Abstract
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Background/Aims
- Randomized controlled trials have confirmed the efficacy and safety of mirikizumab, an anti-interleukin-23p19 monoclonal antibody, for moderate-to-severe active ulcerative colitis (UC). However, there are no real-world data on the efficacy and safety of mirikizumab for UC as maintenance therapy, especially in difficult-to-treat inflammatory bowel disease (DTT-IBD). This study aimed to evaluate the long-term efficacy and safety of mirikizumab in patients with UC of DTT-IBD.
-
Methods
- This was a single-center retrospective observational study involving adult patients with UC who received mirikizumab between January 2023 and April 2025 and met the criteria for DTT-IBD (e.g., failure of biologics and advanced small molecule drugs with at least 2 different mechanisms of action). The primary outcome was the clinical response at week 52. Secondary outcomes included steroid-free clinical remission within 52 weeks and the persistency of mirikizumab use. Adverse events were also recorded.
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Results
- Thirty-two patients were included in this study. The median 2-item patient-reported outcome score at baseline was 3 (interquartile range, 2–4). The proportion of patients with a clinical response at week 52 was 33.3% (95% confidence interval, 14.6%–57.0%). Steroid-free clinical remission was achieved in 26.7% (95% confidence interval, 12.3%–45.9%) of the patients. The cumulative continuous rate of mirikizumab use at week 52 was approximately 60%. Only 1 patient developed a serious adverse event requiring hospitalization (pneumonia), and mirikizumab was successfully resumed after recovery.
-
Conclusions
- The present study demonstrated real-world data regarding maintenance therapy with mirikizumab for UC among patients with DTT-IBD.
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Keywords: Inflammatory bowel diseases; Ulcerative colitis; Mirikizumab; Treatment failure
Graphical abstract
INTRODUCTION
Ulcerative colitis (UC) is a chronic disease characterized by recurrent inflammation of the gastrointestinal tract, for which no curative treatment currently exists. Although colectomy rates have decreased with advances in medical therapy, the current risk of colectomy remains at 9.6% 10 years after diagnosis [1]. Thus, therapeutic strategies for refractory disease are a relevant issue. Recently, the concept of difficult-to-treat inflammatory bowel disease (DTT-IBD) has been proposed. DTT-IBD refers to cases in which biologics and advanced small molecule drugs with at least 2 different mechanisms of action have failed. This has led to increasing attention on the management of refractory cases [2].
Mirikizumab is an anti-interleukin (IL)-23p19 monoclonal antibody. Its efficacy and safety in induction and maintenance therapy for UC were demonstrated in the LUCENT-1 and LUCENT-2 trials, respectively [3]. However, the proportion of patients who failed to respond to 2 or more biologics or Janus kinase inhibitors (JAKi) when they were recruited into the LUCENT-2 trial was only 14% in the mirikizumab-treated group. Furthermore, those who had received 3 or more biologics were excluded from the study. Therefore, further investigation is warranted to evaluate the efficacy of mirikizumab among DTT-IBD patients. Moreover, real-world data (RWD) on long-term efficacy and safety in maintenance therapy with mirikizumab has not been elucidated, although studies on induction therapy [4,5] and small case series have been reported [6,7].
This study aimed to evaluate RWD on the therapeutic efficacy and safety of mirikizumab as maintenance therapy for UC, especially in DTT-IBD.
METHODS
1. Study Design and Patients
This was a single-center retrospective observational study performed at Keio University Hospital (Tokyo, Japan). Patients who met all of the following criteria were included, and their data were analyzed: (1) patients with UC aged ≥ 18 years; (2) received mirikizumab at least once between January 2023 and April 2025; and (3) diagnosed with DTT-IBD. The definition of DTT-IBD was as stated in a consensus paper [2]. Briefly, the failure of biologics and advanced small molecule drugs with at least 2 different mechanisms of action, complex perianal disease, or comorbid psychosocial complications that impair disease management were included in the definition of DTT-IBD, in this study. Patients with a history of colectomy when starting mirikizumab were excluded. The observational period started from the initial date of mirikizumab administration, and the patients were followed up to May 2025 or the end of mirikizumab therapy, whichever came first. For patients who transferred to another hospital or discontinued outpatient visits for more than 6 months during the observation period, the last visit prior to interruption was considered the end of follow-up.
