risk of a composite outcome of IV steroid use and colectomy between the tofacitinib and STELARA cohorts (adjusted OR, 1.25; 95% CI, 0.49-3.17) and between the VDZ and STELARA cohorts (adjusted OR, 1.19; 95% CI, 0.74-1.92).

Safety

• After propensity score matching, there was no difference in the risk of MACE (adjusted OR, 0.98; 95% CI, 0.40-2.39), malignancy (adjusted OR, 0.77; 95% CI, 0.32-1.81), VTE (adjusted OR, 0.92; 95% CI, 0.37-2.25), or opportunistic infections (adjusted OR, 1.21; 95% CI, 0.60-2.46) between the tofacitinib and STELARA cohorts.
• After propensity score matching, there was no difference in the risk of MACE (adjusted OR, 1.31; 95% CI, 0.57-3.01), malignancy (adjusted OR, 1.46; 95% CI, 0.69-3.09), VTE (adjusted OR, 0.96; 95% CI, 0.39-2.33), or opportunistic infections (adjusted OR, 1.61; 95% CI, 0.96-2.70) between the VDZ and STELARA cohorts.

Sabhan et al (2023)⁹ reported long-term real-world data of STELARA in patients with UC in a retrospective study, the Stockholm STELARA study (STOCUSTE).

• The primary outcomes were remission (PGA=0) and response (decrease in PGA ≥1 from baseline) at 3 and 12 months, respectively.
• Overall, 96 patients were included, with 94 exposed to anti-TNF therapy. Among them, 94 (98%), 59 (61%), and 34 (35%) patients failed ≥1, ≥2, and ≥3 anti-TNF therapies, respectively.
• At baseline, 48 (50%) patients were on oral or topical corticosteroids and 13 (14%) were on thiopurines.
• At 12 months, 9% of patients were on oral or topical corticosteroids.
• Among patients who were treated with STELARA, 9/71 (6%) were in remission at 3 months and 26/33 (78%) were in remission at 12 months.
• Treatment was discontinued by 36 (38%) patients during the first 12 months due to following reasons:
  • Persistent disease activity, 20%; AEs, 8%; bowel surgery, 2%; and lost to follow-up, 2%.

Galatowitsch et al (2022)¹⁰ evaluated the clinical effectiveness of STELARA vs tofacitinib in patients with UC who had prior biologic exposure in a retrospective, observational study.

• The primary outcome was the proportion of patients in clinical remission (pMayo score ≤3) at 12 months.
• A total of 60 patients who had failed prior biologic therapy (anti-TNF or VDZ) were included (STELARA, n=30; tofacitinib, n=30).
• A summary of prior biologic failure across treatment groups (STELARA vs tofacitinib) are summarized below:
  • Failed 1 biologic: 53.3% vs 20%
  • Failed 2 biologics: 36.7% vs 46.7%
  • Failed 3+ biologics: 10% vs 33.3%
  • Failed TNF inhibitor: 76.7% vs 96.7%
  • Failed VDZ: 63.3% vs 73.3%
• At 12 months, clinical remission was observed in 66.7% of patients in the STELARA group vs 56.7% of patients in the tofacitinib group (P=0.60). The rate for CFSR was 56.7% vs 43.3% (P=0.44), respectively.
• AEs were reported as rare in both groups.

Ando et al (2022)¹¹ evaluated the effectiveness of STELARA in patients with UC in a Japan-based multicenter, retrospective, observational study (Phoenix cohort study group).

• Clinical response was defined as clinical remission (pMayo score of ≤2) plus clinical improvement (a decrease in pMayo score of 3 points and ≥30%).
• Among the 132 patients enrolled in the study, 50 (37.9%) were bio-naïve, and 74 (56.1%) and 37 (28.0%) had been exposed to anti-TNF agents and VDZ, respectively.
  • Prior exposure to 0, 1, 2, 3, 4, and 5 biologics was observed in 51, 31, 35, 10, 4, and 2 patients, respectively.
• For the clinical outcomes based on prior biologic usage status, see Table: Clinical Outcomes of STELARA Based on Prior Biologic Usage Status.

