A real-world comparison of subcutaneous to intravenous administration of infliximab in patients with inflammatory bowel disease

Kwang Woo Kim; Hyoun Woo Kang; Seong-Joon Koh; Hyuk Yoon; Sihyun Kim; Yukyung Jun; Hyun Jung Lee; Jong Pil Im; Young Soo Park; Ji Won Kim; Joo Sung Kim; Seoul National University Inflammatory Bowel Disease Research Network (SIRN)

doi:10.5217/ir.2025.00001

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Original Article A real-world comparison of subcutaneous to intravenous administration of infliximab in patients with inflammatory bowel disease: Kwang Woo Kim^1,*, Hyoun Woo Kang^1,*, Seong-Joon Koh^2,, Hyuk Yoon^2,3,, Sihyun Kim³, Yukyung Jun³, Hyun Jung Lee², Jong Pil Im², Young Soo Park³, Ji Won Kim¹, Joo Sung Kim², Seoul National University Inflammatory Bowel Disease Research Network (SIRN); DOI: https://doi.org/10.5217/ir.2025.00001
Published online: June 23, 2025

¹Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea

²Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea

³Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea

Correspondence to Seong-Joon Koh, Department of Internal Medicine, Liver Research Institute and Laboratory of Intestinal Mucosa and Skin Immunology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 03080, Korea. E-mail: jel1206@snu.ac.kr

Correspondence to Hyuk Yoon, Department of Internal Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro 173beon-gil, Bundang-gu, Seongnam 13620, Korea. E-mail: yoonhmd@gmail.com

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

• Received: January 5, 2025 • Revised: March 25, 2025 • Accepted: April 2, 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
We compared intravenous and subcutaneous infliximab (IFX) as treatment for inflammatory bowel disease (IBD).
Methods
This retrospective, multicenter, observational study enrolled patients treated with either intravenous or subcutaneous IFX. Sequential parameters were compared at baseline, 6 months, and 12 months following the initiation of treatment with either type of IFX. The primary outcome was the comparison of the IFX trough levels after 12 months of treatment.
Results
In total, 183 participants were included in this study. After 6 months, the subcutaneous group exhibited significant differences compared to the intravenous group; in terms of clinical disease activity (0% vs. 15%, P=0.007) and IFX trough level (21.72±8.71 μg/mL vs. 7.70±16.65 μg/mL, P=0.002). After 12 months, subcutaneous, as compared to intravenous, achieved improved clinical disease activity (0% vs. 15%, P=0.044) and IFX trough level (20.41±12.91 μg/mL vs. 7.06±6.81 μg/mL, P< 0.001). Analyzing the sequential changes compared with baseline data within each group, we observed significant alterations in subcutaneous; 6 months fecal calprotectin (676.3±976.6 μg/g vs. 253.9±483.9 μg/g, P=0.014), 6 months IFX trough level (7.00±5.67 μg/mL vs. 18.44±6.34 μg/mL, P=0.026), and 12 months IFX trough level (7.00±5.67 μg/mL vs. 21.33±4.50 μg/mL, P=0.034).
Conclusions
This study indicates the potential suitability of subcutaneous IFX as an alternative treatment option for IBD.
Keywords: Infliximab; Infusions, intravenous; Injections, subcutaneous; Inflammatory bowel diseases

INTRODUCTION

Anti-tumor necrosis factor α (TNF-α) agents were initially developed and are now widely used to treat inflammatory bowel disease (IBD) [1]. Infliximab (IFX) was the first anti-TNF-α agent approved for the treatment of IBD in 1998 [2]. The IFX biosimilar CT-P13 has been developed and established as non-inferior in efficacy and safety compared to the original IFX [3]. A subcutaneous (SC) type has also been developed, and Schreiber et al. [4] reported their randomized controlled trial showed that the SC IFX trough level is non-inferior to the intravenous (IV) type IFX. Since the IFX trough level is related to drug efficacy [5], this study implied that SC administration could be a viable substitute for IV injection. Furthermore, this formulation provides opportunities for self-administration and reduces the related medical costs. During the COVID-19 pandemic, self-administration became more important from the perspective of drug adherence as the patients could not visit the medical center as per the drug administration schedule due to concerns about nosocomial COVID-19 infection and self-isolation during infection.

Several studies have shown that SC IFX could be a viable alternative to the IV type [6-8], but few real-world studies have compared the 2 types of IFX. This study compared the pharmacokinetics, efficacy, and biomarker responses of SC versus IV IFX in the treatment of IBD in real-world clinical practice.

METHODS

1. Data Source and Study Population

A retrospective, multicenter, observational cohort study was conducted on participants aged ≥18 with IBD who had been treated for >3 months at 1 of 3 academic medical centers: Seoul National University Hospital (SNUH), Seoul National University Bundang Hospital (SNUBH), and Seoul Metropolitan Government Seoul National University (SMG-SNU) Boramae Medical Center in South Korea. The exclusion criteria were as follows: (1) patients with an incomplete diagnosis of IBD by gastroenterologists; (2) subjects administered IFX due to diseases other than IBD; (3) pregnant or lactating subjects; and (4) subjects who were considered to be inappropriate for enrollment in this study. We reviewed the medical records of 4,289 patients with IBD. Among them, 63 and 122 were given SC and IV forms of IFX, entitled SC IFX and IV IFX, respectively.

