Chair, ​David T. Rubin, MD, Jessica R. Allegretti, MD, MPH, and Stephen B. Hanauer, MD, prepared useful Practice Aids pertaining to inflammatory bowel disease for this CME activity titled "Transforming the Management of Inflammatory Bowel Disease: A Closer Look at the Role of JAK Inhibitors and the Patient’s Perspective in Achieving Therapeutic Goals." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/36k0BCJ. CME credit will be available until March 2, 2021.

1. Access the activity, “Transforming the Management of Inflammatory Bowel Disease: A Closer Look
at the Role of JAK Inhibitors and the Patient’s Perspective in Achieving Therapeutic Goals,”
at PeerView.com/QDR40
Proposed Algorithm for the Treatment of Crohn’s
Disease Based on a Treat-to-Target Approach1
PRACTICE AID
a
Consider anti-TNF monotherapy in patients at high risk of AEs, including patients older than 65 y, with history of malignant disease, or male and younger than 35 y.
b
Suggested interval assessment for tight monitoring: clinical assessment every 3 mo for patients with active disease (every 6-12 mo for patients in remission), ileocolonoscopy (or cross-sectional
imaging in patients who cannot be adequately assessed with ileocolonoscopy) every 6-9 mo for patients with active disease, and biomarkers (CRP/fecal calprotecin) every 3-6 mo.
CRP: C-reactive protein; TNF: tumor necrosis factor.
1. Adapted from Torres J et al. Lancet. 2017;389:1741-1755.
Assessment of Crohn’s disease activity by endoscopy and biomarkers
Assess presence of complicated disease risk factors
Target achieved?
Are there any objective signs of inflammation (endoscopy, MRI, CRP, or fecal calprotectin)?
Yes No
Tight
monitoringb
Discussion with patient regarding
treatment options and compliance
Poor prognostic factors include
• Extensive small bowel disease
• Severe upper gastrointestinal disease
• Rectal disease
• Perianal lesions
• Early stricturing or penetrating disease
• Smoking
• Young age at diagnosis (<30 years)
• Severe endoscopic lesions
Mild disease
Budesonide (ileitis and ileocolitis)
or systemic steroids (colitis)
Moderate disease without poor
prognostic factors and without
disease complications
Steroids + thiopurines or
methotrexate
Moderate disease with poor
prognostic factors, bowel
damage, and perianal fistulas
Severe disease
Biologicals
(± thiopurines)a
Tight
monitoringb
Clinical follow-up and measurement
of disease activity
Adjust therapy and consider
• Dose optimization
• Addition of
immunosuppressantsa
• Switch within class for
secondary anti-TNF loss
of response
• Switch out of class for
primary anti-TNF
nonresponse
(vedolizumab,
ustekinumab)
•
or

2. Access the activity, “Transforming the Management of Inflammatory Bowel Disease: A Closer Look
at the Role of JAK Inhibitors and the Patient’s Perspective in Achieving Therapeutic Goals,”
at PeerView.com/QDR40
AGA Institute Ulcerative Colitis
Care Pathway1,a,b
PRACTICE AID
a
Tofacitinib, an oral JAK inhibitor, was approved May 2018 for the treatment of adult patients with moderately to severely active ulcerative colitis who have had an inadequate response or who
are intolerant to TNF blockers. b
Ustekinumab, an interleukin-12 and -23 antagonist, was approved October 2019 for the treatment of adults with moderately to severely active ulcerative colitis.
5-ASA: 5-aminosalicylate; 6-TGN: 6-Thioguanine nucleotide; AGA: American Gastroenterological Association; CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; JAK: Janus kinase;
TNF: tumor necrosis factor.
1. Adapted from Dassopoulos T et al. Gastroenterology. 2015;149:238-245.
Patient at Low Risk for
Colectomy
• Limited anatomic extent
• Mild endoscopic disease
Patient at Moderate/High Risk for Colectomy
• Extensive colitis
• Deep ulcers
• Age <40
• High CRP and ESR
• CMV infection
• Steroid-requiring
disease
• History of
hospitalization
• C. difficile infection
No remission
Remission
• Oral 5-ASA, and/or
• Rectal 5-ASA, and/or
• Oral budesonide or
prednisone, and/or
• Rectal corticosteroids
• Short course of corticosteroids with initiation of
thiopurine, or
• Anti-TNF ± thiopurines
• Vedolizumab ± immunomodulator
• Maintenance with oral
and/or rectal 5-ASA
• Taper corticosteroid over
60 days
Maintenance Options
• Thiopurine and taper
corticosteroids over
60 days
•
•
Options
• Anti-TNF ± thiopurine
• Thiopurine (optimize
6-TGN concentrations)
• Vedolizumab ±
immunomodulator
• Proctocolectomy
Remission No remission
Vedolizumab ±
thiopurine or
methotrexate
Anti-TNF ± thiopurine

