ACG2022VGR Biologics in IBD2

6/24/2022
1
American College of Gastroenterology
6/24/2022
2
6/24/2022
Participating in the Webinar
All attendees will be muted and

will remain in Listen Only Mode.
Type your questions here so

that the moderator can see
them. Not all questions will
be answered but we will get
to as many as possible.
ACG Virtual Grand Rounds

Join us for upcoming Virtual Grand Rounds!
Week 26 – June 30, 2022

Geriatrics and Gastrointestinal Disorders: Is Age Only a Number?
Bharati Kochar, MD, MS
June 23, 2022 at Noon Eastern and NEW! 8pm Eastern!
Week 28 – July 14, 2022

Fertility, Preconception, and Pregnancy in IBD
Eugenia Shmidt, MD
July 14 2022 at Noon Eastern and NEW! 8pm Eastern!
Visit gi.org/ACGVGR to Register
3
6/24/2022
Biologics in IBD: Western Perspectives
Stephen B. Hanauer, MD
Professor of Medicine,
Northwestern University
Feinberg School of Medicine
Medical Director, Digestive Health Center
4
6/24/2022
What have we learned from TNFi and Other Biologic Clinical Trials?
• Effective for treatment of Crohn’s and UC
• All mABs are immunogenic
• High‐dose induction, regular maintenance & immunomodulators reduce
immunogenicity
• Combination therapy is more efficacious than monotherapy*
• Loss of response may be due to immunogenicity, pharmacology, or loss of
mechanism
• Risks include infections and neoplasia & are increased with steroids & thiopurines
• D’Haens G et al. Lancet. 2008;371:660‐67; Schreiber S et al. Am J Gastroenterology. 2010;105:1574‐82; Schreiber S et al. J Crohn’s Colitis. 2013;7:213‐21;
Colombel JF et al. N Engl J Med. 2010;362:1383‐95; Lémann M et al. Gastroenterology. 2006;130:1054‐61; Schreiber S et al. N Engl J Med. 2007;357:239‐
50;
Hanauer S et al. Lancet. 2002;359:1541‐9; Colombel JF et al. Gastroenterology. 2007;132:52‐65.
Room for Improvement With TNF Inhibitors in UC

100
90 Clinical Infliximab (5 mg/kg) [ACT1]
Clinical
1
80 Response Response
Patients Achieving Clinical
Response/Remission (%)
69.4 Clinical Clinical Infliximab (5 mg/kg) [ACT2]

70 64.5 Remission Remission 1
60 Golimumab (100 mg)

51.0 49.7
50 45.5 47.1 44.8
[PURSUIT] 2,3
40 Adalimumab (160 mg)

[ULTRA 1] 4
30
Adalimumab (160 mg)
18.5 16.5 16.9 17.3
20 [ULTRA 2] 5
10 Vedolizumab (300 mg)
N/A [GEMINI] 6
0
Induction Efficacy * Maintenance Efficacy †
Results presented here are from individual clinical trials and not from head‐to‐head trials. Therefore, no comparisons should be made between different agents.
* Induction efficacy was reported at Week 8 for infliximab and adalimumab and Week 6 for golimumab and vedolizumab.
† Maintenance efficacy was reported at Week 30/54 for infliximab, Week 54 for golimumab, and Week 52 for adalimumab and vedolizumab.
1. Rutgeerts P et al. N Engl J Med. 2005;353:2462‐2476. 2. Sandborn WJ et al. Gastroenterology. 2014;146:85‐95. 3. Sandborn WJ et al. Gastroenterology. 2014;146:96‐109. 4. Reinisch W et al. Gut.
2011;60:780‐787. 5. Sandborn WJ et al. Gastroenterology. 2012;142:257‐265. 6. Feagan BG et al. N EnglJ Med. 2013;369:699‐710.
10
5
6/24/2022
Evidence for combination therapy in Crohn’s Disease in

immunosuppressive‐naive patients: SONIC
Corticosteroid‐free clinical remission at Week 26
100
p<0.001
Proportion of patients (%)
80 p=0.006 p=0.022
60 56.8
44.4
40
30.0
20
51/170 75/169 96/169

