SLEEP DISTURBANCES AND FATIGUE IN ANKYLOSING SPONDYLITIS: A NARRATIVE REVIEW OF PREVALENCE, MECHANISMS, CLINICAL IMPACT AND MANAGEMENT
DOI:
https://doi.org/10.31435/ijitss.3(51).2026.6434Keywords:
Ankylosing Spondylitis, Sleep Disturbances, Fatigue, Quality of Life, Patient-reported Outcomes, Clinical ManagementAbstract
Sleep disturbances and fatigue are common and burdensome manifestations of ankylosing spondylitis (AS). They are strongly associated with overall disease burden and impaired health-related quality of life. This narrative review summarises current evidence on their prevalence, underlying mechanisms, clinical consequences, assessment and management. Sleep disturbances affect approximately half of patients with AS, while clinically significant fatigue is reported by a similar proportion of patients across axSpA populations. Both symptoms are associated with greater pain, higher disease activity, impaired physical function, psychological distress, reduced social participation, and poorer quality of life. Fatigue may also affect selected dimensions of occupational functioning. Their pathogenesis is multifactorial. Inflammatory signalling may contribute to both symptoms, with TNF-α having the clearest established role in sleep regulation and broader inflammatory pathways, including TNF-α and IL-17, potentially contributing to fatigue. Pain, restricted mobility, functional impairment, anxiety, depression, chronic insomnia, and coexisting sleep disorders may also play important roles. Anti-inflammatory treatment can improve fatigue and patient-reported sleep outcomes, although objective sleep findings remain inconsistent and residual symptoms may persist despite improvements in disease activity. Exercise, physiotherapy, patient education, and appropriate management of insomnia and coexisting sleep disorders may complement pharmacological treatment. Sleep quality and fatigue should therefore be assessed directly as distinct patient-reported domains. Further longitudinal and interventional studies using standardised outcome measures are needed to clarify causal relationships, determine symptom-specific treatment effects, and support more individualised management.
References
Braun, J., & Sieper, J. (2007). Ankylosing spondylitis. Lancet (London, England), 369(9570), 1379–1390. https://doi.org/10.1016/S0140-6736(07)60635-7
Sieper, J., & Poddubnyy, D. (2017). Axial spondyloarthritis. Lancet (London, England), 390(10089), 73–84. https://doi.org/10.1016/S0140-6736(16)31591-4
Boel, A., López-Medina, C., van der Heijde, D. M. F. M., & van Gaalen, F. A. (2022). Age at onset in axial spondyloarthritis around the world: Data from the assessment in SpondyloArthritis international society peripheral involvement in spondyloarthritis study. Rheumatology (Oxford, England), 61(4), 1468–1475. https://doi.org/10.1093/rheumatology/keab544
Dean, L. E., Jones, G. T., MacDonald, A. G., Downham, C., Sturrock, R. D., & Macfarlane, G. J. (2014). Global prevalence of ankylosing spondylitis. Rheumatology (Oxford, England), 53(4), 650–657. https://doi.org/10.1093/rheumatology/ket387
Bandinelli, F., Martinelli-Consumi, B., Manetti, M., & Vallecoccia, M. S. (2024). Sex bias in diagnostic delay: Are axial spondyloarthritis and ankylosing spondylitis still phantom diseases in women? A systematic review and Meta-Analysis. Journal of personalized medicine, 14(1), 91. https://doi.org/10.3390/jpm14010091
Ramiro, S., Nikiphorou, E., Sepriano, A., Ortolan, A., Webers, C., Baraliakos, X., Landewé, R. B. M., Van den Bosch, F. E., Boteva, B., Bremander, A., Carron, P., Ciurea, A., van Gaalen, F. A., Géher, P., Gensler, L., Hermann, J., de Hooge, M., Husakova, M., Kiltz, U., López-Medina, C., … van der Heijde, D. (2023). Asas-eular recommendations for the management of axial spondyloarthritis: 2022 update. Annals of the rheumatic diseases, 82(1), 19–34. https://doi.org/10.1136/ard-2022-223296
Nhan, D. T., & Caplan, L. (2016). Patient-Reported outcomes in axial spondyloarthritis. Rheumatic diseases clinics of North America, 42(2), 285–299. https://doi.org/10.1016/j.rdc.2016.01.011
