Non-Adherence to Disease-Modifying Antirheumatic Drugs in Early Arthritis Annelieke Pasma ...

200 Pages·2015·2.46 MB·English

Non-Adherence to Disease-Modifying
Antirheumatic Drugs in Early Arthritis
Annelieke Pasma
The work presented in this thesis was funded by the Dutch Arthritis Foundation (Reuma-
fonds). Financial support for the publication of this thesis was kindly provided by UCB Pharma,
Abbvie, Pfizer, the department of Rheumatology, the department of Psychiatry, section Medical
Psychology and Psychotherapy, and the Erasmus University Medical Center Rotterdam

ISBN: 978-94-6299-207-8
© Annelieke Pasma, 2015
All rights reserved. No part of this publication may be reproduced, stored in a retrieval system,
or transmitted in any form or any means, electronic, mechanical, photocopying, recording, or
otherwise, without the prior permission from the author or from the copyright-owning journals
of previously published chapters.
Lay-out: Pepijn Berghout - www.pepijnberghout.com
Printing: Ridderprint BV
Cover design: Annelieke Pasma
Non-Adherence to Disease-Modifying
Antirheumatic Drugs in Early Arthritis
Therapie-ontrouw aan antireumatische
medicatie bij vroege artritis
Proefschrift
ter verkrijging van de graad van doctor aan de
Erasmus Universiteit Rotterdam
op gezag van de
rector magificus
Prof.dr. H.A.P. Pols
en volgens besluit van het College voor Promoties.
De openbare verdediging zal plaatsvinden op
woensdag 25 november 2015 om 15:30 uur
door
Annelieke Pasma
geboren te Vlissingen
Promotiecommisie
Promotoren
Prof.dr. J.M.W. Hazes
Prof.dr. J.J. van Busschbach
Overige leden
Prof.dr. T. van Gelder
Prof.dr. C.L. Mulder
Prof.dr. S. van Dulmen
Copromotor
Dr. A. van ‘t Spijker
Paranimfen
Wietze Pasma
Jantsje Pasma

Table of contents
Chapter 1 General introduction 9
Part 1: Consequences of non-adherence 19
Chapter 2 Non-adherence to DMARDs is associated with higher disease activity in early arthri- 21
tis patients in the first year of the disease
Chapter 3 Does non-adherence to DMARDs influence hospital-related healthcare costs for 39
early arthritis in the first year of treatment?
Part 2: How to measure non-adherence 55
Chapter 4 Non-adherence to disease-modifying antirheumatic drugs in the first year after diag- 57
nosis: comparing three adherence measures in early arthritis patients
Part 3: Determinants of non-adherence 73
Chapter 5 Factors associated with adherence to pharmaceutical treatment for rheumatoid 75
arthritis patients: a systematic review
Chapter 6 Facilitators and barriers to adherence in the initiation phase of disease-modifying 101
antirheumatic drugs (DMARD) use in arthritis patients who recently started with
their first DMARD treatment
Chapter 7 How to study determinants related to medication adherence in newly diagnosed 115
polyarthritis patients for the development of a prediction instrument
Chapter 8 Psychosocial predictors of DMARD adherence in the first three months of treat- 137
ment for early arthritis
Chapter 9 Discussion 157
Summary / Samenvatting 173
PhD portfolio 183
Publications 189
About the author 193
Dankwoord 197

Chapter 1
General introduction
When patients receive their first medication for their rheumatic condition, it is essen-
tial that they use the medication as prescribed by their physician. If not, not only their
disease will get worse, but the rheumatologist might wrongfully conclude that more
intensive medication is needed. In this thesis we investigate the consequences of non-
adherence in early arthritis patients and what causes patients to be non-adherent to the
medication prescribed by the physician.

Early arthritis
Inflammatory rheumatic diseases present themselves in different forms, all being character-
ized by persistent synovitis and systemic inflammation. Rheumatoid arthritis (RA) is prevalent
in about 1% of the Western population, and each year in 5-50 per 100.000 persons RA is
diagnosed. The disease is more common in women and elderly.1 Another form of inflamma-
tory arthritis is accompanied with psoriasis; psoriatic arthritis (PsA). This diagnosis is made in
slightly more males than females. Annual incidence rates range from 6 per 10.000 to 6.8 per
10.000 of the adult population.2 Spondyloarthritis presents itself with inflammatory back pain
and peripheral oligoarthritis. The incidence rate of spondyloarthritis ranges from 6.9 to 7.3 per
100.000 person years.2
What these diseases have in common is that, in the early stage of the disease, they present
themselves with joint inflammation, leading to pain and loss of function. When poorly
managed, the disease can cause joint damage, cardiovascular and other co-morbidities and a
decreased quality of life. Therefore it is essential that patients adhere to the physician’s treat-
ment instructions in this early stage of the disease.
Treatment
Over the last decades the outcome for early arthritis has improved hugely, since it is treated
timely and intensively, following the treat to target principle.3, 4 Early arthritis is commonly
treated with one or a combination of more disease-modifying antirheumatic drugs (DMARDs).
The primary target of treatment is to reach a state of clinical remission, or at least a state of low
disease activity. With a timely and intensive treatment in the first year after diagnosis, remission
will be reached. Until remission is reached, treatment should be adjusted every three months,
following the treat to target guidelines.4 The first step-up in therapy is to higher DMARD
dosages or additional DMARDs. When treatment with conventional, synthetic DMARDs
fails, a step up to more expensive and advanced biological therapy is made. Decisions whether
or not to step up are based on the effectiveness of the treatment as seen by patient and physi-
cian. Obviously, when the patient is non-adherent to the treatment, this insight is blurred and
decisions about stepping up the treatment are made prematurely.
Non-adherence to treatment
Although the importance of adherence to medication is clear, still a large proportion of
patients is non-adherent to their therapy. Research mainly focused on patients with chronic
diseases, where the problem of non-adherence is more serious than in acute diseases. Non-
adherence ranges from 0% to 95.4% with an overall average of 24.8%.5 For HIV disease,
adherence seems to be highest with an average of 88.8% and the lowest in sleep disorders,
with an average adherence percentage of 65.5%.5 The differences in non-adherence between
various diseases might be due to the symptoms with which the disease expresses itself, and the
experienced effect of the medication. For example, adherence to preventive medicine for hy-
10