2. Evaluation of Disease Activity
Clinical disease activity was evaluated using the 2-item patient-reported outcome (PRO2) score. The PRO2 score is the sum of 2 components from the partial Mayo score (rectal bleeding and stool frequency) and excludes the physician’s global assessment [8]. Clinical remission was defined as a PRO2 score of 0 for both the rectal bleeding subscore and the stool frequency subscore [9]. Clinical response was defined as a reduction in the PRO2 score of ≥50% from baseline [9]. Steroid-free clinical remission (SFCR) was defined as clinical remission achieved without the use of corticosteroids, including budesonide, and both systemic and topical formulations. The baseline endoscopic activity was assessed within 30 days prior to the initial administration of mirikizumab using Mayo endoscopic subscores (MES) [10]. Blood hemoglobin, C-reactive protein, and albumin concentrations were evaluated as laboratory indices of disease activity at baseline and weeks 12 ( ±3 weeks), 26 ( ±4 weeks), and 52 ( ±4 weeks).
3. Adverse Events
We investigated adverse events (AEs) that required the suspension of scheduled administration or discontinuation of mirikizumab. Among the AEs, any requiring hospitalization or resulting in death were investigated as serious AEs (SAEs).
4. Outcomes
The primary outcome was a clinical response at week 52 ( ± 4 weeks). The secondary outcomes were clinical response and clinical remission at weeks 12 ( ±3 weeks) and 26 ( ±4 weeks); clinical remission at week 52 ( ±4 weeks) as the proportion of patients achieving SFCR within 52 weeks of starting mirikizumab; the persistency of mirikizumab use; and the development of AEs and SAEs.
5. Statistical Analysis
For descriptive statistics, data were summarized as the number and percentage for categorical variables, and as the median and interquartile range (IQR) for continuous variables. For the primary analysis, the proportions of patients with a clinical response at each time point were calculated with the 95% confidence interval (CI), estimated by the Clopper–Pearson method. Modified non-responder imputation was used for missing values for clinical response or clinical remission. For the imputation, patients who stopped using mirikizumab because they required another induction therapy or developed AEs before each time point were considered non-responders. Additionally, patients who transferred to another hospital or had no follow-up visits for >6 months were censored at the time of the final visit before cessation. Data for these patients were not included in the primary analysis (i.e., clinical response and clinical remission at each time point) after the end of the observational period. For the secondary analysis, time to withdrawal of mirikizumab was depicted with a Kaplan-Meier plot to indicate persistency. SFCR within 52 weeks was investigated in another secondary analysis, and the 95% CI was estimated using the Clopper–Pearson method. The cumulative remission rate after the achievement of clinical remission and SFCR was also depicted in a Kaplan-Meier plot. As an exploratory analysis, univariable and multivariable Cox proportional hazard regression models were used to investigate factors associated with cessation of mirikizumab. Because of the limited sample size, factors that demonstrated a P-value of < 0.10 in the univariable analysis were selected as covariates for the multivariable analysis, and 3 distinct models were used.
We also performed subgroup analyses for therapeutic efficacy, persistency, and safety among patients with or without prior exposure to ustekinumab. The clinical response rate, clinical remission rate, SFCR rate, and incidence of AEs were compared between ustekinumab-exposed and unexposed patients using Fisher’s exact test. The persistency in each group was compared using the log-rank test. Patients who were already in clinical remission when mirikizumab was started were excluded from the analysis of efficacy (i.e., clinical response, clinical remission, and SFCR) but were included in the persistency and safety analyses. Statistical analyses were performed using R version 4.4.1 (R Foundation for Statistical Computing, Vienna, Austria; www.r-project.org) or StataNow BE version 19 (StataCorp, College Station, TX, USA). GraphPad Prism 10 (GraphPad Software, San Diego, CA, USA) was used to create the graphs; P<0.05 was considered significant.
6. Ethical Considerations
This study was approved by the Ethics Committee of Keio University School of Medicine (approval number: 20150210). Written informed consent was not required, but an opt-out was implemented to provide patients with the opportunity to decline to participate in this study, in accordance with local and national guidelines. This study was performed in accordance with the principles of the Declaration of Helsinki.