0
AZA+ placebo IFX + placebo IFX + AZA
Colombel JF, et al. NEJM 2010; 362:1383‐95
11
UC Combination Therapy With a Thiopurine Is

More Efficacious Than Infliximab Monotherapy
Mucosal Healing at Week 16 AZA (N = 76)
IFX (N = 77)
Δ = 8.28; P = 0.295 IFX/AZA combination
(N = 78)
Δ = 25.98; P = 0.001
100 Δ = 17.70; P = 0.028

62.82
Patients With Mucosal
at wk 16, % (95% Cl)
80 54.55
Healing
60 36.84
40
20
Panaccione R, et al. Gastroenterology. 2014;146:392‐400.
12
6
6/24/2022
13
VICTORY: Disease Duration Impacts Steroid‐Free Remission and

Endoscopic Remission in Crohn’s Disease
1.0 1.0
Cumulative rate of endoscopic remission
Disease duration Disease duration

≤2 years ≤2 years
Cumulative rate of corticosteroid-
0.8 ≥2 years and ≤5 years 0.8 ≥2 years and ≤5 years

>5 years >5 years
free clinical remission
0.6 0.6
0.4 0.4
0.2 0.2
0.0 0.0
0 30 60 90 120 150 180 210 240 270 300 330 360 0 30 60 90 120 150 180 210 240 270 300 330 360
Time to corticosteroid-free remission (days) Time to endoscopic remission (days)
Patients with CD for ≤2 years are significantly more likely to achieve a corticosteroid-free
remission or endoscopic remission to VDZ than patients with longer disease duration.
CD: Crohn’s disease; VDZ: vedolizumab.
Faleck D et al. Clin Gastroenterol Hepatol. 2019; S1542-3565:30013–8.
14
7
6/24/2022
Phenotypic Features of Crohn’s Disease Associated with Anti‐TNF

Treatment Failure
Probability of surgery over time after anti‐TNF prescription

depending on phenotype at prescription
Retrospective study using the Alberta IBD Consortium Registry
B2 (stricturing)
B2L1 (ileal stricturing)
B3 (penetrating)
B1 (inflammatory)
Moran et al. Clin Gastroenterol Hepatol. 2014;12(3):434-442.
15
Vedolizumab vs Adalimumab in Moderate‐Severe UC

VARSITY: Mucosal Healing Week 52
Adalimumab SC 16/80/40 mg Vedolizumab IV 300 mg
P=0.0005
60 P=0.0005
P=0.4136
43.1
39.7
Patients, %
40
27.7 29.5
26.6
21
20
n=107/386 n=152/383 n=90/305 n=131/304 n=17/81 n=21/79

0
Overall Anti-TNF naïve Anti-TNF
exposure/failure
Mucosal healing defined as endoscopic Mayo score ≤1.
Sands, B et al. N Engl J Med 2019; 381:1215‐1226
16
8
6/24/2022
Combination Therapy Does Not Improve Clinical/ Endoscopic

Remissions with Vedolizumab or Ustekinumab in CD and UC
Kaplan‐Meier survival curve comparing
• Ustekinumab initiated in CD patients monotherapy vs combination therapy
(n=291) 1.00
 44% on combination therapy with 0.75
thiopurine/MTX 0.50
• Vedolizumab initiated in 381 patients (203 0.25 Ustekinumab monotherapy
CD, 178 UC) 0.00
Ustekinumab + IMM
 25% on combination therapy with 0 100 200 300 400

Analysis time
thiopurine/MTX
1.00
• Patients followed with DAIs (HBI, SCCAI, or
pMayo Score) 0.75
• Primary outcomes were clinical remission 0.50
or response at 14, 30, and 54 weeks 0.25 Vedolizumab monotherapy