This study protocol was approved by the institutional review boards of the medical centers (IRB numbers: H-2202-119-1303 at SNUH, 10-2023-58 at SMG-SNU Boramae Medical Center, and B-2208-773-402 at SNUBH) and was conducted in compliance with the tenets of the Declaration of Helsinki. The board waived the requirement for informed consent.

2. Data Collection

Subjects with SC IFX have previously been treated with IV IFX and subsequently administered subcutaneously every 2 weeks. The baseline for SC IFX was established at the time of initiating SC treatment. Subjects maintaining on IV administration were enrolled as IV IFX and their data were collected over the most recent 1-year period.

The medical history, laboratory examinations, and endoscopic findings of patients with IBD were reviewed in detail. Medical history included age, sex, body mass index (BMI), IBD subtype, duration of IBD, disease activity, 5-aminosalicylic acid (5-ASA) drug administration, immunomodulators, biologics, small molecules, and steroids. Laboratory examinations included C-reactive protein (CRP), erythrocyte sedimentation rate, fecal calprotectin (FCP), IFX trough level, and the presence of anti-drug antibody (ADA). Endoscopic findings were acquired from colonoscopy results.

The BMI was calculated as weight (kg) divided by height (m) squared (kg/m²). IBD disease activity was assessed using pre-recorded clinical scores, such as the Mayo score and Crohn’s Disease Activity Index (CDAI), or with medication records, endoscopic findings, clinical symptoms, and laboratory data, owing to a lack of full data for the scores. For that reason, clinical disease severities by Mayo score or CDAI were briefly categorized into 2 groups: Mayo score ≤ 5 or CDAI ≤ 220 were defined as inactive to mild and more severe disease activities as moderate to severe [9,10]. Immunomodulators included azathioprine, 6-mercaptopurine, methotrexate. Colonoscopies were performed by a board-certified gastroenterologist using CF and CF-H colonoscopies (Olympus, Tokyo, Japan). Endoscopic scores were evaluated using the Mayo Endoscopic Score and the Simple Endoscopic Score for Crohn’s Disease. Mayo Endoscopic Score ≤ 1 or Simple Endoscopic Score for Crohn’s Disease ≤6 was categorized as remission to mild endoscopic disease severity and above the score as moderate to severe endoscopic activity [9,11].

3. Study Endpoints

The primary outcome was the comparison of IFX trough levels at the 12-month follow-up. Rate of IFX trough level >7 μg/mL in each group after 12-month treatment was evaluated with multivariable binominal logistic regression analysis [12]. In addition, clinical disease activity, endoscopic disease activity, FCP, CRP, IFX trough level, and ADA were compared after 6-month and 12-month follow-up, with both SC IFX and IV IFX.

4. Statistical Analysis

Continuous variables were presented as means with standard deviations or percentages, as appropriate. If the data were not normally distributed, they were presented as medians with interquartile ranges. Continuous variables were analyzed using Student t-test or Mann-Whitney U-test, as appropriate. Categorical variables were reported as numbers or percentages, as appropriate. Categorical variables were compared using chi-square test. Paired variables were analyzed using the paired t-test or McNemar’s test, as appropriate. The predictor variables used in the binomial logistic regression were sex, BMI, disease duration, and use of 5-ASA and SC IFX. Each odds ratio is presented with its 95% confidence interval. All statistical analyses were performed using Statistical Package for Social Sciences version 29.0 (SPSS Inc., Chicago, IL, USA). Statistical significance was defined as a two-sided P-value of <0.05.

RESULTS

1. Baseline Demographics and Clinical Characteristics

Among the 4,289 patients with IBD, 61 and 122 were enrolled SC IFX and IV IFX, respectively. The baseline clinical characteristics of the 2 groups are described in Table 1. The mean age of the subjects was 38.80 years old and 135 (74%) were male. Among the enrolled patients, 57 (31%) and 126 (69%) had ulcerative colitis (UC) and Crohn’s disease (CD), respectively.

Male sex was more common in SC IFX than in the IV IFX (86.9% vs. 67.0%, P=0.004). SC IFX resulted in a significantly higher BMI than IV IFX (24.05 kg/m² vs. 22.31 kg/m² P=0.017). The SC IFX and IV IFX groups had significantly different IBD durations (73.0 months vs. 137.5 months, P<0.001). There were no significant differences in portion use of medications, such as immunomodulators, steroids, biologics, or small molecules, except 5-ASA, between the SC IFX and IV IFX groups (27.9% vs. 43.4%, P=0.041).

