One-year effectiveness and safety of ustekinumab treatment in patients with ulcerative colitis: an Asan-Crohn’s and Colitis Association in Daegu-Gyeongbuk (CCAiD) multicenter real-world cohort study

Article information

Intest Res. 2026;.ir.2025.00258

Publication date (electronic) : 2026 April 20

doi : https://doi.org/10.5217/ir.2025.00258

Ji Eun Baek^1,2, Min Kyu Kim¹, Eun Soo Kim³, Kyeong Ok Kim⁴, Hyeong Ho Jo⁵, Sung Wook Hwang^1,6, Sang Hyoung Park^1,6, Byung Ik Jang⁴, Eun Young Kim⁵, Sung Kook Kim³, Suk-Kyun Yang^1,6, Byong Duk Ye^,1,6

¹Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

²Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea

³Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea

⁴Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea

⁵Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, Korea

⁶Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Correspondence to Byong Duk Ye, Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea. E-mail: bdye@amc.seoul.kr

Provisional data were presented as an oral presentation (FP07-01) at the 7th Korea Digestive Disease Week in 2023.

Received 2025 October 12; Revised 2025 December 23; Accepted 2025 December 30.

Abstract

Graphical abstract

INTRODUCTION

Ulcerative colitis (UC) is a chronic idiopathic inflammatory disorder of the colon which is characterized by bloody diarrhea, fecal urgency, abdominal pain, and diffuse mucosal inflammation [1]. Patients with UC require life-long treatments and the choice of treatment depends on multiple factors, including disease activity, extent of disease, prognosis, comorbidities, patients’ preferences, etc [2,3]. In the past, pharmacologic management of UC mainly relied on 5-aminosalicylates (5-ASAs), thiopurines, and corticosteroids, but clinicians now have a wider range of biologics and small molecule drugs, such as tumor necrosis factor inhibitors, anti-integrin agents, anti-interleukin agents, Janus kinase inhibitors, and sphingosine 1-phosphate receptor modulators which enable better disease control by improving mucosal healing rates, deep remission rates, and quality of life [3-5].

Ustekinumab (UST) is a monoclonal antibody to the p40 subunit of interleukin-12/23 and has been approved for the treatment of Crohn’s disease and more recently for the treatment of UC. In the UNIFI trial and long-term extension study, UST demonstrated a long-term efficacy and safety in patients with UC who were either biologic-naive or had failed to conventional or biologic therapy [6,7]. The clinical remission rate at week (W) 8 among patients who received intravenous (IV) UST at a dose of 6 mg/kg was 15.5% and clinical remission rates at W44 of maintenance therapy in patients who received 90 mg of subcutaneous (SC) UST every 12 weeks and 8 weeks were 38.4% and 43.8%, respectively [6]. A subpopulation analysis of the UNIFI trial focused on East Asian patients with UC demonstrated efficacy and safety results that were generally consistent with those observed in the overall study population [8].

To overcome the strict trial designs, which have limitations in reflecting real-life clinical practice, several real-world studies from Western countries have assessed the real-life effectiveness and safety of UST in patients with UC [9-24].

However, the real-world data on UST for Asian patients with UC are still lacking. Given the differences in the epidemiology and natural history of UC between Eastern and Western populations, it is worthwhile to compare therapeutic outcomes of biologic therapies between Eastern and Western patients with UC [25-27]. Therefore, we performed a real-world multicenter study on the 1-year therapeutic effectiveness and safety of UST treatment for Korean patients with UC.

METHODS

RESULTS

1. Patient Characteristics

A total of 60 patients with UC were included; one patient who had initiated UST due to infliximab-related adverse events (AEs) and was already in clinical remission at baseline was excluded from the effectiveness analysis (Supplementary Fig. 1). Baseline characteristics are summarized in Table 1. The median age at UC diagnosis was 36.5 years (IQR, 21.0–53.0 years), and the median age at UST initiation was 44.5 years (IQR, 30.1–61.8 years). The median disease duration at UST initiation was 6.5 years (IQR, 3.7–10.6 years). Forty-two patients (70.0%) had prior exposure to advanced therapies, with a mean number of previous agents of 1.3 (SD, 1.1). Extensive colitis was present in 39 patients (65.0%). At baseline, median Mayo and partial Mayo scores were 8.0 (IQR, 7.0–9.0) and 5.0 (IQR, 5.0–6.0), respectively; median MES was 3.0 (IQR, 2.0–3.0), and UCEIS was 5.5 (IQR, 4.0–6.0). Concomitant medications included oral 5-ASAs in 55 patients (91.7%), 5-ASA suppositories in 29 (48.3%), systemic corticosteroids in 28 (46.7%), and immunomodulators (thiopurines) in 24 (40.0%). Median baseline laboratory values were: WBC, 7,865/mm³ (IQR, 5,950–9,500/mm³); Hb, 13.1 g/dL (IQR, 10.7–14.3 g/dL); serum albumin, 3.7 g/dL (IQR, 3.4–4.1 g/dL); ESR, 30.5 mm/hr (IQR, 16.0–50.3 mm/hr); CRP, 0.5 mg/dL (IQR, 0.1–1.3 mg/dL); and FC, 2,206 mg/kg (IQR, 866–4,138 mg/kg).

