Real-world effectiveness and safety of carotegrast methyl in patients with ulcerative colitis: a multicenter retrospective cohort study

Ryoji Koshiba; Kazuki Kakimoto; Takuya Inoue; Makoto Sanomura; Mitsuyuki Murano; Hiroaki Ito; Yoshihiko Nakanishi; Ken Kawakami; Noboru Mizuta; Keijiro Numa; Naohiko Kinoshita; Kei Nakazawa; Azusa Hara; Yuki Hirata; Naokuni Sakiyama; Shoko Arimitsu; Takako Miyazaki; Shiro Nakamura; Hiroki Nishikawa

doi:10.5217/ir.2025.00066

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Original Article Real-world effectiveness and safety of carotegrast methyl in patients with ulcerative colitis: a multicenter retrospective cohort study: Ryoji Koshiba¹, Kazuki Kakimoto^1,2, Takuya Inoue³, Makoto Sanomura⁴, Mitsuyuki Murano⁵, Hiroaki Ito⁶, Yoshihiko Nakanishi², Ken Kawakami⁷, Noboru Mizuta¹, Keijiro Numa¹, Naohiko Kinoshita¹, Kei Nakazawa¹, Azusa Hara⁶, Yuki Hirata¹, Naokuni Sakiyama⁴, Shoko Arimitsu⁶, Takako Miyazaki¹, Shiro Nakamura¹, Hiroki Nishikawa¹; DOI: https://doi.org/10.5217/ir.2025.00066
Published online: August 12, 2025

¹²nd Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Takatsuki, Japan

²Department of Gastroenterology, Hirakata City Hospital, Hirakata, Japan

³Inoue Gastroenterology and Endoscopy Clinic, Izumiotsu, Japan

⁴Department of Gastroenterology, Hokusetsu General Hospital, Takatsuki, Japan

⁵Murano Clinic, Osaka, Japan

⁶Kinshukai Infusion Clinic, Osaka, Japan

⁷Department of Gastroenterology, Moriguchi Keijinkai Hospital, Moriguchi, Japan

Correspondence to Kazuki Kakimoto, 2nd Department of Internal Medicine, Osaka Medical and Pharmaceutical University, 2-7 Daigakumachi, Takatsuki 569-8686, Japan. E-mail: kazuki.kakimoto@ompu.ac.jp

• Received: April 25, 2025 • Revised: June 24, 2025 • Accepted: June 30, 2025

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Abstract
INTRODUCTION
METHODS
RESULTS
DISCUSSION
NOTES
REFERENCES

Abstract

Background/Aims
Carotegrast methyl is a novel small-molecule drug that inhibits α4 integrin. It is prescribed for up to 6 months in patients with moderate ulcerative colitis who have demonstrated an inadequate response to or intolerance of 5-aminosalicylic acid. However, only a few clinical trials have been conducted to assess its effectiveness. This study aimed to evaluate the efficacy and safety of carotegrast methyl in patients with ulcerative colitis.
Methods
This multicenter retrospective study included patients with active ulcerative colitis treated with carotegrast methyl between March 2022 and October 2024. The primary outcome was the clinical remission rate following treatment with carotegrast methyl. Secondary outcomes included the clinical response rate, predictors of clinical remission, ulcerative colitis relapse rate after discontinuing carotegrast methyl, and incidence of adverse events.
Results
This study included 62 patients who received carotegrast methyl treatment. The median duration of administration was 84 days, with 48.4% of patients achieving clinical remission at the time of carotegrast methyl discontinuation. In 42 patients with corticosteroid/advanced therapies-naive disease, the clinical remission rate was 54.8%. Multivariate analysis identified the baseline partial Mayo score as an independent predictor of clinical remission. Among those who achieved clinical remission, 34.8% experienced a relapse with a median time to relapse of 152 days. Adverse events occurred in 8 patients, but none were serious.
Conclusions
Carotegrast methyl demonstrated good efficacy and safety, potentially benefiting patients with low baseline disease activity. This drug may be a useful treatment option to consider before systemic corticosteroid therapy for ulcerative colitis.
Keywords: Ulcerative colitis; Carotegrast methyl; Integrins

INTRODUCTION

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) of unknown etiology characterised by erosions and ulcers primarily in the colon. The pathology of UC involves lymphocyte infiltration into the lamina propria of the intestinal mucosa. At sites of intestinal inflammation, the expression of adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1) and mucosal addressin cell adhesion molecule 1 (MAdCAM-1) increases in vascular endothelial cells [1-3]. Additionally, integrins—cell surface proteins—are expressed on inflammatory cells such as lymphocytes, in blood vessels. Integrins are heterodimers consisting of one α and one β subunit, and α4β1 integrin binds to VCAM-1, whereas α4β7 integrin binds to MAdCAM-1.4 This binding promotes lymphocyte adhesion, migration, and infiltration into intestinal tissue. VCAM-1 is expressed on the vascular luminal surface of various tissues, whereas MAdCAM-1 is locally expressed in blood vessels of the lamina propria of the intestinal tract [5,6]. Drugs targeting cell adhesion molecules, such as the anti-α4β7 antibody agent vedolizumab, are widely used for UC and Crohn’s disease [7,8]. In contrast, carotegrast methyl (CGM) is a novel oral small-molecule drug that inhibits α4 integrin. CGM is converted to the active metabolite carotegrast in vivo and inhibits α4β1 and α4β7 integrins.9 This action suppresses lymphocyte infiltration from blood vessels into intestinal tissue at inflammation sites, exerting an anti-inflammatory effect [10].

In a phase III clinical trial, the efficacy and safety of CGM were evaluated in patients with moderate UC who had shown an inadequate response to or intolerance of oral 5-aminosalicylic acid (5-ASA) [11]. In total, 203 patients with UC were randomly assigned to receive either 960-mg CGM (n=102) or a placebo (n=101) orally three times daily for 8 weeks. The primary outcome was the clinical response rate based on the Mayo score at 8 weeks. Clinical response was achieved in 45.1% (46/102) of patients in the CGM group compared with 20.8% (21/101) in the placebo group (P<0.001). The endoscopic improvement rate at 8 weeks (Mayo endoscopic subscore [MES] ≤ 1) was 54.9% (56/102) in the CGM group compared with 26.7% (27/101) in the placebo group (P<0.0001). CGM was administered for up to 24 weeks, and the incidence of adverse events was insignificantly different from that in the placebo group, with no serious adverse events.

The efficacy and safety of CGM have been confirmed in phase II and phase III trials, leading to its approval for insurance coverage in Japan in March 2022, making it available for clinical use [11,12]. CGM is indicated for patients with moderate UC who have an inadequate response to or intolerance of 5-ASA, with a maximum treatment duration of 6 months. Systemic corticosteroid therapy is an option for patients with UC with an inadequate response to 5-ASA; however, their use is associated with side effects, and a certain percentage of patients become steroid-dependent or resistant. Achieving remission with CGM can help avoid the use of systemic corticosteroids, providing a therapeutic advantage for patients with UC.

As clinical trials are conducted in a strictly controlled environment and the backgrounds of the participating patients may not be representative of those with IBD in the general population, assessing the therapeutic outcome of a drug in real-world practice is important. However, only a few real-world studies on CGM have been conducted. Therefore, we conducted the first multicenter study to evaluate the efficacy and safety of CGM in real-world clinical practice.