3. Access the activity, “Transforming the Management of Inflammatory Bowel Disease: A Closer Look
at the Role of JAK Inhibitors and the Patient’s Perspective in Achieving Therapeutic Goals,”
at PeerView.com/QDR40
A Closer Look at the Clinical Potential
of JAK Inhibitors for the Treatment of IBD
PRACTICE AID
CD: Crohn’s disease; GM-CSF: granulocyte-macrophage colony-stimulating factor; GP: glycoprotein; IL: interleukin; JAK: Janus kinase; NK: natural killer; STAT: signal transducer and activator of
transcription; TYK: tyrosine kinase; UC: ulcerative colitis.
1. Flamant M et al. Drugs. 2017;77:1057-1068. 2. Danese S et al. Gut. 2019;68:1893-1899.
Compound Tofacitinib Filgotinib Upadacitinib
CD, stage of development
UC, stage of development
—
FDA-approved
Phase 3
Phase 3
Phase 3
Phase 3
Target JAK1, JAK2, JAK3 JAK1 JAK1
Gut selectivity — — —
Hemoglobin level
Lymphocyte number No change
Neutrophil number
Platelet count No data
NK cell number No change
HDL level
LDL Level No change
Liver transaminase level No change
Creatinine level
Creatine phosphokinase level No data
JAK Inhibitors Currently Approved or in Development for IBD2
Ligand IL-6 IL-12/23 IL-9 IL-10 IL-22 GM-CSF IFN-
Receptor
IL-6R
GP130R
IL-12Rβ1
IL-12Rβ2
IL-23R
IL-9Rα
IL-2Rγ
IL-10Rα
IL-10Rβ
IL-22R1
IL-10Rβ
GM-CSFR IFNγR1
IFNγR2
JAKs
JAK1
JAK2
TYK2
JAK2
TYK2
JAK1
JAK3
JAK1
TYK2
JAK1
TYK2
JAK2
JAK1
JAK2
STATs STAT1
STAT3
STAT3
STAT4
STAT1
STAT3
STAT5
STAT3
STAT1
STAT3
STAT5
STAT1
STAT3
STAT5
STAT1
JAK/STAT Pathways Involved in IBD1
Actions on
intestinal
epithelium
Inflammation;
wound
healing
Inflammation
Negative
impact on
wound
healing
Anti-
inflammatory
Wound
healing;
defensin
expression
Epithelium
protection
Inflammation;
epithelium
protection
Nucleus
STAT STAT STAT STAT STAT STAT STAT STATSTAT STAT STAT STATSTAT STAT
STAT STAT

4. Access the activity, “Transforming the Management of Inflammatory Bowel Disease: A Closer Look
at the Role of JAK Inhibitors and the Patient’s Perspective in Achieving Therapeutic Goals,”
at PeerView.com/QDR40
IBD Patient Education Materials From the
Crohn's and Colitis Foundation1
PRACTICE AID
Shared Decision-Making for IBD Treatment Decisions
What is shared decision-making?
A process in which patients,
caregivers, and their healthcare
team work together to make
decisions about the patient’s
treatment and healthcare plan
What are the benefits of shared
decision-making?
• h confidence in treatment choice
• h treatment satisfaction
• May h treatment adherence
Key Steps to Participating in Shared Decision-Making
Support
Share personal goals,
values, preferences, and
insurance coverage, and ask
for support as you review
all options
Discuss
Talk through options
with your healthcare team
and make a decision together
based on medical evidence
and personal needs Follow Through
After making your decision,
remain in contact with your
healthcare team and ask
any follow-up questions
Information
Request and gather all
information about your
treatment options, including
the pros/cons and
benefits/risks
•

5. Access the activity, “Transforming the Management of Inflammatory Bowel Disease: A Closer Look
at the Role of JAK Inhibitors and the Patient’s Perspective in Achieving Therapeutic Goals,”
at PeerView.com/QDR40
IBD Patient Education Materials From the
Crohn's and Colitis Foundation1
PRACTICE AID
Are These Symptoms Related to My IBD?
Abdominal pain, diarrhea, cramping, and weight loss are all very
common symptoms of Crohn’s disease and ulcerative colitis
You can also experience symptoms outside of your digestive tract.
They can appear before you even know you have IBD
Signs and Symptoms Beyond the Gut
Arthritis
Inflammation of joints
Liver Disorders
Hepatitis, gallstones,
fatty liver disease,
primary sclerosing cholangitis
General Symptoms
Dizziness, fatigue,
shortness of breath
Anemia
Fewer red blood cells
than normal
Skin Disorders
Erythema nodosum, skin
tags, pyoderma gangrenosum
Eye Disorders
Uveitis, dry eyes,
keratopathy, episcleritis