0.00 Vedolizumab + IMM
0 100 200 300 400

Analysis time
Hu A et al. Clin Gastroenterol Hepatol 2020 Jul 12;S1542‐3565(20)30973‐3 (on line)
17
Ustekinumab Associated With Superior Effectiveness

Compared With Vedolizumab in CD With Prior TNFi
Patients achieving combined
Cumulative drug survival
corticosteroid-free clinical and
biochemical remission
Vedolizumab (n=69)
Ustekinumab (n=69)
50
40 P=.011
P=.228
Patients, %
30
P=.774 23
20 16
10 10
10 6 5
0
Week 12 Week 24 Week 52
Biemans VBC et al. Aliment Pharmacol Ther. 2020;00:1–12.
18
9
6/24/2022
Adalimumab vs Ustekinumab for Moderate‐Severe Crohn’s

(Seavue)
100
Δ = 4.0% (95% CI: -5.5%, 13.5%)
Percent of Patients (%)
p=0.417
80
61.0 64.9
60
40
20
119/195 124/191
0
Adalimumab Ustekinumab
Late Breaking Abstract DDW 2021
19
Anti‐TNF Agents: When and How to

Use Them
Advantage of anti‐TNF agents1,2 Limitations of anti‐TNF agents1,2
• Infectious risk
• Severe UC (infliximab)
• Reactivation of Hep B, TB
• Rapidity of action
• Need for IMM (at least year 1)
• EIM, independent from disease activity
(PG, AS, uveitis)  ↑ Infec ous and lymphoma
risk
• Associated RA, HS
• Contraindications: MS, CHF, etc.
• Pregnancy safety data
• h/o lymphoma, active malignancy
• No live virus vaccines
AS, ankylosing spondylitis; CHF, congestive heart failure; EIM, extraintestinal manifestations; HS, hidradenitis suppurativa; IMM, immune
modulator;
PG, pyoderma gangrenosum; RA, rheumatoid arthritis; TB, tuberculosis.
1. Rubin DT et al. Am J Gastroenterol. 2019;114:384-413. 2. Hindryckx P et al. J Crohn's Colitis. 2018;12(1):105–119.
20
10
6/24/2022
Improving Initial Response to Biologics
• Treat earlier in course (before complications)

 Impeded by Access
• Ensure “Complete Response”
 Treat to Target
• Combination Therapy
 Infliximab/Adalimumab
 Ustekinumab?/Vedolizumab?
• Consider PK/PD
 Factors contributing to high clearance
• Utilize Therapeutic Drug Monitoring
 Prospective TDM remains to be established
21
Key Safety Considerations with

IBD Therapies
Cytopenias Infection
Anti‐TNF Anti‐TNF
Thiopurines
Methotrexate Corticosteroids
Thiopurines
Tofacitinib
Heart failure
Anti‐TNF Malignancy
Anti‐TNF
Hepatotoxicity
Anti‐TNF Corticosteroids
Thiopurines Thiopurines
Methotrexate
Immunogenicity
Osteoporosis Anti‐TNF
Corticosteroids
Vedolizumab
Note: Prescribing information from the following products contain a boxed warning: Anti‐TNF agents (serious
infections and malignancy), tofacitinib (serious infections and malignancy), methotrexate (bone marrow, lung, and
kidney toxicities); and thiopurines (malignancy).
1. Lichtenstein GR et al. Am J Gastroenterol. 2009;104:465‐483; 2. Lichtenstein GR, et al. Am J Gastroenterol.

