Axial spondyloarthritis in men and women

The work of recent decades has changed the idea that axial spondylitis (axSpA) is an exclusively “male” disease. However, at present, when deciding on further treatment tactics, gender differences in the course of the disease and response to treatment are not taken into account.
The aim – to study gender differences in disease activity indices in patients with axial spondylitis.
Material and methods. The study included 108 patients who met the 2009 ASAS (Assessment of SpondyloArthritis International Society) criteria for axSpA or the modified New York criteria for ankylosing spondylitis (AS) of 1984. The mean age of patients at inclusion in the study was 35.4±10.8 years, most of them were men – 62 (57.4%). The AS criteria were met by 67.2% of women and 88.5% of men. The remaining patients were diagnosed with non-radiographic axSpA.
Results and discussion. The duration of the disease did not differ between patients of different sexes (p=0.3): 60.0 [24.0; 96.0] months in men and 42.0 [21.8; 84.0] months in women. HLA-B27 antigen positivity was detected in 36 (78.3%) women and 55 (88.7%) men. Women were more often (p=0.048) diagnosed with arthritis than men: 37 (80.4%) and 39 (62.9%), as well as dactylitis (p=0.01): 15 (32.6%) and 8 (12.9%), respectively. No differences were found between men and women in the frequency of other extraskeletal and extraaxial manifestations of axSpA. Also, no differences were found in the BASFI (Bath Ankylosing Spondylitis Functional Index), MASES (Maastrich Ankylosing Spondylitis Enthesitis Score) indices and in all domains of the BASMI (Bath Ankylosing Spondylitis Metrology Index) index. In men, the C-reactive protein level was significantly higher than in women (p=0.03). At the same time, the disease activity according to the BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) index, as well as the patient’s pain assessment indicators, global assessment of general well-being according to the numeric rating scale in women of the study group were higher than in men. The average anxiety value according to the HADS (Hospital Anxiety and Depression Scale) scale was higher in women (p=0.01) than in men – 9.0 [6.0; 10.0] and 5.0 [2.0; 8.0], respectively. The average depression value according to the HADS scale did not differ between the groups (p=0.3): 5.5 [3.0; 6.0] and 3 [1.0; 5.6], respectively.
Conclusions. The revealed clinical heterogeneity of axSpA manifestations in men and women, the peculiarities in pain assessment by patients of different genders, allow us to state that gender influences the interpretation of disease activity. Further studies are needed to study gender differences in patients with axSpA to optimize treatment approaches and assess its effectiveness.

1. Liu KA, Mager NA. Women’s involvement in clinical trials: Historical perspective and future implications. Pharm Pract (Granada). 2016;14(1):708. doi: 10.18549/PharmPract.2016.01.708

2. Rudwaleit M. New approaches to diagnosis and classification of axial and peripheral spondyloarthritis. Curr Opin Rheumatol. 2010;22(4):375-380. doi: 10.1097/bor.0b013e32833ac5cc.0

3. Erdes ShF, Rumyantseva DG, Smirnov AV. Evaluation of the progression of axial spondyloarthritis in the early stages of the disease in real clinical practice: The possibilities of using the summary score of radiographic sacroiliitis. Nauchno-Prakticheskaya Revmatologia = Rheumatology Science and Practice. 2018;56(4):461-465 (In Russ.). doi: 10.14412/1995-4484-2018-461-465

4. Baumberger H, Khan MS. Gradual progressive change to equal prevalence of ankylosing spondylitis among males and females in Switzerland: Data from the Swiss Ankylosing Spondylitis Society (SVMB). Ann Rheum Dis. 2017;76:929. doi: 10.1136/annrheumdis-2017-eular.3961

5. Sieper J, van der Heijde D, Review nonradiographic axial spondyloarthritis: New definition of an old disease? Arthritis Rheum. 2013;65(3):543-551. doi: 10.1002/art.37803

6. Erdes ShF, Dubinina TV, Rumyantseva OA, Dyomina AB, Gubar EE, Rumyantseva DG. The evolution of axial spondyloarthritis during 12-month follow-up study of a CoRSaR cohort. Nauchno-Prakticheskaya Revmatologia = Rheumatology Science and Practice. 2016;54(Suppl 1):55- 59 (In Russ.). doi: 10.14412/1995-4484-2016-1S-55-59

7. Tournadre A, Pereira B, Lhoste A, Dubost JJ, Ristori JM, Claudepierre P, et al. Differences between women and men with recentonset axial spondyloarthritis: Results from a prospective multicenter French cohort. Arthritis Care Res (Hoboken). 2013;65(9):1482- 1489. doi: 10.1002/acr.22001

8. Cunha RN, Vieira-Sousa E, Khmelinskii N, Ávila-Ribeiro P, Couto M, Seixas MI, et al. Sex differences in axial spondyloarthritis: Data from a Portuguese spondyloarthritis cohort. ARP Rheumatol. 2022;1(1):42-48.

