Effectiveness, safety, and pharmacokinetics of the infliximab biosimilar CT-P13 after non-medical switch from the infliximab originator in patients with inflammatory bowel disease

Ryohei Nomaru; Teruyuki Takeda; Atsushi Takahashi; Hiroyuki Mikumo; Shigeyoshi Yasukawa; Akihiro Koga; Takao Kanemitsu; Yoichiro Ono; Noritaka Takatsu; Masaki Miyaoka; Takashi Hisabe; Hisatomi Arima; So Imakiire; Eri Yamauchi; Shinya Ashizuka; Fumihito Hirai

doi:10.5217/ir.2025.00118

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Original Article Effectiveness, safety, and pharmacokinetics of the infliximab biosimilar CT-P13 after non-medical switch from the infliximab originator in patients with inflammatory bowel disease: Ryohei Nomaru^1,*, Teruyuki Takeda^2,*, Atsushi Takahashi², Hiroyuki Mikumo², Shigeyoshi Yasukawa², Akihiro Koga², Takao Kanemitsu³, Yoichiro Ono⁴, Noritaka Takatsu², Masaki Miyaoka³, Takashi Hisabe^2,4, Hisatomi Arima⁵, So Imakiire¹, Eri Yamauchi¹, Shinya Ashizuka¹, Fumihito Hirai¹; DOI: https://doi.org/10.5217/ir.2025.00118
Published online: November 27, 2025

¹Department of Gastroenterology, Fukuoka University Faculty of Medicine, Fukuoka, Japan

²Inflammatory Bowel Disease Center, Fukuoka University Chikushi Hospital, Chikushino, Japan

³Department of Endoscopy, Fukuoka University Chikushi Hospital, Chikushino, Japan

⁴Department of Gastroenterology, Fukuoka University Chikushi Hospital, Chikushino, Japan

⁵Department of Preventive Medicine and Public Health, Fukuoka University Faculty of Medicine, Fukuoka, Japan

Correspondence to Fumihito Hirai, Department of Gastroenterology, Fukuoka University Faculty of Medicine, 7-45-1 Nanakuma Jonan-ku, Fukuoka 814-0180, Japan. E-mail: fuhirai@cis.fukuoka-u.ac.jp

*These authors contributed equally to this study as first authors.

• Received: June 30, 2025 • Revised: September 1, 2025 • Accepted: September 4, 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
Supplementary Material
REFERENCES

Abstract

Background/Aims
The introduction of anti-tumor necrosis factor-α antibodies transformed the landscape of inflammatory bowel disease (IBD) treatment. Because biologics are associated with increased medical costs, the use of biosimilars (BS) is recommended. However, high-quality evidence on the efficacy of BS in Japan remains limited. Therefore, this study aimed to evaluate the efficacy and safety of BS in patients with IBD.
Methods
Patients with IBD who underwent a non-medical switch (NMS) from infliximab originator (IFX-O) to IFX-BS at Fukuoka University Chikushi Hospital were prospectively evaluated. The observation period was up to 56 weeks after the NMS, and the rate of continuation, clinical remission at 56 weeks, safety, and changes in trough concentration were analyzed. Moreover, a questionnaire survey regarding BS and NMS was conducted.
Results
A total of 167 patients were included in this study. The continuation rate for IFX-BS therapy after NMS was high (95.6%). The remission maintenance rate at 56 weeks was 85.7% for patients with Crohn’s disease and 77.8% for patients with ulcerative colitis. Adverse events were observed in 22.8% of patients. However, only 2 severe adverse events were recorded. The ratios of trough concentrations at 8, 24, and 56 weeks to that at week 0 were 115.6%, 101.2%, and 123.5%, respectively, indicating statistical non-inferiority. In a questionnaire survey, only 6.2% of the patients were aware of BS, however, more than half of them agreed with the NMS recommendation.
Conclusions
The efficacy and safety of IFX-BS after NMS are high. In addition, its trough concentration is serologically non-inferior to baseline values.
Keywords: Inflammatory bowel diseases; Biosimilar; Bio-switch; Non-medical switch

INTRODUCTION

Infliximab (IFX), an anti-tumor necrosis factor (anti-TNF)-α inhibitor, is the first biologic drug developed for the treatment of inflammatory bowel disease (IBD). IFX was proven to be highly effective for the treatment of Crohn’s disease (CD) and ulcerative colitis (UC) in the ACCENT I trial [1] and the ACT1 trial [2], respectively. Since then, IFX has been widely used in clinical practice worldwide, bringing about a paradigm shift in the treatment of IBD. However, the high cost of anti-TNF-α inhibitors remains a challenge owing to its impact on healthcare economic burden [3]. Biosimilars have been proven to be structurally and functionally similar to originators and are now being used as alternatives to the more expensive originators [4]. Evidence of the efficacy of IFX biosimilars (IFX-BS) has been established in studies conducted in Western countries, such as the NORSWITCH study [5], which advanced the widespread recognition of the usefulness and safety of BS. The NOR-SWITCH study, which was focused on autoimmune diseases such as IBD and rheumatoid arthritis, demonstrated the efficacy and safety of switching from the IFX-originator (IFX-O) to an IFX-BS [5]. Moreover, a randomized controlled trial demonstrated the efficacy and safety of an IFX-BS for the treatment of CD [6], leading to the recommendation of the drug in Western countries [7,8].