2. Comparison of Consequential Outcomes Related to IBD

All serial outcome data comparing IV IFX and SC IFX are summarized in Table 2. There were no significant differences in the outcomes of endoscopic disease activity and FCP, albumin, or ADA levels. In terms of clinical disease activity, after 6 months, there was significant difference between the IV IFX and SC IFX groups (15% vs. 0%, P=0.007). This trend was consistent between the 2 groups at 12 months of treatment (15% vs. 0%, P=0.044). The IFX trough level was sustained as significantly higher in SC IFX than that of IV IFX after 6 and 12 months of treatment (21.72±8.71 μg/mL vs. 7.70±16.65 μg/mL, P=0.002; 20.41±12.91 μg/mL vs. 7.06±6.81 μg/mL, P<0.001, respectively). There were no significant differences in CRP, FCP, albumin, or ADA levels.

In participants with UC, the IFX trough level after 6 months showed a significant difference between IV IFX and SC IFX (3.28±3.54 μg/mL vs. 19.63±11.24 μg/mL, P=0.013). Otherwise, there were no significant differences in the serial outcomes (Table 2). There were different trends in CD subjects. After 6 months, SC IFX revealed significantly improved clinical disease activity (0% vs. 14%, P=0.038), FCP (147.8±114.4 μg/g vs. 445.5±613.9 μg/g, P=0.010), and higher IFX trough level (22.85±7.36 μg/mL vs. 8.46±17.92 μg/mL, P=0.007) than those of IV IFX. IFX trough level after 12 months showed a significant difference between the 2 groups (23.64±13.15 μg/mL vs. 8.24±7.16 μg/mL, P=0.003). Clinical disease activity revealed a numerical difference after 12 months between the 2 groups (0% vs. 17%, P=0.120) (Table 2).

3. Temporal Changes in Each Group over the Study Period

Sequential variations in each group were analyzed for clinical disease activity and FCP, CRP, and IFX trough levels. Due to the statistically insufficient number of patients, variables of clinical and endoscopic activity could not be analyzed. There were no significant changes in the IV IFX levels. In SC IFX, 6 months of treatment revealed significant changes in FCP level and IFX trough level compared with those at baseline (253.9±483.9 μg/g vs. 676.3±976.6 μg/g, P=0.014; 18.44±6.34 μg/mL vs. 7.00±5.67 μg/mL, P=0.026, respectively). After 12 months of treatment, SC IFX sustained a significantly higher IFX trough level than baseline (21.33±4.50 μg/mL vs. 7.00±5.67 μg/mL, P=0.034) (Supplementary Table 1).

4. Multivariable Analysis for IFX Trough Level

The IFX trough level after 12 months of treatment was significant in the SC IFX group after multivariable-adjusted analysis for sex, BMI, IBD duration, and 5-ASA use, and the variables were significantly different between the 2 groups (odds ratio, 8.335; 95% confidence interval, 1.306–53.200; P=0.025). Subgroup analysis of UC and CD showed no significant association between the IFX group and IFX trough level. All data are presented in Table 3.

DISCUSSION

This study demonstrated the real-world efficacy of SC IFX compared to IV IFX in the clinical course of IBD. IV IFX and SC IFX were compared according to the sequential treatment period and analyzed for temporal differences in each group. Most importantly, this study highlighted that SC IFX was more effective in sustaining high IFX trough levels than IV IFX, even after multivariate analysis, in a real-world setting. Subjects with CD showed a similar trend; however, those with UC showed significant differences only in the IFX trough level after 6 months of treatment. Sequential changes in SC IFX were significant in terms of IFX trough levels but not in IV IFX. In addition to the IFX trough level, clinical disease activity substantially improved after 6 and 12 months of treatment. Patients with CD also showed meaningful improvement in clinical disease activity after 6 months of treatment. These findings corroborate that the IFX trough level has been considered an important factor for treatment persistence of IFX by achieving improvement of clinical disease activity, as reported in previous studies and guidelines [4,13-18]. Improvement of CRP and FCP was significant in all subjects with IBD after 12 months of treatment and those with CD after 6 months of treatment, respectively. There was no considerable improvement in the endoscopic response with SC IFX compared to IV IFX. These findings imply that SC IFX could induce high trough levels, resulting in the improvement of clinical activity and biochemical markers in patients with IBD, especially those with CD.

