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Abstract
Objective To identify predictors of poorer physical function in established psoriatic arthritis (PsA).
Methods PsA patients with disease duration of ≥10 years were identified from the Bath longitudinal cohort. Physical function was assessed using the Stanford Health Assessment Questionnaire (HAQ). Sex, age at diagnosis, duration of symptoms prior to diagnosis, smoking, treatment and year of diagnosis were included in a multivariable regression analysis to identify associations with HAQ.
Results 267 patients were identified for inclusion. The median age was 56 years (IQR 45–63), median disease duration was 13 years (IQR 10–18) and median HAQ score was 0.63 (IQR 0.13–1.25). The model predicted significant increases in HAQ related to smoking (0.23, 95% CI 0.04 to 0.42), age >50 years at diagnosis (0.27, 95% CI 0.03 to 0.51), symptom duration of ≥1 year before diagnosis (0.22, 95% CI 0.02 to 0.42), female sex (0.39, 95% CI 0.20 to 0.57) and history of treatment with an anti-TNF agent (0.63, 95% CI 0.32 to 0.93) at follow-up.
Conclusions Smoking, delay to diagnosis, older age at diagnosis, female sex and a history of anti-TNF treatment are associated with worse physical function in established PsA.
- Outcomes research
- Psoriatic Arthritis
- Disease Activity
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Background
Psoriatic arthritis (PsA) is a heterogeneous inflammatory arthritis associated with psoriasis. Patients are affected not only by skin and joint disease, but may also have axial disease, enthesitis, dactylitis, nail disease and the metabolic syndrome. These factors combine to have a detrimental impact on physical function and quality of life.1
Establishing the prognosis of a patient with early PsA is an important part of deciding when to initiate treatment. Observational cohort studies have identified adverse prognostic indicators for destructive disease including high inflammatory markers at presentation, high number of joints affected, high numbers of previous medications used and the presence of radiographic joint damage.2 ,3 In a recently reported study, clinical disease progression was more marked among those patients presenting with established disease. Those with disease duration of greater than 2 years at referral were more likely to be older, have longer duration of PsA and psoriasis, more joint damage and were less likely to be on disease modifying anti-rheumatic drugs (DMARDs).4
Physical function and disability are of central importance to patients with PsA. The Health Assessment Questionnaire (HAQ) is a functional outcome measure in rheumatoid arthritis (RA) and is an increasingly accepted and validated measure in PsA.1 ,5–7 Observational studies of patients with PsA have demonstrated functional disability to be significantly higher than that of the healthy population and comparable to RA.1 ,8 The longitudinal course of physical function in PsA as an outcome has been studied previously, focusing on the transition between predefined HAQ states.6 ,7 Older age, female sex, longer disease duration, and higher number of inflamed joints all predict transition between disability states as measured by the HAQ.6 Female sex is associated with an increased likelihood of progression of disability and increasing age is associated with a decreased likelihood of improvement.6 This study set out to investigate potential predictors of poorer physical function in established PsA.
Methods
Patients were selected from the longitudinal cohort of PsA patients at the Royal National Hospital for Rheumatic Diseases, Bath, UK. We have previously reported that 98.2% of the cohort fulfil the Classification for Psoriatic Arthritis (CASPAR) criteria.9 Patient-reported demographic data were collected at recruitment to the study and clinical data at elective follow-up appointments. Patients who had completed a HAQ at 10 years’ disease duration or greater were selected for inclusion. The HAQ score closest to 10 years disease duration was used as the outcome measure in this study. The origins of the variables (patient or physician reported, baseline or concurrent with HAQ) presented in table 1. Further information on the study methods can be found in the online supplementary methods.
Variables considered for inclusion in the model (267 patients)
Outcome of interest
The HAQ is a patient-reported assessment of ability to perform tasks related to daily living. Twenty questions are asked in eight domains: dressing and grooming, rising, eating, walking, hygiene, reach, grip, and activities. Patients rate their ability to perform tasks in these areas from ‘no difficulty’ to ‘unable to do’, over the prior week. The overall score is reported as a score between 0 and 3.5 Patients can be classified as mildly disabled (0–1), moderately disabled (>1–2) or severely disabled (>2–3).
Statistical analysis
Descriptive statistics were used to provide demographic information. A multivariable regression analysis was undertaken to identify factors that predict poorer physical function as measured with the HAQ. The HAQ score was preserved as a continuous rather than stratified response to preserve as much information in the data as possible. Dependent variables considered for inclusion are shown in table 1. The effect of calendar time, represented by year of diagnosis, exhibited a non-linear relationship with HAQ and was modelled using a smoothing spline preserving its continuous status. Other continuous variables were transformed to categorical variables in order to preserve potential non-linear relationships and to maximise statistical power. All possible two-way interactions were examined. All analyses were carried out using the statistical package R (2011).
