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STELARA® (ustekinumab)

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STELARA - Treatment of Adult Patients with Crohn’s Disease - Real-World Evidence

Last Updated: 01/09/2025

SUMMARY

Summarized in this response are data focused on the clinical effectiveness and safety of STELARA in adult patients with Crohn’s disease (CD) from prospective and retrospective studies and registries.¹^-²⁶

Real-world data in adult patients with crohn’s disease

Real-world evidence in adults with CD treated with STELARA is described in the Table: Summary of Real-World Studies in Adult Patients with CD.

Summary of Real-World Studies in Adult Patients with CD

Study Description and Select Baseline Characteristics	Results
Prospective Studies
Bessissow et al (2024)¹ evaluated the effectiveness and safety of STELARA in bio-naïve patients with moderately-to-severely active CD in the JUSTify (Joint Canadian Ustekinumab Real-world Effectiveness and Safety) study across 7 centers in Canada. Patients included in the study received ≥1 IV induction dose of STELARA and had a minimum of 6 months of follow-up data available from the initiation. Data collection windows after STELARA initiation were: 4, 6 and 12 months. Primary outcome: Clinical remission at 6 months (CDAI<150, HBI<5, or physician assessment of "normal or inactive disease"). Secondary outcomes: Clinical response (CDAI reduction of 70 points accounting for ≥25% reduction from baseline, HBI reduction of ≥3 points from baseline or, if both CDAI and HBI were missing, an improvement from the baseline physician assessment of disease activity), Corticosteroid-free remission (defined as remission achieved without corticosteroid use at the time of evaluating disease activity) Biochemical remission (CRP <5 mg/L or FCP <250 μg/g) Endoscopic remission (SES-CD ≤2 or a physician assessment of "normal or inactive disease") Biochemical response and endoscopic response (SES-CD score of 0-2, a decrease of ≥50% from SES-CD score at baseline, or improvement based on the physician rating of endoscopic findings as compared to baseline evaluation) at 4, 6, and 12 months. For a majority of patients, disease activity was assessed using the HBI scores and physician assessment. In total, 158 eligible patient charts were reviewed. The average age (±SD) was 42.3 years (±16.6) at STELARA initiation. At CD diagnosis, mean age (±SD) diagnosis was 33.7 years (±17.0) and mean disease duration (±SD) was 8.6 years (±12.1).	Effectiveness
	Clinical remission was achieved in 50% (N=72), 67.7% (N=155), and 73.7% (N=114) of patients at 4, 6, and 12 months respectively. Corticosteroid-free remission was achieved in 43.1% (N=72), 67.1% (N=155) and 71.9% (N=114) of patients at 4, 6, and 12 months respectively. Biochemical remission was achieved in 65.2% (N=66); 71.6% (N=88) and 73.9% (N=92) of patients at 4, 6, and 12 months respectively. Endoscopic remission was achieved in 40.5% (N=37) and 56.3% (N=48) of patients at 6 and 12 months respectively. Clinical response was achieved in 62.9% (N=44), 69.9% (N=107), and 72.1% (N=80) of patients at 4, 6, and 12 months respectively after STELARA initiation. Endoscopic response was achieved in 72.7% (N=16) and 70.0% (N=21) of patients, at 6 and 12 months respectively after STELARA initiation.
	Safety
	At 12 months following treatment initiation, 8 ADRs including pyrexia, dizziness, headache, dyspnea, acne, alopecia, and pruritus were observed. Most ADRs (87.5%; 7/8) did not result in any action being taken with STELARA; 87.5% (7/8) of ADRs were resolved by the end of 12 months post-initiation. No serious ADRs were observed.
	Effectiveness
Bamias et al (2024)² evaluated STELARA effectiveness in patients with CD in the REASSURE study across 19 centers in Greece. This was a non-interventional, 24-month prospective study. PROs included the validated Greek version of the IBDQ response (≥16-point increase), FACIT-F improvement (≥4 point increase) and the WPL improvement (≥7 point decrease). Data, including HBI and PROs, were collected through routine assessments at baseline and at 4 follow-up visits at 6-month intervals, with a final visit at 24 months (±2) or at treatment discontinuation, whichever occurred first. A total of 169 patients were included. The median (IQR) age at baseline was 45.0 years (35.0-54.0). Employment status was as follows: Employed: 43.4% (72/166) Unemployed: 29.5% (49/166); 21.6% of these due to CD Retired: 16.3% (27/166); 24.0% of these due to CD Other status: 10.8% (18/166) Among STELARA-treated patients, 35.5% were bio-naïve and 64.5% were bio-experienced.	Effectiveness among bio-naive (N=60) and bio-experienced (N=109) patients are reported below: IBDQ response at 24 months as observed: 60.5% (26/43) vs 54.4% (37/68) and imputed: 49.2% (29/59) vs 41.5% (44/106) FACIT-F among bio-naïve (n=60) vs bio-experienced patients (n=109) at 24 months was as follows: Significant improvement as observed: 62.8% (27/43) vs 57.1% (40/70) Significant improvement imputed: 53.3% (32/60) vs 44.9% (48/107) Activity impairment among bio-naïve (n=60) vs bio-experienced patients (n=109) at 24 months based on WPAI:CD was as follows: Median change from baseline (IQR), as observed: -20.0 (-40.0, 0.0) for both Median change from baseline (IQR), imputed: -10.0 (-30.0 to 0.0) vs -5.0 (-40.0 to 0.0) WPL among bio-naïve (n=60) vs bio-experienced patients (n=109) at 24 months based on WPAI:CD was as follows: CMI as observed: 77.8% (14/18) vs 60.0% (12/20) CMI as imputed: 63.6% (14/22) vs 46.7% (14/30) At 24 months, 72.8% of the overall population, 76.7% of bio-naive patients, and 70.6% of bio-experienced patients remained on treatment with STELARA. STELARA was discontinued in 21.9% (37/169) of patients after a mean (±SD) of 10.2 months (±6.4) months mainly due to lack/loss of response (15/37), safety issues (10/37), or loss to follow-up (6/37).
Lee et al (2024)³ evaluated the effectiveness and safety of STELARA in adult patients with CD in the K-STAR (Post-MarKeting Surveillance for Crohn’s Disease patients treated with STelARa) study across 44 medical centers in South Korea. Patients were treated with weight-based initial STELARA IV infusion (~6 mg/kg), followed by 90 mg SC dose at week 8 and subsequent maintenance therapy with 90 mg SC dose q8w or q12w, following up to week 52 to 66. A total of 464 patients were included, of whom 428 and 457 patients were included in the effectiveness analysis set and safety analysis set, respectively; the mean (±SD) age at the start of STELARA treatment was 35.0 (±12.8) years; 49.9% (228), 28.2% (129), and 55.4% (253) of patients were on concomitant 5-ASA, corticosteroids, and immunomodulators, respectively; 53.4% (243/455) of patients had prior exposure to biologics. The mean (±SD) disease duration was 95.2 (±77.8) years.	Effectiveness
	Weeks 16-20 Clinical response, clinical remission, and corticosteroid-free remission were achieved in 75.0% (321/428), 64.0% (274/428), and 61.9% (265/428) of patients, respectively. Combined effectiveness (clinical response + biochemical response) was achieved in 40.0% (171/428) of patients. Combined effectiveness for bio-naïve vs bio-experienced patients was 50.3% vs 30.7%, P<0.001. Weeks 52-66 Clinical response, clinical remission, and corticosteroid-free remission were achieved in 62.4% (267/428), 52.6% (225/428), and 50.0% (214/428) of patients, respectively. Combined effectiveness (clinical response + biochemical response) was achieved in 41.6% (178/428) of patients. Combined effectiveness for bio-naïve vs bio-experienced patients was 47.7% vs 36.0%, P=0.014. In a multivariable analysis using backward selection, factors inversely associated with achieving clinical remission were: Colonic involvement vs ileal involvement (OR, 0.32; 95% CI, 0.12-0.89; P=0.028) Ileocolonic involvement vs ileal involvement (OR, 0.45; 95% CI, 0.23-0.89; P=0.021) Baseline CRP levels (OR, 0.90; 95% CI, 0.84-0.97; P=0.009) Exposure to two or more biologics vs bio-naïve (OR, 0.38; 95% CI, 0.20-0.73; P=0.003)
	Safety
	AEs and SAEs were observed in 28.2% (129/457) and 12.7% (58/457) of patients, respectively. No new safety signals were observed with STELARA treatment.
