Introduction
Clinical response to vedolizumab has been reported as being significantly lower in patients exposed to anti-TNFs [1,2]. However, in most countries anti-TNFs remain the de facto first biologic therapies for patients with Crohn’s disease (CD). After failure of a first Anti-TNF drug, change of class of therapy is increasingly recommended in lieu of a second anti-TNF [3]. Using corticosteroid-free (CSF) remission as the main clinical outcome, we collected data on vedolizumab used as second biologic in CD patients who failed anti-TNF therapies.
Aims & Methods
PubMed and Embase were searched for real world data from cohorts of adult patients with at least 95% of exposure to anti-TNFs, at least 6 months of data, direct access to patients data (no claims database), and CSF remissions (no cumulative data) were selected. Additionally, the use rates of corticosteroids and other concomitant medications at baseline were extracted.
Results
A total of 10 studies met the search requirements, with patient numbers ranging from N=45 to N=161. One author from the Netherlands reported twice on the same registry, only one dataset was retained to avoid counting patients twice. Clinical remission was defined as either a Harvey Bradshaw index of less than or equal to 4 (8 studies) or as a Crohn’s disease activity index score <150 without resort to surgery (1 study). Across studies, the rates of corticosteroid use at baseline varied from 15.5% in a 2017 French cohort to 51.0% in a 2018 US study. Rates of CSF remission at 6 months were not related to baseline corticosteroid use and ranged from 15.3% in a 2020 UK report to 58.2% in a 2021 French cohort. On average, CSF remission at 6 months was achieved in 37.1%, (95% CI 33.6 - 40.5%) of TNF failed CD patients treated with vedolizumab as second line biological therapy [Table]. Clinical remission rates at 6 months were generally higher, but at 1 year, clinical remission and CSF remission rates were almost identical in most cohorts, highlighting the importance of achieving early CSF remission.
Conclusion
Despite anti-TNF failure, a significant proportion of CD patients may respond to vedolizumab and achieve CSF remission, regardless of the baseline use of concomitant corticosteroids. This benefit is established within 6 months after induction.
Table: Rates of clinical remission and corticosteroid-free (CSF) clinical remission in cohorts reported in the literature
Source
| Clinical remission
| CSF clinical remission
| CD patients, N
| Clinical remission definition
| Baseline concomitant therapies |
Amiot A et al. (2017) Alimentary Pharmacology & Therapeutics 46:310–321.
France
| W6: 31.2%
W14: 36.4%
W22: 37%
W30: 31.8%
W54: 30%
| W6: 19.1%
W14: 30.6%
W22: 33.5%
W30: 27.7%
W54: 27.2%
| 161
| HBI ≤4
| Corticosteroids: 15.5%
Immunosuppressants (IS): 18.6%
Steroids + IS: 6.8%
No Steroids or IS: 59%
|
Christensen B et al. (2018) Inflamm Bowel Dis 24:849–860.
US
| W14: 38%
W30: 62%
W52: 51%
| W14: 22%
W30: 44%
W52: 31%
| 94 | HBI ≤4
| Corticosteroids: 51%
Thiopurines: 29%
Methotrexate: 13%
Calcineurin inhibitor: 9%
|
Kolar M et al. (2019) Gastroenterol Hepatol 73:25–31.
Czech republic
| W30-32: 58.1%
| W30-32: 45.2%
| 45
| HBI ≤4
| Corticosteroids: 20%
Thiopurines/methotrexate: 46.7%
|
Kopylov U et al. (2019) Digestive and Liver Disease 51:68–74.
Israel
| W14: 35%
| W14: 29%
W52: 21%
| 133
| HBI ≤4,
CDAI <150
| Corticosteroids: 36.8%
Immunomodulators: 15.2%
|
ǂ Biemans VBC et al. (2020) Aliment Pharmacol Ther 52:123–134.
The Netherlands
|
| W12: 22.7%
W24: 29.7%
W52: 26.8%
| 128 | HBI ≤4
| Corticosteroids: 31.3%
Immunosuppressant (IS): 18.8%
Steroids + IS: 15.6%
|
*Alric H et al. (2020) Aliment Pharmacol Ther 51:948–957.
France
| W14: 47.7%
W48: 37.1%
| W14: 34.8%
W48: 31.8%
| 132 | HBI ≤4
| Corticosteroids: 48.5%
Thiopurines 33.3%
Methotrexate: 6.8%
Other: 2.3%
No: 57.6%
|
*Townsend T et al. (2020) Aliment Pharmacol Ther 52:1341–1352.
UK
| M2: 16.5%
M4: 21.2%
M6: 16.5%
M12: 25.9%
| M2: 11.8%
M4: 20%
M6: 15.3%
M12: 24.7%
| 85 | HBI <5
| Corticosteroids: 35.3%
Mercaptopurine: 12.9%
Azathioprine: 25.9%
Methotrexate: 8.2%
None: 50.6%
Unknown: 2.4%
|
*Manlay L et al. (2021) Aliment Pharmacol Ther 53:1289–1299.
France
|
| W14: 56.8%
W24: 58.2%
W54: 40.5%
| 88 | CDAI < 150 without resort to surgery
| Corticosteroids: 31.8%
Thiopurines: 14.8%
Methotrexate: 4.6%
No Immunosuppressant: 80.7%
|
ǁOnali S et al. (2022) Am J Gastroenterol 117:1279–1287.
Italy
| W26:44.8%
W52: 55.5%
| W26: 40.7%
W52: 51.1%
| 132 | HBI ≤4
| Corticosteroids: 49.4%
Immunomodulators: 9.5%
|
ǂ Overlaps with Biemans VBC et al. (2020) Clin Pharmacol Ther 107:1189–1199.
*Data from unweighted cohort
ǁ Data from weighted cohort
References
1. Verstockt, B, et al. 2019. “Influence of Drug Exposure on Vedolizumab-Induced Endoscopic Remission in Anti-Tumour Necrosis Factor [TNF] Naïve and Anti-TNF Exposed IBD Patients.” Journal of Crohn’s and Colitis 14 (3): 332–41.
2. Gils, A, et al. 2017. “Recent Anti-TNF Exposure Predicts Lower Vedolizumab Trough Concentrations in Patients with Crohn Disease.” Gastroenterology 152 (5): S380.
3. Zhuleku, E, et al. 2022. “Real-World Outcomes Associated with Switching to Anti-TNFs versus Other Biologics in Crohn’s Disease Patients: A Retrospective Analysis Using German Claims Data.” Therapeutic Advances in Gastroenterology 15: 1–13.
Disclosure
Christian Agboton and Dirk Lindner are employees of Takeda and hold stock/options in Takeda.
This study was sponsored by Takeda.
Medical writing support was provide by Paul Hassan of Excel Medical Affairs and was funded by Takeda.
