Fatigue and Pain Levels Remain High in Patients With Ankylosing Spondylitis


“Managing pain is an important treatment goal in patients with ankylosing spondylitis, however, pain is often underestimated by clinical disease activity scoring tools, and 20% to 30% of patients report pain despite treatment with TNFis,” investigators stated.

Continued unmet needs in ankylosing spondylitis (AS) treatment, both pharmacologic and nonpharmacologic, were suggested by high levels of fatigue and pain in patients with AS receiving tumor necrosis factor inhibitors (TNFis), according to a study published in Journal of Rheumatology.1

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“Managing pain is an important treatment goal in patients with AS, however, pain is often underestimated by clinical disease activity scoring tools, and 20% to 30% of patients report pain despite treatment with TNFis,” investigators stated. “We observed increased levels of inflammatory markers with increasing severity of pain, indicating that patients may not have been adequately responding to therapy or were poorly adherent with their TNFis.”

The Adelphi Spondyloarthritis AS Disease Specific Programme (DSP), a large, multinational survey that identifies disease impact and disease management, collected data between 2015 and 2016 from 13 countries, including those in North America (N America), Europe (EU5), Asia Pacific (APAC), and Turkey and Middle East (T&ME).

Physicians completed forms detailing patient demographics, clinical assessments, concomitant conditions, treatment history, disease status, disease activity, inflammation, and current medication usage. Patients were then invited to complete patient-reported forms, which included Medical Outcomes Study–Short Form (36-item) Health Survey version 2 (SF-36v2), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), a general health status, and Work Productivity and Activity Impairment General Health Questionnaire (WPAI). Questions focused on symptoms, disease activity, health-related quality of life (HRQoL), employment status, and current treatments.

Eligible patients were aged 18 years or older with a clinical diagnosis of AS. This study only analyzed those who were receiving TNFis for at least 3 months and had completed the BASDAI pain and fatigue domains.

A total of 705 patients were ultimately chosen for the analysis (N America, n = 253; EU5, n = 328; APAC, n = 88; T&ME, n = 36). Of these patients, 37.6% reported high BASDAI pain scores and 41.3% reported high BASDAI fatigue scores. The percentage of male patients varied from 75.5% (N America) to 100% (T&ME) and the mean age was 36.1 years (T&ME) to 45.1 (EU5).

Most patients (62.4%) reported low BASDAI pain scores, while 37.6% indicated high BASDAI pain scores. In terms of fatigue, 58.7% reported low BASDAI fatigue scores, while 41.2% had high BASDAI fatigue scores. Body mass index, symptom onset, and symptom diagnosis were similar between both patient groups.

Higher levels of pain and fatigue were associated with higher impairment scores and lower SF-36v2, visual analog scale, and 5-dimensional EuroQoL Questionnaire scores. Unsurprisingly, those with severe disease status were more likely to have higher pain and/or fatigue when compared with their low pain and/or fatigue counterparts (pain: 9.1% vs 2.3%; fatigue: 8.2% vs 2.4%). Additionally, more patients with higher physician-rated “unstable” or “deteriorating” disease status were more likely to have high pain and/or fatigue levels (pain: 14.4% vs 2.5%; fatigue: 14.1% vs 1.9%).

Approximately 29% of patients with high pain and 30% with high fatigue indicated feeling happy “little or none of the time” compared with only 12% of patients with low pain and 10.3% with low fatigue.

Flares were also higher in patients with higher BASDAI pain scores (11.4% vs 3.2%) and BASDAI fatigue levels (11% vs 2.9%) as well as reporting higher joint pain and swelling, severity and duration of morning stiffness, and discomfort.

In terms of mobility, far more patients with high pain and/or fatigue reported either “some” or “extreme” mobility or self-care issues or anxiety and depression when compared with those in the low pain and/or fatigue cohort.

Of those who provided employment information, 83.2% were employed. However, patients with higher pain and fatigue were less likely to be employed (pain: 71.6% vs 89.9%; fatigue: 74.3% vs 89.2%).

Nonsteroidal anti-inflammatory drug (NSAID) usage was higher in patients reporting high pain levels when compared with low pain levels (52.8% vs 39.3%).

The study was strengthened by the real-world data presented for patients with AS treated with TNFis globally as well as demonstrating the negative impact of pain and/or fatigue as it relates to WPAI and HRQoL. However, limitations include the study’s cross-sectional nature with its restricted selection of patients, sample sizes, and data collection, such as confining the working age to younger than 65 years. Further, diagnostic decisions may be subjective as they were based upon a physician’s rating of their patient’s disease activity. Levels of change in pain and/or fatigue could not be assessed as information was only captured at the time of data collection. Lastly, while the study was potentially limited by recall bias, this possibility was reduced by collecting data during appointments.

“Our observations indicate the importance of appropriately treating AS to minimize the impact on patients' social lives, work participation, and economic and health burdens,” investigators concluded. “Lastly, our results highlight the need to explore other therapeutic approaches including nonpharmacologic interventions for the management of AS.”


Strand V, Deodhar A, Alten R, et al. Pain and Fatigue in Patients With Ankylosing Spondylitis Treated With Tumor Necrosis Factor Inhibitors: Multinational Real-World Findings. J Clin Rheumatol. 2021;27(8):e446-e455. doi:10.1097/RHU.0000000000001544

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