Table 1.

Patient Characteristics

2. Clinical and Endoscopic Outcomes

Clinical outcomes after UST are shown in Fig. 1A. Among 59 evaluable patients, clinical remission was achieved in 29 (49.2%) at W8, 35 (59.3%) at W16–20, and 33 (55.9%) at W52–56. Corticosteroid-free clinical remission was achieved in 24 (40.7%), 33 (55.9%), and 31 (52.5%) at the same time points, respectively. Clinical response was observed in 40 (67.8%), 41 (69.5%), and 39 (66.1%). Endoscopic outcomes are presented in Fig. 1B. Endoscopic data were available for 53 of 59 patients at W16–20 (89.8%) and for 35 of 59 patients at W52–56 (59.3%); missing endoscopic outcomes were imputed as not achieving outcomes. At W16–20 and W52–56, endoscopic improvement was achieved in 33 (55.9%) and 22 (37.3%) patients, and endoscopic remission in 9 (15.3%) and 7 (11.9%), respectively.

Fig. 1.

Outcomes of ustekinumab therapy in ulcerative colitis. (A) Clinical outcomes after ustekinumab induction and maintenance therapy for patients with ulcerative colitis. (B) Endoscopic outcomes after ustekinumab induction and maintenance therapy for patients with ulcerative colitis.

3. Changes in Disease Activity Indices, Endoscopic Scores and Laboratory Values

Trends in disease activity indices, endoscopic scores, and laboratory markers during UST therapy are shown in Fig. 2. CRP and FC levels were log-transformed to approximate normality. Global P-values were calculated using linear mixed-effects models to assess changes over time. Least-squares means Mayo and partial Mayo scores, MES, and UCEIS significantly decreased (global P<0.001) (Fig. 2A and B). WBC (P=0.013), ESR, log-transformed CRP, and log-transformed FC also decreased significantly (global P<0.001) (Fig. 2C). Hb (P=0.277) and albumin (P=0.773) did not change significantly.

Fig. 2.

Changes in clinical, endoscopic, and laboratory parameters. (A) Changes in Mayo score and partial Mayo score, expressed as least-squares means±SEMs. (B) Changes in MES and UCEIS, expressed as least-squares means±SEMs. (C) Changes in laboratory values, expressed as least-squares means±SEMs. MES, Mayo endoscopic subscore; UCEIS, Ulcerative Colitis Endoscopic Index of Severity; WBC, white blood cell count; Hb, hemoglobin; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; FC, fecal calprotectin; SEMs, standard error of the means.

4. Factors Associated with Clinical Remission and Endoscopic Improvement

We evaluated the independent factors associated with clinical remission at each time point and reported the results in Table 2, Supplementary Table 1, and Supplementary Table 2. Prior exposure to advanced therapies was negatively associated with clinical remission at W8 (odds ratio [OR], 0.17; 95% confidence interval [CI], 0.05–0.65; P=0.01), whereas concomitant immunomodulator use was positively associated (OR, 3.85; 95% CI, 1.17–12.74; P=0.03) (Table 2). At W16–20, past smoking (OR, 0.19; 95% CI, 0.05–0.76; P=0.02) and prior advanced therapy exposure (OR, 0.23; 95% CI, 0.06–0.93; P=0.04) were negatively associated factors (Supplementary Table 1). At W52–56, higher body mass index (BMI) at baseline (OR, 1.26; 95% CI, 1.00–1.57; P<0.05), concomitant immunomodulator use (OR, 4.69; 95% CI, 1.04–21.06; P=0.04), and endoscopic improvement at W16–20 (OR, 13.47; 95% CI, 2.87–63.30; P<0.01) were positively, whereas prior advanced therapy exposure remained negatively (OR, 0.20; 95% CI, 0.04–0.98; P<0.05) associated factors (Supplementary Table 2). Concomitant immunomodulator use was also the sole factor associated with endoscopic improvement at W52–56 (OR, 3.23; 95% CI, 1.01–10.29; P<0.05) (Table 3).

Table 2.

Univariable and Multivariable Analyses of Factors Associated with Clinical Remission^a at Week 8

Table 3.

