JMCP
`
`J O U R N A L O F M A N A G E D C A R E P H A R M A C Y ®
`
`Meeting the Challenge of Incorporating Injectable Biologics
`Into Managed Care: Multiple Sclerosis and Psoriasis
`
`JMCP
`
`Imelda C. Coleman, PharmD; Richard Cook, PharmD; Jay N. Gade, MD, PhD; Douglas S. Hum, RPh;
`Ben Johnson, RPh, MBA; Terry Maves, RPh; William J. Mazanec, PharmD, MBA; James R. Miller, MD;
`Woodrow J. Proveaux, PharmD; Sheldon J. Rich, RPh, PhD; Howard S. Rossman, DO, FACN; and William H. Stuart, MD
`
`Supplement
`June 2004
`Continuing Education Program
`
`Sawai (IPR2019-00789), Ex. 1043, p. 001
`
`

`

`Supplement
`Policy Statement
`
`Standards for Supplements to the
`
`Journal of Managed Care Pharmacy
`
`Supplements to the Journal of Managed
`Care Pharmacy are intended to support
`medical education and research in areas of
`clinical practice, health care quality
`improvement, or efficient administration
`and delivery of health benefits. The fol-
`lowing standards are applied to all JMCP
`supplements to assure quality and assist
`readers in evaluating potential bias and
`determining alternate explanations for
`findings and results.
`
`1. Disclose the principal sources of fund-
`ing in a manner that permits easy recogni-
`tion by the reader.
`
`2. Disclose the existence of all potential
`conflicts of interest among supplement
`contributors, including financial or per-
`sonal bias.
`
`3. Describe all drugs by generic name
`unless the use of the brand name is neces-
`sary to reduce the opportunity for confu-
`sion among readers.
`
`4. Strive to report subjects of current inter-
`est to managed care pharmacists and other
`managed care professionals.
`
`5. Seek and publish content that does not
`duplicate content in the Journal of Managed
`Care Pharmacy.
`
`6. Subject all supplements to expert peer
`review.
`
`F A C U L T Y
`
`Imelda C. Coleman, PharmD, is currently the clinical pharmacist at BlueCross and BlueShield of
`Louisiana. She received her BS in pharmacy from the University of Mississippi and PharmD from Xavier
`University of Louisiana. Upon completion of her pharmacy practice residency at the University of
`Mississippi Medical Center, she worked at the Ochsner Clinic Foundation, New Orleans, Louisiana,
`managing pharmacy risk for the 500-physician group. Coleman is a member of the Academy of Managed
`Care Pharmacy, where she serves on the Special Projects Committee.
`
`Richard Cook, PharmD, is manager, clinical and quality programs, Blue Care Network of Michigan,
`Grand Rapids.
`
`Jay N. Gade, MD, PhD, is in private practice in southern Oregon at the Dermatology and Laser Center
`of Roseburg. In addition, he is the clinical director of research at the center. He is also a Seminars in
`Psoriasis faculty member at the University of Alabama, Birmingham. Gade is a member of the Oregon
`Dermatology Association, Oregon Medical Association, and American Academy of Dermatology. He
`received his PhD in biochemistry and molecular biology from the Oregon Health Sciences University.
`His research focused on protein crosslinking systems in artificial skin development. Gade received his
`medical degree from the Oregon Health Sciences University and completed his residency in dermatology
`at Wake Forest University, serving as chief resident.
`
`Douglas S. Hum, RPh, is director of pharmacy services at Medica, Minneapolis, having served in that
`capacity since 2001. The department was nominated for a 2003 company-sponsored service/perform-
`ance excellence award for achieving significant medical cost savings toward overall company goals in
`2003. Hum is a graduate of the University of Minnesota College of Pharmacy, where he was awarded a
`Samuel W. Melendy undergraduate research scholarship in pharmacology. He has 24 years of practice as
`a pharmacist in hospital, retail, and managed care settings, including 8 years at AdvancePCS, now
`Caremark.