6. Access the activity, “Transforming the Management of Inflammatory Bowel Disease: A Closer Look
at the Role of JAK Inhibitors and the Patient’s Perspective in Achieving Therapeutic Goals,”
at PeerView.com/QDR40
IBD Patient Education Materials From the
Crohn's and Colitis Foundation1
PRACTICE AID
1. http://www.crohnscolitisfoundation.org. Accessed January 16, 2020.
I’m Still Experiencing IBD Symptoms.
What Now?
If you are taking IBD medication(s) and still experiencing
symptoms, it is important to share the following
information with your healthcare team:
Ask questions
Inquire about other possible treatment options, risks and benefits
of medications, and opportunities to participate in clinical trials
Any changes in
your symptoms
before or during treatment
Have your symptoms
improved, deteriorated,
or stayed the same?
The severity of
abdominal pain
Share pain level on
a 0-10 scale
Quality of life issues
Share your ability/inability
to attend work/school, eat,
socialize, and exercise
Your symptoms
in detail
Some examples:
Number of bowel
movements/day,
amount of weight lost/gained

7. Ongoing Clinical Trials With JAK Inhibitors for the Treatment of
Crohn’s Disease and Ulcerative Colitis1
PRACTICE AID
Access the activity, “Transforming the Management of Inflammatory Bowel Disease: A Closer Look at the Role of
JAK Inhibitors and the Patient’s Perspective in Achieving Therapeutic Goals,” at PeerView.com/QDR40
Trial Patient Population Enrollment
Treatment
Arms
ClinicalTrials.gov
Identifier
SELECTION1
(Phase 3)
Moderate to severe UC; biologic-naïve and
biologic-experienced
1,351
Filgotinib vs
placebo
NCT02914522
SELECTIONLTE
(Phase 3)
Long-term safety in patients with UC who
completed or discontinued a prior filgotinib trial
1,000
Filgotinib vs
placebo
NCT02914535
DIVERSITY1
(Phase 3)
Moderate to severe CD; biologic-naïve and
biologic-experienced
1,320
Filgotinib vs
placebo
NCT02914561
DIVERSITYLTE
(Phase 3)
Long-term safety in CD patients who
completed or discontinued a prior filgotinib trial
1,000
Filgotinib vs
placebo
NCT02914600
DIVERGENCE2
(Phase 2)
Perianal fistulizing CD 75
Filgotinib vs
placebo
NCT03077412
Phase 2 Small bowel CD 100
Filgotinib vs
placebo
NCT03046056
Filgotinib: Ongoing Clinical Trials

8. Ongoing Clinical Trials With JAK Inhibitors for the Treatment of
Crohn’s Disease and Ulcerative Colitis1
CD: Crohn’s disease; JAK: Janus kinase; UC: ulcerative colitis.
1. https://clinicaltrials.gov. Accessed February 10, 2020.
PRACTICE AID
Access the activity, “Transforming the Management of Inflammatory Bowel Disease: A Closer Look at the Role of
JAK Inhibitors and the Patient’s Perspective in Achieving Therapeutic Goals,” at PeerView.com/QDR40
Trial Patient Population
Estimated
Enrollment
Treatment
Arms
ClinicalTrials.gov
Identifier
U-ACCOMPLISH
(Phase 3)
Moderate to severe UC 462
Upadacitinib
vs placebo
NCT03653026
U-ACHIEVE
(Phase 3)
Moderate to severe UC 844
Upadacitinib
vs placebo
NCT02819635
Phase 3
Long-term efficacy and safety in UC patients
who participated in U-ACHIEVE
950
Upadacitinib
vs placebo
NCT03006068
M14-431
(Phase 3)
Moderate to severe CD;
inadequate response or intolerance to biologics
645
Upadacitinib
vs placebo
NCT03345836
M14-433
(Phase 3)
Moderate to severe CD;
inadequate response or intolerance to
conventional and/or biologics
501
Upadacitinib
vs placebo
NCT03345849
Phase 3
Long-term efficacy and safety in CD patients
who completed M14-431 or M14-433 studies
738
Upadacitinib
vs placebo
NCT03345823
Upadacitinib: Ongoing Clinical Trials