Biologics for the Treatment of Rheumatoid Arthritis

139 Pages·2016·3.84 MB·English

by  Ronald F van Vollenhoven (auth.)

Ronald F van Vollenhoven
Biologics for the
Treatment of
Rheumatoid Arthritis
Ronald F van Vollenhoven, MD, PhD
Biologics for the
Treatment of
Rheumatoid Arthritis
Ronald F van Vollenhoven, MD, PhD
Unit for Clinical Therapy Research
Inflammatory Diseases (ClinTRID)
The Karolinska Institute
Stockholm, Sweden
Biologics for the
Treatment of
Rheumatoid Arthritis
Ronald F van Vollenhoven, MD, PhD
Unit for Clinical Therapy Research
Inflammatory Diseases (ClinTRID)
The Karolinska Institute
Stockholm, Sweden
ISBN 978-3-319-13107-8 ISBN 978-3-319-13108-5 (eBook)
DOI 10.1007/978-3-319-13108-5
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Contents
Author biography ix
Abbreviations xi
1 Disease overview 1
Clinical presentation 1
Etiology and pathogenesis 4
Pathophysiology of joint inflammation in rheumatoid arthritis 4
Diagnosis and classification 5
Long-term complications of rheumatoid arthritis 6
References 7
2 General treatment aspects 9
Goals of treatment 9
Measuring disease activity and treatment response 11
Overview of treatment approaches 17
Overview of the non-biologic treatments for rheumatoid arthritis 19
References 24
3 Overview of biologic therapies 29
Brief historical review of the emergence of biologics for
rheumatoid arthritis 29
Overview of currently available biologic therapies 30
Biologic versus synthetic disease modifying antirheumatic drugs:
similarities and differences 30
Current guidelines for biologic use in rheumatoid arthritis 36
References 38
4 Cytokine inhibitors 39
Tumor necrosis factor inhibitors 39
Interleukin-6 inhibitors 57
Interleukin-1 inhibitors 62
References 64
V
VI • CONTENTS
5 B-cell directed therapy 71
Introduction 71
Overview of B-cell therapy for rheumatoid arthritis 72
References 76
6 T-cell directed therapy 79
Overview of T-cell directed therapy for rheumatoid arthritis 79
References 82
7 Novel biologics and small molecules with
biologic-like effects 83
Introduction 83
Novel biologics 83
Novel synthetic antirheumatic medications with biologic-like properties 86
References 89
8 Strategies for the optimal use of biologic agents in
rheumatoid arthritis 93
Introduction 93
Treatment of the patient with an inadequate response to methotrexate 94
Treatment of the patients with newly diagnosed methotrexate-naive
rheumatoid arthritis 96
Induction-maintenance strategies in rheumatoid arthritis 98
Switching after failing an anti-tumor necrosis factor 99
Dose optimization with biologics: dosing up, dosing down 100
Head-to-head comparative studies of biologic agents 102
Determining which therapy is most appropriate for an individual
patient: personalized therapy 102
References 104
9 Considerations for special patient populations 109
Special considerations in the pregnant patient 109
Special considerations in the pediatric patient 113
Special considerations in the elderly patient 117
References 118
CONTENTS • VII
10 Conclusions and future outlook 123
Historical perspective 123
Future perspective 124
Future prospects for treatment strategies in rheumatoid arthritis:
‘treating to target’ 129
Epilogue 129
References 130
Author biography
Professor Ronald F van Vollenhoven is Chief of the Unit for Clinical
Therapy Research, Inflammatory Diseases (ClinTRID) at the Karolinska
Institute, and of the Clinical Trials Unit Rheumatology at the Karolinska
University Hospital. He received his MD and PhD degrees from the
University of Leiden in The Netherlands. After graduating in 1984 he
pursued immunology research at Cornell Medical College in New York,
followed by a residency (specialty training) in internal medicine at
the State University of New York at Stony Brook, and a fellowship in
rheumatology at Stanford University in Palo Alto following which he
received American Board of Internal Medicine certification in both
internal medicine and rheumatology. From 1993 to 1998 Professor van
Vollenhoven held a faculty appointment as Assistant Professor of Medicine
in the Division of Immunology and Rheumatology at Stanford University,
and from 1995 he was the Medical Services Chief and Fellowship
Director in that division. In 1998 Professor van Vollenhoven moved to
Stockholm, Sweden, where he worked as a Senior Physician and Chief
of the Clinical Trials Unit in the Department of Rheumatology at the
Karolinska University Hospital and Associate Professor of Rheumatology;
and in 2010, he was appointed in his current position as Professor and
Unit Chief at the Karolinska Institute.
Professor van Vollenhoven’s research interests focus around the devel-
opment and systematic evaluation of biologic and immunomodulatory
treatments for the rheumatic diseases. With his co-workers, he has
established the Stockholm registry for biological therapies (the STURE
database) for this purpose, which has supported research projects relating
to clinical efficacy, pharmacology, outcomes, and pharmacoeconomics.
He has been principal investigator in many clinical trials of novel thera-
pies in rheumatic diseases and has contributed to a number of important
investigator-initiated trials including the SWEFOT trial. He has published
over 240 original papers, book chapters and reviews, and is Editor of the
textbook Targeted Treatment of the Rheumatic Diseases and associate-editor
Ix
xx •• AAUUTTHHOORR BBIIOOGGRRAAPPHHYY
of Dubois’ Lupus Erythematosus. In 2004, Professor van Vollenhoven was
awarded the Scandinavian Research Foundation Prize for excellence
in clinical research in rheumatology, and he is an honorary member of
several rheumatology societies. He is the Editor-in-Chief of Lupus Science
& Medicine, Chair of the EULAR Standing Committee on Clinical Affairs,
member of many editorial boards, past-chair of the Swedish Rheumatology
Society Professors’ Council, co-founder of the IRBIS registry for biolog-
ics in systemic lupus erythematosus (SLE), the CERERRA registries
collaboration, and the NORD-STAR collaboration for Nordic trials in
the rheumatic diseases, and the initiator of the Treat-to-Target-in-SLE
initiative. Professor van Vollenhoven lives just north of Stockholm with
his wife and children aged 20 and 16. Outside his professional life he is
an avid classical pianist.
Ronald F van Vollenhoven
The Karolinska Institute
Stockholm, Sweden
Abbreviations
ACPA Anti-citrullinated protein antibody
ACR American College of Rheumatology
ANCA Anti-neutrophil cytoplasmic autoantibody
APC Activated protein C
AS Ankylosing spondylitis
ASA Acetyl-salicylic acid
axSpA Axial spondyloarthropathy
AZA Azathioprine
BCG Bacillus Calmette-Guérin
bDMARDs Biological DMARDs
CDAI Clinical Disease Activity Index
cDMARDs Conventional DMARDs
CHO Chinese hamster ovary cell
CINCA Chronic infantile neurological cutaneous and
articular syndrome
CLL Chronic lymphocytic leukemia
Cox Cyclo-oxygenase
CRP C-reactive protein
CTLA-4 Cytotoxic T lymphocyte-associated molecule 4
CyA Cyclosporine A
DAS Disease Activity Score
DMARDs Disease-modifying antirheumatic drugs
EIRA ‘Epidemiology in RA’
EMA European Medicines Agency
EPO Erythropoietin
EQ5D EuroQuol5D
ESR Erythrocyte sedimentation rate
EULAR European League Against Rheumatism
GC Glucocorticoids
GM-CSF Granulocyte-macrophage colony-stimulating factor
HACA Human anti-chimeric antibodies
xI