decision making in rheumatoid arthritis treatment

220 Pages·2014·3.36 MB·English

DECISION MAKING IN RHEUMATOID
ARTHRITIS TREATMENT:
FROM POPULATION TO PATIENTS
Sandhya C. Nair
This research was performed within the framework of the Center for Translational Molecular
Medicine (CTMM), and the Dutch Arthritis Foundation (Reumafonds) under project TRACER
(04I-202-11).
Printing of this thesis was financially supported by the Center for Translational Molecular
Medicine (CTMM), the Dutch Arthritis Foundation (Reumafonds), Pfizer, Abbvie, UCB Pharma
and Roche.
Layout and cover design by Sandeep Kumar.
Cover art based on Warli painting.
Chapter art by Alexei von Jawlensky (1864-1941) painted during different periods as his life
slowly deterioriated with crippling arthritis.
Printed by Ipskamp Drukkers
ISBN: 978-94-6259-357-2
© All rights reserved. No part of this book may be reproduced or transmitted, in any form or by
any means, without prior written permission of the author.
Decision making in rheumatoid arthritis treatment:
from population to patients
Besluitvorming bij behandeling van reumatoïde artritis:
van populatie naar patiënt
(met een samenvatting in het Nederlands)
PROEFSCHRIFT
ter verkrijging van de graad van doctor aan de Universiteit Utrecht
op gezag van de rector magnificus, prof. dr. G.J. van der Zwaan,
ingevolge het besluit van het college voor promoties
in het openbaar te verdedigen op
donderdag 6 november 2014 des ochtends te 10.30 uur
door
Sandhya Chandran Nair
geboren op 26 september 1983
te Kottayam (Kerala), India
Promoters: Prof. dr. F.P.J.G. Lafeber
Prof. dr. J.W.J. Bijlsma
Copromoter: Dr. P.M.J. Welsing
CONTENTS
Chapter 1 Introduction 1
Part 1: Understanding associations between different process and outcome
measures
Chapter 2 Do radiographic joint damage and disease activity influence 21
functional disability through different mechanisms? Direct
and Indirect effects of disease activity in Rheumatoid Arthritis
Chapter 3 Does disease activity add to functional disability in estima- 39
tion of utility for rheumatoid arthritis patients on biological
treatment.
Chapter 4 Generalization and extrapolation of treatment effects from 57
clinical studies in Rheumatoid Arthritis
Part 2: Personalizing treatment: tailoring RA treatment to the individual
patient
Chapter 5 Systematic review on personalized treatment for rheumatoid 83
arthritis: an analytical approach with the focus on clinical ap-
plicability
Chapter 6 Determining the lowest optimally effective methotrexate 111
dose for individual RA patients using their dose response re-
lation in a tight control treatment approach
Chapter 7 Economic evaluation of a tight-control treatment strategy us- 125
ing an imaging device (HandScan) for monitoring joint inflam-
mation in early rheumatoid arthritis
Chapter 8 Personalized treatment using serum drug levels of adalim- 145
umab in rheumatoid arthritis patients: an evaluation of costs
and effects
Chapter 9 A personalized approach to biological therapy using predic- 165
tion of clinical response using MRP8/14 serum complex levels
in rheumatoid arthritis
Chapter 10 Summary and Discussion 181
Addendum Nederlandse Samenvatting 196
Acknowledgements 201
Curriculum Vitae 207
List of Publications 209

CHAPTER 1
INTRODUCTION
Chapter 1
RHEUMATOID ARTHRITIS, TREATMENT AND OUTCOME
MEASURES
1
Rheumatoid arthritis (RA) is a chronic disease marked by inflammation, mainly of the
joints, over time leading to joint destruction and functional disability.[1] [2] The dis-
ease can have different manifestations in different individuals ranging from mild to
severe disease. The resulting functional disability related to the disease also causes
loss of labour capacity, decreases quality of life [2] and shortens life expectancy.[3]
A recent publication reported the prevalence of RA globally to be 0.24 % mainly af-
fecting women (prevalence in women 0.35 % i.e. two times higher than in men).[4]
Joint stiffness and pain are the most commonly present symptoms with frequently
stiffness most severe after periods of prolonged rest and pain after periods of exer-
cise. RA usually starts affecting the small joints of hands and feet but also affects
larger joints. In longstanding RA all joints can be involved. Since 2010 new diagnos-
tic criteria for RA are available as developed by the American College of Rheumatol-
ogy (ACR) and European League Against Rheumatism (EULAR) in which the focus
is more on the features of the disease in the earlier stages that are associated with
persistent and/or erosive disease compared to the former 1987 classification criteria
for RA.[5] However, the final diagnosis of RA remains a clinical diagnosis by the
rheumatologist.
Treatment in RA
The treatment of RA aims to improve and maintain physical function and improve
quality of life by controlling inflammation and pain. Treatment has improved sub-
stantially over the past decades with the use Disease Modifying Anti Rheumatic
Drugs (DMARDS) starting immediately after diagnosis nowadays, compared to the
past, when frequently only non-steroidal anti-inflammatory drugs (NSAIDs) were
used in early or mild disease. Based on several studies over a decade the ‘tight
control’ with ‘treat to target’ (T2T) [6-9] principle has become a standard approach
especially in early disease within the so-called ‘window of opportunity’. Tight con-
trol can be defined as a treatment strategy, aimed at achieving as soon as possible a
specific target of low disease activity or preferably remission (‘treat to target’) in an
individual patient. The aim (target) has moved from achieving decrease in disease
activity to achieve very low disease activity or remission which has resulted in sig-
nificant improvement of structural and quality of life outcomes.[6, 7, 9-12] Metho-
trexate (MTX) is an anchor drug considered to be the optimal effective first line
treatment since it has demonstrated a high effectiveness especially in early disease
with relatively limited side effects. MTX has been tested and found to be effective
in T2T strategies.[13, 14] Apart from this improved approach to treatment several
new drugs have also become available, most notable the so-called biologic DMARDs
2