Introduction

Axial spondyloarthritis (axSpA) is a chronic inflammatory rheumatic disease primarily affecting the spine and sacroiliac joints1. It is classified into radiographic axSpA (r-axSpA, or ankylosing spondylitis) and non-radiographic axSpA (nr-axSpA), distinguished by the presence or absence of structural changes on plain radiographs2. Up to 92% of patients with axSpA experience symptom onset before the age of 453. The male-to-female ratio in axSpA is estimated to be between 2:1 and 3:1 in some studies4.

AxSpA manifests with back pain and stiffness, and other symptoms such as peripheral arthritis, enthesitis, dactylitis, and extra-musculoskeletal manifestations such as uveitis, psoriasis, and inflammatory bowel disease5. There is a strong association between HLA-B27 and axSpA1. AxSpA was linked to HLA-B27 peptide complexes, leading to the autoactivation of cytotoxic T cells6 or through the activation of the IL23/IL17 pathway due to the accumulation of misfolded HLA-B27 in the endoplasmic reticulum6. Environmental factors associated with axSpA are diverse, including smoking, infections, physical stress, and obesity7.

Determining disease activity is crucial in axSpA, as it guides treatment selection and titration and is closely associated with patients’ quality of life and psychological well-being8. Despite the unmet need for reliable biomarkers of disease activity9, an increasing number of studies have evaluated the neutrophil-to-lymphocyte ratio (NLR) as a potential biomarker of disease activity10.. The ASDAS is a comprehensive index that accurately reflects the construct of disease activity while minimizing redundancy11. It is practical, superior to many existing measures, and its established cut-off values enable clinicians and researchers to reliably assess disease activity and monitor patients with AxSpA.

There is a notable lack of research on AxSpA in the Middle East, particularly in Jordan, which leaves a significant gap in our understanding of the disease in this population. In addition, the lack of knowledge about the disease among primary care providers might contribute to the diagnostic delays and the later presentation to the specialized rheumatology clinics. This study addresses this gap by moving beyond a purely descriptive characterization of patients from two major Jordanian centers. While we outline key demographic, clinical, and laboratory features, the primary focus is on examining patient-reported outcomes and the psychosocial burden associated with axial spondyloarthritis, as well as identifying factors linked to higher disease activity. By doing so, the study provides context-specific evidence that can inform clinical decision-making and support the development of targeted health policies in the region.

Methods

Study design

This cross-sectional study was conducted at two tertiary care centers in Jordan: Jordan University Hospital (JUH) in Amman and King Abdullah University Hospital (KAUH) in Irbid. Given the structure of Jordan’s healthcare system, comprising the Ministry of Health, the Royal Medical Services, and semi-governmental institutions such as JUH and KAUH, these centers serve as national referral hubs for rheumatologic diseases, receiving patients from all twelve governorates, including many insured through the Ministry of Health. Therefore, the study population is considered representative of patients with AxSpA receiving formal specialist care across Jordan.

This study builds upon a previously published national project on spondyloarthritis by our group, which used a similar methodology12. All AxSpA patients included here were part of the earlier cohort; however, the present work focuses on a distinct research scope emphasizing psychosocial burden, functional status, quality-of-life outcomes, and predictors of disease activity. Eligible participants were aged ≥ 18 years and met the Assessment of SpondyloArthritis International Society (ASAS) classification criteria13. In patients without radiographic sacroiliitis, the diagnosis of non-radiographic axial spondyloarthritis was established by rheumatologists based on inflammatory back pain in combination with either active sacroiliitis on magnetic resonance imaging or HLA-B27 positivity. Those who provided consent were included, and recruitment started in January of 2023 and was concluded in September 2023, when no further eligible patients presented to the clinics. The study adhered to the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) checklist14 and complied with published guidelines15.

Data collection

Data collection and physical examinations were performed by rheumatology fellows (AAH, HB, and MA) during routine clinic visits, while the treating rheumatologist was not involved to minimize potential bias. The structured questionnaire used in this study was adapted from a larger project previously conducted by our research team12. It was designed to collect sociodemographic and health-related data, including age, sex, marital status, occupation, education level, and smoking status. Clinical information, including disease duration, diagnostic delay, clinical presentation, and comorbidities (e.g., gout, osteoporosis, heart failure, stroke, diabetes mellitus, hypertension, recurrent infection, cancer, ischemic heart disease, and hip replacement), extraarticular manifestations (monoarthritis, polyarthritis, dactylitis, enthesitis, uveitis, and psoriasis), as well as current or prior medications, was also recorded.

Laboratory tests, including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and complete blood count (CBC), were performed on the same day as the clinic visit, which were reported as numerical lab values. HLA-B27 status was reported as positive, negative, or not tested and imaging reports (spine and sacroiliac joint X-rays) were retrieved from patient charts and data was reported as consistent or inconsistent with SpA at the cervical, dorsal, and lumbosacral spine. NLR was calculated from the CBC by dividing the absolute neutrophil count by the absolute lymphocyte count.

