Axial spondyloarthritis (axSpA), a subtype of spondyloarthritis, is a debilitating inflammatory condition involving the spinal and sacroiliac joints, contributing to a significant diminution in quality of life. Historically, characterization of patient outcomes in axSpA has been a challenge due to the lack of data from longitudinal epidemiologic studies and the nonspecific nature of inflammatory laboratory markers to monitor disease activity. In this review, measures developed to address these clinical domains are discussed and compared, of which 3 are commonly used in diagnosis and therapeutic planning. Provider data regarding utilization of these measures are also included to clarify current clinical practice trends.
Key points
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More than 20 separate studies in more than 12,000 patients have validated patient-reported outcome measures in axial spondyloarthritis over the past 30 years.
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Of the available patient-reported outcome measures available for axial spondyloarthritis, only 3 to 4 are currently used routinely.
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About half of North American rheumatologists with expertise in axial spondyloarthritis use formal patient-reported outcome measures in their practice.
Axial spondyloarthritis (axSpA) is a complex, debilitating inflammatory condition characterized by involvement of the joint of the spine and the sacroiliac joints. Ankylosing spondylitis (AS)—a severe and prototypic form of axial spondyloarthritis—includes fibrous or bony bridging of joints in the spine, frequently involving multiple intervertebral discs. Although the history of AS, as the most obvious presentation of axSpA, extends back several centuries, its cause and pathophysiology have yet to be fully defined. The delineation of patient-reported outcomes (PROs) in axSpA and AS has been a longstanding challenge, due to the lack of data from longitudinal epidemiologic studies and the nonspecific nature of inflammatory laboratory markers to monitor disease activity. At least since the execution of therapeutic trials in the 1960s, PROs have been increasingly used to better define this disorder. PRO measures provide a quantifiable and reproducible method of capturing data in the context of medical practice, allowing for efficient measures of quality of life and disease activity. An overview of current patient-reported measures and their validation are provided herein.
History of axial spondyloarthritis and ankylosing spondylitis
The diagnosis of AS traces back to Galen’s initial differentiation from rheumatoid arthritis in 200 ad , but it was not until 1559 that the first historical description of AS appeared in the literature. In that year, Realdo Colombo described 2 skeletons with AS-like characteristics in his book, De Re Anatomica . Other clinical descriptions have been scattered since then, and AS has historically been synonymous with terms such as Bechterew’s disease and Marie-Strumpell disease. As radiographic and clinical reports began to more precisely depict the features of AS, umbrella terms—“spondyloarthropathy” and “spondyloarthritis”—were then introduced in the 1970s, to distinguish this family of related disorders from rheumatoid arthritis. This group of conditions included AS, psoriatic arthritis, reactive arthritis, inflammatory bowel disease–associated arthritis, and undifferentiated spondyloarthritis.
In his 1977 landmark paper, rheumatologist Andrei Calin and colleagues described modern diagnostic criteria for inflammatory back pain (IBP), which was a hallmark of AS, and later, axSpA. Their criteria included: (a) age at onset less than 40 years; (b) back pain greater than 3 months; (c) insidious onset; (d) morning stiffness; and (e) improvement with exercise. A few years later, a simplified version of the concept of IBP was codified in the modified New York criteria, which gained rapid acceptance. Although adequate for identifying the well-established disease represented by AS, these criteria did not capture more subtle and earlier forms of axSpA. Thus, 2 additional classification criteria were constructed in the 1990s that identified a broader disease concept, including early-stage disease and peripheral spondyloarthritis without axial involvement. Finally, in 2009, the Assessment of SpondyloArthritis international Society (ASAS) Criteria were developed using more rigorous methodology to allow for the identification of axSpA by integrating clinical, laboratory, and imaging data.
History of axial spondyloarthritis and ankylosing spondylitis
The diagnosis of AS traces back to Galen’s initial differentiation from rheumatoid arthritis in 200 ad , but it was not until 1559 that the first historical description of AS appeared in the literature. In that year, Realdo Colombo described 2 skeletons with AS-like characteristics in his book, De Re Anatomica . Other clinical descriptions have been scattered since then, and AS has historically been synonymous with terms such as Bechterew’s disease and Marie-Strumpell disease. As radiographic and clinical reports began to more precisely depict the features of AS, umbrella terms—“spondyloarthropathy” and “spondyloarthritis”—were then introduced in the 1970s, to distinguish this family of related disorders from rheumatoid arthritis. This group of conditions included AS, psoriatic arthritis, reactive arthritis, inflammatory bowel disease–associated arthritis, and undifferentiated spondyloarthritis.
