1. Vedolizumab Should Be Used Before Anti-TNFs For Moderate To Severe IBD
William J. Sandborn, MD
Professor and Chief, Division of Gastroenterology
Director, UCSD IBD Center

2. How to decide? Risks and Benefits Vedolizumab Infliximab CTZ ADA GOL
1st line
Bioloigc
Vedolizumab
Infliximab
ADA
CTZ
GOL
Risks and
Benefits

3. Feagan BG. NEJM 2013
Rutgeerts P. NEJM 2005
Sandborn WJ Gastro 2012
Sandborn WJ Gastro 2014

4. Efficacy of induction therapy in biologic naïve
Danese S. Annals 2014

5. Feagan BG. NEJM 2013
Rutgeerts P. NEJM 2005
Sandborn WJ Gastro 2012
Sandborn WJ Gastro 2014

6. Efficacy as first line agent
Good efficacy for Induction and Maintanence therapy in UC
Good efficacy for Induction and Maintanence therapy in UC
Vedolizumab
Anti-TNF

7. Sandborn WJ. NEJM 2013
Targan et al. NEJM 1997
Hanauer et al. Gastro 2006
Sandborn WJ. NEJM 2007

8. Sands BE. Gastro 2014

9. Sandborn WJ. NEJM 2013
Sandborn WJ. NEJM 2007
Colombel et al. Gastro 2007
Hanauer et al. Lancet 2002

10. Efficacy as first line agent
Good efficacy for Induction and Maintanence therapy in UC and CD
Good efficacy for Induction and Maintanence therapy in UC and CD
Vedolizumab
Anti-TNF

11. Feagan BG. NEJM 2013
Sandborn WJ NEJM 2013

12. Feagan BG. NEJM 2013
Sandborn WJ NEJM 2013

13. Outcomes with anti-TNF in biologic exposed
Efficacy of subcutaneous biologics impacted by prior biologic exposure
Impact of prior biologic exposure on efficacy of Infliximab less clear
Chaparro M WJG 2012

14. Efficacy as first line agent
Good efficacy for Induction and Maintanence therapy in UC and CD
Prior biologics WILL impact efficacy
Good efficacy for Induction and Maintanence therapy in UC and CD
Prior biologics MAY impact efficacy
Vedolizumab
Anti-TNF

15. Safety: Is Vedolizumab Gut Selective?
No peripheral blood lymphocytosis
No protective effect in primate model of MS (EAE)
No inversion of CD4\CD8 ratio in CSF of humans
Clinical data – no cases of PML observed
Preservation of systemic humoral responses to T cell dependent antigens with modest impairment to oral antigen (vaccine study)

16. Hepatitis B Surface Antibody (HbsAb) Concentration Through Day 74*
Wyant T A. et al. Gut 2014

17. Serum IgA Response to Oral Cholera Vaccine Through Day 74*
*Dukoral Population
Wyant T A. et al. Gut 2014

18. Black Box Warnings Vedolizumab Ant-TNF None Serious Infections
Increased risk of serious infections leading to hospitalization or death, including tuberculosis (TB), bacterial sepsis, invasive fungal infections (such as histoplasmosis) and infections due to other opportunistic pathogens.
Malignancy
Lymphoma and other malignancies
Fatal hepatosplenic T-cell lymphoma

19. Comparison of Lymphoma (Vedolizumab, Natalizumab)
Lymphoma
Expected Rate
(General Population)
2/10,000 PYF
Anti-TNF therapy
6/10,000 PYF
Anti-integrins
(Vedolizumab, Natalizumab)
3/10,000 PYF
Dulai PS, Siegel CA. GCNA 2014

20. Dermatology (psoriasis)
Other Risks
Vedolizumab
Anti-TNF therapy
Serious Infection -
+/-
Opportunistic +
Demyelinating
Autoimmune
(SLE, vasculitis)
Dermatology (psoriasis)
Cardiac (CHF)
Pulmonary
(Sarcoidosis, ILD)
Caveat: most new drugs have additional toxicities identified during post-marketing surveillance
Kopylov U. GCNA 2014
Feuerstein JD. GCNA 2014

21. Risks of Therapy Anti-TNF Vedolizumab
Good efficacy for Induction and Maintanence therapy in UC and CD
Prior biologics WILL impact efficacy
Low risk of malignancy, driven by IMM
No signal for systemtic risks
Good efficacy for Induction and Maintanence therapy in UC and CD
Prior biologics MAY impact efficacy
Low risk of malignancy, driven by IMM
Systemtic risks well established
Vedolizumab
Anti-TNF

22. Which one would you choose?
Drug A
Drug B
Efficacy similar
Lower if used second
Gut selective with no signal of other risks
Efficacy similar
Unclear if lower as 2nd line
Clear association to other systemic risks