Nagano et al (2023)⁴ compared the effectiveness and safety of STELARA among bio-naive vs bio-experienced Japanese patients in an observational, multicenter, post-marketing surveillance study across 91 medical centers in Japan. Patients were treated with weight-based initial STELARA IV infusion, followed by 90 mg SC dose at week 8 and subsequent maintenance therapy with 90 mg SC dose q12w. The dosing interval could be shortened to every 8 weeks for those who had inadequate response. Effectiveness outcomes: Clinical response (defined as 100-point decrease in CDAI score from the first STELARA administration until week 52, when baseline CDAI score was ≥150), clinical remission (defined as CDAI <150 prior to week 52 in patients with baseline CDAI ≥150), change in CRP from baseline to week 52, endoscopy outcomes (assessment of ileum and/or colon using endoscopy prior to week 52) Among the 341 patients registered, all were included in the safety analysis and 336 were included in the effectiveness analysis. A total of 274 (80.4%) patients continued STELARA treatment. Of the 281 patients on a 12-week dosing interval, 207 shortened the dosing interval to 8 weeks. Safety analysis set: 83.3% (239), 33.8% (97), and 23.9% (68) of patients were on concomitant 5-ASA, corticosteroids, and AZA, respectively; 72.1% had prior exposure to biologics (76.8%, IFX). The mean (±SD) age and disease duration was 37.1 (±13.4) years and 11.0 (±9.1) years, respectively. Effectiveness analysis set (CDAI ≥150): 83.5% (91), 45.0% (49), and 21.1% (23) of patients were on concomitant 5-ASA, corticosteroids, and AZA, respectively; 77.5% had prior exposure to biologics (77.0%, IFX). The mean (±SD) age and disease duration was 38.0 (±12.9) years and 11.4 (±9.2) years, respectively.	Effectiveness
	Clinical remission among bio-naïve vs bio-experienced patients: Week 8: 75.9% (n=29) vs 41.4% (n=99) Week 24: 88.0% (n=25) vs 44.6% (n=74) Week 36: 70.8% (n=24) vs 53.5% (n=71) Week 52: 66.7% (n=24) vs 52.6% (n=76) Steroid-free remission among bio-naïve vs bio-experienced patients: Week 8: 45.5% (n=11) vs 26.7% (n=15) Week 24: 80.0% (n=10) vs 57.1% (n=14) Week 36: 87.5% (n=8) vs 71.4% (n=14) Week 52: 100.0% (n=8) vs 80.0% (n=15) Mean CRP value (mg/dL) among bio-naïve vs bio-experienced patients: Baseline: 1.5 (n=87) vs 1.4 (n=240) Week 8: 0.5 (n=85) vs 1.0 (n=229) Week 24: 0.4 (n=70) vs 0.8 (n=199) Week 36: 0.8 (n=76) vs 1.1 (n=210) Week 52: 0.7 (n=72) vs 0.8 (n=203) Endoscopic remission in patients with ileal vs colonic involvement: Baseline: 5.9% (n=34) vs 23.5% (n=51) Week 8: 42.9% (n=7) vs 47.1 (n=17) Week 52: 39.3% (n=28) vs 57.9% (n=38) At week 52, based on PGA, 53.5% (169/316) of patients had a response, 33.9% (107) had a partial response, and 11.1% (35) had no response. In a logistic regression univariate analysis, negative factors affecting the clinical remission in patients with CDAI ≥150 at baseline were prior biologic use (OR, 0.32; 95% CI, 0.13-0.80; P=0.015), concomitant use of IM (OR, 0.34; 95% CI, 0.15-0.80; P=0.014), surgical history (OR, 0.27; 95% CI, 0.13-0.55; P<0.001) and higher baseline CDAI scores (OR, 0.99; 95% CI, 0.98-0.99; P<0.001)
	Safety
	At week 52, the overall incidence of ADRs and SADRs were 11.7% and 6.7%, respectively. Most common ADRs were worsening of CD (1.8%), pyrexia (1.2%), anal abscess, and upper respiratory tract inflammation (0.9% each). Most common SADRs were worsening of CD (1.8%) and anal abscess (0.9%). In a logistic regression multivariate analysis, the incidence of ADR was significantly higher in patients with comorbidities (OR, 2.36; 95% CI, 1.16-4.78; P=0.017) and significantly lower in patients with ileal involvement of CD (OR, 0.25; 95% CI, 0.07-0.85; P=0.026).
Gonczi et al (2022)⁵ evaluated the clinical effectiveness and safety of STELARA in adult patients with CD from a multicenter cohort study in Hungary. Patients received induction therapy with a single dose of STELARA IV, followed by maintenance therapy with 90 mg SC injections at week 8 and then q12w. Primary outcomes: Clinical disease activity and drug sustainability after 1-year follow-up Secondary outcomes: Corticosteroid-free remission based on CDAI/HBI scores without any systemic corticosteroid medication at the time of the assessment, composite clinical and biomarker remission rates based on CDAI/HBI scores and CRP levels, and dose intensification rates A total of 142 patients were included; 56.3% were female, and the mean (±SD) age was 38.4 (±13.0) years. The median follow-up duration was 60 weeks, and the median (IQR) disease duration, CDAI score, and HBI score were 12.5 (8.0-18.0) years, 270 (189-323), and 10 (6-15), respectively.	Effectiveness
	Weeks 52-56 Clinical response was achieved in 69% (per CDAI score; n=122) and 70.7% (per HBI score; n=82) of patients. Clinical remission was achieved in 58% (per CDAI score; n=100) and 57.3% (per HBI score; n=82) of patients. Corticosteroid-free clinical remission was achieved in 51.1% (per CDAI score; n=92) and 50% (per HBI score; n=80) of patients. Composite clinical and biomarker remission was achieved in 36.6% (CDAI score remission + CRP level <10 mg/L) and 34.2% (HBI score remission + CRP level <10 mg/L) of patients.
	Safety
	A total of 23 patients discontinued therapy during follow-up (loss of response, n=14; pregnancy, n=4; side effects, n=2; lost to follow-up, n=3). No SAEs were observed. Discontinuation due to AEs was observed in 2 patients (arthralgia, n=1; recurrent skin erythema at the injection site, n=1). Skin reaction at injection site was reported in 2 patients, and hair loss was reported in 1 patient. No allergic reactions were observed during IV infusions.
Viola et al (2021)⁶ evaluated the effectiveness and safety of STELARA in adult patients with CD from a multicenter cohort study in Italy. Patients were treated with weight-based initial STELARA IV infusion at week 0, followed by induction therapy with 90 mg SC dose at week 8 and subsequent maintenance therapy with 90 mg SC dose q8w or q12w. Primary outcomes: Steroid-free remission (defined as HBI score ≤4 points without steroid use) and reduction in elevated CRP levels through 1 year (52 weeks) of treatment Secondary outcomes: Clinical response (defined as a reduction of HBI score ≥3), reduction in concomitant steroid use, AEs, and possible causes of withdrawal through 1 year of treatment A total of 131 patients were included; the mean (±SD) age at the start of STELARA treatment was 46 (±15) years, and 56% of patients were male. The mean HBI score was 7, 43% (56) of patients were on concomitant steroids, and 53% (70) of patients had elevated CRP levels. The median (IQR) disease duration was 11 (6-17) years.	Effectiveness
	Week 24 Steroid-free remission and clinical response were achieved in 40% (47/117) and 64% (75/117) of patients, respectively. A positive CRP level was observed in 38% (45) of patients. Overall, 20% (24) of patients were still on concomitant steroids. A significant reduction of HBI score (P<0.001) and steroid use (P<0.001) from baseline to week 24 was observed. Treatment discontinuation was reported in 9% (11/117) of patients (primary failure, 3% [4]; secondary failure, 6% [7]) Week 52 Steroid-free remission and clinical response were achieved in 43% (33/76) and 59% (45/76) of patients, respectively. A positive CRP level was observed in 25% (15) of patients. Overall, 4% (3) of patients were still on concomitant steroids. A significant reduction of HBI score (P=0.001) and steroid use (P=0.012) from baseline to week 52 was observed. Treatment discontinuation was reported in 1.3% (1/76) of patients due to secondary treatment failure.
