Psoriatic arthritis (PsA) is an inflammatory musculoskeletal disease with a chronic, progressive course. Various aspects of PsA, including its clinical features, disease course and response to treatment, are influenced by sociodemographic characteristics of the patient. This includes patient sex, the biological attributes associated with being male or female, and gender, a sociocultural construct that comprises attitudes, traits and behaviours associated with being a man or a woman. An understanding of sex- and gender-related differences in PsA, as well as their underlying mechanisms, is therefore important for individualized care. In this narrative review, the influence of sex and gender on PsA manifestation and course, patient function and quality of life, and their association with comorbidities are described. Sex- and gender-related disparities in response to advanced therapies and their potential underlying mechanisms are delineated. Differences in pathophysiological mechanisms between male and female patients including genetics, immune and hormonal mechanisms are discussed. Finally, fertility and pregnancy outcomes in PsA are outlined. By adopting sex and gender lenses, this review is aimed at highlighting key differences between male and female patients with PsA and uncovering mechanisms underlying these differences, ultimately promoting individualized care of men and women with PsA and informing future research in this area.
The majority of studies show that peripheral arthritis is more common in female patients with PsA, whereas axial disease and severe psoriasis are more common in male patients, emphasizing the need for specific sex-gender considerations in diagnosis and treatment selection.
Female patients with PsA are less likely to develop radiographic damage in axial and peripheral joints than male patients, and therefore require more sensitive imaging modalities (such as MRI and ultrasound) for diagnosis.
Higher levels of pain, fatigue, poor functional status and worse quality of life in female patients with PsA have been reported compared with male patients. Women with PsA might require psycho-social support, occupational modification and targeted pain management.
Female patients with PsA are at a higher risk of discontinuing or switching advanced therapy than male patients, thereby necessitating closer monitoring after drug initiation.
Parameters of PsA disease activity improve during pregnancy and flare up during the postpartum period, emphasizing the need for close monitoring after pregnancy.
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Ritchlin, C. T., Colbert, R. A. & Gladman, D. D. Psoriatic arthritis. N. Engl. J. Med. 376, 957–970 (2017). An updated review on PsA.
Colombo, D., Cassano, N., Bellia, G. & Vena, G. A. Gender medicine and psoriasis. World J. Dermatol. 3, 36–44 (2014).
Moll, J. M. & Wright, V. Psoriatic arthritis. Semin. Arthritis Rheum. 3, 55–78 (1973).
Bem, S. L. The measurement of psychological androgyny. J. Consult. Clin. Psychol. 42, 155–162 (1974).
Johnson, J. L., Greaves, L. & Repta, R. Better science with sex and gender: facilitating the use of a sex and gender-based analysis in health research. Int. J. Equity Health 8, 14 (2009). An important article outlining sex and gender-based analysis in health research.
Litwic, A., Edwards, M., Dennison, E. & Cooper, C. Epidemiology and burden of osteoarthritis. Br. Med. Bull. 105, 185–199 (2013).
Fox, D and Moyser, M. Women in Canada: a gender-based statistical report. in The economic well-being of women in Canada (Statistics Canada, 2018).
Badley, E. M., Canizares, M., Gunz, A. C. & Davis, A. M. Visits to rheumatologists for arthritis: the role of access to primary care physicians, geographic availability of rheumatologists, and socioeconomic status. Arthritis Care Res. 67, 230–239 (2015).
Soriano, E. R. et al. Incidence and prevalence of psoriatic arthritis in Buenos Aires, Argentina: a 6-year health management organization-based study. Rheumatol. Oxf. Engl. 50, 729–734 (2011).
Nossent, J. C. & Gran, J. T. Epidemiological and clinical characteristics of psoriatic arthritis in northern Norway. Scand. J. Rheumatol. 38, 251–255 (2009).
Karmacharya, P. et al. The epidemiology of psoriatic arthritis over five decades: a population-based study. Arthritis Rheumatol. https://doi.org/10.1002/art.41741 (2021).
Yamamoto, T. et al. Epidemiological analysis of psoriatic arthritis patients in Japan. J. Dermatol. 43, 1193–1196 (2016).
Rajendran, C. P., Ledge, S. G., Rani, K. P. & Madhavan, R. Psoriatic arthritis. J. Assoc. Physicians India 51, 1065–1068 (2003).
Eder, L. et al. The epidemiology of psoriatic arthritis in Israel — a population-based study. Arthritis Res. Ther. 20, 3 (2018).
Alamanos, Y. et al. Epidemiology of psoriatic arthritis in northwest Greece, 1982–2001. J. Rheumatol. 30, 2641–2644 (2003).
Kerola, A. M. et al. Incidence, sociodemographic factors and treatment penetration of rheumatoid arthritis and psoriatic arthritis in Norway. Semin. Arthritis Rheum. 51, 1081–1088 (2021).
Grellmann, C. et al. Epidemiology and treatment of patients with rheumatoid arthritis, psoriatic arthritis and psoriasis in Germany: a real-world evidence study. Adv. Ther. 38, 366–385 (2021).
Pina Vegas, L., Sbidian, E., Penso, L. & Claudepierre, P. Epidemiologic study of patients with psoriatic arthritis in a real-world analysis: a cohort study of the French health insurance database. Rheumatol. Oxf. Engl. 60, 1243–1251 (2021).
Egeberg, A. et al. Incidence and prevalence of psoriatic arthritis in Denmark: a nationwide register linkage study. Ann. Rheum. Dis. 76, 1591–1597 (2017).
