OUTCOME STUDY REPORTS

Transcription

1 OUTCOME STUDY REPORTS 2008 Emerging Challenges in Treating Rheumatic Diseases: Jacksonville, Florida Cincinnati, Ohio These activities were supported through an educational grant or donation from the following companies: Genentech and Biogen Idec, Amgen and Wyeth Pharmaceuticals, Bristol-Myers Squibb, Lilly, Centocor, and UCB National Association for Continuing Education (NACE) 7860 Peters Road, Suite F-111, Plantation, Florida

2 Copyright 2008 National Association for Continuing Education All rights reserved. No part of this book may be reproduced without written permission from the authors except for the brief inclusion of quotations in a review. Requests for permission or further information should be addressed to: National Association for Continuing Education 7860 Peters Road, Suite F 111 Plantation, FL Phone: (954) info@naceonline.com Internet:

3 Table of Contents 1 Pages Introduction to Outcome Study 2 Overview of CME Activity Conference Agenda Learner Participation Learner Satisfaction and Comments Topics Desired by Attendees for Future CME Activities Outcome Studies for Individual Topics 7 Mechanistic Insights into New Biologics for Treatment of RA and Lupus 13 Emerging Biologic Therapies for RA: Efficacy and Safety 20 An Update in Treatments for Osteoporosis and Osteonecrosis of the Jaw Case Studies and Discussion 26 Change in Practice Behavior: Follow Up Survey

4 2 Introduction to Outcome Study Overview of CME Activity The National Association for Continuing Education (NACE), held two CME activities entitled Emerging Challenges in Treating Rheumatic Diseases: Update These activities were held on December 6, 2008 in Jacksonville, Florida and on December 13, 2008 in Cincinnati, Ohio. The course director for these activities was Alan Brown, MD. The target audience for these activities was physicians, physician assistants, and nurse practitioners treating patients in a primary care setting and Rheumatologists. The mission of NACE is to offer continuing education opportunities to provide learners in the fields of medicine, behavioral health, education, and related disciplines, with the most up-to-date, science-based information that will enable them to maintain or increase their knowledge, skills, and professional performance. NACE is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. NACE designates this educational activity for a maximum of 4 AMA PRA Category 1 Credits. The planning and delivery of this CME activity conformed with the policies of the ACCME. This activity had also been reviewed and was acceptable for Prescribed credit(s) by the American Academy of Family Physicians. This program was supported through educational grants from the following companies: Amgen, Bristol-Myers Squibb Company, Centocor, Genentech and Biogen Idec, Lilly, UCB, Wyeth. The content of this activity was derived through a needs assessment of a variety of therapeutic areas that included identified gaps in knowledge, competence or performance of physicians and educational objectives in each therapeutic area to narrow these gaps. This CME activity was assessed with respect to Kirkpatrick s first four levels of evaluation: learner participation, learner satisfaction, effect on learner knowledge (and confidence), and effect on practice behavior. Data was collected via paper and pencil survey instruments and electronically via an audience response system at live symposia. NACE used case-based vignettes to demonstrate competence in applying critical knowledge and to measure practitioner practice patterns. The use of case vignettes for this purpose has considerable predictive value. Vignettes, or written case simulations, have been widely used as indicators of actual practice behavior. Peabody et al. (2000; 2004) compared the validity of three methods to assess quality of health care: case vignettes, observation of "standard patient" visits, and chart abstractions. Vignettes were found to be a valid and comprehensive method of assessing quality of health care provided in actual clinical practice. Vignettes can be used for diverse clinical settings, diseases, physician types, and situations in which case-mix variation is a concern. They can be useful to measure the effect of interventions intended to change clinical practice behavior. Peabody, J.W., J. Luck, P. Glassman, S. Jain, J. Hansen, M. Spell and M. Lee (2004). Measuring the quality of physician practice by using clinical vignettes: a prospective validation study. Ann Intern Med14(10): NACE collaborated with Health Link Systems Inc. and Educational Measures Inc. to design the methodology used in the outcome study and to collect and analyze the data with respect to each of topics presented. Conference Agenda The conference agenda was as follows: 7:15-7:45 Registration and Continental Breakfast 7:45-8:00 Welcome Remarks David Dempster, PhD 8:00-9:00 Mechanistic Insights into New Biologics for Treatment of RA and Lupus Gary Gilkeson, MD or James Oates, MD 9:00-10:00 Emerging Biologic Therapies for RA: Efficacy and Safety Alan Brown, MD 10:00-10:15 Break 10:15-11:15 An Update in Treatments for Osteoporosis and Osteonecrosis of the Jaw Case Studies and Discussion Yvonne Sherrer, MD or Nelson Watts, MD 11:15-12:00 Interactive Panel and Case Discussion Learner Participation A total of 87 people attended this activity in the two locations: Jacksonville, Florida and Cincinnati, Ohio. Of those attending, 74% were providers in primary care, 16% were providers in rheumatology, 1% were providers in pulmonology, 1% in gastroenterology, and 8% were providers in other areas unidentified. The breakdown in terms of degree is provided in the table below

5 3 City MD DO NP PA RN Other No Response Total Jacksonville, FL Cincinnati, OH Learner Satisfaction and Comments Attendees were asked to complete survey instruments regarding their satisfaction with the CME activity, whether they found the information presented to be relevant to their practice needs, and the likelihood that they would incorporate new information learned at the activity into their patient care. Compared to other CME activities that I have participated in over the past year, I would rate this activity as.. How effective was this activity in meeting the stated learning objectives? How useful and relevant was the information provided to your practice.