RESULTS
1. Patient Characteristics
Mirikizumab was administered to 41 patients with UC. Eight patients did not meet the criteria for DTT-IBD, and 1 patient had already undergone colectomy. After excluding these 9 patients, 32 patients were included in the analysis. The patients’ characteristics are presented in Table 1. The median age was 35 years (IQR, 28–49 years), and the median disease duration was 9 years (IQR, 6–15 years). The median PRO2 score at baseline was 3 (IQR, 2–4). The baseline endoscopic activity was assessed in 46.9% (15/32) of the patients. Among them, 1, 9, and 5 patients had an MES of 1, 2, and 3, respectively, whereas no patient had an MES of 0. In all patients, the reason for a diagnosis of DTT-IBD was failure of at least 2 advanced therapies with different mechanisms of action. The number of advanced therapies prior to mirikizumab was 2 in 18.8% (6/32) of the patients, 3 in 31.3% (10/32), 4 in 15.6% (5/32), and ≥ 5 in 34.3% (11/32). Anti-tumor necrosis factor was used in 96.9% (31/32) of the patients.
2. Efficacy
Two patients who were already in clinical remission at the initial date of mirikizumab therapy were excluded, and data for the remaining 30 patients were analyzed for efficacy. The median observational period was 33.5 weeks (IQR, 12.0–52.3 weeks). The primary outcome, clinical response at week 52, was achieved in 33.3% (7/21; 95% CI, 14.6%–57.0%) of the patients (Fig. 1A). The baseline characteristics of patients with and without a clinical response at week 52 are summarized in Supplementary Table 1. For the secondary outcome, the proportions of patients with a clinical response at weeks 12 and 26 were 21.4% (6/28; 95% CI, 8.3%–41.0%) and 33.3% (9/27; 95% CI, 16.5%–54.0%), respectively. Clinical remission was achieved in 10.7% (3/28; 95% CI, 2.3%–28.2%), 18.5% (5/27; 95% CI, 6.3%–38.1%), and 4.8% (1/21; 95% CI, 0.1%–23.8%) of the patients at weeks 12, 26, and 52, respectively. Tacrolimus was used in 7 patients at baseline, and clinical remission without tacrolimus was achieved in 10.7% (95% CI, 2.3%–28.2%), 14.8% (95% CI, 4.2%–33.7%), and 0% (95% CI, 0%–16.1%) of the patients at week 12, 26, and 52, respectively. SFCR was achieved in 26.7% (8/30; 95% CI, 12.3%–45.9%) of the patients within 52 weeks (Fig. 1B). Trends in laboratory indices related to disease activity at each time point are shown in Supplementary Fig. 1. The cumulative clinical remission rate after the achievement of clinical remission or SFCR is shown in Supplementary Fig. 2. After achievement of SFCR, 3 patients experienced relapse (i.e., not in clinical remission), and 2 patients discontinued mirikizumab because of ineffectiveness during the observation period.
3. Persistency
The cumulative continuation rate of mirikizumab for the entire population (n=32) is shown in Fig. 2. The cumulative continuous rate was approximately 60% at week 52. Mirikizumab was withdrawn because of ineffectiveness and AEs in 12 and 2 patients, respectively. In the exploratory analysis investigating factors associated with discontinuation of mirikizumab, concomitant use of systemic corticosteroids at baseline was associated with early cessation of mirikizumab (crude hazard ratio, 9.35; 95% CI, 1.53–57.00; P=0.015) (Supplementary Table 2). Numerically, patients who received high numbers of prior advanced therapies tended to have a low risk of mirikizumab discontinuation (crude hazard ratio, 0.70; 95% CI, 0.46–1.07; P=0.097).
4. Safety
The AEs observed during the observational period were UC exacerbation in 12 cases (37.5%), headache in 1 (3.1%), and dyspnea complicated with fatigue and pruritus in 1 (3.1%) (Table 2). An SAE was observed in 1 patient (pneumonia), which required hospitalization, and mirikizumab was suspended until recovery. Mirikizumab was successfully resumed, thereafter. There were no deaths.