Tekin, H. G., Wu, J. J., Burge, R., Birt, J. & Egeberg, A. Burden and disease characteristics of patients with psoriatic arthritis: a population-based cross-sectional study. J. Rheumatol. 46, 716–720 (2019).
Love, T. J., Gudbjornsson, B., Gudjonsson, J. E. & Valdimarsson, H. Psoriatic arthritis in Reykjavik, Iceland: prevalence, demographics, and disease course. J. Rheumatol. 34, 2082–2088 (2007).
Kojanova, M. et al. Demographic data, comorbidities, quality of life, and survival probability of biologic therapy associated with sex-specific differences in psoriasis in the Czech Republic. Dermatol. Ther. 34, e14849 (2021).
Dönmez, S., Pamuk, Ö. N., Akker, M. & Ak, R. Clinical features and types of articular involvement in patients with psoriatic arthritis. Clin. Rheumatol. 34, 1091–1096 (2015).
Ogdie, A. et al. Prevalence and treatment patterns of psoriatic arthritis in the UK. Rheumatol. Oxf. Engl. 52, 568–575 (2013).
Theander, E. et al. Early psoriatic arthritis: short symptom duration, male gender and preserved physical functioning at presentation predict favourable outcome at 5-year follow-up. Results from the Swedish early psoriatic arthritis register (SwePsA). Ann. Rheum. Dis. 73, 407–413 (2014).
Eder, L., Thavaneswaran, A., Chandran, V. & Gladman, D. D. Gender difference in disease expression, radiographic damage and disability among patients with psoriatic arthritis. Ann. Rheum. Dis. 72, 578–582 (2013). This study was pivotal in describing important sex-related differences in clinical features, imaging and patient-reported outcomes in PsA.
Kalyoncu, U. et al. The psoriatic arthritis registry of Turkey: results of a multicentre registry on 1081 patients. Rheumatol. Oxf. Engl. 56, 279–286 (2017).
Nas, K. et al. Gender specific differences in patients with psoriatic arthritis. Mod. Rheumatol. 27, 345–349 (2017).
Duruöz, M. T. et al. Gender-related differences in disease activity and clinical features in patients with peripheral psoriatic arthritis: a multi-center study. Jt. Bone Spine 88, 105177 (2021).
Gladman, D. D., Antoni, C., Mease, P., Clegg, D. O. & Nash, P. Psoriatic arthritis: epidemiology, clinical features, course, and outcome. Ann. Rheum. Dis. 64, ii14–ii17 (2005).
Møller, P. & Vinje, O. Arthropathy and sacro-iliitis in severe psoriasis. Scand. J. Rheumatol. 9, 113–117 (1980).
Mease, P. J. et al. Influence of axial involvement on clinical characteristics of psoriatic arthritis: analysis from the Corrona Psoriatic Arthritis/Spondyloarthritis Registry. J. Rheumatol. 45, 1389 (2018).
Mease, P. J. et al. Clinical characteristics, disease activity, and patient-reported outcomes in psoriatic arthritis patients with dactylitis or enthesitis: results from the Corrona Psoriatic Arthritis/Spondyloarthritis Registry. Arthritis Care Res. 69, 1692–1699 (2017).
Nas, K. et al. The effect of gender on disease activity and clinical characteristics in patients with axial psoriatic arthritis. Mod. Rheumatol. 31, 869–874 (2021).
Orbai, A.-M. et al. Determinants of patient-reported psoriatic arthritis impact of disease: an analysis of the association with sex in 458 patients from fourteen countries. Arthritis Care Res. 72, 1772–1779 (2020).
Perez-Chada, L. M. & Merola, J. F. Comorbidities associated with psoriatic arthritis: review and update. Clin. Immunol. 214, 108397 (2020).
Orbai, A.-M. et al. International patient and physician consensus on a psoriatic arthritis core outcome set for clinical trials. Ann. Rheum. Dis. 76, 673–680 (2017).
Augustin, M. et al. Nail psoriasis in Germany: epidemiology and burden of disease. Br. J. Dermatol. 163, 580–585 (2010).
Hägg, D., Sundström, A., Eriksson, M. & Schmitt-Egenolf, M. Severity of psoriasis differs between men and women: a study of the clinical outcome measure psoriasis area and severity index (PASI) in 5438 Swedish register patients. Am. J. Clin. Dermatol. 18, 583–590 (2017).
Maul, J.-T. et al. Efficacy and survival of systemic psoriasis treatments: an analysis of the Swiss registry SDNTT. Dermatol. Basel Switz. 232, 640–647 (2016).
Hägg, D., Eriksson, M., Sundström, A. & Schmitt-Egenolf, M. The higher proportion of men with psoriasis treated with biologics may be explained by more severe disease in men. PLoS One 8, e63619 (2013).
Hernández-Fernández, C. et al. Effect of sex in systemic psoriasis therapy: differences in prescription, effectiveness and safety in the BIOBADADERM prospective cohort. Acta Derm. Venereol. 101, adv00354 (2021).
Ji, C. et al. Challenge of nail psoriasis: an update review. Clin. Rev. Allergy Immunol. 61, 377–402 (2021).
Martínez-Ortega, J. M. et al. Quality of life, anxiety and depressive symptoms in patients with psoriasis: a case-control study. J. Psychosom. Res. 124, 109780 (2019).
Zeboulon, N., Dougados, M. & Gossec, L. Prevalence and characteristics of uveitis in the spondyloarthropathies: a systematic literature review. Ann. Rheum. Dis. 67, 955–959 (2008).