The Patient Health Questionnaire-9 (PHQ-9) was used to screen for depression, the Fibromyalgia Rapid Screening Tool (FiRST) to screen for fibromyalgia, the Ankylosing Spondylitis Quality of Life (ASQOL) instrument to assess quality of life, and the Ankylosing Spondylitis Disease Activity Score using C-reactive protein (ASDAS-CRP) to evaluate disease activity, which were all administered by our research team.

Ethical considerations

The study protocol was approved by the Institutional Review Board at Jordan University Hospital (protocol number 10/2023/9355). All patients were informed and consented, and they were assured of data protection and confidentiality. The study was conducted in accordance with the principles outlined in the Declaration of Helsinki.

Statistical analysis

The data analysis was performed using IBM-SPSS v27. Demographic data, comorbidities, laboratory values, treatments, and extraarticular were reported as counts and percentages or means and standard deviations, as appropriate. NLR was analyzed as a continuous numerical variable16. Variables associated with high disease activity, as determined by ASDAS, were tested using Fisher’s exact test, Chi-square test, or T-test, as applicable. Factors significantly associated with very high disease activity on univariate analysis were assessed using a multivariate logistic regression analysis, and the results were reported as odds ratios (OR) and 95% confidence interval (95% CI). The data for HLA-B27 status was presented as a count and percentage of the total cohort, including a separate category for patients who were not tested to show the extent of the missing data. GraphPad Prism 8.0 was used to visualize data and generate figures. Using GraphPad Prism 8.0, Receiver operating characteristic (ROC) curve analyses were performed to evaluate the discriminatory performance of laboratory parameters in predicting very high ASDAS activity > 3.5. The area under the curve (AUC) was calculated for each parameter to quantify its diagnostic accuracy.

Results

Demographic and clinical characteristics of patients with axial spondyloarthritis

We analyzed the data of 79 patients with ax-SpA; 67 were diagnosed with AS, whereas 12 patients were diagnosed with nr-axSpA. The mean age of the sample was 41.1 ± 11.86 years, and 59.5% (N = 47) of the patients were male. On average, patients have complained of their symptoms for 5.67 ± 6.13 years before being diagnosed with the disease.

Most patients are current smokers (53.2%, N = 42) and currently married (73.4%, N = 58), while only 38% are non-smokers (N = 30). Regarding educational status, most of the patients attended college (45.6%, N = 36). Regarding patients’ occupations, 16.5% of the participants were retired (n = 13), while 36.7% were unemployed (n = 29). White-collar occupations were reported by 39.2% of patients (n = 31). In contrast, only six patients (7.6%) were engaged in blue-collar jobs.

A family history of ax-SpA was present in 18 patients (22.8%). Among all patients included in our study, only 23 patients (29.1%) were not tested for HLA-B27. On the other hand, 45.6% of patients (N = 36) tested positive for HLA-B27. From a symptomatology perspective, most patients had polyarthritis (63.3%, N = 50), while only seventeen patients had enthesitis (21.5%). Uveitis was present at the clinical encounter only in eight patients (10.1%). Hypertension was the most prevalent comorbidity, affecting 16 patients (20.3%). There was no statistically significant difference (i.e., P-value < 0.05) between AS and nr-axSpA groups. Table 1 shows demographics and baseline characteristics of 79 ax-SpA patients.

Table 1 Demographics and baseline characteristics of 79 ax-SpA patients.
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Treatment, imaging, labs, and disease activity in axSpA

Among the patients included in our study, 75.9% (N = 60) were currently receiving treatment with tumor necrosis factor (TNF) inhibitors. Additionally, nonsteroidal anti-inflammatory drugs (NSAIDs) were used by 38.0% (N = 30) of patients, and interleukin-17 (IL-17) inhibitors were used by 10 patients (12.7%). Around two-thirds of patients (65.8%, N = 52) exhibited a imaging finding of sacroiliac joint involvement.

When disease activity was assessed using the ASDAS, five patients (6.3%) had inactive disease, eleven patients (13.9%) had moderately active disease, forty-one patients (51.9%) had highly active disease, and twenty-three patients (29.1%) had very highly active disease. When screened for depression using the PHQ-9, most patients (41.8%, N = 33) had scores consistent with mild depression, while three patients had scores indicative of severe depression. Additionally, sixteen patients (20.3%) screened positive for fibromyalgia based on the Fibromyalgia Rapid Screening Tool (FiRST).

