Abstract
Introduction
Moderate-to-severe ulcerative colitis (UC) is commonly treated with oral corticosteroids. However, in cases of oral corticosteroid failure, no clear consensus exists on whether to transition to intravenous corticosteroids (IVCS) or initiate advanced therapies. The aim of this study was to evaluate whether responsiveness to oral corticosteroids is associated with differences in the efficacy of IVCS.
Methods
This multicenter cohort study (conducted at 10 facilities) included patients with moderate-to-severe UC who were transitioned to IVCS after failure of oral corticosteroid therapy. The patients were categorized into the partial responder and nonresponder groups based on their response to oral corticosteroids, as measured by improvements in their PRO-2 scores. The primary outcome was clinical remission at day 30, defined as a total PRO-2 score ≤1 with a rectal bleeding subscore of 0. Logistic regression was used to estimate the odds ratio (OR) of achieving clinical remission.
Results
A total of 123 patients with UC were included, with 41 and 82 patients in the partial responder and nonresponder groups, respectively. Clinical remission at day 30 was achieved in 41.4% of the partial responders and 18.3% of the nonresponders (multivariable-adjusted OR, 0.35 [95% CI: 0.15–0.83]; p = 0.017). The nonresponder group had a higher risk of requiring advanced therapies within 90 days than the partial responder group (multivariable-adjusted OR, 2.48 [95% CI: 1.09–5.66]; p = 0.030).
Conclusions
In patients with UC and oral corticosteroid failure, responsiveness to oral corticosteroids may be associated with differences in IVCS efficacy.
Keywords: Ulcerative colitis, Corticosteroids, Cohort study, Treatment response, Inflammatory bowel disease
Introduction
Ulcerative colitis (UC) is an idiopathic chronic inflammatory disease characterized by a relapsing and remitting course [1]. Systemic corticosteroids are a key treatment for moderate-to-severe UC. In cases of moderate-to-severe UC, insufficient response to oral corticosteroids necessitates either increasing the dosage, switching to intravenous corticosteroids (IVCS), or initiating advanced therapy. However, no clear or established criteria exist to guide the choice between IVCS and advanced therapy for oral corticosteroid failure. Although the effectiveness of switching to IVCS has been reported even in cases where oral corticosteroids are ineffective [2], other studies suggest advanced therapy is more effective than IVCS for managing oral corticosteroid failure requiring hospitalization [3].
Corticosteroids are associated with side effects from long-term use [4]; furthermore, their use during surgery increases the risk of perioperative complications [5–7]. Although the adoption of advanced therapies is expanding among patients unresponsive to standard therapy, immediate escalation may not be required for all patients. For some patients who are refractory to oral corticosteroids, IVCS may still induce remission, obviating the need for advanced therapy and thus reducing healthcare costs and limiting additional immunosuppression. Hence, predicting cases in which IVCS may be effective despite refractoriness to oral corticosteroids remains a clinically important challenge.
We hypothesized that the degree of clinical response to oral corticosteroids may be associated with differences in IVCS efficacy. Although numerous studies have explored the predictors of IVCS effectiveness [8–14], to our knowledge, none have examined whether the response to oral corticosteroids itself is associated with differential therapeutic efficacy of IVCS in patients with UC experiencing oral corticosteroid failure. The aim of this study was to evaluate this association. By understanding these relationships, clinicians can better individualize treatment strategies, potentially avoiding unnecessary escalation to advanced therapy for certain patients while ensuring timely initiation of appropriate therapy.
Methods
Ethical Considerations
This study was conducted in accordance with the Declaration of Helsinki and was approved by the Central Institutional Review Board, with subsequent approvals obtained from the Institutional Review Boards of all participating institutions. The approval number from Keiyu Hospital’s Ethics Committee was K2024013. Written informed consent was not required owing to the study’s retrospective nature. Data handling followed institutional privacy guidelines. All authors had access to the study data and reviewed and approved the final manuscript.