Queiro, R. et al. Clinical features and predictive factors in psoriatic arthritis-related uveitis. Semin. Arthritis Rheum. 31, 264–270 (2002).
Paiva, E. S., Macaluso, D. C., Edwards, A. & Rosenbaum, J. T. Characterisation of uveitis in patients with psoriatic arthritis. Ann. Rheum. Dis. 59, 67–70 (2000).
Egeberg, A. et al. Association of psoriatic disease with uveitis: a Danish nationwide cohort study. JAMA Dermatol. 151, 1200–1205 (2015).
Peluso, R. et al. Extra-articular manifestations in psoriatic arthritis patients. Clin. Rheumatol. 34, 745–753 (2015).
Bengtsson, K. et al. Incidence of extra-articular manifestations in ankylosing spondylitis, psoriatic arthritis and undifferentiated spondyloarthritis: results from a national register-based cohort study. Rheumatol. Oxf. Engl. 60, 2725–2734 (2021).
Egeberg, A. et al. Association between psoriasis and inflammatory bowel disease: a Danish nationwide cohort study. Br. J. Dermatol. 175, 487–492 (2016).
Geijer, M. et al. The Swedish early psoriatic arthritis registry 5-year followup: substantial radiographic progression mainly in men with high disease activity and development of dactylitis. J. Rheumatol. 42, 2110–2117 (2015). This study outlined important radiological differences in PsA between men and women.
Braaten, T. J. et al. Gender differences in psoriatic arthritis with fatigue, pain, function, and work disability. J. Psoriasis Psoriatic Arthritis 4, 192–197 (2019).
Gudu, T. et al. Fatigue in psoriatic arthritis — a cross-sectional study of 246 patients from 13 countries. Jt. Bone Spine 83, 439–443 (2016).
Kenar, G. et al. Gender does not make a difference in ‘composite psoriatic disease activity index (CPDAI)’ in patients with psoriatic arthritis. Rheumatol. Int. 38, 2069–2076 (2018).
Turner, D. E. et al. Metatarsophalangeal joint pain in psoriatic arthritis: a cross-sectional study. Rheumatol. Oxf. Engl. 53, 737–740 (2014).
Tan, J. S. Q., Fong, W., Kwan, Y. H. & Leung, Y. Y. Prevalence and variables associated with fatigue in psoriatic arthritis: a cross-sectional study. Rheumatol. Int. 40, 1825–1834 (2020).
Leung, Y. Y., Fong, W., Lui, N. L. & Thumboo, J. Effect of ethnicity on disease activity and physical function in psoriatic arthritis in a multiethnic Asian population. Clin. Rheumatol. 36, 125–131 (2017).
Wallenius, M. et al. Work disability and health-related quality of life in males and females with psoriatic arthritis. Ann. Rheum. Dis. 68, 685–689 (2009).
Kristensen, L. E. et al. Long-term work disability in patients with psoriatic arthritis treated with anti-tumour necrosis factor: a population-based regional Swedish cohort study. Ann. Rheum. Dis. 72, 1675–1679 (2013).
Verstappen, S. M. M. et al. Working status in patients with rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis: results from the British Society for Rheumatology Biologics Register. Rheumatology 49, 1570–1577 (2010).
Ulus, Y., Akyol, Y., Bilgici, A. & Kuru, O. The impact of the presence of fibromyalgia on fatigue in patients with psoriatic arthritis: comparison with controls. Adv. Rheumatol. Lond. Engl. 60, 1 (2019).
Lindström Egholm, C. et al. Discordance of global assessments by patient and physician is higher in female than in male patients regardless of the physician’s sex: data on patients with rheumatoid arthritis, axial spondyloarthritis, and psoriatic arthritis from the DANBIO registry. J. Rheumatol. 42, 1781–1785 (2015).
Michelsen, B. et al. Impact of discordance between patient’s and evaluator’s global assessment on treatment outcomes in 14 868 patients with spondyloarthritis. Rheumatol. Oxf. Engl. 59, 2455–2461 (2020).
Desthieux, C. et al. Determinants of patient-physician discordance in global assessment in psoriatic arthritis: a multicenter European Study. Arthritis Care Res. 69, 1606–1611 (2017).
Wang, C. T. M., Kwan, Y. H., Fong, W., Xiong, S. Q. & Leung, Y. Y. Factors associated with patient-physician discordance in a prospective cohort of patients with psoriatic arthritis: an Asian perspective. Int. J. Rheum. Dis. 22, 1209–1215 (2019).
Widdifield, J. et al. Access to rheumatologists among patients with newly diagnosed rheumatoid arthritis in a Canadian universal public healthcare system. BMJ Open 4, e003888 (2014).
Rida, M. A. & Chandran, V. Challenges in the clinical diagnosis of psoriatic arthritis. Clin. Immunol. 214, 108390 (2020).
Firestein, G. S., Budd, R. C., Gabriel, S. E., McInnes, I. B. & O’Dell, J. R. (eds) Psoriatic Arthritis. in Kelley and Firestein’s Textbook of Rheumatology 1459–1486 (Elsevier, 2017).
Bain, B. J. Some influences on the ESR and the fibrinogen level in healthy subjects. Clin. Lab. Haematol. 5, 45–54 (1983).
Johnson, S. R., Schentag, C. T. & Gladman, D. D. Autoantibodies in biological agent naive patients with psoriatic arthritis. Ann. Rheum. Dis. 64, 770–772 (2005).