In Japan, CT-P13, an IFX-BS, became available for the treatment of patients with IBD in 2014 through extrapolation of the outcomes of rheumatoid arthritis treatment. Considering the increasing number of patients with IBD [9] and the recent increase in direct medical costs, the Ministry of Health, Labour, and Welfare in Japan recommends the use of biosimilars. In Japan, patients with CD and moderate-to-severe UC are designated as patients with intractable disease and receive medical cost deductions. In other words, patients with IBD in Japan will not have significantly increased medical expenses, regardless of whether they use IFX-O or not.

Regarding research on the use of biosimilars in Japan, only a few reports from post-marketing surveillance studies [10,11] and retrospective studies [12,13] have been published. High-quality evidence of the efficacy and safety of BS in Japanese patients has not yet been established. Furthermore, although the Japanese guidelines recommend the use of IFX-BS based on evidence from Europe and the United States [14], the lack of studies on the use of BS in Japanese patients hinders the use of IFXBS in Japan. Therefore, we conducted a prospective observational study to evaluate the efficacy and safety of IFX-BS in patients with IBD based on real-world clinical practice of nonmedical switching (NMS) in Japan.

METHODS

1. Ethical Considerations

This prospective observational study was conducted in accordance with the ethical principles of the Declaration of Helsinki and related guidelines, regulations, and requirements for approval. This study was approved by Fukuoka University Hospital Ethics Committee (No. C21-01-001).

2. Patients

1) Eligibility

Patients who provided written consent to participate in this prospective study and completed a questionnaire survey on NMS at Fukuoka University Chikushi Hospital were considered eligible for inclusion into this study. Patients who had been on maintenance therapy for at least 14 weeks after the introduction of IFX-O were included, whereas those in the induction phase were excluded. Pregnant women were also excluded from the study. In Japan, double dose and shortened duration of IFX therapy are approved for the treatment of CD. Therefore, patients with CD who had an increased dose and shortened duration of therapy were also included in this study.

2) Non-Medical Switching

Since April 2021, informed consent for NMS at our facility is obtained by explaining to patients that “In Europe and the United States, there is evidence of the safety and efficacy of IFX-BS in patients with IBD, and the switch to IFX-BS has already been implemented as a national policy. In addition, IFX-BS has been covered by health insurance since 2014, and the Ministry of Health, Labour, and Welfare currently recommends switching from IFX-O to IFX-BS.” After providing this explanation to eligible patients, patients who consented to the alternative therapy underwent NMS from IFX-O to IFX-BS (CT-P13).

3) Endpoints

The observation period for this study ranged from 8 weeks before NMS to 56 weeks after NMS, and the primary endpoint was the clinical remission rate after NMS. The secondary endpoints were as follows: (1) incidence and details of adverse events (AEs); (2) treatment continuation rate; (3) changes in disease activity (based on Crohn’s Disease Activity Index [CDAI] for patients with CD and partial Mayo score [PMS] for patients with UC); (4) changes in biomarker levels (C-reactive protein, albumin [Alb], leucine-rich alpha 2 glycoprotein [LRG]); (5) changes in trough concentrations; and (6) findings from the questionnaire survey regarding biosimilars and NMS. Regarding AEs, serious AEs were defined as death, discontinuation of treatment due to AEs, and hospitalization due to AEs. Liver dysfunction was defined as an increase in alanine transaminase and alkaline phosphatase levels to more than twice the upper limit of the reference range. Clinical remission was defined as a CDAI <150 for patients with CD and a PMS ≤ 2 for patients with UC. Non-clinical remission was defined as discontinuation of CT-P13 owing to surgery, AEs, clinical relapse, or treatment intensification during the observation period. In IBD, treatment intensification was defined as cases in which steroids or thiopurine were added, based on CDAI or PMS as indicators. In UC, cases in which rectal budesonide enemas were added, and in CD, cases in which the dosing interval of IFX was shortened or the dose was doubled, were defined as treatment intensification. Regarding disease activity, patients who could be followed up until week 56 were included, and if treatment intensification was performed even once, they were subsequently defined as non-remission.

4) Measurement of IFX Blood Concentration

IFX blood concentration was measured using Buhlmann’s Quantum Blue Infliximab (Quantum Blue Infliximab: Quantitative Lateral Flow Assay, Bühlmann, Schönenbuch, Switzerland). The possible measurements that can be obtained using this kit range from 0.4 μg/mL to 20 μg/mL. IFX concentrations less than 0.4 μg/mL were recorded as 0.2 μg/mL. For concentrations above 20 μg/mL, the sample was diluted 10-fold and re-measured, following the manufacturer’s instructions. The trough concentrations of IFX were measured at weeks 0, 8, 24, and 56. IFX blood concentration measurements were excluded for patients in whom the interval from the previous administration exceeded 8 days, those who received IFX for a shortened duration (within 6 weeks), those who received increased doses, and those who received thiopurine as adjunct therapy after baseline [15,16].

