Targeting the JAK/STAT Pathway in Immune-mediated Inflammatory Diseases: Current and Future Directions

Transcription

1 Targeting the JAK/STAT Pathway in Immune-mediated Inflammatory Diseases: Current and Future Directions Interim Outcomes Report February 2019 Gilead Sciences, Inc. Grant ID: 02669

2 Overview Activity Description: This clinical commentary features a video-based digital classroom which includes a didactic clinical review, faculty discussion, and an augmented reality MOA animation. This educational activity provides clinicians with clinical data and expert opinion to aid them in providing the best possible care to their patients with RA and IBD. Launch Date: April 13, 2018 Expiration Date: April 13, 2019 Credit: 1.00 AMA PRA Category 1 Credit TM Sponsored by: The Academy for Continued Healthcare Learning (ACHL) Supported by: An educational grant from Gilead Sciences, Inc. Intended Audience: US-based gastroenterologists, rheumatologists and other clinicians interested in learning more about the JAK/STAT signaling pathway. Activity Availability: Outcomes Methodology: Activity-related changes in clinician knowledge, competence, and performance were evaluated by using pre/posttest questions, evaluation data and post-curriculum assessment survey.

3 Activity Page

4 Executive Summary: Levels 1-2 Participation as of February Clinician Participants; 448 Certificates (1000 participant guarantee) Practicing Type 24% Physicians, 32% Physician Assistants, 11% NP/RNs Participant Satisfaction Objectivity and balance rated as good/excellent by 92% of learners Learning Objectives 99% of learners strongly agree or agree that all learning objectives were met, with an average rating of 3.33/4.0 Faculty Drs. Cohen, Rigby, and Pekow were highly rated 3.48/4.0

5 Executive Summary: Levels % indicated they will change their practice as a result of their participation, with 50% of learners stating that they plan to select a different therapy for their patients. In a 30-day follow-up survey, 100% of learners indicated they made a change in their practice. Learners report a need for continued education on the efficacy and safety of the JAK inhibitors, yet 44% plan to offer new agents in the class to their patients as soon as they are available. Changes made from this activity will impact 2,015 to more than 6,266 IBD patients each month and 4,032 to more than 9,191 RA patients each month. Insurance, lack of knowledge and cost were reported as the most common barriers to implementing changes in practice. Following the activity learners demonstrated increased knowledge of the JAK/STAT signaling pathway, including knowledge of the signaling molecules and the MOA of investigational agents.

6 Executive Summary: Future Education For Gastroenterologists (new MOA for this audience): Continue to differentiate the targets and selectivity of investigational JAK inhibitors Outline available clinical trial data, including population studied (ie, UC vs. CD and treatment-naïve vs. treatment-experienced) Review and provide discussion on available safety data For Rheumatologists: Review clinical trial efficacy and safety data of JAK inhibitors, including population studied, dosing, and efficacy endpoints Discuss selection of therapy in patients with inadequate response to initial therapy, and the role of JAK inhibitors in current treatment paradigms since learners demonstrated a lack of awareness of available guidelines and the role of JAK inhibitors Incorporate education specific to PAs given the number of learners in this activity and increasing role in rheumatology

7 Level 1: Participation Participants Certificates Participation by Specialty Family Medicine/General Practice Participation by Clinician Type Physician 34% Physician Assistant Nurse Practitioner Nurse Other HCP 24% Orthopedics Internal Medicine Rheumatology/Gastroenterology Emergency Medicine Surgery 4% Pain Medicine Other 6% 19% 14% 10% 7% 6% 5% 32% 29% 11%

8 Level 2: Learning Objectives Please rate the following objectives to indicate if you are better able to: Discuss the role of the JAK/STAT signaling pathway in the inflammation and disease progression of immune-mediated inflammatory diseases Evaluate the use of JAK inhibitors in immune-mediated inflammatory diseases such as RA and IBD Interpret clinical trial efficacy and safety data of JAK inhibitors under investigation across inflammatory diseases Outline approaches to educating patients on the role of JAK inhibition, including efficacy and safety data Analysis of Respondents Rating scale: 4=Strongly Agree; 1=Strongly Disagree % of learners strongly agree or agree that all learning objectives were met, with an average rating of 3.33/4.0 N=440