• For the clinical outcomes at week 8 per prior usage of anti-TNF therapy or VDZ, see Table: Clinical Outcomes of STELARA at Week 8 per Prior Usage of Anti-TNF Therapy or Vedolizumab.

• The cumulative persistence rate of STELARA at 6 months and 1 year was 91.7% and 88.6%, respectively.
• AEs were reported in 7 (9.3%) cases (1 case each of pulmonary embolism, arthritis, paranasal sinusitis and COVID-19, fatigue and headache, herpes zoster, infectious colitis, and CMV colitis).

Honap et al (2022)¹² evaluated the effectiveness and safety of STELARA in patients with UC in a multicenter, retrospective, observational cohort study.

Study Design/Methods

• STELARA was administered at a dosage of approximately 6 mg/kg IV followed by 90 mg SC at week 8 and then q8w to q12w per clinical assessment (escalated to q4w in a few patients).
• The primary endpoints were CSFR rates at weeks 16 and 26. The secondary endpoints were clinical response and remission, and endoscopic response and remission at weeks 8, 16, and 26.
• CSFR was defined as remission without the use of steroid at the time, irrespective of steroid use at baseline.
  • Clinical response was defined as a decrease in the SCCAI score by ≥3 points and clinical remission as an SCCAI score of ≤2.
  • Endoscopic response was defined as any improvement in MES or Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and endoscopic remission as MES ≤1 or UCEIS ≤1.

Results

Efficacy

• Among the 110 patients included in the study, 106 (96%) had prior exposure to a biologic or tofacitinib and 4 (4%) were bio-naïve.
  • Prior exposure to ≥1 anti-TNF agent was observed in 71 (65%) patients, ≥2 anti-TNF agents in 21 (19%), VDZ in 59 (54%), and both anti-TNF and VDZ in 36 (33%).
• For treatment outcomes, see Table: Clinical and Endoscopic Outcomes.

• For changes in biochemical parameters at weeks 8, 16, and 26 vs baseline, see Table: Changes from Baseline in Biochemical Parameters at Weeks 8, 16, and 26.

• Over a median follow-up duration of 28 weeks (IQR, 17-47), 17 (15%) patients discontinued treatment. The reasons for discontinuation of STELARA were PNR (n=4), loss of response (n=9), AEs (n=3), and family planning (n=1).
• The probability of STELARA treatment persistence at weeks 8, 16, 26, and 52 was 97.1%, 94.9%, 89.8%, and 76.4%, respectively.
  • On univariate analyses, prior advanced therapy failures, except exposure to only anti-TNF agents, were associated with STELARA discontinuation. However, on multivariate analysis, prior advanced therapy failures were not associated with STELARA treatment discontinuation.

Safety

• AEs were reported in 20 (18%) patients. The most common AEs were worsening diarrhea (n=7) and arthralgia (n=3). Treatment discontinuation due to AEs occurred in 3 patients (nonanaphylactic infusion reaction, n=1; urticarial rash, n=1; marked inflammatory demyelinating polyneuropathy, n=1).
• SAEs were reported in 13 (12%) patients. The most common SAE was hospitalization due to disease progression (n=9; 7 patients required colectomy, and 2 patients required IV corticosteroid administration and STELARA dose escalation).

Chiappetta et al (2021)¹³ assessed the effectiveness, safety, and treatment persistence of STELARA in patients with moderate to severe refractory UC in a multicenter, retrospective study.

Study Design/Methods

• STELARA was administered at a weight-based dosage IV (<55 kg, 260 mg; 55 kg-85 kg, 390 mg; and >85 kg, 520 mg) and then 90 mg SC at week 8, followed by maintenance dosage of 90 mg SC q8w or q12w per the treating physician’s discretion.
• The primary outcome was CSFR at weeks 24 and 52, defined as the pMayo score of <2 without the use of steroids.
• The secondary outcomes were clinical response (defined as a decrease from baseline in pMayo score of ≥3 points), decrease in concomitant steroid use, decrease in the number of patients with elevated CRP at baseline during follow-up, and mucosal healing (endoscopic Mayo score of 0 points).

