Global 
Deutschland Esophagus to Small Intestine
Lancet Gastroenterol Hepatol. 2026;11(1):12-21
Vedolizumab in early and late Crohn’s disease (LOVE-CD): A phase 4 open-label cohort study
Background: Vedolizumab is efficacious in inducing and maintaining clinical remission in Crohn’s disease. However, prospective data about its efficacy in early Crohn’s disease are scarce. The study aimed to evaluate the ability of vedolizumab to promote clinical, endoscopic, and histological remission in patients with early and late active Crohn’s disease over a 1-year period.
Methods: This phase 4 investigator-initiated, open-label cohort study was conducted at 22 hospitals in Belgium, Hungary, and the Netherlands. Eligible patients were adults aged 18–80 years with moderate to severe Crohn’s disease (Crohn’s Disease Activity Index [CDAI] 220–450, with ulcers at endoscopy). Patients were divided into two groups: those with early Crohn’s disease (defined as a diagnosis less than 2 years ago and naive to advanced treatment [naive or only treated with corticosteroids or immunomodulators, or both]); and those with late Crohn’s disease (defined as a diagnosis more than 2 years ago and previously treated with corticosteroids, immunomodulators, and anti-TNF agents). Patients received intravenous vedolizumab (300 mg) at weeks 0, 2, and 6, and every 8 weeks thereafter for 52 weeks, with an additional 300 mg infusion at week 10 in the absence of a decrease in CDAI of more than 70 at week 6. Colonoscopies with biopsies were done at screening, week 26, and week 52, and assessed by masked independent readers with the Simple Endoscopic Score for Crohn’s disease (SES-CD). The primary endpoint was the proportion of patients with clinical and endoscopic remission (defined as CDAI ≤ 150 and SES-CD < 4) at both week 26 and 52. Primary and safety analyses included patients who received at least one dose of the study drug.
Findings: Between July 10, 2015, and July 1, 2022, 86 patients with early Crohn’s disease (45 [52.3%] female and 41 [47.7%] male) and 174 with late Crohn’s disease (111 [63.8%] female and 63 [36.2%] male) were enrolled. Clinical and endoscopic remission at both week 26 and 52 was achieved in 27 (31.4%) of 86 patients with early Crohn’s disease versus 15 (8.6%) of 174 patients with late Crohn’s disease (difference 22.8%, 95% CI: 12.6–33.7). Serious adverse events occurred in three (3.5%) of 86 patients with early Crohn’s disease versus 46 (26.4%) of 174 patients with late Crohn’s disease and included infections (1 [1.2%] vs. 13 [7.5%]), surgery (0 vs. 8 [4.6%]), intestinal obstruction (0 vs. 4 [2.3%]), exacerbation of Crohn’s disease (1 [1.2%] vs. 6 [3.4%]), and malignancy (0 vs. 3 [1.7%]).
Interpretation: Vedolizumab treatment is safer and more effective in early than in late Crohn’s disease. Vedolizumab could be considered as a favourable treatment option for patients with biologic-naive Crohn’s disease with a short disease duration.
DOI: 10.1016/s2468-1253(25)00233-x
Prof. Dr. Peter Hasselblatt
Deputy Director Department of Internal Medicine II, University Medical Center Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany
Efficacy of vedolizumab in early and late Crohn’s disease – does disease duration matter?
Vedolizumab has been approved for the treatment of moderately-to-severely active Crohn’s disease for many years. Early concerns about lower efficacy relative to other treatment options led to cautious prescribing practices. In the early days following its approval, vedolizumab was frequently used in patients with advanced disease, a population in which its effectiveness may have been limited by the chronic nature of the disease. Adding to these concerns, the phase 3 trials GEMINI2 (DOI: 10.1056/NEJMoa1215739) and GEMINI3 (DOI: 10.1053/j.gastro.2014.05.008) reported only modest clinical remission rates at relatively early time points of 6 and 10 weeks and provided no data on “robust” endoscopic end points. The authors led by Gert d’Haens now present the final results of the LOVE-CD study, an investigator-initiated, multicenter phase 4 trial enrolling patients with moderately to highly active Crohn’s disease. Patients received vedolizumab (300 mg at weeks 0, 2, and 6, with an additional infusion at week 10 for those without a response at week 6) and were assessed both clinically and endoscopically at defined time points of 26 and 52 weeks.
For analysis, patients were divided into two groups: those with “early-stage” Crohn’s disease (disease duration < 2 years, biologic-naïve) and those with “advanced-stage” disease (disease duration > 2 years, failure of at least one TNF inhibitor). Among patients with early-stage disease, 31.4% achieved the primary end point of combined clinical and endoscopic remission at both 26 and 52 weeks, compared with 8.6% of those with advanced-stage disease. The authors also reported better clinical and endoscopic response rates, more frequent mucosal healing, and higher rates of steroid-free remission in early- as compared to advanced-stage patients. Adverse events and complications were more frequent in the advanced-stage group. Based on these findings, the authors conclude that vedolizumab represents a highly effective therapeutic option when used in the early disease stages.
These findings are consistent with observations from the German real-world cohort study VEDO-IBD, which similarly demonstrated high remission rates with vedolizumab in biologic-naïve patients (DOI: 10.1093/ibd/izad138). Furthermore, the remission rates observed in LOVE-CD are comparable to those observed in the SEAVUE trial for ustekinumab and adalimumab (DOI: 10.1016/S0140-6736(22)00688-2) and the PROFILE trial for infliximab/azathioprine (DOI: 10.1016/S2468-1253(24)00034-7). Taken together, these data suggest that the timing of biologic initiation may matter more than the specific mechanism of action.
However, a direct comparison between early- and advanced-stage groups within LOVE-CD is complicated by an important confound: Patients in the advanced-stage group had already received at least one TNF antibody prior exposure, which is known to be associated with a poorer response to subsequent therapies. These results suggest that vedolizumab may be a reasonable first-line advanced therapy for Crohn’s disease, particularly given its low rate of secondary loss of response over 2 years observed in the VEDO-IBD study. Further health economic analyses and, ideally, head-to-head trials would help to more definitively establish the role of vedolizumab in treating both early- and advanced-stage Crohn’s disease. Interestingly, the similarly designed LOVE-UC study (DOI: 10.1093/ecco-jcc/jjad179) found no difference in clinical response between patients with early- (< 4 years) or advanced-stage disease (> 4 years and anti-TNF-pretreated) in ulcerative colitis. This contrast with the LOVE-CD findings suggests that there may be disease-specific differences between the two entities.
Given its “gut-selective” mechanism of action, vedolizumab is generally considered to have a favorable safety profile. The numerically higher rates of adverse events and complications (including infections and malignant disease) observed in advanced-stage patients in LOVE-CD may reflect the underlying disease course, the effects of prior therapies, or even the impact of vedolizumab itself in this specific therapeutic setting. These questions will likely be further addressed in the near future by other trials such as iCARE. Ultimately, both efficacy and safety will play essential roles for the selection of drugs within our treatment algorithms for Crohn’s disease.