`
`Ben Johnson, RPh, MBA, is pharmacy contract manager for Intermountain Health Care, Salt Lake City,
`Utah. He is responsible for all pharmacy contracting in the integrated delivery system. Johnson works
`on several clinical committees including asthma, lower respiratory tract infection, cardiology, multiple
`sclerosis, and preventive medicine. He served as the pharmacy director for the 2002 Olympic Winter
`Games in Salt Lake City.
`
`Terry Maves, RPh, has been a community and pharmacy leader in northeast Wisconsin for more than
`25 years. He is the pharmacy director for Touchpoint Health Plan, based in Appleton, Wisconsin, which,
`for the second consecutive year, has been named by the National Committee for Quality Assurance as
`the number one health plan in the nation in delivering preventive care and managing chronic diseases.
`Maves has recognized the pharmacist’s ability to intervene on the patient’s behalf to improve patient
`therapies. He helped create the Everyone Teaching Compliance program, which helps health care
`providers coordinate care to improve medication utilization for 12 disease states. This program earned
`Maves recognition as the Innovative Pharmacist of the Year in 2000 for the state of Wisconsin. In addi-
`tion to increasing pharmacist’s involvement in the delivery of health care, he has created and imple-
`mented a cognitive reimbursement program and made this program available to all pharmacies in the
`Touchpoint Health Plan area. A leader in patient consultation and education, his role as a well-known
`preceptor, professional, and public speaker also demonstrates his commitment to the field of pharmacy.
`
`William J. Mazanec, PharmD, MBA,
`is vice president, clinical and formulary management, of
`CuraScript Inc., based in Orlando, Florida. He is responsible for support of its strategic clinical mission
`by providing clinical support to client account management. Mazanec works with managed care part-
`ners to develop and implement programs that integrate pharmacy activities with health plan manage-
`ment to control costs and utilization of pharmaceuticals. In his role, he conducts pipeline monitoring for
`product development within the biotechnology and pharmaceutical industry.
`For the past 15 years, Mazanec has served in various capacities in managed care, including director
`of pharmacy for AvMed Health Plan and director of pharmacy operations, Aetna U.S. Healthcare, where
`he oversaw Integrated Pharmacy Solutions Inc., a business component of Prudential Healthcare.
`Mazanec received his doctor of pharmacy degree from the University of Florida College of Pharmacy,
`with a special emphasis on disease state management and clinical interventions. He earned an MBA from
`the Crummer Graduate School of Business at Rollins College and a bachelor’s degree in pharmacy with
`a minor in radiopharmacy, in cooperation with the Harvard University joint program in nuclear medi-
`cine, from the Massachusetts College of Pharmacy.
`
`Sawai (IPR2019-00789), Ex. 1043, p. 002
`
`

`

`James R. Miller, MD, has recently retired after serving as director of the Multiple Sclerosis Center of Columbia-Presbyterian Medical
`Center in New York City for 20 years. He has lectured widely on the pathogenesis and treatment of multiple sclerosis and allied dis-
`eases as well as in the field of infections of the central nervous system. He has also written a variety of articles on these subjects and
`contributed chapters to several standard neurological textbooks. In retirement, Miller continues to lecture both to medical and patients
`groups concerning multiple sclerosis.
`
`Woodrow J. Proveaux, PharmD, is the clinical pharmacy director at CareFirst BlueCross BlueShield in Baltimore, Maryland, and
`precepts a post-PharmD resident and a pharmacoeconomics fellow each year. He has extensive experience in teaching and coordi-
`nating clinical pharmacy practices at both West Virginia University and King Saud University. His research and scholarly activities
`include 14 journal publications as well as various chapter and book reviews and presentations to local, state, national, and interna-
`tional groups. He received his doctor of pharmacy degree from the University of Michigan after completing undergraduate work at
`the University of Georgia and the Southern Technical Institute.