Study Design and Participants
This multicenter retrospective cohort study was conducted at 10 facilities in Japan, including university and non-university hospitals. We used the data of consecutive patients with UC who required IVCS owing to insufficient clinical response to oral corticosteroid therapy between January 1, 2011, and March 31, 2024. All data were extracted from the medical records of each participating institution. The inclusion criteria were as follows: (a) diagnosis of UC, (b) aged ≥18 years, (c) two-item patient-reported outcome (PRO-2) score of ≥3 at the initiation of oral corticosteroid therapy and IVCS, and (d) patients who were deemed to have failed during oral corticosteroid therapy and transitioned to IVCS. The exclusion criteria were as follows: (a) history of total colorectal resection, (b) use of oral corticosteroids or IVCS not meeting dosage standards recommended by Japanese guidelines [5], and (c) history of advanced therapy use – advanced therapy was defined as the use of biological agents, Janus kinase inhibitors, calcineurin inhibitors, indigo naturalis, or investigational new drugs.
Definition of Partial Responder and Nonresponder
Patients failing to achieve clinical remission with oral corticosteroid therapy were classified into partial responder and nonresponder groups according to their clinical response to oral corticosteroid therapy. The clinical response to oral corticosteroids was evaluated on the basis of clinical symptoms within 4 weeks of initiating therapy or until IVCS initiation if oral corticosteroids were administered for <4 weeks. The clinical symptoms at the time of the most significant effect during this period were assessed. The 4-week period was defined in accordance with the European Crohn’s and Colitis Organisation guidelines on steroid resistance [15]. Partial responders were defined as patients whose total PRO-2 score decreased by at least one point from baseline, whereas nonresponders were defined as those whose total PRO-2 score worsened or remained unchanged from baseline. The cohort of partial responders was subjected to exploratory subanalysis by stratifying the patients into two subgroups based on the degree of improvement in PRO-2 score: high-improvement (defined as ≥50% reduction from baseline) subgroup and low-improvement (defined as <50% reduction from baseline) subgroup.
Definition of Oral Corticosteroid Therapy and IVCS
Oral corticosteroid therapy was defined as the use of 30–40 mg of prednisolone, whereas IVCS was defined as the use of prednisolone at a daily dose of ≥40 mg intravenously. Furthermore, when switching from oral corticosteroids to IVCS, the dosage was increased. The decision to switch was determined at the discretion of the treating physician at each participating institution, based on individual patient conditions. Following IVCS administration, corticosteroids were gradually tapered, and patients were transitioned back to oral corticosteroids as the dose was reduced. These dosages were consistent with Japanese guidelines [5]. The duration of IVCS administration and timing of transition to oral corticosteroids were not standardized; however, they were determined by institutional protocols and the treating physicians’ clinical judgment based on each patient’s clinical response.
Outcomes
The primary outcome was clinical remission at day 30 [16]. If data at day 30 were unavailable because of patient discharge, data collected within 2 weeks of day 30 were used. Clinical remission was defined as a total PRO-2 score ≤1, with a rectal bleeding subscore of 0. Patients who required colectomy or received additional rescue treatments such as advanced therapies or systemic steroids (re-induction) were classified as having failed intravenous steroid therapy and were analyzed as not in remission.
The secondary outcomes included clinical remission at days 3, 7, 14, and 90; advanced therapy use within 90 days; colectomy within 90 days; corticosteroid-free remission at day 90; and adverse events within 90 days. If data at day 90 were unavailable owing to patient discharge, data collected within 2 weeks of day 90 were used. Clinical remission was based on the aforementioned criteria. Corticosteroid-free remission at day 90 was defined as clinical remission at day 90 without the use of corticosteroids.
Adverse events related to infection were defined as those requiring antimicrobial drugs or surgical procedures, such as debridement, for infection control. Venous thrombosis and corticosteroid side effects were defined according to a definitive diagnosis in the medical records.