5. Subgroup Analysis among Ustekinumab-Exposed and Unexposed Patients
We performed a subgroup analysis between patients with (n=23) and without (n=9) previous exposure to ustekinumab. The patient characteristics in each group are presented in Supplementary Table 3. The baseline PRO2 score in the ustekinumab-exposed group was relatively low compared with that in the unexposed group (P=0.025). The number of advanced therapies prior to mirikizumab was higher in the ustekinumab-exposed group than that in the unexposed group (P=0.002). The proportions of patients with a clinical response at week 52 was 35.7% (5/14; 95% CI, 12.8%–64.9%) in ustekinumab-exposed patients and 28.6% (2/7; 95% CI, 3.7%–71.0%) in unexposed patients (P=1.00) (Fig. 3A). The clinical remission rates at week 52 were 7.1% (1/14; 95% CI, 0.2%–33.9%) and 0% (0/7; 95% CI, 0%–41.0%) in ustekinumab-exposed and unexposed groups, respectively (P=1.00). SFCR within 52 weeks was achieved in 23.8% (5/21; 95% CI, 8.2%–47.2%) of the exposed patients, which was comparable to that in unexposed patients (P=0.67) (Fig. 3B). Regarding persistency, the cumulative continuation rate of mirikizumab was slightly higher in the ustekinumab-exposed group than that in the unexposed group (P=0.049) (Fig. 3C). However, in the exploratory multivariable analysis, prior exposure to ustekinumab was not associated with withdrawal of mirikizumab after adjustment for concomitant use of systemic steroids at baseline, or number of prior advanced therapies (Supplementary Table 4). Finally, the proportions of patients who experienced AEs were similar between the 2 groups (P=0.243) (Supplementary Table 5).
DISCUSSION
The present study was performed to evaluate the efficacy and safety of maintenance therapy with mirikizumab for UC among patients with DTT-IBD in a real-world setting. In this study, approximately one-third of the patients treated with mirikizumab showed a clinical response at week 52 despite having DTT-IBD, whereas the clinical remission rate was 4.8%. Furthermore, SAEs developed in only one case (pneumonia), indicating the drug’s safety.
The efficacy and safety of mirikizumab in maintenance therapy was demonstrated in the LUCENT-2 double-blind placebo-controlled trial. However, patients who had received anti-IL-12/23p40 antibody, anti-IL-23p19 antibodies, and 3 or more different biologic therapies prior to mirikizumab were excluded from the study [3]. Therefore, the efficacy and safety of mirikizumab among those patients needs to be evaluated using RWD. To date, 2 observational studies and 2 small case series have been published regarding the real-world effectiveness and safety of mirikizumab [4-7]. The 2 observational studies reported the short-term efficacy and safety of induction therapy (up to 12 weeks or 3 months) but did not report on maintenance therapy. To the best of our knowledge, ours is the first report using RWD on the efficacy and safety of maintenance therapy with mirikizumab for UC for up to 52 weeks, including patients with prior exposure to ustekinumab, and specific to DTT-IBD. Parigi et al. [11] reported that the prevalence of DTT-IBD among 1,736 IBD patients (754 with UC, 971 with Crohn’s disease, and 11 with unclassified IBD) with prior exposure to at least one biologic or advanced small molecule drug in large referral centers was 24.8%, of which 77% failed to respond to therapy with drugs with at least 2 mechanisms of action. Although the frequency of such refractory cases varies across facilities, the finding of a high prevalence of patients with DTT-IBD with multidrug failure in tertiary care institutions emphasizes the need for RWD on therapeutic efficacy and safety in this population. The use of RWD in the DTT-IBD population is a strength of the present study.