`
`Sheldon J. Rich, RPh, PhD, is president of SJR Associates, LLC, a health care consulting company in West Bloomfield, Michigan. He
`has more than 20 years experience in the pharmacy field, having practiced in hospital, retail, and managed care pharmacy. Nationally
`recognized as a lecturer and moderator, his recent consulting assignments have included acting as interim pharmacy director at a large
`managed care plan, developing a pharmaceutical manufacturer rebate program for a large group purchasing organization, assisting
`numerous physician practice groups in managing pharmacy costs and shared risk contracts, providing managed care training for var-
`ious pharmaceutical manufacturers, and developing and moderating clinical advisory boards.
`Prior to starting his own consulting practice, Rich was director of pharmacy programs at SelectCare, Troy, Michigan, where he
`developed a nationally recognized, cost-effective pharmacy program and pharmacy network. He was responsible for development of
`drug utilization review programs, served as the chairperson of the pharmacy and therapeutics committee, and developed a compre-
`hensive drug formulary. Rich earned his pharmacy degree from the University of Michigan. He also holds a doctorate in theocentric
`business ethics. He has held the position of clinical assistant professor at the University of Michigan since 1982 and has held a dual
`appointment as an adjunct assistant professor with the College of Pharmacy and Allied Health Professions at Wayne State University
`since 1994.
`Rich has moderated more than 100 meetings and advisory boards, published numerous journal articles, and contributed to
`2 textbooks. He served for 8 years on the Michigan Board of Pharmacy, 3 years as chairperson. Rich has received numerous profes-
`sional awards and honors and is a member of several professional organizations.
`
`Howard S. Rossman, DO, FACN, is a senior partner of the Michigan Institute of Neurological Disorders (MIND) in Farmington
`Hills, an organization with which he has been associated since 1978. He is medical director of the Multiple Sclerosis Center at MIND
`and has been involved in 10 major clinical trials for potential new MS therapeutics since 1999, 7 of which are currently ongoing. In
`addition, Rossman is a clinical professor of neurology at Michigan State University and chairman of the neurology department at
`Botsford General Hospital, an affiliate of Michigan State University, where he directed the residency training program for 19 years until
`2002. He is still actively involved in the training of medical students, interns, and neurology residents.
`Rossman received his undergraduate degree from the University of Michigan and his medical training at the Michigan State
`University College of Osteopathic Medicine. He completed his residency in neurology at Botsford General Hospital, an affiliate of
`Michigan State University. Rossman is a member of the Consortium of MS Centers and a fellow of the American College
`of Neuropsychiatrists, where he served as president from 1994 to 1995.
`
`William H. Stuart, MD, received his medical degree from Northwestern University Medical School and completed an internship at
`Cleveland Metropolitan General Hospital and a residency in internal medicine at Northwestern. He subsequently served as an
`epidemic intelligence service officer at the Communicable Disease Center (CDC) in Atlanta, Georgia, and completed a fellowship in
`neurology at Emory University Medical School. Upon completion of this training and serving at the National Institute of Neurological
`Disorders and Stroke, Rockville, Maryland, he entered private practice in the Atlanta area, forming the Atlanta Neurological Clinic,
`subsequently renamed the Peachtree Neurological Clinic in 1990.
`One of the founding members of the American Society of Neuroimaging in 1975, Stuart served as its president in 1984 and 1985.
`In 1980, he became a member of the Practice Committee of the American Academy of Neurology, (AAN), remaining active on that
`committee until 1991 and serving as its chairman from 1985 through 1991. He was a member of the Executive Committee of AAN
`for several years and served as treasurer. His most recent activity with AAN was aiding in the formation of the academy’s MS section
`and serving on the Long-Range Planning Committee.
`Stuart began his focused interest in multiple sclerosis in 1988, developing the Multiple Sclerosis Comprehensive Care and
`Research Center at Shepherd Center, Atlanta, in 1991. In 2001, he became medical director of the MS Center of Atlanta and the MS
`Research Network of Georgia. His interest in MS has focused on early treatment and aggressive combination therapy for patients with
`breakthrough disease.
`He has maintained a broad interest in education and served as a clinical professor of neurology at Emory University Medical
`School from 1987 to 2003. He was named Clinical Teacher of the Year at Piedmont Hospital in 1987 and 1988. He has lectured wide-
`ly in evolving treatments in MS. Stuart’s board certification includes the American Board of Internal Medicine and the American Board
`of Psychiatry and Neurology. He serves on the boards of the National MS Society—Georgia Chapter (and its Medical Advisory Board)
`and Millennium Medical Communications, Inc.