Covariates
Data were collected on sex, body weight, age, age of onset, disease duration, disease extent, use of 5-aminosalicylic acid (5-ASA), use of immunomodulators, granulocyte-monocyte apheresis (GMA), smoking status, maximum dose of oral corticosteroids, dose of IVCS, PRO-2 score, Mayo endoscopic subscore (MES), C-reactive protein (CRP), platelet count, serum albumin level, and hemoglobin level at baseline. The PRO-2 score and MES were retrospectively assessed using clinical records at the time of inclusion (before initiation of IVCS treatment). Additionally, MES was assessed by inflammatory bowel disease specialists at each facility.
Statistical Analysis
Baseline characteristics of the patients were described using medians with interquartile ranges (IQRs) for continuous variables and absolute numbers with percentages for categorical variables. Dichotomous variables were analyzed using the chi-square test, and continuous variables were analyzed using the Wilcoxon rank-sum test.
For the primary analysis, clinical remission on day 30 between the partial responder and nonresponder groups was compared. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) and determine the association between baseline oral corticosteroid response and clinical remission. In multivariable analyses, adjustments were made for oral corticosteroid response, baseline PRO-2 score, and disease duration. These covariates were also selected in previous studies [9, 17]. Similarly, clinical remission at days 3, 7, 14, and 90 and corticosteroid-free remission at day 90 were evaluated using the same methods. Furthermore, in an exploratory analysis, the partial responder group was stratified into two subgroups based on the improvement degree: high-improvement subgroup (≥50% improvement in PRO-2 score) and low-improvement subgroup (<50% improvement). In the exploratory analysis, logistic regression models were used to compare clinical remission rates between the high- and low-improvement subgroups within the partial responder group, using the nonresponder group as the reference.
For additional analyses, advanced therapy-free survival and colectomy-free survival were calculated using the Kaplan-Meier method. The association between the baseline oral corticosteroid response and risk of requiring advanced therapy or colectomy was evaluated using the log-rank test and Cox proportional hazards regression. Multivariate analysis using the Cox proportional hazards model included age, sex, body weight, disease extent, age of onset, dose of oral corticosteroid, and PRO-2 score as covariates, selected for their known clinical relevance to disease outcomes, as mentioned in the literature [9, 16, 17]. We reported two-sided 95% CIs as an informal measure of uncertainty and followed the recommendation of the American Statistical Association to avoid using terms such as “statistically significant” [18]. Analyses were performed using Stata, version 18.0 (StataCorp).
Results
Baseline Characteristics
A total of 123 patients with UC who met the eligibility criteria and did not meet any exclusion criteria across ten facilities were included in the analysis. Of these, 41 patients (33.3%) were classified into the partial responder group, and 82 patients (66.7%) were classified into the nonresponder group (Fig. 1). The baseline characteristics of the patients are summarized in Table 1. The median PRO-2 scores were 5 (IQR: 4–6) in the partial responder group and 5 (IQR: 5–6) in the nonresponder group (p = 0.035). The median duration of oral corticosteroid use was longer in the partial responder group than in the nonresponder group: 15 days (IQR: 9–34) vs. 10.5 days (IQR: 6–17), respectively (p = 0.003).
Fig. 1.
Participant flowchart. A total of 123 patients were included in the analysis and categorized into two groups: partial responder group and nonresponder group.
Table 1.