Compared with the results of the LUCENT-1 trial [3] and other previous reports using RWD [4-6], the clinical response and clinical remission rates at week 12 were low in this study (Fig. 1A). This discrepancy could be attributed to differences in previous advanced therapies, severity at the initial time point, and the definition of clinical outcomes. In the LUCENT-1 trial, nearly 60% of the mirikizumab-treated patients were biologics/JAKinaive and 20.7% had failure after 1 biologics/JAKi. Therefore, only approximately 20% of the patients experienced failure after at least 2 biologics/JAKis and none failed with 3 or more different biologic therapies, as stated. In the present study, all patients met the criteria for DTT-IBD for failure after at least 2 advanced therapies with different mechanisms of action (Table 1). Differences in the proportions of refractory cases might have resulted in the low therapeutic efficacy in the present study compared with that in the LUCENT-1 trial. This interpretation can also be extended to the comparison between efficacy in maintenance therapy in the LUCENT-2 trial and that in this study. Furthermore, the efficacy of maintenance therapy with mirikizumab in the LUCENT-2 trial was evaluated in patients who responded to induction therapy in the LUCENT-1 trial. In comparison, the clinical response and clinical remission rates at week 52 in this study were estimated for all patients, regardless of their responsiveness to induction therapy. Furthermore, patients who failed to respond to induction therapy were considered non-responders at week 52 using modified non-responder imputation. Thus, it should be noted that the data on the efficacy of maintenance therapy in the LUCENT-2 trial cannot be compared directly with that in the present study. Regarding RWD, Takagi et al. [4] reported that clinical remission, defined as a partial Mayo score <2 and a rectal bleeding subscore of 0, was achieved in 44.2% of the patients at week 12, which was higher than the rate in our study (10.7%; 95% CI, 2.3–28.2). At baseline, the median partial Mayo score was 5 (IQR, 3–6.3) in the study by Takagi et al., and the median PRO2 score was 3 (IQR, 2–4) in our study. Considering that the partial Mayo score includes the physician’s global assessment subscore in addition to the PRO2 score, the baseline severity appears almost comparable between the 2 studies. However, the number of previous advanced therapies differed between the 2 studies. Takagi et al. reported that approximately one-third of the patients were biologics/JAKi-naive or failed to respond to 1 agent, and those exposed to ≥ 3 biologics/JAKis accounted for 42.3% of the patients. In our study, patients who were biologics/JAKi-naive or who failed to respond to one agent were not included, and >80% of the patients had been treated with ≥ 3 biologics/JAKis prior to mirikizumab. This difference could explain the discrepancy in the therapeutic efficacy between the studies. St-Pierre et al. [5] also reported RWD on induction therapy with mirikizumab among 20 patients. The findings revealed that clinical remission was achieved in 83% of the patients at week 12; however, 30% of the patients were already in clinical remission at baseline. Furthermore, systemic steroids were being used in 60% of the patients at baseline, which could have increased the clinical remission rate. Moreover, the less stringent definition of clinical remission (i.e., simple clinical colitis activity index <3) compared with that used in our study (PRO2 score=0) could also explain the differences between the findings in St-Pierre et al.’s study and that in our study. The findings of the present study should be interpreted in the context of patients with DTT-IBD. The SFCR rate within 52 weeks was higher than the clinical remission rate at specific time points (Fig. 1). This could be attributed to differences in the timing of SFCR achievement between patients and relatively short period of sustained clinical remission (Supplementary Fig. 2), which resulted in not all patients achieving remission at the same time point.
Some discrepancy was observed between therapeutic efficacy and persistency of mirikizumab in the present study. As shown in Supplementary Fig. 2, the cumulative SFCR or clinical remission rate was relatively low compared with treatment continuity (Fig. 2). A plausible reason for this discrepancy may be the burden of treatment modification in patients with DTT-IBD who had already failed multiple advanced therapies. Specifically, treatment modification was often deferred in patients with mild residual disease activity until scheduled endoscopic reassessment. Therefore, the persistency of mirikizumab might not necessarily reflect its efficacy. In the stratified analysis of prior exposure to ustekinumab, the proportions of patients with a clinical response and clinical remission at week 52, and SFCR within 52 weeks were similar between the ustekinumab-exposed and unexposed patients (Fig. 3A and B). Takagi et al. [4] revealed similar effectiveness of mirikizumab as induction therapy regardless of the prior use of ustekinumab. Our study indicates robust results regarding the therapeutic efficacy of mirikizumab among ustekinumab-exposed patients. Regarding the continuity of mirikizumab therapy, the cumulative continuation rate was higher in the ustekinumab-exposed group than that in the ustekinumab-unexposed group (P=0.049) (Fig. 3C), in our study. However, we also demonstrated that prior exposure to ustekinumab was unassociated with the continuity of mirikizumab after adjustment for the number of prior advanced therapies. It is possible that patients who receive high numbers of advanced therapies have few remaining treatment options, and this may have introduced a bias that increases the threshold for initiating a new therapeutic intervention. Indeed, the number of previous advanced therapies was significantly higher in the ustekinumab-exposed group than that in the ustekinumab-unexposed group (Supplementary Table 3). Further research is warranted to clarify this potential bias, which could lead to prolonged use of mirikizumab, especially in ustekinumab-exposed patients.
