Exploring the Future of IBD Care: The Role of JAK Inhibitors

Live Visiting Professorship Program: Outcomes Report Gilead Sciences Grant ID: 06209 Overview

Activity Description: One-hour live educational visiting professorship programs (VPPs) implemented in academic and community hospitals throughout the U.S. offered an update on the latest research and treatment recommendations for inflammatory disease. Topics included the role of the JAK/STAT signaling pathway in immune mediated diseases, up-to-date knowledge of the efficacy and safety of investigational JAK inhibitors, and the role of new and emerging JAK inhibitors in the treatment paradigm in IBD. These grand round meetings incorporated case presentations, didactic lectures, and clinical topic discussions. Enduring activity launched November 26, 2019 (outcomes reported separately).

Activities occurred: August 21, 2019 – January 27, 2020 15 VPPs supported; 17 VPPs executed

Credit: 1.0 AMA PRA Category 1 Credit(s)TM

Sponsored by: The Academy for Continued Healthcare Learning (ACHL)

Supported by: An educational grant from Gilead Sciences, Inc.

Intended Audience: US-gastroenterologists, and other allied health care professionals interested in the JAK/STAT signaling pathway and applications to treatment of IBD Activity Page (Print and Digital) Live Activity Snapshots Program Dates & Locations

INSTITUTION NAME LOCATION PROGRAM FACULTY TOTAL PERCENT TARGET DATE LEARNERS SPECIALITY AUDIENCE Northwell Health- The Center for Manhasset, NY 8/21/19 Bruce Sands, MD 20 90% (Gastroenterology) Liver Disease Valley Hospital Medical Center 43% (Gastroenterology) Las Vegas, NV 9/18/19 Gil Melmed, MD 23 (GI Workshop) 22% (Internal Medicine)

University of Maryland (GI Division) Baltimore, MD 9/18/19 Raymond Cross, MD 25 88% (Gastroenterology)

Emory University School of Medicine 100% (Gastroenterology) Atlanta, GA 10/7/19 Thomas Ullman, MD 16 (Division of Digestive Diseases)

The University of Vermont Medical 100% (Gastroenterology) Burlington, VT 10/15/19 Thomas Ullman, MD 18 Center (GI Division)

Advocate Lutheran General Hospital 36% (Gastroenterology) Park Ridge, IL 10/23/19 Joel Pekow, MD 25 (GI Division) 64% (Internal Medicine)

24% (Gastroenterology) Aventura Hospital and Medical Aventura, FL 10/23/19 David Kerman, MD 17 76% (Internal Medicine) Center

26% (Gastroenterology) Dignity Health- St. Bernardine San Bernardino, 10/28/19 Gil Melmed, MD 19 37% (Internal Medicine) Medical Center CA

St. Jude Comprehensive Digestive 100% (Gastroenterology) Fullerton, CA 10/28/19 Gil Melmed, MD 7 Health Program Dates & Locations (cont.)

INSTITUTION NAME LOCATION PROGRAM FACULTY TOTAL PERCENT TARGET DATE LEARNERS SPECIALITY AUDIENCE Beth Israel Deaconess Medical Center 86% (Gastroenterology) Boston, MA 10/30/19 Thomas Ullman, MD 14 (Division of Gastroenterology) 80% (Gastroenterology) Howard University (GI Division) Washington, DC 11/13/19 Raymond Cross, MD 15

92% (Gastroenterology) Atrium Health (GI Division) Charlotte, NC 11/21/19 Joel Pekow, MD 12

The University of Oklahoma College of 10% (Gastroenterology) Medicine- Digestive Diseases and Oklahoma City, OK 12/04/19 Bincy Abraham, MD, MS 39 62% (Internal Medicine) Nutrition 76% (Gastroenterology) Parkview Medical Center Pueblo, CO 12/04/19 Joel Pekow, MD 21

Lehigh Valley Health Network-Cedar Crest Campus 71% (Gastroenterology) Allentown, PA 12/17/19 Raymond Cross, MD 24 (bi-monthly combined colorectal-GI IBD case conference) 4% (Gastroenterology) 18% (Internal Medicine) Raymond Cross, MD George Washington University Washington, D.C. 12/19/19 83 78% (Other: Primary Care, Rheumatology, Pulmonology etc.) MedStar Georgetown University Washington, D.C. Raymond Cross, MD 93% (Gastroenterology) 1/27/2020 27 Hospital (GI Division) Faculty Information