As biologics have become important IBD treatments, the maintenance of these drugs has become one of the most important topics. Anti-TNF-α agents, especially IFX, have been maintained as an important treatment option, including their unique position [19-21]. Maintenance issues have also remained, especially in terms of secondary loss-of-response [22]. The IFX trough level has been revealed as an important factor for maintenance, and dose intensification, such as shortening of administration intervals or dose-escalation, has been suggested to achieve this goal [23]. Recently, SC administration has emerged as an alternative method for dose intensification. Schreiber et al. [4] presented the results of randomized clinical trial comparing SC and IV IFX, including the aspects of trough level. After the study, there have been a few studies evaluating the clinical efficacy of SC IFX in the subjects with IBD who were in clinical remission [6-8]. Smith et al. [6] reported that 92.3% of patients switching IV to SC IFX persisted treatment in their single arm study. Buisson et al. [7] presented adequate efficacy of SC IFX changing from IV IFX except the patients receiving 10 mg/kg every 4 weeks. In the study, they showed the trends in each group categorized by dose and interval of IFX. There was no trend of increasing IFX trough levels in the group treated with 10 mg/kg every 4 weeks, which showed a significantly higher relapse rate than the other groups. Those who experienced relapse within 6 months received a dose escalation of IFX to 240 mg, and 93.3% of them reached clinical remission. Also, Hong et al. [8] published an article comparing SC and IV IFX in patients with clinical remission. There were no significant differences between patients with IV- and SC IFX in clinical remission, biochemical remission, and endoscopic response, but there revealed notably difference in terms of durable remission defined as concomitant clinical and biochemical remission with IFX trough level 3 μg/mL or above. Recently, Bae et al. [24] reported that SC IFX may be an alternative for drug escalation to the patients with prior IV IFX failure. This study showed higher portion of clinical or biochemical response achievement than our report. The 2 studies differed notably in baseline characteristics: our cohort had substantially longer prior IV IFX treatment (34.0–55.0 months vs. 44.1–63.8 weeks) and transitioned mostly during stable remission, whereas the referenced study involved transitions primarily after disease aggravation [24].

As shown in this study, SC IFX provided subjects with many clinical benefits. It demonstrated improved pharmacokinetic activity, such as a stable high trough level, without modifying the administration interval or dose-escalation [6,25]. Furthermore, there was no trend of increasing ADA in SC IFX compared with IV IFX in this study. Because there was a concern that a high trough level would elicit high ADA, resulting in decreased efficacy and increased adverse events of the drug [26], this result might alleviate apprehension. In addition to clinical efficacy, there were also practical conveniences such as reducing the number of visit to healthcare center, shortening the time of administration, and independence from drug administration schedule [27]. During the period of coronavirus disease 2019 pandemic, the benefits of SC IFX have become more evident. This makes the clinical strengths of SC IFX more favorable.

This study has several limitations. First, because this was a retrospective study, there might have been a selection bias in the study population. In addition, there was a relatively small sample size due to sequential pairing, and not all subjects were enrolled for the full 12 months. Furthermore, the baseline characteristics between the 2 groups were different, especially disease duration and previous IFX treatment period. It was not sufficient for statistical compensation, such as propensity score matching, because there was not enough numbers of subjects in the subgroups according to the types of IBD after the analysis, not revealed in this manuscript. In the case of SC formulation, its later introduction compared to IV IFX inevitably influenced real-world clinical practice, as patients who had maintained long-term stable responses to IV IFX tended to be reluctant to switch to the SC IFX. However, although male sex, higher BMI, and lower 5-ASA, which indicate poor prognosis in the clinical course of IBD, were associated more with SC IFX than with IV IFX, clinical disease activity was significantly better in the former than in the latter. This indicates that SC administration of IFX may overcome unfavorable factors in the clinical course of IBD. Furthermore, the total enrolled subjects were larger than previous randomized controlled trial comparing SC and IV IFX [4]. Second, the small sample size and some missing data at the follow-up period, resulted in statistically obscure meanings. Nevertheless, the SC IFX group showed considerably better outcomes in terms of trough levels and clinical activity. Further research with more subjects could elucidate other favorable clinical outcomes such as FCP and endoscopic activity. Third, most patients were biologic-naive. Recently, the rate of IFX use in first-line treatment has decreased owing to the development of novel agents such as ustekinumab and vedolizumab. Therefore, the efficacy of SC IFX was evaluated in biologic-treated subjects.

In conclusion, SC IFX was significantly associated with higher trough levels and better clinical activity than IV IFX, which was consistent during the 12-month follow-up period in patients with IBD, especially CD. Partial biochemical results showed greater improvement with SC IFX than with IV IFX. These results suggest that SC IFX is a good alternative to IV IFX, even in real-world settings. Further large-scale studies involving various clinical statuses are required to comprehensively elucidate the utility and efficacy of SC IFX.

NOTES

Funding Source

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2022R1F1A1076019) and a general clinical research grant-in-aid from the Seoul Metropolitan Government Seoul National University (SMG-SNU) Boramae Medical Center (04-2023-0012). This work was also supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. RS-2023-00227939). This work was also supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (No. 2021R1F1A1062000). The study was also funded by CELLTRION PHARM, Inc. (Cheongju, Republic of Korea) (Grant No. CR 2022-2). This research was also supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) & funded by the Korean government (MSIT) (NRF-2022M3A9F3017371). This study was also supported by grant no. 03-2019-0120 from the SNUH Research Fund.

Conflict of Interest

The study was funded by Celltrion Pharm, Inc. (Cheongju, Republic of Korea) (Grant No. CR 2022-2). Kim KW, Im JP, and Kim JW are editorial board members of the journal but were not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflicts of interest relevant to this article were reported.