	Safety
	AEs were reported in 16% (21) of patients, of which, 3 led to treatment discontinuation (treatment failure and consequent surgery, n=2; reduction in visual acuity, n=1).
Retrospective Studies
Bello et al (2024)⁷ evaluated long-term real-world clinical outcomes of STELARA in adult patients with CD at 4 hospitals in Stockholm, Sweden. Patients included were those with CD treated with ≥1 STELARA IV induction dose, as well as patients who initiated treatment with SC injection prior to the IV formulation became available. Primary outcomes: Clinical steroid-free response and remission at 3, 6, 12, 24 and 36 months Secondary outcomes: Endoscopic response (defined as reduction of the SES-CD score by ≥50% from baseline) and endoscopic remission (defined as SES-CD scores between 0 and 2) A total of 322 patients were included. The median (IQR) age was 38 (24) years. The median (IQR) follow-up duration was 13.5 (28.5) months, and the median (IQR) disease duration was 8 (12.5) years.	Effectiveness
	Among 322 patients, clinical response, and steroid-free remission at 3 (n=284) vs 12 (n=165) months were 56% vs 77% and 19% vs 64%, respectively. Among the 299 patients treated with STELARA, clinical remission and clinical response at 3 months were observed in 14% and 43%, respectively. At 12 months, the rates were 32% and 42%. Among the 23 patients in clinical remission at baseline, 83% (19) maintained remission at 3 months, 65% (15) at 12 months, and 43% (10) through 24 months. Among the 165 patients with baseline endoscopic activity, 24 had follow-up. At 3 and 12 months, 46% (11/24) and 42% (10/24) achieved endoscopic remission, respectively. The median (IQR) SES-CD for 9 patients at baseline and 3 months was 5 (6) and 3 (6), respectively, P<0.01. For 15 patients who had a colonoscopy at baseline and 12 months, the median SES-CD was 6 (IQR:4) and 3 (IQR:2), respectively, P<0.01. At 12 months, 165 patients were still on STELARA treatment and 160 had disease activity, 69% (111) achieved clinical remission, and 65% maintained remission until 24 months. Among the 49 patients with active disease at 12 months, 18% (9) achieved remission by 24 months, 57% (28) maintained mild disease activity, and 3 patients with mild disease activity worsened by 24 months. Among the 121 patients who had STELARA treatment withdrew, outcomes during 12-month post withdrawal were: 64% (77) with active disease, 26% (32) in remission, 10% (12) with unknown disease activity, 68% (82) needed additional biologic treatment, 43% (52) received corticosteroids, 29% hospitalized, 24% undergoing abdominal (n=21) and/or fistula surgery (n=9), and 2 patients withdrew due to pregnancy or death.
	Safety
	Overall, 2% of patients (7) were hospitalized due to disease worsening, and 2% (8) were withdrawn due to pending bowel surgery. After 12 months, 3 patients withdrew due to adverse events/intolerance; 1 patient with fistulizing disease experienced severe perianal infection requiring surgery; 1 patient each had prurigo or 'other'. No late malignancy or pregnancy occurred. Reasons for STELARA discontinuation at 12 months among 98 patients were: primary non-response (n=53), loss of response (n=16), AEs/intolerance (n=16), 2 due to surgery, 2 lost to follow-up, 1 each due to pregnancy, remission, and malignancy, and 6 due to other reasons.
Johnson et al (2023)⁸ evaluated the real-world effectiveness and safety of STELARA in adult patients with CD from the IBD Health Outcomes Consortium substudy group (SUCCESS), a multicenter, multinational consortium. Patients included were those with CD treated with STELARA on-label (after approval in September 2016). Primary effectiveness outcomes: Cumulative rates of clinical remission (defined as complete resolution of all CD-related symptoms) and endoscopic remission (defined as absence of ulcers and/or erosions) at 6 and 12 months Secondary effectiveness outcomes: Cumulative rates of corticosteroid-free remission (defined as complete corticosteroid taper, clinical remission, and no repeat corticosteroid prescription within 4 weeks after completing taper), durable remission (achieving and maintaining clinical remission through the end of the follow-up period), radiographic remission (absence of imaging features of active inflammation), and loss of remission (recurrence of CD symptoms, need for surgery, therapy switch, or STELARA dosing modification in patients achieving clinical remission) A total of 1113 patients were included, with a median (IQR) follow-up duration of 386 (204-562) days; 51.8% were female, and median (IQR) age was 38 (28-52) years. The median (IQR) follow-up duration was 386 (204-562) days, and the median (IQR) disease duration was 11 (5-20) years.	Effectiveness
	At 6 vs 12 months, the cumulative rates of clinical remission, endoscopic remission (evaluated in patients who had available endoscopy with ulcerations at baseline), steroid-free remission, and radiographic remission were 21% vs 40%, 17% vs 39%, 15% vs 32%, and 19% vs 30%, respectively. Rates of durable remission were significantly reduced based on the number of prior biologic exposures, even after adjusting for disease duration, albumin, history of stricturing or penetrating disease, prior perianal disease, and history of bowel surgery (adjusted HR per biologic exposure, 0.829; 95% CI, 0.74-0.94). Overall event rates for clinical remission, endoscopic remission, steroid-free remission, radiographic remission, and loss of remission were 38.8% (432/1113), 45.2% (304/671), 28% (123/437), 32.1% (61/190), and 23.6% (102/432), respectively. Cumulative rate of loss of remission over 6 months for biologic-naïve patients was 9%. The rates increased progressively with each additional prior biologic exposure and were 18%, 24%, 28%, and 47% in patients with prior exposure to 1, 2, 3, and 4 biologics (P<0.001 for linear trend). Among patients with primary nonresponse or incomplete response (<50% reduction in symptom activity), 22.3% (152/681) underwent dose optimization, leading to clinical response (>50% reduction in symptom activity) in 40.1% (61/152) of patients. Dose optimization strategies, including IV reintroduction alone, IV reintroduction plus q4w dosing interval, and q4w dosing interval led to clinical response in 41.2% (7/17), 47.5% (19/40), and 36.8% (35/95) of patients, respectively. Among patients with loss of remission during follow-up, dose optimization was done in 76% (77/102), leading to clinical response in 57% (44/102) of patients. Dose optimization strategies, including IV reintroduction alone, IV reintroduction plus q4w dosing interval, and q4w dosing interval led to clinical response in 72.7% (8/11), 65% (13/20), and 50% (23/46) of patients, respectively.
	Safety
	Infections were observed in 7.6% (85) of patients, with serious infections occurring in 3.4% of patients. The most common infection (n=28) was Clostridiodes difficile colitis, and 46% of these individuals had a prior episode of Clostridiodes difficile infection before STELARA treatment. A single patient with a documented history of lymphoma prior to initiating STELARA developed lymphoma while receiving STELARA. Other AEs were joint pain (0.5%), rash (0.5%), hair loss (0.3%), headache (0.3%), hepatitis (0.3%), hypersensitivity reaction (0.2%), lymphoma (0.1%), neuropathy (0.1%), and vasculitis (0.1%).
Banon et al (2022)⁹ evaluated the treatment patterns and safety outcomes of STELARA in adult patients with CD using data from the state healthcare database in Israel. Biologic-experienced patients with CD who had received ≥1 prescription of STELARA during index period (2017 and 2018) were included. Patients were required to have a record of STELARA induction therapy (130 mg vial) for analyses of treatment patterns. Outcomes: Treatment discontinuation (defined as switching biologic or a treatment gap [≥90 days after the calculated STELARA runout date]), CD-related surgery, CD-related hospitalization, and corticosteroid discontinuation A total of 162 patients who were initiated on STELARA (n=47 in 2017; n=115 in 2018) were included; 49.4% were female, and the median (IQR) age at baseline was 34.4 (23.2-46.3) years. The median (IQR) duration since CD diagnosis was 8.6 (4.8-16.0) years. At baseline, 6.8% (11) and 9.9% (16) of patients had a history of hospitalizations and CD-related surgeries.	Effectiveness
	Among patients who persisted on STELARA treatment, surgery, hospitalization, and corticosteroid discontinuation were observed in 1.0% (1/104), 7.7% (8/104), and 0 patients, respectively. Among patients who discontinued STELARA treatment during the study period, surgery, hospitalization, and corticosteroid discontinuation were observed in 8.6% (8/58), 19.0% (11/58), and 19.0% (11/58) of patients, respectively.
