Assessing fatigue in ankylosing spondylitis: the importance of frequency and severity

Abstract

Objective. The aim of this study was to explore the value of assessing fatigue frequency and its relationship with fatigue severity in a UK cohort of AS patients.

Methods. Single items from the Evaluation of AS Quality of Life and BASDAI were used to measure fatigue frequency and severity, respectively. Items were included in a questionnaire containing AS-specific and generic measures, completed by participants in a postal survey at baseline and 6 months. Respondents were categorized at baseline into four groups according to fatigue frequency and severity and compared on other measures of health status.

Results. Of baseline responders who experienced fatigue (n = 451, 74%), 75% reported it to be frequent and severe, 15% frequent not severe and 10% severe not frequent. There was no difference between groups on gender, age or years with AS. Patients reporting frequent and severe fatigue had worse scores than other groups across all other health status measures. Patients reporting only frequent fatigue had similar scores to those reporting only severe fatigue, but worse than those without fatigue. Eighty-one per cent of non-fatigued patients and 79% of those with frequent and severe fatigue at baseline did not change their level of fatigue at 6 months. However, 80% of patients with frequent or severe fatigue at baseline changed, mainly to no fatigue (43%) or both frequent and severe fatigue (30%).

Conclusion. Routinely assessing both the frequency and severity of fatigue is important in understanding the impact of fatigue and its change over time. Not assessing frequency could result in the failure to identify patients with significant fatigue. However, the multidimensional nature of fatigue should be further explored.

Introduction

AS is an inflammatory condition presenting in young adults, characterized by widespread pain and stiffness and involvement of extra-articular sites [1]. Population prevalence is unknown, but estimates range from 0.1 to 1.4% [2]. AS may lead to progressive disability and impact on well-being [1, 2]. Many patients are unable to work [3] or their work productivity is significantly reduced by active disease, functional impairment and depression [3]. The long-term burden to individuals, health care systems and the economy is considerable [1–4].

Health economic burden accelerates steeply with increasing disease activity—a major component of which is fatigue [4]. Estimates suggest that up to 66% of AS patients are affected by fatigue [5], a figure comparable to other long-term conditions such as RA [6]. Growing acknowledgment of the relative importance of AS fatigue [7, 8] has fuelled interest in its treatment and management [9, 10] and the need for accurate and credible assessment [10]. Current guidance for AS fatigue assessment is limited to a single item, global assessment of severity [11]. Although quick to complete, such global assessments are criticized for poor measurement and practical properties and limited contribution to clinical decision-making and treatment evaluation [12, 13].

The complex, multidimensional nature of fatigue associated with a range of rheumatological conditions has been distinguished from normal everyday tiredness by frequency, persistence, unpredictability and failure to be resolved by rest [6, 14, 15]. The potentially complex nature of fatigue experience in AS challenges the extent to which a single-item assessment of severity could be considered accurate or relevant, with limited assessment potentially failing to identify patients at risk of fatigue-related impairment. Qualitative research with a large group of AS patients highlighted the relative importance of fatigue frequency compared with fatigue severity [16]. The aim of this study was to explore the value of assessing fatigue frequency and its relationship with fatigue severity in a large UK AS cohort and to make recommendations for future assessment practice.

Methods

Study methodology is detailed elsewhere [16]. It is discussed briefly below.

Subjects

A total of 1000 AS patients (modified New York criteria, 1984) from 10 specialist rheumatology centres across the UK were invited to participate in a postal survey. The study size was powered on the main study objective of evaluating a new AS measure of quality of life [16]. However, given a response of 60%, a sample size of 600 would give a margin of error of 4% for estimated prevalences of fatigue frequency and fatigue severity of 50%. Exclusion criteria included learning difficulties and an inability to comprehend English.

Method

Ethical approval was granted by the North Staffordshire Local Research Ethics Committee [16]. Patients provided written consent and self-completed a mailed questionnaire at baseline and at 6 months. Those not wishing to participate were asked to return uncompleted, pre-coded questionnaires in a prepaid envelope. Non-responders were sent reminders at 2 and 4 weeks.