2012;107:409‐1422;
3. Yadav S et al. Mayo Clin Proc. 2015;90(6):738‐746.
22
11
6/24/2022
Positioning Therapies in Moderate to Severe IBD
JAK inhibitors S1P Modulator

Lymphocyte Anti-IL12/23(Ustekinumab)
TNF antagonists trafficking Anti-IL/23 (Risankizumab, (Tofacitinib, (Ozanimod,
(Vedolizumab) Mirikizumab, Guzelkumab) Upatacitinib) Etrasimod)
• IV vs SC options • IV option (SC?) • Similar induction • Oral • Oral

success as • Rapid onset of action • Rapid onset of action
• Rapid onset of action • Low rate of TNFi agents
(IV hospitalized immunogenicity • Monotherapy, • Monotherapy
• Efficacy in TNFi-naïve indicated after
patients) • Onset of action? • Dose-Titration
and -failure patients
• Best with anti-TNF failure
• Better results in TNF • Safety superior to • Cardiac conduction
immunomodulator naïve patients anti-TNF therapies
• Maintenance dosing
• Infection risk vs transition?
• Monotherapy or • Low rate of
• Lymphoma risk combination immunogenicity • Infection risk (zoster)
(with therapy? • Good use if • MACE
immunomodulator) • ”Gut-Selective” concomitant psoriasis • Lymphoma
• Long-term safety
23
Positioning Therapies in IBD

Scenario Strongly Consider Why?
Fast onset of
Severe inpatient IFX or cyclosporine to VDZ action, Weight‐
based dosing, TDM
Traveler, values convenience of injections USK or ADA Subcutaneous
Age > 65 VDZ or USK Safety
Immunosuppressed, post‐transplant VDZ or USK Safety
Lymphoma, melanoma VDZ or USK Safety
Often none needed during
chemo. VDZ or USK
Solid tumor Safety
Anti‐TNF does not increase risk
of recurrence
Diffuse EIM Anti‐TNF Systemic
ADA, adalimumab; EIM, extraintestinal manifestation; USK, ustekinumab;

VDZ, vedolizumab.
24
12
6/24/2022
Inadequate Treatment Leads

to Serious Consequences
Flare and Colectomy

hospitalization ≈ 30% of patients
Up to 25% of patients are require colectomy;
hospitalized for severe significant morbidity,
UC1 persistent QoL issues2‐4
Cardiovascular
Colorectal cancer disease
2.4‐fold greater risk in Increased risk of MI, stroke,
patients with UC5 CV mortality—especially
during flares6
1. Pola S et al. Clin Gastroenterol Hepatol. 2012;10:1315‐1325; 2. Brown C et al. Springerplus.

2015;4:573; 3. Hefti MM et al. Dis Colon Rectum. 2009;52:193‐197; 4. Ordas I et al. Lancet.
2012;380:1606‐1619; 5. Jess T et al. Clin Gastroenterol Hepatol. 2012;10:639‐645; 6. Filimon
AM et al. World J Gastroenterol. 2015;21:9688‐9692.
25
Signature Cytokines and Their Functions in the Inflammatory Process of

Arthritis and Colitis
Schett G, et al. N Engl J Med. 2021;385(7):628‐639.
26
13
6/24/2022
Current and Emerging Strategies for IBD
Anti-IL-12/23 agents
Anti-TNF agents
JAK inhibitors
Infliximab Ustekinumab S1P1 inhibitor
Tofacitinib
Adalimumab Brazikumab* Filgotinib* Ozanimod
Golimumab Risankizumab* Upadacitinib* Etrasimod*
Mirikizumab*
Guselkumab*
Anti-integrins
Vedolizumab
Etrolizumab*
Adapted from Coskun M, et al. Trends Pharmacol Sci. 2017;38(2):127‐142.
27
Comments on Biologics for IBD
•Despite “humanness” they are all immunogenic

Immunogenicity is reduced by Immune suppressants…..
•Anticipate dose adjustment with all
•There will be diminishing returns with 2nd and/or 3rd agent
Duration of Disease
Refractory Disease
Immunogenicity
28
14
6/24/2022
Biosimilars in the West

 Biosimilars are highly similar to originiator biologic products
• They cannot be considered generic biologics
• Designed to decrease medication costs and increased access to treatment
 Biosimilar TNF inhibitors are now available for the treatment of adults with IBD
 Interchangeability is a critical issue for patients and physicians that bears careful monitoring
• Currently, only one biosimilar has interchangeable designation
• Third‐party payers may mandate switches or initiation of biosimilar
 Transitioning patients to biosimilars
• Educate
• Allow patient time to make decision
• Requires multidisciplinary approach to ensure best outcomes
29
Status of Biosimilars for IBD in the United States
• Adalimumab biosimilars Infliximab biosimilars