	Safety
	At the end of follow-up, among the 58 patients who discontinued STELARA treatment, 16 switched to a different biologic treatment. Treatment discontinuation occurred in 10.6%, 27.8%, and 35.6% of patients at 180, 365, and 540 days, respectively, after the treatment was initiated.
Chapparo et al (2022)¹⁰ evaluated the long-term real-world effectiveness and safety of STELARA in adult patients with CD in a multicenter study in Spain. Patients with active CD who received ≥1 IV dose of STELARA for ≥6 months prior to start of the study were included. Patients received SC STELARA 90 mg at week 8, followed by maintenance therapy with SC STELARA 90 mg at regular intervals q8w and q12w. Primary outcomes: STELARA retention rate (defined as proportion of patients maintained under STELARA treatment at a certain point) from the start of treatment to the last recorded dose Select secondary outcomes: Short-term (weeks 8 and 16) and longterm (months 6, 12, and 18) effectiveness (defined as remission [HBI score ≤4] and clinical response [decrease in HBI score ≥3]) Safety outcomes: Tolerability and AEs A total of 463 patients were included; ~50% were female, and the mean age at baseline was 47 years. The median (IQR) follow-up duration was 15.5 (12.6-18.5) months, and the mean disease duration was 14.1 years.	Effectiveness
	STELARA retention rate at a median follow-up of 15.5 months was 76.9% (95% CI, 72.8-80.7) Short-term Effectiveness Clinical remission at weeks 8 and 16 was achieved in 44% and 56.1% of patients, respectively. Clinical response at weeks 8 and 16 was achieved in 57.6% and 70.2% of patients, respectively. Long-term Effectiveness Long-term effectiveness was analyzed in patients achieving clinical remission at week 16 (n=256) with a median (IQR) time of follow-up of 15.7 (12.9-19.0) months. The median (IQR) time to loss of response was 11.1 (7.1-14.7) months. The incidence of loss of response was 29.7% per patient-year of follow-up. The probability of sustaining remission at 6, 12, and 18 months was 84%, 74%, and 66%, respectively. Clinical remission at 6, 12, and 18 months was achieved in 57.9% (268/463), 57.2% (250/437), and 41.5% (113/272) of patients, respectively. Steroid-free remission at 6, 12, and 18 months was achieved in 53.3% (247/463), 50.8% (222/437), and 35.7% (97/272) of patients, respectively. Treatment Discontinuation After a median follow-up of 15.5 months, 23.1% (107) of patients discontinued treatment. The incidence of STELARA discontinuation was 18.4% per patient-year of follow-up. The incidence was similar between patients receiving STELARA monotherapy vs combination therapy with immunosuppressants (17.5% vs 18.9%; P=0.71). The reasons for treatment discontinuation were primary failure (27.1%), loss of response (26.2%), partial response (25.2%), AE (5.6%), patient’s decision (4.7%), and other reasons (11.2%).
	Safety
	A total of 50 AEs occurred in 8.4% (39) of patients, of which, 4 were severe (2 infections, 1 malignancy, and 1 fever). The AEs were possibly, probably, and very likely related to STELARA treatment in 72% (36), 26% (13), and 2% (1) of patients, respectively.
Scribano et al (2022)¹¹ evaluated the real-world effectiveness and safety of STELARA in adult patients with refractory CD in a multicenter cohort study in Italy. Patients with CD who failed to respond or were intolerant to ≥1 anti-TNF agent were included. Patients received the weight-based induction therapy with STELARA IV, followed by maintenance therapy with STELARA 90 mg SC after 8 weeks and then q8w or q12w. The dose was escalated to q8w in patients with a loss of response to STELARA maintenance therapy. Coprimary outcome: Corticosteroid-free clinical remission (HBI score ≤4) at weeks 26 and 52 Secondary outcomes: Changes in the HBI score and CRP level and normalization of CRP level (to ≤0.5 mg/dL) at weeks 8, 26, and 52 A total of 140 patients with active refractory CD were included; 51.4% were male, and the median (IQR) age at baseline was 45.0 (36.3-54.0) years. The median (IQR) disease duration was 16.0 (8.0-22.0) years, and the mean (SD) HBI score, and CRP level were 6.9 (3.4) and 4.1 (6.0) mg/dL, respectively.	Effectiveness
	At weeks 26 and 52, corticosteroid-free remission was achieved in 56.5% (61/108) and 58.3% (63/108) of patients (with baseline HBI score >4), respectively, and was achieved in 93.8% (30/32) and 96.9% (31/32) of patients (with baseline HBI score ≤4), respectively. Significant decreases in median CRP level were reported between baseline and weeks 8, 26, and 52 in the 119 patients whose CRP levels were available at baseline (P<0.0001). At baseline, 79.8% (95/119) of patients had a high CRP level, which was normalized in 34.9%, 37.8%, and 49.3% of patients at weeks 8, 26, and 52, respectively. Among patients with an HBI score of ≤4 at baseline (median [IQR], 1.3 [0.44.0] mg/dL), 56.3% had a high CRP level. CRP levels decreased from baseline to 0.9 mg/dL (IQR, 0.3-2.5; P=0.0013), 1.0 mg/dL (IQR, 0.2-0.5; P=0.0140), and 1.0 mg/dL (IQR, 0.2-0.9; P=0.0259) at weeks 8, 26, and 52, respectively.
	Safety
	Ten AEs occurred in 6.4% (9) of patients, of which, 3 lead to treatment discontinuation (allergic reaction to STELARA IV infusion, n=2; peripheral arthropathy exacerbation, n=1). During the study period 4.3% (6) of patients underwent surgery for CD. Patients who received a maintenance SC dose of 90 mg q8w (90%) did not experience more AEs than those treated with the maintenance dose q12w (10%). No infections were observed.
Dolby et al (2021)¹² conducted a retrospective audit of clinical data from the Cross Pennine IBD Initiative to evaluate the effectiveness and safety of STELARA in patients with CD. Outcomes: Clinical remission (PGA 0), clinical response (PGA 1), and safety A total of 259 patients were included; 160 were female. The mean age was 39.99 years, and the mean disease duration was 11.78 years.	Effectiveness
	At 3 months, clinical remission and clinical response were achieved in 34.4% (89) and 32.4% (84) of patients, respectively. By 12 months, 25% (65) of patients discontinued STELARA, 24.3% (63) were in remission, and 13.1% (34) achieved response. Outcomes were unavailable in 37.6% of patients.
	Safety
	Reported AEs included headaches (n=8), joint pains/arthralgia (n=8), body rashes/urticaria (n=6), and flu-type symptoms (n=5). SAEs included hospitalizations with infection (n=17), gastrointestinal operations (n=26), CD flare (n=46), abdominal pain (n=6), and medical admissions (n=8). Additionally, 1 death from a pre-existing primary malignant melanoma was reported along with: 3 newly diagnosed cancers (1 small bowel adenocarcinoma, 1 breast cancer, and 1 hepatocellular carcinoma), and 2 recurrences of previously known cancers (1 basal cell carcinoma of the skin and 1 bladder transitional cell carcinoma).
Fenech et al (2021)¹³ evaluated the real-world effectiveness of STELARA in adult patients with CD in an observational study across 3 hospitals in London. Primary outcome: Clinical response (3-point change in HBI score) at week 12 A total of 106 patients were included; 47.2% were male, and the median (range) age at the time of STELARA induction was 35 (20-69) years. The median (range) follow-up duration was 12 (1-33) months.	Effectiveness
	Clinical response was achieved in 58.9% of patients at week 12. After the 1- and 2-year follow-ups, 72% (95% CI, 62-81) and 67% (95% CI, 5577) of patients remained on STELARA, respectively.