METHODS

1. Study Design

This was a multicenter, retrospective study of patients with active UC treated with CGM between March 2022 and October 2024. This study was conducted at 7 medical institutions that treat patients with IBD. Patients were administered 960-mg CGM orally three times daily, and treatment was discontinued within 6 months. When CGM was administered to patients treated with azathioprine, biologics, or Janus kinase inhibitors, the latter medications were discontinued to avoid concomitant use. Baseline laboratory testing, including markers of systemic inflammation, was performed within 1 week before initiating CGM treatment. Response evaluations were performed at weeks 2, 4, and 8, and every 8 weeks thereafter. All patients were followed up through physical examination and blood tests.

2. Outcomes

The primary outcome was the clinical remission rate, as assessed by the partial Mayo (pMayo) score, at the end of the CGM treatment period. Secondary outcomes included the clinical response rate following CGM treatment, cumulative clinical remission rate up to week 24, predictors of clinical remission, relapse rate of UC after CGM discontinuation, and incidence of adverse events. Clinical remission and response rates at the end of CGM treatment were analyzed using the full analysis set, defined as all patients for whom CGM efficacy could be evaluated. Cumulative clinical remission was defined as achieving clinical remission at least once by the time of each visit (weeks 2, 4, 8, 16, and 24). Clinical remission and response rates at weeks 2, 4, 8, 16, and 24 were evaluated using an intent-to-treat (ITT) approach. The ITT population included all patients who initiated treatment with the study drug, regardless of the treatment response or subsequent discontinuation. In this analysis, patients who achieved clinical remission and subsequently discontinued the drug were still followed for relapse. If a relapse occurred after drug discontinuation, the patient was considered not to have maintained clinical remission from the time of relapse onward.

Clinical disease activity in UC was assessed primarily using the pMayo score [13]. The MES was used to assess endoscopic activity. Clinical remission was defined as a pMayo score of 2 or less, with each subscore of 1 or less, and a decrease of 2 or more points in the pMayo score compared with baseline. Clinical response was defined as a decrease in the pMayo score from a baseline of ≥25% and ≥ 2 points, and a decrease in the rectal bleeding subscore from a baseline of ≥ 1 point or a rectal bleeding subscore of ≤ 1 point. Patients who achieved clinical remission at the time of CGM discontinuation were classified as the remission group, whereas those who did not achieve remission were classified as the non-remission group. Clinical relapse was defined as an increase in the pMayo score of 3 or more points, a rectal bleeding subscore of 1 or more points, and the investigator’s decision.

To reduce physician-related subjective bias, clinical disease activity at the end of the CGM treatment period was additionally assessed on the basis of the Patient-Reported Outcome 2 (PRO2) [13]. Clinical remission based on PRO2 was defined as a PRO2 score of 0, and clinical response was defined as a decrease of at least 50% from baseline. All adverse events potentially associated with CGM were recorded for all patients whose safety could be assessed.

3. Statistical Analysis

Continuous variables are summarized as medians with interquartile ranges (IQRs) and compared between groups using the Mann-Whitney U test. Categorical variables are summarized as frequencies and percentages and compared using the Pearson chi-square test. Kaplan-Meier analysis was performed to evaluate the cumulative incidence of CGM discontinuation and differences between groups. Discontinuation of CGM due to lack of efficacy was defined as a discontinuation event, whereas discontinuation due to clinical remission or side effects was defined as censoring. The cumulative relapse-free rate after CGM discontinuation was also analyzed using Kaplan-Meier analysis. Univariate logistic regression analysis was used to identify factors associated with CGM clinical remission. Multivariate logistic regression analysis included variables from the univariate analysis with P<0.20 that were not interrelated. Predictive factors associated with clinical remission are presented as odds ratios (ORs) with 95% confidence intervals (CIs). Receiver operating characteristic (ROC) curves were plotted to calculate the area under the ROC curve and evaluate the predictive performance of these factors. Statistical significance was set at P<0.05 (two-sided test). All statistical analyses were performed using EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan), a graphical user interface for R (R Foundation for Statistical Computing, Vienna, Austria) [14]. GraphPad Prism 6 was used to generate bar graphs, line graphs, and box-and-whisker plots.

4. Ethical Statements

The study was conducted in accordance with the principles outlined in the Declaration of Helsinki. The Ethics Committee of Osaka Medical and Pharmaceutical University approved the study protocol (protocol code 2024-051, 18 July 2024). The need for consent was waived by the ethics committee owing to the retrospective nature of the study, and an opt-out approach was applied.

RESULTS

1. Patients and Baseline Characteristics

We identified 66 patients with UC who underwent CGM treatment at 7 medical institutions. Three patients were excluded owing to transfer, leaving 63 patients for the safety evaluation (Fig. 1). One patient was excluded because CGM was administered in a state of clinical remission despite endoscopic activity. The treatment efficacy was evaluated in 62 patients. Table 1 shows the clinical characteristics of 62 patients (32 men and 30 women) at the start of treatment. The median age was 44 years (IQR, 30–58 years), and the median disease duration was 64 months (IQR, 26–111 months). The median serum C-reactive protein value, pMayo score, and MES were 0.18 mg/dL (IQR, 0.10–0.56 mg/dL), 5.0 (IQR, 3.0–6.0), and 2.0 (IQR, 1.0–2.0; n=29), respectively. Regarding medications that were being administered immediately prior to CGM administration, most patients were being treated with 5-ASA (88.7%), and 1 (1.6%) and 7 (11.3%) patients were being treated with oral prednisolone and azathioprine, respectively. Four (6.5%) and 15 (24.2%) patients had been receiving oral budesonide multimatrix and budesonide rectal foam, respectively, and 2 patients had been receiving these drugs concomitantly. Three patients (4.8%) had a history of treatment failure with advanced therapies (ATs), including 1 patient each who received vedolizumab and filgotinib immediately before CGM. No patient received concomitant corticosteroids (prednisolone and budesonide), azathioprine, or ATs after starting CGM treatment.

2. CGM Efficacy

The median duration of CGM treatment was 84 days (IQR, 42–151 days), with all patients completing treatment within 6 months. Among the 62 patients evaluated for efficacy, 48.4% (30/62) achieved clinical remission, and 56.5% (35/62) achieved a clinical response at the time of CGM discontinuation, as assessed by the pMayo score (Fig. 2A). Based on the PRO2, 46.8% (29/62) achieved clinical remission, and 56.5% (35/62) achieved a clinical response, demonstrating results consistent with those assessed by the pMayo score (Fig. 2B). In 42 patients with corticosteroid/AT-naive, clinical remission and clinical efficacy rates were 54.8% (23/42) and 64.3% (27/42), respectively (Fig. 2C). In 17 patients with budesonide failure immediately before CGM, clinical remission and clinical efficacy rates were 35.3% (6/17) and 41.2% (7/17), respectively (Fig. 2D). The cumulative clinical remission rates in all 62 patients were 37.1%, 46.8%, 50.0%, 54.8%, and 54.8% at 2, 4, 8, 16, and 24 weeks after treatment, respectively, reaching a maximum at 16 weeks (Fig. 3). The ITT analysis revealed that the clinical remission rates at weeks 2, 4, 8, 16, and 24 were 37.1% (23/62), 41.9% (26/62), 45.2% (28/62), 48.4% (30/62), and 45.2% (28/62), respectively (Fig. 4A).