Baseline characteristics of patients at the start of IVCSs
| | Partial responder group | Nonresponder group | p value |
|---|---|---|---|
| n = 41 | n = 82 | ||
| Male, n (%) | 21 (51.2) | 48 (58.5) | 0.44a |
| Body weight, kg (IQR) | 55.1 (50.0–59.8) | 56.5 (49.0–65.6) | 0.78b |
| Age, years (IQR) | 38 (28–53) | 39 (25–50) | 0.48b |
| Age of onset, years (IQR) | 35 (22–48) | 30 (23–44) | 0.32b |
| Disease duration, years (IQR) | 2 (0–6) | 2 (0–9) | 0.39b |
| Disease extent, n (%) | |||
| Extensive | 38 (92.7) | 72 (87.8) | 0.69a |
| Left-sided | 3 (7.3) | 9 (11.0) | |
| Proctitis | 0 (0) | 1 (1.2) | |
| Smoker, n (%) | 11 (29.7) | 30 (37.0) | 0.56a |
| Baseline concomitant therapy | |||
| 5-ASA use, n (%) | 30 (73.1) | 60 (73.2) | 1.00a |
| Immunomodulator use, n (%) | 9 (21.9) | 11 (13.4) | 0.23a |
| GMA, n (%) | 9 (22.0) | 17 (20.7) | 0.88a |
| Corticosteroid naïve (before oral corticosteroid administration) | 27 (65.9) | 51 (62.2) | 0.69a |
| Maximum dose of oral corticosteroid, mg/day (IQR) | 30 (30–40) | 30 (30–40) | 0.76b |
| Duration of oral corticosteroid use, days (IQR) | 15 (9–34) | 10.5 (6–17) | 0.003b |
| Dose of IVCS, mg/day (IQR) | 60 (50–60) | 60 (50–60) | 0.17b |
| PRO-2 score, n (%) | 5 (4–5) | 5 (4–6) | 0.035b |
| MES, n (%) | | | 0.94a |
| 2 | 10 (25.0) | 20 (25.6) | |
| 3 | 30 (75.0) | 58 (74.4) | |
| CRP, mg/dL (IQR) | 3.73 (1.34–7.8) | 3.93 (1.3–7.2) | 0.90b |
| Alb, g/dL (IQR) | 3.1 (2.8–3.55) | 3.0 (2.5–3.5) | 0.30b |
| Hb, g/dL (IQR) | 11.8 (10.1–13.4) | 12.1 (10.0–13.9) | 0.93b |
Values are presented as medians and IQRs or n (%). Missing data: MES (n = 4).
DM, diabetes mellitus; CRC, colorectal cancer; 5-ASA, 5-aminosalicylic acid; GMA, granulocyte and monocyte apheresis; IVCS, intravenous corticosteroids; PRO-2 score, two-item patient-reported outcome score; MES, Mayo endoscopic subscore; CRP, C-reactive protein; Alb, albumin; Hb, hemoglobin; IQR, interquartile range.
aChi-square test.
bMann-Whitney U test.
Comparison of Clinical Remission between the Partial Responder and Nonresponder Groups
Table 2 shows the primary and secondary outcomes for the partial responder and nonresponder groups. At day 30, the proportion of patients achieving clinical remission, the primary outcome, was 41.4% (17/41) in the partial responder group and 18.3% (15/82) in the nonresponder group (OR, 0.32 [95% CI: 0.13–0.79], p = 0.006, adjusted OR, 0.35 [95% CI: 0.15–0.83], p = 0.017). Table 2 presents the data on clinical remission at days 3, 7, 14, and 90 as secondary outcomes.
Table 2.
