Health-related quality of life in patients with rheumatoid arthritis

169 Pages·2009·15.38 MB·English

by  Jacob Hansen

Health-related quality of life in patients with rheumatoid arthritis
A comparative validation of selected measurement instruments

Louise Linde, MD

The DANBIO registry
Department of Rheumatology
Hvidovre Hospital

Phd thesis
Faculty of Health Sciences
University of Copenhagen
May 2009

Forsvaret finder sted fredag den 27. november 2009 kl. 14.00 i auditorium 3+4, Hvidovre Hospital.

Preface
This PhD thesis is based on studies carried out at the Department of Rheumatology, Hvidovre Hospital in
collaboration with 10 other Danish centers. The successful completion relies on many people to whom I
would like to express my gratitude.

Schering-Plough A/S is gratefully acknowledged for supporting the study with an unrestricted research grant.
The DANBIO registry, the Danish Rheumatism Association, Hvidovre Hospital and the Copenhagen
University, Faculty of Health Sciences Foundation are also acknowledged for supporting the study.

In particular, I would like to thank:
My academic advisor Merete Lund Hetland, who has been a never ending inspiration with her positive
attitude and enthusiasm for research. Her experienced guidance reflects a deep knowledge in the field of
rheumatology, and her communicative skills are second to none. Through many fruitful scientific
discussions, she has assisted in lifting the academic level of the thesis.
My advisor Jan Sørensen for invaluable guidance in the statistical analyses and in solving technical
problems. With his background in health economics, he has provided alternative views and challenged my
“medical” way of thinking.
My advisor Mikkel Østergaard, who has put a great amount of effort into creating a well-coming and
inspiring environment for young researchers – and has succeeded in the task. He has moreover offered
constructive, academic criticism throughout the process.
All the patients who entered the study and the staff at the participating Departments of Rheumatology at
Hvidovre, Gråsten, Hjørring, Hørsholm, Vejle, Bispebjerg, Holbæk, Odense, Slagelse, Herlev,
Frederiksberg. The data collection would not have been possible without you. Special thanks go to Lena
Unkerskov for assistance with the data entry and Lykke Midtbøll Ørnbjerg for help with the data collection in
population I.
My co-authors Kim Hørslev-Petersen, Claus Rasmussen and Dorte Vendelbo Jensen for providing valuable
comments in the preparation of the manuscripts, and Tuulikki Sokka for sharing scientific ideas and data from
Finland and QUEST.
All my dear collegues and friends at the Department of Rheumatology, Hvidovre Hospital: Anne Duer-
Jensen, Charlotte Wiell, Uffe Møller Døhn, Brigitta Pedersen-Zbinden, Grethe Iversen, Hanne Bagger
Christiansen, Linda Thomsen, Sophine Krintel and Teresa Rozenfeld who have created a warm and cheerful
atmosphere. Coming to work has been much more fun because of you!
My familiy and friends for providing joyful times and moral support when needed.
Very special thoughts go to my father, who sadly passed away during my work on the PhD study.
List of terms and abbreviations

15D 15 Dimensions of health
ADL Activities of Daily Living
AIMS Arthritis Impact Measurement Scale
BMI Body Mass Index
BP Bodily Pain
CDAI Clinical Disease Activity Index
CRP Serum C-Reactive Protein
DAS28 Disease Activity Score (based on 28 swollen and tender joint counts)
DMARD Disease-Modifying AntiRheumatic Drug
EQ-5D The EuroQoL 5 dimensions
ES Effect Size
GH General Health
HAQ Health Assessment Questionnaire
HRQoL Health-Related Quality of Life
HUI Health Utilities Index
ICC Intraclass Correlation Coefficient
IgM-RF IgM Rheumatoid Factor
LBP Low Back Pain
MCS Mental Component Score
MH Mental Health
MHAQ Modified HAQ
NHP Nottingham Health Profile
NSAID Non-Steroidal Anti-Inflammatory Drug
PCS Physical Component Score
PF Physical Functioning
RA Rheumatoid Arthritis
RAQoL Rheumatoid Arthritis Quality of Life scale
RE Role Emotional
RP Role Physical
SES SocioEconomic Status
SF Social Functioning
SF-36 Short-Form 36 Health Survey
SF-12 Short-Form 12 v2 Health Survey
Sociodemography Gender, age, residence, ethnicity, marital status, educational level and SES
SRM Standardized Response Mean
VAS Visual Analogue Scale
VT Vitality
Publications

The present PhD thesis is based on the following three papers, which will be referred to in the text
as paper 1, paper 2 and paper 3, respectively. The papers are enclosed as Appendices I, II and III,
respectively.