Results

• Among the 68 patients included in the study, 66 (97%) had prior exposure to ≥1 biologic (anti-TNF agents, n=19 [29%]; VDZ, n=1 [2%]; VDZ and 1 anti-TNF agent, n=18 [27%]; VDZ and 2 anti-TNF agents, n=27 [41%]; and VDZ and 3 anti-TNF agents, n=3 [5%]).
• For the primary and secondary outcome measures, see Table: Treatment Outcomes at Weeks 8, 24, and 52.

• Endoscopy data was available for all patients at baseline, and the median endoscopic Mayo score was 3 (range, 2-3).
  • Among 18 (47.4%) patients who continued STELARA treatment through week 52 with available endoscopy data, 11 showed endoscopic improvement, including 4 who achieved mucosal healing.

Safety

• STELARA discontinuation was observed in 9 patients (primary failure, n=1; secondary failure, n=7; and AEs, n=1). Probability of STELARA treatment persistence was 87% (95% CI, 11.4-12.1).
• Pituitary adenoma was reported in a patient after 12 months of STELARA therapy.

Dalal et al (2021)¹⁴ evaluated the baseline predictors of colectomy-free drug survival in patients with UC who received STELARA therapy in a multicenter, retrospective cohort study.

• The primary outcome was STELARA treatment failure, which was determined by colectomy-free drug survival (defined as the time from STELARA initiation to discontinuation or colectomy due to uncontrolled disease).
• The secondary outcomes included clinical response at weeks 12-16 (defined as a decrease from baseline in the SCCAI score by ≥2 points), corticosteroid-free response, and loss of response requiring STELARA dose intensification.
• Among the 108 patients who initiated STELARA therapy, 99 (91.7%) had prior exposure to anti-TNF agents, 43 (39.8%) had prior exposure to >2 biologics, and 72 (66.7%) had prior exposure to anti-integrin agents.
• STELARA treatment failure was observed in 27/108 (25%) patients after a median duration of 175 days (IQR, 88-270).
• Based on the multivariable Cox regression analysis, there was a significant association between STELARA treatment failure and prior exposure to >2 biologics (HR, 2.22; 95% CI, 1.00-4.97; P<0.05).
• Clinical response at weeks 12-16 was achieved in 64/98 (65.3%) patients and corticosteroid-free response in 43/98 (43.9%) patients.
• Dose intensification from q8w to q4-6w was needed in 39/108 (36.1%) patients after a median duration of 89 days (IQR, 49-182) since STELARA initiation.

Ecker et al (2021)¹⁵ assessed the clinical response to STELARA in patients with UC in a retrospective study.

• Disease activity was assessed using the Mayo subscore (0-9 points) and the endoscopic Mayo subscore (0-3) before STELARA initiation. FC was also analyzed by taking the mean of 2 FC levels before and after initiation of therapy.
• Among the 26 patients included in the analysis, 69%, 19%, and 8% had prior exposure to 1, 2, and 3 anti-TNF agents, respectively; 4% of patients were anti-TNF-naïve. Additionally, 65.4% of patients had a prior history of treatment with VDZ.
• Eleven weeks (IQR, 7) after STELARA initiation, the FC levels decreased by an average of 58.4% (n=14).
• At the first patient contact in the outpatient clinic (n=17), the clinical Mayo subscore decreased from 6 points at baseline to 3 points.
  • The clinical Mayo subscore decreased by ≥3 points in 76.5% of patients.
• No cases of drug discontinuation due to SAEs were reported.
• Drug discontinuation was observed in 3 patients (2 patients switched treatment due to lack of response and 1 underwent colectomy for colorectal cancer). One patient who had a colonic reactivation of CMV continued STELARA maintenance therapy.

Fumery et al (2021)¹⁶ evaluated the long-term effectiveness and safety of STELARA maintenance therapy in a retrospective study in patients with UC from the Groupe d’Étude Thérapeutique des Affections Inflammatoires du Tube Digestif (GETAID).

Study Design/Methods

• STELARA was administered at a dosage of 6 mg/kg IV at week 0 followed by 90 mg SC q8-12w at the investigator’s discretion.
• The primary outcome measure was CSFR at 12 months.
• Clinical remission was defined as a pMayo score of ≤2, including stool frequency, rectal bleeding, and PGA subscores, with a combined stool frequency and rectal bleeding subscore of ≤1. The secondary outcomes measures included STELARA therapy persistence, dose intensification, Mayo endoscopic subscore and UCEIS, and colectomy.