6 How effective will the information you learned during this activity be in helping you improve your skills or judgment? 4 How well did this activity include opportunities to learn interactively from faculty/participants? How likely are you to make changes in your practice based on the information presented during this CME activity?

7 In what areas will you make changes in practice? (Please check all that apply.) 5 How soon will you incorporate the information from this CME activity into your practice? Which statement(s) best reflects your reasons for participating in this activity (Please check all that apply.):

8 6 Future CME activities in these subject areas are necessary. Topic Desired by Attendees for Future CME Activities Vaccines and/or travel consultations Biologic Rx of rheumatoid diseases. Osteoporosis and Inflamatory Bowel Disease Hazards of radiological exposure and its preventive measures Update on results of new biologics for Rx of RA and recommendations Office GYN for PCP's MDS Chronic pain/hiv/chronic infections/osteoarthritis/bone cancer DM/HTN/HIV Diabetes/Hypertension COPD/Dementia/Stroke/Obesity/Epilepsy Psoriatic arthritis treatments/medical-legal aspects of treatment and risk Diabetes Mellitus Communicable diseases like Scabies/Shingles/Bed Bugs/Parasites Diabetes More clinical and less academic Lupus Hypertension and Infectious Diseases Antibiotics and Infectious Disease Fibromyalgia DM/Migraines Anticoagulant therapy/hypo and Hyperthyroidism Diabetes/Obesity/Depression/Bipolar disorder/thyroid Disease Thyroid Disorders/Abnormal Uterine Bleeding/Gestational Updates Overview of diagnosis and treatment of Rheumatic Diseases Any topic concerning Adult Rheumatology Diagnosis and treatment of Rheumatoid Arthritis Fibromylgia/Chronic Fatigue Syndrome Pulmonary/Cardiology Fibromyalgia/OA Nutritional Medicine/Anti-aging Medicine Male hormone deficiency and replacement dynamics Dermatological indicators of systemic disease The following pages describe the responses of attendees to questions specific to each topic presented.

9 7 Mechanistic Insights into New Biologics for Treatment of RA and Lupus Emerging Challenges in Treating Rheumatic Diseases Jacksonville, FL December 6, 2008 Cincinnati, OH December 13, 2008 Course Director Alan Brown, MD Associate Professor of Medicine Division of Rheumatology and Immunology Vice Chairman for Education Department of Medicine Medical University of South Carolina Charleston, SC Presenters Gary Gilkeson, MD Professor and Vice Chair for Research Department of Medicine Medical University of South Carolina Staff Physician, Ralph H. Johnson VAMC Charleston, SC James Oates, MD Department of Medicine Medical University of South Carolina Charleston, SC

10 8 Mechanistic Insights into New Biologics for Treatment of RA and Lupus Presenters: Gary Gilkeson, MD and James Oates, MD Executive Summary The topic, Mechanistic Insights into New Biologics for Treatment of RA and Lupus, was presented in Jacksonville, Florida and Cincinnati, Ohio as part of a half-day CME activity entitled Emerging Challenges in Treating Rheumatic Diseases: Update The need for continued education in the evaluation and management of patients at risk for, and suffering from, rheumatoid arthritis and systemic lupus erythematosus, was demonstrated based on the literature review and survey data described below. Gary Gilkeson, MD and James Oates, MD received very high ratings on their effectiveness in delivering this material that would improve understanding of the immunopathology of Rheumatic diseases such as RA and Systemic Lupus Erythematosus and new therapies to treat these conditions. Attendee knowledge was assessed using the questions and case vignettes listed above. Results indicated some improvement between pre and post-testing, but not to the level of significance expected. There was a moderate increase in confidence levels in the management of these patients as reported by conference attendees. There remains a clear gap in knowledge and an unmet need amongst Rheumatologists and primary care clinicians to learn more about the immunopathology of diseases such as RA and SLE and new therapies. This continues to be an important area for future educational programs. Additional programming should continue to educate clinicians on the pathogenesis of RA and SLE and emerging possibilities for treatment of each of these diseases. Statement of Need for Mechanistic Insights into New Biologics for Treatment of RA and Lupus Literature Review Many of the rheumatic diseases involve disorders of the immune system, and a better understanding of the immunopathology of diseases such as rheumatoid arthritis, ankylosing spondylitis and systemic lupus erythematosus, is leading to exciting new therapies. The diagnostic and predictive value of autoantibodies is well recognized, and a variety of autoantibodies have been studied. [1-3] Early and aggressive management of rheumatic diseases with immunomodulators and biologics is increasingly being emphasized, and response rates are being further enhanced by using combinations of these agents. [4, 5] Methotrexate and leflunomide are disease modifying antirheumatic drugs (DMARDs) that exert immunomodulatory effects. [6] Etanercept inhibits tumour necrosis factor alpha (TNFα), a key cytokine in the inflammatory cascade. [7] Infliximab and adalimumab are monoclonal antibodies that also inhibit TNFα. [8] Rituximab is a mononclonal antibody to CD20 that reduces the number of circulating B-cells. [9] Abatacept prevents complement fixation and modulates the signals required for T-cell activation. [10] Survey Data Needs assessment surveys given to 88 Rheumatologists and primary care providers. These respondents indicated a strong interest in learning more about immunological process involved in rheumatic diseases. At the conclusion of this CME activity, attendees will be able to: Explain the immunological process involved in rheumatic diseases Discuss basic immunology as it applies to current therapies for rheumatic disease List various biologic therapies undergoing clinical development Discuss the mechanisms of action of emerging biologic therapies