Gadhok et al (2021)¹⁴ evaluated the real-world effectiveness and safety of STELARA in adult patients with CD in a multicenter cohort study in the UK. Outcomes: Clinical remission (HBI score ≤4), clinical response (decrease in HBI score ≥3 or sustained HBI score ≤4), biological remission (CRP level <5 mg/L in patients with a baseline CRP level >5 mg/L), and biological response (a 50% reduction in CRP levels) A total of 120 patients were included; 49% (59) were male, and the median (IQR) age of 34 (26-44) years. The median (IQR) disease duration was 12 (717) years. The mean (SD) HBI score was 5 (5) in 112 patients, and the mean (SD) CRP level was 15 (18) mg/L in 117 patients. Overall, 13% (15) of patients were on steroids at baseline.	Effectiveness
	At 3 months, clinical remission, clinical response, steroid-free remission, biological response, and biological remission were achieved in 35%, 35%, 34%, 24%, and 22.7% of patients, respectively. At 6 months, clinical remission, clinical response, steroid-free remission, biological response, and biological remission were achieved in 28%, 34.6%, 25%, 23.3%, and 13% of patients, respectively. At 12 months, clinical remission, clinical response, steroid-free remission, biological response, and biological remission were achieved in 33.3%, 34.3%, 33.3%, 19.2%, and 11.8% of patients, respectively. At 6 and 12 months, 74% (79) and 78% (68) of patients, respectively, were on escalated 8-weekly dosing, but the dosing regimen did not affect the outcomes. At 3, 6, and 12 months, treatment discontinuation occurred in 1.7% (2), 10.8% (13), and 27.5% (33) of patients, respectively. Reasons included primary nonresponse (n=23), loss of response (n=9), suboptimal response (n=4), and side effects (n=4).
	Safety
	AEs occurred in 19% (23) of patients, including 12 patients requiring surgical intervention for progressive disease.
Gold et al (2021)¹⁵ evaluated the impact of disease duration on the effectiveness of STELARA in adult patients with CD using data from a multicenter consortium. Outcomes: Cumulative rates of clinical remission (defined by PGA), steroid-free clinical remission, endoscopic remission (healing of ulcers), and radiographic remission in patients with shorter (≤5 or ≤2 years [early disease]) vs those with longer disease duration (>5 or >2 years [late disease]) A total of 1113 patients were included; 295 had early disease. Patients with early disease were younger vs those with late disease (32 vs 40 years).	Effectiveness
	At the 2-year cutoff, cumulative rates of clinical remission, steroidfree remission, and endoscopic remission in patients with early (≤2 years) vs late disease (>2 years) duration were 51% vs 38%, 52% vs 38%, and 58% vs 36%, respectively, at 12 months. At the 5-year cutoff, cumulative rates of clinical remission, steroidfree remission, endoscopic remission, and radiographic remission in patients with early (≤5 years) vs late disease (>5 years) duration were 49% vs 37%, 39% vs 29%, 52% vs 35%, and 42% vs 33%, respectively, at 12 months.
Kamperidis et al (2021)¹⁶ evaluated the real-world effectiveness and safety of STELARA in adult patients with CD in an observational study in London. Patients received induction therapy with STELARA IV (6 mg/kg), followed by STELARA 90 mg SC at week 8 and then maintenance therapy with STELARA 90 mg SC q8w or q12w. Primary outcome: Clinical response (3-point decrease in HBI score) after the first SC dose at week 12 Secondary outcomes: Clinical remission (defined as HBI score ≤4 without corticosteroid use) at week 12, clinical response and remission at week 52, AEs, biochemical disease activity (defined as CRP level >5 mg/L and/or FCP >250 µg/g), endoscopic disease activity (defined as improvement in mucosal inflammation and resolution of deep ulcers), and need for rescue interventions or drug discontinuation during follow up A total of 134 patients were included; 50% (67) were male, and the median (range) age at STELARA induction was 36 (20-80) years. The median (range) follow-up and disease duration were 12 (1-33) months and 140 (1-528) months, respectively. The median (range) HBI score was 9 (1-26), and the median (range) CRP level was 10 (0.5-105) mg/L.	Effectiveness
	Week 12 Clinical response and clinical remission were achieved in 58% (69/119) and 46.3% (56/121) of patients, respectively. Biochemical disease activity was observed in 65% (78/120) of patients. Week 52 Clinical response and clinical remission were achieved in 63.9% (46/72) and 57.5% (42/73) of patients, respectively. Biochemical disease activity was observed in 47.2% (42/89) of patients. Based on the endoscopy data available from 11.2% (15) of patients, mucosal healing, improvement, no change, and worsening of disease were reported in 3, 5, 5, and 2 patients, respectively. Treatment Discontinuation Treatment discontinuation occurred in 21.6% (29) of patients (treatment failure, n=19; AE, n=6; other, n=4). The median (range) time to treatment discontinuation was 6 (1-18) months. Rescue therapy was required in 31.3% (42) of patients (endoscopy balloon dilation, n=1; abdominal surgery, n=18; perianal surgery, n=9; steroids, n=33).
	Safety
	Overall, ≥1 AE occurred in 11.9% (16) of patients (infection, n=4; arthralgia, n=3; headache, n=3; others [cough, chest pain, and ankylosing spondylitis], n=3; rash, n=2; injection reaction, n=1; fatigue, n=1; malignancy, n=1)
Monin et al (2021)¹⁷ evaluated the effectiveness and safety of STELARA in adult patients with CD in a single-center study in Belgium. Select outcomes: Initial response (defined by the absence of maintenance therapy beyond week 16), sustained response (defined by the cessation of therapy for another reason than stopping in sustained remission), and a full biologic response (defined by CRP level <5 mg/L or FCP <250 µg/g). Assessment of effectiveness was limited to patients who reached week 16 after induction at the time of analysis A total of 148 patients were included; 45.9% (68) were male. The mean (SD) age at diagnosis was 28.16 (13) years. The mean (SD) disease duration was 16 (11.6) years. The mean (SD) CRP level was 14.8 (23.9) mg/L in 142 patients, and the mean (SD) FCP was 659.6 (903) µg/g in 89 patients.	Effectiveness
	Overall, 20.3% (30) of patients did not receive STELARA maintenance therapy beyond week 16. Initial Response In a univariate analysis, initiation of maintenance therapy showed borderline significance with a series of the following parameters: Initial response was less frequent with an increasing number of stool/day before treatment (OR, 0.93; 95% CI, 0.85-1.01; P=0.08), abdominal pain (OR, 0.26; 95% CI, 0.06-1.18; P=0.08), and lower CRP level decrease after induction (OR, 0.62; 95% CI, 0.39-1.00; P=0.05). In a multivariate analysis, no parameter was significant. Sustained Response Among the 118 patients who continued, 14.4% (17) discontinued treatment during the maintenance therapy over a median follow-up of 14.9 months, with 5 of them discontinuing treatment before 1 year. In a univariate analysis, treatment cessation increased with active smoking (HR, 2.20; 95% CI, 1.18-4.11; P=0.01), number of stools/day at baseline (HR, 1.06; 95% CI, 1.00-1.13; P=0.05), previous exposure to VDZ (HR, 1.96; 95% CI, 1.08-3.56; P=0.03), and lower decrease in CRP level between baseline and postinduction (HR, 1.38; 95% CI, 1.02-1.86; P=0.04). In a multivariate analysis, active smoking remained significant (HR, 3.1; 95% CI, 1.5-6.7; P=0.003). Biologic Response Biologic response was observed in 45.3% (62/137), 63.8% (37/58), and 52.4% (33/63) of patients after induction, at 1-year, and at last follow-up, respectively.
	Safety
	AEs leading to STELARA interruption were reported in 9 patients (induction, n=5; maintenance, n=4). AEs resulting in treatment discontinuation were headache (n=2), pulmonary infection (n=1), skin lesions (n=1), arthralgia (n=1), breast cancer (n=1), thymic problem (n=1), and unspecified general intolerance (n=2). No deaths were reported during the study period.