3. CGM Discontinuation

The median treatment duration was 133 days (IQR, 79–168 days) in the remission group (n =30) at the time of CGM discontinuation compared with 49 days (IQR, 15–89 days) in the non-remission group (n =32) (P<0.001) (Fig. 5A). CGM was discontinued owing to clinical remission in 43.5% (27/62), lack of efficacy in 45.2% (28/62), and adverse events in 11.3% (7/62). Overall, 78.6% (22/28) of CGM discontinuations due to lack of efficacy occurred within 14 weeks (Fig. 5B).

4. Changes in Disease Activity and Biomarkers

We examined changes in the pMayo score and blood test data over time after CGM treatment. In the remission group, the pMayo score was significantly lower from week 2 onwards than at baseline (Fig. 6A). In the remission group, the serum C-reactive protein level tended to decrease after week 4 compared with baseline (Fig. 6B). The lymphocyte counts increased significantly after CGM treatment in the remission and non-remission groups (Fig. 6C).

5. Factors Associated with Clinical Remission

The non-remission group had a significantly higher pMayo score at baseline than the remission group (6 [IQR 5–7] vs. 4 [IQR 3–5], P< 0.001) (Table 2). Logistic regression analysis was performed to identify factors associated with clinical remission at the time of CGM discontinuation. In the univariate analysis, the baseline pMayo score was inversely associated with clinical remission during CGM treatment (OR, 0.53; 95% CI, 0.36–0.78; P=0.001) (Table 3). Additionally, a trend toward higher efficacy was observed in corticosteroid/AT-naive patients (OR, 2.25; 95% CI, 0.75–6.76; P=0.149). The multivariate analysis confirmed the pMayo score as an independent factor of clinical remission (OR, 0.55; 95% CI, 0.37–0.81; P=0.003).

A ROC curve was constructed to determine the optimal baseline pMayo score threshold for CGM efficacy (Fig. 7). When the statistical analysis was performed with clinical remission after CGM discontinuation as the endpoint, the area under the curve of the pMayo score was 0.75, indicating the high accuracy of the ROC curve. The sensitivity and specificity were 75.0% and 66.7%, respectively, with a cutoff value of 5 for pMayo scores. We subsequently compared the cumulative incidence rate of CGM discontinuation due to a lack of efficacy based on the baseline pMayo score (Fig. 5C). The proportion of patients who discontinued CGM owing to ineffectiveness was significantly higher in those with a baseline pMayo score of ≥6 than those with a score of ≤5 (P<0.001).

6. UC Relapse Following CGM Discontinuation

In the 30 patients with UC who achieved clinical remission at the time of CGM discontinuation, maintenance therapy included 5-ASA alone in 16 patients (53.3%), 5-ASA plus azathioprine in 4 patients (13.3%), azathioprine alone in 4 patients (13.3%), and no treatment in 2 patients (6.7%) (Table 4). In 3 of those cases, azathioprine was newly initiated. Additionally, 2 patients (6.7%) received vedolizumab and 2 patients (6.7%) received granulocyte and monocyte adsorptive apheresis as maintenance therapy. We examined the maintenance rate of clinical remission from UC up to 52 weeks after CGM discontinuation in 23 patients, excluding the 4 patients who received either vedolizumab or granulocyte and monocyte adsorptive apheresis, and 3 patients who newly initiated azathioprine. The median follow-up period was 201 days (range, 103–373 days), and 34.8% (8/23) of the patients relapsed. The median time to relapse was 152 days (range, 64–279 days). Cumulative relapse-free rates at 8, 26, and 52 weeks after CGM discontinuation were 90.5%, 78.9%, and 62.5%, respectively (Fig. 8).

In 30 patients who achieved clinical remission at the time of CGM discontinuation, factors associated with relapse after CGM withdrawal were analyzed. Patients were classified into remission and relapse groups. Clinical background factors at CGM initiation and discontinuation, CGM duration, and use of additional maintenance therapy after discontinuation were assessed; however, no factors were significantly associated with relapse (Table 5).

7. Safety

Adverse events occurred in 12.7% (8/63) patients (Table 6). The most common adverse events were liver dysfunction (4.8%, 3/63) and nausea (4.8%, 3/63). None of the adverse events were severe; however, 11.1% (7/63) of the patients discontinued CGM treatment. All adverse events promptly resolved after treatment discontinuation.

DISCUSSION

This study was the first multicenter study to explore the efficacy of CGM in patients with UC. The findings make a significant contribution to the literature because real-world clinical data were only available from a single center study with a small sample size [15]. In this study, approximately half of patients with UC achieved clinical remission at the time of CGM discontinuation, demonstrating good efficacy in clinical practice. The study also showed that patients with UC with low baseline disease activity had good treatment outcomes, suggesting a preferred case profile for CGM. Adverse events occurred in 12.7% of patients, but none were serious, indicating a favorable safety profile.

In the Japanese treatment guidelines, CGM is indicated for patients with moderate UC who are inadequate responders or intolerant of 5-ASA [16]. It is considered an alternative treatment option to systemic corticosteroid therapy with prednisolone. In this study, only 3 patients received prednisolone or ATs before CGM treatment, suggesting that CGM was primarily introduced to avoid systemic corticosteroids. Seventeen patients (27.4%) received oral or topical budesonide before CGM treatment. Whether remission can be achieved without systemic corticosteroid therapy by administering CGM in patients with budesonide-refractory UC is an important consideration in developing treatment strategies. In our real-world clinical study, CGM demonstrated moderate efficacy in budesonide-refractory UC, and the univariate analysis revealed no significant negative correlation between budesonide use and clinical remission. However, the limited number of cases in these sub-analyses necessitates further evidence from larger patient cohorts.

In a phase III CGM trial, the cumulative clinical response rates were 63% and 70% at 8 and 24 weeks, respectively [11]. In our cohort, the cumulative clinical response rates were similar (62.9% at 8 weeks and 67.7% at 24 weeks). In contrast, the cumulative response rate at 2 weeks was 43.5% in our study compared with 29% in the phase III trial, suggesting that a response is achieved relatively early after starting treatment in clinical practice [11]. This difference may be because the median pMayo scores for UC disease activity at baseline in the phase III trial and our cohort were 5.7 and 5, respectively, indicating that CGM was administered to patients with UC with somewhat lower disease activity in clinical practice.

The multivariate analysis of factors associated with clinical remission showed that CGM was less effective in patients with UC and higher baseline disease activity, as measured by the pMayo score. The threshold pMayo score for predicting CGM efficacy was determined using ROC curves and was identified as 5. The rate of CGM discontinuation due to a lack of response was significantly higher in patients with a pMayo score ≥6 (P<0.001). Mühl et al. [17] reported that baseline disease activity was an independent predictor of response to vedolizumab, an α4β7 integrin antibody, in patients with UC and Crohn’s disease. Collectively, these findings suggest that disease activity could serve as a useful predictor of response to anti-integrin therapy. Recently, with the emergence of various molecularly targeted drugs for IBD, identifying clinical and biological markers that predict drug responses has become increasingly important [18-22]. Our findings are clinically significant, as they provide a profile of suitable patients with UC for whom CGM may be most effective.

As the administration period of CGM is limited to 6 months, maintenance therapy after its discontinuation is crucial in clinical practice. In this study, 5-ASA or azathioprine was the most commonly used maintenance therapy, accounting for 80% of cases (24/30). Ohmori [15] reported a cumulative relapse-free rate of 77.8% at 26 weeks after CGM discontinuation in 9 patients with UC who achieved endoscopic improvement (MES of 0 or 1). In our multicenter study, the cumulative relapse- free rate at 26 weeks was 81.4%, indicating comparable outcomes.