5) Questionnaire Survey

The patient questionnaire survey was self-administered at weeks 0, 24, and 56. The questionnaire included items on the following topics: (1) satisfaction, (2) physical condition, (3) anxiety about the bio-switch, and (4) reasons for anxiety (1, treatment effect; 2, side effects; 3, other), and the changes that were examined. Items other than item 4 (reasons for anxiety) were scored using an 11-point numerical rating scale, with points ranging from 0 to 10. At week 0, we asked the patients about their awareness of biosimilars (possible responses: 1, know; 2, have heard of; 3, do not know), willingness to NMS (1, want to; 2, do not want to; 3, not bothered; 4, do not know), and NMS recommendations (1, agree; 2, disagree; 3, do not know). The scoring of the questionnaire items using the numerical rating scale was analyzed in patients who were able to continue IFX-BS at 24 weeks.

3. Statistical Analysis

All data were analyzed using median and interquartile range (IQR). Per-protocol population analysis was performed to examine changes in disease activity, trends in laboratory data (Alb, C-reactive protein, and LRG), and trough concentrations of IFX. An intention-to-treat analysis was performed for the evaluation of the clinical remission rate after NMS and findings from the questionnaire survey. The Kaplan-Meier curve was used to examine the rate of treatment continuation. For remission maintenance rates, cases in which follow-up could not be continued until week 56 due to reasons such as transfer to another hospital were supplemented using Last Observation Carried Forward. Regarding analysis of the non-inferiority of IFX trough concentrations, we referred to previous studies [16,17] and defined inferiority as a baseline IFX trough concentration of 85% or less. The test was conducted using a two-sided 95% confidence interval (CI) (the original test was conducted with a 90% CI). We used analysis of variance or the Friedman test for the analysis of test and questionnaire survey data. If a significant difference was observed, the Wilcoxon signed-rank test was used for analysis. SPSS (version 29; IBM Corp., Armonk, NY, USA) was used for all statistical analyses. Statistical significance was set at P<0.05.

RESULTS

1. Patient Background Characteristics

The baseline patient background data are shown in Table 1. All patients underwent a non-medical switch from IFX-O to CT-P13. Among those who switched, only 2 patients declined to participate in this study. A total of 167 patients with IBD were included in this study. Of these, 136 (81.4%) had CD and 31 (18.6%) had UC. The median observation period was 57 weeks. The male-to-female ratio was 123:44, the median age of the patients was 43 years (IQR, 32–51 years), and the median disease duration was 16.1 years (IQR, 10.8–25.9 years). The concomitant medications used by the patients included 5-aminosalicylates (125 patients) and azathioprine/6-mercaptopurine (92 patients). Sixteen patients had a history of adalimumab use. The median duration of IFX-O therapy before switching to IFX-BS was 9.8 years. The IFX dosage at the time of NMS was 5 mg/kg in 132 cases and 10 mg/kg in 21 cases. Shortening of therapy duration was applied in 14 cases. The clinical remission rate at baseline was 87.5% (105/120, excluding patients with stomas) for patients with CD and 87.1% (27/31) for patients with UC.

Among the patients with CD, 91 (67%) had a history of abdominal surgery and 16 (11.8%) had a stoma after surgery. Regarding disease behavior based on the Montreal classification [15], 33 cases were the non-stricturing, non-penetrating type (B1), 50 were the stricturing type (B2), and 53 were the penetrating type (B3). Anal lesions were observed in 96 patients, 18 of whom had active lesions.

Among the patients with UC, 27 had pancolitis and 4 had left-sided colitis. Regarding clinical patterns, 8 patients had chronic persistent UC and 23 had remitting-relapsing UC. Twenty-three patients were steroid-dependent, 7 were steroidresistant, and 1 was steroid-naive.

2. Clinical Remission Rate after NMS

In total, 132 patients (CD, 105; UC, 27) were in remission at baseline. The remission rate in week 56 was 84.1% (111/132). Regarding remission status, 85.7% (90/105) of the patients with CD and 77.8% (21/27) of patients with UC remained in complete remission at week 56.

1) Safety

During the observation period, AEs (41 events) occurred in 22.8% (38/167) of the patients. The details of the AEs are presented in Table 2. One of the serious AEs was an infusion reaction, and the other was sepsis. The first case involved an infusion reaction. During the third administration of CT-P13, the patient developed dyspnea, which improved with the administration of anti-allergic medication. After the fourth administration, a skin rash occurred, leading to the discontinuation of the fifth dose. The patient had no prior history of infusion reactions. CT-P13 was discontinued, and the treatment was switched to adalimumab. Furthermore, in this case, no infusion reactions were observed during the administration of IFX-O. The second case was a case of sepsis in which the peripheral route was considered to be the infectious focus. The patient developed disseminated intravascular coagulation (DIC), and treatment was initiated with antibiotics and therapy for DIC, leading to rapid improvement. This adverse event was considered to be related to CT-P13; however, administration was subsequently continued, and it has been possible to safely maintain the treatment.