Landi, M. et al. Gender differences among patients with primary ankylosing spondylitis and spondylitis associated with psoriasis and inflammatory bowel disease in an iberoamerican spondyloarthritis cohort. Medicine 95, e5652 (2016).
Pattison, E., Harrison, B. J., Griffiths, C. E. M., Silman, A. J. & Bruce, I. N. Environmental risk factors for the development of psoriatic arthritis: results from a case–control study. Ann. Rheum. Dis. 67, 672–676 (2008).
Ortolan, A. et al. Are gender-specific approaches needed in diagnosing early axial spondyloarthritis? Data from the SPondyloArthritis Caught Early cohort. Arthritis Res. Ther. 20, 218 (2018).
Tournadre, A. et al. Differences between women and men with recent-onset axial spondyloarthritis: results from a prospective multicenter French cohort. Arthritis Care Res. 65, 1482–1489 (2013).
Diaz, P., Feld, J., Eshed, I. & Eder, L. Characterising axial psoriatic arthritis: correlation between whole spine MRI abnormalities and clinical, laboratory and radiographic findings. RMD Open 8, e002011 (2022).
Agten, C. A. et al. Postpartum bone marrow edema at the sacroiliac joints may mimic sacroiliitis of axial spondyloarthritis on MRI. Am. J. Roentgenol. 211, 1306–1312 (2018).
Rusman, T., van Bentum, R. E. & van der Horst-Bruinsma, I. E. Sex and gender differences in axial spondyloarthritis: myths and truths. Rheumatology 59, iv38–iv46 (2020).
Mathew, A. J., Østergaard, M. & Eder, L. Imaging in psoriatic arthritis: status and recent advances. Best. Pract. Res. Clin. Rheumatol. 35, 101690 (2021).
Arout, C. A., Sofuoglu, M., Bastian, L. A. & Rosenheck, R. A. Gender differences in the prevalence of fibromyalgia and in concomitant medical and psychiatric disorders: a national veterans health administration study. J. Womens Health 27, 1035–1044 (2018).
Mease, P. J. et al. Comparison of men and women with axial spondyloarthritis in the US-based Corrona Psoriatic Arthritis/Spondyloarthritis Registry. J. Rheumatol. 48, 1528–1536 (2021).
Arslan Alhussain, F. et al. Greater magnitude of entheseal microdamage and repair in psoriatic arthritis compared with ankylosing spondylitis on ultrasound. Rheumatology 58, 299–303 (2019).
Sapsford, M., Evans, J., Clunie, G. & Jadon, D. A comparison of clinical examination and ultrasound enthesitis indices in patients with psoriatic arthritis, adjusted for concomitant fibromyalgia. Ther. Adv. Musculoskelet. Dis. 13, 1759720X211003812 (2021).
Passia, E. et al. Sex-specific differences and how to handle them in early psoriatic arthritis. Arthritis Res. Ther. 24, 22 (2022).
McGonagle, D., Hermann, K.-G. A. & Tan, A. L. Differentiation between osteoarthritis and psoriatic arthritis: implications for pathogenesis and treatment in the biologic therapy era. Rheumatol. Oxf. Engl. 54, 29–38 (2015).
Saalfeld, W., Mixon, A. M., Zelie, J. & Lydon, E. J. Differentiating psoriatic arthritis from osteoarthritis and rheumatoid arthritis: a narrative review and guide for advanced practice providers. Rheumatol. Ther. 8, 1493–1517 (2021).
Marchesoni, A. et al. The problem in differentiation between psoriatic-related polyenthesitis and fibromyalgia. Rheumatol. Oxf. Engl. 57, 32–40 (2018).
Zhang, Y. & Jordan, J. M. Epidemiology of osteoarthritis. Clin. Geriatr. Med. 26, 355–369 (2010).
Smolen, J. S. et al. Rheumatoid arthritis. Nat. Rev. Dis. Prim. 4, 1–23 (2018).
Marques, A. P. et al. Prevalence of fibromyalgia: literature review update. Rev. Bras. Reumatol. Engl. Ed. 57, 356–363 (2017).
Pinkhasov, R. M. et al. Are men shortchanged on health? Perspective on health care utilization and health risk behavior in men and women in the United States. Int. J. Clin. Pract. 64, 475–487 (2010).
Samulowitz, A., Gremyr, I., Eriksson, E. & Hensing, G. “Brave Men” and “Emotional Women”: a theory-guided literature review on gender bias in health care and gendered norms towards patients with chronic pain. Pain. Res. Manag. 2018, 6358624 (2018).
Zhang, L., Losin, E. A. R., Ashar, Y. K., Koban, L. & Wager, T. D. Gender biases in estimation of others’ pain. J. Pain. 22, 1048–1059 (2021).
Chandran, S. et al. Prevalence and risk factors of low bone mineral density in psoriatic arthritis: a systematic review. Semin. Arthritis Rheum. 46, 174–182 (2016).
Zhu, T. Y., Li, E. K. & Tam, L.-S. Cardiovascular risk in patients with psoriatic arthritis. Int. J. Rheumatol. 2012, 714321 (2012).
Maas, A. H. E. M. & Appelman, Y. E. A. Gender differences in coronary heart disease. Neth. Heart J. 18, 598–602 (2010).
Eder, L., Wu, Y., Chandran, V., Cook, R. & Gladman, D. D. Incidence and predictors for cardiovascular events in patients with psoriatic arthritis. Ann. Rheum. Dis. 75, 1680–1686 (2016).