Salari, N., Sadeghi, N., Hosseinian-Far, A., Hasheminezhad, R., Khazaie, H., Shohaimi, S., & Mohammadi, M. (2023). Prevalence of sleep disturbance in patients with ankylosing spondylitis: A systematic review and meta-analysis. Advances in rheumatology (London, England), 63(1), 33. https://doi.org/10.1186/s42358-023-00315-1
Tang, H., Singh, B. S. M., & Fong, W. (2023). Prevalence and factors associated with fatigue in patients with axial spondyloarthritis: A systematic review and meta-analysis. Rheumatology advances in practice, 7(3), rkad084. https://doi.org/10.1093/rap/rkad084
Wadeley, A., Clarke, E., Leverment, S., & Sengupta, R. (2018). Sleep in ankylosing spondylitis and non-radiographic axial spondyloarthritis: Associations with disease activity, gender and mood. Clinical rheumatology, 37(4), 1045–1052. https://doi.org/10.1007/s10067-018-3984-7
Aissaoui, N., Rostom, S., Hakkou, J., Berrada Ghziouel, K., Bahiri, R., Abouqal, R., & Hajjaj-Hassouni, N. (2012). Fatigue in patients with ankylosing spondylitis: Prevalence and relationships with disease-specific variables, psychological status, and sleep disturbance. Rheumatology international, 32(7), 2117–2124. https://doi.org/10.1007/s00296-011-1928-5
Taurog, J. D., Chhabra, A., & Colbert, R. A. (2016). Ankylosing spondylitis and axial spondyloarthritis. The New England journal of medicine, 374(26), 2563–2574. https://doi.org/10.1056/NEJMra1406182
Navid, F., Chen, L., Bowness, P., & Colbert, R. A. (2025). HLA-B27 and spondyloarthritis: At the crossroads of innate and adaptive immunity. Nature reviews. Rheumatology, 21(2), 77–87. https://doi.org/10.1038/s41584-024-01189-3
Maksymowych W. P. (2010). Disease modification in ankylosing spondylitis. Nature reviews. Rheumatology, 6(2), 75–81. https://doi.org/10.1038/nrrheum.2009.258
Webers, C., Boonen, A., Vonkeman, H. E., & van Tubergen, A. (2023). Factors associated with residual disease in axial spondyloarthritis: Results from a clinical practice registry. The Journal of rheumatology, 50(11), 1430–1438. https://doi.org/10.3899/jrheum.2023-0194
D'Angelo, S., Salvarani, C., Marando, F., Gualberti, G., Novelli, L., Curradi, G., Tripepi, G., Pitino, A., Ramonda, R., & Marchesoni, A. (2022). Residual disease in patients with axial spondyloarthritis: A Post-Hoc analysis of the quasar study. Journal of clinical medicine, 11(12), 3553. https://doi.org/10.3390/jcm11123553
Leverment, S., Clarke, E., Wadeley, A., & Sengupta, R. (2017). Prevalence and factors associated with disturbed sleep in patients with ankylosing spondylitis and non-radiographic axial spondyloarthritis: A systematic review. Rheumatology international, 37(2), 257–271. https://doi.org/10.1007/s00296-016-3589-x
Li, Z., Fu, T., Wang, Y., Dong, C., Shao, X., Li, L., & Gu, Z. (2019). Sleep disturbances in ankylosing spondylitis: A systematic review and meta-analysis. Psychology, health & medicine, 24(8), 911–924. https://doi.org/10.1080/13548506.2019.1574357
Solak, O., Fidan, F., Dündar, U., Türel, A., Ayçiçek, A., Kavuncu, V., & Unlü, M. (2009). The prevalence of obstructive sleep apnoea syndrome in ankylosing spondylitis patients. Rheumatology (Oxford, England), 48(4), 433–435. https://doi.org/10.1093/rheumatology/kep021
Wiginder, A., Sahlin-Ingridsson, C., Geijer, M., Blomberg, A., Franklin, K. A., & Forsblad-d'Elia, H. (2022). Prevalence and factors related to sleep apnoea in ankylosing spondylitis. Clinical rheumatology, 41(2), 491–498. https://doi.org/10.1007/s10067-021-05924-z
Tekatas, A., & Pamuk, O. N. (2015). Increased frequency of restless leg syndrome in patients with ankylosing spondylitis. International journal of rheumatic diseases, 18(1), 58–62. https://doi.org/10.1111/1756-185X.12323
Demirci, S., Demirci, K., Doğru, A., İnal, E. E., Koyuncuoğlu, H. R., & Şahin, M. (2016). Restless legs syndrome is associated with poor sleep quality and quality of life in patients with ankylosing spondylitis: A questionnaire-based study. Acta neurologica Belgica, 116(3), 329–336. https://doi.org/10.1007/s13760-015-0564-3
İn, E., Turgut, T., Gülkesen, A., Yolbaş, S., Akgöl, G., & Koca, S. S. (2016). Sleep quality is related to disease activity in patients with ankylosing spondylitis: A polysomnographic study. Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases, 22(5), 248–252. https://doi.org/10.1097/RHU.0000000000000355