• Abrilada™ (adalimumab-afzb) – November 2019 • IXIFI™ (Infliximab‐qbtx) – December 2017
• Hadlima (adalimumab-bwwd) – July 2019 • RENFLEXIS® (Infliximab‐abda) – April 2017
• Hymiroz (Adalimumab-adaz) – October 2018 • INFLECTRA™ (Infliximab‐dyyb) – April 2016
• CYLTEZO™ (Adalimumab-adbm) – August 2017
• AMJEVITA™ (Adalimumab-atto) – September 2016
These materials are provided to you solely as an educational resource for your personal use. Any commercial use or distribution of these materials or any portion thereof is strictly prohibited.
30
15
6/24/2022
The Future of IBD Therapy
Diagnosis
Assess disease severity New predictive tools

Omics, serologic markers,
Predict disease course serum and fecal biomarkers
High risk patients Selection of therapy

Predicting response to therapy
Early combination therapy
Low risk patients Determining who needs
Rapid step-up therapy early surgery?
Treat-to-target Tight control

No symptoms and Frequent reassessment/PK monitoring/
mucosal healing objective disease monitoring
Current proposed management strategies Future personalized management strategies

Colombel JF et al. Gastroenterology. 2017;152:351–361.
31
Biologicals in IBD: Indian Perspective
Vineet Ahuja
Department of Gastroenterology
All India Institute of Medical Sciences, New Delhi
32
16
6/24/2022
33
34
17
6/24/2022
The first five questions

which a patient asks :
1. Is it the right time to start biologicals ?
2. Is the biosimilar going to be as effective ?
3. Anti TNF leads to TB reactivation, how to avoid it ?
4. Are biologicals going to be life long ?
5. Can a short course of biologicals work ?
35
Is it the right time to start biologicals ?
36
18
6/24/2022
• Anti‐TNFs within 2 years of diagnosis

742 CD cases had lower health care utilization in
the subsequent 5 years
• The same effect was not seen in UC

318 UC cases cases
37
• Patients with CD for 2 years or

650 CD cases less are significantly more likely
to achieve a complete response
• Disease duration does not

437 UC cases associate with response
vedolizumab in patients with UC
Clinical Gastroenterology and Hepatology 2019;17:2497–2505
38
19
6/24/2022
Relationships between short disease duration and better

outcomes was found in Crohn’s Disease but NOT in
Ulcerative Colitis
Gastroenterology 2022;162:482–494
39
Is it the right time to start biologicals ?
Early use of biologicals may provide an advantage in

Crohn’s Disease but this effect is not seen in Ulcerative
Colitis
40
20
6/24/2022
Is the biosimilar going to

be as effective?
41
Adalimumab biosimilar in usual clinical

practice is safe and effective in inducing
and maintaining remission
42
21
6/24/2022
Efficacy and safety of biosimilar versus originator infliximab in patients with

inflammatory bowel disease: a real‐world cohort analysis
137 patients (82 CD; 55 UC)

102 : Remicade
35 : Biosimilar IFX
Infliximab biosimilar is comparable to

originator infliximab in terms of safety
profile and its efficacy
Kumar P , et al IJG 2022
43
Anti TNF leads to TB

reactivation, how to avoid it ?
44
22
6/24/2022
The risk of TB is proportional to local TB incidence, being

highest in high TB burden countries,
and is independent of disease (CD vs UC)
or treatment type (IFX vs ADA)
Am J Gastroenterol 2020
45
Aliment Pharmacol Ther. 2022
Stringent Latent TB Liberal