9 Level 2: Faculty Evaluation Please rate the faculty on the criteria listed Rating scale: 4=Excellent; 1=Poor Ability to effectively convey the subject matter Expertise on the subject matter Russell Cohen, MD William Rigby, MD Joel Pekow, MD The faculty were rated good or excellent across all areas by 97% of learners, with an average rating of 3.48/4.0 96% of participants would recommend this activity to a colleague! N=438

10 Objectivity & Balance Did you perceive any bias? 8% 100% 90% 80% 70% 60% 50% 40% 30% Objectivity & Balance 57% 42% 92% Yes No 20% 10% 0% 2% Excellent Good Fair Poor N=440 Activity was perceived as objective, balanced and non-biased

11 Clinicians Who Manage IBD: Confidence How would you rate your level of confidence describing the JAK inhibitors under investigation for IBD? Pre (n=399) Post (n=229) Extremely confident 11% 28% Very confident 22% 50% Not very confident 21% 50% Not at all confident 1% 17% 0% 10% 20% 30% 40% 50% 60% These data indicate a substantial shift in confidence with the JAK inhibitors under investigation for IBD: 78% of learners reported being extremely or very confident after their participation compared with 33% preparticipation.

12 Clinicians Who Manage RA: Confidence How comfortable are in you prescribing the available JAK inhibitors for your patients with RA? Pre (n=441) Post (n=217) Extremely confident 14% 29% Very confident 24% 50% Not very confident 20% 44% Not at all confident 1% 18% 0% 10% 20% 30% 40% 50% 60% These data indicate a substantial shift in confidence with prescribing the available JAK inhibitor at the time of launch; 78% of learners reported being extremely or very confident after their participation compared with 38% before participation. Tofacitinib was the only JAK inhibitor approved at the time of launch; this question has been updated

13 Levels 3-4: Pretest vs. Posttest Overview of Correct Responses Topic % Change JAK/STAT Molecules* 120% 100% 97% 88% 91% Pre Post JAK/STAT Pathway* 129% Filgotinib MOA* 120% Adverse Events* 160% 80% 60% 40% 44% 28% 64% 40% 35% 49% 51% 46% 41% 25% 34% Filgotinib Clinical Trial Data 20% 20% Tofacitinib Guideline Recommendation 11% Efficacy of JAK Inhibitors 36% 0% Topic 1 Topic 2 Topic 3 Topic 4 Topic 5 Topic 6 Topic 7 Participants demonstrated improved knowledge and competence on seven of seven pre/posttest questions. * Includes combined data from clinicians who see RA and IBD patients

14 Levels 3-5: Pretest vs. Posttest vs. Follow-up JAK/STAT family Pre (n=589) Post (n=449) Follow-up (n=5) 1. To date, how many members of the JAK family of nonreceptor tyrosine kinases have been identified? A. 1 B. 2 C. 4 D. 6 The percent of learners correctly answering this question increased from 44% to 97%, indicating a robust increase in knowledge of members of the JAK/STAT signaling pathway. In a 30-day follow-up survey 80% of participants were still able to correctly identify the number of JAK family nonreceptor tyrosine kinases members. 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 97% 80% 44% 29% 20% 20% 7% 0% 2% 0% 1% A B C D