Univariable and Multivariable Analyses of Factors Associated with Endoscopic Improvement^a at Week 52–56

6. Persistence of UST

UST was discontinued in 9 (15%) patients by W52–56. Patients who discontinued UST had higher baseline Mayo (median: 9 vs. 8; P=0.02) and partial Mayo scores (6 vs. 5; P=0.02) and lower albumin (3.4 g/dL vs. 3.7 g/dL; P=0.02) (Supplementary Table 4). Main reasons for discontinuation were secondary loss of response (n=5, 8.3%) and primary non-response (n=4, 6.7%). No patient discontinued UST due to intolerance. Kaplan–Meier persistence rates of UST were 95.0% at 2 months, 90.0% at 6 months, and 84.9% at 12 months; median UST exposure was 72.6 weeks (IQR, 54.7–104.7 weeks) (Fig. 3).

Fig. 3.

Persistence of ustekinumab in patients with ulcerative colitis.

7. Adverse Events

Twenty-four patients (40.0%) experienced ≥1 AEs, most commonly infections (n=8, 13.3%): upper respiratory infections (n=5, 8.3%), herpes zoster (n=1, 1.7%), and cytomegalovirus colitis (n=1, 1.7%). One patient (1.7%) experienced a serious AE (SAE) and underwent colectomy for UC-associated colorectal cancer after 1.7 years on UST. Additional AE details are presented in Table 4.

Table 4.

Adverse Events During Ustekinumab Treatment (n=60)

DISCUSSION

In this retrospective multicenter cohort study, UST demonstrated favorable effectiveness as both induction and maintenance therapy for Korean patients with UC, with more than half of the patients achieving clinical remission at W52–56. Approximately 40% also achieved endoscopic improvement at W52–56, accompanied by favorable trends in biochemical markers over time. UST exhibited a reassuring safety profile, with only 1 patient (1.7%) experiencing a SAE and no new safety concerns identified.

To our knowledge, this is the first study to confirm the real-world effectiveness and safety of UST in Korean patients with UC. Notably, the clinical remission (49.2%) and response (67.8%) rates at W8 in our study appear higher than those reported in the pivotal UNIFI trial (clinical remission 15.5%; clinical response 61.8%) and its East Asian subgroup (clinical remission 11.1%; clinical response 60.0%) following a single IV UST dose (6 mg/kg) [6,8]. However, direct comparison is limited, as UNIFI used the total Mayo score, whereas our study used the partial Mayo score [6]. Additionally, W8 endoscopic data and total Mayo scores could not be collected because Korean reimbursement policy requires endoscopic assessment at W16–20. Controlled trials may also apply stricter eligibility and outcome measures, as shown in a Spanish analysis where only 12.7% of biologic-treated UC patients would have met pivotal trial criteria [36].

Our findings align with real-world data from Western cohorts reporting clinical remission and response rates of 17.0%–61.0% and 44.2%–77.0% after UST induction (W12–16) [9-24]. Japanese studies have reported comparable remission rates (29.0%–70.0%) and response rates (50.0%–82.3%) at W8, and a multicenter Japanese study showed 53.7% clinical remission and 71.1% clinical response rates at W16 [37-40]. These similarities likely reflect comparable baseline characteristics, including ethnic factors. Moreover, the proportions of patients previously exposed to advanced therapies (64.0%–83.3%) and treated with concomitant immunomodulators (25.8%–40.0%) paralleled with those in our study population and these also might have resulted in similar results [37-40].

In the Delphi-like process in the STRIDE-II consensus, endoscopic response was ranked as important as clinical response as a short-term treatment goal in UC [41]. Unlike most previous studies, including both Western and Eastern ones, which reported endoscopic outcomes at 6–12 months [10,12-15,18,20,24,39], our study additionally demonstrated favorable short-term endoscopic improvement rate at W16–20 (55.9%). In addition, our result coincides with the data from small-sized studies, which showed endoscopic improvement (MES of 0–1) rates of 18.4%–52% at W12–16 [9,42]. Considering the importance of endoscopic outcomes as a short-term treatment goal in UC, further studies with short-term endoscopic evaluation are warranted.

We uniquely report temporal trends in disease activity indices, endoscopic scores, and inflammatory markers, demonstrating significant reductions in WBC, ESR, CRP, and FC during UST therapy, extending beyond the CRP/FC focus of UNIFI long-term extension and most prior real-world studies [7,10,17,20,21]. In contrast, Hb and serum albumin levels showed no significant improvement, differing from a U.K. cohort study demonstrating marginal but significant improvements in Hb, platelet count, serum albumin, and CRP levels at W8, as well as improvements in platelet count and serum albumin at W16 [18]. Given the potential prognostic value of early albumin recovery in UC therapy, larger studies are needed to clarify its role in patients treated with UST [43,44].