These favorable results may be because most patients treated with CGM did not have refractory UC. Therefore, if clinical remission can be achieved in patients with non-refractory UC using CGM, maintaining clinical remission with 5-ASA or immunosuppressants alone without the need for systemic corticosteroid therapy may be possible.

The uncertainty regarding the appropriate duration of CGM administration is one of the clinical challenges associated with relapse following CGM discontinuation. For example, whether CGM should be discontinued immediately after achieving clinical remission or continued for up to 6 months remains unclear. Additionally, the relapse rate may be lower if mucosal healing is achieved at the time of CGM discontinuation. Further investigations are required to determine the optimal timing and conditions for discontinuing CGM.

Integrins are transmembrane glycoproteins expressed on various cell surfaces that mediate cell-cell and cell-extracellular matrix adhesion [23]. Integrin signaling regulates changes in cell morphology and controls the migration of hematopoietic cells into tissues. These proteins are heterodimers composed of α and β subunits. The 18 α subunits and 8 β subunits have been identified, resulting in at least 24 distinct integrins based on their combinations [24]. The integrin α4β1 is primarily expressed on lymphocytes, monocytes, and eosinophils, interacting with VCAM-1 expressed on vascular endothelial cells in various tissues [6]. The α4β7 integrin, predominantly expressed on lymphocytes and eosinophils, interacts with MAdCAM-1 on vascular endothelial cells in the intestine [7]. In patients with IBD, the expression levels of gut-tropic integrins and cell adhesion molecules are upregulated in inflamed intestinal tissues, making these integrins and adhesion molecules potential therapeutic targets [25-27]. Vedolizumab, an anti-α4β7 integrin monoclonal antibody, specifically inhibits the infiltration of inflammatory cells into the intestine and is known for its high safety profile [28]. In contrast, natalizumab, an anti-α4 integrin monoclonal antibody, targets α4β7 and α4β1 integrins [29]. CGM inhibits α4β7 and α4β1 integrins and shares a similar mechanism of action with natalizumab. Owing to the increased risk of developing progressive multifocal leukoencephalopathy (PML) a phase III trial on CGM limited its use to a maximum of 6 months and prohibited its concomitant use with immunosuppressive agents. These same precautions apply to the clinical use of CGM in Japan, and no PML cases related to CGM have been reported. No new safety concerns were identified in this study, suggesting that CGM has a favorable safety profile.

This study has some limitations. First, given the multicenter and retrospective nature of the study, selection bias in the choice of patients introduced to CGM and differences in treatment strategies among centers cannot be ruled out. Second, only a limited number of patients underwent colonoscopy before and after CGM administration. Therefore, analysis of endoscopic activity at baseline is limited, and whether mucosal healing is achieved at the time of discontinuation remains unclear. Additionally, missing blood test data may have contributed to variability in the comparison between baseline and posttreatment data. Finally, the short observation period after CGM discontinuation indicates that long-term outcomes are unknown. Further prospective studies are warranted to address these issues.

In conclusion, our multicenter real-world clinical study demonstrated the favorable efficacy and acceptable safety profile of CGM in patients with UC with inadequate response or intolerance to 5-ASA. Our results also suggest that baseline disease activity may be a predictor of clinical remission. Furthermore, favorable outcomes were observed in maintaining clinical remission following CGM discontinuation. CGM could potentially be a treatment option to consider prior to systemic corticosteroid therapy for UC.

NOTES

Funding Source

The authors received no financial support for the research, authorship, and/or publication of this article.

Conflict of Interest

Sakiyama N reports receiving speaking fees from AbbVie GK, EA Pharma Co., Ltd., Mitsubishi Tanabe Pharma Corporation., Mochida Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K., Kyorin Pharmaceutical Co., Ltd., Gilead Sciences, Inc., and Pfizer Inc. All other authors declare no conflicts of interest.

Data Availability Statement

All data associated with the present study will be available from the corresponding author upon reasonable request.

Author Contributions

Conceptualization: Kakimoto K. Data curation: Koshiba R. Formal analysis: Koshiba R. Investigation: Koshiba R, Kakimoto K, Inoue T, Sanomura M, Murano M, Ito H, Nakanishi Y, Kawakami K, Mizuta N, Numa K, Kinoshita N, Nakazawa K, Hara A, Hirata Y, Sakiyama N, Arimitsu S, Miyazaki T. Methodology: Kakimoto K. Project administration: Kakimoto K. Resources: Kakimoto K. Supervision: Inoue T, Nakamura S, Nishikawa H. Visualization: Koshiba R, Kakimoto K. Writing - original draft: Koshiba R, Kakimoto K. Writing - review & editing: Inoue T, Sanomura M, Murano M, Ito H, Nakanishi Y, Kawakami K, Mizuta N, Numa K, Kinoshita N, Nakazawa K, Hara A, Hirata Y, Sakiyama N, Arimitsu S, Miyazaki T, Nakamura S, Nishikawa H. Approval of final manuscript: all authors.

Fig. 1.

Flowchart of the study population. Overall, 63 patients with UC were included in the safety assessment, whereas 62 were included in the efficacy assessment. UC, ulcerative colitis; CGM, carotegrast methyl.

Fig. 2.

Clinical remission and response rates at the end of carotegrast methyl treatment. (A) Clinical remission and response rates based on the partial Mayo (pMayo) score in all patients. (B) Clinical remission and response rates based on Patient-Reported Outcome 2 (PRO2) in all patients. (C) Clinical remission and response rates based on the pMayo score in patients naive to corticosteroids or advanced therapies (ATs). (D) Clinical remission and response rates based on the pMayo score in patients with budesonide-refractory ulcerative colitis.

Fig. 3.

Cumulative clinical remission rate at weeks 2, 4, 8, 16, and 24 in all patients with ulcerative colitis.

Fig. 4.

Clinical remission rate (A) and clinical response rate (B) at weeks 2, 4, 8, 16, and 24. Data were assessed using intent-to-treat analysis.

Fig. 5.

Kaplan–Meier curve showing continuation of carotegrast methyl or discontinuation due to insufficient efficacy. (A) Kaplan-Meier curve showing treatment continuation rates in the remission and non-remission groups. (B) The cumulative incidence of carotegrast methyl discontinuation owing to insufficient efficacy in all patients. (C) Comparison of the cumulative incidence of discontinuation, divided into 2 groups based on the pMayo score threshold.

Fig. 6.

Changes over time from baseline to 24 weeks in mean (A) pMayo sore, (B) serum C-reactive protein (CRP) levels, (C) lymphocyte counts, and (D) white blood cell (WBC) counts. *P<0.05, **P<0.01.

Fig. 7.

Receiver operating characteristic curve of the baseline partial Mayo score for predicting clinical remission at the end of carotegrast methyl treatment.

Fig. 8.

Kaplan-Meier curve of the cumulative relapse-free rate after discontinuing carotegrast methyl in 26 patients who achieved clinical remission.

Table 1.