Af Bjorkesten et al (2020)¹⁸ evaluated the long-term clinical outcomes and dosing patterns of STELARA in adult patients with CD in a chart review study (FINUSTE2) using data from 17 hospitals in Finland. Patients received initial therapy with weight-based STELARA IV. Until week 16, patients had received 1-2 SC injections of STELARA 90 mg. Patients who continued STELARA therapy beyond week 16 received maintenance therapy with STELARA 90 mg SC q8w or q12w. Primary objectives: Clinical outcomes such as clinically active disease (defined as modified HBI score >4), clinical response (defined as reduction in modified HBI score ≥3 points from baseline), clinical remission (modified HBI score ≤4), clinical benefit (defined as both patients with clinical response and patients with clinically active disease at baseline who reached clinical remission during follow-up), biomarker-assessed active disease (FCP >250 µg/g), biomarker response (reduction in FCP ≥50% from baseline), and biomarker remission (FCP ≤250 µg/g). Secondary objectives: Changes in endoscopic activity such as endoscopically active disease (defined as SES-CD >2), endoscopic response (defined as reduction in SES-CD ≥50% from baseline), and endoscopic remission (defined as SES-CD ≤2) and laboratory tests during follow-up A total of 155 patients were included; 52.3% (81) were male, and the median (IQR) age was 37.3 (29.353.0) years. The median (IQR) disease duration was 12.6 (5.0-19.2) years. At baseline, 75.6% (93) of patients had biomarker-assessed active disease (FCP >250 µg/g), whereas all 43 patients who underwent baseline endoscopy had endoscopically active disease (SES-CD >2). Among 130 patients with baseline data on FCP and/or SES-CD, 16.2% (21) had no objectively detectable disease activity. In 97 patients with baseline data on modified HBI score, 64.9% (63) had clinically active disease (modified HBI score >4).	Effectiveness
	The median (IQR) follow-up time was 14.2 (7.8-17.4) months. Follow-up data at 16 weeks, 1 year, and 2 years were available for 155, 93, and 18 patients, respectively. Clinical Outcomes Proportion of patients with clinically active disease decreased from 64.9% (63/97) at baseline to 29.5% (23/78; P<0.001) at week 16 and to 30.2% (13/43; P<0.001) at 1 year. Clinical benefit was observed in 82.6% (38/46) of patients at week 16 and 77.8% (21/27) of patients at 1 year. Proportion of patients with biomarker-assessed active disease decreased from 75.6% (93/123) at baseline to 64.2% (70/109; P=0.0582) at week 16 and to 51.7% (30/58; P=0.001) at 1 year. Biomarker remission was achieved in 48.3% (28/58) of patients at 1 year; of them, 41.4% (24) were in corticosteroid-free biomarker remission. Biomarker response increased from 37.1% (36/97) at week 16 to 53.9% (28/52) at 1 year. Endoscopic Outcomes Proportion of patients with endoscopically active disease decreased from 100% (43/43) at baseline to 64.7% (11/17; P<0.001) at week 16 and was 66.7% (12/18; P<0.001) at 1 year. Treatment Discontinuation At the end of follow-up, 20.3% (31) of patients discontinued STELARA, and the main reasons were loss of response (n=17) and economic reason or patient choice (n=7). Reasons for treatment discontinuation related to tolerability (<5 patients) included: elevated liver enzymes, abdominal abscess, perianal fistula complications and septicemia, and prolonged respiratory infection. Other reasons that led to treatment discontinuation (<5 patients) were: diagnosis of diffuse large B-cell lymphoma, pregnancy, and other physician’s advice.
	Safety
	Safety of STELARA therapy was not assessed in this study.
Plevris et al (2020)¹⁹ evaluated the long-term real-world effectiveness and safety of STELARA in patients with CD using Scottish prescription data. Patients with active CD who completed induction therapy with STELARA IV followed by a 90 mg SC dose at week 8 and had a clinical follow-up at week 8 plus ≥1 routine secondary care attendance were included. Patients received induction therapy with STELARA IV, followed by 90 mg SC injection at week 8. Primary outcomes: Clinical remission (defined as complete resolution of CD-related symptoms without steroids) and mucosal healing (defined as absence of mucosal ulceration/erosions without steroids) at 12 months. Secondary outcomes: Clinical response (≥50% decrease in CD symptoms/severity), deep remission (clinical remission plus mucosal healing), perianal fistula response, and safety A total of 216 patients were included; 57.9% (125) were female, and the median (IQR) age was 39.0 (28.8-51.8) years. The median (IQR) follow-up duration and disease duration were 35.0 (17.4-52.0) weeks and 9.9 (6.0-16.5) years, respectively.	Effectiveness
	At 6 vs 12 months, cumulative rates of clinical remission, mucosal healing, and deep remission were 13.5% vs 32.0%, 10.8% vs 32.7%, and 8.5% vs 19.3%, respectively. At 6 vs 12 months, cumulative rates of perianal fistula response in patients with active perianal disease (n=37) at treatment initiation were 12.5% vs 53.1%, respectively. During follow-up, ≥1 assessment of mucosal healing was available in 56.9% (123/214) of patients. The cumulative rates of mucosal healing at 6 and 12 months were 10.8% and 32.7%, respectively. At week 8, clinical remission and clinical response were achieved in 6.0% (13/216) and 45.4% (98/216) of patients, respectively.
	Safety
	The rate of SAEs was 13.6 per 100 PY. Serious infections occurred in 4.6% (10) of patients or 7.1 events per 100 PY, with most patients restarting STELARA after treatment of their infection. The rate of SAEs was 13.6 per 100 PY. Serious infections occurred in 4.6% (10) of patients or 7.1 events per 100 PY, with most patients restarting STELARA after treatment of their infection. Arthralgia was the most common noninfective SAE which occurred in 1.9% (4) of patients or 2.9 events per 100 PY. One patient died during treatment. A >60-year-old patient with a history of complex CD and multiple operations for severe penetrating and perianal disease. The patient received 2 doses of STELARA as a last attempt to control the disease since the patient was not fit for further surgeries. Following the first STELARA SC dose, the patient presented with severe intra-abdominal/perianal sepsis which did not respond to therapy.
Kubesch et al (2019)²⁰ evaluated the short- and long-term effectiveness of STELARA in adult patients with CD in a multicenter study in Germany. Patients with CD who initially received a weight-based dose of STELARA IV, followed by STELARA 90 mg SC at week 8 and then q8w or q12w and had a follow-up of ≥8 weeks after the first STELARA infusion were included. Primary outcome: Combined remission (defined as a decrease in HBI score of 3 points and an FCP <250 µg/g or a decrease in FCP by 50%) at week 48. Secondary outcomes: Clinical remission (defined as HBI score ≤4 and/or FCP <250 µg/g) at weeks 16, 32, 48, 56, 72, and 88; clinical response (defined as a decrease in HBI score ≥3 or FCP ≥50% or FCP <250 µg/g) at weeks 8, 16, 32, 48, 56, 72, and 88 A total of 106 patients were included, of whom, 58.5% (62) were female. The median (range) age was 39.5 (19-73) years. Baseline disease activity was seen in 93 patients. The median (95% CI) follow-up duration was 49.1 (42.03-56.25) weeks, and the median (range) disease duration was 11 (2-39) years. The median (range) HBI score was 8 (0-26), median (range) CRP level was 0.95 (0.1–12.2) mg/dL, and median (range) FCP level was 539 (5-2100) µg/g.	Effectiveness
	The following rates (calculated using the population with baseline disease activity [n=93]) were observed at weeks 8, 16, 32, 48, and 72, respectively: Combined remission: 24.7% (23), 20.4% (19), 21.5% (20), 26.9% (25), 17.2% (16), and 5.4% (5). Combined response: 54.8% (51), 39.8% (37), 52.7% (49), 51.6% (48), 24.7% (23), and 8.6% (8).
	Safety
	AEs were reported in 3 patients (abscess formation and in need of drainage, n=2; palpitations and reduced sex drive, n=1), with none leading to treatment discontinuation.
Liefferinckx et al (2019)²¹ evaluated the long-term effectiveness of STELARA in patients with CD who failed biologic therapies in a multicenter cohort study in Belgium. Patients received a weight-based IV infusion followed by 90 mg SC q8w. Outcomes: Clinical response (decrease in HBI score ≥3), clinical remission (HBI score ≤4), biological response (50% decrease in CRP level and/or CRP level ≤5 mg/L), steroid-free clinical response and remission (response and remission without the use of concomitant systemic or oral controlled-release steroids), and AEs at weeks 8, 16, and 52 A total of 152 patients were analyzed; 69.1% (105) were female, and the age (range) at diagnosis was 23 (666) years. The median (IQR) HBI score was 10 (7-14) in 140 patients, and the median (IQR) CRP level was 16.2 (10.6-28.8) mg/L in 28 patients.	Effectiveness
	The following rates were observed at weeks 8, 16, and 52, respectively: Clinical response: 59.2% (90), 51.9% (79), 42.1% (64). Clinical remission: 28.2% (44), 30.9% (47), 25.7% (39). Steroid-free clinical response: 38.2% (58), 45.4% (69), 38.8% (59). Steroid-free clinical remission: 19.7% (30), 26.9% (41), 24.3% (37). The median (IQR) CRP level significantly decreased from baseline to 8.5 mg/L (3.914; P<0.0001), 9.1 mg/L (4-16; P<0.0001), and 6.6 mg/L (6.6-15.1; P<0.0001) at weeks 8, 16, and 52, respectively. Biologic response was observed in 41.1% (46) and 34.8% (39) of patients at weeks 8 and 16, respectively.
