Efficacy of biologics—1st- & 2nd-Line Tx of IBD

Efficacy of biologics—1st- & 2nd-Line Tx of IBD

January 16, 2024

Issue 02

Clinical Question

Does the sequence of biologics impact first- and second-line treatment success?

Editor’s Bottom Line

These observational data support use of vedolizumab first-line for ulcerative colitis, and infliximab first-line for perianal Crohn’s disease, but should be interpreted with caution in light of their many potential sources of bias.


Kapizioni C, Desoki R, Lam D, et al. Biologic therapy for inflammatory bowel disease: Real-world comparative effectiveness and impact of drug sequencing in 13,222 patients within the UK IBD BioResource. J Crohn’s Colitis. Epub ahead of print December 2, 2023; https://academic.oup.com/ecco-jcc


This British retrospective multicenter study compared the effectiveness of biologic therapies and sequences of biologic therapies in 13,222 patients with IBD who received at least one biologic since 2017. The group included 4,185 with ulcerative colitis (UC) and 9,037 with Crohn’s disease (CD). The patients were registered in the UK IBD BioResource, a national database with demographic, disease, treatment and clinical information. Treatment failure was defined as either bowel surgery during treatment or a clinical code specifying treatment failure.

Nearly 9,630 individuals were exposed to one biologic, 2,876 had received two biologics, and 694 received three biologics over the study period. Another 110 and four patients had been exposed to four or five biologics, respectively, during the study period. Infliximab (IFX) was the most frequent first-line therapy in both UC and CD patients.

In UC patients, first-line vedolizumab (VDZ) recipients were significantly less likely to experience treatment failure over five years of follow-up than those receiving an anti-tumor necrosis factor (anti-TNF) drug (p=0.006). This advantage was also maintained when VDZ was used as second-line therapy following failure with IFX or adalimumab (ADA) (p<0.001).

For anti-TNF agents specifically, IFX had a lower five-year treatment failure rate than ADA and golimumab in UC patients, with treatment success rates at this time of 41%, 25% and 24% for the three agents, respectively. Anti-TNF drugs were equally effective whether used as first-line treatment or as second-line treatment after VDZ failure in the UC population.

In the CD population, failure rates at one, three and five years were similar with first-line treatment with IFX and ADA. VDZ first-line treatment had similar failure rates at one and three years, which was the longest follow-up period available for analysis with this drug as first-line treatment. Too few patients had received first-line ustekinumab to be included in this analysis.

Failure rates ten years after first-line treatment outset with IFX were significantly lower than with ADA (p=0.045).

In CD patients with perianal disease, first-line IFX use was associated with significantly lower overall failure rates than ADA, but failure rates in this population were similar to VDZ.

Following first-line failure with an anti-TNF, non-anti-TNF biologics had lower failure rates than a second anti-TNF (p=0.035). The presence of perianal disease did not affect this association.


Study Design: Retrospective national cohort analysis
Funding: None
Allocation: None
Setting: Multicenter
Level of Evidence: 2b