Management of Early Rheumatoid Arthritis

191 Pages·2013·10.29 MB·Dutch

Management of Early Rheumatoid Arthritis:
Solving the Unresolved.

the tREACH trial
Financial support for the publication of this thesis was kindly provided by: Pfizer B.V.,
AbbVie B.V., Dutch Arthritis Foundation and Masters in Business B.V.

ISBN: 978-90-5335-734-7

Cover design by Ridderprint B.V., J. Bakker, P.H.P. de Jong.
Design and lay-out of thesis by Ridderprint B.V., P.H.P. de Jong.
Printed by Ridderprint B.V.

No part of this thesis may be reproduced or transmitted in any form or by any means
without prior permission of the author, P.H.P. de Jong, or when appropriate, of the
scientific journal in which parts of this thesis have been published.

© 2013 P.H.P. de Jong
Management of Early Rheumatoid Arthritis:
Solving the Unresolved.

the tREACH trial

Behandeling van vroege reumatoïde artritis:
Het onopgeloste opgelost

het tREACH onderzoek

Proefschrift

ter verkrijging van de graad van doctor aan de
Erasmus Universiteit Rotterdam
op gezag van de
rector magnificus

Prof.dr. H.A.P. Pols
en volgens besluit van het College voor Promoties.

De openbare verdediging zal plaatsvinden op
10 december 2013 om 15:30 uur

door

Pascal Hendrik Pieter de Jong

geboren te Rotterdam
PROMOTIECOMMISSIE

Promotor: Prof.dr. J.M.W. Hazes

Overige leden: Prof.dr. J.L.C.M. van Saase
Prof.dr. T. van Gelder
Prof.dr. M. Boers

Co-promotor: Dr. A.E.A.M. Weel

Table of contents

9 CHAPTER 1
General introduction

21 CHAPTER 2 Ann Rheum Dis. 2013 Jan; 71 :72-8.
Induction therapy with a combination of DMARDs is better than methotrexate
monotherapy: first results of the tREACH trial.

43 CHAPTER 3 Submitted
Initial triple DMARD therapy is more efficient than methotrexate monotherapy in
recent onset rheumatoid arthritis; 1-year data of a randomized clinical trial (tREACH)

77 CHAPTER 4 Submitted
Best cost-effectiveness and worker productivity with initial triple DMARD therapy
compared with methotrexate monotherapy in early rheumatoid arthritis;
Cost-utility analysis of the tREACH trial.

107 CHAPTER 5 Rheumatology (Oxford). 2012 Jul; 51: 1269-77.
Treatment decisions and related costs differ significantly depending on the
choice of a disease activity index in rheumatoid arthritis, according to 1987 and
2010 classification criteria.

127 CHAPTER 6 Ann Rheum Dis. 2013 Sep; 72: 1659-1663.
Response to glucocorticoids at 2 weeks predicts the effectiveness of DMARD
induction therapy at 3 months: post hoc analyses from the tREACH study.

143 CHAPTER 7 Arthritis Rheum. 2012 Oct; 64: 3095-101.
Brief Report: To squeeze or not to squeeze, that is the question! Optimizing the
disease activity score in 28 joints by adding the squeeze test of
metatarsophalangeal joints in early rheumatoid arthritis.

155 CHAPTER 8
General discussion

169 CHAPTER 9
Summary

175 CHAPTER 10
Nederlandse samenvatting

181 ADDENDUM
PhD portfolio
Publications
About the Author
Acknowledgements
Role of funding source
Dankwoord

CHAPTER 1

General introduction
RHEUMATOID ARTHRITIS

Rheumatoid arthritis (RA) is a systemic auto-immune disease, which is characterized by
chronic inflammation of multiple joints. About 1% of the people in western countries
have RA, and each year in 5 – 50 per 100.000 persons the diagnose of RA is made. The
prevalence of RA varies geographically.1 In the Netherlands the prevalence of RA in
2007, based of primary care registries, was 0.7% (95% confidence interval (CI): 0.48% -
1.03%) for men and 1.1% (95% CI: 0.76% - 1.60%) for women. The mean annual
incidence in the Netherlands in 2007 was respectively 75 and 120 per 100.000 for men
and women. Disease onset is most often between 40 and 60 years of age. The mortality
rate for men and women with RA in 2010 was respectively 0.3 and 0.9 per 100.000.2
Clinical and radiographic outcomes have improved enormously in the last two
decades, due to major paradigm changes in the management of RA.3-4 Evolvement of
clinical trial methodology, emergement of new therapeutic options – in particular
biologicals – and reevaluating treatment strategies caused these major paradigm
changes. These paradigm changes are:
• Early detection of the disease;
• Early initiation of ‘intensive’ therapy;
• A treat-to-target approach
The 2010 ACR/EULAR classification criteria for RA and formulation of the EULAR
recommendations for the management of RA were developed, so rheumatologists
could apply these changes in daily practice.3-4 The 2010 EULAR recommendations
advocate, in patients with newly diagnosed RA, that: (1) the initial treatment strategy
encompasses at least methotrexate (MTX) with or without glucocorticoids (GCs), (2)
treatment is targeted to achieve remission, or low disease activity, preferably within 3
months, and (3) treatment should be adjusted, every 1-3 months, until the target is
reached.4 Complying with these recommendations result in better functional and
radiological outcomes.1, 5
Despite of the new classification criteria and treatment recommendations,
important unresolved questions for daily practice remain. Therefore, the focus of this
thesis will be on the management of early RA. In the next section I will elaborate on the
argumentation for each paradigm change and accentuate the unresolved questions,
which need to be solved for daily practice.

Early detection of the disease
Various studies suggest the existence of a ‘window of opportunity’, which encompasses
the first 12 weeks after symptom onset. Early initiation of Disease Modifying Anti-
Rheumatic Drugs (DMARDs) during this 12 week period improved clinical outcome and
delayed or even prevented radiographic damage.6-11 Distinguishing RA from other
arthritic disorders is rather difficult, especially in the very early stages of the disease.
Until 2010 only the 1987 classification criteria for RA, made by the American College of