The objective of this population-based study was to examine the prevalence of comorbidities and their association with disease activity and functional impairment in a large well-characterised cohort of patients with axSpA.
Our study found that comorbid conditions in axSpA are common, affecting over 80% of the cohort. This prevalence is higher than in the recent worldwide ASAS-COMOSPA cohort, where the prevalence of comorbid conditions was approximately 51% [5]. However, this is likely due to the larger number of comorbidities assessed in our study and to differences in the methodology of data collection. Hypertension was the most common comorbidity (52%) and had a higher prevalence in the current study than in the worldwide ASAS-COMOSPA cohort (34%) but was comparable to the German ASAS-COMOSPA cohort (47%). Almost all patients with complicated forms of hypertension were treated, and almost 90% of patients with uncomplicated hypertension received related pharmacological treatment. Depression was the second most prevalent comorbidity, affecting approximately a quarter of our cohort (26%), of whom about a half were treated with anti-depressants. Depression was not described in ASAS-COMOSPA; however, it has been reported elsewhere that the prevalence of depressive symptoms in axSpA patients is high [12], and depression was found to be one of the most frequent comorbidities in SpA [3]. The prevalence of diabetes, the fourth most common comorbidity, was slightly increased compared to the German ASAS-COMOSPA cohort (16% vs 12%). However, patients in our study were on average 10 years older than in the German ASAS-COMOSPA cohort and thus, that difference might be age-related.
We also examined the prevalence of comorbid conditions in non-axSpA patients matched by age and sex. The prevalence of almost all investigated comorbidities was higher in the axSpA patients than in the non-axSpA patients. Similar trends were observed in a previous study exploring the prevalence of comorbidities among Chinese patients with AS and a general Chinese population in Taiwan, which found that patients with AS have a higher prevalence of multiple comorbidities than the general population [17]. These differences are likely explained by the fact that comorbid conditions are better recognised in axSpA patients than in the general population due to the presence of a chronic disease (axSpA), which is generally associated with more physician visits and examinations. In our study, the most striking difference between patients with axSpA and non-axSpA was observed for osteoporosis (13% vs 4%). The prevalence of osteoporosis among the axSpA patients was very similar to that observed in ASAS-COMOSPA (worldwide, 13%; Germany, 15%).
Differences in disease-related characteristics across the groups of patients with none, 1–2, 3–4, and 5 or more comorbid conditions were also investigated. Patients with no comorbidities were, on average, 20 years younger, with shorter disease duration and with shorter diagnostic delay than patients with 5 or more comorbidities. This trend is comparable to what has been reported in the literature in the general population, where comorbidities increase with age [18, 19]. Furthermore, we found that patients with more comorbidities were less often in rheumatologic care and received biologic agents less often than axSpA-only patients. Similar results were demonstrated for patients with RA, showing that coverage by rheumatologic care decreases with an increasing number of comorbidities [20] and that the initiation of biological therapy was less likely in the presence of comorbidities [21, 22]. These findings are also consistent with the trend to undertreat elderly patients [23, 24] and might also be a consequence of concerns regarding adverse events or polypharmacy [25]. A striking difference in terms of lifestyle characteristics was found for suffering from stress, which was reported almost twice as much in patients with no comorbid conditions (46%) than in patients with 5 or more comorbid conditions (25%). This might be related to the proportion of patients in full-time employment, which was considerably increased among patients with no comorbid conditions (54%) compared to patients with 5 or more comorbid conditions (6%). Furthermore, patients with no comorbid conditions were middle-aged (45 years), whereas the mean age of patients with 5 or more comorbid conditions was 66 years. Thus, suffering from stress is likely related to career-oriented and family demands.
The impact of comorbidities on disease outcomes is well outlined for the general population, where the co-occurrence of at least 2 chronic diseases was associated with impaired daily functioning and lower health-related quality of life, especially if a rheumatic disease was involved [26], and for patients with RA, where increasing numbers of comorbidities were associated with worse functional status and lower well-being [20]. These associations are less well described for SpA. In separate models, analysing the impact of an increasing number of comorbidities on disease outcomes in axSpA patients, we demonstrated that the presence of each additional comorbidity was associated with a BASDAI increase of 0.17 points and a BASFI increase of 0.24 points, independently of other factors, including treatment, which is in particular relevant for patients with a high comorbidity burden. Similar results for SpA patients were found in two recent studies which showed that a rising comorbidity burden was associated with a higher disease activity, worse functional outcomes, and poorer quality of life [5, 27]. However, the difference with our study is that, in those studies, there was a selective reporting of comorbidities known to occur most commonly in SpA. When including diseases based on prevalence, important comorbidities might be overlooked and thus the proportion of axSpA patients having at least one additional comorbidity may have been affected. This potential limitation is not present in our study where comorbidities were selected using the Elixhauser coding algorithms, slightly modified by excluding rheumatoid arthritis/collagen vascular diseases and including osteoporosis and fibromyalgia. Furthermore, we demonstrated that two of the most common comorbidities, depression and chronic pulmonary disease, were associated with disease activity and functional status, highlighting the need for the careful evaluation of depressive symptoms as a part of the management strategy for axSpA. Hypertension showed an association with functional status only.
There are some limitations to our study. First, the cross-sectional design of this study does not allow conclusions to be drawn on the direction of causation. Higher disease activity and higher levels of functional disability might be indicators of more severe disease resulting in the development of comorbid conditions. In addition, axSpA patients might have been screened for comorbidities related to the disease, leading to an overestimation of the prevalence of these comorbidities and, thus, to an overestimation of the difference in the prevalence of comorbidities between axSpA patients and non-axSpA patients. Left censoring also represents a potential limitation: patients with a severe comorbidity burden might have been unable to respond to the survey or were no longer alive, preventing them from being included in the present study. However, the sample of axSpA patients was stratified by age, and thus, the error due to underestimation of the prevalence of some comorbidities is likely to be limited. Lastly, care should be taken when interpreting recorded diagnoses based on claims data that are normally collected for administrative purposes rather than for scientific purposes. The health insurance claims approach to define comorbidities enables a comprehensive assessment of comorbidities without pre-selection of particular conditions, but the diagnoses cannot be validated with this research approach. However, comorbidity-relevant drug prescriptions were examined, and furthermore, the initial diagnosis of axSpA based on claims data was validated using survey data by selecting only patients who confirmed the presence of axSpA. The characteristics of the resulting group in terms of age, sex distribution, prevalence of extra-musculoskeletal manifestations and pharmacological therapy were comparable to those of prospectively recruited axSpA cohorts [28,29,30]. While age, female sex, and the number of comorbidities were comparable between patients who responded to the survey and those who did not respond, there was some non-response bias regarding the prescription of axSpA-related treatment, which was increased among responders.
There are important strengths to this study, including the range and number of captured comorbidities. Comorbidities were defined using the Elixhauser coding algorithms and were not disease-specific in order to preclude the possibility of overlooking important comorbid conditions. A key strength of this study was the large population-based sample of axSpA patients and the linkage of survey data to health insurance data allowing a comprehensive assessment of comorbidities and their association with disease outcomes in a real-life setting.
In summary, we found a high prevalence of comorbidities in patients with axSpA. A higher number of comorbidities was independently associated with higher disease activity and higher levels of functional impairment while controlling for other factors, including treatment. Depression and chronic pulmonary disease were two of the most common comorbidities, and their presence was associated with higher disease activity and worse functional status, while hypertension showed an association with functional status only. These findings highlight the importance of a holistic patient-tailored management strategy in axSpA.