2) Treatment Continuation Rate

The treatment continuation rate at 56 weeks was 95.6% for all the patients with IBD (Fig. 1). Of 7 patients who discontinued the treatment, 3 underwent surgery due to gastrointestinal stricture, 2 had malignant tumors, 1 had an infusion reaction, and 1 showed loss of response. One patient who became pregnant during the study period was censored. The treatment continuation rate at 56 weeks was 94.7% for patients with CD and 100% for patients with UC.

3) Changes in Disease Activity

Changes in disease activity were analyzed in patients who were able to continue treatment until week 56: 106 of 120 patients with CD (after excluding 16 of 136 patients with a stoma) and 28 of 31 patients with UC, based on the per-protocol analysis. The remission rates at week 0 for the patients with CD and patients with UC were 87.7% (93/106) and 92.9% (26/28), respectively, whereas the rate at week 56 were 80.2% (85/106) and 71.4% (20/28), respectively (Fig. 2). The remission rate at week 56 for patients in remission at baseline was 89.2% for patients with CD (83/93) and 76.9% for patients with UC (20/26).

4) Changes in Biomarker Levels

Biomarker levels were calculated for all patients; however, only 119 of the 167 patients were included in the analysis of changes in biomarker levels based on the results of the perprotocol analysis. The results of the Friedman test showed significant differences in Alb and LRG levels at weeks 0, 8, 24, and 56 (P<0.001 for both) (Supplementary Fig. 1). The Wilcoxon test showed that, compared to the time of NMS, Alb level decreased at 56 weeks (median at week 0, 4.3 g/dL [IQR, 4.1–4.6]; median at 56 weeks, 4.2 g/dL [IQR, 3.9–4.4]; P < 0.001), whereas LRG level decreased at 24 weeks (median at week 0, 12.2 μg/mL [IQR, 9.8–16.7]; median at 24 weeks, 11.5 μg/mL [IQR, 9.5–16.5]; P=0.040) and increased at 56 weeks (median at 56 weeks, 12.8 μg/mL [IQR, 10.1–17.4]; P=0.040). Similar results were obtained when the data for the patients with CD and patients with UC were analyzed separately (data not shown).

5) Changes in Trough Concentrations of IFX-O and CT-P13

Similar to the biomarker analyses, 119 participants were included in the per-protocol analysis. The median trough concentrations at weeks 0, 8, 24, and 56 were 3.9 μg/mL (IQR, 2.4–6.3), 4.3 μg/mL (IQR, 2.8–7.1), 3.8 μg/mL (IQR, 2.3–5.6), and 4.1 μg/mL (IQR, 2.9–6.6) (Fig. 3). The ratios of trough concentrations at weeks 8, 24, and 56 to that at week 0 were 115.6% (95% CI, 107.1%–123.9%), 101.2% (95% CI, 91.7%–110.7%), and 123.5% (95% CI, 109.0%–137.9%), respectively. In addition, non-inferiority of IFX-BS was statistically proven at all timepoints after initiation of NMS.

In the CD group, which included 99 patients, the ratios of trough concentrations at 8, 24, and 56 weeks to that at week 0 were 114.5% (95% CI, 105.2%–123.9%), 101.5% (95% CI, 90.6%–112.4%) and 123.0% (95% CI, 106.7%–139.3%), respectively (Supplementary Fig. 2A). Non-inferiority was statistically proven at all timepoints after initiation of NMS.

In the UC group, which included 20 patients, the ratios of trough concentrations at weeks 8, 24, and 56 to that at week 0 were 120.7% (95% CI, 100.4%–141.0%), 99.9% (95% CI, 81.5%–118.2%), and 125.8% (95% CI, 92.8%–158.7%) (Supplementary Fig. 2B). Only the trough concentration at 24 weeks was significantly lower than that at week 0 (P=0.045).

6) Questionnaire Survey

All 167 patients responded to the questionnaire survey regarding their awareness of biosimilars, willingness to NMS, and opinions on the recommendation of NMS. A total of 162 patients responded to the questionnaire on their satisfaction, physical condition, and anxiety regarding NMS before and after NMS.

Responses to the question on the patients’ awareness of biosimilars at baseline indicated that many patients were unaware of IFX-BS. Specifically, 6.0% selected “know,” 9.0% selected “have heard,” and 85.0% selected “do not know” (Fig. 4A). Regarding the question on willingness to NMS, no patient chose NMS strategy themselves: 0% selected “want to,” 18.0% selected “do not want to,” 57.5% selected “not bothered,” and 24.6% selected “do not know,” (Fig. 4B). Regarding the recommendation of NMS, 54.5% selected “agree,” 3.6% selected “disagree,” and 41.9% selected “do not know” (Fig. 4C).