11 Speaker Bias Attendees were also asked to rate the extent to which each speaker presented information in a manner that was fair, balanced, and free of commercial bias on a five-point scale, with one being Unsatisfactory and five being Excellent. Speaker Excellent Very Good Good Fair Unsatisfactory Gilkeson 80% 13% 6% 2% 0% Oates 87% 10% 3% 0% 0% Effect on Learner Knowledge Case Vignettes, Questions, and Preferred Answers (bolded) The following questions were delivered through an ARS system to attendees at the CME activities in which this topic was presented. Pre and post test responses were collected from attendees who responded to the ARS questions. The graphs below (first bar=pre; second bar=post; preferred answer in bold) display the results of each question below. Which of the following therapies would be least likely to be effective? 1. Increasing the etanercept to twice a week 2. Get compassionate use for anti-alpha interferon 3. Switch to rituximab 4. Switch to abatacept P Value: Not Significant 9 Which B cell function is likely to be playing an important pathogenic role in disease in this patient? 1. Production of autoantibodies 2. Serving as an antigen presenting cell 3. Production of inflammatory cytokines 4. All of the above

12 10 Which T cell subset is potentially suppressed in autoimmune diseases? 1. Th1 subset 2. Th2 subset 3. Th17 subset 4. Treg subset P Value: Not Significant Effect on Learner Confidence Confidence in treating patients with this condition was measured during the pre and post-tests. Practitioner confidence relates directly to the likeliness of actively using knowledge. Practitioner confidence in his/her ability to diagnose and treat a disease or condition can affect practice behavior patterns. On a scale of 1 to 7 please rate how confident you would be in treating a patient with this condition. 1. Not at all confident 2. Only slightly confident 3. Somewhat confident 4. Moderately confident 5. A little more than moderately confident 6. Pretty much confident 7. Very confident Summary and Conclusions The need for continued education in the evaluation and management of patients at risk for, and suffering from, rheumatoid arthritis and systemic lupus erythematosus, was demonstrated based on the literature review and survey data described below. Gary Gilkeson, MD and James Oates, MD received very high ratings on their effectiveness in delivering this material that would improve understanding of the immunopathology of Rheumatic diseases such as RA and Systemic Lupus Erythematosus and new therapies to treat these conditions. Attendee knowledge was assessed using the questions and case vignettes listed above. Results indicated some improvement between pre and post-testing, but not to the level of significance expected. There was a moderate increase in confidence levels in the management of these patients as reported by conference attendees.

13 11 There remains a clear gap in knowledge and an unmet need amongst Rheumatologists and primary care clinicians to learn more about the immunopathology of diseases such as RA and SLE and new therapies. This continues to be an important area for future educational programs. Additional programming should continue to educate clinicians on the pathogenesis of RA and SLE and emerging possibilities for treatment of each of these diseases. References 1. Hueber W, Utz PRobinson W. Autoantibodies in early arthritis: Advances in diagnosis and prognostication. Clin Exp Rheumatol 2003;21 (Suppl 31):S59-S Pope RM, Keightley R McDuffy S. Circulating autoantibodies to IgD in rheumatic diseases. J Immunol 1982;128(4): Leslie D, Lipsky PNotkins A. Autoantibodies as predictors of disease. J. Clin. Invest 2001;108(10): Fleischmann RM. Is there a need for new therapies for rheumatoid arthritis? J Rheumatol Suppl 2005;73:3-7; discussion Blumenauer B, Judd M, Wells G, Burls A, Cranney A, Hochberg M, Tugwell P. Infliximab for the treatment of rheumatoid arthritis. Cochrane Database of Systematic Reviews 2002, Issue 3. Art. No.: CD DOI: / CD Kraan M, Smeets T, van Loon M, et al. Differential effects of leflunomide and methotrexate on cytokine production in rheumatoid arthritis. Ann Rheum Dis 2004;63: Blumenauer B, Judd M, Cranney A, Burls A, Coyle D, Hochberg M, Tugwell P,Wells G. Etanercept for the treatment of rheumatoid arthritis. Cochrane Database of Systematic Reviews 2003, Issue 4. Art. No.: CD DOI: / CD Y-F Chen Y-F, Jobanputra P, Barton P, et al. A systematic review of the effectiveness of adalimumab, etanercept and infliximab for the treatment of rheumatoid arthritis in adults and an economic evaluation of their cost-effectiveness. Health Technology Assessment 2006;10(42). 9. Summers KM, Kockler DR. Rituximab Treatment of Refractory Rheumatoid Arthritis. Ann Pharmacother 2005;39(12): Genovese MC, Becker J-C, Schiff M, et al. Abatacept for Rheumatoid Arthritis Refractory to Tumor Necrosis Factor {alpha} Inhibition. N Engl J Med 2005;353(11):

14 12 Emerging Biologic Therapies: Efficacy and Safety Emerging Challenges in Treating Rheumatic Diseases: Update 2008 Jacksonville, FL December 6, 2008 Cincinnati, OH December 13, 2008 Presenter Alan Brown, MD Associate Professor of Medicine Division of Rheumatology and Immunology Vice Chairman for Education Department of Medicine Medical University of South Carolina Charleston, SC