In his 1977 landmark paper, rheumatologist Andrei Calin and colleagues described modern diagnostic criteria for inflammatory back pain (IBP), which was a hallmark of AS, and later, axSpA. Their criteria included: (a) age at onset less than 40 years; (b) back pain greater than 3 months; (c) insidious onset; (d) morning stiffness; and (e) improvement with exercise. A few years later, a simplified version of the concept of IBP was codified in the modified New York criteria, which gained rapid acceptance. Although adequate for identifying the well-established disease represented by AS, these criteria did not capture more subtle and earlier forms of axSpA. Thus, 2 additional classification criteria were constructed in the 1990s that identified a broader disease concept, including early-stage disease and peripheral spondyloarthritis without axial involvement. Finally, in 2009, the Assessment of SpondyloArthritis international Society (ASAS) Criteria were developed using more rigorous methodology to allow for the identification of axSpA by integrating clinical, laboratory, and imaging data.
Different patient-reported outcome measures
The emergence of each of these classification criteria has often ushered in a complementary set of PRO measures. As a result, outcome measures for describing spondyloarthritides have exploded within the last 15 to 20 years, with significant progress in documentation of PROs, clinical and physical assessments, and characterization of disease stages for treatment protocols. The characterization of disease activity in axSpA, on the other hand, has been somewhat delayed by comparison.
The following discusses the current uses, critiques, and evidence of validation for the currently published series of axSpA measures. Basic information regarding the content, format, method of calculation, and both respondent burden and time to score is provided in Table 1 .
| PRO | General Description/Components | No. of Items Comprising the PRO | Format | Common Method of Calculation | Respondent Burden (min) | Time to Score (min) | Languages |
|---|---|---|---|---|---|---|---|
| ASDAS | Back pain, duration of am stiffness, peripheral joint pain/swelling, general well-being, CRP/ESR | 5 | Likert: 0–7 | ASDAS calculator | <1 min | <1 min | US English, Spanish, French, multiple+ |
| ASQoL | Impact of disease on sleep, mood, motivation, coping, ADL, relationships, social life | 18 | Likert: Y/N | Summation | 2–16 min | <1 min | US English, Canadian French/English, German, Spanish, Chinese, multiple+ |
| BASDAI | Back pain, fatigue, peripheral joint pain/swelling, tenderness, disease and severity of am stiffness | 6 | Numeric: 0–10 ( am stiffness = 0–2+ h); VAS, 0–10 cm | Mean of Q1-4 + (Mean of Q5/Q6) | 30 s–2 min | <1 min | English, French, Swedish, German, Arabic, Spanish, multiple+ |
| BASFI | Functional anatomy and coping with daily life | 6 | Numeric: 0–10; VAS (0–10 cm) | Mean of 6 subscores | <3 | <1 min | English, French, German, Spanish, Chinese, multiple+ |
| BAS-G | Well-being, over last week and last 6 mo | 2 | Numeric: 0–10 | N/A | <1 min | <1 min | Dutch and Norwegian, few others |
| BASMI | Cervical rotation, tragus to wall, lumbar flexion, lumbar side flexion, intermalleolar distance | 5 | Numeric: 0–10; ROM | Mean of 5 subscores | 5–10 min | <1 min | English, German, Finnish, multiple+ |
| DFI | ADLs | 20 | Likert: 0(n)–2 (y) | Summation | >BASFI | <1 min | English, German, Spanish, German, multiple+ |
| HAQ-S | Dressing, eating, walking, chores, neck function, and posture | 25 | Likert: 0(n)–3 (y) | Mean of 10 subscores | N/A | <1 min | English, Dutch, Spanish, Turkish, multiple+ |
Quality of Life
The Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire was originally developed using a needs-based model of health from 3 hospitals in northern England and 3 hospitals in southern Netherlands to monitor the impact of AS on a patient’s ability to satisfy their needs of sleep, motivation, activities of daily living, relationships, and social life. The investigators established a goal of using the information to provide practitioners with a tool to guide clinical decision-making and improve patient outcomes. Since its publication, the ASQoL has been the most frequently used disease-specific measure of health quality of life in AS studies, including the assessment of tumor necrosis factor inhibitor (TNFi) therapy among AS patients.
The ASQoL questionnaire was originally derived from interview transcripts in the field and ultimately condensed to an 18-item measure that uses dichotomous format (yes/no) choices. On average, the measure takes a median of 4 minutes (2- to 16-minute range) to complete and less than 1 minute to score. The results are then converted to a score by summation. The ASQoL has received wide acclaim as a validated disease-specific health-related quality-of-life measure among AS patients. Further research is necessary to clarify the cutoff marks for clinically significant quality-of-life change, but overall psychometric evaluations have supported this measure because of its ease of use in research with little administrative or respondent burden.
Functional Status and Disability
A measure of disability in AS patients, the Bath Ankylosing Spondylitis Functional Index (BASFI), was created by a similar group of rheumatologists and physiotherapists as the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in 1994 (see later discussion). It has since been the standard functional index for quantifying the impact of AS and corresponds to the Health Assessment Questionnaire equivalent for monitoring functional index in rheumatoid arthritis. Like the BASDAI, the questionnaire uses a visual analog scale (ranging from 0 to 10 cm) anchored by the descriptors “easy” and “impossible” to assess self-reported functioning in 8 activities of everyday life and 2 items documenting the patients’ ability to cope with everyday life. Scores are averaged, and an overall index score is calculated. The measure takes less than 3 minutes to complete, and scoring is rapid.