Regarding safety, the proportion of patients who developed SAEs was 3.1% (1/32), and there were no deaths. The only SAE was pneumonia, from which the patient recovered, and mirikizumab was successfully resumed. Among other AEs requiring treatment suspension or discontinuation, most were exacerbations of UC (37.5%, 12/32). Except for UC itself, 1 patient (3.1%, 1/32) developed headache and another (3.1%, 1/32) developed concurrent dyspnea, fatigue, and pruritus. In the LUCENT-2 trial, SAEs developed in 3.3% of the mirikizumabtreated patients, which is consistent with our result [3]. Discontinuation of mirikizumab due to AEs was observed in 1.5% of the patients in the LUCENT-2 trial; this rate was slightly higher in our study. Headache was a common AE in the LUCENT-2 trial. Overall, the safety of mirikizumab in maintenance therapy for UC among patients with DTT-IBD in our study was similar to that in the LUCENT-2 trial.
There are limitations in our study. First, this was a single-center, retrospective study. The number of patients was limited, and potential biases in patient selection and data collection may exist. However, the investigation was limited to DTT-IBD patients, and this restriction reduced selection bias in patient characteristics regarding refractoriness. Second, therapeutic efficacy was evaluated on the basis of PRO2 and not on endoscopic activity, leucine-rich alpha-2 glycoprotein, and fecal calprotectin because of insufficient data. Third, therapeutic drug monitoring for mirikizumab was not performed because examination of drug trough levels and anti-drug antibody levels were unavailable in general clinical settings because of the lack of medical health reimbursement for these measurements in Japan. Finally, therapeutic efficacy of mirikizumab might have been overestimated in some patients receiving concomitant tacrolimus. To overcome these limitations, a larger scale prospective study is warranted.
This study provided RWD regarding maintenance therapy with mirikizumab for UC among patients with DTT-IBD. Mirikizumab may offer clinical benefit even in patients with prior exposure to ustekinumab.
NOTES
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Funding Source
This work was supported by the Japan Society for the Promotion of Science (JSPS) (JSPS Grant-in-Aid for Early-Career Scientists [JP24K18986 to YY and JP22K16005 to Kiyohara H]); the Japan Foundation for Applied Enzymology.
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Conflict of Interest
Kiyohara H received lecture fees from Mochida Pharmaceutical Co., Ltd. Kanai T received joint research support from Miyairisan Pharma Corporation, Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Co., Ltd., KYORIN Pharmaceutical Co., Ltd., ZERIA Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Mochida Pharmaceutical Co., Ltd.; lecture fees from Miyairisan Pharma Corporation and Takeda Pharmaceutical Co., Ltd.; and endowed chair funding from EA Pharma Co., Kyorin Pharmaceutical Co., Ltd., ZERIA Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, JIMRO Co., Ltd., Mochida Pharmaceutical Co., Ltd., and Miyarisan Pharma Corporation. The other authors have no conflicts of interest.
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Data Availability Statement
The data that support the findings of this study are not publicly available because of privacy reasons, but are available from the corresponding author upon reasonable request.
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Author Contributions
Conceptualization; Data curation; Formal analysis: Mizushima I, Yoshimatsu Y, Kiyohara H. Funding acquisition: Mikami Y, Kanai T. Investigation; Project administration: Mizushima I, Yoshimatsu Y, Kiyohara H. Supervision: Takabayashi K, Mikami Y, Kanai T. Resources: all authors. Methodology: Mizushima I, Yoshimatsu Y, Kiyohara H, Sugimoto S, Sujino T. Software; Visualization: Mizushima I, Yoshimatsu Y, Kiyohara H. Writing–original draft: Mizushima I, Yoshimatsu Y, Kiyohara H. Writing–review & editing: all authors. Approval of final manuscript: all authors.
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Additional Contributions
The authors are grateful to the members of the Keio IBD Group for assisting with this study. We thank Jane Charbonneau, DVM, from Edanz for editing a draft of this manuscript.
Supplementary Material
Supplementary materials are available at the Intestinal Research website (https://www.irjournal.org).
Supplementary Fig. 1.
Trends in laboratory indices related to disease activity. Hemoglobin, serum C-reactive protein, and serum albumin levels at baseline (week 0), weeks 12, 26, and 52 are shown as box-and-whisker plots. Alb, Albumin; CRP, C-reactive protein; Hb, Hemoglobin.
ir-2025-00176-Supplementary-Fig-1.pdf
Supplementary Fig. 2.