	Safety
	Among the 46 patients experiencing arthralgia at baseline, 63% (29), 45.6% (21), and 17.4% (8) of patients still experienced symptoms at weeks 8, 16, and 52, respectively. De novo arthralgia was reported in 17.9% (16/89), 19.1% (17/89), and 13.5% (12/89) of patients at weeks 8, 16, and 52, respectively. During follow-up at 12 months, 11 AEs were reported other than the aforementioned de novo arthralgia. Treatment discontinuation occurred in 1 patient due to intense myalgia/arthralgia. Overall, 10% (17) of patients underwent surgery due to CD-related complications.
Registry-Based Studies
Casas-Deza et al (2023)²² evaluated the clinical effectiveness and safety of STELARA in elderly patients with CD using data from the ENEIDA registry in Spain. Adult patients with CD who received ≥1 dose of STELARA were included. Outcomes: Clinical effectiveness including clinical response (defined as an improvement in disease symptoms without achieving remission, with a decrease of ≥3 points in the HBI score compared with baseline) and steroid-free remission (defined as clinical remission [HBI score <5] without use of any steroids), and safety were evaluated at weeks 16, 32, and 54 A total of 648 patients were included in the study, comprising 212 elderly (>60 years) and 436 nonelderly patients. The age (range) for elderly and nonelderly patients was 67.0 (63.6-72.8) years and 41.6 (32.6-50.0) years, respectively. Among the elderly and nonelderly patients, 48.6% (103) and 52.3% (228), respectively, were female.	Effectiveness
	No significant difference in clinical response was observed in elderly vs nonelderly patients at weeks 16 (64.9% vs 65.9%; P=0.20), 32 (63.6% vs 66.7%; P=0.10), and 54 (61.9% vs 67.1%; P=0.40). Similarly, no significant difference in steroid-free remission was observed in elderly vs nonelderly patients at weeks 16 (51.4% vs 54.6%; P=0.20), 32 (54.5% vs 53.0%; P=0.26), and 54 (51.1% vs 57.8%; P=0.21). No statistically significant age differences were observed in CRP or FCP levels. A subgroup analysis was conducted among patients with active disease (defined as an HBI score ≥5 points and/or objective evidence of active CD [endoscopic/radiological activity and/or CRP >0.5 and/or FCP >250 µg/g]) at baseline (elderly, n=109; nonelderly, n=262). No significant difference in clinical response was observed in elderly vs nonelderly patients at weeks 16 (49.5% vs 47.3%; P=0.71), 32 (54% vs 58.2%; P=0.18), and 54 (53.8% vs 59.6%; P=0.38). Similarly, no significant difference in steroid-free remission was observed in elderly vs nonelderly patients at weeks 16 (37.4% vs 35.9%; P=0.44), 32 (43% vs 37.9%; P=0.33), and 54 (38.5% vs 46.5%; P=0.38).
	Safety
	Overall, AEs were similar in elderly vs nonelderly patients (14.2% vs 11.2%; P=0.350). No significant difference was observed in serious infections between elderly and nonelderly patients (7.08% vs 7.34%; P=1.000). Neoplasm was more frequently reported in elderly (4.25%, n=9) vs nonelderly patients (0.69%, n=3; P=0.003). In the elderly vs nonelderly patients, worsening of extraintestinal manifestations and perianal disease were reported in 4.74% vs 5.28% and 0.94% vs 3.44% of patients, respectively. AEs reported in the elderly patient group, excluding serious infections and de novo neoplasms, included respiratory infection (n=6), increased joint pain (n=4), headache (n=3), thrombotic event (n=2), mild gastrointestinal infection, iron deficiency anemia, nausea, spondyloarthritis, onychomycosis, eczematous lesions, cutaneous viral infection, malnutrition, infusional reaction, cough, and interstitial pneumonitis (n=1, each). One infusion reaction was reported in the elderly group. No treatment-related deaths occurred in either group.
Forss et al (2023)²³ conducted a nationwide prospective multicenter noninterventional study to evaluate the long-term clinical effectiveness and safety of STELARA in patients with CD using data from the SWIBREG registry in Sweden. Adult patients with CD treated with STELARA for the first time who were initiated on STELARA ≤2 weeks ago or <12 months ago (if sufficient data were documented in the registry within ±2 weeks of treatment initiation) were included. Patients received a weight-based IV infusion (~6mg/kg), followed by 90 mg SC injection at week 8 and maintenance treatment with 90 mg SC injection q8w or q12w. Primary outcome: Clinical remission (HBI score ≤4) at weeks 52 and 104 Secondary outcome: Clinical response (reduction in HBI score ≥3 among patients with baseline HBI score ≥5) and remission at weeks 52 and 104 among remitters at week 16 A total of 114 patients were included; 47% were female, and the median (IQR) age was 40 (31-54) years. A total of 28% (27/96) of patients were in clinical remission (HBI score <5) at baseline.	Effectiveness
	Week 52 Clinical remission and response were observed in 32% (31/96) and 36% (25/69) of patients, respectively. Week 104 Clinical remission and response were observed in 29% (28/96) and 29% (20/69) of patients, respectively. Clinical remission among the patients in remission at week 16 was achieved in 44% (11/25).
	Safety
	During follow-up, 23 AEs were reported in 13 patients (mild, n=16 [9.5 events per 100 PY]; moderate, n=3 [1.8 events per 100 PY]; and severe, n=4 [2.4 events per 100 PY). The most common AEs were pain and skin rashes. SAEs were reported in 5 patients (ruptured appendix, n=1; gastroenteritis, n=1; acute cholecystitis, n=1; and death, n=2). One death was reported in a middle-aged male, who died at week 71 of treatment due to opportunistic infection (Pneumocystis jirovecii). The patient was on combination therapy with STELARA and methotrexate. The second death was reported in a middle-aged male, who died from a cardiac arrest 8 months after STELARA discontinuation (due to lack of response). No malignancies were reported.
Thomas et al (2023)²⁴ evaluated the long-term clinical effectiveness and safety of STELARA in adult patients with CD using data from the IBDREAM registry in Netherlands. Patients received a weight-based IV infusion (~6mg/kg), followed by maintenance therapy with STELARA 90 mg SC q8w or q12w. Primary outcome: Corticosteroid-free remission (defined as clinical remission [HBI score ≤4] without corticosteroids) at week 104 Secondary outcomes: Clinical remission (HBI score ≤4), clinical response (a reduction in HBI score ≥3), biochemical remission (CRP level ≤10 mg/L or FCP ≤200 µg/g), endoscopic disease activity, safety, and treatment discontinuation A total of 101 patients were included; 57.4% were female, and the median (IQR) age was 39.9 (29.652.6) years. The median (IQR) disease duration was 13.0 (5.2-22.4) years. The median (IQR) HBI score was 5 (2-9), CRP level was 11 (2-28) mg/L, and FCP was 445 (190-1417) µg/g.	Effectiveness
	Corticosteroid-free clinical remission at weeks 13, 26, 52, and 104 was achieved in 46.5% (47/101), 43.6% (44/101), 35.0% (35/100), and 35.5% (35/99) of patients, respectively. Among patients with baseline biochemical disease activity, corticosteroid-free clinical remission at weeks 13, 26, 52, and 104 was achieved in 47.1% (33/70), 44.3% (31/70), 39.1% (27/69), and 40.6% (28/69), respectively. Among patients with clinically active disease at baseline, corticosteroid-free clinical remission at weeks 13, 26, 52, and 104 was achieved in 34.3% (23/67), 34.3% (23/67), 31.8% (21/66), and 30.3% (20/67), respectively. Among patients with biochemical disease activity and clinically active disease at baseline, corticosteroid-free clinical remission at weeks 13, 26, 52, and 104 was achieved in 37.8% (17/45), 33.3% (15/45), 34.1% (15/44), and 36.4% (16/44), respectively. Among patients with baseline endoscopic disease, corticosteroid-free clinical remission at weeks 13, 26, 52, and 104 was achieved in 41.3% (19/46), 41.3% (19/46), 28.9% (13/45), and 31.1% (14/45), respectively. Among patients with endoscopic disease and clinically active disease at baseline, corticosteroid-free clinical remission was achieved at weeks 13, 26, 52, and 104 in 28.6% (10/35), 28.6% (10/35), 17.6% (6/34), and 23.5% (8/34), respectively. Clinical remission was achieved in 52.5% (53/101), 50.5% (51/101), 40.0% (40/100), and 40.4% (40/991) of patients at weeks 13, 26, 52, and 104, respectively. Biochemical remission was achieved in 30.7% (31/101), 33.7% (34/101), 34.7% (35/101), 25.0% (25/100), and 30.3% (30/99) of patients at baseline and weeks 13, 26, 52, and 104, respectively.