Summary of primary and secondary outcomes
| | Partial responder group | Nonresponder group | Univariable analysis | Multivariable analysis | ||||
|---|---|---|---|---|---|---|---|---|
| n (%) | n (%) | OR | 95% CI | p value | OR | 95% CI | p value | |
| Primary outcome | ||||||||
| Clinical remission at day 30 | 17 (41.4) | 15 (18.3) | 0.32 | 0.13–0.79 | 0.006 | 0.35 | 0.15–0.83 | 0.017 |
| Secondary outcome | ||||||||
| Clinical remission at day 3 | 2 (4.87) | 3 (3.66) | 0.74 | 0.82–9.22 | 0.75 | 0.83 | 0.13–5.41 | 0.84 |
| Clinical remission at day 7 | 9 (22.0) | 7 (8.53) | 0.33 | 0.10–1.11 | 0.037 | 0.33 | 0.11–0.99 | 0.047 |
| Clinical remission at day 14 | 15 (36.6) | 12 (14.6) | 0.29 | 0.11–0.79 | 0.006 | 0.30 | 0.12–0.75 | 0.010 |
| Clinical remission at day 90 | 15 (36.6) | 14 (17.1) | 0.36 | 0.14–0.92 | 0.016 | 0.35 | 0.15–0.85 | 0.021 |
| Use of advanced therapy at day 90 | 24 (58.5) | 63 (76.8) | 2.42 | 1.01–5.79 | 0.027 | 2.48 | 1.09–5.66 | 0.030 |
| Colectomy at day 90 | 4 (9.76) | 14 (17.1) | 1.90 | 0.54–8.48 | 0.28 | 1.27 | 0.41–3.95 | 0.67 |
| Corticosteroid-free remission at day 90 | 9 (22.0) | 6 (7.3) | 0.28 | 0.08–0.98 | 0.019 | 0.31 | 0.10–0.97 | 0.044 |
Multivariate logistic regression models were adjusted for response of oral corticosteroids, baseline PRO-2 score, and disease duration.
CI, confidence interval; OR, odds ratio.
The partial responder group was stratified based on the degree of PRO-2 score improvement into high-improvement and low-improvement groups. Clinical remission at day 30 was achieved in 80% (8/10) and 29.0% (9/31) of patients in the high-improvement and low-improvement groups, respectively. The high-improvement group had a higher remission rate than the nonresponder group (p < 0.001); in contrast, the remission rate were similar between the low-improvement and nonresponder groups (p = 0.21). Among the 104 non-colectomy patients, at day 30, 82 had already transitioned from intravenous to oral corticosteroids. Of the remaining 22 patients, 18 were subsequently switched to oral corticosteroids, whereas four underwent rapid tapering of IVCS alongside the initiation of advanced therapy, completing intravenous therapy within 30 days. The median corticosteroid dose at day 30 was 20 mg (IQR: 20–30 mg).
Comparison of Advanced Therapy Initiation between Partial Responder and Nonresponder Groups
In the partial responder group, 24 patients (58.5%), and in the nonresponder group, 63 patients (76.8%) required advanced therapy within 90 days (OR = 2.42 [95% CI: 1.01–5.79], p = 0.027; adjusted OR = 2.48 [95% CI: 1.09–5.66], p = 0.030) (Table 2). Of those, in the partial responder group 20/24 (83.3%) and in the nonresponder group 50/63 (79.4%) did not respond to IVCS. These patients subsequently received advanced therapy while avoiding surgery within 90 days of IVCS initiation. Four patients underwent surgery without receiving advanced therapy after IVCS. Kaplan-Meier plots illustrating the rate of advanced therapy in the partial responder and nonresponder groups are presented in Figure 2. The log-rank test indicated that the nonresponder group had a higher rate of requiring advanced therapy than the partial responder group (p = 0.035). Cox proportional hazards regression analysis confirmed that the nonresponder group had a higher risk of requiring advanced therapy than the partial responder group (HR: 1.71; 95% CI: 1.04–2.84; p = 0.036). No difference was observed in the proportion of surgeries performed within 90 days between the partial responder and nonresponder groups (Table 2). Kaplan-Meier analysis of surgery-free survival showed that the colectomy rate was similar between the two groups (Fig. 3). Additionally, corticosteroid-free remission at day 90 was achieved in 9 patients (22.0%) in the partial responder group and 6 patients (7.3%) in the nonresponder group (OR = 0.28 [95% CI: 0.08–0.98], p = 0.019; adjusted OR = 0.31 [95% CI: 0.10–0.97], p = 0.044) (Table 2).
Fig. 2.
Kaplan-Meier curves of survival for patients requiring advanced therapy in the partial responder and nonresponder groups.
Fig. 3.
Kaplan-Meier curves of survival for patients requiring colectomy in the partial responder and nonresponder groups.