Demographic and Clinical Characteristics at Baseline

Variable	Value (n = 62)
Sex
Male	32 (51.6)
Female	30 (48.4)
Age (yr)	44 (30–58)
Duration of disease (mo)	64 (26–111)
UC location
Pancolitis	29 (48.8)
Left side	31 (50.0)
Proctitis	2 (3.2)
Medications immediately before CGM
5-ASA (oral)	50 (88.7)
5-ASA (topical)	13 (21.0)
Oral prednisolone	1 (1.6)
Oral budesonide MMX	4 (6.5)
Budesonide rectal form	15 (24.2)
Azathioprine	7 (11.3)
Vedolizumab	1 (1.6)
Filgotinib	1 (1.6)
History of treatment failure with ATs	3 (4.8)
WBC (/μL)	6,460 (5,480–8,420)
Neutrophil (/μL)	4,082 (3,440–5,476)
Lymphocytes (/μL)	1,581 (1,320–2,140)
Hb (g/dL)	13.2 (12.1–14.5)
Platelet (× 10⁴/μL)	28.0 (26.0-31.9)
Albumin (g/dL)	4.2 (4.0–4.4)
CRP (mg/L)	0.18 (0.10–0.56)
Partial Mayo score	5.0 (3.0–6.0)
Mayo endoscopic subscore (n = 29)	2.0 (1.0–2.0)
Concomitant 5-ASA	50 (80.6)
Concomitant corticosteroids	0
Concomitant azathioprine	0

Values are presented as number (%) or median (interquartile range).

UC, ulcerative colitis; CGM, carotegrast methyl; 5-ASA, 5-aminosalicylic acid; MMX, multi-matrix; ATs, advanced therapies; WBC, white blood cell; Hb, hemoglobin; CRP, C-reactive protein.

Table 2.

Baseline Characteristics between the Remission Group and the Non-Remission Group

Variable	Remission group (n = 30)	Non-remission group (n = 32)	P-value
Sex			0.617
Male	14 (46.7)	18 (56.3)
Female	16 (53.3)	14 (43.8)
Age (yr)	45 (28–54)	42 (35–62)	0.833
Duration of disease (mo)	64 (39–99)	78 (16–200)	0.841
UC location			0.367
Pancolitis	14 (46.7)	15 (46.9)
Left side	16 (53.3)	15 (46.9)
Proctitis	0	2 (6.3)
Medications immediately before CGM
5-ASA (oral)	24 (80.0)	26 (81.3)	1.000
5-ASA (topical)	7 (23.3)	6 (18.8)	0.759
Oral prednisolone	0	1 (3.1)	1.000
Oral budesonide MMX	2 (6.7)	2 (6.3)	1.000
Budesonide rectal form	5 (16.7)	10 (31.3)	0.297
Azathioprine	5 (16.7)	2 (6.3)	0.249
History of treatment failure with ATs	1 (3.3)	2 (6.3)	1.000
Partial Mayo score	4.0 (3.0–5.0)	6.0 (5.0–7.0)	0.001
Mayo endoscopic subscore (n = 29)	2.0 (1.0–2.0)	1.5 (1.0–2.0)	0.862
Concomitant 5-ASA	24 (80.0)	26 (81.3)	1.000
WBC (/μL)	6,460 (5,600–8,440)	6,390 (5,480–8,350)	0.673
Neutrophils (/μL)	4,320 (3,420–5,520)	3,970 (3,470–4,900)	0.722
Lymphocytes (/μL)	1,600 (1,310–2,140)	1,550 (1,320–2,140)	0.698
Hb (g/dL)	13.2 (12.5–14.0)	13.1 (12.0–14.8)	0.906
Albumin (g/dL)	4.3 (4.0–4.4)	4.2 (3.8–4.3)	0.176
CRP (mg/L)	0.25 (0.10–0.56)	0.16 (0.09–0.50)	0.795
Platlet (× 10⁴/L)	28.0 (25.9–31.8)	28.0 (26.4–31.9)	0.727
Neutrophil-lymphocyte ratio	2.43 (2.05–3.44)	2.44 (1.59–2.99)	0.370
Platelet-lymphocyte ratio	178.3 (147.0–211.4)	194.1 (133.7–233.4)	0.918

Values are presented as number (%) or median (interquartile range).

UC, ulcerative colitis; CGM, carotegrast methyl; 5-ASA, 5-aminosalicylic acid; MMX, multi-matrix; ATs, advanced therapies; WBC, white blood cell; Hb, hemoglobin; CRP, C-reactive protein.

Table 3.

Univariate and Multivariate Analyses to Assess Predictive Factors Associated with Clinical Remission at the End of Carotegrast Methyl

Predictive factor	No.	Univariate analysis		Multivariate analysis
Predictive factor	No.	OR (95% CI)	P-value	OR (95% CI)	P-value
Sex (male)	32	0.68 (0.25–1.85)	0.451
Age	62	1.00 (0.97–1.02)	0.663
Duration of disease (year)	62	1.04 (0.97–1.10)	0.255
UC location (left-sided)	31	0.82 (0.34–2.02)	0.670
Previous budesonide	17	0.48 (0.15–1.51)	0.209
History of treatment failure with ATs	3	0.52 (0.04–6.02)	0.599
Corticosteroids/ATs naive	42	2.25 (0.75–6.76)	0.149	2.87 (0.80–10.40)	0.107
Partial Mayo score	62	0.53 (0.36–0.78)	0.001	0.55 (0.37–0.81)	0.003
Mayo endoscopic subscore	29	0.95 (0.28–3.22)	0.931
Concomitant 5-ASA	50	0.92 (0.26–3.26)	0.901
WBC	60	0.96 (0.74–1.26)	0.766
Hb	60	1.00 (0.73–1.37)	0.994
Platelet	60	0.98 (0.90–1.07)	0.663
Albumin	60	2.54 (0.61–10.5)	0.198	2.44 (0.50–11.80)	0.268
CRP	60	0.92 (0.65–1.31)	0.643
Neutrophil-Lymphocyte ratio	57	1.12 (0.83–1.51)	0.455
Platelet-Lymphocyte ratio	57	1.00 (0.99–1.01)	0.950

OR, odds ratio; CI, confidence interval; UC, ulcerative colitis; ATs, advanced therapies; 5-ASA, 5-aminosalicylic acid; WBC, white blood cell; Hb, hemoglobin; CRP, C-reactive protein.

Table 4.

Maintenance Therapy after Discontinuation of Carotegrast Methyl (n=30)

Treatment	No. (%)
5-ASA alone	16 (53.3)
5-ASA + azathioprine (restarted)	3 (10.0)
Azathioprine alone (restarted)	2 (6.7)
No treatment	2 (6.7)
5-ASA + azathioprine (newly initiated)	1 (3.3)
Azathioprine alone (newly initiated)	2 (6.7)
5-ASA + vedolizumab (newly initiated)	2 (6.7)
5-ASA + GMA (newly initiated)	2 (6.7)

5-ASA, 5-aminosalicylic acid; GMA, granulocyte and monocyte adsorptive apheresis.

Table 5.