CHAIR Russell Cohen, MD, FACG, AGAF* Bruce Sands, MD, MS Director, Inflammatory Bowel Disease Center Chief of the Dr. Henry D. Janowitz Co-Director, Advanced IBD Fellowship Division of Gastroenterology Program Dr. Burrill B. Crohn Professor of Medicine The University of Chicago Medical Center Icahn School of Medicine at Mount Sinai Chicago, IL Mount Sinai Health System New York, NY *Content and faculty advisor, no speaking engagements

Bincy Abraham, MD, MS Raymond Cross, MD, MS, AGAF, FACG Director, Gastroenterology Fellowship Program Director, Inflammatory Bowel Disease Program Director & Distinguished Professor, Co-Director, Digestive Health Center Fondren Inflammatory Bowel Disease Program University of Maryland Medical Center Houston Methodist Baltimore, MD Houston, TX Faculty Information (cont.)

Joel Pekow, MD David Kerman, MD Assistant Professor of Medicine Associate Professor of Clinical Medicine Section of Gastroenterology, Director, Gastroenterology Fellowship Program Hepatology, and Nutrition University of Miami Miller School of Medicine University of Chicago Medicine and Jackson Memorial Hospital Biological Sciences Miami, FL Chicago, IL

Gil Melmed, MD, MS Thomas Ullman, MD Co-Director, Chief, Division of Gastroenterology Clinical Inflammatory Bowel Disease Montefiore Medical Center Division of Gastroenterology Albert Einstein College of Medicine Department of Medicine New York, NY Cedars-Sinai Medical Center Los Angeles, CA Executive Summary

Final Participation 405 Clinical Participants; 196 Certificates Issued

Practicing Type 85% Physicians, 3% Fellows, 4% NPs/PAs, 2% Nurses, 2% Pharmacists, 3% Other HCPs

Objectivity & Balance Objectivity and balance rated as good/excellent by 100% of learners

Learning Objectives

100% of learners strongly agree or agree that all learning objectives were met, with an average rating of 4.0/4.0

Faculty

The faculty were rated good or excellent across all areas by 100% of learners, with an average rating of 3.97. Executive Summary

An effect size of 0.91 indicates that learners are now ~51.98% more knowledgeable of the content assessed than prior to participating in this education.

83% of learners intend to make one more change in their practice as a result of this education. Specifically, 64% of learners plan to select a different therapy for their IBD patients who fail to demonstrate mucosal healing.

Changes will impact 1,099 to more than 4,067 IBD patients each month.

A 30-day follow-up survey data reveals that 73% of survey respondents made one or more changes to their practice following exposure to this education.

Cost, patient compliance issues and lack of time to assess/counsel patients were reported as the most common barriers to implementing changes in practice

Following the activity learners demonstrated increased knowledge with the MOA of emerging JAK inhibitors and the available safety data from JAK inhibition in RA. Future Education Opportunities

Case based education on selection of therapy, monitoring response, and application of new agents.

Clinical trial efficacy and safety data with the JAKs in IBD as data become available.

Role of the JAK/STAT signaling pathway in the inflammation and disease progression of IBD.

Expert based perspectives reviewing applications in practice once therapy is available. Cohen’s d Effect Size

This Effect Size calculation includes baseline and posttest completers and encompasses all five pre/post-test questions.

Baseline Post-Test Mean 31% Mean 54%

Standard Standard Deviation 0.248 Deviation 0.257 Sample Size 50 Sample Size 141

Cohen’s d Effect Size = 0.91

An effect size of 0.91 indicates that learners are now ~51.98% more knowledgeable of the content assessed than prior to participating in this education.