The median satisfaction scores before and after NMS were 10 (IQR, 8–10) at week 0, 9 (IQR, 7–10) at 24 weeks, and 9 (IQR, 7–10) at 56 weeks. There was a significant decrease in satisfaction at 24 and 56 weeks compared to that at week 0 (P<0.001 for both). In addition, there was no significant difference in satisfaction between 24 and 56 weeks (P=0.822). Anxiety was statistically significantly lower at 24 weeks (median, 1; IQR, 0–4) than at 0 week (median, 5; IQR, 1.75–6) (P<0.001). Anxiety at 56 weeks (median, 0; IQR, 0–5) was significantly lower than at 0 week (median, 5; IQR, 1.75–6) at 0 weeks (P<0.001). However, there was no significant difference in anxiety between week 24 and 56 weeks (P=0.408) (Supplementary Fig. 3). The reasons for anxiety reported by the patients were “treatment effect” (59.9%), “side effects” (58.0%), and “others” (3.7%) (duplicate responses included).

DISCUSSION

The development of anti-TNF-α antibodies significantly changed the treatment paradigm for IBD due to their dramatic treatment effects. The top-down and accelerated step-up treatment strategies have been widely adopted worldwide [17-19], and anti-TNF-α antibodies are now used in the relatively early phase after the diagnosis of IBD. As a result, in many countries, including Japan, approximately half of all patients with IBD are treated with an anti-TNF-α antibody within 5 years of diagnosis [20,21]. However, despite the considerable treatment benefits of anti-TNF-α antibodies, their use has been associated with medical economic issues worldwide. For example, in Manitoba, Canada, the total medical expenses in 2015 were more than twice those in 2005, mainly due to the increased use of anti-TNF-α antibodies [22]. Switching to a biosimilar anti-TNF-α antibody is expected to alleviate the economic burden of using anti-TNF-α antibodies. However, the prevalence of biosimilar use differs across countries and regions [23-25]. In Europe, evidence of the efficacy and safety of bio-switching has been established in studies such as the NOR-SWITCH study, in which biosimilars achieved a very high success rate [5,26-28].

NMS strategy is not widely adopted in Japan. One of the reasons for this is that it is difficult for patients with IBD to appreciate the cost benefits of the strategy owing to the reduction in medical expenses for patients with IBD under the universal medical insurance system and the intractable disease system. In addition, awareness of NMS strategy in Japan is insufficient. Furthermore, there is insufficient evidence to support the use of NMS in Japanese patients. Therefore, both doctors and patients are hesitant about using the strategy. From this perspective, the results of this present study, which showed that NMS from IFX-O to IFX-BS in real-world clinical practice maintained a high remission rate and low frequency of adverse reactions in patients with IBD, are extremely significant. In a review by Bernard et al. [29], the remission rate after NMS was reported to be 70%–94% in patients with CD and 78%–100% in patients with UC. In the present study, the remission continuation rate at 56 weeks for patients who were in remission at baseline was 85.7% for patients with CD and 77.8% for those with UC. These findings showed that IFX-BS achieved relatively high remission maintenance rates, equivalent to those reported in previous studies [30]. Previous studies have indicated that the incidence of serious adverse reactions that require treatment discontinuation within approximately 1 year after NMS is 2.7%–9.8% [30-33]. Similarly, the incidence of serious AEs in the present study was quite low (1.2%). In the questionnaire survey conducted in this study, 58.0% of patients who expressed concerns about NMS strategy cited side effects as the reason for their concern. Therefore, the results of this study may help alleviate patients’ concerns regarding NMS.

There are only a few reports on pharmacokinetics after NMS [34,35]. Therefore, clear evidence that supports the high remission maintenance rate and safety of NMS is important. In the present study, we focused on the blood concentration of IFX before and after NMS and measured the trough concentrations of IFX. The results showed that the trough concentrations at 8, 24, and 56 weeks were non-inferior to the trough concentration at week 0 in all patients with IBD or CD. However, in patients with UC, the trough concentration at week 24 was significantly lower than that at week 0. One factor that may have affected this result is the small number of patients with UC (n=20) enrolled in this study.

To our knowledge, this is the first study that included a questionnaire survey of patients’ awareness of biosimilars and NMS. The survey confirmed that awareness of biosimilars among patients with IBD is low, indicating that patient education is necessary. In addition, although a few patients requested NMS themselves, more than half of the patients agreed with its recommendation; only 4% of the patients disagreed. We inferred that proper explanation and literacy would not prevent patients from promoting NMS. Anxiety regarding NMS significantly improved by 24 weeks and continued up till 56 weeks. We considered that actual use of the biosimilar allowed the patients to experience the comparable effectiveness and safety of IFX-BS and IFX-O. However, satisfaction with NMS was slightly lower at week 24 than at week 0. This may be examined in future studies by employing different approaches, such as analysis of the nocebo effect [36-38].