9. Cortes A, Maksymowych WP, Wordsworth BP, Inman RD, Danoy P, Rahman P, et al.; Association study of genes related to bone formation and resorption and the extent of radiographic change in ankylosing spondylitis. Ann Rheum Dis. 2015;74(7):1387- 1393. doi: 10.1136/annrheumdis-2013-204835

10. Rusman T, John MB, van der Weijden MAC, Boden BJH, van der Bijl CMA, Bruijnen STG, et al. Presence of active MRI lesions in patients suspected of non-radiographic axial spondyloarthritis with high disease activity and chance at conversion after a 6-month follow-up period. Clin Rheumatol. 2020;39(5):1521- 1529. doi: 10.1007/s10067-019-04885-8

11. Ward MM, Hendrey MR, Malley JD, Learch TJ, Davis JC Jr, Reveille JD, et al. Clinical and immunogenetic prognostic factors for radiographic severity in ankylosing spondylitis. Arthritis Rheum. 2009;61(7):859-866. doi: 10.1002/art.24585

12. Lee W, Reveille JD, Davis JC Jr, Learch TJ, Ward MM, Weisman MH. Are there gender differences in severity of ankylosing spondylitis? Results from the PSOAS cohort. Ann Rheum Dis. 2007;66(5):633-638. doi: 10.1136/ard.2006.060293

13. Rudwaleit M, Haibel H, Baraliakos X, Listing J, Märker-Hermann E, Zeidler H, et al. The early disease stage in axial spondylarthritis: Results from the German Spondyloarthritis Inception Cohort. Arthritis Rheum. 2009;60(3):717-727. doi: 10.1002/art.24483

14. Cansu DU, Calışır C, Savaş Yavaş U, Kaşifoğlu T, Korkmaz C. Predictors of radiographic severity and functional disability in Turkish patients with ankylosing spondylitis. Clin Rheumatol. 2011;30(4):557-562. doi: 10.1007/s10067-010-1665-2

15. Mease PJ, McLean RR, Dube B, Liu M, Rebello S, Glynn M, et al. Comparison of men and women with axial spondyloarthritis in the US-based Corrona psoriatic arthritis/spondyloarthritis registry. J Rheumatol. 2021;48(10):1528-1536. doi: 10.3899/jrheum.201549

16. Almousa S, Alshamaa N, Wannous H, Khder K, Qasem H. Gender-related differences in axial spondyloarthritis (axSpA) patients. Egypt Rheumatol. 2023;45(1):13-16. doi: 10.1016/j.ejr.2022.08.003

17. Landi M, Maldonado-Ficco H, Perez-Alamino R, MaldonadoCocco JA, Citera G, Arturi P, et al.; RESPONDIA Group. Fundación Reumatológica Argentina “Dr. Osvaldo García Morteo. Gender differences among patients with primary ankylosing spondylitis and spondylitis associated with psoriasis and inflammatory bowel disease in an Iberoamerican Spondyloarthritis Cohort. Medicine (Baltimore). 2016;95(51):e5652. doi: 10.1097/MD.0000000000005652

18. Feldtkeller E, Bruckel J, Khan MA. Scientific contributions of ankylosing spondylitis patient advocacy groups. Curr Opin Rheumatol. 2000;12(4):239-247. doi: 10.1097/00002281-200007000-00002

19. Di Giuseppe D, Lindström U, Aaltonen K, Relas H, Provan S, Gudbjornsson B, et al. The occurrence of multiple treatment switches in axial spondyloarthritis. Results from five Nordic rheumatology registries. Rheumatology (Oxford). 2022;61(9):3647-3656. doi: 10.1093/rheumatology/keab946

20. Benavent D, Capelusnik D, Ramiro S, Molto A, López-Medina C, Dougados M, et al. Does gender influence outcome measures similarly in patients with spondyloarthritis? Results from the ASASperSpA study. RMD Open. 2022;8(2):e002514. doi: 10.1136/rmdopen-2022-002514

21. Webers C, Essers I, Ramiro S, Stolwijk C, Landewé R, van der Heijde D, et al. Gender-attributable differences in outcome of ankylosing spondylitis: Long-term results from the Outcome in Ankylosing Spondylitis International Study. Rheumatology (Oxford). 2016;55(3):419-428. doi: 10.1093/rheumatology/kev340

22. Fakih O, Desmarets M, Martin B, Prati C, Monnet E, Verhoeven F, et al. Difficult-to-treat axial spondyloarthritis is associated with psoriasis, peripheral involvement and comorbidities: Results of an observational nationwide study. RMD Open. 2023;9(4):e003461. doi: 10.1136/rmdopen-2023-003461

23. Rusman T, van Vollenhoven RF, van der Horst-Bruinsma IE. Gender differences in axial spondyloarthritis: Women are not so lucky. Curr Rheumatol Rep. 2018;20(6):35. doi: 10.1007/s11926-018-0744-2