Screening Chemoprophylaxis
Any of screening test positive • Latent TB positive

• TST CT chest : evidence of old
• IGRA TB, calcification >5mm,
• CECT Chest pleural thickening, upper lobe
• Past history of TB fibronodular disease.
46
23
6/24/2022
A cohort comparison was done to evaluate for risk reduction of TB following the
stringent screening strategy
Jan 2019-Dec 2020 • 59 patients on anti TNF with

(Cohort A) stringent screening strategy
2005-Dec 2018 • 112 patients on anti TNF

(Cohort B)
Risk reduction of TB
from 17% to 1.7%.
47
TB reactivation risk can be significantly mitigated with stringent

LTB screening and LTB prophylaxis
Stringent Latent TB Liberal

Screening Chemoprophylaxis
Any of screening test positive • Latent TB positive

• TST CT chest : evidence of old
• IGRA TB, calcification >5mm,
• CECT Chest pleural thickening, upper lobe
• Past history of TB Risk reduction of TB fibronodular disease.
from 17% to 1.7%.
Aliment Pharmacol Ther. 2022
48
24
6/24/2022
Is biological therapy going

to be life long ?
49
• When a patient is in clinical and mucosal remission after receiving biologicals for
1year or more
• Continue Azathioprine/methotrexate
• 40‐50% relapse rate at 1 and 2 years
• Most relapses occur within 6‐12 months
• Retreatment with biologicals is Safe and Successful
• Groups where relapse rate high : Perianal , Complicated or relapsing disease,
Previous dose escalation, Longer disease duration
• De‐escalation is a case‐by‐case decision and should be shared with the patient
50
25
6/24/2022
44 of the 78 perianal CD patients (56.4%) relapsed after stopping anti‐TNF
• More than half of the perianal CD patients developed relapse after

stopping anti‐TNF therapy. Most regained response after resuming anti‐
TNF.
• Radiological assessment before stopping anti‐TNF is crucial in perianal CD
51
Can a short course of

biologicals work ?
52
26
6/24/2022
IFX (5 mg/kg intravenously at weeks 0, 2, 6) had been used only as an

induction therapy and thereafter maintained with AZA/5ASA
137 patients :77 (56.2%) achieved clinical remission

Cumulative corticosteroid‐free remission in
60% at 2 years
35% at 6 years
53
• 1093 patients ( 788 UC; 305 CD)

• 254 patients > 5 years thiopurines
• 68 patients > 10 years thiopurines
• No patient developed lymphoma or non‐melanoma skin cancer
54
27
6/24/2022
55
Predictors of Non Response to Anti‐TNF Therapy

Disease‐ • Long duration of Drug related • Inadequate drug levels
related disease factors • Anti‐ drug antibodies
factors • Initial non‐response to • Hypoalbuminemia
anti‐TNF treatment • High TNF tissue burden
• Smoking
• Stricturing disease
56
28
6/24/2022
North Indian Cohort :186 patients

Predictors of primary non‐response in patients on biologicals ( ant TNF)
Crohn’s Disease Univariate P Value Multivariate P Value
HR(95%CI) HR(95%CI)
118 patients
Albumin 0.075(0.02‐0.2) <0.001 0.04(0.002‐0.90) 0.04
Post Op Recurrence 5.24(1.8‐14.5) 0.001 0.95(0.51‐18.01) 0.31
IL‐7R 1.5(1.04‐2.15) 0.027 1.49(0.86‐2.56) 0.14
UC Univariate P Value Multivariate P Value

HR(95%CI) HR(95%CI)
68 patients
Albumin 0.07(0.03‐0.20) <0.001 0.58 (0.006‐0.5) 0.012
CRP 1.18 (1.07‐1.29) <0.001 1.03(0.97‐1.09) 0.31
Oncostatin M 1.87(1.18‐295) 0.007 1.3(0.76‐2.3) 0.29
57
• EEN is effective both as an adjunct and as well as

the only treatment in inducing remission
• Approximately 2/3rd experience clinical response
by 8 weeks
• Oligomeric as well as polymeric formulas provide
similar benefit
58
29
6/24/2022
Are Crohn’s disease

strictures responsive to
drug therapy?
59
60
30
6/24/2022
Adalimumab Adalimumab 40 Treat to target