15 Emerging Biologic Therapies: Efficacy and Safety Presenter: Alan Brown, MD 13 Executive Summary The topic, Emerging Biologic Therapies: Efficacy and Safety, was presented in Jacksonville, Florida and Cincinnati, Ohio as part of a half-day CME activity entitled Emerging Challenges in Treating Rheumatic Diseases: Update The need for continued education concerning emerging biologic therapies in the evaluation and management of patients at risk for, and suffering from, rheumatoid arthritis, was demonstrated based on the literature review and survey data described below. Dr. Alan Brown received very high ratings on his effectiveness in delivering this material. Attendee knowledge was assessed using the questions and case vignettes listed above with results indicating a small, but not significant, improvement in knowledge. Participants were somewhat more likely, as a result of this lecture, to gain a greater understanding of the mechanisms of action of emerging biologic therapies in the management of rheumatoid arthritis, however, differences in pre and post-test data was not significant in any of three questions asked of attendees. Attendees who completed a follow up survey sent four weeks after the educational activity indicated that they have greater knowledge of various biologic therapies undergoing clinical development for Rheumatic diseases. Emerging biologic therapies continues to be an important area for future educational programs. Additional programming should continue to educate clinicians on the rapidly expanding field of biologic therapy for rheumatoid arthritis. Statement of Need for Postmenopausal Osteoporosis and Osteoporosis in Men Literature Review The treatment of rheumatic diseases is being revolutionized by "biologic agents," including tumor necrosis factor (TNF) inhibitors and monoclonal antibodies. The efficacy of etanercept, infliximab, adalimimab, rituximab, and abatacept is already known, but even more promising biologics are on the way. Ocrelizumab, a humanized anti-cd20 monoclonal antibody, has demonstrated clinical activity at various doses in patients with rheumatoid arthritis (RA), and is generally well tolerated. [1] Ofatumumab, another humanized monoclonal anti-cd20 antibody, induces less apoptosis than rituximab, and has been associated with an ACR50 in 20-25% in RA patients who had incomplete responses with DMARDs. [2, 3] Tocilizumab, an IL-6 receptor antagonist, can improve the signs and symptoms of active RA in patients with an inadequate response to MTX monotherapy, [4] and has also demonstrated benefit in children with systemic-onset juvenile idiopathic arthritis. [5] Rilonacept, an IL-1 inhibitor, can suppress pain and reduce hs-crp levels in patients with refractory chronic active gouty arthritis. [6] Certolizumab and golimumab are TNF antagonists with advantages of infrequent subcutaneous administration, and can be useful in managing patients with RA or psoriatic arthritis (PSA). [7-9] Several clinical trials involving these agents are in progress. Survey Data Needs assessment surveys given to 88 Rheumatologists and primary care providers. These respondents indicated a strong interest in learning more biologic therapies for RA undergoing clinical development. Gaps in understanding the mechanisms of action of emerging biologic therapies and potential consequences of treatment with new biologic agents were identified. This program, Emerging Biologic Therapy: Efficacy and Safety, covered the following learning objectives. Evaluate potential consequences of treatment with new biologic agents Describe the risks versus benefits of biologic agents in rheumatic diseases Discuss current data on adverse effects of biologic agents and safety issues

16 Speaker Bias Attendees were also asked to rate the extent to which each speaker presented information in a manner that was fair, balanced, and free of commercial bias on a five-point scale, with one being Unsatisfactory and five being Excellent. Speaker Excellent Very Good Good Fair Unsatisfactory Alan Brown, MD Effect on Learner Knowledge Case Vignettes, Questions, and Preferred Answers (bolded) The following questions were delivered through an ARS system to attendees at the CME activities in which this topic was presented. Pre and post test responses were collected from attendees who responded to the ARS questions. The graphs below (first bar=pre; second bar=post; preferred answer in bold) display the results of each question below. Which of the following therapies would be least likely to be effective? 1. Increasing the etanercept to twice a week 2. Get compassionate use for anti-alpha interferon 3. Switch to rituximab 4. Switch to abatacept P Value: Not Significant 14 Which B cell function is likely to be playing an important pathogenic role in disease in this patient? 1. Production of autoantibodies 2. Serving as an antigen presenting cell 3. Production of inflammatory cytokines 4. All of the above P Value: Not Significant

17 15 Which T cell subset is potentially suppressed in autoimmune diseases? 1. Th1 subset 2. Th2 subset 3. Th17 subset 4. Treg subset P Value: Not Significant Effect on Learner Confidence Confidence in treating patients with this condition was measured during the pre and post-tests. Practitioner confidence relates directly to the likeliness of actively using knowledge. Practitioner confidence in his/her ability to diagnose and treat a disease or condition can affect practice behavior patterns. On a scale of 1 to 7 please rate how confident you would be in treating a patient with this condition. 1. Not at all confident 2. Only slightly confident 3. Somewhat confident 4. Moderately confident 5. A little more than moderately confident 6. Pretty much confident 7. Very confident Summary and Conclusions The need for continued education concerning emerging biologic therapies in the evaluation and management of patients at risk for, and suffering from, rheumatoid arthritis, was demonstrated based on the literature review and survey data described above. Dr. Alan Brown received very high ratings on his effectiveness in delivering this material. Attendee knowledge was assessed using the questions and case vignettes listed above with results indicating a small, but not significant, improvement in knowledge. Participants were somewhat more likely, as a result of this lecture, to gain a greater understanding of the