This study has several limitations. First, this was a single-center study with a relatively small sample size. In addition, as the number of patients with UC was small, it was not possible to conduct a robust analysis according to disease type. Second, it was not possible to perform endoscopy, which is the most useful objective measure of disease activity in IBD. In addition, evaluations using biomarkers such as fecal calprotectin (FC) could not be performed. Notably, endoscopic assessments were not performed in previous studies as well. Therefore, further studies incorporating endoscopic assessments and FC are warranted. However, LRG, a novel biomarker for IBD, was measured in many cases and included as an analytical parameter. Previous studies have reported that LRG correlates not only with clinical disease activity in both UC and CD, but also with endoscopic disease activity [39-42]. Therefore, although this study does not include FC levels or endoscopic assessments, we believe that these limitations are compensated for by the measurement and analysis of LRG. Third, although we were able to confirm the trough concentrations of IFX, we did not measure the levels of anti-drug antibodies; therefore, we could not assess immunogenicity. However, the clinical remission and continuation rates were very high; there were very few cases of loss of response, and safety was assured. Therefore, it can be inferred that there are only a few cases in which antidrug antibodies were produced due to NMS.

In conclusion, this study demonstrated that NMS from IFX-O to IFX-BS can achieve high rates of remission maintenance and continuation in Japanese patients with IBD. In addition, the results of this study proved that the safety of the biosimilar is acceptable. The changes in trough concentration values observed in this study supported these results. The findings from this study will help promote the future adoption of NMS by patients and physicians.

NOTES

Funding Source

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

Conflict of Interest

Hirai F has received grants or contracts from AbbVie GK, EA Pharma Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Mochida Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Janssen Pharmaceutical K.K., and MSD Co., Ltd.; and honoraria for lectures, presentations, manuscript writing, or educational events from AbbVie GK, EA Pharma Co., Ltd., Mochida Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Ltd., and Takeda Pharmaceutical Co., Ltd., within the past 36 months. Hisabe T has received grants or contracts from Mochida Pharmaceutical Co., Ltd., and Nippon Kayaku Co., Ltd.; and honoraria for lectures, presentations, manuscript writing, or educational events from AbbVie GK, Pfizer Inc., EA Pharma Co., Ltd., Mochida Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Ltd., Daiichi Sankyo Co., Ltd., Nippon Kayaku Co., Ltd., Fuji Pharma Co., Ltd., JIMRO Co., Ltd., and ZERIA Pharmaceutical Co., Ltd., within the past 36 months. Ashizuka S has received grants or contracts from Pfizer Japan Inc. within the past 36 months. Takatsu T has received honoraria for lectures from AbbVie GK, EA Pharma Co., Ltd., Mochida Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Ltd., and Gilead Sciences, Inc. within the past 36 months. All other authors declare no conflicts of interest.

Data Availability Statement

The datasets generated and/or analyzed during the current study are not publicly available due to patient privacy and ethical restrictions but are available from the corresponding author on reasonable request.

Author Contributions

Conceptualization: Hirai F, Nomaru R, Takeda T, Hisabe T. Data curation: Hirai F, Imakiire S, Yamauchi E. Formal analysis: Hirai F, Nomaru R, Takeda T, Arima H. Methodology: Hirai F. Visualization: Hirai F, Nomaru R. Writing - original draft: Hirai F, Nomaru R, Takeda T. Writing - review & editing: Takahashi A, Mikumo H, Yasukawa S, Koga A, Kanemitsu T, Ono Y, Takatsu N, Miyaoka M, Hisabe T, Arima H, Imakiire S, Yamauchi E, Ashizuka S. Approval of final manuscript: all authors.

Additional Contributions

We thank all the patients who agreed to participate in this study, including those who switched from an infliximab originator to an infliximab biosimilar. We are also grateful for their cooperation during the blood sampling procedures and the questionnaire surveys.

Supplementary Material

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

Supplementary Fig. 1.

Change in biomarkers over time (n=119). LRG, leucine-rich alpha 2 glycoprotein; CRP, C-reactive protein.

ir-2025-00118-Supplementary-Fig-1.pdf

Supplementary Fig. 2.

Changes in trough concentration of infliximab over time: (A) Crohn’s disease and (B) ulcerative colitis.

ir-2025-00118-Supplementary-Fig-2.pdf

Supplementary Fig. 3.

Changes of anxiety before and after non-medical switch (n=162).

ir-2025-00118-Supplementary-Fig-3.pdf

Fig. 1.

Cumulative treatment continuation rate (Kaplan-Meier method). The rate of treatment continuation at 56 weeks was 95.6% for all patients with inflammatory bowel disease, 94.7% for patients with Crohn’s disease, and 100% for patients with ulcerative colitis.

Fig. 2.

Changes in disease activity over time. (A) For patients with CD, clinical remission rates at weeks 0 and 56 were 87.7% (93/106) and 80.2% (85/106), respectively. Clinical remission was defined as CDAI <150. The patients with CD who had a stoma were excluded from this analysis because their CDAI could not be calculated. (B) For patients with UC, clinical remission rates at weeks 0 and 56 were 92.9% (26/28) and 71.4% (20/28), respectively. Clinical remission was defined as a partial Mayo score ≤2. CD, Crohn’s disease; CDAI, Crohn’s Disease Activity Index; UC, ulcerative colitis.

Fig. 3.

