Highlights
– In the multicentre phase 4 LOVE‑CD cohort, vedolizumab induced sustained clinical and endoscopic remission in 31.4% of patients with early Crohn’s disease versus 8.6% in patients with late disease (difference 22.8%, 95% CI 12.6–33.7).
– Serious adverse events were substantially lower in the early group (3.5%) than the late group (26.4%), with fewer infections, surgeries, obstructions, and malignancies reported among early‑treated patients.
– These prospective, real‑world–style data support consideration of vedolizumab as an early biologic option for biologic‑naive patients with short disease duration, while randomized comparative trials are still needed.
Background
Crohn’s disease is a chronic inflammatory condition of the gastrointestinal tract characterized by relapsing intestinal inflammation, progressive structural damage, and variable extra‑intestinal manifestations. Control of inflammation early in the disease course has been proposed to alter the trajectory of disease, limiting complications such as strictures, fistulae, and the need for surgery. The therapeutic landscape for moderate to severe Crohn’s disease includes corticosteroids, immunomodulators, anti‑tumour necrosis factor (anti‑TNF) agents, and newer gut‑selective agents such as vedolizumab (an anti‑α4β7 integrin monoclonal antibody).
Although vedolizumab is established for induction and maintenance of remission in Crohn’s disease, prospective data specifically evaluating its effectiveness and safety when used early after diagnosis—compared with later use after treatment failure or exposure to other biologics—have been limited. The LOVE‑CD study was designed to address this gap by prospectively assessing clinical, endoscopic, and histological outcomes over one year in cohorts defined by disease duration and prior treatment exposure.
Study design
LOVE‑CD was a phase 4, investigator‑initiated, open‑label cohort study conducted across 22 hospitals in Belgium, Hungary, and the Netherlands. Adults aged 18–80 years with moderate to severe Crohn’s disease (CDAI 220–450) and endoscopically confirmed ulcers were eligible. Patients were divided into two predefined cohorts:
- Early Crohn’s disease: diagnosis <2 years and naive to advanced therapy (either treatment‑naive or only exposed to corticosteroids and/or conventional immunomodulators);
- Late Crohn’s disease: diagnosis >2 years and previously treated with corticosteroids, immunomodulators, and anti‑TNF agents.
All participants received intravenous vedolizumab 300 mg at weeks 0, 2, and 6, and every 8 weeks thereafter to week 52; an additional week 10 infusion was given if CDAI had not fallen by >70 points at week 6. Colonoscopy with biopsies was performed at screening, week 26, and week 52 and centrally scored using the Simple Endoscopic Score for Crohn’s disease (SES‑CD) by masked readers.
The primary endpoint was the proportion of patients achieving both clinical remission (CDAI ≤150) and endoscopic remission (SES‑CD <4) at both week 26 and week 52. Primary and safety analyses included patients who received at least one dose of vedolizumab. The study was registered on the EU Clinical Trial Register (EudraCT 2014‑005376‑29).
Key findings
Between July 2015 and July 2022, 86 patients with early Crohn’s disease and 174 with late Crohn’s disease were enrolled and received vedolizumab. Baseline characteristics reported in the manuscript indicate representation of both sexes and a range of disease locations and severities appropriate to a moderate‑to‑severe cohort.
Primary outcome
The combined outcome of clinical and endoscopic remission at both week 26 and week 52 (sustained remission) was achieved by 27 of 86 patients (31.4%) in the early cohort versus 15 of 174 patients (8.6%) in the late cohort. The absolute difference was 22.8% (95% CI 12.6–33.7), favouring early treatment with vedolizumab. This is a clinically meaningful difference in sustained composite remission between cohorts defined by disease duration and prior biologic exposure.
Safety outcomes
Serious adverse events (SAEs) were reported much less frequently in the early cohort: 3 of 86 (3.5%) versus 46 of 174 (26.4%) in the late cohort. Reported SAEs included infections (1 [1.2%] early vs 13 [7.5%] late), surgery related to Crohn’s disease (none vs 8 [4.6%]), intestinal obstruction (none vs 4 [2.3%]), exacerbation of Crohn’s disease (1 [1.2%] vs 6 [3.4%]) and malignancy (none vs 3 [1.7%]). The markedly higher SAE rate in the late cohort likely reflects a combination of more refractory disease, prior treatment exposures, and accrued disease‑related complications.
