Table Of ContentLinköping University Medical Dissertation
No. 966
Disease activity, function and costs in early
rheumatoid arthritis
the Swedish TIRA project
Eva Hallert
Division of Rheumatology /AIR, Department of Molecular and
Clinical Medicine, Faculty of Health Sciences, Linköping
University, SE-581 85 Linköping, Sweden
Center for Medical Technology Assessment, Department of Health
and Society, Linköping University, SE-581 83 Linköping, Sweden
Linköping 2006
© Eva Hallert, 2006
Published articles have been reprinted with the permission of the
respective copyright holders.
Annals of the Rheumatic Diseases / BMJ Publishing Group (Paper I),
Rheumatology (Oxford) / Oxford University Press (Paper II and Paper
III).
Printed by LiU-Tryck, Linköping, Sweden, 2006
ISBN 91-85643-93-9
ISSN 0345-0082
To Claes
Anna, Åsa, Sara and Erik
CONTENTS
ABSTRACT 7
ABBREVIATIONS 9
LIST OF ORIGINAL PUBLICATIONS 11
INTRODUCTION 13
Rheumatoid arthritis 13
Assessments 15
Disease activity 15
Function 16
Economic burden 17
General 17
Direct costs 18
Indirect costs 19
Intangible costs 19
Treatment 20
The Swedish TIRA project 20
AIMS OF THE STUDY 23
PATIENTS AND METHODS 25
Disease and disease activity 26
Function and general health 27
Health care questionnaire 28
Statistical analyses 29
RESULTS 31
Course of disease and function (papers I and III) 31
Costs and predictors of costs (paper II) 33
Costs over 3 years (paper III) 36
Early predictors of TNF-targeted therapy (paper IV) 40
DISCUSSION 47
Disease and function (papers I and III) 47
Direct and indirect costs and predictors of high costs
(papers II and III) 50
Predictors of TNF-targeted therapy (paper IV) 57
CONCLUSIONS 59
SUMMARY IN SWEDISH/SAMMANFATTNING PÅ SVENSKA 61
ACKNOWLEDGEMENTS 63
REFERENCES 67
ABSTRACT
Rheumatoid arthritis (RA) is a major cause of progressive joint damage
and disability, and is associated with decline in quality of life, reduced
ability to work and increased health care utilisation. The economic
consequences of the disease are substantial for the individuals and
their families and for the society as a whole. This thesis describes a 5-
year follow up of 320 patients with early RA, enrolled between January
1996 and April 1998 in the Swedish multi-centre inception cohort
TIRA (early interventions in rheumatoid arthritis). Health status,
function and costs were investigated. Predictors of high costs were
calculated, and an algorithm was constructed to predict future need
for TNF-inhibitor treatment in patients not responding to traditional
disease-modifying antirheumatic drugs (DMARDs).
Clinical and laboratory data, measuresof functional capacity and self-
reported assessments were collected regularly. In addition, patients
completed biannual/annual questionnaires concerning all health care
utilisation and days lost from work due to the disease. Within 3
months, improvements were seen regarding all variables assessing
disease activity and functional ability, but 15% of the patients had
sustained high or moderate disease activity throughout the study
period. The scores of ‘health assessment questionnaire’ (HAQ) were
similar for men and women at baseline, but had a less favourable
course in women, who also had DMARDs more frequentlyprescribed.
Ambulatory care accounted for 76% of the direct costs during the first
year. Women had more ambulatory care visits and higher usage of
complementary medicine compared to men. Men (cid:149)65 years had low
costs compared to younger men and compared to women of all ages. In
multiple logistic regression tests, HAQ, high levels of IgM-class
rheumatoid factor (RF), and poor hand function increased the odds of
incurring high direct costs. Poor hand function and pain increased the
odds of incurring high indirect costs. Indirect costs exceeded direct
costs all three years. The average direct costs were €3,704 (US$ 3,297)
year 1 and €2,652 (US$ 2,360) year 3. All costs decreased over the
years, except those for medication and surgery. The indirect costs were
€8,871 (US$ 7,895) year 1 and remained essentially unchanged,
similarly for both sexes. More than 50% were on sick leave or early
retirement at inclusion. Sick leave decreased but was offset by increase
in early retirement. 14 patients (5%) were prescribed TNF-inhibitors at
the 3-year follow up, thus increasing drug costs substantially.
However, they incurred higher costs even before prescription of anti-
TNF therapy. At the 5-year follow-up (2001-2003), 31 patients (12%)
were prescribed TNF-inhibitors. Baseline values of erythrocyte
7
sedimentation rate, C-reactive protein, anti-CCP antibodies and
morning stiffness were significantly higher in this group. These
patients were also to a larger extent RF-positive and carriers of the
‘shared epitope’ (SE). Anti-TNF treated patients were significantly
younger and more often women. For men, a predictive model was
constructed using baseline data including SE+ and IgA-RF >100 U/L
and anti-CCP >240 U/L yielding a specificity of 98% and a sensitivity
of 71%. For women, disease activity score (DAS28) at the 3-month
follow-up proved to be a better predictor, and the final model
comprised SE+ and 3-month DAS28>5.2, giving a specificity of 95%
and a sensitivity of 59%.
8
ABBREVIATIONS
ACR American College of Rheumatology
Anti-CCP anti-cyclic citrullinated peptide
ACPA antibodies against citrullinated peptides/proteins
ARA American Rheumatism Association
CAM complementary medicine
CI confidence interval
CRP C-reactive protein
DAS28 28-joint count disease activity score
DMARD disease-modifying antirheumatic drug
ELISA enzyme-linked immunosorbent assay
ESR erythrocyte sedimentation rate
EULAR European League Against Rheumatism
FCA friction cost approach
HAQ Stanford Health Assessment Questionnaire
HCA human capital approach
HLA human leukocyte antigen
ICF International Classification of Functioning, Disability,
and Health
Ig immunoglobulin
MCP metacarpophalangeal (joint)
MTP metatarsophalangeal (joint)
NSAID non-steroidal anti-inflammatory drug
OMERACT Outcome Measures for Arthritis Clinical Trials
OR odds ratio
OT occupational therapist
PIP proximal interphalangeal (joint)
PGA physician’s global assessment of disease activity
PT physiotherapist
RA rheumatoid arthritis
RF rheumatoid factor
ROC receiver operating curve
SD standard deviation
SE shared epitope
SEK Swedish kronor
SEM standard error of the mean
SOFI Signals of Functional Impairment
TIRA Swedish acronym for ‘early intervention in RA’
TNF tumor necrosis factor
VAS visual analogue scale
WHO World Health Organization
9
Description:longitudinal observational studies, namely health status, disease process, organ damage, drug . ambulatory care visits to physician, physiotherapist, occupational therapist and nurse drugs . medication, all patients were offered rehabilitation such as supervised dynamic exercises, pool training and