`
`Sawai (IPR2019-00789), Ex. 1043, p. 003
`
`

`

`The full text of this supplement is available at http://amcp.cecity.com/login.htm.
`
`Table of Contents
`Meeting the Challenge of Incorporating Injectable
`Biologics Into Managed Care: Multiple Sclerosis and Psoriasis
`
`S3
`
`S4
`
`Program Overview
`Sheldon J. Rich, RPh, PhD
`
`The Importance of Early Diagnosis of Multiple Sclerosis
`James R. Miller, MD
`
`S12 Neutralizing Antibodies to Multiple Sclerosis Treatments
`Howard S. Rossman, DO, FACN
`
`S19 Clinical Management of Multiple Sclerosis:
`The Treatment Paradigm and Issues of Patient Management
`William H. Stuart, MD
`
`S26 Stepped-Care Approach to Treating MS: A Managed Care Treatment Algorithm
`Sheldon J. Rich, RPh, PhD; Imelda C. Coleman, PharmD; Richard Cook, PharmD; Douglas S. Hum, RPh;
`Ben Johnson, RPh, MBA; Terry Maves, RPh; William J. Mazanec, PharmD, MBA; James R. Miller, MD;
`Woodrow J. Proveaux, PharmD; Howard S. Rossman, DO, FACN; and William H. Stuart, MD
`
`S33 Clinical Update on Alefacept: Consideration for Use in Patients With Psoriasis
`Jay N. Gade, MD, PhD
`
`S38 Considerations for Assessing the Cost of Biologic Agents in the Treatment of Psoriasis
`Sheldon J. Rich, RPh, PhD
`
`S42 Continuing Education*: Record of Completion, Posttest, and Program Evaluation
`
`Target Audience:
`This program has been designed to meet the educational needs of pharmacists and other health care practitioners
`in a managed care environment.
`
`3.
`
`Learning Objectives
`After completing this continuing education module, the pharmacist will be able to
`1. verbalize the importance and long-term potential of injectable biologic therapies for the treatment of
`multiple sclerosis (MS) and psoriasis;
`2. describe strategies and considerations that optimize treatment success and ensure appropriate resource
`utilization for biologic therapies in MS and psoriasis;
`recognize the complexity of treating MS and the importance of individualizing therapy and planning for
`long-term management of the disease;
`4. employ (a) treatment protocols developed by neurologists for appropriate use of biologics in MS and
`(b) interventions for managing MS symptoms and treatment side effects;
`5. describe an MS treatment algorithm developed by managed care professionals that provides guidelines for
`long-term disease management, including treatment initiation, recommended evaluations, and disease
`progression;
`6. understand current clinical data concerning alefacept’s use in the treatment of patients with moderate-to-severe
`psoriasis, including long-term benefits and safety and tolerability considerations; and
`identify key considerations for evaluating the cost implications and drug utilization for biologic therapies in
`psoriasis.
`
`7.
`
`This supplement was supported by an unrestricted grant from Biogen Idec Inc.
`*A total of .20 CEUs (2 contact hours) will be awarded for successful completion of this continuing education program
`(Program No. 233-000-04-040-H04).
`Copyright© 2004, Academy of Managed Care Pharmacy, Inc. All rights reserved. No part of this publication may be reproduced or transmitted
`in any form or by any means, electronic or mechanical, without written permission from the Academy of Managed Care Pharmacy.
`All articles published represent the opinions of the authors and do not reflect the official policy or views of the Academy of Managed Care Pharmacy, the
`authors’ institutions, or Biogen Idec Inc., unless so specified.
`
`Sawai (IPR2019-00789), Ex. 1043, p. 004
`
`

`

`P R O G R A M O V E R V I E W
`
`SHELDON J. RICH, RPh, PhD
`
`T he development of injectable biologic agents has revolution-
`
`ized the treatment of numerous diseases, including multiple
`sclerosis (MS) and psoriasis. These agents have the potential
`for long-term benefits, including reduced disease activity, improved
`quality of life, and decreased utilization of total health care services.