Data collection and analysis

Single items taken from the Evaluation of AS Quality of Life (EASi-QoL) [16] and the BASDAI [11] were used to measure fatigue frequency and severity, respectively. The EASi-QoL item asked patients to indicate how often during the last week their AS had caused them to feel tired or lacking in energy on a 5-point scale of none of the time, a little of the time, some of the time, most of the time or all of the time. This question was developed taking into consideration face validity, importance, relevance and acceptability through face-to-face interviews with patients [16]. The BASDAI item asked patients to indicate the severity of fatigue or tiredness during the last week due to their AS on a 10-point numerical rating scale (NRS). Respondents’ were categorized at baseline according to item cut-off points for fatigue frequency (none/a little of the time vs some/most/all of the time) and severity [<5 (no/non-severe fatigue) vs ≥5 (severe fatigue)], as described in other studies [17]. Four groups were defined: (i) no fatigue (where frequency is none/a little of the time and severity is <5), (ii) frequent not severe, (iii) severe not frequent and (iv) frequent and severe.

The questionnaire also included questions relating to disease duration, anti-TNF treatment, function (BASFI), pain (NRS), emotional well-being (Hospital Anxiety and Depression Scale), self-efficacy, AS-specific quality of life [EASi-QoL [16] and Ankylosing Spondylitis Quality of Life (ASQoL)] and generic health status [36-item Short Form Health Survey (SF-36)].NSAID use was not recorded due to marked variations in administration frequency. Sociodemographic information, including age, gender and level of education and social deprivation was collected.

The four fatigue groups were compared across all measures included in the questionnaire at baseline, using one-way analysis of variance (ANOVA) for continuous data, with the Welch test used when equal variances could not be assumed based on the Levene test, and the chi-squared test for categorical variables. At 6 months, the change in fatigue status between baseline and 6 months was determined. For all statistical tests, the threshold of significance was set at α = 0.05. All analyses were performed using SPSS (version 20 for Windows; IBM, Armonk, NY, USA).

Results

Demographics and response rates

A total of 612 patients participated in the study (Table 1), with an adjusted baseline response rate of 64%. A total of 470 respondents (77%) participated at 6 months. Baseline respondents were predominantly male (71.6%) with a mean age of 50.8 years (s.d. 12.22). Most respondents had established disease, with a mean duration of diagnosis of 17.3 years (s.d. 11.68). Respondents at 6 months were slightly older than non-respondents (mean age 51.9 years vs 47.0) with resultant differences in disease duration (mean 17.9 years vs 15.1). There was no difference in baseline fatigue status between responders and non-responders at 6 months. A total of 611/612 (99.8%) respondents completed both fatigue items at baseline and 466/470 (99.1%) completed both at 6 months

Fatigue at baseline

There was a strong association between the two fatigue items at baseline, supporting an a priori hypothesized level of association (Spearman’s ρ = 0.80). Baseline responders experiencing fatigue (n = 451, 74%) were categorized into frequent and severe fatigue (75%), frequent not severe (15%) and severe not frequent (10%) (Tables 1 and 2). There was no difference between groups on gender, age or years with AS. However, patients reporting frequent and severe or severe but not frequent fatigue were more likely to use anti-TNF therapies (P = 0.01). Patients reporting frequent and severe fatigue had worse scores than other groups across all measures (Table 2). Patients reporting only frequent fatigue had similar scores compared with those reporting only severe fatigue but worse than those without fatigue across all measures.

Fatigue status at 6 months

A total of 104/128 (81%) non-fatigued patients and 205/259 (79%) of those with frequent and severe fatigue at baseline did not change their level of fatigue at 6 months. However, 80% of patients with frequent or severe fatigue at baseline changed, mainly to no fatigue (34/79, 43%) or to both frequent and severe fatigue (24/79, 30%). Of the patients who reported frequent not severe fatigue at baseline, 8/49 (16%) did not change at 6 months. Of the patients who reported severe not frequent fatigue at baseline, 8/30 (27%) did not change. There was little change in the treatment received or scores on other measures at 6 months in any group.

Discussion

This study is the largest of its kind to describe the high prevalence of fatigue in a nationally representative AS population, showing considerable impairment experienced by up to 75% of this group. This study highlights the importance of routinely assessing both the frequency and severity of AS fatigue to support a greater understanding of the impact of fatigue and its change over time. Failure to assess fatigue frequency could result in failure to identify patients with significant fatigue and fatigue-related impairment, to detect change in the impact of fatigue over time or to provide necessary information about the nuances of fatigue essential to delivering tailored health care.

