A literature survey on follow-up definitions on the use of infliximab in Crohn’s disease

Abstract

Many clinical studies arbitrarily define follow-up durations as short-term, mid-term, or long-term, without standardized criteria. To examine existing research on the use of infliximab in Crohn’s disease to understand how these terms are defined and applied, a literature survey was conducted. Relevant studies were identified by querying Web of Science and Scopus with predefined keywords, focusing on articles that mentioned “short-term,” “mid-term,” or “long-term” in their title, abstract, or author keywords. The majority of the papers were published in gastroenterology and hepatology journals (75.6%), since 2010 (77.3%), and primarily involved retrospective data (64.8%). Most studies measured follow-up duration from the first infliximab infusion (65.3%). The mean follow-up durations were 4.06 months for short-term (based on 46 papers), 9.47 months for mid-term (based on 3 papers), and 37.58 months for long-term studies (based on 155 papers). Retrospective studies tended to have significantly longer mean durations for long-term follow-up than prospective studies. Notably, the ranges for short-term and long-term follow-ups overlapped, indicating inconsistent definitions across studies. Currently, there is no consensus on the durations associated with these terms. Standardized reporting with explicit timeframes in months or years is essential to improve comparability and clarity in future research.

Keywords

Crohn’s disease discontinuation infliximab infusion maintenance therapy

Introduction

Crohn’s disease is a chronic, autoimmune inflammatory disorder of the gastrointestinal tract that affects millions worldwide, impacting patients’ quality of life and placing substantial burdens on healthcare systems.^1,2 Characterized by intermittent flares and remissions, Crohn’s disease presents ongoing challenges for effective management, requiring therapies that not only provide symptomatic relief but also sustain prolonged remission.³ Since the 1990s, the emergence of biologic agents, particularly tumor necrosis factor-alpha inhibitors, such as infliximab, has revolutionized the treatment paradigm for Crohn’s disease.^4,5 These therapies have demonstrated significant efficacy in inducing and maintaining remission, reducing hospitalizations, and decreasing the need for surgical intervention.⁶ Consequently, infliximab has become a cornerstone in the management of moderate to severe Crohn’s disease, supported by an increasing amount of clinical trial data and real-world evidence.⁷

Despite these advances, heterogeneity in how outcomes are reported across studies remains an obstacle to effectively synthesizing the evidence base. In particular, the terms “short-term,” “mid-term,” and “long-term” are frequently used to describe different follow-up periods over which therapeutic efficacy and safety are evaluated. For example, “short-term” response often refers to remission achieved within weeks of initiating infliximab therapy, reflecting induction efficacy. “Mid-term” outcomes may include sustained response or relapse rates during maintenance therapy, providing insight into response durability and the need for retreatment or dose escalation. Meanwhile, “long-term” outcomes typically relate to disease progression, safety of prolonged medication use, and the sustainability of remission, whether or not infliximab is discontinued.

However, these terms are often used inconsistently, with varying definitions that may not be well-defined. Such variability hinders direct comparison of study results, complicates meta-analyses, and may impair the translation of research findings into clinical practice guidelines. When the literature contains studies with unclearly defined follow-up durations, it becomes challenging to quickly determine which findings are applicable to specific patients under care. For instance, a report has argued that studies reporting sustained remission at 6–12 months may not be directly compared to studies reporting outcomes at 3–8 years, even if all of them could be defined as having a “long-term” follow-up.⁸ This variability complicates the development of evidence-based decisions and guidelines and can lead to differing interpretations.

Given these issues, a comprehensive survey of the existing literature was undertaken, focusing specifically on how studies defined and utilized terms related to follow-up durations in infliximab research for Crohn’s disease. This effort aimed to map current practices, identify inconsistencies, and provide recommendations on reporting standards to enhance the applicability of research findings in clinical practice, similar to initiatives undertaken in clinical orthopedic research literature.⁹ Therefore, this report systematically surveyed the literature to elucidate how studies investigating infliximab in Crohn’s disease defined and utilized the terms “short-term,” “mid-term,” and “long-term” in relation to follow-up durations. By mapping the current landscape, the study aimed to identify patterns and inconsistencies in outcome timeframe reporting. The objective was to determine whether there was consensus or variability in these definitions across different study designs and publication years. Ultimately, this work is intended to provide a foundation for recommending standardized definitions and reporting practices, facilitating more consistent interpretation of the efficacy and safety outcomes of infliximab in Crohn’s disease research.

Materials and methods

On April 29, 2025, a literature search was conducted to identify original articles that (1) reported the use of infliximab on Crohn’s disease patients, and (2) mentioned the phrases of short-term, mid-term, and/or long-term in their title, abstract, or author keywords. Both Web of Science and Scopus were queried. The exact search strings are as follows.