Intensive 160 mg every mg every 2 with dose
week for four weeks + escalation
dose arm weeks Thiopurines 12months
Adalimumab 40
Standard Adalimumab
160 mg Week 0 mg every 2 No treat to
weeks + target approach
Dose arm 80 mg Week 2 Thiopurines
www.thelancet.com/gastrohep Vol 7 April 2022
61
Crohn’s disease strictures are responsive to drug therapy

Most patients in both treatment groups had symptom improvement
Intensification of therapy resulted in fewer patients failing treatment
www.thelancet.com/gastrohep Vol 7 April 2022
62
31
6/24/2022
Biologicals
No
Biologicals
Yes
63
Treating fistulizing
Crohn’s Disease with
Biologicals
64
32
6/24/2022
Antibiotics Top Down Therapy

Infection Inflammation
Biologicals
Drain Perianal abscess
Azathioprine
Seton Thread
65
Anti‐TNF therapy appears to be as effective

as and it may be indicated in the absence of
abscess and other complications
66
33
6/24/2022
Active high perianal fistula with a single internal opening
4‐month anti‐TNF therapy and surgical closure Anti‐TNF therapy for 1 year, after seton insertion
Primary outcome : Radiological healing assessed by MRI at 18 months
Surgery +anti TNF Anti TNF Significance

N=38 N=56
Radiologic healing 12(32%) 5(9%) 0.005
at 18 months
Clinical closure 26(68%) 29(52%) 0.079
Lancet Gastroenterol Hepatol. 2022 Jul;7(7):617‐626
67
Can you add one

biological to another
biological/small
molecule ?
68
34
6/24/2022
Author (year) Study design IBD subtype Type of combination Clinical Infectious Median
(n) therapy remission adverse events duration of
(%) (%) therapy
Buer (2018) Prospective CD (4) ADA/IFX + VDZ 80 30 6 months
observational UC (6)
Glassner Retrospective CD (31) VDZ + TOFA 50 34 8 months
(2020) UC (18) VDX + anti‐TNF
anti‐TNF + TOFA
TOFA + UST
ADA + APR
Alayo (2021) Retrospective CD (25) TOFA + VDZ 10.7 2.8 4 months
UC (10) TOFA + IFX
TOFA + UST
Yang (2020) Retrospective CD (22) VDZ+ anti‐TNF 41 NA 9 months
UST + anti‐TNF
UST + VDZ
Goessens Retrospective CD (58) VDZ + TOFA 26 10 8 months
(2021) UC (40) VDX + anti‐TNF
anti‐TNF + TOFA
TOFA + UST
UST + VDZ
UST + anti‐TNF
( Kumar S, et al , Curr Opin Gastro 2022 in review)
69
Anchor agent Additive drug
Anti TNF
Vedolizumab
Inhibitors
Vedolizumab Tofacitinib
Anti TNF Tofacitinib

Inhibitors
70
35
6/24/2022
Patient’s perspectives
Is it the right time to start biologicals ? Early initiation in CD may be helpful but not in UC
Is the biosimilar going to be as effective ? Yes

Anti TNF leads to TB reactivation, how to Stringent screening and liberal chemoprophylaxis
avoid it ? Prev h/o TB very important
Are biologicals going to be life long ? 50% relapse rates at 1‐2 years after stopping
Azathioprine maintenance therapy helps
Physician’s perspectives
Predictors of success of biological therapy Serum Albumin a very strong predictor
CD stricturing disease Yes, responsive to biologicals
Avoid if large prestenotic dilatation
Perianal Fistulizing therapy Adjunct therapy : Seton + antibiotics +
Immunomodulators very important
Dual Biological therapy In very select cases a possible modality
71
Panel Discussion
Questions and Answers
Mahesh K. Goenka, MD, FACG Rakesh Kochhar, MBBS, MD