18 16 mechanisms of action of emerging biologic therapies in the management of rheumatoid arthritis, however, differences in pre and post-test data was not significant in any of three questions asked of attendees. Attendees who completed a follow up survey sent four weeks after the educational activity indicated that they have greater knowledge of various biologic therapies undergoing clinical development for Rheumatic diseases. Emerging biologic therapies continues to be an important area for future educational programs. Additional programming should continue to educate clinicians on the rapidly expanding field of biologic therapy for rheumatoid arthritis. References 1. Genovese M, Kaine J, Kohen M, et al. 6 (Poster). Safety and Clinical Activity of Ocrelizumab (a Humanized Antibody Targeting CD20+ B Cells) in Combination with Methotrexate in Moderate-Severe Rheumatoid Arthritis Patients (Ph I/I I ACTION Study). ACR 2006 Highlights. Available from: 2. Østergaard M, Baslund B, Rigby W, et al. Ofatumumab, a human CD20 monoclonal antibody, in the treatment of rheumatoid arthritis: early results from an ongoing, double-blind, randomized, placebo controlled clinical trial. Program and abstracts of the American College of Rheumatology (ACR) 71st Annual Meeting; November 6-11, 2007; Boston, Massachusetts [Abstract #2086] In Update on Novel and Emerging Therapies for RA: Report From the ACR 2007 Annual Meeting Available from: 3. Bello C, Sotomayor EM. Monoclonal Antibodies for B-Cell Lymphomas: Rituximab and Beyond. Hematology 2007;2007(1): The IL-6 Receptor Antagonist Tocilizumab Shows Promise for the Treatment of RA. Summary of the study by Maini et al. Chugai Humanized Anti-Human Recombinant Interleukin-Six Monoclonal Antibody Study (CHARISMA). Arthritis Rheum 2006; 54: Available from: 5. Yokota S, Miyamae T, Imagawa T, et al. Clinical Study of Tocilizumab in Children With Systemic-Onset Juvenile Idiopathic Arthritis. Clin Rev Allergy Immunol 2005;28: Terkeltaub R, Schumacher H, Sundy J, et al. Abstract 518: Placebo-Controlled Pilot Study of Rilonacept (IL- 1 Trap), A Long Acting IL-1 Inhibitor, In Refractory Chronic Active Gouty Arthritis. ACR/ARHP Scientific Meeting Available from: 7. Tracey D, Klareskog L, Sasso EH, et al. Tumor necrosis factor antagonist mechanisms of action: A comprehensive review. Pharmacol Ther 2008;117(2): Zhou H, Jang H, Fleischmann RM, et al. Pharmacokinetics and Safety of Golimumab, a Fully Human Anti- TNF-{alpha} Monoclonal Antibody, in Subjects With Rheumatoid Arthritis. J Clin Pharmacol 2007;47(3): Mease P. Psoriatic Ar thritis: Treatment Advances with Biologic Agents. US Dermatol Rev 2006:1-6.

19 17 An Update in Treatments for Osteoporosis and Osteonecrosis of the Jaw Case Studies and Discussion Emerging Challenges in Treating Rheumatic Diseases: Update 2008 Jacksonville, FL December 6, 2008 Cincinnati, OH December 13, 2008 Presenter Yvonne Sherrer, MD Medical Director/Director Clinical Research Center for Rheumatology, Immunology and Arthritis Fort Lauderdale, FL Nelson Watts, MD Professor of Medicine Director, Osteoporosis and Bone Health Program University of Cincinnati Cincinnati, OH

20 An Update in Treatments for Osteoporosis and Osteonecrosis of the Jaw Presenters: Yvonne Sherrer, MD and Nelson Watts, MD 18 Executive Summary The topic, Treatments for Osteoporosis and Osteonecrosis of the Jaw, was presented in in Jacksonville, Florida and Cincinnati, Ohio as part of the half day program, Emerging Challenges in Treating Rheumatic Diseases. The need for continued education in the evaluation and management of patients at risk for, and suffering from, Osteoporosis and Osteonecrosis of the jaw was demonstrated based on the literature review, survey data, and outcome findings described below. Gaps in knowledge of the application of 2008 NOF Guidelines and the WHO algorithm were narrowed. Both Yvonne Sherrer, MD and Nelson Watts, MD received very high ratings on their effectiveness in delivering this material in an unbiased manner. Pre-test and post-test question regarding knowledge of 2008 NOF Guidelines and the WHO algorithm (FRAX) and pharmacologic management of Osteoporosis and Osteonecrosis of the jaw was asked of attendees. Participants in this activity were significantly more likely, as a result of this program, to recognize who should be screened for Osteoporosis using the 2008 NOF Guidelines and how they should be managed. There was also an increase in confidence levels in the management of these patients, as reported by conference attendees. Education about Osteoporosis and Osteonecrosis of the jaw appears to be an important area for future medical education programs. Additional programming should continue to educate clinicians on the National Osteoporosis Foundation Guidelines, use of the FRAX scoring system for management of Osteoporosis, and recognition of risks and benefits of various non-pharmacologic and pharmacologic treatment regimens. Statement of Need for Pathophysiology and Treatment of Paget s Disease Literature Review The US Surgeon General s report [1]stated that bone health is critically important to the overall health and quality of life of Americans and that the bone health status of Americans appears to be in jeopardy. Fractures caused by bone disease are common and costly. More than 1.5 million people suffer a bone-disease related fracture annually and this figure underestimates the true impact of bone disease as it captures the problem at one point in time. The report goes on to point out that significant progress has been made in recent years both in terms of diagnostic imaging and the introduction of effective treatments for osteoporosis, hyperparathyroidism, rickets and osteomalacia, and Paget s. Despite this, however, too little of what has been learned about bone health has been applied in practice. According to the report, one of the key reasons for this gap between knowledge and practice is a lack of awareness of bone disease among both the public and health care professionals, many of whom are unaware of the magnitude of the problem, let alone the ways in which bone disease can be prevented and treated. In February 2008 the National Osteoporosis Foundation (NOF) issued guidelines intended as a reference for clinicians in diagnosing and treating osteoporosis in men 50 years old and older and in post menopausal women. The guidelines remind clinicians that osteoporosis can be prevented and detected and treated before any fracture occurs and even after the first fracture has occurred. Updated recommendations by the NOF discuss prevention, risk assessment, diagnosis and treatment and provides indications for performing bone densitometry as well as fracture risk thresholds mandating pharmacologic intervention. [2] This program will address this discrepancy between knowledge and practice by discussing unmet needs evidencebased guidelines for the detection, prevention and treatment of common disorders of bone and mineral metabolism. Survey Data Needs assessment surveys given to 88 Rheumatologists and primary care providers. These respondents indicated a strong interest in learning more current guidelines for the assessment, diagnosis and treatment of Osteoporosis and Osteonecrosis of the jaw.

