Second-Line Biologic Therapy Following Tumor Necrosis Factor Antagonist Failure: A Real-World Propensity Score-Weighted Analysis

Susanne Ibing; Judy H Cho; Erwin P Böttinger; Ryan C Ungaro

doi:10.1016/j.cgh.2023.01.038

Second-Line Biologic Therapy Following Tumor Necrosis Factor Antagonist Failure: A Real-World Propensity Score-Weighted Analysis

Clin Gastroenterol Hepatol. 2023 Sep;21(10):2629-2638. doi: 10.1016/j.cgh.2023.01.038. Epub 2023 Feb 12.

Authors

Susanne Ibing¹, Judy H Cho², Erwin P Böttinger¹, Ryan C Ungaro³

Affiliations

¹ Hasso Plattner Institute for Digital Health at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York, New York; Digital Health Center, Hasso Plattner Institute, University of Potsdam, Potsdam, Germany.
² Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
³ The Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: ryan.ungaro@mssm.edu.

PMID: 36787837
DOI: 10.1016/j.cgh.2023.01.038

Abstract

Background& aims: Tumor necrosis factor (TNF) antagonists often are used as first-line medications to treat moderate to severe inflammatory bowel disease (IBD), but many patients do not achieve or maintain response. Our aim was to compare the effectiveness of second-line treatments (ustekinumab, vedolizumab, or a second TNF antagonist) after TNF antagonist exposure in patients with Crohn's disease (CD) and ulcerative colitis (UC) from 2 electronic health records-based cohorts.

Methods: We identified patients with prior TNF antagonist exposure who switched to a different biologic in the Mount Sinai Health System (MSHS) electronic health records (CD, n = 527; UC, n = 165) and the Study of a Prospective Adult Research Cohort (SPARC) from the Inflammatory Bowel Disease Plexus Program of the Crohn's & Colitis Foundation (CD, n = 412; UC, n = 129). Treatment failure was defined as the composite of any IBD-related surgery, IBD-related hospitalization, new prescription of oral/intravenous corticosteroids, or need to switch to a third biologic agent. Time-to-event analysis was conducted with inverse probability of treatment-weighted data.

Results: Overall, treatment failure occurred in 85% of MSHS and 72% of SPARC CD patients. In SPARC, the likelihood of treatment failure was significantly lower with ustekinumab compared with vedolizumab as second-line treatment (adjusted hazard ratio, 0.66; 95% CI, 0.54-0.82; P < .001), a trend confirmed in MSHS (adjusted hazard ratio, 0.89; 95% CI, 0.77-1.04; P = .15). In both cohorts, the superiority of ustekinumab compared with vedolizumab was shown when considering treatment failure as prescription of steroids or a third biologic agent. In UC, no differences between second-line treatment groups were identified.

Conclusions: In 2 independent real-world cohort settings, second-line therapy in CD with ustekinumab after TNF antagonist treatment failure was associated with a lower likelihood of treatment failure than second-line vedolizumab.

Keywords: Crohn’s Disease; Sequencing; Treatment Positioning; Ulcerative Colitis.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Adult
Biological Factors / therapeutic use
Biological Therapy
Colitis, Ulcerative* / drug therapy
Crohn Disease* / drug therapy
Humans
Inflammatory Bowel Diseases* / drug therapy
Propensity Score
Prospective Studies
Treatment Outcome
Tumor Necrosis Factor Inhibitors / therapeutic use
Tumor Necrosis Factor-alpha
Ustekinumab / therapeutic use

Substances

Tumor Necrosis Factor Inhibitors
Ustekinumab
Biological Factors
Tumor Necrosis Factor-alpha

Abstract

Publication types

MeSH terms

Substances

Grants and funding