Fragoulis, G. E. et al. Higher depression rates and similar cardiovascular comorbidity in psoriatic arthritis compared with rheumatoid arthritis and diabetes mellitus. Ther. Adv. Musculoskelet. Dis. 12, 1759720×20976975 (2020).
Fagerli, K. M. et al. Malignancy and mortality rates in patients with severe psoriatic arthritis requiring tumour-necrosis factor alpha inhibition: results from the British Society for Rheumatology Biologics Register. Rheumatol. Oxf. Engl. 58, 80–85 (2019).
Özkan, S. G. et al. Prevalence of metabolic syndrome and degree of cardiovascular disease risk in patients with psoriatic arthritis. Eur. J. Rheumatol. 4, 40–45 (2017).
Dal Bello, G., Gisondi, P., Idolazzi, L. & Girolomoni, G. Psoriatic arthritis and diabetes mellitus: a narrative review. Rheumatol. Ther. 7, 271–285 (2020).
Haque, N., Lories, R. J. & de Vlam, K. Comorbidities associated with psoriatic arthritis compared with non-psoriatic spondyloarthritis: a cross-sectional study. J. Rheumatol. 43, 376–382 (2016).
Roubille, C. et al. The effects of tumour necrosis factor inhibitors, methotrexate, non-steroidal anti-inflammatory drugs and corticosteroids on cardiovascular events in rheumatoid arthritis, psoriasis and psoriatic arthritis: a systematic review and meta-analysis. Ann. Rheum. Dis. 74, 480–489 (2015).
Yang, Z.-S., Lin, N.-N., Li, L. & Li, Y. The effect of TNF inhibitors on cardiovascular events in psoriasis and psoriatic arthritis: an updated meta-analysis. Clin. Rev. Allergy Immunol. 51, 240–247 (2016).
Rohekar, S. et al. Prevalence of malignancy in psoriatic arthritis. Arthritis Rheum. 58, 82–87 (2008).
Hellgren, K. et al. Ankylosing spondylitis, psoriatic arthritis, and risk of malignant lymphoma: a cohort study based on nationwide prospectively recorded data from Sweden. Arthritis Rheumatol. 66, 1282–1290 (2014).
Polachek, A. et al. Malignancy in psoriatic disease: results from prospective longitudinal cohorts. Semin. Arthritis Rheum. 51, 144–149 (2021).
Hagberg, K. W. et al. Rates of cancers and opportunistic infections in patients with psoriatic arthritis compared with patients without psoriatic arthritis. J. Clin. Rheumatol. Pract. Rep. Rheum. Musculoskelet. Dis. 22, 241–247 (2016).
Haddad, A. et al. The incidence and predictors of infection in psoriasis and psoriatic arthritis: results from longitudinal observational cohorts. J. Rheumatol. 43, 362–366 (2016).
van Lunzen, J. & Altfeld, M. Sex differences in infectious diseases-common but neglected. J. Infect. Dis. 209 (Suppl 3), S79–S80 (2014).
Wu, C.-Y. et al. Depression and insomnia in patients with psoriasis and psoriatic arthritis taking tumor necrosis factor antagonists. Medicine 95, e3816 (2016).
Albert, P. R. Why is depression more prevalent in women? J. Psychiatry Neurosci. 40, 219–221 (2015).
McLean, C. P., Asnaani, A., Litz, B. T. & Hofmann, S. G. Gender differences in anxiety disorders: prevalence, course of illness, comorbidity and burden of illness. J. Psychiatr. Res. 45, 1027–1035 (2011).
Mathew, A. J. & Chandran, V. Depression in psoriatic arthritis: dimensional aspects and link with systemic inflammation. Rheumatol. Ther. 7, 287–300 (2020).
Lee, M.-S., Yeh, Y.-C., Chang, Y.-T. & Lai, M.-S. All-cause and cause-specific mortality in patients with psoriasis in Taiwan: a nationwide population-based study. J. Invest. Dermatol. 137, 1468–1473 (2017).
Haddad, A. et al. The association of psoriatic arthritis with all-cause mortality and leading causes of death in psoriatic arthritis. J. Rheumatol. https://doi.org/10.3899/jrheum.210159 (2021).
Mok, C. C., Kwok, C. L., Ho, L. Y., Chan, P. T. & Yip, S. F. Life expectancy, standardized mortality ratios, and causes of death in six rheumatic diseases in Hong Kong, China. Arthritis Rheum. 63, 1182–1189 (2011).
Serdarevic, M., Striley, C. W. & Cottler, L. B. Gender differences in prescription opioid use. Curr. Opin. Psychiatry 30, 238–246 (2017).
Dominick, K. L., Ahern, F. M., Gold, C. H. & Heller, D. A. Gender differences in NSAID use among older adults with osteoarthritis. Ann. Pharmacother. 37, 1566–1571 (2003).
Kingsley, G. H. & Scott, D. L. Assessing the effectiveness of synthetic and biologic disease-modifying antirheumatic drugs in psoriatic arthritis — a systematic review. Psoriasis Auckl. NZ 5, 71–81 (2015).
Zardin-Moraes, M. et al. Prevalence of psoriatic arthritis patients achieving minimal disease activity in real-world studies and randomized clinical trials: systematic review with metaanalysis. J. Rheumatol. 47, 839–846 (2020).
Mateo Soria, L. et al. Long-term survival of biological therapy in psoriatic arthritis: 18-year analysis of a cohort in a tertiary hospital. Rheumatol. Int. 42, 1043–1051 (2022).
Chimenti, M. S. et al. A 2-year observational study on treatment targets in psoriatic arthritis patients treated with TNF inhibitors. Clin. Rheumatol. 36, 2253–2260 (2017).