21 19 Educational Goal and Learning Objectives This educational program, An Update in Treatments for Managing Osteoporosis and Osteonecrosis of the Jaw, for rheumatologists, rheumatology nurse practitioners and primary care providers treating rheumatic diseases, will discuss national guidelines for treatment of Osteoporosis and the mechanism of action as well as safety and efficacy of therapies. At the conclusion of this CME activity, attendees will be able to: Discuss and implement current guidelines for the assessment, diagnosis and treatment of Osteoporosis and Osteonecrosis of the Jaw Explain the mechanism of action, safety, and efficacy of therapies Speaker Bias Attendees were also asked to rate the extent to which each speaker presented information in a manner that was fair, balanced, and free of commercial bias on a five-point scale, with one being Unsatisfactory and five being Excellent. Speaker Excellent Very Good Good Fair Unsatisfactory Sherrer 78% 16% 6% 0% 0% Watts 87% 13&% 0% 0% 0% Effect on Learner Knowledge (Dr. Sherrer s Presentation in Jacksonville) Case Vignettes, Questions, and Preferred Answers (bolded) The following questions were delivered through an ARS system to attendees at the CME activities in which this topic was presented. Pre and post-test responses were collected from attendees who responded to the ARS questions. The graphs below (first bar=pre; second bar=post; preferred answer in bold) display the results of each question below. Ms. S is a 79 y.o African American. 8 years ago she tripped on a broken side walk and fractured her wrist. She recovered quickly and well. She has had no other health problems. She takes no medications. She is a non smoker and non drinker. Calcium intake is 1500mg daily. She still works at a job where she mostly stands or walks about approx 5 hours/day 5 days a week. Every morning she arises and walks 3 miles. A BMD is done at the request of her pushy daughter. L1-L4 T score is -0.5, the femoral neck T score is You should tell her daughter that: 1. Mom is healthy and active and in a low risk group for osteoporosis. No treatment is necessary. 2. Mom has osteopenia but is healthy and active. Optimize vitamin D, calcium, and exercise. Repeat the BMD in 1-2 years. 3. Based on T score results, Mom has osteopenia requiring treatment. Start therapy with Evista. 4. Mom needs a FRAXtm Score calculation to assess whether or not treatment is indicated. 5. Rheumatoid Arthritis 6. 3 & & 2

22 P Value: < Significant 20 You calculate the FRAX score for Ms S. The score for MOFX is 22%and for the hip is 6.7%. The following is true concerning these scores: 1. The FRAX is based on 5 year fracture risk. 2. The FRAX is based on 10 year fracture risk. 3. Ms. S does not require drug treatment because the MOFx is less than 25% 4. Ms S does not require drug treatment because the hip risk is less than 10%. P Value: < Significant Based on Ms S T scores (spine -0.5, fem neck -1.8) and FRAX Scores (MOFx-22%, Hip-6.7%), which of the following is the best course of action: 1. Optimize Vit D and calcium, start therapy with raloxifene 2. Optimize Vit D and calcium, start therapy with a bisphosphonate 3. Optimize Vit D and calcium, start therapy with teriparatide 4. Optimize Vit D and calcium, start therapy with calcitonin 5. Optimize Vit D, calcium and exercise. Repeat BMD in one year to asses response. P Value: < Significant

23 21 Effect on Learner Confidence (Dr. Sherrer s Presentation in Jacksonville) Confidence in treating patients with this condition was measured during the pre and post-tests. Practitioner confidence relates directly to the likeliness of actively using knowledge. Practitioner confidence in his/her ability to diagnose and treat a disease or condition can affect practice behavior patterns. On a scale of 1 to 7 please rate how confident you would be in treating a patient with this condition. 1. Not at all confident 2. Only slightly confident 3. Somewhat confident 4. Moderately confident 5. A little more than moderately confident 6. Pretty much confident 7. Very confident Effect on Learner Knowledge (Dr. Watts Presentation in Cincinnati) Case Vignettes, Questions, and Preferred Answers (bolded) The following questions were delivered through an ARS system to attendees at the CME activities in which this topic was presented. Pre and post-test responses were collected from attendees who responded to the ARS questions. The graphs below (first bar=pre; second bar=post; preferred answer in bold) display the results of each question below. She is a candidate for pharmacologic therapy because of 1. Her age 2. Her weight 3. Her loss of height 4. Her fracture risk Data not collected do to technical difficulties. Her risk of fracture 1. Is greater for hip than for spine 2. Is ~20% over the next 10 years 3. Is 5-fold higher than a healthy young woman 4. Will be reduced by ~20% with treatment