Data Availability Statement

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Author Contributions

Conceptualization: Kim KW, Kang HW, Koh SJ, Yoon H, Jun Y, Lee HJ, Im JP, Park YS, Kim JW, Kim JS. Data curation: Kim KW, Kang HW, Kim S, Im JP, Park YS, Kim JW, Kim JS. Formal analysis: Kim KW, Kang HW, Koh SJ, Yoon H. Supervision: Kim KW, Kang HW, Koh SJ, Yoon H. Writing – original draft: Kim KW, Kang HW, Koh SJ, Yoon H. Writing – review & editing: Kim S, Jun Y, Lee HJ, Im JP, Park YS, Kim JW, Kim JS. Approval of final manuscript: all authors.

Supplementary Material

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

Supplementary Table 1.

Sequential Changes in Each Group over the Study Period

ir-2025-00001-Supplementary-Table-1.pdf

Table 1.

Baseline Clinical Characteristics

Characteristics	IV (n = 122)	SC (n = 61)	P-value
Age (yr), mean ± SD	40.16 ± 14.68	36.08 ± 14.49	0.077
Male sex, No. (%)	82 (67.2)	53 (86.9)	0.004
BMI (kg/m²), mean ± SD	22.31 ± 4.47	24.05 ± 4.66	0.017
Disease duration (mo), median (IQR)	137.5 (87.3–210.0)	73.0 (30.5–138.5)	< 0.001
Type of IBD, No. (%)			0.310
UC	35 (28.7)	22 (36.1)
CD	87 (71.3)	39 (63.9)
Use of immunomodulator, No. (%)	44 (36.1)	23 (37.7)	0.828
Use of 5-ASA, No. (%)	53 (43.4)	17 (27.9)	0.041
Use of steroid, No. (%)	12 (9.8)	9 (14.8)	0.325
Duration of infliximab administration before baseline (mo), mean ± SD	55.34 ± 39.54	33.64 ± 40.68	< 0.001
Previous use of biologics or small molecules, No. (%)	9 (7.4)	5 (8.2)	0.844
Reason for switching administration method IV to SC, No. (%)			NA
Patient preference	NA	46 (75.4)
Subtherapeutic trough level of IFX	NA	15 (24.6)
Previous IV dosage and interval, No. (%)			NA
5 mg/kg, 8 wk	NA	52 (84.1)
5 mg/kg, 4 wk	NA	4 (6.3)
10 mg/kg, 8 wk	NA	5 (7.9)

IV, intravenous; SC, subcutaneous; SD, standard deviation; BMI, body mass index; IQR, interquartile range; IBD, inflammatory bowel disease; UC, ulcerative colitis; CD, Crohn’s disease; 5-ASA, 5-aminosalicylate.; IFX, infliximab; NA, not applicable.

Table 2.

Comparison of Serial Outcomes in Inflammatory Bowel Disease

Outcomes	Baseline			6 mo			12 mo
Outcomes	IV	SC	P-value	IV	SC	P-value	IV	SC	P-value
Ulcerative colitis (n)	35	22		35	17		35	11
Clinical disease activity^a	1 (2.9)	1 (4.5)	1.000	2 (5.7)	0	1.000	3 (8.6)	0	1.000
Endoscopic disease activity^b	3 (8.6)	5 (22.7)	0.179	4 (11.4)	3 (17.6)	0.596	6 (17.1)	2 (18.2)	0.547
FCP (μg/g)	345.3 ± 549.3	943.2 ± 1223.7	0.149	378.8 ± 751.4	329.9 ± 631.4	0.877	468.2 ± 606.8	785.6 ± 951.6	0.412
CRP (mg/dL)	0.42 ± 0.91	0.69 ± 2.19	0.512	0.22 ± 0.32	0.20 ± 0.41	0.906	0.24 ± 0.38	0.22 ± 0.40	0.895
Albumin (mg/dL)	4.27 ± 0.96	4.43 ± 0.51	0.577	4.54 ± 0.40	4.51 ± 0.40	0.862	4.46 ± 0.40	4.61 ± 0.38	0.332
IFX trough level (μg/mL)	0.39 ± 0.52	0.66 ± 0.74	0.634	3.28 ± 3.54	19.63 ± 11.24	0.013	5.18 ± 6.09	15.34 ± 11.61	0.065
ADA	0	1 (4.5)	0.333	1 (2.9)	0	1.000	1 (2.9)	0	1.000
Crohn’s disease (n)	87	39		86	21		81	17
Clinical disease activity^a	15 (17.2)	2 (5.1)	0.090	12 (14.0)	0	0.038	14 (17.3)	0	0.120
Endoscopic disease activity^b	3 (3.4)	0	0.274	7 (8.1)	0	0.114	2 (2.5)	0	1.000
FCP (μg/g)	899.5 ± 1,941.0	362.1 ± 429.5	0.151	445.5 ± 613.9	147.8 ± 114.4	0.01	575.9 ± 956.0	508.9 ± 719.0	0.831
CRP (mg/dL)	0.59 ± 1.46	0.44 ± 0.88	0.547	0.49 ± 0.79	0.37 ± 0.65	0.255	0.51 ± 0.98	0.21 ± 0.35	0.202
Albumin (mg/dL)	4.31 ± 0.54	4.42 ± 0.39	0.344	4.30 ± 0.47	4.45 ± 0.27	0.123	4.35 ± 0.50	4.65 ± 0.20	0.065
IFX trough level (μg/mL)	8.25 ± 9.92	6.69 ± 6.23	0.644	8.46 ± 17.92	22.85 ± 7.36	0.007	8.24 ± 7.16	23.64 ± 13.15	0.003
ADA	0	0	NA	3 (3.5)	NA	NA	0	0	NA