Comparison of Remission-Maintained and Relapse Groups after Discontinuation of CGM

Variable	Remission-maintained group (n = 20)	Relapse group (n = 10)	P-value
Sex			1.000
Male	9 (45.0)	5 (50.0)
Female	11 (55.0)	5 (50.0)
Age (yr)	47 (30–53)	38 (28–57)	0.860
Duration of disease (mo)	64 (52–102)	65 (22–77)	0.373
UC location			0.442
Pancolitis	8 (40.0)	6 (60.0)
Left side	12 (60.0)	4 (40.0)
Proctitis	0	0
Previous medications before CGM
5-ASA (oral)	16 (80.0)	8 (80.0)	1.000
5-ASA (topical)	4 (20.0)	3 (30.0)	0.657
Oral prednisolone	0	0
Oral budesonide MMX	2 (10.0)	0	0.540
Budesonide suppository	3 (15.0)	2 (20.0)	1.000
Azathioprine	4 (20.0)	1 (10.0)	0.640
History of treatment failure with ATs	1 (5.0)	0	1.000
At the start of CGM
Partial Mayo score	4.0 (3.0–4.0)	4.5 (3.0–6.0)	0.573
Mayo endoscopic subscore (n = 17)	2.0 (2.0–2.0)	1.0 (1.0–1.0)	0.076
WBC (/μL)	6,420 (5,450–8,740)	7,110 (6,150–7,700)	0.725
Neutrophils (/μL)	4,200 (3,420–5,800)	4,690 (3,470–4,900)	0.980
Lymphocytes (/μL)	1,530 (1,290–1,840)	1,830 (1,400–2,260)	0.304
Hb (g/dL)	13.0 (12.3–14.0)	13.3 (12.7–14.4)	0.537
CRP (mg/L)	0.27 (0.10–0.62)	0.21 (0.05–0.42)	0.877
Platelet (× 10⁴/L)	29.3 (26.2–32.4)	26.7 (25.4–29.3)	0.218
Albumin (g/dL)	4.2 (3.9–4.4)	4.4 (4.3–4.4)	0.150
At the time of CGM discontinuation
WBC (/μL)	6,700 (,4490–7,820)	8,290 (7,120–9,240)	0.163
Hb (g/dL)	13.4 (12.3–14.1)	12.1 (11.7–13.3)	0.504
CRP (mg/L)	0.05 (0.02–0.25)	0.03 (0.02–0.04)	0.300
Platelet (× 10⁴/L)	24.3 (22.5–29.5)	29.2 (27.3–31.0)	0.170
Albumin (g/dL)	4.1 (3.9–4.5)	4.2 (4.1–4.3)	0.540
Additional maintenance therapy after discontinuation of CGM	5 (25.0)	2 (20.0)	1.000
Time to clinical remission from CGM initiation (day)	19 (9–43)	18 (12–26)	0.912
Duration of CGM therapy (day)	124 (82–168)	105 (78–155)	0.537

Values are presented as number (%) or median (interquartile range).

CGM, carotegrast methyl; UC, ulcerative colitis; 5-ASA, 5-aminosalicylic acid; MMX, multi-matrix; ATs, advanced therapies; WBC, white blood cell; Hb, hemoglobin; CRP, C-reactive protein.

Table 6.

Adverse Events (n=63)

Adverse event	No. (%)
Any adverse event	8 (12.7)
Liver dysfunction	3 (4.8)
Nausea	3 (4.8)
Headache	1 (1.6)
Skin rash	1 (1.6)
Adverse events leading to discontinuation	7 (11.1)

REFERENCES

1. Briskin M, Winsor-Hines D, Shyjan A, et al. Human mucosal addressin cell adhesion molecule-1 is preferentially expressed in intestinal tract and associated lymphoid tissue. Am J Pathol 1997;151:97–110.PubMed PMC
2. Koizumi M, King N, Lobb R, Benjamin C, Podolsky DK. Expression of vascular adhesion molecules in inflammatory bowel disease. Gastroenterology 1992;103:840–847.Article PubMed
3. Thomas S, Baumgart DC. Targeting leukocyte migration and adhesion in Crohn’s disease and ulcerative colitis. Inflammopharmacology 2012;20:1–18.Article PubMed PDF
4. Gubatan J, Keyashian K, Rubin SJS, et al. Anti-integrins for the treatment of inflammatory bowel disease: current evidence and perspectives. Clin Exp Gastroenterol 2021;14:333–342.Article PubMed PMC PDF
5. Park SC, Jeen YT. Anti-integrin therapy for inflammatory bowel disease. World J Gastroenterol 2018;24:1868–1880.Article PubMed PMC
6. Erle DJ, Briskin MJ, Butcher EC, et al. Expression and function of the MAdCAM-1 receptor, integrin alpha 4 beta 7, on human leukocytes. J Immunol 1994;153:517–528.Article PubMed PDF
7. Feagan BG, Rutgeerts P, Sands BE, et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med 2013;369:699–710.Article PubMed
8. Sandborn WJ, Feagan BG, Rutgeerts P, et al. Vedolizumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med 2013;369:711–721.Article PubMed
9. Fukase H, Kajioka T, Oikawa I, Ikeda N, Furuie H. AJM300, a novel oral antagonist of α4-integrin, sustains an increase in circulating lymphocytes: a randomised controlled trial in healthy male subjects. Br J Clin Pharmacol 2020;86:591–600.Article PubMed PMC PDF
10. Sugiura T, Kageyama S, Andou A, et al. Oral treatment with a novel small molecule alpha 4 integrin antagonist, AJM300, prevents the development of experimental colitis in mice. J Crohns Colitis 2013;7:e533. –e542.Article PubMed
11. Matsuoka K, Watanabe M, Ohmori T, et al. AJM300 (carotegrast methyl), an oral antagonist of α4-integrin, as induction therapy for patients with moderately active ulcerative colitis: a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Gastroenterol Hepatol 2022;7:648–657.Article PubMed
12. Yoshimura N, Watanabe M, Motoya S, et al. Safety and efficacy of AJM300, an oral antagonist of α4 integrin, in induction therapy for patients with active ulcerative colitis. Gastroenterology 2015;149:1775–1783.e2.Article PubMed
13. Turner D, Ricciuto A, Lewis A, et al. STRIDE-II: an update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): determining therapeutic goals for treat-to-target strategies in IBD. Gastroenterology 2021;160:1570–1583.Article PubMed
14. Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant 2013;48:452–458.Article PubMed PDF
15. Ohmori T. Real-world effectiveness and safety of carotegrast methyl in Japanese patients with moderately active ulcerative colitis. Inflamm Intest Dis 2024;9:271–282.Article PubMed PMC PDF
16. Japanese Society for Inflammatory Bowel Disease. Diagnostic criteria and treatment guidelines for ulcerative colitis and Crohn’s disease [Internet]. c2024 [cited 2025 Jul 16]. http://ibdjapan.org/pdf/doc15.pdf.
17. Mühl L, Becker E, Müller TM, et al. Clinical experiences and predictors of success of treatment with vedolizumab in IBD patients: a cohort study. BMC Gastroenterol 2021;21:33.PubMed PMC
18. West NR, Hegazy AN, Owens BMJ, et al. Oncostatin M drives intestinal inflammation and predicts response to tumor necrosis factor-neutralizing therapy in patients with inflammatory bowel disease. Nat Med 2017;23:579–589.PubMed PMC
19. Verstockt B, Verstockt S, Dehairs J, et al. Low TREM1 expression in whole blood predicts anti-TNF response in inflammatory bowel disease. EBioMedicine 2019;40:733–742.Article PubMed PMC
20. Sands BE. Biomarkers of inflammation in inflammatory bowel disease. Gastroenterology 2015;149:1275–1285.e2.Article PubMed
21. Butera A, Di Paola M, Vitali F, et al. IL-13 mRNA tissue content identifies two subsets of adult ulcerative colitis patients with different clinical and mucosa-associated microbiota profiles. J Crohns Colitis 2020;14:369–380.Article PubMed PDF
22. Kinoshita N, Kakimoto K, Shimizu H, et al. Serum IL-13 predicts response to golimumab in bio-naïve ulcerative colitis. J Clin Med 2022;11:4952.Article PubMed PMC
23. Kelly AJ, Long A. Targeting T-cell integrins in autoimmune and inflammatory diseases. Clin Exp Immunol 2024;215:15–26.Article PubMed PMC PDF
24. Shattil SJ, Kim C, Ginsberg MH. The final steps of integrin activation: the end game. Nat Rev Mol Cell Biol 2010;11:288–300.Article PubMed PMC PDF
25. Meenan J, Spaans J, Grool TA, et al. Altered expression of alpha 4 beta 7, a gut homing integrin, by circulating and mucosal T cells in colonic mucosal inflammation. Gut 1997;40:241–246.Article PubMed PMC
26. Rubin SJS, Bai L, Haileselassie Y, et al. Mass cytometry reveals systemic and local immune signatures that distinguish inflammatory bowel diseases. Nat Commun 2019;10:2686.Article PubMed PMC PDF
27. Soriano A, Salas A, Salas A, et al. VCAM-1, but not ICAM-1 or MAdCAM-1, immunoblockade ameliorates DSS-induced colitis in mice. Lab Invest 2000;80:1541–1551.Article PubMed PDF
28. Colombel JF, Sands BE, Rutgeerts P, et al. The safety of vedolizumab for ulcerative colitis and Crohn’s disease. Gut 2017;66:839–851.Article PubMed
29. Rudick RA, Sandrock A. Natalizumab: alpha 4-integrin antagonist selective adhesion molecule inhibitors for MS. Expert Rev Neurother 2004;4:571–580.PubMed

