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. 2023 Mar 26;12(7):2503.
doi: 10.3390/jcm12072503.

Comparison of Short- and Long-Term Effectiveness between Anti-TNF and Ustekinumab after Vedolizumab Failure as First-Line Therapy in Crohn's Disease: A Multi-Center Retrospective Cohort Study

Ahmad Albshesh  1   2 , Lian Bannon  2   3 , Tali Sharar Fischler  4 , Marie Truyens  5 , Stephan R Vavricka  6 , Katja Tepes  7 , Daniela Pugliese  8 , Edoardo V Savarino  9 , Eran Zittan  10   11 , David Drobne  12   13 , Xavier Roblin  14 , Ariella Bar-Gil Shitrit  15   16 , Alessandro Armuzzi  17   18 , Triana Lobaton  5 , Nitsan Maharshak  2   3 , Henit Yanai  2   4 , Shomron Ben-Horin  1   2 , Uri Kopylov  1   2
Affiliations

Comparison of Short- and Long-Term Effectiveness between Anti-TNF and Ustekinumab after Vedolizumab Failure as First-Line Therapy in Crohn's Disease: A Multi-Center Retrospective Cohort Study

Ahmad Albshesh et al. J Clin Med. .

Abstract

Background: The effectiveness of anti-TNF or ustekinumab (UST) as a second-line biologic after vedolizumab (VDZ) failure has not yet been described.

Aims and methods: In this retrospective multicenter cohort study, We aim to investigate the effectiveness of anti-TNF and UST as second-line therapy in patients with Crohn's disease (CD) who failed VDZ as a first-line treatment. The primary outcome was clinical response at week 16-22. Secondary outcomes included the rates of clinical remission, steroid-free clinical remission, CRP normalization, and adverse events.

Results: Fifty-nine patients who failed on VDZ as a first-line treatment for CD were included; 52.8% patients received anti-TNF and 47.2% UST as a second-line therapy. In initial period (Week 16-22), the clinical response and remission rate was similar between both groups: 61.2% vs. 68%, p = 0.8 and 48.3% vs. 56%, p = 0.8 on anti-TNF and UST therapy, respectively. Furthermore, in the maintenance period the rate was similar: 75% vs. 82.3%, p = 0.8 and 62.5% vs. 70.5%, p = 0.8, respectively. Of the patients, 12 out of the 59 stopped the therapy, without a significant difference between the two groups (p = 0.6).

Conclusion: Second-line biological therapy after VDZ failure therapy was effective in >60% of the patients with CD. No differences in effectiveness were detected between the use of anti-TNF and UST as a second line.

Keywords: Crohn’s disease; anti-TNF; drug positioning; treatment failure; treatment response; ustekinumab; vedolizumab.

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Conflict of interest statement

Ahmad Albshesh—received speaking fees from Takeda; Stephan Vavricka—has received consulting fees, speakers honorary and unrestricted research grants from Abbott, Alfasigma, Amgen, Arenapharm, Falk Pharma GmbH, Ferring Pharmaceuticals, Gilead, iQuone, Janssen, MSD, Permamed, Pfizer Inc, Sanofi-Aventis, Takeda, Tillotts, UCB, and Vifor; Eran Zittan—received research support and consulting fees from Janssen, AbbVie, Takeda, Neopharm, Celgene and Pfizer; David Drobne—has served as a speaker, a consultant and an advisory board member for MSD, Abbvie, Takeda, Pfizer, Janssen, and Krka; Alessandro Armuzzi—consulting, advisory board and/or lecture fees and/or research support: AbbVie, Allergan, Amgen, Arena, Biogen, Bristol-Myers Squibb, Celltrion, Eli Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Mylan, Novartis, Pfizer, Protagonist-Therapeutics, Roche, Samsung Bioepis, Sandoz, Takeda; Triana lobaton—Financial support for research from Abbvie, Viatris, MSD, Mundipharma, Biogen, Janssen, Pfizer and Takeda; Speaker fees from Ferring, MSD, Abbvie, Janssen, Amgen, Fresenius Kabi, Galapagos, Viatrisand Takeda; Consultancy fee from Janssen, Galapagos, Amgen, Bristol Myers Squibb Fresenius Kabiand Takeda; Nitsan Maharshak—has received speaking and/or consulting fees from Pfizer, Takeda, Janssen, Ferring, BiomX, BMS, Nestle and grant support from Takeda, Janssen, Abbott, Abbvie, Pfizer, BMS, Nestle, Trobix; Henit Yanai: reports institutional research grants from Pfizer and the ISF; consulting fees from Abbvie, Janssen, Pfizer, and Takeda; honoraria for lectures from Abbvie, Janssen, Pfizer, and Takeda; participation in a Data Safety Monitoring Board or Advisory Board from Abbvie, Pfizer, and Takeda; Shomron Ben-Horin—consulting and advisory board fees and/or research support—Abbvie, MSD, Janssen, Takeda, and CellTrion; Uri Kopylov—research support- Jannsen Medtronic Takeda, advisory and speaker fees- Abbvie BMS Janssen Medtronic Novartis Pfizer Takeda. All other authors have no conflicts of interest to report.

Figures

Figure 1
Figure 1
Chart of the patients’ flow during the study period. Abbreviations: CD, Crohn’s disease; anti-TNF, anti-Tumor Necrosis Factor; UST, ustekinumab.
Figure 2
Figure 2
Outcomes in the initial (A) and maintenance period (B). The proportion of patients achieving clinical remission (HBI ≤ 4), clinical response (delta HBI ≥ 3) and steroid-free remission during the initial period (week 16–22) (A), and the proportion of patients achieving clinical remission, clinical response and steroid free remission during the maintenance period (week 52) (B); HBI: Harvey–Bradshaw index; UST: ustekinumab; anti-TNF: anti-tumor necrosis factor.
Figure 3
Figure 3
Biomarker normalization. The proportion of patients with CRP normalization (A) (CRP serum concentration levels less than normal range as per cut-off used in the corresponding institutions) and FCP normalization (B) (FCP < 250 µg/g); CRP, C-reactive protein; FCP, Fecal Calprotectin; UST, ustekinumab; anti-TNF, anti-tumor necrosis factor.
Figure 4
Figure 4
Cox regression test of treatment discontinuation-free analysis; UST1, ustekinumab; TNF2, anti-tumor necrosis factor; HR, hazard ratio; CI, confidence interval; p, p-value.
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