Values are presented as number (%) or mean±standard deviation.

^a Moderate to severe disease activity as Mayo score and Crohn’s Disease Activity Index in ulcerative colitis and Crohn’s disease, respectively.

^b Moderate to severe endoscopic disease activity as Mayo Endoscopic Score and Simple Endoscopic Score for Crohn’s Disease in ulcerative colitis and Crohn’s disease, respectively.

IV, intravenous; SC, subcutaneous; FCP, fecal calprotectin; CRP, C-reactive protein; IFX, infliximab; ADA, anti-drug antibody; NA, not applicable.

Table 3.

Multivariable Analysis of Factors Affecting IFX Trough Level at 12-Month Treatment

Factors	Ulcerative colitis		Crohn’s disease
Factors	OR (95% CI)	P-value	OR (95% CI)	P-value
Male sex	0.983 (0.035–27.571)	0.992	4.770 (0.262–86.728)	0.291
BMI	0.804 (0.567–1.139)	0.220	0.913 (0.717–1.162)	0.458
Duration of IBD	1.003 (0.986–1.021)	0.698	1.008 (0.991–1.025)	0.365
Use of 5-ASA	3.245 (0.114–92.262)	0.491	0.066 (0.001–4.061)	0.196
Use of SC IFX	5.453 (0.255–116.757)	0.278	25.508 (0.834–780.220)	0.063

IFX, infliximab; OR, odds ratio; CI, confidence interval; BMI, body mass index; IBD, inflammatory bowel disease; ASA, aminosalicylic acid; SC, subcutaneous.