24. Van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum. 1984;27(4):361-368. doi: 10.1002/art.1780270401

25. Sieper J, Rudwaleit M, Baraliakos X, Brandt J, Braun J, BurgosVargas R, et al. The Assessment of SpondyloArthritis international Society (ASAS) handbook: A guide to assess spondyloarthritis. Ann Rheum Dis. 2009;68(Suppl 2):ii1-ii44. doi: 10.1136/ard.2008.104018

26. Dubinina TV, Gaidukova IZ, Godzenko AA, Lapshina SA, Rebrov AP, Rumyantseva OA, et al. Guidelines for the assessment of disease activity and functional status in patients with ankylosing spondylitis in clinical practice. Nauchno-Prakticheskaya Revmatologia = Rheumatology Science and Practice. 2017;55(4):344-350 (In Russ.)]. doi: 10.14412/1995-4484-2017-344-3

27. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983;67(6):361-370. doi: 10.1111/j.1600-0447.1983.tb09716.x

28. Bjelland I, Dahl AA, Haug TT, Neckelmann D. The validity of the Hospital Anxiety and Depression Scale. An updated literature review. J Psychosom Res. 2002;52(2):69-77. doi: 10.1016/s0022-3999(01)00296-3

29. Ramiro S, Nikiphorou E, Sepriano A, Ortolan A, Webers C, Baraliakos X, et al. ASAS-EULAR recommendations for the management of axial spondyloarthritis: 2022 update. Ann Rheum Dis. 2023;82(1):19-34. doi: 10.1136/ard-2022-223296

30. Ward MM, Deodhar A, Gensler LS, Dubreuil M, Yu D, Khan MA, et al. 2019 update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis. Arthritis Care Res (Hoboken). 2019;71(10):1285-1299. doi: 10.1002/acr.24025

31. Seo MR, Yeo J, Park JW, Lee YA, Lee JH, Kang EH, et al. Korean treatment recommendations for patients with axial spondyloarthritis. J Rheum Dis. 2023;30(3):151-169. doi: 10.4078/jrd.2023.0025

32. Tam LS, Wei JC, Aggarwal A, Baek HJ, Cheung PP, Chiowchanwisawakit P, et al. 2018 APLAR axial spondyloarthritis treatment recommendations. Int J Rheum Dis. 2019;22(3):340-356. doi: 10.1111/1756-185X.13510

33. Wendling D, Hecquet S, Fogel O, Letarouilly JG, Verhoeven F, Pham T, et al. 2022 French Society for Rheumatology (SFR) recommendations on the everyday management of patients with spondyloarthritis, including psoriatic arthritis. Joint Bone Spine. 2022;89(3):105344. doi: 10.1016/j.jbspin.2022.105344

34. Machado P, Landewe R. Spondyloarthritis: Is it time to replace BASDAI with ASDAS? Nat Rev Rheumatol. 2013;9(7):388-390. doi: 10.1038/nrrheum.2013.93

35. Pedersen SJ, Sørensen IJ, Garnero P, Johansen JS, Madsen OR, Tvede N, et al. ASDAS, BASDAI and different treatment responses and their relation to biomarkers of inflammation, cartilage and bone turnover in patients with axial spondyloarthritis treated with TNFα inhibitors. Ann Rheum Dis. 2011;70(8):1375-1381. doi: 10.1136/ard.2010.138883

36. Cooksey R, Choy E. Exploring gender differences, medical history, and treatments used in patients with fibromyalgia in the UK using primary-care data: A retrospective, population-based, cohort study. Lancet Rheumatol. 2022;4:20. doi: 10.1016/S2665-9913(22)00296-X

37. Wach J, Letroublon MC, Coury F, Tebib JG. Fibromyalgia in spondyloarthritis: Effect on disease activity assessment in clinical practice. J Rheumatol. 2016;43(11):2056-2063. doi: 10.3899/jrheum.160104

38. Lee S, Kang S, Kim H, Lee J, Kim MJ, Cha HS. Sex-specific disparities in disease activity scores among patients with axial spondyloarthritis and their implications for evaluating the response to tumor necrosis factor alpha inhibitor therapy. Arthritis Res Ther. 2024;26(1):90. doi: 10.1186/s13075-024-03320-x

39. Ruau D, Liu LY, Clark JD, Angst MS, Butte AJ. Sex differences in reported pain across 11,000 patients captured in electronic medical records. J Pain. 2012;13(3):228-234. doi: 10.1016/j.jpain.2011.11.002

40. Korsakova YuL, Korotaeva TV, Loginova EIu, Gubar EЕ, Petrov AV, Patrikeeva IM, et al. Clinical and instrumental characteristics of psoriatic arthritis in men and women. Data from a cohort observational study. Terapevticheskii arkhiv. 2024;96(5):479-485. (In Russ.). doi: 10.26442/00403660.2024.05.202703

41. Blasco-Blasco M, Castrejon I, Jovani V, Pascual E, Ruiz-Cantero MT. Reviewing disease activity indices in spondyloarthritis from the sex perspective: A systematic review and metaanalysis. J Rheumatol. 2021;48(9):1395-1404. doi: 10.3899/jrheum.200967