`As newly approved biologics for the treatment of MS and psoriasis
`become available, managed care decision makers must determine the
`appropriate use of these agents based on long-term efficacy, safety, and
`cost. The goal of this supplement is to provide information from clin-
`ical trials and from the experience of renowned specialists to aid in
`this endeavor.
`Multiple sclerosis is a chronic, multifocal, demyelinating disease
`of the central nervous system (CNS). The onset of MS typically occurs
`in early adulthood,1 and MS is the leading cause of nontraumatic CNS
`morbidity in young and middle-aged adults.2 In the United States, the
`annual per-patient cost of MS has been estimated at $34,000, with a
`total lifetime per-patient cost of $2.2 million; a conservative estimate
`of the national annual cost is $6.8 billion.3 MS is a complex and het-
`erogeneous disease, with high intrapatient and interpatient variability
`in its clinical course and manifestations. Consequently, physicians
`who treat patients with MS must tailor treatment to individual
`patients and actively plan for the long-term management of the
`disease.
`Four articles in this supplement focus on the role of biologics in
`the management of MS. The first article, by James R. Miller, MD, pro-
`vides an overview of the 4 biologic agents that are available in the
`United States for the treatment of relapsing-remitting MS as well as
`the complexities involved in the diagnosis and clinical course of MS.
`Data supporting early treatment of patients at high risk for MS also are
`discussed. The second article, by Howard S. Rossman, DO, FACN,
`reviews data on the development of neutralizing antibodies (NAbs) to
`biologic agents used to treat MS. Studies show that differences exist
`among biologics regarding the risk of developing NAbs and that these
`NAbs reduce or abolish the therapeutic effects of biologics. The
`article also discusses the implications of NAbs for neurologists and
`managed care professionals.
`The third article, by William H. Stuart, MD, presents an MS treat-
`ment algorithm recently developed by a panel of neurologists who are
`MS experts. This algorithm provides best-practice guidelines on choos-
`ing the appropriate biologic agent for initiating therapy, managing
`occasional relapses, and selecting agents that can be added to
`biologics in patients whose disease progresses while they are on
`treatment. The fourth article, by my colleagues and me, provides a
`model treatment algorithm for use in the managed care setting, which
`was developed by a group of managed care professionals. This model
`
`Author
`
`SHELDON J. RICH, RPh, PhD, is president, SJR Associates, LLC, West
`Bloomfield, Michigan; clinical assistant professor, University of Michigan, Ann
`Arbor; and adjunct assistant professor, Wayne State University, Detroit, Michigan.
`
`AUTHOR CORRESPONDENCE: Sheldon J. Rich, RPh, PhD, President, SJR
`Associates, LLC, 4223 Fieldbrook Rd., West Bloomfield, MI 48323-3207.
`Tel: (248) 932-8500; Fax: (248) 932-2972; E-mail: SJRAssociates@aol.com
`
`Copyright© 2004, Academy of Managed Care Pharmacy. All rights reserved.
`
`MS algorithm provides health care professionals with guidelines on the
`following disease management issues: when to initiate treatment, how
`to select a biologic agent as the initial therapy, the use of magnetic
`resonance imaging in the diagnosis and management of patients with
`MS, when to test for NAbs and how to manage patients who have
`positive test results for NAbs, and how to manage patients who
`experience progression during treatment. An algorithm for NAb
`testing also has been proposed that, while recognizing the authority of
`the physician to make ultimate prescribing decisions, can be
`incorporated into a patient’s care path to ensure the quality of care
`without placing a burden on the patient.
