Transcript Anti-TNFs Should be Used Before Vedolizumab for Moderate

Anti-TNFs Should be Used
Before Vedolizumab for
Moderate to Severe IBD
Asher Kornbluth, MD
Clinical Professor of Medicine
The Henry D. Janowitz Division of
Gastroenterology
The Icahn School of Medicine at Mount
Sinai
Asher Kornbluth: Disclosures
•
•
•
Janssen
Abbvie
Millenium/Takeda
Last Year’s Debate:
22 year old, Severe UC Failing
5 Days IV Steroids
MY OPPENENT’S
POSITION:
Infliximab 5 mg/kg and
subtotal colectomy if no
improvement in 5 days
My Position:
22 year old, Severe UC Failing 5 Days
IV Steroids
•
Order Bedside Commode
•
Prescribe Kosher Diet
Anti-TNFs Should be Used
Before Vedolizumab for
Moderate to Severe IBD
Asher Kornbluth, MD
Clinical Professor of Medicine
The Henry D. Janowitz Division of
Gastroenterology
The Icahn School of Medicine at Mount
Sinai
The Mount Sinai in New York
Ulcerative Colitis
Anti-TNF Therapy vs.
Vedolizumab in
Ulcerative Colitis
ACT 1
Clinical Response at Week 8
Proportion of Patients (%)
Primary Endpoint
100
90
80
70
60
50
40
30
20
10
0
*p<0.001
69.4*
61.5*
37.2
Placebo
5 mg/kg Infliximab
10 mg/kg Infliximab
Rutgeerts, Sandborn , et al NEJM 2005;353:2462-71
Feagan,…Sandborn NEJM 2013
How Quick Does it Really
Take?
VDZ UC Trials: Induction and Maintenance
VDZ (n=125)
VDZ (n
=521)
VDZ Q4
week (n
=125)
VDZ Q 8w
(n=122)
No dose escalation permitted
All VDZ doses = 300 mg IV infusion
Open label
VDZ Q 4w
(non- ITT)
ACT 1
Proportion of Patients (%)
Clinical Response at Week 54
100
90
80
70
60
50
40
30
*p<0.001
45.5*
44.3*
19.8
20
10
0
Placebo
5 mg/kg Infliximab
10 mg/kg Infliximab
Rutgeerts, Sandborn , et al NEJM 2005;353:2462-71
AT 52 Weeks in WEEK 6 RESPONDERS (47%!!)
47% x 42% = 20%
47% x 21% = 10%
2
10%
Infliximab Induction and Maintenance Therapy
in Patients With UC: Clinical Remission
ACT 1
ACT 2
Patients (%)
Placebo
45
40
35
30
25
20
15
10
5
0
†
39
†
*
8 Weeks
†
37
16
†
35 34
34
32
15
†
IFX 5 mg/kg
17
30 Weeks 54 Weeks
40
35
30
25
20
15
10
5
0
IFX 10 mg/kg
†
†
34
36
†
*
28
26
11
6
8 Weeks
30 Weeks
*P0.003 vs placebo
†P<0.001 vs placebo
Rutgeerts
P et, al.
J Med.
2005;353:2462.
Rutgeerts,
Sandborn
et N
alEngl
NEJM
2005;353:2462-71
AT 52 Weeks in WEEK 6 RESPONDERS (47%!!)
47% x 42% = 20%
47% x 21% = 10%
2
10%
ACT 1
Mucosal Healing at Week 8, 30 and 54
Proportion of Patients (%)
Endoscopic Subscore of 0 or 1
100
*p<0.001
80
62 * 59 *
60
40
50.4* 49.2*
*
*
45.5 46.7
33.9
24.8
18.2
20
0
Week 8
Placebo
Week 30
Week 54
5 mg/kg Infliximab
10 mg/kg Infliximab
Rutgeerts, Sandborn , et al NEJM 2005;353:2462-71
Mucosal Healing with VDZ in UC
AT 52 Weeks in WEEK 6 RESPONDERS (47%!!)
47% x 42% = 20%
47% x 51% =
24%
2
%
24%
20%
ACT 1 and 2: Infliximab Extension
Studies
Reinisch W, Sandborn WJ, et al. IBD 2011
Adalimumab Maintenance of Remission in
UC for 3 years
Colombel, Sandborn et al,
AJG:109;1771-8, 2014
Crohn’s disease
Anti-TNF Drugs vs.