Changes in trough concentration of infliximab over time. A total of 119 patients were included in the per-protocol analysis. The median trough concentrations at weeks 0, 8, 24, and 56 were 3.9 μg/mL (IQR, 2.4–6.3), 4.3 μg/mL (IQR, 2.8–7.1), 3.8 μg/mL (IQR, 2.3–5.6), and 4.1 μg/mL (IQR, 2.9–6.6), respectively. The ratios of trough concentrations at 1, 8, 24 and 56 weeks to that at week 0 were 115.6% (95% CI, 107.1%–123.9%), 101.2% (95% CI, 91.7%–110.7%), and 123.5% (95% CI, 109.0%–137.9%), respectively. All the values were statistically non-inferior to the baseline values. IQR, interquartile range; CI, confidence interval.

Fig. 4.

Questionnaire survey on awareness of biosimilars and NMS at baseline (n=167). (A) Awareness of biosimilars. (B) Preference for NMS. (C) Recommendation of NMS. Responses to the question on awareness of biosimilars and NMS at baseline indicated many patients were unaware of IFX-BS. NMS, non-medical switching; IFS-BS, infliximab biosimilars.

Table 1.

Patient Background Characteristics

Characteristic	Total (n = 167)	CD (n = 136)	UC (n = 31)
Sex (male:female)	123:44	106:30	17:14
Age (yr), median (IQR)	43 (32–51)	43 (32–49)	44 (36–55)
Disease duration (yr)	16.1 (10.8–25.9)	16.2 (11.3–26.1)	13.2 (8.8–23.9)
IFX administration period (yr)	9.8 (5.8–11.9)	10.7 (6.7–12.8)	7.5 (2.9–8.9)
Body weight (kg)	63.6 (55.9–72.9)	64.4 (56.5–72.8)	61.0 (53.7–72.6)
Body mass index (kg/m²)	22.3 (19.9–25.6)	22.3 (20.1–25.1)	22.3 (19.6–26.6)
Smoking	39 (23.4)	34 (25.0)	5 (16.1)
History of surgery	NA	91 (66.9)	NA
Anal lesion	NA	96 (70.6)	NA
CD^a
A1/A2/A3		17/109/10
L1/L2/L3		35/14/87
B1/B2/B3		33/50/53
CDAI		63.0 (30.0-114.5)
HBI		2 (0–4)
UC
Total colitis/left-sided colitis/proctitis			27/4/0
First attack/chronic persistent/relapsing-remitting			0/8/23
pMayo score (IQR)			0 (0–1)
Concomitant treatments
5-ASA	125	99	26
Topical therapy	NA	NA	6
Steroid	1	1	0
AZA/6-MP	92	73	19
Enteral nutrition	NA	10	NA

^a A1/A2/A3: age groups based on the Montreal classification; L1/L2/L3: disease location groups based on the Montreal classification; B1/B2/B3: disease behavior groups based on the Montreal classification.

CD, Crohn’s disease; UC, ulcerative colitis; IQR, interquartile range; IFX, infliximab; CDAI, Crohn’s Disease Activity Index; HBI, Harvey-Bradshaw Index; pMayo score, partial Mayo score (in which endoscopic sub-scores are omitted from the full Mayo score); 5-ASA, 5-aminosalicylic acid; AZA, azathioprine; 6-MP, 6-mercaptopurine; NA, not available.

Table 2.

Details of Adverse Events (n=38)

Adverse events	Cases, No. (%)
Infection^a	24 (14.4)
Dermatoid lesions^b	7 (4.2)
Arthralgia	4 (2.4)
Tumor^c	2 (1.2)
Abnormal laboratory findings^d	2 (1.2)
Others^e	2 (1.2)

41 Adverse events in 38 patients (3 duplicate cases).

^a Infections: COVID-19 infection (n=5); pharyngitis (n=4); urinary tract infection (n=3); sinusitis (n=2); common cold (n=2); herpes zoster (n=2); esophageal candidiasis (n=2); Streptococcus pyogenes infection (n=1); infectious colitis (n=1); cholecystitis (n=1); sepsis (n=1).

^b Dermatoid lesions: eruption (n=1); itching (n=1); eczema (n=1); dermatitis (n=1); skin rash (n=1); psoriasis (n=1); pyoderma gangrenosum (n=1).

^c Tumors: small bowel malignant lymphoma (n=1); endometrial cancer (n=1).

^d Abnormal laboratory findings: hyperamylasemia (n=1); liver dysfunction (n=1).

^e Others: urinary stones (n=1); cervical lymphadenitis (n=1).

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Effectiveness, safety, and pharmacokinetics of the infliximab biosimilar CT-P13 after non-medical switch from the infliximab originator in patients with inflammatory bowel disease

DOI: https://doi.org/10.5217/ir.2025.00118

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Figure

Effectiveness, safety, and pharmacokinetics of the infliximab biosimilar CT-P13 after non-medical switch from the infliximab originator in patients with inflammatory bowel disease

Fig. 1. Cumulative treatment continuation rate (Kaplan-Meier method). The rate of treatment continuation at 56 weeks was 95.6% for all patients with inflammatory bowel disease, 94.7% for patients with Crohn’s disease, and 100% for patients with ulcerative colitis.