`An estimated 4.5 million adults in the United States have psoria-
`sis, and approximately one third (1.5 million) of these individuals
`have moderate-to-severe disease.4 The financial burden of psoriasis is
`substantial, with annual U.S. economic costs estimated at $4.3 bil-
`lion.5 Patients with moderate-to-severe psoriasis typically require
`chronic treatment with systemic therapy or phototherapy. Although
`conventional systemic agents can be effective in producing short-term
`reductions in disease severity, the long-term, chronic use of these treat-
`ments is limited by safety and tolerability concerns. Novel injectable
`biologics, which have been developed based on an understanding of
`the role of T cells in the pathogenesis of psoriasis, have advanced the
`treatment of moderate-to-severe psoriasis.
`Alefacept was the first biologic therapy approved for the treatment
`of moderate-to-severe chronic plaque psoriasis in the United States,
`and it has been available here for more than 1 year. Two articles in this
`supplement review the use of alefacept in the treatment of psoriasis.
`The article by Jay N. Gade, MD, PhD, provides an update on the clin-
`ical efficacy and safety of alefacept in patients with psoriasis. Alefacept
`has proven to be an effective intermittent therapy for psoriasis that
`offers patients extended treatment-free and disease-free periods. As a
`result of prolonged remissions, overall drug utilization may be reduced.
`In the second article, I review key considerations for the long-
`term assessment of biologic therapies in psoriasis. These
`considerations establish the importance of efficacy, safety, and cost
`parameters measured over a longer course of therapy than the
`traditional 3-month or 6-month time period utilized to date.
`It is hoped that the timeliness and clinical relevance of the infor-
`mation provided in this Journal supplement will assist you in improv-
`ing the care of your patients with MS or psoriasis and will ensure the
`use of biologic therapies in the most cost-efficient manner.
`
`REFERENCES
`
`1. Wingerchuk DM, Lucchinetti CF, Noseworthy JH. Multiple sclerosis: current
`pathophysiological concepts. Lab Invest. 2001;81:263-81.
`2. The Canadian Burden of Illness Study Group. Burden of illness of multiple
`sclerosis: Part II: quality of life. Can J Neurol Sci. 1998;25:31-38.
`3. Whetten-Goldstein K, Sloan FA, Goldstein LB, Kulas ED. A comprehensive
`assessment of the cost of multiple sclerosis in the United States. Mult Scler.
`1998;4:419-25.
`4. National Psoriasis Foundation. Benchmark survey on psoriasis and psoriatic
`arthritis. Summary of top-line results. Available at: http://www.psoriasis.org/
`files/pdfs/press/npfsurvey.pdf. Accessed April 4, 2004.
`5. National Psoriasis Foundation. How much does skin disease cost? Available
`at: http://www.psoriasis.org/news/news/2002/20020919_ burden.php.
`Accessed April 18, 2004.
`
`www.amcp.org Vol. 10, No. 3, S-b June 2004 JMCP Supplement to Journal of Managed Care Pharmacy S3
`
`Sawai (IPR2019-00789), Ex. 1043, p. 005
`
`

`

`Stepped-Care Approach to Treating MS:
`A Managed Care Treatment Algorithm
`
`SHELDON J. RICH, RPh, PhD; IMELDA C. COLEMAN, PharmD; RICHARD COOK, PharmD; DOUGLAS S. HUM, RPh;
`BEN JOHNSON, RPh, MBA; TERRY MAVES, RPh; WILLIAM J. MAZANEC, PharmD, MBA; JAMES R. MILLER, MD;
`WOODROW J. PROVEAUX, PharmD; HOWARD S. ROSSMAN, DO, FACN; and WILLIAM H. STUART, MD
`
`ABSTRACT
`
`OBJECTIVE: To introduce a model treatment algorithm for use in the managed
`care setting as a strategy to provide ongoing disease management and long-term
`care for patients with multiple sclerosis (MS), with the goal of delaying disease
`progression and the associated disability and cognitive dysfunction.
`
`SUMMARY: MS is a chronic inflammatory disorder of the central nervous system
`that is associated with progressive disability and cognitive dysfunction. Currently,
`management of MS involves planning an effective long-term treatment strategy
`that can delay the progression of the disease. This article reviews a typical
`stepped-care approach to treating MS that is based on the concept of a platform
`drug, which is an agent that provides baseline immunomodulatory action
`throughout the course of the disease.
