Association Between Comorbidities and Disease Activity in Axial Spondyloarthritis

Results From the BSRBR-AS

Sizheng Steven Zhao; Gareth T. Jones; Gary J. Macfarlane; David M. Hughes; Robert J. Moots; Nicola J. Goodson


Rheumatology. 2021;60(7):3189-3198. 

In This Article

Abstract and Introduction


Objective: Whether comorbidities influence disease activity assessment in axial SpA (axSpA) is unclear. Comorbidities inflate DAS28 in rheumatoid arthritis through the patient global score. We examined whether axSpA disease activity measures are differentially affected, and whether comorbidities inflate the AS disease activity score (ASDAS) through the patient global component.

Methods: We used baseline data from the British Society for Rheumatology Biologics Register for AS, including 14 physician diagnosed comorbidities. Linear models were used to compare disease activity (BASDAI, spinal pain, ASDAS) and ESR/CRP according to comorbidity count, adjusted for age, gender, BMI, smoking, socioeconomic status, and education. The same models were used to examine whether the patient global score was associated with comorbidities, additionally adjusting for other ASDAS components.

Results: The number of participants eligible for analysis was 2043 (67% male, mean age 49 years); 44% had at least one comorbidity. Each additional comorbidity was associated with higher BASDAI by 0.40 units (95% CI: 0.27, 0.52) and spinal pain by 0.53 (95% CI: 0.37, 0.68). Effect size for ASDAS (0.09 units; 95% CI: 0.03, 0.15) was not clinically significant. ESR and CRP were not associated with comorbidity count. Depression, heart failure and peptic ulcer were consistently associated with higher disease activity measures, but not CRP/ESR. Patient global was associated with comorbidity count, but not independently of other ASDAS components (P = 0.75).

Conclusion: Comorbidities were associated with higher patient reported disease activity in axSpA. Clinicians should be mindful of the potential impact of comorbidities on patient reported outcome measures and consider additionally collecting ASDAS when comorbidities are present.


Axial SpA (axSpA) is a chronic inflammatory disease causing pain and functional impairment.[1] Assessing axial disease activity presents unique challenges since the spine and sacroiliac joints—unlike peripheral joints—are not easily accessible for clinical examination. It has been suggested that traditional biomarkers of inflammation—CRP and ESR—do not always reflect the underlying disease activity.[2] Disease activity assessment has traditionally relied on patient-reported outcome measures (PROMs); for example, eligibility to commence and continue biologics is defined using thresholds of BASDAI and spinal pain in the UK.[3]

PROMs are important but subjective. Studies have shown that patient perspectives are closely associated with function and fatigue, whereas physician assessments of disease activity are more associated with metrology and CRP.[4] The former may not be specific to axSpA disease activity; for example, cardiorespiratory diseases can significantly reduce function,[5,6] while concurrent depression and fibromyalgia will influence fatigue.[7]

ASDAS was developed to address some of these concerns.[8,9] ASDAS combines three questions from BASDAI (stiffness, back and peripheral symptoms) with CRP/ESR and the patient global score, analogous to the DAS28 for RA. Unlike BASDAI, it has been shown to associate with radiographic progression.[10] However, whether ASDAS is robust to the influence of comorbidities compared with patient-reported disease activity has not been examined. In RA, comorbidity count inflates DAS28 through the patient global score, independently of swollen/tender joints and inflammatory markers.[11] It is unknown whether the same vulnerability exists for ASDAS. Understanding whether and how comorbidities influence assessment of disease activity is crucial given their high prevalence.[12,13]

The aims of this study were to (i) compare whether measures of disease activity (BASDAI, spinal pain, ASDAS) and inflammation (CRP/ESR) are differentially influenced by comorbidities, (ii) replicate these comparisons for other important measures of disease severity (fatigue, function and quality of life), and (iii) examine whether the patient global component of ASDAS is influenced by comorbidities independent of the other components.