Regarding laboratory tests, the mean NLR was 2.07 ± 1.11. However, NLR was significantly higher among AS patients than nr-axSpA (2.16 vs. 1.48). Similarly, ESR and CRP were significantly higher among AS patients than nr-axSpA (31.17 vs. 19.54) and (18.22 vs. 8.31), respectively. Table 2 presents treatment regimens, imaging and laboratory findings, and disease activity in axSpA patients.

Table 2 Treatment regimens, imaging and laboratory findings and disease activity of axSpA patients.
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Factors associated with very high disease activity

When factors associated with very high ASDAS scores (≥ 3.5) were assessed, males were found to be significantly more likely to have a very high ASDAS score (50.0% vs. 82.6%, p-value = 0.007). On the other hand, patients with AS were more likely to have ASDAS < 3.5 (91.1% vs. 69.9%) with a p-value of 0.016. Similarly, patients with monoarthritis were significantly more likely to have ASDAS < 3.5 (23.2% vs. 4.35%, p-value = 0.046). Patients with higher ASQOL scores (i.e., worse quality of life) were more likely to have very high disease activity, as indicated by ASDAS (6.62 vs. 10.13, p-value = 0.003). The neutrophils-to-lymphocytes ratio (NLR) was significantly higher among patients with high disease activity according to ASDAS (1.75 vs. 2.65, p-value = 0.001). On the other hand, PHQ-9 scores of 10 or more weren’t statistically different among patients with very high disease activity and the other patients. Table 3 presents factors associated with high disease activity, as determined by the ASDAS score. Factors significantly associated with very high ASDAS scores on univariate analysis were assessed using a multivariate logistic regression analysis. Only the AS subtype was a significant predictor of lower disease activity (OR = 0.150; 95%CI: 0.025–0.898).

Table 3 Factors associated with high disease activity according to ASDAS score.
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ROC curve analyses were performed to evaluate the ability of inflammatory markers to predict very high disease activity, as defined by ASDAS (ASDAS ≥ 3.5). Among all patients (n = 79) (Fig. 1A), the NLR demonstrated the highest discriminatory capacity, with an AUC of 0.691 (95% CI: 0.543–0.840). Neutrophil count followed closely (AUC = 0.678), while the platelet-to-lymphocyte ratio (PLR) and lymphocyte count had lower AUC values of 0.617 (95% CI: 0.459–0.775) and 0.572 (95% CI: 0.415–0.729), respectively.

Fig. 1
Fig. 1The alternative text for this image may have been generated using AI.
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Receiver-operating characteristic curve (ROC) for predicting very high disease activity according to ASDAS (ASDAS ≥ 3.5). (A) ROC for predicting very high disease activity according to ASDAS among all patients (N = 79). (B) ROC for predicting very high disease activity according to ASDAS among patients using TNF inhibitors (N = 60).

Among patients using TNF inhibitors (n = 60) (Fig. 1.B), the discriminatory ability was slightly reduced. NLR again showed the highest AUC at 0.676 (95% CI: 0.517–0.834), followed by neutrophil count (AUC = 0.619), PLR (AUC = 0.568), and lymphocyte count (AUC = 0.507), which approached no discriminatory ability.

Discussion

axSpA is a chronic inflammatory rheumatic disease that typically affects individuals during their most productive years. Despite its clinical and socioeconomic impact, data from the Arab world, particularly Jordan, remain limited. In this multicenter cross-sectional study, we evaluated 79 patients with axSpA recruited from the two main tertiary academic referral centers in Jordan, providing a contemporary snapshot of axSpA in routine specialist care. Similar cohort sizes have been reported in regional cross-sectional studies, including a Saudi cohort of 106 patients17 and an Egyptian multicenter study enrolling approximately 75 patients18, despite larger underlying populations. These sample sizes are consistent with the low prevalence of spondyloarthritis in the Middle East and North Africa region, estimated at 0.32%19,20. Within this context, the present study offers an insight into patients’ reported outcomes of the disease and its psychosocial burden. In addition to an in-depth characterization of axSpA clinical features in Jordan, treatment use, imaging and laboratory findings, and determinants of disease activity in an underrepresented population.

According to the PROOF study, which involved 1553 patients from 29 countries, the male-to-female ratio among AxSpA patients was 1.7:1, and the mean duration of symptoms was 56.4 months21. In comparison, the male-to-female ratio in our study was slightly lower at 1.4:1, and the average duration of symptoms was notably longer at 106 months. While the male-to-female ratio in our population is generally consistent with previous reports, the extended delay in diagnosis highlights a significant gap in recognizing AxSpA. This may reflect both patient-related factors, such as delayed care-seeking behavior, and physician-related factors, particularly in primary care, where awareness and suspicion of AxSpA may be limited. Smoking was associated with a dose-dependent negative impact on the disease progression and quality of life among patients with AxSpA22. However, 53.2% of our study population were smokers. This may be explained by the limited awareness among smokers in general, including those in high-risk groups, regarding the health risks of smoking, which can be attributed to the scarcity of targeted anti-smoking campaigns in Jordan23.