REFERENCES

1. D’Haens GR, van Deventer S. 25 Years of anti-TNF treatment for inflammatory bowel disease: lessons from the past and a look to the future. Gut 2021;70:1396–1405.Article PubMed
2. Melsheimer R, Geldhof A, Apaolaza I, Schaible T. Remicade® (infliximab): 20 years of contributions to science and medicine. Biologics 2019;13:139–178.PubMed PMC
3. Ye BD, Pesegova M, Alexeeva O, et al. Efficacy and safety of biosimilar CT-P13 compared with originator infliximab in patients with active Crohn’s disease: an international, randomised, double-blind, phase 3 non-inferiority study. Lancet 2019;393:1699–1707.Article PubMed
4. Schreiber S, Ben-Horin S, Leszczyszyn J, et al. Randomized controlled trial: subcutaneous vs intravenous infliximab CT-P13 maintenance in inflammatory bowel disease. Gastroenterology 2021;160:2340–2353.Article PubMed
5. Wilson A, Choi B, Sey M, et al. High infliximab trough concentrations are associated with sustained histologic remission in inflammatory bowel disease: a prospective cohort study. BMC Gastroenterol 2021;21:77.Article PubMed PMC PDF
6. Smith PJ, Critchley L, Storey D, et al. Efficacy and safety of elective switching from intravenous to subcutaneous infliximab [CT-P13]: a multicentre cohort study. J Crohns Colitis 2022;16:1436–1446.Article PubMed PMC PDF
7. Buisson A, Nachury M, Reymond M, et al. Effectiveness of switching from intravenous to subcutaneous infliximab in patients with inflammatory bowel diseases: the REMSWITCH study. Clin Gastroenterol Hepatol 2023;21:2338–2346.e3.Article PubMed
8. Hong SN, Song JH, Kim SJ, et al. One-year clinical outcomes of subcutaneous infliximab maintenance therapy compared with intravenous infliximab maintenance therapy in patients with inflammatory bowel disease: a prospective cohort study. Inflamm Bowel Dis 2024;30:517–528.Article PubMed PDF
9. Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis: a randomized study. N Engl J Med 1987;317:1625–1629.Article PubMed
10. Best WR, Becktel JM, Singleton JW, Kern F. Development of a Crohn’s disease activity index: National Cooperative Crohn’s Disease Study. Gastroenterology 1976;70:439–444.Article PubMed
11. af Björkesten CG, Nieminen U, Turunen U, et al. Surrogate markers and clinical indices, alone or combined, as indicators for endoscopic remission in anti-TNF-treated luminal Crohn’s disease. Scand J Gastroenterol 2012;47:528–537.Article PubMed
12. Drobne D, Kurent T, Golob S, et al. Success and safety of high infliximab trough levels in inflammatory bowel disease. Scand J Gastroenterol 2018;53:940–946.Article PubMed
13. Miranda EF, Nones RB, Kotze PG. Correlation of serum levels of anti-tumor necrosis factor agents with perianal fistula healing in Crohn’s disease: a narrative review. Intest Res 2021;19:255–264.Article PubMed PDF
14. Koh SJ, Hong SN, Park SK, et al. Korean clinical practice guidelines on biologics for moderate to severe Crohn’s disease. Intest Res 2023;21:43–60.Article PubMed PDF
15. Na SY, Choi CH, Song EM, et al. Korean clinical practice guidelines on biologics and small molecules for moderate-to-severe ulcerative colitis. Intest Res 2023;21:61–87.Article PubMed PDF
16. Papamichael K, Cheifetz AS, Melmed GY, et al. Appropriate therapeutic drug monitoring of biologic agents for patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol 2019;17:1655–1668.e3.Article PubMed PMC
17. Papamichael K, Rakowsky S, Rivera C, Cheifetz AS, Osterman MT. Infliximab trough concentrations during maintenance therapy are associated with endoscopic and histologic healing in ulcerative colitis. Aliment Pharmacol Ther 2018;47:478–484.Article PubMed PDF
18. Roblin X, Nancey S, Papamichael K, et al. Higher serum infliximab concentrations following subcutaneous dosing are associated with deep remission in patients with inflammatory bowel disease. J Crohns Colitis 2024;18:679–685.Article PubMed PDF
19. Aardoom MA, Veereman G, de Ridder L. A review on the use of anti-TNF in children and adolescents with inflammatory bowel disease. Int J Mol Sci 2019;20:2529.Article PubMed PMC
20. Sands BE, Anderson FH, Bernstein CN, et al. Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med 2004;350:876–885.Article PubMed
21. Sun XL, Chen SY, Tao SS, et al. Optimized timing of using infliximab in perianal fistulizing Crohn’s disease. World J Gastroenterol 2020;26:1554–1563.Article PubMed PMC
22. Van Assche G, Vermeire S, Rutgeerts P. Management of loss of response to anti-TNF drugs: change the dose or change the drug? J Crohns Colitis 2008;2:348–351.Article PubMed
23. Savelkoul EH, Thomas PW, Derikx LA, et al. Systematic review and meta-analysis: loss of response and need for dose escalation of infliximab and adalimumab in ulcerative colitis. Inflamm Bowel Dis 2023;29:1633–1647.Article PubMed PDF
24. Bae JH, Park JB, Baek JE, et al. Effectiveness of switching to subcutaneous infliximab in ulcerative colitis patients experiencing intravenous infliximab failure. Gut Liver 2024;18:667–676.Article PubMed PMC
25. Irving PM, Gecse KB. Optimizing therapies using therapeutic drug monitoring: current strategies and future perspectives. Gastroenterology 2022;162:1512–1524.Article PubMed
26. Song S, Yang L, Trepicchio WL, Wyant T. Understanding the supersensitive anti-drug antibody assay: unexpected high anti-drug antibody incidence and its clinical relevance. J Immunol Res 2016;2016:3072586.Article PubMed PMC PDF
27. Alten R, An Y, Kim DH, Yoon S, Peyrin-Biroulet L. Re-routing infliximab therapy: subcutaneous infliximab opens a path towards greater convenience and clinical benefit. Clin Drug Investig 2022;42:477–489.Article PubMed PDF

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A real-world comparison of subcutaneous to intravenous administration of infliximab in patients with inflammatory bowel disease

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A real-world comparison of subcutaneous to intravenous administration of infliximab in patients with inflammatory bowel disease

Characteristics	IV (n = 122)	SC (n = 61)	P-value
Age (yr), mean ± SD	40.16 ± 14.68	36.08 ± 14.49	0.077
Male sex, No. (%)	82 (67.2)	53 (86.9)	0.004
BMI (kg/m²), mean ± SD	22.31 ± 4.47	24.05 ± 4.66	0.017
Disease duration (mo), median (IQR)	137.5 (87.3–210.0)	73.0 (30.5–138.5)	< 0.001
Type of IBD, No. (%)			0.310
UC	35 (28.7)	22 (36.1)
CD	87 (71.3)	39 (63.9)
Use of immunomodulator, No. (%)	44 (36.1)	23 (37.7)	0.828
Use of 5-ASA, No. (%)	53 (43.4)	17 (27.9)	0.041
Use of steroid, No. (%)	12 (9.8)	9 (14.8)	0.325
Duration of infliximab administration before baseline (mo), mean ± SD	55.34 ± 39.54	33.64 ± 40.68	< 0.001
Previous use of biologics or small molecules, No. (%)	9 (7.4)	5 (8.2)	0.844
Reason for switching administration method IV to SC, No. (%)			NA
Patient preference	NA	46 (75.4)
Subtherapeutic trough level of IFX	NA	15 (24.6)
Previous IV dosage and interval, No. (%)			NA
5 mg/kg, 8 wk	NA	52 (84.1)
5 mg/kg, 4 wk	NA	4 (6.3)
10 mg/kg, 8 wk	NA	5 (7.9)