24 P Value: Significant 22 If she takes a bisphosphonate for osteoporosis, her risk of ONJ is 1. 1 in in in 100, in 1,000, 000 P Value: Not Significant Effect on Learner Confidence (Dr. Watts Presentation in Cincinnati) Confidence in treating patients with this condition was measured during the pre and post-tests. Practitioner confidence relates directly to the likeliness of actively using knowledge. Practitioner confidence in his/her ability to diagnose and treat a disease or condition can affect practice behavior patterns. On a scale of 1 to 7 please rate how confident you would be in treating a patient with this condition. 1. Not at all confident 2. Only slightly confident 3. Somewhat confident 4. Moderately confident 5. A little more than moderately confident 6. Pretty much confident 7. Very confident

25 23 Summary and Conclusions The need for continued education in the evaluation and management of patients at risk for, and suffering from, Osteoporosis and Osteonecrosis of the jaw was demonstrated based on the literature review, survey data, and outcome findings described above. Gaps in knowledge of the application of 2008 NOF Guidelines and the WHO algorithm were narrowed. Both Yvonne Sherrer, MD and Nelson Watts, MD received very high ratings on their effectiveness in delivering this material in an unbiased manner. Pre-test and post-test question regarding knowledge of 2008 NOF Guidelines and the WHO algorithm (FRAX) and pharmacologic management of Osteoporosis and Osteonecrosis of the jaw was asked of attendees. Participants in this activity were significantly more likely, as a result of this program, to recognize who should be screened for Osteoporosis using the 2008 NOF Guidelines and how they should be managed. There was also an increase in confidence levels in the management of these patients, as reported by conference attendees. Education about Osteoporosis and Osteonecrosis of the jaw appears to be an important area for future medical education programs. Additional programming should continue to educate clinicians on the National Osteoporosis Foundation Guidelines, use of the FRAX scoring system for management of Osteoporosis, and recognition of risks and benefits of various non-pharmacologic and pharmacologic treatment regimens. References 1. U.S. Department of Health and Human Services. Bone Health and Osteoporosis: A Report of the Surgeon General. Rockville, MD: U.S. Department of Health and Human Services, Office of the Surgeon general, National Osteoporosis Foundation. Published online February 21,

26 Change in Practice Behavior Follow Up Survey Data 24 The ultimate goal of the CME activity was to influence participants to apply competencies and critical knowledge learned in the CME activity in their medical practice. Practitioner's self-ratings on a survey measuring perceived change in practice behavior in each of the learning objectives was used as an indicator of actual changes that could ultimately lead to improved patient care and health outcomes. Approximately four weeks after the CME activity, attendees were asked to rate how much they agree with the following statements on a five point scale: As a result of attending this program I have made changes in my practice behavior and I am able to describe the epidemiology and pathogenesis of common bone diseases: Osteoporosis, Bone Cancer, Paget s Disease. I have made changes in my practice behavior that enable me to understand and implement current guidelines for the assessment, diagnosis and treatment of bone diseases. I have made changes in my practice behavior and I am more aware of the gap between knowledge and practice in the management of bone diseases and strategies for rectifying this.

27 I have made changes in my practice behavior and I can understand the mechanism of action of current approved therapies for bone diseases, as well as those in development. 25 Sample Comments Keep up the good work-very good new information Very good seminar The first lecture was way too much in-depth Very good Dr. Gilkeson's talk was a bit over my head but it was well done. Dr. Brown's talk was very informative but a little fast for me to group Common problems encountered by general practitioners Very good speakers and highly informative Excellent job. Thank you. Lots of grey areas and limitations in research data that translates to practice guidelines. Women on long Excellent CME! Dr. Gilkeson was a little too advanced for me. I felt I needed a pathophysiology class before. Dr. Brown was very entertaining. Dr. S Great speakers and content. When a question is asked from the audience please repeat the question before answering Please enlarge some of the busy handout questions particulary in the 1st lecture I would have preferred more clinical information Thank you This was an excellent program. I like most primary care involvement so they can appreciate T/T rheumatologists Excellent presentation! Thanks! Some information was too specialized. Unable to apply this to my daily practice Great conference!! One of the best CME's I have attended thanks I feel that Dr. Oates was a very good presenter but there was quite a lot on his slides to digest in 1 hour. I've read a lot about the TN I'm in administrative medicine now Great topics and speakers. Would appreciate bibliography of resources. Very good

28 Conference Registration Please print or type. Register online at or this form may be mailed or faxed. Onsite registration will be accepted provided space is available. Return completed form to: National Association for Continuing Education (NACE), 7860 Peters Road, F-111, Plantation, Florida For Registration Phone Toll Free: Fax: Personal Information First Name Middle Initial Last Name Degree License Number Mailing Address City State Zip Code/Postal Code Day Phone Number Eve. Phone Number Fax Address (Required) Check one: Physician Physician Assistant Nurse Practitioner Nurse Other Emerging Challenges in Treating Rheumatic Diseases: 2008 Saturday, December 6, 2008 At the Omni Jacksonville Hotel 245 Water Street, Jacksonville, FL (904) Emerging Challenges in Treating Rheumatic Diseases: 2008 EARN CONTINUING MEDICAL EDUCATION CREDITS This activity is for rheumatologists, rheumatology nurse practitioners and physician assistants, and primary care providers treating rheumatic diseases. Join us Jacksonville, FL December 6, Peters Road F-111 Plantation, Florida at the Omni Jacksonville Hotel NACE designates this educational activity for a maximum of 4 AMA PRA Category 1 Credits. There is no charge for this activity. Attendees must register in advance. Reservations for this program will be taken on a first come, first reserved basis. Space is limited so please register early. You will receive a confirmation as to your registration by mail or . This confirmation will serve as your admission ticket for the program. PRESORT STD US POSTAGE PAID Permit 439 Ft Lauderdale FL There is No Charge for this Symposium.

