Interpreting vedolizumab persistence: lessons from real-world trajectories in ulcerative colitis
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Vedolizumab (VDZ), a humanized monoclonal antibody targeting α4β7 integrin, has become an established and well-tolerated therapeutic option for ulcerative colitis (UC) following its approval based on the phase III GEMINI trial [1,2]. However, evidence on long-term treatment persistence in real-world settings, especially across Asian populations, remains limited. In this issue of Intestinal Research, the multicenter retrospective study by Kobayashi et al. [3] provides valuable insights into 1-year persistence with VDZ and identifies clinical predictors of treatment discontinuation.
Kobayashi et al. [3] report outcomes from a large multicenter Japanese cohort of 370 patients with UC, with a median follow-up of 53 weeks and 1-year persistence rate of 64.5%. Despite the retrospective design, the large sample size and relatively long follow-up observation period strengthen the reliability of the results. Primary nonresponse accounted for 42.0% and among patients who initially achieved remission, 12.5% discontinued due to loss of response (LOR). Multivariable analysis revealed that concomitant tacrolimus use (odds ratio [OR], 2.76) and shorter disease duration (OR, 0.33 for ≥7.8 years compared with <7.8 years) were associated with discontinuation due to LOR. In contrast, prior anti-tumor necrosis factor (anti-TNF) exposure, age, and baseline disease severity were not associated with LOR. Importantly, persistence was consistent across both biologic-naive and previously exposed patients, underscoring the broad utility of VDZ in clinical practice.
The results align with other real-world data. Despite inherent limitations of claims-based studies, a large Japanese analysis demonstrated 12-month persistence rates of 69.7% for VDZ; lower than ustekinumab (84.0%), but comparable to tofacitinib (61.6%), infliximab (62.9%), adalimumab (57.6%) and golimumab (54.9%) [4]. Likewise, Scottish real-world data showed VDZ persistence of 80.7% at 1 year, gradually declining to 47.9% over 5 years [5]. Viewed collectively, this Japanese multicenter study suggests VDZ persistence in Asian populations is broadly comparable—albeit slightly lower—to Western cohorts, and comparable to other advanced biologics.
Beyond persistence related to efficacy, VDZ is widely recognized for its favorable safety profile, attributable to its gut-selective mechanism. This characteristic often makes VDZ a preferred biologic option for elderly patients in many countries. These real-world data analyses by Kobayashi et al. [3] support comparable persistence across age groups. In another study by a large Japanese claims dataset, patients prescribed VDZ were older than those receiving anti-TNF agents, yet persistence remained independent of age [4]. This is consistent with the post hoc analysis of GEMINI, which demonstrated no significant age-related differences in safety or efficacy [6].
Whereas immunogenicity is the most common cause of secondary LOR in anti-TNF agents, the mechanisms underlying the low immunogenicity of VDZ remain uncertain. In this study, 12.5% experienced LOR, yet concomitant immunomodulatory use, prior anti-TNF exposure, and disease severity were not significantly associated with LOR. The recent randomized controlled trial suggested a potential benefit of thiopurine combination for achieving deeper remission in selected patients, although thiopurines did not affect VDZ trough levels [7]. Why certain patients develop secondary LOR remains unclear and warrants further investigation.
Sequencing UC therapies has become increasingly complex with the expanding array of novel biologics and small molecules. The present study demonstrated that VDZ persistence was consistent across both biologic naive and exposed patients. Combined with findings from another study by the same group showing higher week 2 remission rates among biologic-naive patients, these data support the potential role of VDZ as a first-line biologic agent [8]. Western data echo this trend. In a Scottish cohort, prior exposure to 1 or more biologics significantly increased the risk of treatment failure (hazard ratio [HR], 1.54 for 1 prior agent; HR, 2.12 for ≥2). Furthermore, a real-world Australian cohort study suggested that first-line VDZ had superior persistence compared to infliximab, but VDZ did not compromise the efficacy of subsequent infliximab therapy [9].
A particularly noteworthy contribution of the current study is the identification of 2 predictors of LOR: tacrolimus use and short disease duration. Tacrolimus is typically concomitantly used in severe, steroid-refractory UC, and patients transitioning directly from calcineurin inhibitors to VDZ may represent a difficult-to-treat subgroup with unstable disease behavior. This finding adds a nuance that clinicians be cautious when switching such patients to VDZ and may need to carefully anticipate early LOR or consider alternative early strategies.
The observation that patients with disease duration <1 year exhibited a markedly high LOR rate (32.0%) is especially intriguing. This challenges the conventional belief that early biologic intervention uniformly improves outcomes. Instead, it suggests the existence of a subset of newly diagnosed patients with a biologically aggressive phenotype that responds poorly to VDZ alone. This interpretation is reinforced by a companion analysis from the same group showing that patients with early primary nonresponse to anti-TNF therapy—particularly those who failed within 3 months—also had poor response to VDZ [10]. Taken together, these findings imply the presence of a “biologic-refractory phenotype” defined by short disease duration, rapid anti-TNF failure, and need for tacrolimus, for whom VDZ may be less effective.
Several limitations should be considered. As with all retrospective studies, unmeasured confounding cannot be excluded. Differences in policy environments—including availability of subcutaneous injection and dose intensification strategies— limit cross-regional comparability. In Japan, dose intensification is not reimbursed by the insurance system, thus the slightly lower 1-year persistence compared to other reference may be explained. Moreover, data on the transition from intravenous to subcutaneous administration, increasingly relevant in modern clinical practice, were not available.
The real-world data presented by Kobayashi et al. [3] provide a pivotal clinical message: the success of VDZ is shaped not only by its mechanism of action but also by the patient’s prior therapeutic trajectory. Short disease duration to considering biologic agent, early anti-TNF failure, and concomitant tacrolimus characterize a phenotype of heightened treatment resistance in which VDZ may be less durable. Conversely, patients with stable disease courses—even if previously biologic-experienced—can achieve sustained benefit. Integrating these insights into clinical decision-making may enhance patient selection, personalize therapeutic strategies, and ultimately guide future treatment algorithms.
Notes
This manuscript was edited for clarity with assistance from ChatGPT (OpenAI). All final interpretations and conclusions are the authors’ own.
Funding Source
The author received no financial support for the research, authorship, and/or publication of this article.
Conflict of Interest
Moon JM is an editorial board member of the journal but was 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
Not applicable.
Author Contributions
Writing and approval of the final manuscript: Moon JM.