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Real-world effectiveness and safety of carotegrast methyl in patients with ulcerative colitis: a multicenter retrospective cohort study

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Real-world effectiveness and safety of carotegrast methyl in patients with ulcerative colitis: a multicenter retrospective cohort study

Fig. 1. Flowchart of the study population. Overall, 63 patients with UC were included in the safety assessment, whereas 62 were included in the efficacy assessment. UC, ulcerative colitis; CGM, carotegrast methyl.

Fig. 2. Clinical remission and response rates at the end of carotegrast methyl treatment. (A) Clinical remission and response rates based on the partial Mayo (pMayo) score in all patients. (B) Clinical remission and response rates based on Patient-Reported Outcome 2 (PRO2) in all patients. (C) Clinical remission and response rates based on the pMayo score in patients naive to corticosteroids or advanced therapies (ATs). (D) Clinical remission and response rates based on the pMayo score in patients with budesonide-refractory ulcerative colitis.

Fig. 3. Cumulative clinical remission rate at weeks 2, 4, 8, 16, and 24 in all patients with ulcerative colitis.

Fig. 4. Clinical remission rate (A) and clinical response rate (B) at weeks 2, 4, 8, 16, and 24. Data were assessed using intent-to-treat analysis.

Fig. 5. Kaplan–Meier curve showing continuation of carotegrast methyl or discontinuation due to insufficient efficacy. (A) Kaplan-Meier curve showing treatment continuation rates in the remission and non-remission groups. (B) The cumulative incidence of carotegrast methyl discontinuation owing to insufficient efficacy in all patients. (C) Comparison of the cumulative incidence of discontinuation, divided into 2 groups based on the pMayo score threshold.

Fig. 6. Changes over time from baseline to 24 weeks in mean (A) pMayo sore, (B) serum C-reactive protein (CRP) levels, (C) lymphocyte counts, and (D) white blood cell (WBC) counts. *P<0.05, **P<0.01.

Fig. 7. Receiver operating characteristic curve of the baseline partial Mayo score for predicting clinical remission at the end of carotegrast methyl treatment.

Fig. 8. Kaplan-Meier curve of the cumulative relapse-free rate after discontinuing carotegrast methyl in 26 patients who achieved clinical remission.

Fig. 1.

Fig. 2.

Fig. 3.

Fig. 4.

Fig. 5.

Fig. 6.

Fig. 7.

Fig. 8.

Real-world effectiveness and safety of carotegrast methyl in patients with ulcerative colitis: a multicenter retrospective cohort study

Variable	Value (n = 62)
Sex
Male	32 (51.6)
Female	30 (48.4)
Age (yr)	44 (30–58)
Duration of disease (mo)	64 (26–111)
UC location
Pancolitis	29 (48.8)
Left side	31 (50.0)
Proctitis	2 (3.2)
Medications immediately before CGM
5-ASA (oral)	50 (88.7)
5-ASA (topical)	13 (21.0)
Oral prednisolone	1 (1.6)
Oral budesonide MMX	4 (6.5)
Budesonide rectal form	15 (24.2)
Azathioprine	7 (11.3)
Vedolizumab	1 (1.6)
Filgotinib	1 (1.6)
History of treatment failure with ATs	3 (4.8)
WBC (/μL)	6,460 (5,480–8,420)
Neutrophil (/μL)	4,082 (3,440–5,476)
Lymphocytes (/μL)	1,581 (1,320–2,140)
Hb (g/dL)	13.2 (12.1–14.5)
Platelet (× 10⁴/μL)	28.0 (26.0-31.9)
Albumin (g/dL)	4.2 (4.0–4.4)
CRP (mg/L)	0.18 (0.10–0.56)
Partial Mayo score	5.0 (3.0–6.0)
Mayo endoscopic subscore (n = 29)	2.0 (1.0–2.0)
Concomitant 5-ASA	50 (80.6)
Concomitant corticosteroids	0
Concomitant azathioprine	0

Variable	Remission group (n = 30)	Non-remission group (n = 32)	P-value
Sex			0.617
Male	14 (46.7)	18 (56.3)
Female	16 (53.3)	14 (43.8)
Age (yr)	45 (28–54)	42 (35–62)	0.833
Duration of disease (mo)	64 (39–99)	78 (16–200)	0.841
UC location			0.367
Pancolitis	14 (46.7)	15 (46.9)
Left side	16 (53.3)	15 (46.9)
Proctitis	0	2 (6.3)
Medications immediately before CGM
5-ASA (oral)	24 (80.0)	26 (81.3)	1.000
5-ASA (topical)	7 (23.3)	6 (18.8)	0.759
Oral prednisolone	0	1 (3.1)	1.000
Oral budesonide MMX	2 (6.7)	2 (6.3)	1.000
Budesonide rectal form	5 (16.7)	10 (31.3)	0.297
Azathioprine	5 (16.7)	2 (6.3)	0.249
History of treatment failure with ATs	1 (3.3)	2 (6.3)	1.000
Partial Mayo score	4.0 (3.0–5.0)	6.0 (5.0–7.0)	0.001
Mayo endoscopic subscore (n = 29)	2.0 (1.0–2.0)	1.5 (1.0–2.0)	0.862
Concomitant 5-ASA	24 (80.0)	26 (81.3)	1.000
WBC (/μL)	6,460 (5,600–8,440)	6,390 (5,480–8,350)	0.673
Neutrophils (/μL)	4,320 (3,420–5,520)	3,970 (3,470–4,900)	0.722
Lymphocytes (/μL)	1,600 (1,310–2,140)	1,550 (1,320–2,140)	0.698
Hb (g/dL)	13.2 (12.5–14.0)	13.1 (12.0–14.8)	0.906
Albumin (g/dL)	4.3 (4.0–4.4)	4.2 (3.8–4.3)	0.176
CRP (mg/L)	0.25 (0.10–0.56)	0.16 (0.09–0.50)	0.795
Platlet (× 10⁴/L)	28.0 (25.9–31.8)	28.0 (26.4–31.9)	0.727
Neutrophil-lymphocyte ratio	2.43 (2.05–3.44)	2.44 (1.59–2.99)	0.370
Platelet-lymphocyte ratio	178.3 (147.0–211.4)	194.1 (133.7–233.4)	0.918