Comparison of Adverse Events between Partial Responder Group and Nonresponder Group
Table 3 summarizes the adverse events potentially associated with corticosteroid use observed in this study. Adverse events were identified in 6 patients in the partial responder group and 12 patients in the nonresponder group. The detailed breakdown of adverse events is as follows: infections occurred in 3 patients (7.3%) in the partial responder group and nine (11.0%) in the nonresponder group; venous thrombosis was reported in 1 patient (2.4%) in the partial responder group and 2 patients (2.4%) in the nonresponder group; diabetes was observed in 1 patient (2.4%) in the partial responder group; and psychiatric symptoms were noted in 1 patient (2.4%) in the partial responder group and one (1.2%) in the nonresponder group.
Table 3.
Summary of adverse events
| | Partial responder group | Nonresponder group |
|---|---|---|
| n = 41 | n = 82 | |
| Infection, n (%) | 3 (7.3) | 9 (11.0) |
| Venous thrombosis, n (%) | 1 (2.4) | 2 (2.4) |
| Diabetes, n (%) | 1 (2.4) | 0 (0) |
| Psychiatric symptoms, n (%) | 1 (2.4) | 1 (1.2) |
Discussion
To our knowledge, this study is the first to suggest that the degree of clinical response to oral corticosteroids is associated with the differential therapeutic efficacy of IVCS in patients with UC experiencing oral corticosteroid failure, highlighting the importance of individualized treatment strategies. At 30 days post-IVCS initiation, clinical remission rates were 41.4% and 18.3% in the partial responder and nonresponder groups, respectively. Patients who exhibited partial response to oral corticosteroids demonstrated greater IVCS efficacy than those who showed no response.
In a previous report, the clinical remission rate at day 30 after IVCS initiation was approximately 60%, exceeding the rate observed in this study [16]. This discrepancy may be attributed to the inclusion of patients with oral corticosteroid failure in this study, potentially leading to worse outcomes than those reported in the previous study. In another study, even among patients with oral corticosteroid failure, the efficacy rate on day 7 after switching to IVCS was reported to be 78% [2]. However, that study used the Montreal Severity Score, which includes subjective evaluations, and its retrospective design may have introduced selection bias favoring positive outcomes. Additionally, a separate study using a similar clinical remission definition reported a 10% remission rate at day 7 among hospitalized patients with oral corticosteroid failure transitioning to IVCS [3]. Our study showed a comparable day 7 remission rate of 13.0% (16/123). Collectively, these results suggest that the efficacy of IVCS may be lower in patients who experience oral corticosteroid failure than in those who do not, and our findings are consistent with those of previous reports.
Glucocorticoids exert anti-inflammatory effects by binding to glucocorticoid receptors (GRs) in the cytoplasm and subsequently modulating gene expression in the nucleus [19, 20]. Previous mice studies have indicated that high doses of glucocorticoids increase GR occupancy [21]. Therefore, when GR activation is insufficient at 30–40 mg doses, increasing the dose may enhance therapeutic efficacy. In contrast, if no response is observed at 30–40 mg doses, this may indicate that GR occupancy is already suboptimal, and further dose escalation will not provide additional benefits. Additionally, from a pharmacokinetic perspective, prednisolone achieves higher plasma concentrations more rapidly when administered intravenously than when administered orally [22]. This point implies that the route of administration can influence therapeutic efficacy. Additionally, pharmacokinetic studies have shown that absorption of oral corticosteroids may be impaired in patients with active and severe UC, likely owing to mucosal inflammation and accelerated intestinal transit, which could partially explain non-response to oral therapy [23]. These mechanistic and pharmacokinetic considerations support the validity of the findings presented in this study.