Stober, C. et al. Prevalence and predictors of tumour necrosis factor inhibitor persistence in psoriatic arthritis. Rheumatol. Oxf. Engl. 57, 158–163 (2018).
Iannone, F. et al. Longterm clinical outcomes in 420 patients with psoriatic arthritis taking anti-tumor necrosis factor drugs in real-world settings. J. Rheumatol. 43, 911–917 (2016).
Flouri, I. D. et al. Comparative analysis and predictors of 10-year tumor necrosis factor inhibitors drug survival in patients with spondyloarthritis: first-year response predicts longterm drug persistence. J. Rheumatol. 45, 785–794 (2018).
Glintborg, B. et al. Treatment response, drug survival, and predictors thereof in 764 patients with psoriatic arthritis treated with anti-tumor necrosis factor α therapy: results from the nationwide Danish DANBIO registry. Arthritis Rheum. 63, 382–390 (2011).
Saad, A. A. et al. Persistence with anti-tumour necrosis factor therapies in patients with psoriatic arthritis: observational study from the British Society of Rheumatology Biologics Register. Arthritis Res. Ther. 11, R52 (2009).
Saad, A. A. et al. Efficacy and safety of anti-TNF therapies in psoriatic arthritis: an observational study from the British Society for Rheumatology Biologics Register. Rheumatol. Oxf. Engl. 49, 697–705 (2010).
Van den Bosch, F. et al. Effectiveness of adalimumab in treating patients with active psoriatic arthritis and predictors of good clinical responses for arthritis, skin and nail lesions. Ann. Rheum. Dis. 69, 394–399 (2010).
da Silva, M. R. R. et al. Biological therapy in the treatment of psoriatic arthritis: economic and epidemiological considerations. Expert. Rev. Clin. Immunol. 15, 879–887 (2019).
Ribeiro da Silva, M. R. et al. Medication persistence for psoriatic arthritis in a Brazilian real-world setting. Future Sci. OA 5, FSO369 (2019).
Fagerli, K. M. et al. Long-term persistence of TNF-inhibitor treatment in patients with psoriatic arthritis. Data from the British Society for Rheumatology Biologics Register. RMD Open. 4, e000596 (2018).
Favalli, E. G. et al. Eight-year retention rate of first-line tumor necrosis factor inhibitors in spondyloarthritis: a multicenter retrospective analysis. Arthritis Care Res. 69, 867–874 (2017).
Haddad, A. et al. Minimal disease activity and anti-tumor necrosis factor therapy in psoriatic arthritis. Arthritis Care Res. 67, 842–847 (2015).
Iannone, F. et al. Golimumab effectiveness in biologic inadequate responding patients with rheumatoid arthritis, psoriatic arthritis and spondyloarthritis in real-life from the Italian registry GISEA. Jt. Bone Spine 88, 105062 (2021).
Lubrano, E., Parsons, W. J. & Perrotta, F. M. Assessment of response to treatment, remission, and minimal disease activity in axial psoriatic arthritis treated with tumor necrosis factor inhibitors. J. Rheumatol. 43, 918–923 (2016).
Perrotta, F. M., Marchesoni, A. & Lubrano, E. Minimal disease activity and remission in psoriatic arthritis patients treated with anti-TNF-α drugs. J. Rheumatol. 43, 350–355 (2016).
Vieira-Sousa, E. et al. Real-world longterm effectiveness of tumor necrosis factor inhibitors in psoriatic arthritis patients from the rheumatic diseases Portuguese register. J. Rheumatol. 47, 690–700 (2020).
Højgaard, P. et al. Gender differences in biologic treatment outcomes-a study of 1750 patients with psoriatic arthritis using Danish Health Care Registers. Rheumatol. Oxf. Engl. 57, 1651–1660 (2018). The first study investigating sex differences in treatment response to biologics in PsA.
Ramonda, R. et al. Effectiveness and safety of secukinumab in 608 patients with psoriatic arthritis in real life: a 24-month prospective, multicentre study. RMD Open 7, e001519 (2021).
Navarini, L. et al. Retention rates and identification of factors associated with anti-TNFα, anti-IL17, and anti-IL12/23 R agents discontinuation in psoriatic arthritis patients: results from a real-world clinical setting. Clin. Rheumatol. 39, 2663–2670 (2020).
Geale, K. et al. Persistence of biologic treatments in psoriatic arthritis: a population-based study in Sweden. Rheumatol. Adv. Pract. 4, rkaa070 (2020).
Favalli, E. G. et al. Retrospective evaluation of patient profiling and effectiveness of apremilast in an Italian multicentric cohort of psoriatic arthritis patients. Clin. Exp. Rheumatol. 38, 19–26 (2020).
Mease, P. J. et al. Baseline patient characteristics associated with response to biologic therapy in patients with psoriatic arthritis enrolled in the Corrona Psoriatic Arthritis/Spondyloarthritis Registry. RMD Open 4, e000638 (2018).
Murray, K. et al. Long-term remission and biologic persistence rates: 12-year real-world data. Arthritis Res. Ther. 23, 25 (2021).
Glintborg, B. et al. Clinical response, drug survival, and predictors thereof among 548 patients with psoriatic arthritis who switched tumor necrosis factor α inhibitor therapy: results from the Danish Nationwide DANBIO Registry. Arthritis Rheum. 65, 1213–1223 (2013).