15 Levels 3-4: Pretest vs. Posttest JAK/STAT Pathway Pre (n=587) Post (n=483) 2. Which of the following describes the relationship between TNFalpha and the JAK/STAT signaling pathway? A. TNF-alpha is a negative inhibitor of the JAK/STAT pathway B. TNF-alpha signals via JAK1 homodimers C. TNF-alpha signals via JAK1/JAK2 heterodimers D. TNF-alpha has a different signal transduction pathway The number of learners correctly answering this question increased by 129%. This finding suggests increased knowledge of the JAK/STAT signaling pathway and the differences between TNF-alpha signaling. However, additional education may be warranted since approximately one-third of learners demonstrated a continued lack of knowledge after participation. 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 64% 27% 27% 28% 22% 18% 7% 7% A B C D

16 Levels 3-4: Pretest vs. Posttest Filgotinib MOA Pre (n=586) Post (n=449) 3. The available and emerging JAK inhibitors inhibit different members of the JAK family. The investigational agent filgotinib works by inhibiting which of the following? A. JAK1 B. JAK1/2 C. JAK1/3 D. JAK1/2/3 and Tyk2 The percentage of learners correctly identifying the mechanism of action of filgotinib increased from 40% preactivity to 88% postactivity. The results on this question and the preceding questions confirm that learners in this activity gained knowledge of the JAK/STAT signaling pathway as a target for immune-mediated diseases. 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 88% 40% 28% 19% 12% 2% 4% 6% A B C D

17 Levels 3-4: Pretest vs. Posttest Adverse Events Pre (n=589) Post (n=449) 4. AM, a 45-year old woman who is considering initiation of a JAK inhibitor asks about the potential risk of developing cancer given her knowledge of the biologic therapies. Based on a long-term analysis of the safety of tofacitinib for the treatment of RA, which of the following would you highlight as having the highest incidence rate during your discussion with AM? A. Malignancies B. Serious infections C. Herpes zoster infection D. GI perforations The percentage of learners correctly responding to this question on counseling patients on potential adverse events with the available JAK inhibitor increased by 160% after participation. This finding suggests increased familiarity with accumulating data on the safety of this class of agents. 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 91% 34% 35% 22% 9% 2% 4% 3% A B C D

18 Levels 3-4: Pretest vs Posttest* Filgotinib Clinical Trial Data Pre (n=335) Post (n=204) 5. Which of the following statements on available clinical trial data with filgotinib in IBD is correct? A. One-third of ulcerative colitis patients receiving filgotinib achieved clinical remission, but benefits have not been demonstrated in Crohn s disease 100% 90% 80% 70% B. Filgotinib was effective as induction therapy for IBD, but not as maintenance therapy C. Approximately one-half of Crohn s disease patients achieved clinical remission in a clinical trial D. Filgotinib failed to demonstrate benefits in a clinical trial of Crohn s disease patients due to a high placebo Baseline knowledge of the clinical trial data with filgotinib was low and remained low despite faculty discussions and review of the FITZROY study. Future education should continue to focus on the clinical trial efficacy and safety data, emphasizing differences in patient populations, the mechanisms of action of the JAK inhibitors, and efficacy endpoints. 60% 50% 40% 30% 20% 10% 0% 49% 41% 26% 26% 22% 21% 11% A B C D 4% *Clinicians who manage patients with IBD

19 Levels 3-4: Pretest vs Posttest* Tofacitinib Guideline Recommendation Pre (n=386) Post (n=215) 6. The 2015 American College of Rheumatology (ACR) guidelines recommend the use of tofacitinib: 100% 90% A. After patients have an inadequate response to at least two TNF inhibitors B. In patients who fail MTX monotherapy or conventional DMARDs C. As monotherapy in patients with early or established RA D. In combination with a biologic DMARD for established RA 80% 70% 60% 50% 40% 30% 35% 34% 46% 51% Although there was a slight increase in the percent of learners accurately identifying the ACR guideline on the use of tofacitinib, these data indicate that clinicians continue to perceive that JAK inhibitors should be reserved after the course of two or more anti-tnf agents. Case-based education in patients with an inadequate response to initial therapy may be a good avenue to address the role of JAK inhibitors in treatment paradigms and their sequential use with biologics. 20% 10% 0% 10% 10% 9% 5% A B C D *Clinicians who manage patients with RA