Predictive factor	No.	Univariate analysis		Multivariate analysis
Predictive factor	No.	OR (95% CI)	P-value	OR (95% CI)	P-value
Sex (male)	32	0.68 (0.25–1.85)	0.451
Age	62	1.00 (0.97–1.02)	0.663
Duration of disease (year)	62	1.04 (0.97–1.10)	0.255
UC location (left-sided)	31	0.82 (0.34–2.02)	0.670
Previous budesonide	17	0.48 (0.15–1.51)	0.209
History of treatment failure with ATs	3	0.52 (0.04–6.02)	0.599
Corticosteroids/ATs naive	42	2.25 (0.75–6.76)	0.149	2.87 (0.80–10.40)	0.107
Partial Mayo score	62	0.53 (0.36–0.78)	0.001	0.55 (0.37–0.81)	0.003
Mayo endoscopic subscore	29	0.95 (0.28–3.22)	0.931
Concomitant 5-ASA	50	0.92 (0.26–3.26)	0.901
WBC	60	0.96 (0.74–1.26)	0.766
Hb	60	1.00 (0.73–1.37)	0.994
Platelet	60	0.98 (0.90–1.07)	0.663
Albumin	60	2.54 (0.61–10.5)	0.198	2.44 (0.50–11.80)	0.268
CRP	60	0.92 (0.65–1.31)	0.643
Neutrophil-Lymphocyte ratio	57	1.12 (0.83–1.51)	0.455
Platelet-Lymphocyte ratio	57	1.00 (0.99–1.01)	0.950

Treatment	No. (%)
5-ASA alone	16 (53.3)
5-ASA + azathioprine (restarted)	3 (10.0)
Azathioprine alone (restarted)	2 (6.7)
No treatment	2 (6.7)
5-ASA + azathioprine (newly initiated)	1 (3.3)
Azathioprine alone (newly initiated)	2 (6.7)
5-ASA + vedolizumab (newly initiated)	2 (6.7)
5-ASA + GMA (newly initiated)	2 (6.7)

Variable	Remission-maintained group (n = 20)	Relapse group (n = 10)	P-value
Sex			1.000
Male	9 (45.0)	5 (50.0)
Female	11 (55.0)	5 (50.0)
Age (yr)	47 (30–53)	38 (28–57)	0.860
Duration of disease (mo)	64 (52–102)	65 (22–77)	0.373
UC location			0.442
Pancolitis	8 (40.0)	6 (60.0)
Left side	12 (60.0)	4 (40.0)
Proctitis	0	0
Previous medications before CGM
5-ASA (oral)	16 (80.0)	8 (80.0)	1.000
5-ASA (topical)	4 (20.0)	3 (30.0)	0.657
Oral prednisolone	0	0
Oral budesonide MMX	2 (10.0)	0	0.540
Budesonide suppository	3 (15.0)	2 (20.0)	1.000
Azathioprine	4 (20.0)	1 (10.0)	0.640
History of treatment failure with ATs	1 (5.0)	0	1.000
At the start of CGM
Partial Mayo score	4.0 (3.0–4.0)	4.5 (3.0–6.0)	0.573
Mayo endoscopic subscore (n = 17)	2.0 (2.0–2.0)	1.0 (1.0–1.0)	0.076
WBC (/μL)	6,420 (5,450–8,740)	7,110 (6,150–7,700)	0.725
Neutrophils (/μL)	4,200 (3,420–5,800)	4,690 (3,470–4,900)	0.980
Lymphocytes (/μL)	1,530 (1,290–1,840)	1,830 (1,400–2,260)	0.304
Hb (g/dL)	13.0 (12.3–14.0)	13.3 (12.7–14.4)	0.537
CRP (mg/L)	0.27 (0.10–0.62)	0.21 (0.05–0.42)	0.877
Platelet (× 10⁴/L)	29.3 (26.2–32.4)	26.7 (25.4–29.3)	0.218
Albumin (g/dL)	4.2 (3.9–4.4)	4.4 (4.3–4.4)	0.150
At the time of CGM discontinuation
WBC (/μL)	6,700 (,4490–7,820)	8,290 (7,120–9,240)	0.163
Hb (g/dL)	13.4 (12.3–14.1)	12.1 (11.7–13.3)	0.504
CRP (mg/L)	0.05 (0.02–0.25)	0.03 (0.02–0.04)	0.300
Platelet (× 10⁴/L)	24.3 (22.5–29.5)	29.2 (27.3–31.0)	0.170
Albumin (g/dL)	4.1 (3.9–4.5)	4.2 (4.1–4.3)	0.540
Additional maintenance therapy after discontinuation of CGM	5 (25.0)	2 (20.0)	1.000
Time to clinical remission from CGM initiation (day)	19 (9–43)	18 (12–26)	0.912
Duration of CGM therapy (day)	124 (82–168)	105 (78–155)	0.537

Adverse event	No. (%)
Any adverse event	8 (12.7)
Liver dysfunction	3 (4.8)
Nausea	3 (4.8)
Headache	1 (1.6)
Skin rash	1 (1.6)
Adverse events leading to discontinuation	7 (11.1)

Table 1. Demographic and Clinical Characteristics at Baseline

Values are presented as number (%) or median (interquartile range).

UC, ulcerative colitis; CGM, carotegrast methyl; 5-ASA, 5-aminosalicylic acid; MMX, multi-matrix; ATs, advanced therapies; WBC, white blood cell; Hb, hemoglobin; CRP, C-reactive protein.

Table 2. Baseline Characteristics between the Remission Group and the Non-Remission Group

Values are presented as number (%) or median (interquartile range).

UC, ulcerative colitis; CGM, carotegrast methyl; 5-ASA, 5-aminosalicylic acid; MMX, multi-matrix; ATs, advanced therapies; WBC, white blood cell; Hb, hemoglobin; CRP, C-reactive protein.

Table 3. Univariate and Multivariate Analyses to Assess Predictive Factors Associated with Clinical Remission at the End of Carotegrast Methyl

OR, odds ratio; CI, confidence interval; UC, ulcerative colitis; ATs, advanced therapies; 5-ASA, 5-aminosalicylic acid; WBC, white blood cell; Hb, hemoglobin; CRP, C-reactive protein.

Table 4. Maintenance Therapy after Discontinuation of Carotegrast Methyl (n=30)

5-ASA, 5-aminosalicylic acid; GMA, granulocyte and monocyte adsorptive apheresis.

Table 5. Comparison of Remission-Maintained and Relapse Groups after Discontinuation of CGM

Values are presented as number (%) or median (interquartile range).

CGM, carotegrast methyl; UC, ulcerative colitis; 5-ASA, 5-aminosalicylic acid; MMX, multi-matrix; ATs, advanced therapies; WBC, white blood cell; Hb, hemoglobin; CRP, C-reactive protein.