Results
There were 267 of 609 patients in the long-term follow-up study with a HAQ at disease duration >10 years. The median age was 56 years (IQR 45–63), 47% were female, median disease duration was 13 years (IQR 10–18), median symptom duration was 14 years (IQR 11–19) and median HAQ score was 0.63 (IQR 0.13–1.25). A total of 175 (65.5%) had mild disability, 63 (23.6%) had moderate disability and 29 (10.9%) had severe disability (figure 1). Demographic details of patients not included in the final model are available for comparison in online supplementary table S1. In the final model significant associations were found for female sex, older age at diagnosis, longer symptom duration before diagnosis, smoking and history of treatment (table 2). Mode of onset of PsA (individually or grouped), time from diagnosis to HAQ and current DMARD or anti-tumour necrosis factor (TNF) treatment at the time of HAQ assessment were not found to be significant and were therefore not included in the final model. No two-way interactions were found to be significant.
Summary of associations with Health Assessment Questionnaire (HAQ) score at a minimum of 10 years’ psoriatic arthritis disease duration (235 patients)
Health Assessment Questionnaire (HAQ) score at a minimum of 10 years’ psoriatic arthritis (PsA) disease duration (median 13 years).
Discussion
In this study we observed that smoking, delay of at least 1 year between symptom onset and diagnosis, female sex, age of >50 years at diagnosis and those who require treatment with anti-TNF are likely to have poorer physical function in established disease.
To our knowledge this is the first study to suggest that smoking is associated with worse physical function in established PsA and the question arises as to whether this association is causal. Smoking is a well documented risk factor for many diseases and the detrimental effects in the spondyloarthritidies have been recently reviewed.10 Psoriasis studies have demonstrated that smoking adversely affects psoriasis and this may occur in a dose dependent fashion.11 ,12 There are three case control studies investigating the association of smoking with PsA. Tey et al13 reported worse psoriasis severity among smokers but no association with PsA. Pattison et al14 reported a non-significant trend towards PsA cases being less likely to have smoked. Eder et al15 reported fewer smokers among their PsA group versus psoriasis controls (40% vs 56%), leading to a significant negative association (OR 0.6, 95% CI 0.36 to 0.89).15 A recent large observational study from the longitudinal Nurses’ Health Study II showed that smoking is associated with an increasing risk of developing PsA, and this risk increases with smoking duration and intensity.16 The findings of our present study add to the weight of evidence for the detrimental effects of smoking on disease outcome.
The findings of poorer function in established disease among those presenting with longer symptom duration before diagnosis add to the recent data from Toronto reporting worse clinical outcome among those presenting to their unit with disease duration of >2 years.4 The benefits of early referral, diagnosis and treatment for patients with RA with poor prognostic markers are well established. The findings of our present study are consistent with reports in RA demonstrating that prolonged delay between symptom onset and diagnosis adversely influences outcome.17
Treatment has been included in the model as a surrogate of disease severity, not as an estimate of treatment effect on HAQ. Current treatment with DMARDs or anti-TNF was considered for inclusion (table 1) but no significant association was found and it was therefore not included in the final model. Mode of onset was also not associated with a significant difference in HAQ at 10 years. We speculate that this may be related to the small numbers available or the recognised transition between phenotypes during the course of disease.
The findings of our study should be interpreted with caution, taking into consideration some potential methodological issues. Loss to follow-up is a reality of long-term observational studies, although previous findings from another long-term follow-up study demonstrated that loss to follow-up appeared to be at random and without association with any specific clinical characteristics.18 We have taken a single HAQ score to represent a functional outcome measure in established disease. Discrete assessments are subject to variation and therefore may be a less reliable estimate of the true cumulative burden of disability. However the transition between HAQ states and the influence of current disease activity on HAQ both diminish with increasing disease duration.6 ,7 Therefore to us using a single HAQ score as an outcome is a valid strategy in patients with well established PsA. Finally we were not able to include data on socioeconomic status, co-morbidities, obesity, baseline radiographic damage or joint inflammation. Smoking in particular is a well recognised risk factor for diseases that may adversely affect function, such as chronic lung disease and ischaemic heart disease.
In conclusion, our study suggests that smoking, delay to diagnosis, older age at diagnosis, female sex and a history of anti-TNF treatment are associated with worse physical function in established PsA. Smoking and delay to diagnosis are the two potentially modifiable risk factors, and further study to determine whether these associations are causal is warranted.
Acknowledgments
Mrs M Knight (database administrator), Sr N Waldron (specialist research nurse) and Sr Nina Griffith (research nurse).
References
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Files in this Data Supplement:
- Data supplement 1 - Online supplement
- Data supplement 2 - Online table 1
Footnotes
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Handling editor Tore K Kvien
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Contributors Each individual named as an author meets the uniform requirements for manuscripts submitted to biomedical journals criteria for authorship.
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Funding LOPAS I is funded through an unrestricted grant from Abbott Laboratories Ltd.
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Competing interests None.
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Patient consent Obtained.
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Ethics approval The study was approved by the Bath Research Ethics Committee and has been conducted in accordance with the Declaration of Helsinki. All participants signed informed consent.
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Provenance and peer review Not commissioned; externally peer reviewed.