Vedolizumab in Crohn’s
disease
Response at Week 4: TNF Inhibitors
Infliximab
100
P<0.01
Adalimumab
Certolizumab
P<0.05P=0.01P=0.007
P=0.003 P=0.003
81.5
80
P<0.002
64.3
Percent
p=0.01
59.0
60
59.0
54.0
50.0
54.2
54.2
200 mg
N=72
400 mg
N=72
41.9
37.0
40
20
31.1
16.0
0
Placebo
N=25
5 mg/kg
N=27
10 mg/kg
N=28
20 mg/kg
N=28
Placebo
N=74
40/20 mg
N=74
80/40 mg 160/80 mg Placebo
N=75
N=76
N=73
100 mg
N=74
Targan et al. N Engl J Med. 1997;337:1029-1035. Hanauer et al. Gastroenterol. 2006;130:323-333. Schreiber et al. Gastroenterol. 2005 Sep;129:807-18
Remission at Week 4: TNF Inhibitors
100
Infliximab
Percent
80
Certolizumab
Adalimumab
60
48.2
40
36.0
P=0.05P=0.05
25.0
25.0
P<0. P<0.05P<0.05
0523.0
22.2
20.8
24.0
18.0
20
12.0
8.2
4.0
0
Placebo
N=25
5 mg/kg
N=27
10 mg/kg
N=28
20 mg/kg
N=28
Placebo
N=74
40/20 mg
N=74
80/40 mg 160/80 mg Placebo
N=75
N=76
N=73
100 mg
N=74
200 mg
N=72
400 mg
N=72
Targan et al. N Engl J Med. 1997;337:1029-1035. Hanauer et al. Gastroenterol. 2006;130:323-333. Schreiber et al. Gastroenterol. 2005 Sep;129:807-18
SONIC
35
Proportion of Patients (%)
Corticosteroid-Free Clinical
Remission at Weeks 26 and 50
Primary endpoint:
steroid-free remission
Long-term
steroid-free remission
(all randomized patients)
p<0.001
p<0.001
p=0.006 p=0.020
p=0.030 p=0.040
100
80
56,8
60
46,2
44,4
40
34,9
30
24,1
20
0
51/170 75/169
96/169
41/170
Week 26
AZA+ placebo
59/169
78/169
Week 50
IFX + placebo
IFX + AZA
SONIC
36
Corticosteroid-Free Clinical Remission at
Week 26
Post-hoc sub-analysis
Proportion of patients (%)
Patients with CRP  0.8 mg/dL and Lesions on Baseline Endoscopy (n=204)
100
p<0.001
p<0.001
p=0.17
80
68.8
56.9
60
40
28.0
20
0
21/75
AZA+ placebo
37/65
IFX + placebo
44/64
IFX + AZA
SONIC
37
Corticosteroid-Free Clinical Remission
at Week 50
Post-hoc sub-analysis
All randomized patients with CRP  0.8 mg/dL and lesions on baseline
endoscopy (N=204)
Proportion of patients (%)
100
80
p=0.002
p=0.016
p=0.354
60
50.0
41.5
40
22.7
20
0
AZA+ placebo
IFX + placebo
IFX + AZA
VDX (
n=220)DZ
VDZ
VDZ
VDZ (n=747)
Open label
VDZ q 4 weeks
(non-ITT)
31% x 39% =
12%
31% x 32%=
10%
VDZ in anti-TNF Exposed Patients in
Crohn’s disease
Sands B, …..Sandborn WJ, et al, Gastro, 2014
What Additional Data do We
Have to Guide the Use of
Vedolizumab?
Clinical Trial Results on
Vedolizumab and
Combination Therapy:
Zero
Clinical Trial Results in IV
Steroid Refractory UC
Zero
Clinical Trial Results on
Therapeutic Drug
Monitoring and Dose
Escalation:
Zero
“Toward A More Personalized Medicine
Approach to the Management of IBD”
• Risk profiling is a fundamental
concept that should be used to
guide initial selection of treatment.
Hi – risk patients should receive the
best treatment available that,
currently is: a TNF antagonist in
combination with a thiopurine
Mosli, M, Sandborn WJ, AM J Gastro, July
2014;109:994
Thank you, Bill