Cohen (1988): .2 = small, .5 = medium, .8 = large Wolf (1986): .25 = educationally significant, .50 = clinically significant Outcomes Reporting Methodology

• Activity-related changes in clinical knowledge, competence and confidence were evaluated by using a baseline survey of gastroenterologists and internal medicine healthcare professionals of comparable competency to the VPP attendees. • A posttest and evaluation were distributed to VPP attendees and the two datasets were used for baseline-versus-post-educational comparison. • Total responses (n) may fluctuate as all feedback and survey questions were optional. Participation

Participants Certificates Participation by Specialty 405 196 Gastroenterology Participation by Clinician Type Internal Medicine Primary Care 8% 2%2%3% 2% Physician 2% Rheumatology 2% 3% 85% Fellow Cardiology 3% 3% Nurse Pulmonology 4% Nurse Practitioner Surgery 50% Physician Assistant 5% Other Pharmacists Other HCPs

25% Learning Objectives

Please rate the following objectives to indicate if you are better able to: Analysis of Respondents Rating scale: 4=Strongly Agree; 1=Strongly Disagree Discuss the role of the JAK/STAT signaling pathway in the inflammation and 4.0 disease progression of IBD Compare and contrast the cytokine pathways targeted by JAK inhibitors under 4.0 investigation for IBD Interpret the clinical trial efficacy and safety data of available and emerging 4.0 JAK inhibitors investigated for Crohn’s disease and ulcerative colitis Identify IBD patients who may require a change in therapy due to lack or loss 4.0 of response 100% of learners agreed that all learning objectives were met, with an average rating of 4.0!

Clinicians who agree that the content contributes valuable information that will 99% assist in improving quality of care for patients

N=194 Faculty Evaluation

Please rate the faculty on the criteria listed Ability to effectively convey the subject matter Respondents Rating scale: 4=Excellent; 1=Poor Bruce Sands, MD, MS (Chair) (n=1) 4.0 (n=4) Bincy Abraham, MD, MS (n=1) 3.93 (n=15) Raymond Cross, MD, MS, AGAF, FACG (n=5) 3.98 (n=100) David Kerman, MD (n=1) 4.0 (n=11) Gil Melmed, MD (n=3) 4.0 (n=30) Thomas Ullman, MD (n=3) 3.97 (n=29) Joel Pekow, MD (n=3) 3.93 (n=27)

The faculty were rated good or excellent across all areas by 100% of learners, with an average rating of 3.97. Objectivity & Balance

Did you perceive any bias? Rating of objectivity & balance

100% 93% 1% 90% 80% 70% 60% 50% 40% 30% 20% 10% 7% 99% 0% Excellent Good Fair Poor

Yes No

Activity was perceived as objective, balanced and non-biased. N=181 Confidence Assessment: Prescribing Patterns

Baseline (n=57) Post (n=190) Follow-up (n=11)

How confident are in you prescribing the currently FDA-approved JAK inhibitor for 100% your patients with IBD? 90% A. Very confident 80% B. Moderately confident 70%

C. Not at all confident 57% 60% 55% D. I do not see patients with IBD 50% 40% 42% 40% 32% 30% 27% 18% The proportion of learners who felt confident utilizing available JAK 20% 11%9% inhibitor IBD therapies increased 357% after completion of this activity. 10% 7% This increased confidence may correlate with a greater proportion of 2% 0% patients eligible for these therapies being treated with appropriate, A B C D quality care. Small slippage in confidence (-15%) was observed in a 30-day follow-up survey. Confidence Assessment: Application of New JAK Inhibitors

Baseline (n=57) Post (n=184)

As new JAK inhibitors become available, how will you apply them in clinical 100% practice? 90% A. I will offer them to patients as soon as they are available 80% B. I will wait to hear of experiences from my colleagues 70% C. I will wait until additional safety data are available 60%

50% 44% 43% 40% 40% 29% 28% 30% After completion of this activity, the proportion of learners stating that 20% 16% they will offer newer JAK inhibitors to their patients as soon as they 10% become available increased 81%. This may correlate with a greater 0% number of patients being treated with the most current care. A B C Pretest vs. Posttest Summary

Overview of Correct Responses Pre Post 100% Topic % Change*

80% JAK/STAT Pathway 100% 73% 63% 60% Response Monitoring 93% 60% 47% 42% 43% Safety 88% 40% 38% 37% 27% 27% Filgotinib Clinical Trial Data 6% 20%

Emerging JAK Inhibitors 347% 0% Topic 1 Topic 2 Topic 3 Topic 4 Topic 5

*Relative percent change between pre-assessment scores and post-assessment scores. Knowledge Acquisition: JAK/STAT Pathway