Paper 1 (Appendix I)
Health-related quality of life: validity, reliability, responsiveness of SF-36, 15D, EQ-5D, RAQoL
and HAQ in patients with rheumatoid arthritis.
Linde L, Sørensen J, Østergaard M, Hørslev-Petersen K, Hetland ML.
J Rheumatol 2008;35(8):1528-37

Paper 2 (Appendix II)
What factors influence the health status of RA patients as measured by the SF-12 and HAQ?
Linde L, Sørensen J, Østergaard M, Hørslev-Petersen, K, Rasmussen C, Vendelbo Jensen D,
Hetland ML
J Rheumatol 2009;36:2183-2189

Paper 3 (Appendix III)
Does clinical remission lead to normalization of health status in rheumatoid arthritis patients? A
comparison of EQ-5D in 3156 RA patients with 16136 individuals from the general population.
Linde L, Sørensen J, Østergaard M, Hørslev-Petersen, K, Hetland ML.
Submitted April 2009.*

* A revision of paper 3 entitled: “Does clinical remission lead to normalization of EQ-5D in patients with RA and is the
selection of remission criteria important? A comparative study of 3156 patients and 16136 individuals from the general
population” was accepted for publication in the Journal of Rheumatology in September 2009.

Contents

1. Introduction..........................................................................................................................6
2. Objectives..............................................................................................................................7
2.1. Main objective...................................................................................................................................7
2.2. Specific objectives............................................................................................................................7
3. Background...........................................................................................................................8
3.1. Rheumatoid arthritis.........................................................................................................................8
3.2. Health-related quality of life............................................................................................................9
3.3. HRQoL instruments........................................................................................................................11
3.4. Measurement properties.................................................................................................................14
3.5. What factors influence HRQoL in patients with RA?..................................................................17
4. Methods...............................................................................................................................20
4.1. Patients.............................................................................................................................................20
4.2. Population I.....................................................................................................................................21
4.3. Population II....................................................................................................................................22
4.4. Population III..................................................................................................................................22
4.5. Data collection................................................................................................................................22
4.6. HRQoL instruments used in the PhD-study..................................................................................23
4.7. Clinical assessment.........................................................................................................................23
4.8. Statistical analysis...........................................................................................................................24
5. Results.................................................................................................................................26
5.1. Study population.............................................................................................................................26
5.2. Validity, reliability and responsiveness.........................................................................................27
5.3. Factors associated with HRQoL....................................................................................................29
5.4. Disease activity and HRQoL..........................................................................................................31
6. Discussion............................................................................................................................33
6.1. Study population.............................................................................................................................33
6.2. Validity, reliability and responsiveness.........................................................................................33
6.3. Factors associated with HRQoL....................................................................................................39
6.4. Disease activity and HRQoL..........................................................................................................42
6.5. Strengths and limitations................................................................................................................44
7. Conclusions.........................................................................................................................46
8. Future perspectives ............................................................................................................48
9. English Summary...............................................................................................................49
10. Danish Summary................................................................................................................51
11. References...........................................................................................................................53

Appendices I-V

1. Introduction
Rheumatoid arthritis (RA) is a chronic, inflammatory disease affecting physical, mental and social
aspects of patients´ lives. Traditional clinical disease markers such as joint counts and serum C-
reactive protein (CRP) describe some of the physical aspects of RA, but do not embrace the full
spectrum of patient-perceived disease consequences. To apply a broader assessment of RA, patient-
reported instruments such as the SF-36 Health Survey (SF-36) and the Health Assessment
Questionnaire (HAQ), are often incorporated in clinical trials of RA and to a lesser extent in routine
care (50). Such instruments are often said to describe health-related quality of life (HRQoL).
Basic measurement properties should be satisfied in order for such instruments to be clinically
useful, and as they include a heterogeneous group ranging from visual analogue scales to multi-
dimensional questionnaires, comparative research across instruments is needed to confirm their
measurement properties. Such research especially in routine care settings is scarce (68;69;87).
HRQoL measurement may be influenced by a range of factors that vary between individuals
(23;62;73;81;86), and ideally, such elements should be adequately taken into account in studies of
HRQoL. Unfortunately, a thorough knowledge of such factors is not available, which hampers the
interpretation and comparability of the results across different populations.
In the past decade, the treatment goal for RA has been tightened due to the introduction of novel
and improved therapies (48;65;108). More patients achieve clinical remission, but whether
remission leads to normalization of HRQoL in these patients, has not been investigated. Therefore
studies comparing the HRQoL in patients with RA stratified according to disease activity with the
HRQoL of the general population are needed.
Several issues regarding HRQoL measurement thus remain unanswered and research is needed to
facilitate the interpretation of HRQoL studies and to put the results into a clinical perspective.
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2. Objectives
2.1. Main objective
To validate and compare selected HRQoL instruments by an evaluation of their measurement
properties and an investigation of their association with factors related to RA, sociodemography,
comorbidity and lifestyle in cross-sectional and longitudinal studies of patients with RA in clinical
practice.
2.2. Specific objectives
The main objective was subdivided into the following specific objectives:
1. To study the construct validity, reliability and responsiveness of the selected HRQoL
instruments.
2. To identify which factors related to RA, sociodemography, comorbidity and lifestyle that
influence the selected HRQoL instruments.
3. With remission as the benchmark and the general population as the standard of reference, to
investigate the association between the selected HRQoL instruments and disease activity,
adjusted for factors related to RA, sociodemography, comorbidity and lifestyle.

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