Our multivariable analysis confirmed that prior exposure to advanced therapies predicted lower clinical remission across induction and maintenance, consistent with UNIFI and other real-world studies [6,9,12,40,45]. Concomitant immunomodulator use was positively associated with clinical remission at W8 and W52–56 and with endoscopic improvement at W52–56, although previous evidence suggests combination therapy does not uniformly improve outcomes with non-infliximab biologics [37,46,47]. Interestingly, our study demonstrated that higher baseline BMI was associated with an increased probability of clinical remission at W52–56. Although higher body weight could theoretically lead to lower drug concentrations during fixed-dose SC administration of UST, this concern is less applicable to our study, as BMI was assessed only at baseline and the initial IV UST dosing was weight-based. Alternatively, higher baseline BMI may reflect a surrogate marker of lower disease severity at baseline that was not fully captured by conventional clinical or endoscopic indices. Patients with relatively preserved nutritional status and less systemic inflammation might have higher BMI at baseline and, in turn, might have demonstrated more favorable long-term treatment responses to UST. This hypothesis warrants further investigation in larger studies incorporating longitudinal BMI assessment and therapeutic drug monitoring.

According to a recent meta-analysis, 28.4% of patients with UC needed dose escalation (decreasing the dose intervals of 90 mg UST SC from 12 to 8 weeks, or from 8 to every 6 or even 4 weeks) due to suboptimal response or loss of response [48]. In addition, several long-term real-world studies proved that interval shortening of UST SC every 4 or 6 weeks were effective and safe in UC patients who lost response to SC dosing every 8 weeks [12,19]. In our study, 9 patients (34.6%) have reduced SC injection interval time from every 12 to 8 weeks, but 2 patients (7.7%) swapped to tofacitinib therapy due to loss of response even after interval shortening of UST. However, no patients in our study received dosing shorter than 8 weeks, as this is not yet approved in Korea. Moreover, our sample size was too small and the follow-up period was not long enough to evaluate the clinical outcomes after interval shortening from every 12 to 8 weeks. Larger and longer-term studies are necessary to define optimal interval shortening strategies.

UST persistence was high, approaching 85% at 1 year, with discontinuations mainly due to secondary loss of response or primary non-response, similar to Western data [49,50]. Persistence of an advanced therapy is important in clinical practice because it reflects not only the drug’s effectiveness but also its tolerability and the preferences of both patients and clinicians. In this regard, our study reinforces UST’s practical value in UC management.

Our study reported tolerable AEs (40.0%) and SAEs (1.7%) after UST treatment. Infections were the most common AEs (13.3%), with upper respiratory infections being the most frequent, occurring in 8.3% of patients. In a real-world induction study of UST for Korean patients with Crohn’s disease, AEs and SAEs have been reported in 41.5% and 4.6% of patients, respectively [51]. We believe that the findings of this study reinforce the safety profile of UST for Asian patients with IBD. With regard to one case of an SAE, colectomy performed for UC-associated colorectal cancer was considered unrelated to UST treatment, as the malignancy was attributed to long-standing colitis-related dysplasia. The interval from the diagnosis of UC to the diagnosis of colorectal cancer was approximately 7 years, during which the disease remained active, not responding to thiopurines, infliximab, and adalimumab before introduction of UST. Importantly, colorectal cancer was diagnosed 1.7 years after the initiation of UST, a timeframe generally regarded as too short to support de novo tumorigenesis attributable to immunosuppressive biologic therapy.

Taken together, our findings offer meaningful clinical implications for the management of UC in Korea. For patients initiating their first advanced therapy, UST may represent an attractive treatment option given its favorable long-term effectiveness and safety profile. Furthermore, combination therapy with UST and an immunomodulator may be considered during the first year of therapy to potentially improve outcomes.

This study has limitations, primarily related to its retrospective design and potential heterogeneity in practices between participating centers. However, strict regulation of IBD advanced treatments by a single universal reimbursement criterion by the Health Insurance Review and Assessment Service of Korea likely minimized center-to-center variation [51]. Nevertheless, due to the absence of a pre-defined protocol like controlled trials, some of outcome data, such as endoscopic scores, were missing at each time point. For conservative interpretation, missing endoscopic outcomes were imputed as not achieving endoscopic outcomes, which might have led to an underestimation of the true endoscopic effectiveness. Although a centralized image-reading process, as in controlled trials, was not performed, the use of standardized scoring systems and regular IBD-endoscopy training programs within these academic centers is expected to reduce inter-observer variability. Second, data were from tertiary hospitals, potentially skewing toward more severe cases, but advanced therapies in Korea are largely prescribed in such centers. Finally, histologic outcomes, which is getting more attention as another endpoint of UC treatment, could not be assessed, as it is not yet an established therapeutic target in Korea [52]. In conclusion, UST was effective and well tolerated as induction and maintenance therapy for up to 1 year in Korean patients with UC, supporting its use in real-world clinical practice.

Supplementary Material

Supplementary materials are available at the Intestinal Research website (https://www.irjournal.org).

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