(1) Web of Science Core Collection search string: (TS = (short-term OR long-term OR mid-term OR shortterm OR longterm OR midterm) NOT KP = (short-term OR long-term OR mid-term OR shortterm OR longterm OR midterm)) AND (TS = infliximab NOT KP = infliximab) AND (TS = crohn* NOT KP = crohn*). Document type was limited to the original article. This search yielded 236 publications.

(2) Scopus search string: (TITLE-ABS-KEY (short-term OR long-term OR mid-term OR shortterm OR longterm OR midterm) not INDEXTERMS (short-term OR long-term OR mid-term OR shortterm OR longterm OR midterm)) AND (TITLE-ABS-KEY (infliximab) not INDEXTERMS (infliximab)) AND (TITLE-ABS-KEY (crohn*) not INDEXTERMS (crohn*)). Document type was limited to the original article. This search yielded 138 publications.

The complicated search strings were designed to exclude papers that could be potentially hit by KeyWords Plus tagged by Web of Science or Index Terms tagged by Scopus, as these extra “keywords” could be less precise in representing the article content.¹⁰ All 374 publication records were exported into an Excel spreadsheet for data processing. After removing duplicates, 346 papers remained. Among the 346 papers, 170 of them were excluded after screening due to these reasons: not dealing with infliximab (n = 50), not dealing with Crohn’s disease patients (n = 22), not written in English (n = 10), not original article (e.g., guideline or review papers labeled as original articles, n = 41), irrelevance (e.g., mentioned “long-term” in statements for future perspectives, n = 44), and no access to the full-text (n = 3). Finally, 176 papers entered the analysis (Figure 1).

Figure 1.

Flow chart that illustrates the literature screening process.

Then, the 176 papers were manually coded for the following parameters:

(1) Data collection: prospective versus retrospective.

(2) Patient population: adult, pediatric, mixed, or cannot be determined.

(3) The follow-up durations of short-term, mid-term, and long-term, in months. If a paper reported duration in weeks, it would be converted into months. One year has 52 weeks, implying that: 52 weeks /12 months = 4.33 weeks per month.

● If a clear definition was explicitly provided by a paper, it would be recorded. If not, the respective mean follow-up period would be recorded. Some papers reported a median value instead of a mean value. If the sample size was ⩾25, the median value would be recorded and treated as a mean value. If the sample size was <25, the median value would be converted to a mean value with the following formula: x = (a + 2m + b)/4, where x is the mean, a and b are the minimum and maximum, and m is the median. This methodology followed that of Ahmad et al.⁹ If there was inadequate information, the duration would be coded as unspecified and omitted from the calculations.

(4) The event that defined the start of the follow-up duration (e.g., from diagnosis or the first infliximab infusion). If a study measured follow-up from the time of study enrollment rather than a specific treatment stage, this would be coded as unspecified and omitted from the calculations.

This work did not involve human or animal subjects, and hence ethical approval was not applicable. Statistical analysis was conducted by SPSS Version 28.0 (IBM, NY, USA). Independent samples t test and one-way ANOVA were conducted, whenever appropriate, to evaluate if there were significant differences in the mean durations of short-term and long-term follow-up between papers (1) published in gastroenterology and hepatology journals versus their counterparts, (2) published in 2009 or before, in 2010s, versus 2020s, (3) collected data retrospectively versus prospectively, and (4) investigated adults, pediatric patients, mixed type, versus undetermined.

Results

The coded data sheet for the 176 papers was provided as Supplemental File 1. The overall characteristics of the papers are illustrated in Table 1. The majority of the papers were published in journals classified by Web of Science as gastroenterology and hepatology journals (75.6%), published since 2010 (77.3%), collected retrospective data (64.8%), and measured follow-up duration from the first infliximab infusion (65.3%). More studies investigated adult patients (35.2%) than pediatric patients (14.2%), whereas the rest of the studies either recruited both adult and pediatric patients, or it could not be determined based on the reported patient age data.

Table 1.

Overall characteristics of the papers.

Characteristics	No. of papers	% of 176
Journal category
Gastroenterology and hepatology	133	75.6
Others	43	24.4
Publication year
2009 or before	40	22.7
2010–2019	81	46.0
2020–present	55	31.3
Data collection
Prospective	62	35.2
Retrospective	114	64.8
Patient population
Adult	62	35.2
Pediatric	25	14.2
Mixed	42	23.9
Cannot be determined	47	26.7
Event defining the start of follow-up
Unspecified	20	11.4
Diagnosis	4	2.3
First infliximab infusion	115	65.3
Start of infliximab maintenance	4	2.3
Discontinuation of infliximab	8	4.5
First intensified infliximab infusion	3	1.7
Others	22	12.5

The mean (±SD) duration of short-term follow-up was 4.06 ± 3.55 months (range: 0.23–17) from 46 papers (26.1% of 176; Figure 2). Five papers did not specify their short-term duration. Meanwhile, only three papers reported mid-term follow-up, with a mean of 9.47 ± 3.59 months (data points: 6.93, 12, and unspecified). Finally, the mean (±SD) duration of long-term follow-up was 37.58 ± 28.24 months (range: 2–156) from 155 papers (88.1% of 176). Eleven papers did not specify their long-term duration.