Although limited to single-item assessments of severity and frequency (EASi-QoL [16]), fatigue assessment was informed by international guidelines [11]. The inclusion of fatigue frequency was driven by the relative importance placed on this concept by a large patient cohort [16]. The size and representativeness of this sample suggests that the results have national and potentially international relevance for patients with AS and key health professionals. Identifying patients from a secondary care setting may result in a patient cohort with more severe AS than a community-based sample. Good practice guidance, however, directs primary care physicians (general practitioners) in the UK to refer patients suspected of having AS to secondary care rheumatologists for diagnosis and ongoing care [18]. Unfortunately we do not have access to any data concerning study non-responders to assess the extent to which responders were similar to non-responders in terms of fatigue frequency or severity or AS severity. The detailed postal questionnaire may have introduced bias by reducing the number of responders who found completion of the questionnaire too tiring. The limited proportion of patients receiving anti-TNF therapies in this cohort, and variation in anti-TNF initiation related to baseline, reduces the clinical relevance of any evaluation of the impact of anti-TNF therapies on fatigue.

When defined as frequent and/or severe, almost three-quarters of this large patient cohort experienced fatigue; somewhat greater than AS fatigue prevalence in other studies [5, 6]. However, prevalence is affected by the definition of fatigue: 11% of the cohort with frequent but not severe fatigue would not have been identified using current Assessment of SpondyloArthritis International Society (ASAS) fatigue severity guidance. Moreover, a greater number of patients reported frequent but not severe fatigue. The extent of other health impairment was extensive in patients reporting both frequent and severe fatigue, and was greater across all measures than for those with just frequent or severe fatigue compared with those without fatigue. The majority of the patients without fatigue, or with severe and frequent fatigue at baseline, reported no change in their experience of fatigue at the 6-month follow-up point. However, the majority of patients who experienced frequent or severe fatigue at baseline did change, either to no symptoms or to both severe and frequent fatigue.

As expected, there was a strong association between fatigue severity and frequency items, suggesting that they measure similar, but not the same, aspects of fatigue. Moreover, patients can clearly distinguish between aspects of their AS fatigue experience [7, 10, 16]. Evidence from a range of long-term conditions has highlighted the multifactorial, inconsistent and complex nature of fatigue [13–15]. A growing number of multi-item questionnaires, or patient-reported outcome measures (PROMs), have been developed that attempt to capture this complexity. However, several reviews have highlighted the poor quality and acceptability of many multi-item and single-item measures in specific patient populations, such as in RA [12], SLE [15] and chronic fatigue syndrome/myalgic encephalitis [19], and the need for robust measures that accurately represent patients’ experiences. A recent increase in the use of single- and multi-item fatigue-specific PROMs in AS is evident [20], but evidence of essential measurement properties is limited and the relevance and acceptability to patients is unknown.

The findings of this research suggest that the current assessment guidelines for AS fatigue [11] are limited and should be revised. Recent advances in understanding the experience and consequences of RA fatigue have informed new management strategies and assessment guidance [13, 14]. Despite the growing recognition of its importance [7, 8], the experience of fatigue in AS is poorly understood and inadequately assessed [10]. Future research should focus on the impact and consequences of fatigue in AS, compared with other conditions and the general population, to inform clinical management and assessment and to explore the relevance and performance of existing multi-item fatigue PROMs. Moreover, the relationship between fatigue and other quality of life measures in AS could be explored. The involvement of patients as collaborative partners will enhance our understanding of the experience and management of fatigue in AS, improving any recommendations for appropriate fatigue assessment, interpretation and use.

The high prevalence of fatigue in AS emphasizes the need for further research to inform our understanding of its aetiology, course, management and assessment. Routinely assessment of both the frequency and severity of fatigue is important in understanding the impact of fatigue and its change over time. Failure to include fatigue frequency in routine assessment could result in failure to identify patients with significant fatigue-related impairment. However, the patient-reported experience of fatigue should be further explored in AS to identify the most appropriate and acceptable method of assessment.

Acknowledgements

The authors wish to thank all the patients who participated in the study and consultant rheumatologists, physiotherapists and research nurses in the EASi-QoL study group (Dr K. McKay, Torbay Hospital; Prof R. Sturrock, Glasgow Royal Infirmary; Dr M. Bukhari, Royal Lancaster Infirmary; Dr P. Creamer, Southmead Hospital; Dr S. Linton, Nevill Hall Hospital; Prof H. Gaston, Addenbrookes Hospital; Dr L. Kay, Freeman Hospital; Dr D. Mulherin, Cannock Chase Hospital; Dr R. Withrington and Liz van Rossen, Kent and Canterbury Hospital).

Funding: This study was funded by an unrestricted educational research grant from Wyeth UK.

Disclosure statement: The authors have declared no conflicts of interest.

References