Learning Objective: Discuss the role of the JAK/STAT signaling Baseline (n=51) Post (n=156) pathway in the inflammation and disease progression of IBD

100% By what mechanism do the JAK inhibitors interfere with signaling pathways involved in the pathogenesis of immune-related inflammatory diseases such as 90% IBD? 80% A. Prevention of cytokine binding to cell surface receptors 70%

B. Via binding to complementary RNA targets and modifying gene expression 60%

C. They prevent phosphorylation of kinases associated with cytokine 50% 47% receptors 40% 31%33% D. By degrading the STAT components of cytokine signaling pathways 28% 30% 27% 18% 20% 14% 10% After completion of the activity, the proportion of learners correctly 2% identifying the role of JAK inhibition and signaling pathway disruption in the 0% inflammation and disease progression of IBD increased 74%. This A B C D increased understanding of JAK inhibition may correlate with an amplified use of these therapies; yet, these data suggest a need for continued education on their MOA. Clinical Competence: Response Mentoring

Learning Objective: Identify IBD patients who may require a change in therapy due to lack or loss of response Baseline (n=52) Post (n=141)

EZ, a 36-year-old woman recently diagnosed with UC after experiencing bloody stools 6 times a day and determination of a Mayo endoscopic subscore of 2, is 100% initiating therapy. How would you monitor her response to therapy? 90% A. Assess biomarkers 80%

B. Patient reports of bowel habits 70% 63% C. Therapeutic drug monitoring 60% 50% D. Mucosal healing on endoscopy 42% 40% 36% E. Access fecal calprotectin levels 30%

20% 15% 8%8% 10%10% After completion of this activity, the proportion of learners who were 10% able to indicate how to monitor patients with IBD for a potential lack or 4%4% loss of response (and subsequently change therapy) increased 50%. 0% A B C D E This increased knowledge may assist learners in better managing their patients with IBD and personalizing care. Knowledge Acquisition:

Learning Objective: Compare and contrast the cytokine pathways targeted by JAK inhibitors under investigation for IBD Baseline (n=51) Post (n=157) Follow-up (n=10)

The available and emerging JAK inhibitors inhibit different members of the JAK 100% family. The investigational agent filgotinib works by inhibiting which of the following? 90% 80% A. JAK1 70% B. JAK 1/2 60% 60% 60% C. JAK 1/3 50%

D. JAK 1/2/3 and Tyk2 40% 35%

30% 27% 18% 20% 20% 20% 17% After completion of this activity, the proportion of learners who were 13% 10% 10%10% able to differentiate the selectivity of the investigational JAK inhibitor 10% filgotinib increased 122%. Further, the increases in knowledge were 0% sustained at 30-day follow up. These knowledge gains may correlate A B C D with more widespread use of these agents once they become available. Knowledge Acquisition:

Learning Objective: Interpret the clinical trial efficacy and safety data of available and emerging JAK inhibitors investigated for Crohn’s disease Baseline (n=50) Post (n=153) and ulcerative colitis 100% Which of the following statements best describes results from clinical trials with the available and emerging JAK inhibitors in Crohn’s disease? 90% A. The JAK inhibitors induce clinical remission in Crohn’s disease patients to 80% a greater extent than biologic therapies 70% B. Significantly more patients receiving tofacitinib, filgotinib, and upadacitinib achieved measures of clinical remission in Crohn’s disease patients 60% compared with placebo 50% 43% 43% 40% 38% C. Filgotinib and upadacitinib have demonstrated efficacy in Crohn’s 40% disease; however, tofacitinib did not achieve efficacy endpoints in clinical trials 30% D. The JAK inhibitors have not demonstrated efficacy in patients with Crohn’s 20% disease 12% 10% 10% 7% 7% After completion of this activity, the proportion of learners who 0% understood the latest evidence regarding the available and emerging A B C D JAK inhibitors for Crohn’s disease and ulcerative colitis increased 13%. Still, a large proportion of learners selected incorrect answers at-post, suggesting improvement is still needed in this area. Clinical Competence: Response Mentoring