The BASFI has been supported by the ASAS community as a measure to monitor functional status; however, it may be insensitive to patients with milder disease due to its floor effect. Despite this concern, the BASFI has empiric evidence supporting its implementation in the clinic and research setting. It has since been incorporated into the formal recommendations by the ASAS as the PRO for assessing functional index.
The Dougados Functional Index (DFI) provides an assessment of the functional abilities in AS patients. Although similar in outcome to the BASFI, the DFI implements a 5-point Likert response scale and includes 20 items assessing daily living. It has been endorsed by the ASAS as an alternative to the BASFI for assessment of core physical functioning in AS. The DFI was originally created by 3 rheumatologists but did not involve initial trial testing with patients in the development phase.
Given its focus on axial and large joint functionality, the DFI has been recommended for use in individuals with predominantly axial involvement, and less so for patients with extra-articular involvement. Of note, it demonstrates a significant flooring effect, and some have questioned the simplistic nature of the Likert scale to capture subtle changes in functioning. Its use is appropriate for research but probably less favored in the clinic due to its larger respondent burden compared with the shorter, equally valid BASFI.
Disease Activity
Originally published in 1994, the BASDAI represents a measure of patient-reported disease activity in patients with AS. The questionnaire assesses patient-reported severities of back pain, fatigue, peripheral joint pain, localized tenderness, and both the duration and the severity of morning stiffness using a visual analog scale from 0 to 10 cm anchored with descriptors of “none” and “very severe.” As the ASQoL has been the most widely used measure for assessing quality of life, the BASDAI has been the gold standard for measuring disease activity in clinical trials and has been recommended for use in provider by ASAS.
The BASDAI was initially created in Bath, England by a team of rheumatologists and physiotherapists. On average, the measure takes 67 seconds to complete (generally 30–120 seconds for most respondents) and the scoring takes less than a minute. The questionnaire consists of 6 questions and is scored as the mean of 5 domains, with 2 morning stiffness items averaged. Scores of 4 or more suggest suboptimal control of disease activity, whereas scores greater than 4 are typically good candidates for either a change in their therapy or enrollment in clinical trials for new drug therapies for AS. Given its ease in administration and interpretation, and quick turnaround in results, the BASDAI has been successfully used in clinical practice. However, ASAS has described issues with the use of the traditional visual analog scale (used to rate 5 of the 6 components of the score) and instead now advocates for a switch to a numeric rating scale.
Another simple measure, the Bath Ankylosing Spondylitis Global score (BAS-G), was created by Jones and colleagues in 1996 and provides a global assessment of the AS patient’s health using 2 visual analog scales over 2 time periods: within the last week and over the last 6 months. The questions simply ask respondents, “how have you been over the last week?” and “how have you been over the last 6 months?” Scales range between 0 and 10 cm with anchors of “none” to “very severe.” The BAS-G is also endorsed by ASAS as an effective measure of globally assessing the patient and has been recommended as part of the core set of measures for monitoring AS. Higher scores indicate a more significant impact on health quality.
As the shortest of all the measures, the BAS-G may provide a good marker of self-reported global well-being in an efficient manner. However, by reducing multiple domains drastically, the instrument may represent very different patient experiences similarly.
One of the most recently developed measures, the Ankylosing Spondylitis Disease Activity Score (ASDAS), was created in 2008 by integrating objective aspects of disease activity with traditional patient-reported items represented in the BASDAI. The ASDAS reports a composite score relating to back pain, duration of morning stiffness, peripheral joint pain, and either erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) levels. Selected cutoffs to distinguish between disease states include less than 1.3 for inactive disease, 1.3 to 2.1 for moderate disease, 2.1 to 3.5 for high disease, and greater than 3.5 for very high disease activity. In terms of changes in ASDAS scores for monitoring improvement, a change greater than or equal to 1.1 is clinical important improvement, whereas a change greater than 2.0 represents major improvement. Four different versions of the ASDAS were initially developed, but the standard used in practice has been the ASDAS-CRP (and less so, the ASDAS-ESR). As such, these 2 are the versions treated in this review.
The instrument was created without using any patients directly in a 3-round Delphi process. The ASDAS score is ultimately calculated using a fairly complicated equation that weights each of the 5 criteria. The time for completion is short, requiring less than 1 minute. Provided the formula and a calculator are available, the scoring is also quick and facilitated by the presence of dedicated online calculators. Thus far, the ASDAS has been used for use in axSpA and psoriatic arthritis.
Related posts:
Patient Reported Outcomes in Rheumatic Diseases
Patient-Reported Outcomes in Rheumatoid Arthritis
Patient-Reported Outcomes in Systemic Lupus Erythematosus
Patient-Reported Outcomes in Psoriatic Arthritis
Challenges and Opportunities in Using Patient-reported Outcomes in Quality Measurement in Rheumatology
The Promise of Patient-Reported Outcomes Measurement Information System—Turning Theory into Reality
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