20 Levels 3-4: Pretest vs Posttest* Efficacy of JAK Inhibitors Pre (n=371) Post (n=256) 7. LG, a 61-year old woman with a 1-year history of RA is considering her next step in therapy after experiencing work-limiting symptoms with methotrexate. How would you counsel her on the time to onset of efficacy with the JAK inhibitors compared with the biologic agents based on randomized clinical trial data? A. The two classes of agents have a comparable time to onset of efficacy B. The time to onset of efficacy varies across the different JAK inhibitors C. The time to onset of efficacy with the JAK inhibitors is longer D. The JAK inhibitors have a faster time to onset of efficacy Despite Dr. Rigby s discussion on the short duration to onset of action in the clinical trials with tofacitinib and investigational JAK inhibitors, learners did not accurately reply to this question. Once additional clinical trial efficacy data are available, education should include discussions on the onset of action. Results from this question and others demonstrate that learners who see patients with RA have a high level of comfort with the biologic agents over newer therapies. 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 34% 28% 28% 28% 26% 25% 19% 12% A B C D *Clinicians who manage patients with RA

21 Level 4: Practice Application As new JAK inhibitors become available, how will you apply them in clinical practice? I will offer them to patients as soon as they are available 44% I will wait to hear of experiences from my colleagues 33% I will wait until additional safety data are available 23% 0% 20% 40% 60% 44% of participants will offer new JAK inhibitors to patients as soon as they are available. N=440

22 Clinicians Who Manage IBD: Patient Impact Number of patients you see with IBD per month: 3% >50 21% 26% 50% Changes will impact 2,015 to more than 6,266 IBD patients each month. This assumes data in chart above is representative of all healthcare professionals that treat patients with IBD (1331), who indicated they would offer JAK inhibitors to their patients as soon as they become available (44%).

23 Clinicians Who Manage RA: Patient Impact Number of patients you see with RA per month: 7% 4% 23% % >50 45% Changes will impact 4,032 to more than 9,191 RA patients each month. This assumes data in chart above is representative of all healthcare professionals that treat patients with RA (1471), who indicated they would offer JAK inhibitors to their patients as soon as they become available (44%).

24 Levels 4-5: Practice Change Please identify how you will change your practice as a result of participating in this activity Select a different therapy for my patients 40% 50% Post-activity (n=440) Follow-up (n=5) Create/revise protocols, policies, and/or procedures 36% 80% Other changes 5% This activity validated my current practice; no changes will be made 25% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 75% of learners will change their practice! Specifically, 50% of those learners indicated that they plan to select a different therapy for their patients. Following a 30-day follow-up survey, 100% of learners indicated they changed their practice following exposure to this education with 80% stating they created/revised protocols, policies and/or procedures. multiple responses allowed

25 Topics of Interest Efficacy of JAK inhibitors Safety of JAK inhibitors Case-based education Assisting patients with access to JAK inhibitor therapy Clinical trial updates in JAK therapies Incorporating JAK therapy into treatment Other 1% 13% 15% 18% 26% 39% 46% 0% 20% 40% 60% Efficacy and safety of JAK inhibitors was rated with the highest interest for future education. N=440; multiple responses allowed

26 Barriers to Planned Change Self-reported barriers to planned change Cost Insurance coverage Finances and expense Health promotion Insurance company willing to pay for the medication Lack of knowledge and time Little experience with safety profile Patient cooperate, I will slowly talk and explain detail to them Have to get approval from supervising physician Insurance coverage, time spent with patients Knowledge and experience Lack of patients Lack of skills and knowledge Managed care protocols regarding step care of patients Scope of practice Treatment cost, insurance coverage Time limitations with patients N=199

27 Contact Information Brittany Puster Director, Education Development Academy for Continued Healthcare Learning (ACHL) E: P: ext. 134 C: