Targeted Immune Modulators for Rheumatoid Arthritis

514 Pages·2017·7.51 MB·English

by  Matt Seidner

Targeted Immune Modulators for
Rheumatoid Arthritis: Effectiveness & Value

Draft Evidence Report

January 20, 2017

Prepared for

©Institute for Clinical and Economic Review, 2017
ICER Staff/Consultants University of Colorado School of Pharmacy
(Anschutz Medical Campus) Modeling Group*
Daniel A. Ollendorf, PhD Jonathan Campbell, PhD
Chief Scientific Officer Associate Professor
Institute for Clinical and Economic Review Department of Clinical Pharmacy

Center for Pharmaceutical Outcomes Research
Rick Chapman, PhD, MS

Director of Health Economics
Melanie D. Whittington, PhD
Institute for Clinical and Economic Review
Professional Research Assistant

Department of Clinical Pharmacy
Steven D. Pearson, MD, MSc

President
R. Brett McQueen, PhD
Institute for Clinical and Economic Review
Assistant Professor

Department of Clinical Pharmacy
Varun Kumar, MBBS, MPH, MSc
Center for Pharmaceutical Outcomes Research
Health Economist

Institute for Clinical and Economic Review

Foluso Agboola, MBBS, MPH
Research Scientist
Institute for Clinical and Economic Review

Patricia Synnott, MALD, MS
Senior Research Associate
Institute for Clinical and Economic Review

Shanshan Liu, MS, MPH
Research Associate

Institute for Clinical and Economic Review

Celia Segel, MPP

Program Manager, New England CEPAC

Institute for Clinical and Economic Review

Sonya Khan, MPH

Program Director, Midwest CEPAC
*The role of the University of Colorado Skaggs School
Institute for Clinical and Economic Review
of Pharmacy Modeling Group is limited to the
development of the cost-effectiveness model, and the
resulting ICER reports do not necessarily represent
the views of the UC.

DATE OF
PUBLICATION: JANUARY 20, 2017
We would also like to thank Margaret Webb, Noah Mwandha, and Erin Lawler of ICER for their
contributions to this report.
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Draft Evidence Report: Targeted Immune Modulators for Rheumatoid Arthritis
About ICER
The Institute for Clinical and Economic Review (ICER) is an independent non-profit research
organization that evaluates medical evidence and convenes public deliberative bodies to help
stakeholders interpret and apply evidence to improve patient outcomes and control costs. ICER
receives funding from government grants, non-profit foundations, health plans, provider groups,
and health industry manufacturers. For a complete list of funders, visit http://www.icer-
review.org/about/support/. Through all its work, ICER seeks to help create a future in which
collaborative efforts to move evidence into action provide the foundation for a more effective,
efficient, and just health care system. More information about ICER is available at http://www.icer-
review.org

About New England CEPAC
The New England Comparative Effectiveness Public Advisory Council (New England CEPAC) – a core
program of ICER – provides a public venue in which the evidence on the effectiveness and value of
health care services can be discussed with the input of all stakeholders. New England CEPAC seeks
to help patients, clinicians, insurers, and policymakers interpret and use evidence to improve the
quality and value of health care.
The New England CEPAC is an independent committee of medical evidence experts from across
New England, with a mix of practicing clinicians, methodologists, and leaders in patient engagement
and advocacy. All Council members meet strict conflict of interest guidelines and are convened to
discuss the evidence summarized in ICER reports and vote on the comparative clinical effectiveness
and value of medical interventions. More information about New England CEPAC is available at
http://icer-review.org/programs/new-england-cepac/.

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Draft Evidence Report: Targeted Immune Modulators for Rheumatoid Arthritis
Expert Review
In the development of this report, ICER’s researchers consulted with clinical experts, patients,
manufacturers and other stakeholders. In addition, the Arthritis Foundation worked with ICER to
deploy surveys of the Foundation’s membership on access to care issues, patient experience per type
of treatment received, and other concerns. The results of these surveys are summarized in the report.
The following experts provided input and data that helped guide the ICER team as we shaped our
scope and report. None of these individuals is responsible for the final contents of this report or should
be assumed to support any part of this report, which is solely the work of the ICER team and its
affiliated researchers.
For a complete list of stakeholders from whom we requested input, please visit:
https://icer-review.org/material/ra-stakeholder-list/

Patient/Advocacy Reviewers
Kayla Amodeo, PhD, Legislative Research Manager
Guy S. Eakin, PhD, Senior Vice President, Scientific Strategy
Sandie Preiss, MPA, National Vice President, Advocacy and Access
Arthritis Foundation
Jan Wyatt, PhD, RN, FAANP
Patient Advocate

Clinical Reviewers
Andrew L. Concoff, MD, Medical Policy Committee
Max Hamburger MD, President
Andrew J Laster MD FACR, Board of Directors and Medical Policy Committee Member
United Rheumatology

Kent Johnson, MD
University of New South Wales—Sydney

Matthew H. Liang, MD, MPH
Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital

Elizabeth Tindall, MD, FACR
Rheumatology Consultants of Oregon, LLC

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Draft Evidence Report: Targeted Immune Modulators for Rheumatoid Arthritis
Table of Contents
Executive Summary ............................................................................................................................ ES1
1. Background ........................................................................................................................................ 2
1.1 Introduction ................................................................................................................................. 2
2. The Topic in Context .......................................................................................................................... 7
2.1 Overview ...................................................................................................................................... 7
2.2 Treatments for Rheumatoid Arthritis ........................................................................................ 10
2.3 Other Aspects of Treatment ...................................................................................................... 13
2.4 Insights Gained from Discussions with Patients and Patient Groups ........................................ 17
2.5 Definitions .................................................................................................................................. 21
3. Summary of Coverage Policies and Clinical Guidelines ................................................................... 24
Clinical Guidelines ............................................................................................................................ 26
4. Comparative Clinical Effectiveness .................................................................................................. 29
4.1 Overview .................................................................................................................................... 29
4.2 Methods ..................................................................................................................................... 30
4.3 Results ........................................................................................................................................ 36
5. Other Benefits or Disadvantages ..................................................................................................... 67
6. Long-Term Cost-Effectiveness.......................................................................................................... 68
6.1 Overview .................................................................................................................................... 68
6.2 Cost-Effectiveness Model: Methods ......................................................................................... 68
6.3 Cost-Effectiveness Model: Results ............................................................................................ 79
6.4 Prior Published Evidence on Costs and Cost-Effectiveness ....................................................... 86
6.5 Potential Budget Impact ............................................................................................................ 88
6.6 Value-based Benchmark Prices .................................................................................................. 91
6.7 Summary and Comment ............................................................................................................ 91
References ........................................................................................................................................... 93
Appendix A. Search Strategies and Results ........................................................................................ 112
Appendix B. Public and Representative Private Insurer Coverage Policies ....................................... 118
Appendix C. Comparative Clinical Effectiveness Supplemental Information .................................... 123
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Draft Evidence Report: Targeted Immune Modulators for Rheumatoid Arthritis
Methods: Supplemental Information ............................................................................................ 123
Additional Comparative Clinical Effectiveness Results .................................................................. 124
Appendix D. Comparative Value Supplemental Information ............................................................ 174
Appendix E. Previous Systematic Reviews and Technology Assessments ......................................... 200
Appendix F.Evidence Tables ............................................................................................................... 204
Appendix G. Ongoing Studies............................................................................................................. 501