	Safety
	During follow-up, 130 ADRs (87.1 per 100 PY) were reported. During the first year, treatment was discontinued in 6.9% (7) of patients due to AEs (progression of arthralgia, n=2; infusion reaction, n=1; seizure, n=1; frequent infections, n=1; pancreatitis, n=1; and headache, n=1). Infections (mild, n=43 [29.6 events per 100 PY]; moderate, n=19 [12.7 events per 100 PY]; and severe, n=2 [1.3 events per 100 PY]) were the most commonly reported ADRs (44.2 per 100 PY). The overall incidence rate of ADR was lower in the second vs first year of treatment (43.0 vs 119.0 per 100 PY).
Straatmijer et al (2021)²⁵ evaluated the 2-year effectiveness and safety of STELARA in adult patients with CD using data from the ICC registry in Netherlands. Patients received a weight-based IV infusion (~6 mg/kg), followed by maintenance therapy with STELARA 90 mg SC q8w or q12w. Primary outcome: Corticosteroid-free clinical remission (HBI score ≤4) at week 104 Secondary outcomes: Clinical response (HBI score reduction by ≥3), clinical remission (HBI score ≤4), biochemical remission (FCP ≤200 µg/g and/or CRP level ≤5 mg/L), ulcerative disease during endoscopy, and treatment discontinuation A total of 252 patients who completed ≥2 years of follow-up were included; 60.3% were female. The median (IQR) age and disease duration were 41 (32-55) years and 15 (10-22) years, respectively. The median (IQR) HBI score was 7 (4-11), CRP level was 8.0 (2.520.0) mg/L, and FCP was 633.5 (260.8-1524.8) µg/g.	Effectiveness
	Corticosteroid-free remission was achieved in 34% (84/247) of patients. Clinical response and remission were achieved in 27.1% (67/247) and 37.2% (92/247) of patients, respectively. Biochemical remission was achieved in 21.5% (53/247) of patients. Endoscopic Disease Activity After a median duration of 8 months, among the 46 patients with baseline endoscopic disease activity with ≥1 endoscopy during follow-up, 21.7% (10) of patients achieved remission of ulcers. A total of 17/46 patients underwent a second endoscopy during follow-up, of whom, 1 patient showed remission of ulcers. Endoscopy was performed shortly before withdrawal of therapy in 20/46 patients, and ulcers were observed in 80% (16/20) of patients. Treatment Discontinuation Overall, 45.6% (115) of patients discontinued treatment after a median (IQR) treatment duration of 28 (11-48) weeks (lack of response [61.7%], loss of response [18.3%], and AEs [7.0%]). Patients discontinued treatment early (n=3) due to malignancy, pregnancy (n=2), and on their own (n=1) after achieving clinical remission. Among 97 patients in corticosteroid-free clinical remission at week 52, 11.3% (n=11) stopped treatment after a median (IQR) duration of 89 (80-94) weeks (loss of response, n=9; malignancy, n=2).
	Safety
	Treatment discontinuation due to AE was reported in 3.2% (8) of patients after a median (IQR) treatment duration of 14 (1.75–34.50) weeks. Two patients discontinued treatment due to an infection (mild fever and moderate upper airway infection), and 6 patients discontinued due to noninfectious AEs (mostly musculoskeletal, n=3; headache, n=2). Infections reported to be related to treatment were mild (n=65 [18.7 events per 100 PY]); moderate (n=48 [13.8 events per 100 PY]); and severe (n=13 [3.7 events per 100 PY]). The most common AEs were headache, skin reaction, and musculoskeletal complaints. SAEs were reported in 9 patients (2.6 events per 100 PY). During follow-up, malignancies were reported in 3 patients (SCC at week 7 and melanoma and metastatic colorectal cancer after week 52). One death was reported due to an abdominal sepsis after a colonoscopic perforation.
Iborra et al (2020)²⁶ evaluated the long-term effectiveness of STELARA in adult patients with refractory CD using data from the ENEIDA registry in Spain. Patients received weight-based IV infusion (~6 mg/kg), followed by second induction dose of 90 mg SC at week 8. Primary outcome: Clinical remission (HBI score ≤4) and corticosteroid-free remission (remission without corticosteroids) at weeks 26 and 52 Other outcomes: Clinical response (HBI score ≥3) at weeks 26 and 52, impact on biomarkers (CRP and FCP), endoscopic improvement (based on SES-CD score), and safety A total of 407 patients were included; 52% were female, and the median (IQR) age was 45.28 (34.86-55.93) years. The median (IQR) disease duration was 11.06 (5.7-19.03) years. The mean (SD) HBI score was 6.7 (3.6), CRP level was 20.1 (29.8) mg/L, and FCP was 887 (909) µg/g.	Effectiveness
	At weeks 26 and 52, respectively, clinical remission was achieved in 57.3% (169/295) and 64.4% (190/295) of patients with HBI score >4 at baseline. Among patients with HBI ≤4 at baseline, 90.2% (101/112) and 94.6% (106/112) of patients remained in remission at weeks 26 and 54, respectively. Among patients taking corticosteroids at the beginning of treatment, corticosteroid-free remission was achieved in 59% (80/135) at week 52. At weeks 26 and 52, respectively, clinical response was achieved in 16.6% (49/295) and 11.9% (35/295) of patients with HBI score >4 at baseline. At weeks 26 and 52, respectively, CRP normalization was observed in 36.5% and 36.7% of patients, and FCP normalization was observed in 44.2% and 54.3% of patients. Among 159 patients with available endoscopic data at the end of follow-up, 16% (25) were in remission and 36% (58) had mild activity. Among 116 patients with available endoscopic data from baseline and end of follow-up, 55% (64) achieved an endoscopic response, 12% (14) experienced worsening of disease, and 33% (38) did not respond.
	Safety
	During the 52-week follow-up, 71 AEs were reported in 14.7% (60) of patients, and most were bacterial infections (34%). Overall, 18% (73) of patients were hospitalized during treatment, and 13% (53) required surgery (perianal disease, n=3; stoma closure, n=1; and ileal/ileocolonic resections, n=49). Two deaths were reported (1 was due to advanced brain cancer and 1 was a result of surgery complication [endocarditis]).
Abbreviations: 5-ASA, 5-aminosalicylic acid; ADR, adverse drug reaction; AE, adverse event; AZA, azathioprine; CD, Crohn’s disease, CDAI, Crohn’s Disease Activity Index; CI, confidence interval; CMI, clinically meaningful improvement; CRP, C-reactive protein; ENEIDA, Estudio Nacional en Enfermedad Inflamatoria Intestinal sobre Determinantes Genéticos y Ambientales; FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue; FCP, fecal calprotectin; HBI, Harvey-Bradshaw Index; HR, hazard ratio; IBD, inflammatory bowel disease; IBDQ, Inflammatory Bowel Disease Questionnaire; IFX, infliximab; IQR, interquartile range; IV, intravenous; OR, odds ratio; PGA, Physician’s Global Assessment; PY, patient-years; q4w, every 4 weeks; q8w, every 8 weeks; q12w, every 12 weeks; SAE, serious adverse event; SC, subcutaneous; SCC, squamous cell carcinoma; SD, standard deviation; SES-CD, Simple Endoscopic Score for Crohn disease; SWIBREG, Swedish Inflammatory Bowel Disease Registry; TNF, tumor necrosis factor; VDZ, vedolizumab; vs, versus; WPAI, Work Productivity and Activity Impairment; WPL, work productivity loss.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 23 October 2024.

Summarized in this response are data focused on clinical effectiveness and safety from prospective and retrospective studies and registries.

References

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