Feuth T. (2024). Interactions between sleep, inflammation, immunity and infections: A narrative review. Immunity, inflammation and disease, 12(10), e70046. https://doi.org/10.1002/iid3.70046
Besedovsky, L., Lange, T., & Haack, M. (2019). The Sleep-Immune crosstalk in health and disease. Physiological reviews, 99(3), 1325–1380. https://doi.org/10.1152/physrev.00010.2018
Rockstrom, M. D., Chen, L., Taishi, P., Nguyen, J. T., Gibbons, C. M., Veasey, S. C., & Krueger, J. M. (2018). Tumor necrosis factor alpha in sleep regulation. Sleep medicine reviews, 40, 69–78. https://doi.org/10.1016/j.smrv.2017.10.005
Karatas, G., Bal, A., Yuceege, M., Firat, H., Gurcay, E., Ardic, S., & Cakci, F. A. (2018). Evaluation of sleep quality in patients with ankylosing spondylitis and efficacy of anti-TNF-α therapy on sleep problems: A polisomnographic study. International journal of rheumatic diseases, 21(6), 1263–1269. https://doi.org/10.1111/1756-185X.13102
Batmaz, İ., Sarıyıldız, M. A., Dilek, B., Bez, Y., Karakoç, M., & Çevik, R. (2013). Sleep quality and associated factors in ankylosing spondylitis: Relationship with disease parameters, psychological status and quality of life. Rheumatology international, 33(4), 1039–1045. https://doi.org/10.1007/s00296-012-2513-2
Park, J. Y., Howren, A. M., Zusman, E. Z., Esdaile, J. M., & De Vera, M. A. (2020). The incidence of depression and anxiety in patients with ankylosing spondylitis: A systematic review and meta-analysis. BMC rheumatology, 4, 12. https://doi.org/10.1186/s41927-019-0111-6
Hakkou, J., Rostom, S., Mengat, M., Aissaoui, N., Bahiri, R., & Hajjaj-Hassouni, N. (2013). Sleep disturbance in moroccan patients with ankylosing spondylitis: Prevalence and relationships with disease-specific variables, psychological status and quality of life. Rheumatology international, 33(2), 285–290. https://doi.org/10.1007/s00296-012-2376-6
Cano-García, L., Mena-Vázquez, N., Manrique Arija, S., Hernández-Sánchez, M. D., Segura-Ruiz, R., Domínguez-Quesada, C., & Fernández-Nebro, A. (2021). Psychological factors associated with sleep disorders in patients with axial spondyloarthritis or psoriatic arthritis: A multicenter cross-sectional observational study. Journal of clinical nursing, 30(1-2), 266–275. https://doi.org/10.1111/jocn.15546
Poddubnyy, D., Kiltz, U., Danve, A., Wright, G., Haberman, R., Biljan, A., Clewell, J., Urbanik, J., Jones, H., & Magrey, M. (2025). Psychosocial burden of axial spondyloarthritis and impact of different disease domains: A systematic literature review. Rheumatology advances in practice, 9(3), rkaf063. https://doi.org/10.1093/rap/rkaf063
Ying, X., Zhao, Q., Wu, Y., Deng, S., Ma, Q., & Fang, R. (2025). Analysis of sleep disorders and their influencing factors in patients with ankylosing spondylitis. PloS one, 20(5), e0323324. https://doi.org/10.1371/journal.pone.0323324
Delcourt, C., Fakih, O., Prati, C., Chouk, M., Wendling, D., & Verhoeven, F. (2025). Impact of treatments on fatigue in axial spondyloarthritis: A systematic review and meta-analysis. Rheumatology (Oxford, England), 64(4), 1585–1597. https://doi.org/10.1093/rheumatology/keae549
van Tubergen, A., Coenen, J., Landewé, R., Spoorenberg, A., Chorus, A., Boonen, A., van der Linden, S., & van der Heijde, D. (2002). Assessment of fatigue in patients with ankylosing spondylitis: A psychometric analysis. Arthritis and rheumatism, 47(1), 8–16. https://doi.org/10.1002/art1.10179
Pearson, N. A., Packham, J. C., Tutton, E., Parsons, H., & Haywood, K. L. (2018). Assessing fatigue in adults with axial spondyloarthritis: A systematic review of the quality and acceptability of patient-reported outcome measures. Rheumatology advances in practice, 2(2), rky017. https://doi.org/10.1093/rap/rky017
Dantzer, R., O'Connor, J. C., Freund, G. G., Johnson, R. W., & Kelley, K. W. (2008). From inflammation to sickness and depression: When the immune system subjugates the brain. Nature reviews. Neuroscience, 9(1), 46–56. https://doi.org/10.1038/nrn2297
Jones, S. D., Koh, W. H., Steiner, A., Garrett, S. L., & Calin, A. (1996). Fatigue in ankylosing spondylitis: its prevalence and relationship to disease activity, sleep, and other factors. The Journal of rheumatology, 23(3), 487–490.