`Considerations for selecting a platform therapy include the effect on the full
`spectrum of MS (disability, relapses, lesion load, and atrophy as well as patient
`compliance and the potential impact of neutralizing antibodies [NAbs]). Currently,
`4 first-line therapies are approved for relapsing MS: the 3 interferon beta (IFNβ)
`products and glatiramer acetate. Of these, the IFNβs are generally recommended
`as platform therapy because all have shown significant effects on relapses, mag-
`netic resonance imaging parameters of the disease, and because intramuscular
`(IM) IFNβ-1a (Avonex) and subcutaneous (SC) IFNβ-1a (Rebif) have been shown
`to slow the progression of sustained disability.
`Patients being treated with IFNβs can develop NAbs to the drug, which can
`lead to a loss of efficacy and subsequent occurrence of breakthrough disease.
`The 3 different formulations of IFNβ are associated with a varying incidence of
`NAbs (IM IFNβ-1a, 5%; SC IFNβ-1a, 24%; IFNβ-1b [Betaseron], 45%). Antibodies
`also form against glatiramer acetate, although their clinical significance needs
`to be elucidated. As the disease progresses or has periods of aggressive activity,
`the stepped-care approach is to add other agents onto the platform therapy to
`improve control of the disease.
`
`CONCLUSION: Stepped care, as outlined in this model treatment algorithm for the
`managed care setting, is an effective method to achieve the fundamental goal of
`MS treatment, that is, to delay disease progression and the associated disability
`and cognitive impairment.
`
`KEYWORDS: Multiple sclerosis, Stepped care, Treatment algorithm
`
`J Manag Care Pharm. 2004;10(3)(suppl S-b):S26-S32
`
`Multiple sclerosis (MS) is a chronic demyelinating disease
`
`of the central nervous system. Natural history data sug-
`gest that in a majority of patients diagnosed with clini-
`cally definite MS, the disease progresses from an initial relapsing-
`remitting form to a secondary progressive type.1 Delaying pro-
`gression of the disease and the associated disability and cognitive
`dysfunction is one of the fundamental goals of MS therapy. To
`achieve this objective, an individualized, dynamic, long-term
`treatment strategy should be implemented along with ongoing
`monitoring of disease activity. The treatment plan should be able
`to adapt to the changing needs of the individual patient, based on
`clinical findings of disease progression, severity of MS symptoms,
`increase of disease burden on magnetic resonance imaging (MRI),
`and development of neutralizing antibodies (NAbs).
`Approved first-line therapies for relapsing-remitting MS
`include the 3 interferon beta (IFNβ) products: intramuscular (IM)
`IFNβ-1a, (IM IFNβ-1a [Avonex, Biogen Idec Inc., Cambridge,
`MA]); subcutaneous (SC) IFNβ-1a (SC IFNβ-1a [Rebif, Serono,
`Inc., Rockland, MA]); and IFNβ-1b (Betaseron, Berlex
`Laboratories, Montville, NJ) and glatiramer acetate (Copaxone,
`Teva Neuroscience, Inc., Kansas City, MO).2 Consequently, these
`drugs are used as baseline immunomodulatory agents (platform
`drugs) in the treatment of MS. These treatments are proven to
`slow various aspects of MS; however, most patients will experi-
`
`Authors
`
`SHELDON J. RICH, RPh, PhD, is president, SJR Associates, LLC, West Bloomfield,
`Michigan; clinical assistant professor, University of Michigan, Ann Arbor; and
`adjunct assistant professor, Wayne State University, Detroit, Michigan; IMELDA C.
