Biosimilar and Biologic Use Increasing in Greek Patients With IBD

A retrospective study from a single inflammatory bowel disease (IBD) center in Greece reported that from 2018 to 2022 the use of biologics increased by 28% yearly, and the proportion of patients using biosimilars grew from 33% to 67%.

Although anti-tumor necrosis factor (TNF)-α drugs “retained their central position in the armamentarium,” the authors said, there was also an increase in prescriptions of non–anti-TNF biologics, especially vedolizumab and ustekinumab, in both biologic-naive and experienced patients. Finally, they found first-line treatment persistence was similar between biologics in both Crohn disease (CD) and ulcerative colitis (UC), and ustekinumab was superior as a second-line treatment to vedolizumab in CD and to infliximab in UC.

IBD, including CD and UC, are immune-mediated inflammatory disorders of the gastrointestinal tract. The retrospective, observational cohort study of 409 consecutive patients treated at a single tertiary IBD center in Greece. All patients were diagnosed with either CD (60%) or UC (40%) and treated with at least 1 biologic between 2018 and 2022. Mean disease duration was 9.3 years. Data on biologics, intervals of administration, dose and dose intensification, persistence, and clinical outcomes were recorded over a mean follow-up of 3.8 years (range, 1-6 years).

The number of patients receiving biologics increased from 133 in 2018 (55% of the center’s IBD population) to 368 (78%) in 2022, a 28% increase per year. Over the entire study period, more than 50% of the IBD population was treated with anti-TNF biologics, mainly infliximab and adalimumab. The use of non-anti-TNF biologics ustekinumab, a monoclonal antibody targeting the p40 protein subunit of interleukin-12 and interleukin 23, and vedolizumab, a monoclonal antibody targeting α-4- β-7 integrin, also increased over time, especially in biologic-naive patients. In 2022, vedolizumab was prescribed for 46% of biologic-naive patients with UC and 16% with CD, and ustekinumab for 16% UC and 31% in CD.

Adalimumab was the most frequently prescribed medication for CD, with approximately 35% of patients with CD receiving adalimumab in each of the 4 years. Ustekinumab use grew over the study period, and by 2022 was the second most frequently prescribed medication for CD, used in 28% of patients. Adalimumab was the most frequently prescribed medication for biologic-naive patients with CD, and ustekinumab for biologic-experienced patients with CD.

Vedolizumab was the most frequently prescribed medication in UC, although there was a “slight decline” in its use in 2021 and 2022. In biologic-naive patients with UC, vedolizumab was the preferred first-line treatment, although both infliximab and ustekinumab prescriptions “sharply” increased in 2022.

Among patients receiving anti-TNF biologics, there was an increase in the share of biosimilars over time, from 33% of patients in 2018 to 67% of patients in 2022. Among patients on infliximab, 33%, 48%, 45%, 39%, and 67% were treated with a biosimilar in each year of the study. Among patients on adalimumab, 4%, 2%, 17%, 27%, and 47% were treated with biosimilars each year. Biosimilars referencing vedolizumab and ustekinumab were not available in Greece during the study period.

The authors said their data suggested that patients who underwent dose escalation in the first year following treatment initiation were more likely to become less responsive to treatment compared to those who had dose escalation later on, which could reflect the increased inflammatory burden in patients requiring early dose escalation. They also noted the proportion of patients on vedolizumab and ustekinumab who underwent dose escalation was “much smaller” than those for infliximab or adalimumab, as 6% of patients with CD and 10% patients with UC on vedolizumab, 10% and 8% of patients on ustekinumab, 36% and 35% of patients on infliximab, and 36% and 53% of patients on adalimumab underwent dose escalation during the study period.

The 3-year persistence rates of infliximab in this study were 64% in CD and 56% in UC. Three-year persistence of adalimumab was 61% in CD. Three-year persistence rates of vedolizumab as a first-line treatment were 82% in CD and 69% in UC. Three-year persistence of ustekinumab as a first-line treatment was 65% in CD.

The authors used survival analysis to compare the effectiveness of biologics as first-line or later-line treatments. There was no significant difference in treatment effectiveness in CD between infliximab, adalimumab, vedolizumab, and ustekinumab in biologic-naive patients. In anti–TNF-experienced patients with CD, ustekinumab was more effective than vedolizumab. In patients who had failed to respond to adalimumab, infliximab was more effective than vedolizumab.

In UC, vedolizumab and infliximab were similarly effective as first-line treatments for moderate to severe disease, and ustekinumab and vedolizumab were similarly effective when administered following failure to respond to anti-TNF therapy. Following non-response to vedolizumab, ustekinumab was more effective than infliximab in UC.

The introduction of biologics, and the administration of biologics at early stages of disease, “has significantly improved patients’ outcomes and quality of life,” the authors said. They said their findings on temporal trends reflect the shift toward early administration of biologics in IBD, and their data on treatment persistence and effectiveness could help health care providers select first-line and later-line treatments for their patients.

Reference

Markopoulos P, Gaki A, Kokkotis G, et al. Temporal trends in the use of biological agents in patients with inflammatory bowel disease: real-world data from a tertiary inflammatory bowel disease Greek center during a 5-year period. J Clin Med. 2025;14(4):1357. doi:10.3390/jcm14041357