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Draft Evidence Report: Targeted Immune Modulators for Rheumatoid Arthritis
List of Acronyms Used in this Report
ABT Abatacept
ACPA Anticitrullinated Protein Antibody
ACR American College of Rheumatology
ADA Adalimumab
AHRQ Agency for Healthcare Research and Quality
ARHP Association of Rheumatology Health Professionals
BAR Baricitinib
CADTH Canadian Agency for Drugs and Technologies in Health
CCP Cyclic Citrullinated Peptide
CDAI Clinical Disease Activity Index
cDMARD Conventional Disease-Modifying Anti-Rheumatic Drugs
CMS Centers for Medicare and Medicaid Services
COPD Chronic Obstructive Pulmonary Disease
CORRONA Consortium of Rheumatology Researchers of North America
CRP C-reactive Protein
CTZ Certolizumab pegol
DAS28 Disease Activity Score with 28-Joint Counts
DIC Deviance Information Criterion
DMARDs Disease-Modifying Anti-Rheumatic Drugs
DREAM Dutch Rheumatoid Arthritis Monitoring
EQ-5D EuroQol-5 domain
ESR Erythrocyte Sedimentation Rate
ETN Etanercept
EULAR European League Against Rheumatism
GOL Golimumab
HAQ Health Assessment Questionnaire
HAQ-DI Health Assessment Questionnaire for Rheumatoid Arthritis Disability Index
ICER Incremental Cost-Effectiveness Ratio
IFAA International Foundation for Autoimmune Arthritis
IFX Infliximab
IV Intravenous
JAK Janus Kinase
JIA Juvenile Idiopathic Arthritis
MCID Minimum Clinically Important Difference
MCS Mental Component Score
MDHAQ Multi-Dimensional Health Assessment Questionnaire
mTSS Modified Total Sharp Score
MTX Methotrexate
NICE National Institute for Health and Care Excellence
NMA Network Meta-Analysis
PAS Patient Activity Scale
PCS Physical Component Score
PML Progressive Multifocal Leukoencephalopathy
PRISMA Preferred Reporting Items for Systematic Reviews and Meta-Analyses
PROMIS Patient-Reported Outcomes Measurement Information System
QALY Quality-Adjusted Life Year
RA Rheumatoid Arthritis
RAPID-3 Routine Assessment of Patient Index Data
RCT Randomized Controlled Trial
RF Rheumatoid Factor
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Draft Evidence Report: Targeted Immune Modulators for Rheumatoid Arthritis
RISE Rheumatology Informatics System for Effectiveness
RTX Rituximab
SAR Sarilumab
SC Subcutaneous
SDAI Simplified Disease Activity Index
SF-36 Short Form-36
SMD Standardized Mean Difference
TCZ Tocilizumab
TIMs Targeted Immune Modulators
TNF Tumor Necrosis Factor
TOF Tofacitinib
TRD Total Residual Deviance
USPSTF U.S. Preventive Services Task Force
VAS Visual Analog Scale
WAC Wholesale Acquisition Cost
WTP Willingness-to-pay

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Draft Evidence Report: Targeted Immune Modulators for Rheumatoid Arthritis
Executive Summary
To be included in our revised Evidence Review.
©Institute for Clinical and Economic Review, 2017 Page ES1
Draft Evidence Report: Targeted Immune Modulators for Rheumatoid Arthritis
Return to Table of Contents
1. Background
1.1 Introduction
Background
Rheumatoid arthritis (RA) is the most common chronic inflammatory arthritis in adults, affecting
between 1.3 and 1.8 million Americans.1,2 It is a disease of unknown but immunologically mediated
origin. RA is more common in women and may occur at any age, with peak incidence occurring at
ages 50-60 years.3 RA is typically characterized by morning stiffness and symmetrical joint swelling
of the feet, hands, and knees, although any joint (and in some cases, internal organs and skin) may
be involved.3 RA is considered a clinical syndrome that, if not controlled, leads to permanent joint
damage and deformity in some individuals.4 The course of RA may also occasionally be complicated
by skin, eye, heart, lung, hematologic, and other extra-articular manifestations.3
Over its course, the management of RA involves patient education, psychosocial support and
therapy, physical and occupational therapy, medications, and joint surgery as required. The
medications used are distinguished by whether they treat symptoms only versus those that target
mechanisms of tissue damage, collectively referred to as disease-modifying anti-rheumatic drugs
(DMARDs). Conventional DMARDs include older systemic agents with broad immunomodulatory
effects such as methotrexate, leflunomide, hydroxychloroquine, and sulfasalazine. More recently, a
number of biologic and non-biologic agents targeted at mediators of inflammation in RA known
collectively as “targeted immune modulators” (TIMs) have come into widespread use. Historically,
RA was associated with both progressive disability and a shortened lifespan, but improvements in
earlier diagnosis as well as aggressive use of TIMs have greatly improved survival and other key
outcomes in the past 20 years.5
Methotrexate is the most widely used conventional DMARD and is considered the “anchor drug”
because of its effectiveness and relative tolerability as well as its potential to enhance the
effectiveness of TIMs.3 However, only about 50% of patients treated with methotrexate alone will
experience sufficient reduction in disease activity or symptoms. Over the past two decades, the
introduction of TIMs has transformed the clinical course of disease for many RA patients.
Uncertainty remains, however, regarding the relative effectiveness and value of the different types
of TIMs and the most effective sequence of TIM therapy. This review focuses on the comparative
clinical effectiveness, potential harms, and comparative value of the major TIMs used in the
treatment of RA as well as several currently under regulatory review for this indication.

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Draft Evidence Report: Targeted Immune Modulators for Rheumatoid Arthritis
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