Results

Efficacy

• Prior exposure to anti-TNF agents was observed in 102 (99%) patients (1 anti-TNF agent, n=30 [29.1%]; ≥2 anti-TNF agents, n=72 [69.9%]) and VDZ in 88 (85.4%) patients.
• A total of 103 patients who received at least 1 dose of STELARA and were included in the study.
• For the primary and secondary outcome measures, see Table: Outcome Measures at Weeks 26 and 52.

• Median CRP levels were 3.0 mg/L (IQR, 1.5-7.8) at week 26 and 2.5 mg/L
  (IQR, 1.0-7.0) at week 52 vs 7.1 mg/L (IQR, 3.1-15.0) at baseline (P=0.04).
• During follow-up, 65 patients (63.1%) were optimized to the STELARA 90 mg SC q4w injection regimen, including 6 patients who were again de-escalated to the q8w regimen.
  • After optimization to the q4w regimen, clinical response and remission were achieved in 20 (30.7%) and 17 (26.1%) patients, respectively.
• Among the 93 patients who underwent endoscopic assessment at week 0, 65 (63.1%) were reassessed between weeks 26 and 52.
  • The mean±SD UCEIS score decreased from 5.0±1.1 at baseline to 3.6±1.1 between weeks 26 and 52 (P<0.001).
  • The mean±SD Mayo endoscopic subscore decreased from 2.7±0.5 at baseline to 2.0±1.0 between weeks 26 and 52.
• Among the 30 patients who underwent endoscopic assessment at week 52, a UCEIS score of 0 or 1 was observed in 5 (16.6%) and a Mayo endoscopic subscore of 0 or 1 was observed in 10 (33.0%).
• At week 52, STELARA was discontinued in 45 (44%) patients.
  • Reasons for drug discontinuation were lack of effectiveness (n=41), pregnancy (n=1), an AE (n=1), and personal decision after 2 episodes of mild skin rash (n=1).
  • Cumulative probability of STELARA persistence after 3, 6, 9, and 12 months was 96.1%, 81.6%, 71.7%, and 58.4%, respectively.
• After a median duration of 6.7 months (IQR, 4.3-10.6) since STELARA initiation, colectomy was needed in 10 (9.7%) patients.

Safety

• Between weeks 12-16 and 52, 16 AEs were reported in 15 (14.8%) patients and led to STELARA withdrawal in 4 (3.9%) patients.
• SAEs were reported in 4 (3.9%) patients.
  • SAEs included exacerbation of UC leading to hospitalization in 3 patients and myocardial infarction leading to death in a 62-year-old male patient 4 months after STELARA initiation.

Hong et al (2021)¹⁷ assessed the efficacy and safety of STELARA in patients with moderately to severely active UC through a retrospective cohort study.

Study Design/Methods

• STELARA was administered at the standard weight-based induction dose of 260, 390, or 520 mg IV, followed by 90 mg SC q8w.
• The primary outcome was clinical remission at 3 and 12 months after STELARA induction.
  • Clinical remission was defined as a pMayo score of ≤2, with a combined rectal bleeding and stool frequency subscore of ≤1.
• The secondary endpoints were clinical response at 3 and 12 months, CSFR, endoscopic remission, mucosal healing, histo-endoscopic healing, STELARA treatment persistence, and increase in STELARA dosing frequency.
  • Clinical response was defined as a reduction in pMayo score of ≥3 points or 30% from baseline with ≥1 point decrease in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1.
  • Endoscopic remission was defined as a Mayo endoscopic subscore of 0 or 1, mucosal healing as histologic quiescence, and histo-endoscopic healing as a combined Mayo endoscopic subscore of 0 and histologic quiescence.

Results

Efficacy

• Among the 66 patients included in the study, prior exposure to biologics or tofacitinib was observed in 92.4% (anti-TNF agents, 84.8%; VDZ, 75.8%).
  • Prior exposure to ≥2 anti-TNF agents was observed in 24.2% patients.
• For treatment outcomes at 3 and 12 months, see Table: Treatment Outcomes at 3 and 12 Months.