The transition from oral corticosteroids to IVCS raises concerns about prolonged steroid use, which may lead to side effects and a potential impact on immune suppression and subsequent treatments. For patients with complete oral corticosteroid failure, avoiding transitioning to IVCS and directly switching to advanced therapy may be advisable, as 75.6% of these patients ultimately required advanced therapy within 90 days in our study. However, patients with partial oral corticosteroid response may benefit from IVCS, given its relatively high efficacy in this subgroup. Moreover, in patients with acute severe UC, IVCS-induced clinical remission followed by maintenance therapy with 5-ASA or immunomodulators achieved 5-year remission maintenance rates of 33.9–43.1%, whereas anti-TNF-α antibody achieved 55.8% [24]. When remission is maintained with 5-ASA or immunomodulators after IVCS, preventing prolonged or unnecessary corticosteroid use, the overall healthcare cost can be lower than that with the introduction of advanced therapy [25]. These findings suggest that for some patients, remission with IVCS followed by maintenance therapy with 5-ASA or immunomodulators may obviate the immediate need for advanced therapy, potentially reducing long-term exposure to intensive immunosuppressive treatment and healthcare costs. In this study, even among patients for whom IVCS was ineffective and who subsequently required advanced therapy, the short-term surgery avoidance rate remained high in the partial responder and nonresponder groups. However, clinicians should avoid unnecessary or prolonged corticosteroid use because this can increase healthcare costs compared with timely initiation of advanced therapy [26], particularly in patients with oral corticosteroid failure. Therefore, IVCS may still be a viable initial treatment approach in cases where some therapeutic benefit can be expected.
This study had several limitations. First, this was a retrospective, observational study. Oral corticosteroids are usually initiated in outpatient settings, where it is possible to determine treatment efficacy; however, precisely measuring the extent of improvement in the PRO-2 scores was challenging. Therefore, it was difficult to accurately determine whether the included cases were those with minimal improvement in the PRO-2 score, such as steroid-refractory or steroid-dependent cases with relatively better responsiveness. As a result, both types of cases may have been included in the present study. Nonetheless, this limitation reflects real-world clinical practice, where precise symptom improvement measurements are not always feasible in outpatient settings. Furthermore, information on adverse events was collected through chart review to the extent possible. Therefore, the capture of adverse events was limited. Second, the steroid tapering protocol and the timing of transition from intravenous to oral corticosteroid therapy were not standardized across institutions and were determined by each treating physician according to individual patient response. In fact, our results showed a difference in the number of patients achieving clinical remission and corticosteroid-free remission at day 90. This difference is likely due to variations in the pace of steroid tapering across institutions, with some patients still receiving a small amount of corticosteroids by day 90. However, the speed of tapering does not affect treatment success or failure, making this limitation unlikely to impact the results of our study [27]. Third, we did not directly compare the therapeutic efficacy of IVCS and advanced therapy. Consequently, we cannot definitively conclude which treatment option yields better outcomes for UC patients with oral corticosteroid failure. Although partial responders may show better outcomes with IVCS than nonresponders, this does not necessarily mean IVCS is the best option. We did not collect data on patients who transitioned to advanced therapy without prior IVCS, so a direct comparison could not be made. Finally, the decision to switch from oral corticosteroids to IVCS before study enrollment, as well as decisions regarding subsequent advanced therapy and surgery after IVCS initiation, may have been influenced by institutional and individual differences. However, all participating institutions specialized in inflammatory bowel disease and the treatments generally followed Japanese guidelines [5].
In conclusion, this study suggests that the efficacy of IVCS may differ according to the degree of clinical response to oral corticosteroids in patients with UC experiencing oral corticosteroid failure. When clinical response is not achieved with oral corticosteroids, the decision to transition to IVCS should be guided by the patient’s prior response to oral corticosteroids.