Fig. 2. Changes in disease activity over time. (A) For patients with CD, clinical remission rates at weeks 0 and 56 were 87.7% (93/106) and 80.2% (85/106), respectively. Clinical remission was defined as CDAI <150. The patients with CD who had a stoma were excluded from this analysis because their CDAI could not be calculated. (B) For patients with UC, clinical remission rates at weeks 0 and 56 were 92.9% (26/28) and 71.4% (20/28), respectively. Clinical remission was defined as a partial Mayo score ≤2. CD, Crohn’s disease; CDAI, Crohn’s Disease Activity Index; UC, ulcerative colitis.

Fig. 3. Changes in trough concentration of infliximab over time. A total of 119 patients were included in the per-protocol analysis. The median trough concentrations at weeks 0, 8, 24, and 56 were 3.9 μg/mL (IQR, 2.4–6.3), 4.3 μg/mL (IQR, 2.8–7.1), 3.8 μg/mL (IQR, 2.3–5.6), and 4.1 μg/mL (IQR, 2.9–6.6), respectively. The ratios of trough concentrations at 1, 8, 24 and 56 weeks to that at week 0 were 115.6% (95% CI, 107.1%–123.9%), 101.2% (95% CI, 91.7%–110.7%), and 123.5% (95% CI, 109.0%–137.9%), respectively. All the values were statistically non-inferior to the baseline values. IQR, interquartile range; CI, confidence interval.

Fig. 4. Questionnaire survey on awareness of biosimilars and NMS at baseline (n=167). (A) Awareness of biosimilars. (B) Preference for NMS. (C) Recommendation of NMS. Responses to the question on awareness of biosimilars and NMS at baseline indicated many patients were unaware of IFX-BS. NMS, non-medical switching; IFS-BS, infliximab biosimilars.

Fig. 1.

Fig. 2.

Fig. 3.

Fig. 4.

Effectiveness, safety, and pharmacokinetics of the infliximab biosimilar CT-P13 after non-medical switch from the infliximab originator in patients with inflammatory bowel disease

Characteristic	Total (n = 167)	CD (n = 136)	UC (n = 31)
Sex (male:female)	123:44	106:30	17:14
Age (yr), median (IQR)	43 (32–51)	43 (32–49)	44 (36–55)
Disease duration (yr)	16.1 (10.8–25.9)	16.2 (11.3–26.1)	13.2 (8.8–23.9)
IFX administration period (yr)	9.8 (5.8–11.9)	10.7 (6.7–12.8)	7.5 (2.9–8.9)
Body weight (kg)	63.6 (55.9–72.9)	64.4 (56.5–72.8)	61.0 (53.7–72.6)
Body mass index (kg/m²)	22.3 (19.9–25.6)	22.3 (20.1–25.1)	22.3 (19.6–26.6)
Smoking	39 (23.4)	34 (25.0)	5 (16.1)
History of surgery	NA	91 (66.9)	NA
Anal lesion	NA	96 (70.6)	NA
CD^a
A1/A2/A3		17/109/10
L1/L2/L3		35/14/87
B1/B2/B3		33/50/53
CDAI		63.0 (30.0-114.5)
HBI		2 (0–4)
UC
Total colitis/left-sided colitis/proctitis			27/4/0
First attack/chronic persistent/relapsing-remitting			0/8/23
pMayo score (IQR)			0 (0–1)
Concomitant treatments
5-ASA	125	99	26
Topical therapy	NA	NA	6
Steroid	1	1	0
AZA/6-MP	92	73	19
Enteral nutrition	NA	10	NA

Adverse events	Cases, No. (%)
Infection^a	24 (14.4)
Dermatoid lesions^b	7 (4.2)
Arthralgia	4 (2.4)
Tumor^c	2 (1.2)
Abnormal laboratory findings^d	2 (1.2)
Others^e	2 (1.2)

Table 1. Patient Background Characteristics

A1/A2/A3: age groups based on the Montreal classification; L1/L2/L3: disease location groups based on the Montreal classification; B1/B2/B3: disease behavior groups based on the Montreal classification.

Table 2. Details of Adverse Events (n=38)

41 Adverse events in 38 patients (3 duplicate cases).

Infections: COVID-19 infection (n=5); pharyngitis (n=4); urinary tract infection (n=3); sinusitis (n=2); common cold (n=2); herpes zoster (n=2); esophageal candidiasis (n=2); Streptococcus pyogenes infection (n=1); infectious colitis (n=1); cholecystitis (n=1); sepsis (n=1).

Dermatoid lesions: eruption (n=1); itching (n=1); eczema (n=1); dermatitis (n=1); skin rash (n=1); psoriasis (n=1); pyoderma gangrenosum (n=1).

Tumors: small bowel malignant lymphoma (n=1); endometrial cancer (n=1).

Abnormal laboratory findings: hyperamylasemia (n=1); liver dysfunction (n=1).

Others: urinary stones (n=1); cervical lymphadenitis (n=1).