Outcomes	Baseline			6 mo			12 mo
Outcomes	IV	SC	P-value	IV	SC	P-value	IV	SC	P-value
Ulcerative colitis (n)	35	22		35	17		35	11
Clinical disease activity^a	1 (2.9)	1 (4.5)	1.000	2 (5.7)	0	1.000	3 (8.6)	0	1.000
Endoscopic disease activity^b	3 (8.6)	5 (22.7)	0.179	4 (11.4)	3 (17.6)	0.596	6 (17.1)	2 (18.2)	0.547
FCP (μg/g)	345.3 ± 549.3	943.2 ± 1223.7	0.149	378.8 ± 751.4	329.9 ± 631.4	0.877	468.2 ± 606.8	785.6 ± 951.6	0.412
CRP (mg/dL)	0.42 ± 0.91	0.69 ± 2.19	0.512	0.22 ± 0.32	0.20 ± 0.41	0.906	0.24 ± 0.38	0.22 ± 0.40	0.895
Albumin (mg/dL)	4.27 ± 0.96	4.43 ± 0.51	0.577	4.54 ± 0.40	4.51 ± 0.40	0.862	4.46 ± 0.40	4.61 ± 0.38	0.332
IFX trough level (μg/mL)	0.39 ± 0.52	0.66 ± 0.74	0.634	3.28 ± 3.54	19.63 ± 11.24	0.013	5.18 ± 6.09	15.34 ± 11.61	0.065
ADA	0	1 (4.5)	0.333	1 (2.9)	0	1.000	1 (2.9)	0	1.000
Crohn’s disease (n)	87	39		86	21		81	17
Clinical disease activity^a	15 (17.2)	2 (5.1)	0.090	12 (14.0)	0	0.038	14 (17.3)	0	0.120
Endoscopic disease activity^b	3 (3.4)	0	0.274	7 (8.1)	0	0.114	2 (2.5)	0	1.000
FCP (μg/g)	899.5 ± 1,941.0	362.1 ± 429.5	0.151	445.5 ± 613.9	147.8 ± 114.4	0.01	575.9 ± 956.0	508.9 ± 719.0	0.831
CRP (mg/dL)	0.59 ± 1.46	0.44 ± 0.88	0.547	0.49 ± 0.79	0.37 ± 0.65	0.255	0.51 ± 0.98	0.21 ± 0.35	0.202
Albumin (mg/dL)	4.31 ± 0.54	4.42 ± 0.39	0.344	4.30 ± 0.47	4.45 ± 0.27	0.123	4.35 ± 0.50	4.65 ± 0.20	0.065
IFX trough level (μg/mL)	8.25 ± 9.92	6.69 ± 6.23	0.644	8.46 ± 17.92	22.85 ± 7.36	0.007	8.24 ± 7.16	23.64 ± 13.15	0.003
ADA	0	0	NA	3 (3.5)	NA	NA	0	0	NA

Factors	Ulcerative colitis		Crohn’s disease
Factors	OR (95% CI)	P-value	OR (95% CI)	P-value
Male sex	0.983 (0.035–27.571)	0.992	4.770 (0.262–86.728)	0.291
BMI	0.804 (0.567–1.139)	0.220	0.913 (0.717–1.162)	0.458
Duration of IBD	1.003 (0.986–1.021)	0.698	1.008 (0.991–1.025)	0.365
Use of 5-ASA	3.245 (0.114–92.262)	0.491	0.066 (0.001–4.061)	0.196
Use of SC IFX	5.453 (0.255–116.757)	0.278	25.508 (0.834–780.220)	0.063

Table 1. Baseline Clinical Characteristics

Table 2. Comparison of Serial Outcomes in Inflammatory Bowel Disease

Values are presented as number (%) or mean±standard deviation.

Moderate to severe disease activity as Mayo score and Crohn’s Disease Activity Index in ulcerative colitis and Crohn’s disease, respectively.

Moderate to severe endoscopic disease activity as Mayo Endoscopic Score and Simple Endoscopic Score for Crohn’s Disease in ulcerative colitis and Crohn’s disease, respectively.

IV, intravenous; SC, subcutaneous; FCP, fecal calprotectin; CRP, C-reactive protein; IFX, infliximab; ADA, anti-drug antibody; NA, not applicable.

Table 3. Multivariable Analysis of Factors Affecting IFX Trough Level at 12-Month Treatment

IFX, infliximab; OR, odds ratio; CI, confidence interval; BMI, body mass index; IBD, inflammatory bowel disease; ASA, aminosalicylic acid; SC, subcutaneous.