Learning Objective: Interpret the clinical trial efficacy and safety data of available and emerging JAK inhibitors investigated for Crohn’s disease Baseline (n=52) Post (n=157) Follow-up (n=11) and ulcerative colitis

100% KB, a 41-year old woman who is considering initiation of a JAK inhibitor asks 91% about the potential risk of developing cancer after reading about risks with the 90% biologic therapies. Based on safety data on the use of tofacitinib in RA, which of 80% the following would you highlight as having the highest incidence rate during your 73% discussion with KB? 70% A. Herpes zoster infection 60% B. Malignancies 50% 40% 37% C. Serious infections 31% 30% D. Thromboembolism 19% 21% 20% 13% 9% 10% 5% 1% Upon completion of this activity, the proportion of learners who 0% understood the safety data with the available JAK inhibitor increased A B C D 97%. At 30-day follow-up, this proportion of learners increased even more (25%). These changes in knowledge may correlate with increased confidence in the use of newer JAK inhibitors secondary to safety concerns with the current treatment options. Practice Change

Select a different therapy for my patients who fail to demonstrate IBD disease remission/mucosal healing as part 64% 55% of a treat-to-target strategy.

Create/revise targeted therapeutic IBD protocols, policies, 26% and/or procedures. 64%

4% Other changes Posttest (n=179) Follow-up (n=11) This activity validated my current practice; no changes will be 17% made 27%

0% 10% 20% 30% 40% 50% 60% 70%

83% of learners intend to make one more change in their practice as a result of this education. Specifically, 64% of learners plan to select a different therapy for their IBD patients who fail to demonstrate mucosal healing. A 30-day follow-up survey data reveals that 73% of survey respondents made one or more changes to their practice following exposure to this education.

Multiple responses allowed IBD Patient Impact

Number of patients with IBD seen per week:

5% 1% 0 9% 13% 1-10

11-20 73% 21-50

>50

Changes will impact 1099 to more than 4,067 IBD patients each month. This assumes data in chart above is representative of all participating healthcare professionals (405), who indicated they would change their practice as a result of participating in this activity (83%).

N=183 Topics of Interest

Safety of JAK inhibitors 47% Case-based education 41% Efficacy of JAK inhibitors 36% Clinical trial updates in JAK therapies 34% Incorporating JAK therapy into treatment 25% Assisting patients with access to JAK inhibitor therapy 15% Other 1%

0% 20% 40% 60% 80% 100%

Efficacy and safety of JAK inhibitors were rated with the highest interest as well as case-based discussion for future education.

N=169; multiple responses allowed Take-away Pearls

Self-reported increase in knowledge • Consider JAK therapy as treatment for IBD patients (7) • Discuss JAK option with GI • Check AB levels, repeat endoscopy sooner • Asymptomatic patients with actric inflammation, how to treat • Offer JAK Inhibitors to patients, escalate IBD care more refractory/non-responses aggressively • Refer and evaluate for stageup • Monitor antibody level • Consider using JAK inhibitor in patients who fail bios • Consider adding JAK-1 in treatment and provide better • Incorporate JAK inhibitors to practice, get more familiar with education this class • Advance medical therapy for IBD in my patients, Use after • Consult GI earlier, Pay attention to how they are being biologics monitored by GI • Treat to target and consider JAK therapies (5) • Consider use in patients who fail TNF drugs, consider use • Understanding mechanism , and option of new medication prior • Consider oral options for IBD and learn about different • Monitor drug level biological markers for IBD • Use JAK inhibitors in IBD patients • Consider JAK inhibitors for difficult to treat IBD patients, • Utilize JAK inhibitors, treat to endoscopic remission. discuss risk with patients and IBD being treated with such • Collaborate with GI doctors, and refer patients to GI for medications therapy • Watch out for Phase 2 trials • Will look into use as first option • Be more aggressive with endoscopy prior to changing • Use scores (mayo, CDA and more) therapy • Proactive assessment of response to therapy • Increase T2T approach, class of medications earlier • Increase endoscopic assessment of remission • Consider as first line, a switch after previous failure • Drug level monitoring, changing med classes Contact Information Brittany Puster VP, Education Development Academy for Continued Healthcare Learning (ACHL) E: [email protected] P: 773-714-0705 ext. 134 C: 303-829-2562