Druce, K. L., Aikman, L., Dilleen, M., Burden, A., Szczypa, P., & Basu, N. (2018). Fatigue independently predicts different work disability dimensions in etanercept-treated rheumatoid arthritis and ankylosing spondylitis patients. Arthritis research & therapy, 20(1), 96. https://doi.org/10.1186/s13075-018-1598-8
Cella, D., de la Loge, C., Fofana, F., Guo, S., Ellis, A., Fleurinck, C., Massow, U., Dougados, M., Navarro-Compán, V., & Walsh, J. A. (2024). The functional assessment of chronic illness Therapy-Fatigue (FACIT-Fatigue) scale in patients with axial spondyloarthritis: Psychometric properties and clinically meaningful thresholds for interpretation. Journal of patient-reported outcomes, 8(1), 92. https://doi.org/10.1186/s41687-024-00769-x
Karadağ, O., Nakas, D., Kalyoncu, U., Akdoğan, A., Kiraz, S., & Ertenli, I. (2012). Effect of anti-TNF treatment on sleep problems in ankylosing spondylitis. Rheumatology international, 32(7), 1909–1913. https://doi.org/10.1007/s00296-011-1907-x
Sieper, J., Kivitz, A., van Tubergen, A., Deodhar, A., Coteur, G., Woltering, F., & Landewé, R. (2015). Impact of certolizumab pegol on Patient-Reported outcomes in patients with axial spondyloarthritis. Arthritis care & research, 67(10), 1475–1480. https://doi.org/10.1002/acr.22594
Mease, P., Walsh, J. A., Baraliakos, X., Inman, R., de Vlam, K., Wei, J. C., Hunter, T., Gallo, G., Sandoval, D., Zhao, F., Dong, Y., Bolce, R., & Marzo-Ortega, H. (2019). Translating improvements with ixekizumab in clinical trial outcomes into clinical practice: ASAS40, pain, fatigue, and sleep in ankylosing spondylitis. Rheumatology and therapy, 6(3), 435–450. https://doi.org/10.1007/s40744-019-0165-3
Kvien, T. K., Conaghan, P. G., Gossec, L., Strand, V., Østergaard, M., Poddubnyy, D., Williams, N., Porter, B., Shete, A., Gilloteau, I., & Deodhar, A. (2022). Secukinumab and sustained reduction in fatigue in patients with ankylosing spondylitis: Long-Term results of two phase iii randomized controlled trials. Arthritis care & research, 74(5), 759–767. https://doi.org/10.1002/acr.24517
Ortolan, A., Webers, C., Sepriano, A., Falzon, L., Baraliakos, X., Landewé, R. B., Ramiro, S., van der Heijde, D., & Nikiphorou, E. (2023). Efficacy and safety of non-pharmacological and non-biological interventions: A systematic literature review informing the 2022 update of the asas/eular recommendations for the management of axial spondyloarthritis. Annals of the rheumatic diseases, 82(1), 142–152. https://doi.org/10.1136/ard-2022-223297
Zhang, M., Liang, Z., Tian, L., Han, Y., Jiang, X., Li, Y., Su, Z., & Liu, T. (2025). Effects of exercise therapy in axial spondyloarthritis: A systematic review, meta-analysis, and meta-regression of randomized trials. Archives of physical medicine and rehabilitation, 106(1), 113–123. https://doi.org/10.1016/j.apmr.2024.06.005
Sveaas, S. H., Bilberg, A., Berg, I. J., Provan, S. A., Rollefstad, S., Semb, A. G., Hagen, K. B., Johansen, M. W., Pedersen, E., & Dagfinrud, H. (2020). High intensity exercise for 3 months reduces disease activity in axial spondyloarthritis (axSpA): A multicentre randomised trial of 100 patients. British journal of sports medicine, 54(5), 292–297. https://doi.org/10.1136/bjsports-2018-099943
Riemann, D., Espie, C. A., Altena, E., Arnardottir, E. S., Baglioni, C., Bassetti, C. L. A., Bastien, C., Berzina, N., Bjorvatn, B., Dikeos, D., Dolenc Groselj, L., Ellis, J. G., Garcia-Borreguero, D., Geoffroy, P. A., Gjerstad, M., Gonçalves, M., Hertenstein, E., Hoedlmoser, K., Hion, T., Holzinger, B., … Spiegelhalder, K. (2023). The european insomnia guideline: An update on the diagnosis and treatment of insomnia 2023. Journal of sleep research, 32(6), e14035. https://doi.org/10.1111/jsr.14035
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