Figure 2.

Mean durations of short-, mid-, and long-term among the analyzed papers.

Papers published in gastroenterology and hepatology journals had a significantly longer mean duration for short-term follow-up than their counterparts published in other journals (4.70 ± 3.76 vs 1.75 ± 0.82 months, p < 0.001; Figure 3(a)). In contrast, they had a shorter mean duration for long-term follow-up than their counterparts, but such a difference did not reach statistical significance (35.74 ± 25.21 vs 43.32 ± 35.92 months, p = 0.252).

Figure 3.

Mean durations of short-term and long-term follow-up among the analyzed papers with respect to (a) journal type, (b) publication year, (c) data collection type, (d) patient population, and (e) event from which follow-up started to count.

Papers published in 2009 or before had a significantly shorter mean duration for short-term follow-up than their counterparts both published in the 2010s and 2020s (2.22 ± 0.85, 5.73 ± 4.16 vs 5.90 ± 4.61 months, p = 0.003; Figure 3(b)). Similarly, papers published in 2009 or before had a significantly shorter mean duration for long-term follow-up than their counterparts both published in the 2010s and 2020s (24.41 ± 15.71, 39.66 ± 24.56 vs 42.71 ± 37.31 months, p = 0.018).

Papers collecting retrospective data had a longer mean duration for short-term follow-up than papers collecting prospective data, but the difference was not statistically significant (4.90 ± 4.48 vs 3.39 ± 2.53 months, p = 0.213; Figure 3(c)). Meanwhile, retrospective studies had a significantly longer mean duration for long-term follow-up than prospective studies (43.89 ± 29.79 vs 22.78 ± 16.80 months, p < 0.001).

Patient type did not significantly affect the mean duration for short-term or long-term follow-up (all p > 0.05, Figure 3(d)). Meanwhile, Figure 3(e) shows the mean duration of short-term and long-term follow-up from various reference events. The mean durations for short-term follow-up were comparable to each other. At the same time, long-term follow-up from discontinuation of infliximab had a longer mean duration than from first infliximab infusion or start of infliximab maintenance, which in turn had a longer mean duration than from first intensified infliximab infusion. No statistical test was performed to compare these results due to the small number of studies using events other than the first infliximab infusion (see Table 1).

Discussion

The findings of this study revealed the definitions of follow-up intervals reported in the Crohn’s disease research literature. To enable more meaningful comparisons of patient outcomes across studies, it is important for clinical research to specify appropriate post-intervention follow-up periods for recording the predefined outcome measures. This study found that the mean durations for short-term, mid-term, and long-term follow-up in studies related to infliximab for Crohn’s disease were approximately 4.06, 9.47, and 37.58 months, respectively. Besides, most of the analyzed papers reported long-term follow-up, while around one-fourth reported short-term follow-up, and very few studies reported mid-term follow-up.

As Ahmad et al.⁹ have pointed out, there are no universal definitions for short-term, mid-term, and long-term in healthcare or medicine literature. For the treatment of inflammatory bowel disease with biologics, a recent systematic review and meta-analysis of randomized controlled trials defined disease duration as short-term if it was ⩽18 months, and long-term if >18 months.¹¹ Another meta-analysis of placebo-controlled trials on the efficacy of antibiotic treatment of Crohn’s disease has defined long-term antibiotic treatment as >3 months.¹² The same inconsistency was applicable to other healthcare research fields. In clinical orthopedic research, it was proposed that these terms should correspond to approximately 30, 60, and 150 months based on the settings of 590 analyzed papers.⁹ Meanwhile, the definitions for these terms were suggested to be 12, 12–60, and >60 months for follow-up periods after bariatric surgery.¹³ Some researchers might even define more complex terms, such as 24–48 months, as “late mid-term” compared with >48 months as long-term.^14,15 If the current study follows Ahmad et al.⁹ to propose definitions for minimal follow-up durations categorized as short-term, mid-term, and long-term, resulting from data from existing literature, then for Crohn’s disease research with infliximab, the durations should be approximately 4, 9, and 38 months, respectively (Table 2). Meanwhile, the current study would also like to advocate that explicit reporting of time durations in terms of months or years should be used, and that the use of subjective, qualitative descriptors should be discontinued.