• Univariate and multivariate analyses showed that a history of anti-TNF PNR was a significant negative predictor (univariate analysis: OR, 0.28 [95% CI, 0.08-1.02], P=0.05; multivariable analysis: OR, 0.03 [95% CI, 0.01-0.82], P=0.04) of clinical remission at 3 months. Based on univariate analysis, a history of anti-TNF PNR was not a significant negative predictor (OR, 0.40; 95% CI, 0.05-3.42; P=0.40) of clinical remission at 12 months.
• Histologic-endoscopic healing was achieved in 4/12 (33.3%) of the patients who had endoscopy data available at 12 months.
  • Patients who achieved histologic-endoscopic healing had significantly lower mean±SD pMayo scores (0.5±0.6 vs 3.5±1.7; P <0.01) and stool frequency scores (0.3±0.5 vs 1.4±0.7; P=0.02) compared with those who did not.
  • Patients who achieved histologic-endoscopic healing had lower mean±SD FC levels (190.8±247.9 vs 690.0±671.8; P=not significant [NS; FC data available, n=5]) and CRP levels (1.2±0.9 vs 10.5±10.1; P=NS) compared with those who did not.

Safety

• AEs were reported in 8 patients (12.1%), including: UC exacerbations (n=3), infectious complications (n=4), and leukocytoclastic vasculitis attributed to STELARA (n=1).
• SAEs leading to hospitalization were reported in 4 patients (UC exacerbations, n=3; vasculitis, n=1), including 3 who needed colectomy.
• No malignancies or deaths were reported.

Registry-Based Study

Chaparro et al (2021)¹⁸ evaluated the durability of STELARA treatment and the short- and long-term effectiveness of STELARA in patients with UC from the ENEIDA registry in an observational, multicenter study.

• For short-term effectiveness, the proportion of patients who achieved clinical response and remission after induction (week 16) was analyzed. For long-term effectiveness, the proportion of patients who achieved clinical remission and CSFR at weeks 24 and 52 was analyzed.
• Among the 95 patients included in the study, all had prior exposure to biologics or tofacitinib. Previous treatment with anti-TNF agents, VDZ, and both anti-TNF agents and VDZ was observed in 93 (98%), 78 (82%), and 76 (80%) patients, respectively.
• At week 16, clinical remission was achieved in 33 (35%) patients and clinical response (including patients with remission) in 50 (53%) patients.
  • Prior exposure to anti-TNF agents did not differ significantly between patients who achieved clinical remission (n=32 [97%]) and those who did not (n=61 [98%]; P=NS).
  • Prior exposure to VDZ did not differ significantly between patients who achieved clinical remission (n=25 [76%]) and those who did not (n=53 [86%]).
• At week 24, among the 83 patients who initiated STELARA therapy ≥24 weeks before data analysis, clinical remission was achieved in 32 (39%) and CSFR in 25 (30%).
• At week 52, among the 54 patients who initiated STELARA therapy ≥52 weeks before data analysis, clinical remission was achieved in 18 (33%) and CSFR in 17 (32%).
• STELARA discontinuation occurred in 34 patients (36%) with exposure to STELARA for a median duration of 31 weeks (IQR, 18-59).
  • The probability of STELARA persistence at weeks 16, 56, and 72 was 87%, 63%, and 59%, respectively.
  • The reasons for STELARA discontinuation were PNR (n=21 [22%]), loss of response (n=12 [13%]), and an AE (n=1 [1%]).
• Colectomy due to STELARA treatment failure occurred in 9 (9.5%) patients with a median duration of 14 weeks (IQR, 7.5-18) since STELARA initiation to the surgery.
• AEs were reported in 3 patients.
  • One patient developed dry skin and itching (probably related to STELARA) with mild symptoms that did not cause treatment discontinuation.
  • One patient developed pneumonia (probably not related to STELARA) that did not cause STELARA discontinuation.
  • A 54-year-old male patient with extensive UC and no comorbidities developed severe COVID-19 pneumonia and died. After previously failed treatment with infliximab, adalimumab, golimumab, VDZ, and tofacitinib, the patient was treated with STELARA 90 mg every 6 weeks for 43 weeks without steroids or immunomodulators at the time of infection.

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 07 November 2024.

Summarized above is relevant data from observational studies, retrospective studies, and a registry-based study.