29 PROGRAM SUMMARY This educational activity is designed to provide physicians, nurse practitioners, physician assistants and other providers treating patients with rheumatic diseases the opportunity to learn about new biologics for treatment of RA and lupus, safety issues in biologic therapy, and treatments for osteoporosis and osteonecrosis of the jaw. In planning this CME activity, the National Association for Continuing Education (NACE) performed a needs assessment. A literature search was conducted, national guidelines were reviewed, survey data was analyzed, and experts in each therapeutic area were consulted to determine gaps in practitioner knowledge, competence or performance. Learning objectives (see below), linked to identified gaps, were developed and will be addressed by each presenter. This multidisciplinary program will utilize a variety of educational techniques incorporating the various aspects of Adult Learning Principles. There will be emphasis on audience participation utilizing interactive case-based presentations to deliver educational material. Participants will be asked to engage in pre and post testing to collect data for outcome studies and to uncover unmet needs for future programming. Each participant will be provided with a syllabus containing presentations, clinical tools, and practical guidelines at the start of the program to be used for future reference. LEARNING OBJECTIVES At the conclusion of this CME activity, attendees will be able to: Explain the immunological process involved in rheumatic diseases Describe basic immunology as it applies to current therapies for rheumatic diseases List various biologic therapies undergoing clinical development Discuss the mechanisms of action of emerging biologic therapies Evaluate potential consequences of treatment with new biologic agents Describe the risks versus benefits of biologic agents in rheumatic diseases Discuss current data on adverse effects of biologic agents and safety issues Discuss and implement current guidelines for the assessment, diagnosis and treatment of Osteoporosis and Osteonecrosis of the Jaw Explain the mechanism of action, safety, and efficacy of osteoporosis therapies FACULTY Alan Brown, MD Associate Professor of Medicine Division of Rheumatology and Immunology Vice Chairman for Education Department of Medicine Medical University of South Carolina Charleston, SC Gary Gilkeson, MD Professor and Vice Chair for Research Department of Medicine Medical University of South Carolina Staff Physician, Ralph H. Johnson VAMC Charleston, SC Yvonne Sherrer, MD Medical Director/Director of Clinical Research Center for Rheumatology, Immunology and Arthritis Fort Lauderdale, FL AGENDA 7:15-7:45 AM Registration and Continental Breakfast 7:45-8:00 AM Welcome Remarks and Pre-Test Alan Brown, MD 8:00-9:00 AM Mechanistic Insights Into New Biologics for the Treatment of RA and Lupus Gary Gilkeson, MD 9:00-10:00 AM Emerging Biologic Therapies for RA: Efficacy and Safety Alan Brown, MD 10:00-10:15 AM Break 10:15-11:15 AM An Update in Treatments for Osteoporosis and Osteonecrosis of the Jaw Yvonne Sherrer, MD 11:15-12:00 PM Interactive Panel and Case Discussion CONTINUING EDUCATION SUPPORTERS The National Association for Continuing Education is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The National Association for Continuing Education designates this educational activity for a maximum of 4 AMA PRA Category 1 Credits. Physicians should only claim credit commensurate with the extent of their participation in the activity. Policy on Faculty and Provider Disclosure: It is the policy of the National Association for Continuing Education to ensure fair balance, independence, objectivity and scientific rigor in all activities. All faculty participating in CME activities sponsored by the National Association for Continuing Education are required to present evidencebased data, identify and reference off-label product use and disclose all relevant financial relationships with those supporting the activity or others whose products or services are discussed. Faculty disclosure will be provided in the activity materials. This program was supported through educational grants from COURSE DIRECTOR Alan Brown, MD ACTIVITY DIRECTOR Michelle Frisch, MPH

30 Conference Registration Please print or type. Register online at or this form may be mailed or faxed. Onsite registration will be accepted provided space is available. Return completed form to: National Association for Continuing Education (NACE), 7860 Peters Road, F-111, Plantation, Florida For Registration Phone Toll Free: Fax: Personal Information First Name Middle Initial Last Name Degree License Number Mailing Address City State Zip Code/Postal Code Day Phone Number Eve. Phone Number Fax Address (Required) Check one: Physician Physician Assistant Nurse Practitioner Nurse Other Emerging Challenges in Treating Rheumatic Diseases: 2008 Saturday, December 13, 2008 At the Kingsgate Marriott Conference Hotel at the University of Cincinnati 151 Goodman Drive Cincinnati, OH There is no charge for this activity. Attendees must register in advance. Reservations for this program will be taken on a first come, first reserved basis. Space is limited so please register early. You will receive a confirmation as to your registration by mail or . This confirmation will serve as your admission ticket for the program. Emerging Challenges in Treating Rheumatic Diseases: 2008 EARN CONTINUING MEDICAL EDUCATION CREDITS This activity is for rheumatologists, rheumatology nurse practitioners and physician assistants, and primary care providers treating rheumatic diseases. Join us Cincinnati, Ohio December 13, Peters Road F-111 Plantation, Florida PRESORT STD US POSTAGE PAID Permit 439 Ft Lauderdale FL at the Kingsgate Marriott Conference Hotel NACE designates this educational activity for a maximum of 4 AMA PRA Category 1 Credits. There is No Charge for this Symposium.