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Vedolizumab Should Be Used BeforeAnti-TNFs For Moderate To Severe IBD
William J. Sandborn, MD Professor and Chief, Division of Gastroenterology Director, UCSD IBD Center
How to decide?
1st lineBioloigcVedolizumab Infliximab
ADACTZGOL
Risks andBenefits
Response Remission Mucosal Healing0
5
10
15
20
25
30
35
Incremental benefit (delta)Induction therapy in ulcerative colitis
VDZ IFX ADA GOLFeagan BG. NEJM 2013Rutgeerts P. NEJM 2005
Sandborn WJ Gastro 2012Sandborn WJ Gastro 2014
Efficacy of induction therapy in biologic naïve
Danese S. Annals 2014
Durab
le Res
pons
e
Durab
le Rem
ission
CSFREM
Muc
osal
heali
ng0
5
10
15
20
25
30
35
Incremental benefit (delta)Maintenance therapy in ulcerative colitis
VDZ IFX ADA GOLFeagan BG. NEJM 2013Rutgeerts P. NEJM 2005
Sandborn WJ Gastro 2012Sandborn WJ Gastro 2014
Good efficacy for Induction and Maintanence therapy in UC
Good efficacy for Induction and Maintanence therapy in UC
Efficacy as first line agent
Vedolizumab Anti-TNF
Response Remission0
5
10
15
20
25
30
35
Incremental benefit (delta)Induction therapy in Crohn’s disease
VDZ IFX ADA CTZ
Sandborn WJ. NEJM 2013Targan et al. NEJM 1997
Hanauer et al. Gastro 2006Sandborn WJ. NEJM 2007
Response Remission0
5
10
15
20
25
Impact of time on incremental benefit (delta) of Vedolizumab induction therapy
6 week 10 week
Sands BE. Gastro 2014
Response Remission CSFREM0
5
10
15
20
25
30
35
40
45
50
Incremental benefit (delta)Maintenance therapy in Crohn’s disease
VDZ IFX ADA CTZ
Sandborn WJ. NEJM 2013Sandborn WJ. NEJM 2007
Colombel et al. Gastro 2007Hanauer et al. Lancet 2002
Good efficacy for Induction and Maintanence therapy in UC and CD
Good efficacy for Induction and Maintanence therapy in UC and CD
Efficacy as first line agent
Vedolizumab Anti-TNF
Response Remission Mucosal Healing0
5
10
15
20
25
Incremental benefit (delta) with prior biologic exposure: Vedolizumab induction therapy
VDZ UC VDZ UC Biologic exposed VDZ CD VDZ CD Biologic exposed
Feagan BG. NEJM 2013Sandborn WJ NEJM 2013
Durable Response Durable Remission CSFREM Mucosal healing0
5
10
15
20
25
30
35
Incremental benefit (delta) with prior biologic exposure: Vedolizumab maintenance therapy
VDZ UC VDZ UC Biologic exposed VDZ CD VDZ CD Biologic exposed
Feagan BG. NEJM 2013Sandborn WJ NEJM 2013
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
Efficacy as first line agent
Good efficacy for Induction and Maintanence therapy in UC and CD
Prior biologics MAY impact efficacy
Good efficacy for Induction and Maintanence therapy in UC and CD
Prior biologics WILL impact efficacy
VedolizumabAnti-TNF
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)
Baseline Day 18 Day 32 Day 60 Day 740
20
40
60
80
100
120
140
0
114.4
0
129.6Placebo Vedolizumab
Nominal Visit Day
Geo
met
ric
Mea
n H
BsA
b Co
ncen
trati
on,
IU/L
* Per Protocol Population
Hepatitis B Surface Antibody (HbsAb) Concentration Through Day 74*
Wyant T A. et al. Gut 2014
Baseline Day 18 Day 32 Day 60 Day 740
500
1000
1500
2000
2500
3000
3500Placebo Vedolizumab
Geo
met
ric
Mea
n Ig
A T
iter,
IU/L
% responders (95% CI): PBO 50.0 (37.6, 62.4) 83.9 (74.7, 93.0) 74.2 (63.3, 85.1) 59.7 (47.5, 71.9) VDZ 30.2 (18.8, 41.5) 63.5 (51.6, 75.4) 57.1 (44.9, 69.4) 50.8 (38.4, 63.1)
*Dukoral Population
Serum IgA Response to Oral Cholera Vaccine Through Day 74*
Wyant T A. et al. Gut 2014
Black Box Warnings
None Serious InfectionsIncreased 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.
MalignancyLymphoma and other malignanciesFatal hepatosplenic T-cell lymphoma
Vedolizumab Ant-TNF
Comparison of Lymphoma
Dulai PS, Siegel CA. GCNA 2014
Lymphoma
Expected Rate(General Population) 2/10,000 PYF
Anti-TNF therapy 6/10,000 PYF
Anti-integrins(Vedolizumab, Natalizumab) 3/10,000 PYF
Other RisksVedolizumab 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 2014Feuerstein JD. GCNA 2014
Risks of Therapy
Vedolizumab
Anti-TNF
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
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
Which one would you choose?
Drug A
• Efficacy similarLower if used second
• Gut selective with no signal of other risks
Drug B
• Efficacy similarUnclear if lower as 2nd line
• Clear association to other systemic risks