`COLEMAN, PharmD, is clinical pharmacist, BlueCross/BlueShield of Louisiana,
`Baton Rouge; RICHARD COOK, PharmD, is manager, clinical and quality pro-
`grams, Blue Care Network of Michigan, Grand Rapids; DOUGLAS S. HUM, RPh,
`is director of pharmacy services, Medica Health Plans, Minnetonka, Minnesota;
`BEN JOHNSON, RPh, MBA, is pharmacy contract manager, Intermountain Health
`Care, Salt Lake City, Utah; TERRY MAVES, RPh, is pharmacy director, Touchpoint
`Health Plan, Appleton, Wisconsin; WILLIAM J. MAZANEC, PharmD, MBA, is
`vice president, clinical and formulary management, CuraScript, Orlando, Florida;
`JAMES R. MILLER, MD, was director, Multiple Sclerosis Center, Columbia-
`Presbyterian Medical Center, Columbia University, New York, New York (now
`retired); WOODROW J. PROVEAUX, PharmD, is clinical pharmacy director, Care
`First BlueCross/BlueShield, Baltimore, Maryland; HOWARD S. ROSSMAN, DO,
`FACN, is medical director, Multiple Sclerosis Center, Michigan Institute For
`Neurological Disorders, Farmington Hills; WILLIAM H. STUART, MD, is medical
`director, Multiple Sclerosis Center of Atlanta, Georgia.
`
`AUTHOR CORRESPONDENCE: Sheldon J. Rich, RPh, PhD, President, SJR
`Associates LLC, 4223 Fieldbrook Rd., West Bloomfield, MI 48323-3207.
`Tel: (248) 932-8500; Fax: (248) 932-2972; E-mail: SJRAssociates@aol.com
`
`Copyright© 2004, Academy of Managed Care Pharmacy. All rights reserved.
`
`S26 Supplement to Journal of Managed Care Pharmacy JMCP June 2004 Vol. 10, No. 3, S-b www.amcp.org
`
`Sawai (IPR2019-00789), Ex. 1043, p. 006
`
`

`

`Stepped-Care Approach to Treating MS: A Managed Care Treatment Algorithm
`
`FIGURE 1
`
`Diagnosis and Therapy Selection
`
`Clinically isolated
`syndrome + MRI to
`support diagnosis
`
`Patient meets diagnostic criteria for MS
`
`Develop therapeutic plan
`and select platform therapy
`
`IFNβ-1a
`(Avonex)
`
`IFNβ-1a
`(Rebif)
`
`IFNβ-1b
`(Betaseron)
`
`Glatiramer
`acetate
`(Copaxone)
`
`Neurologist recommends appropriate therapy based on:
`• Evidence-based efficacy
`• Patient lifestyle: likelihood patient will comply with dosing
`and administration regimen
`• Low immunogenicity
`• Ability for long-term treatment (suitability and tolerability)
`
`•Care management plan
`•Setting expectations
`•Patient education
`
`The decision to initiate treatment for multiple sclerosis (MS) is followed by careful consid-
`eration of the available first-line or “platform” therapies. Educating patients and setting
`realistic treatment expectations are also important factors in designing an effective long-
`term treatment plan. IFNβ = interferon beta; MRI = magnetic resonance imaging.
`
`the platform drug, based on symptoms and disease progression.
`Platform therapy options are the 4 drugs that are approved by the
`U.S. Food and Drug Administration (FDA) for use in relapsing MS:
`IFNβ-1b, IM IFNβ-1a, SC IFNβ-1a, and glatiramer acetate. The rel-
`ative efficacy, side effects, convenience, and compliance issues relat-
`ing to these drugs (discussed in the article by William H. Stuart in
`this supplement) should be considered when evaluating the differ-
`ent platform drugs. IFNβs are recommended as platform therapy
`because they have an impact on relapses and lesions on MRI. In
`addition, IM and SC IFNβ-1a have been shown to slow the pro-
`gression of sustained disability13-16 and IM and SC IFNβ-1b therapies
`have been shown to significantly decrease brain atrophy.17,18
`Given the long-term nature of MS treatment, the clinical aspects
`of the available platform drugs should be given careful considera-
`tion before initiating treatment. The complications that may arise
`due to the generation of NAbs to IFNβ also should be taken into
`account (for a detailed discussion, see the article by Howard S.
`Rossman in this supplement). These complications include
`reduced efficacy of the drug and cross-reactivity of NAbs that make
`switching between IFNβ products impractical. The neurologist
`must consider these factors and assist individual patients in select-
`ing the appropriate agent rather than simply providing general
`information to patients and having