Moderator Moderator
Govind K. Makharia, MD, DM, DNB Samir A. Shah, MD, FACG Ajit Sood, MD, DM
72
36
6/24/2022
ACG 2021
October 22‐27
Las Vegas, NV
73
37

ACG2022VGR Biologics in IBD2

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

ACG2022VGR Biologics in IBD2

Uploaded by

Copyright:

Available Formats

6/24/2022

Participating in the Webinar

All attendees will be muted and

Type your questions here so

ACG Virtual Grand Rounds

Week 26 – June 30, 2022

Week 28 – July 14, 2022

Visit gi.org/ACGVGR to Register

Biologics in IBD: Western Perspectives

Room for Improvement With TNF Inhibitors in UC

69.4 Clinical Clinical Infliximab (5 mg/kg) [ACT2]

60 Golimumab (100 mg)

40 Adalimumab (160 mg)

Evidence for combination therapy in Crohn’s Disease in

51/170 75/169 96/169

Colombel JF, et al. NEJM 2010; 362:1383‐95

UC Combination Therapy With a Thiopurine Is

100 Δ = 17.70; P = 0.028

at wk 16, % (95% Cl)

Panaccione R, et al. Gastroenterology. 2014;146:392‐400.

VICTORY: Disease Duration Impacts Steroid‐Free Remission and

Disease duration Disease duration

0.8 ≥2 years and ≤5 years 0.8 ≥2 years and ≤5 years

Phenotypic Features of Crohn’s Disease Associated with Anti‐TNF

Probability of surgery over time after anti‐TNF prescription

Moran et al. Clin Gastroenterol Hepatol. 2014;12(3):434-442.

Vedolizumab vs Adalimumab in Moderate‐Severe UC

Adalimumab SC 16/80/40 mg Vedolizumab IV 300 mg

n=107/386 n=152/383 n=90/305 n=131/304 n=17/81 n=21/79

Mucosal healing defined as endoscopic Mayo score ≤1.

Sands, B et al. N Engl J Med 2019; 381:1215‐1226

Combination Therapy Does Not Improve Clinical/ Endoscopic

 25% on combination therapy with 0 100 200 300 400

• Primary outcomes were clinical remission 0.50

or response at 14, 30, and 54 weeks 0.25 Vedolizumab monotherapy

0 100 200 300 400

Hu A et al. Clin Gastroenterol Hepatol 2020 Jul 12;S1542‐3565(20)30973‐3 (on line)

Ustekinumab Associated With Superior Effectiveness

Biemans VBC et al. Aliment Pharmacol Ther. 2020;00:1–12.

Adalimumab vs Ustekinumab for Moderate‐Severe Crohn’s

Late Breaking Abstract DDW 2021

Anti‐TNF Agents: When and How to

Improving Initial Response to Biologics

• Treat earlier in course (before complications)

Key Safety Considerations with

1. Lichtenstein GR et al. Am J Gastroenterol. 2009;104:465‐483; 2. Lichtenstein GR, et al. Am J Gastroenterol.

Positioning Therapies in Moderate to Severe IBD

JAK inhibitors S1P Modulator

• IV vs SC options • IV option (SC?) • Similar induction • Oral • Oral

Positioning Therapies in IBD

ADA, adalimumab; EIM, extraintestinal manifestation; USK, ustekinumab;

Inadequate Treatment Leads

Flare and Colectomy

1. Pola S et al. Clin Gastroenterol Hepatol. 2012;10:1315‐1325; 2. Brown C et al. Springerplus.

Signature Cytokines and Their Functions in the Inflammatory Process of

Schett G, et al. N Engl J Med. 2021;385(7):628‐639.

Current and Emerging Strategies for IBD

Adapted from Coskun M, et al. Trends Pharmacol Sci. 2017;38(2):127‐142.

Comments on Biologics for IBD

•Despite “humanness” they are all immunogenic

Biosimilars in the West

Status of Biosimilars for IBD in the United States

• Adalimumab biosimilars Infliximab biosimilars