Among our study population, only six patients (7.6%) were currently engaged in blue-collar jobs, reflecting the impact of the disease on work capacity. This burden is further demonstrated by the fact that more than half of the patients were either retired or unemployed, despite a relatively young mean age of 41.1 years. These findings highlight not only the loss of employment but also the potential work absenteeism associated with the disease24. The burden of the disease is also reflected in the clinical symptoms of the disease; most patients had monoarthritis or polyarthritis, and one-fifth had enthesitis. In addition, the disease activity scores reflected this problem, as almost 80% of patients had a high or a very high disease activity according to ASDAS. The effects of AxSpA on patients’ quality of life are not limited to the physical aspects, but further extend to involve the psychosocial aspects of patients25. This was evident in our study population, where only 26.6% showed no/minimal depression, and the rest had depressive symptoms ranging from mild to severe. In our study population, 20.3% of patients screened positive for fibromyalgia using the FiRST questionnaire, which is comparable to the prevalence reported by Jones et. al.’s meta-analysis on 5214 patients with AxSpA, the prevalence of fibromyalgia was 16.4% (95% CI 12.3–20.5%)26. The observed prevalence of fibromyalgia and depression may be influenced by healthcare access and under-recognition in the community, potentially overestimating rates by capturing only the most severe cases. Additionally, cultural factors could affect symptom reporting, making direct comparisons to international cohorts difficult without further context.

The 2019 treatment guidelines from the American College of Rheumatology (ACR), Spondylitis Association of America (SAA), and Spondyloarthritis Research and Treatment Network (SPARTAN) recommend regularly monitoring disease activity in axSpA using validated tools such as BASDAI or ASDAS27. In contrast, the recently updated Assessment of Spondyloarthritis International Society (ASAS)–European Alliance of Associations for Rheumatology (EULAR) guidelines identify ASDAS, preferably calculated with C-reactive protein (CRP), as the preferred instrument for assessing disease activity28. Using ASDAS, 51.9% of patients had high disease activity, and 29.1% had scores suggestive of very high disease activity.

TNF inhibitors are considered a cornerstone in the treatment of AxSpA29. We evaluated the accuracy of laboratory markers in predicting disease activity by calculating their AUC against the ASDAS score. Among all tested markers, the NLR demonstrated the highest predictive performance in both the overall patient cohort and in the subgroup receiving biologic therapy. Notably, all laboratory markers assessed (as shown in Graph 1) exhibited lower predictive accuracy in patients treated with biologics compared to those not receiving biologic therapy. This reflects the need for novel markers that are less affected by this type of treatment.

This study represents the largest and most up-to-date investigation of AxSpA patients in Jordan. It is also among the few studies to explore demographic characteristics and predictors of disease activity in this population. The high rates of diagnostic delay, psychosocial burden, and work disability we identified in this study are not merely descriptive; they represent critical health disparities and unmet clinical needs in our country. These findings lay a vital foundation for future, larger-scale longitudinal studies and are highly relevant to rheumatology practice and health policy in the region. Patients were recruited from two major tertiary care centers that receive referrals from across the country, enhancing the study’s representativeness of the Jordanian population. However, we acknowledge that our study has some limitations. The relatively small sample size may limit statistical power for subgroup analyses and our ability to adjust for confounding variables. However, the low sample size needs to be interpreted within the context of regional epidemiology and the scarcity of specialized rheumatological data in the Middle East. Our recruitment strategy targeted the two largest tertiary referral centers in Jordan, which manage the most complex spondyloarthritis cases in the country. While larger, multi-national registries are ideal, the current work provides high-granularity data that is essential for understanding the psychosocial and functional burden in this specific, understudied geographic demographic. Nevertheless, recruitment from tertiary centers may overrepresent patients with more severe or complex diseases, and findings should be interpreted accordingly. Given the exploratory nature of the study, no formal correction for multiple testing was applied. Therefore, the observed associations should be interpreted cautiously and confirmed in larger, hypothesis-driven studies.

Conclusion

This multicenter study offers valuable insights into the demographic profile, clinical characteristics, and predictors of disease activity among patients with AxSpA in Jordan. Our findings highlight substantial diagnostic delays, high smoking prevalence, significant work disability, and a notable psychosocial burden among this patient population. The neutrophil-to-lymphocyte ratio was the strongest marker, among the laboratory values tested in this study, for predicting disease activity, even among patients receiving TNF inhibitor therapy. However, its predictive accuracy was decreased in this subgroup. These observations underscore the urgent need to enhance early detection strategies, raise public and healthcare provider awareness, and develop more robust biomarkers for monitoring disease activity, particularly in patients on biologic treatments. Future longitudinal studies are warranted to confirm these findings and assess disease progression and treatment outcomes over time.