Sewerin, P., Borchert, K., Meise, D., Schneider, M. & Mahlich, J. Real-world treatment persistence with biologic disease-modifying antirheumatic drugs among German patients with psoriatic arthritis — a retrospective database study. Rheumatol. Ther. 8, 483–497 (2021).
Michelsen, B. et al. Four-year follow-up of inflammatory arthropathy patients treated with golimumab: data from the observational multicentre NOR-DMARD study. Semin. Arthritis Rheum. 50, 12–16 (2020).
Iannone, F. et al. Two-year survival rates of anti-TNF-α therapy in psoriatic arthritis (PsA) patients with either polyarticular or oligoarticular PsA. Scand. J. Rheumatol. 44, 192–199 (2015).
D’Angelo, S. et al. Effectiveness of adalimumab for the treatment of psoriatic arthritis: an Italian real-life retrospective study. Front. Pharmacol. 10, 1497 (2019).
Sokka, T. et al. Women, men, and rheumatoid arthritis: analyses of disease activity, disease characteristics, and treatments in the QUEST-RA Study. Arthritis Res. Ther. 11, R7 (2009).
Rusman, T., van Vollenhoven, R. F. & van der Horst-Bruinsma, I. E. Gender differences in axial spondyloarthritis: women are not so lucky. Curr. Rheumatol. Rep. 20, 35 (2018).
Klein, S. L. & Flanagan, K. L. Sex differences in immune responses. Nat. Rev. Immunol. 16, 626–638 (2016).
Klein, S. L. & Morgan, R. The impact of sex and gender on immunotherapy outcomes. Biol. Sex. Differ. 11, 24 (2020).
Strand, V., Goncalves, J. & Isaacs, J. D. Immunogenicity of biologic agents in rheumatology. Nat. Rev. Rheumatol. 17, 81–97 (2021).
Hiltunen, J. et al. Immunogenicity of subcutaneous TNF inhibitors and its clinical significance in real-life setting in patients with spondyloarthritis. Rheumatol. Int. 42, 1015–1025 (2022).
Murage, M. J. et al. Medication adherence and persistence in patients with rheumatoid arthritis, psoriasis, and psoriatic arthritis: a systematic literature review. Patient Prefer. Adherence 12, 1483–1503 (2018).
de Vries, S. T. et al. Sex differences in adverse drug reactions reported to the national pharmacovigilance centre in the Netherlands: an explorative observational study. Br. J. Clin. Pharmacol. 85, 1507–1515 (2019).
Kim, J.-R. & Kim, H. A. Molecular mechanisms of sex-related differences in arthritis and associated pain. Int. J. Mol. Sci. 21, E7938 (2020). This Review summarizes sex-related differences in the pathogenesis of arthritis and pain relevant to PsA.
Nascimento, M. G., Kosminsky, M. & Chi, M. Gender role in pain perception and expression: an integrative review. BrJP 3, 58–62 (2020).
Queiro, R. et al. Minimal disease activity and impact of disease in psoriatic arthritis: a Spanish cross-sectional multicenter study. Arthritis Res. Ther. 19, 72 (2017).
O’Rielly, D. D. & Rahman, P. Genetics of psoriatic arthritis. Best. Pract. Res. Clin. Rheumatol. 28, 673–685 (2014).
Rahman, P., Gladman, D. D., Schentag, C. T. & Petronis, A. Excessive paternal transmission in psoriatic arthritis. Arthritis Rheum. 42, 1228–1231 (1999). This study reported sexual dimorphism in inheritance patterns in PsA.
Pollock, R. A. et al. Further evidence supporting a parent-of-origin effect in psoriatic disease. Arthritis Care Res. 67, 1586–1590 (2015).
Karason, A. et al. A susceptibility gene for psoriatic arthritis maps to chromosome 16q: evidence for imprinting. Am. J. Hum. Genet. 72, 125–131 (2003).
Scher, J. U., Ogdie, A., Merola, J. F. & Ritchlin, C. Preventing psoriatic arthritis: focusing on patients with psoriasis at increased risk of transition. Nat. Rev. Rheumatol. 15, 153–166 (2019).
Eder, L. et al. Association between environmental factors and onset of psoriatic arthritis in patients with psoriasis. Arthritis Care Res. 63, 1091–1097 (2011).
Oertelt-Prigione, S. in Principles of Gender-Specific Medicine 3rd edn (ed. Legato, M. J.), Ch. 21, 309–321 (Academic Press, 2017).
Taneja, V. Sex hormones determine immune response. Front. Immunol. 9, 1931 (2018).
Cornelius, D. C. in Sex Differences in Cardiovascular Physiology and Pathophysiology (eds LaMarca, B. & Alexander, B. T.), Ch. 3, 205–217 (Academic Press, 2019).
Lefèvre, N. et al. The number of X chromosomes influences inflammatory cytokine production following toll-like receptor stimulation. Front. Immunol. 10, 1052 (2019).
Haley, E. K. et al. The impact of genetic background and sex on the phenotype of IL-23 induced murine spondyloarthritis. PLoS One 16, e0247149 (2021).
Pongratz, G., Straub, R. H., Schölmerich, J., Fleck, M. & Härle, P. Serum BAFF strongly correlates with PsA activity in male patients only-is there a role for sex hormones? Clin. Exp. Rheumatol. 28, 813–819 (2010).
Mollard, E. et al. The impact of menopause on functional status in women with rheumatoid arthritis. Rheumatology 57, 798–802 (2018).
Wu, S., Cho, E., Li, W., Grodstein, F. & Qureshi, A. A. Hormonal factors and risk of psoriasis in women: a cohort study. Acta Derm. Venereol. 96, 927–931 (2016).