Acknowledgments
This project was supported by the Kanagawa IBD study Group. We would like to thank Editage (www.editage.jp) for English language editing. The members of Kanagawa IBD Study Group are listed as below. The members of the Kanagawa IBD study Group are Tomohiro Fukuda (Keiyu Hospital and Yokohama Municipal Citizen’s Hospital), Atsushi Yoshida (Ofuna Chuo Hospital), Kenji Tatsumi (Yokohama Municipal Citizen’s Hospital), Naoko Inagaki (Yokohama City University Hospital and Fujisawa City Hospital), Aya Ikeda (Yokohama City University Hospital), Noriyuki Ogata (Showa University Northern Yokohama Hospital), Jun Kanazawa (Kitasato University School of Medicine), Yoshinori Nakamori (Yokohama City University Medical Center), Toshiyuki Endo (Showa University Fujigaoka Hospital), Hirosuke Kuroki (Yokohama Municipal Citizen’s Hospital), Yuichiro Kuroki (St Marianna University School of Medicine), Takashi Ueda (Tokai University School of Medicine), Masaki Kato (St Marianna University School of Medicine), Kouki Goto (Yokohama Municipal Citizen’s Hospital), and Tomohiko Sasaki (Yokohama Gate Tower Clinic).
Statement of Ethics
This study protocol was reviewed and approved by the Keiyu Hospital Ethics Committee, Keiyu Hospital (Approval No. K2024013), with subsequent approvals obtained from the Institutional Review Boards of all participating institutions, including Yokohama Municipal Citizen’s Hospital (Approval No. C24-06), Yokohama City University (F241000031), Fujisawa City Hospital (F2024023), Showa University Northern Yokohama Hospital (C-T2024-1445), Kitasato University (E2024040), Showa University Fujigaoka Hospital (J240829-036), St Marianna University (6663), Tokai University (24RC042), and Ofuna Chuo Hospital (No. 2024-003). Written informed consent was not required due to the study’s retrospective nature. Patient consent was not required in accordance with local or national guidelines. The requirement for written informed consent was waived by the Keiyu Hospital Ethics Committee due to the retrospective nature of the study. This study was conducted in accordance with the principles of the World Medical Association Declaration of Helsinki. Data handling followed institutional privacy guidelines. All authors had access to the study data and reviewed and approved the final manuscript.
Conflict of Interest Statement
N.O. received honoraria from Takeda Pharma, Mitsubishi Tanabe Pharma, EA Pharma, AbbVie GK, Mochida Pharma, Zeria Pharma, and Nippon Kayaku. A.Y. received personal fees from Mitsubishi Tanabe Pharma, Janssen Pharmaceutical K.K., AbbVie Inc., EA Pharma Co., Ltd., Nippon Kayaku Co. Ltd., Takeda Pharmaceutical Co. Ltd., Pfizer Inc., and Mochida Pharmaceutical Co., Ltd. T.F., K.T., N.I., A.I., J.K., Y.N., T.E., H.K., Y.K., and T.U. have no conflicts of interest to declare.
Funding Sources
This study was not supported by any sponsor or funder.
Author Contributions
T. Fukuda: conceptualized and designed the study, acquired data, performed statistical analyses, interpreted the data, drafted the manuscript, and performed critical revision of the manuscript for important intellectual content. K. Tatsumi, N. Inagaki, and A. Ikeda: conceptualized and designed the study, acquired data, and performed critical revision of the manuscript for important intellectual content. N. Ogata, J. Kanazawa, Y. Nakamori, T. Endo, H. Kuroki, Y. Kuroki, and T. Ueda: acquired data and performed critical revision of the manuscript for important intellectual content. A. Yoshida: conceptualized and designed the study, acquired data, supervised the study, and performed critical revision of the manuscript for important intellectual content.
Funding Statement
This study was not supported by any sponsor or funder.
Data Availability Statement
The data that support the findings of this study are not publicly available due to the presence of potentially identifiable or sensitive patient information. However, the data may be made available upon reasonable request to the study’s Steering Committee, subject to review and approval, provided that the researchers meet the criteria for access to confidential data.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that support the findings of this study are not publicly available due to the presence of potentially identifiable or sensitive patient information. However, the data may be made available upon reasonable request to the study’s Steering Committee, subject to review and approval, provided that the researchers meet the criteria for access to confidential data.