Persistency of clinical remission. Cumulative clinical remission rate and the 95% CI after achieving clinical remission (A) and steroid-free clinical remission (B) is depicted in a Kaplan-Meier plot. CI, confidence interval; SFCR, steroid-free clinical remission.
ir-2025-00176-Supplementary-Fig-2.pdf
Fig. 1.Efficacy of mirikizumab up to 52 weeks. (A) The proportions of patients who achieved a clinical response and clinical remission at weeks 12, 26, and 52. The 95% confidence intervals were estimated and shown as error bars. (B) The proportion of patients who achieved steroid-free clinical remission (SFCR) within 52 weeks. The error bar shows the 95% confidence interval.
Fig. 2.Cumulative continuation rate of mirikizumab. Time to withdrawal of mirikizumab as the cumulative continuation rate is shown as a Kaplan-Meier plot with 95% confidence intervals (CI).
Fig. 3.Efficacy and cumulative continuation rate of mirikizumab stratified by prior exposure to ustekinumab. (A) Clinical response and clinical remission rates at week 52 were calculated for ustekinumab-exposed and unexposed patients. (B) The proportion of patients who achieved SFCR within 52 weeks. The error bars show the 95% confidence intervals. Fisher exact test was used for the comparison (A and B). (C) The cumulative continuation rate of mirikizumab was estimated for ustekinumab-exposed and unexposed patients and is shown as a Kaplan-Meier plot with 95% confidence intervals. The log-rank test was used to compare persistency between the 2 groups. UST, ustekinumab; SFCR, steroid-free clinical remission.
Table 1.Baseline Patient Characteristics
|
Characteristic |
Value (n=32) |
|
Age (yr), median (IQR) |
35 (28–49) |
|
Female sex, No. (%) |
16 (50.0) |
|
Disease duration (yr), median (IQR) |
9 (6–15) |
|
Montreal classification of disease extent, No. (%) |
|
|
E1 |
2 (6.3) |
|
E2 |
4 (12.5) |
|
E3 |
26 (81.3) |
|
PRO2 score, median (IQR) |
3 (2–4) |
|
Endoscopic activity, No. (%)a
|
|
|
MES 1 |
1 (6.7) |
|
MES 2 |
9 (60.0) |
|
MES 3 |
5 (33.3) |
|
Laboratory data, median (IQR) |
|
|
CRP (mg/L) |
1.2 (0.2-3.2) |
|
Albumin (g/dL) |
4.3 (4.0-4.4) |
|
Hemoglobin (g/dL) |
13.1 (11.6–14.5) |
|
Concomitant medication, No. (%) |
|
|
5-Aminosalicylic acid |
25 (78.1) |
|
Systemic corticosteroid |
3 (9.4) |
|
Immunomodulator |
6 (18.8) |
|
Tacrolimus |
9 (28.1) |
|
Number of exposed advanced therapy, No. (%) |
|
|
2 |
6 (18.8) |
|
3 |
10 (31.3) |
|
4 |
5 (15.6) |
|
≥ 5 |
11 (34.3) |
|
Prior exposed advanced therapy, No. (%) |
|
|
Anti-TNF (IFX, ADA, GLM) |
31 (96.9) |
|
Anti-IL-12/23p40 (UST) |
23 (71.9) |
|
Anti-a4b7 integrin (VDZ) |
19 (58.4) |
|
JAK inhibitor (FIL, TOF, UPA) |
18 (56.3) |
|
Tacrolimus |
9 (28.1) |
|
Reason for DTT-IBD, No. (%) |
|
|
Failed ≥ 2 advanced therapies with different MoA |
32 (100) |
|
Complex perianal disease |
0 |
|
Comorbid psychosocial complications |
0 |
Table 2.Adverse Events and Serious Adverse Events
|
Adverse events |
No. (%) (n = 32) |
|
Any adverse event |
15 (46.9) |
|
Ulcerative colitis exacerbation |
12 (37.5) |
|
Headache |
1 (3.1) |
|
Dyspneaa
|
1 (3.1) |
|
Fatiguea
|
1 (3.1) |
|
Pruritusa
|
1 (3.1) |
|
Serious adverse event |
|
|
Pneumonia |
1 (3.1) |
|
Death |
0 |
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