Ceovic, R. et al. Psoriasis: female skin changes in various hormonal stages throughout life — puberty, pregnancy, and menopause. BioMed. Res. Int. 2013, 571912 (2013).
Jeong, H. et al. Estrogen attenuates the spondyloarthritis manifestations of the SKG arthritis model. Arthritis Res. Ther. 19, 198 (2017). An important study reporting the relationship between sex hormones and development of arthritis.
Jeong, H. et al. Selective estrogen receptor modulator lasofoxifene suppresses spondyloarthritis manifestation and affects characteristics of gut microbiota in zymosan-induced SKG mice. Sci. Rep. 11, 11923 (2021).
White, H. D. & Robinson, T. D. A novel use for testosterone to treat central sensitization of chronic pain in fibromyalgia patients. Int. Immunopharmacol. 27, 244–248 (2015).
Bartley, E. J. & Fillingim, R. B. Sex differences in pain: a brief review of clinical and experimental findings. Br. J. Anaesth. 111, 52–58 (2013). A Review outlining sex-related differences in pain.
Myers, C. D., Riley, J. L. & Robinson, M. E. Psychosocial contributions to sex-correlated differences in pain. Clin. J. Pain. 19, 225–232 (2003).
Eudy, A. M., McDaniel, G. & Clowse, M. E. Pregnancy outcomes, fertility, and family planning in women with psoriatic arthritis. Obstet. Med. 13, 70–75 (2020).
Bourg, M., Ruyssen-Witrand, A., Bettiol, C. & Parinaud, J. Fertility and sexuality of women with inflammatory arthritis. Eur. J. Obstet. Gynecol. Reprod. Biol. 251, 199–205 (2020).
Caldarola, G. et al. Untreated psoriasis impairs male fertility: a case-control study. Dermatol. Basel Switz. 233, 170–174 (2017).
Ursin, K., Lydersen, S., Skomsvoll, J. F. & Wallenius, M. Psoriatic arthritis disease activity during and after pregnancy: a prospective multicenter study. Arthritis Care Res. 71, 1092–1100 (2019).
Polachek, A. et al. Outcome of pregnancy in women with psoriatic arthritis compared to healthy controls. Clin. Rheumatol. 38, 895–902 (2019).
Berman, M. et al. The effect of pregnancy on disease activity in patients with psoriatic arthritis. J. Rheumatol. 45, 1651–1655 (2018).
Smith, C. J. F., Bandoli, G., Kavanaugh, A. & Chambers, C. D. Birth outcomes and disease activity during pregnancy in a prospective cohort of women with psoriatic arthritis and ankylosing spondylitis. Arthritis Care Res. 72, 1029–1037 (2020).
Genest, G., Spitzer, K. A. & Laskin, C. A. Maternal and fetal outcomes in a cohort of patients exposed to tumor necrosis factor inhibitors throughout pregnancy. J. Rheumatol. 45, 1109–1115 (2018).
Xie, W., Huang, H., Ji, L. & Zhang, Z. Maternal and neonatal outcomes in pregnant women with psoriasis and psoriatic arthritis: a systematic review and meta-analysis. Rheumatol. Oxf. Engl. 60, 4018–4028 (2021).
Remaeus, K., Stephansson, O., Johansson, K., Granath, F. & Hellgren, K. Maternal and infant pregnancy outcomes in women with psoriatic arthritis: a Swedish nationwide cohort study. BJOG Int. J. Obstet. Gynaecol. 126, 1213–1222 (2019).
Eastell, R. et al. Pharmacological management of osteoporosis in postmenopausal women: an Endocrine Society* clinical practice guideline. J. Clin. Endocrinol. Metab. 104, 1595–1622 (2019).
Pearson, G. J. et al. 2021 Canadian Cardiovascular Society guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in adults. Can. J. Cardiol. 37, 1129–1150 (2021).
Vlassoff, C. Gender differences in determinants and consequences of health and illness. J. Health Popul. Nutr. 25, 47–61 (2007).
Y.-Y.L. has been supported by National Medical Research Council, Singapore (NMRC/CSA-Inv/0022/2017). S.R.J. has been awarded a Canadian Institutes of Health Research New Investigator Award. J.W. receives support from the Arthritis Society Stars Career Development Award (STAR-19-0610). P.R. holds the RTOERO Chair in Geriatric Medicine at the University of Toronto. L.E. has been awarded the Early Researcher Award from the Ontario Ministry of Research, Innovation and Science and Canada Research Chair (Tier 2) in Inflammatory Rheumatic Diseases.
Y.-Y.L. received an honorarium from AbbVie, DKSH, Janssen, Novartis and Pfizer. V.S. has received consultation fees from AbbVie, Amgen Corporation, Arena, Aria, AstraZeneca, BMS, Boehringer Ingelheim, Celltrion, Galapagos, Genentech/Roche, Gilead, GSK, Horizon, Ichnos, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Rheos, Samsung, Sandoz, Sanofi, Sorrento, Sun Pharma, and UCB. L.E. received educational and research grants and consultation fees from AbbVie, UCB, Eli Lily, Novartis, Sandoz and Pfizer. S.R.J., J.W., S.T. and P.R. declare no competing interests.
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Tarannum, S., Leung, YY., Johnson, S.R. et al. Sex- and gender-related differences in psoriatic arthritis. Nat Rev Rheumatol (2022). https://doi.org/10.1038/s41584-022-00810-7