Table 2.

Durations of short-term, mid-term, and long-term follow-up proposed by or compiled from the medical literature.

Domain	Follow-up duration (months)
Domain	Short-term	Mid-term	Long-term
Clinical orthopaedic⁹	30	60	150
After bariatric surgery¹³	12	12–60	>60
Treating Crohn’s disease with infliximab (current study)	4	9	38

In addition, various aspects of reporting in Crohn’s disease involve varying criteria, such as disease classification systems including the Rome classification (devised in 1991), the Vienna classification (1998), and the Montreal classification (2005), each of which differ in terms of categorization of age at diagnosis, disease location, and behavior.¹⁶ To minimize confusion, it is recommended that follow-up durations be reported using precise time intervals, such as exact weeks, months, or years, instead of subjective terms. This approach is particularly relevant considering that maintenance therapy with infliximab (or other biologics) can be lifelong, unlike some treatments for other diseases that may lead to a complete cure within a fixed period. In such cases, long-term follow-up could be more practically defined as a specific period following disease remission or cure.

The heterogeneity in how follow-up durations were defined and reported has posed significant challenges for synthesizing evidence across studies. When phrases such as “short-term” or “long-term” are used variably or without explicit timeframes, it becomes difficult to accurately compare outcomes or aggregate data in meta-analyses. This inconsistency can lead to potential misclassification or disagreement of study results,¹⁴ potentially skewing interpretations of treatment efficacy and safety. Consequently, the lack of standardized follow-up periods may hinder the development of clear, evidence-based clinical guidelines and limit the reliability of conclusions drawn from the existing literature.

The current results indicate that retrospective studies have a longer average long-term follow-up duration than prospective studies. One possible explanation is that conducting prospective studies with extended follow-up periods is often expensive. In contrast, retrospective studies utilize already available outcomes, and researchers only need to retrieve data from patients or their medical records, which may span a long period of time. This may be illustrated by the group of studies that investigated the discontinuation of infliximab. Among those eight studies, half were prospective and half were retrospective. Three prospective studies focused on short-term outcomes with a follow-up period of 6 months, whereas only one study reported long-term outcomes at 28 months. On the other hand, all four retrospective studies reported long-term outcomes ranging from 49.2 to 116.4 months.

One clear limitation of this study is that papers that did not explicitly use the phrases of short-term, mid-term, or long-term would be excluded from the analysis. They were excluded because this study specifically aimed to investigate how researchers defined short-term, mid-term, and long-term. Hence, the findings from this study could only represent a small portion of the overall Crohn’s disease literature. Second, this study only searched the Web of Science and Scopus. Searching more databases, such as PubMed and ScienceDirect, may potentially include more studies in the dataset. Notwithstanding, it was reported that Web of Science and Scopus had broader coverage than PubMed and could cover the majority of papers indexed by the latter,^17,18 whereas ScienceDirect is owned by Elsevier, the company that hosts Scopus.

Moving forward, adopting precise reporting of follow-up durations with explicit timeframes such as months or years should be a priority in research on Crohn’s disease treatments, unless the authoritative bodies of Crohn’s disease (such as European Crohn’s and Colitis Organisation, and American Gastroenterological Association) publish guidelines that provide clear, standardized definitions of short-term, mid-term, and long-term in the future. Accurate and consistent reporting can enhance the design of future studies, enabling researchers to better define endpoints, assess treatment durability, and evaluate long-term safety. For clinicians, clear knowledge of specific follow-up periods supports more informed decision-making and individualized patient management. Overall, standardization of follow-up reporting will promote more robust evidence generation and facilitate translation of research findings into clinical practice.

Conclusion

To conclude, the results of this study have found that the mean follow-up of short-term, mid-term, and long-term studies pertaining to the use of infliximab on Crohn’s disease were 4.06, 9.47, and 37.58 months, respectively. Retrospective studies had a significantly longer mean duration for long-term follow-up than prospective studies. However, the ranges of short-term and long-term durations overlapped with each other within the analyzed dataset. Future studies should have precise reporting of follow-up durations with explicit timeframes in months or years.

Supplemental Material

sj-xlsx-1-tag-10.1177_17562848251370099 – Supplemental material for A literature survey on follow-up definitions on the use of infliximab in Crohn’s disease

Supplemental material, sj-xlsx-1-tag-10.1177_17562848251370099 for A literature survey on follow-up definitions on the use of infliximab in Crohn’s disease by Andy Wai Kan Yeung in Therapeutic Advances in Gastroenterology

Footnotes

Acknowledgements

None.

Declarations

Supplemental material

Supplemental material for this article is available online.

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