Other efficacy measures
The manuscript reports endoscopic healing and histological outcomes assessed via central readers, supporting the primary endpoint findings. Although absolute numbers for secondary measures are not reproduced here, the overall pattern was consistent: better mucosal outcomes and fewer complications in early‑treated, biologic‑naive patients.
Statistical and clinical interpretation
The absolute increase in sustained clinical and endoscopic remission of ~23% in early‑treated patients is clinically significant, especially given the durability at both 26 and 52 weeks. The use of a combined clinical and endoscopic endpoint strengthens the relevance to disease modification and not merely symptomatic control. The lower incidence of SAEs adds an important safety dimension to the efficacy signal.
Expert commentary
LOVE‑CD contributes prospective cohort evidence that earlier initiation of vedolizumab in patients with Crohn’s disease who are biologic‑naive and have shorter disease duration can achieve higher rates of sustained clinical and endoscopic remission and lower rates of serious adverse events compared with initiating vedolizumab later in the disease course after anti‑TNF exposure and prolonged disease.
Strengths of the study include prospective design, central blinded endoscopic assessment, histological sampling, pragmatic inclusion across multiple centres, and a clinically relevant composite primary endpoint evaluated at two timepoints. The safety data are notable and plausibly reflect a lower baseline risk in the early cohort combined with fewer prior immunosuppressive exposures.
Important limitations should guide interpretation. LOVE‑CD was open‑label and non‑randomized, with cohorts defined by disease duration and prior therapy rather than randomized allocation; therefore, residual confounding and selection bias cannot be excluded. Patients in the late cohort likely had more refractory phenotypes and accrued structural damage that could reduce responsiveness to any biologic. The study does not directly compare vedolizumab with other biologic agents in the early disease setting, nor does it provide health‑economic analyses relevant to adopting an early biologic strategy in routine practice. Finally, industry funding (Takeda Nederland) is reported and should be considered in the context of study design and reporting.
Clinical implications and next steps
For clinicians, LOVE‑CD suggests that vedolizumab is an effective and well‑tolerated option when used early in biologic‑naive patients with moderate‑to‑severe Crohn’s disease and endoscopic ulcers. These data support discussion of vedolizumab alongside other biologics as part of an early intervention or “top‑down” approach, taking into account individual patient factors such as infection risk, extra‑intestinal disease, prior medication history, patient preference, and local access policies.
Key unanswered questions remain: Would early vedolizumab be superior, non‑inferior, or complementary to early anti‑TNF therapy for different patient subgroups (e.g., perianal disease, ileal stricturing)? Does early vedolizumab alter long‑term outcomes such as surgery rates, cumulative steroid exposure, and quality of life beyond 1 year? Comparative randomized trials and longer‑term observational data, including cost‑effectiveness analyses, are needed to inform guideline recommendations and reimbursement decisions.
Conclusion
The LOVE‑CD phase 4 cohort provides compelling prospective evidence that vedolizumab produces higher sustained clinical and endoscopic remission and fewer serious adverse events when used early in the course of Crohn’s disease in biologic‑naive patients, compared with its use after prolonged disease and prior anti‑TNF exposure. These findings support consideration of vedolizumab as a favourable early biologic option, while highlighting the need for randomized comparative trials and long‑term outcome data to guide optimal sequencing of therapies.
Funding and trial registration
Funding: Takeda Nederland. Trial registration: EU Clinical Trial Register (EudraCT 2014‑005376‑29).
References
1. D’Haens GR, Löwenberg M, Baert F, Bossuyt P, Molnár T, Hoentjen F, Clasquin E, Gecse KB, Hulshoff MS, De Hertogh G, Lenfant M, Oldenburg L, Vermeire S. Vedolizumab in early and late Crohn’s disease (LOVE‑CD): a phase 4 open‑label cohort study. Lancet Gastroenterol Hepatol. 2025 Oct 27:S2468‑1253(25)00233‑X. doi: 10.1016/S2468‑1253(25)00233‑X. Epub ahead of print. PMID: 41167233.