Available online 25 November 2023, 101875

Author links open overlay panel, , , , , , , Abstract

Axial spondyloarthritis (axSpA) was historically considered a disease of men, largely due to the recognition of a more severe, progressive phenotype, ankylosing spondylitis (AS; or radiographic axSpA, r-axSpA) aiding the clinical diagnosis [[1], [2]]. Data demonstrating the near equal prevalence of axSpA in women only started to emerge in the last decades, highlighting intrinsic differences in disease phenotype, and clinical and imaging characteristics between sexes, which partly explain the issue of underdiagnosis in women. Similar to the evolving understanding of spondyloarthritis and the diseases that term describes, the concepts of gender and sex also warrant further clarification to accurately assess their potential role in disease pathophysiology and phenotypic expression. This narrative review delves into the most recent evidence from the literature on the true prevalence of sex differences in axSpA, and the impact of sex and gender on diagnosis, disease characteristics and treatment response in this, still underserved, chronic disease.

Section snippetsIntroduction: Sex and gender in axial spondyloarthritis

Awareness of the role of sex and gender in the understanding of rheumatic musculoskeletal disorders has only recently increased. Often, the terms “sex” and “gender” are used interchangeably, yet their constructs differ. Sex refers to the biological attributes and physiological differences between males, females, and intersex persons, whereas gender refers to the socially and culturally constructed roles, behaviors, and expectations typically associated with male or female sex. Gender is a

The challenge of diagnosis in axial spondyloarthritis

The diagnosis of axSpA is hindered by the lack of specific biomarkers, relying on the clinician's ability to identify patterns of the disease based on clinical features, laboratory, and imaging data. While imaging is fundamental to the diagnosis of axSpA, conventional radiographs of the sacroiliac joints have low sensitivity and poor intra-reader reliability [6,7]. Currently, there are no diagnostic criteria for axSpA with both the modified New York Criteria (mNYC) and the Association of

Sex and outcomes in axial spondyloarthritis clinical trials

Despite the increased recognition of axSpA amongst females, and the growing number of therapeutic agents licensed for the treatment of axSpA, data are still lacking on how sex and gender differences impact treatment outcomes both in clinical trials and real life. Indeed, most clinical trials in rheumatology do not analyze outcomes by sex or report them only as post hoc analyses that are inadequately powered to detect statistically significant differences [35,40]. This portion of the review

Outcomes in observational studies

Real world evidence coming from observational studies has been instrumental in our understanding of sex differences in axSpA including disease characteristics, patient-reported outcomes, and treatment response. Table 1 and Table 2 summarize part of the growing pool of observational data supporting this.

Patient-reported outcome measures (PROMS) data are integral to our management of axSpA across several countries and are regularly used to monitor disease activity and response to treatment. To

Summary

In this review, we summarized the literature on sex and gender differences affecting axSpA clinical care. We discussed the challenges of diagnosing axSpA, including the lack of specific biomarkers and reliance on clinical features and imaging. Diagnostic delays are common, especially in women, and can be attributed to differences in disease manifestations, imaging findings, and biases among healthcare professionals. We explored the literature on pathways to timely diagnosis and highlighted

Practice points●

It is important to recognize both typical and atypical clinical manifestations of axSpA in women to make an early and accurate diagnosis and initiate appropriate treatment.

●

Women with axSpA may have lower response rates to biologics compared with men and may have more need for treatment discontinuation or switching. Treatment should be based on individual patient characteristics, including comorbidities, medication history, patient preferences, disease burden, and severity.

●

Pregnant women with

Research agenda●

Further examination of the relationships between gender or sex with axSpA presentation and clinical outcomes is essential for improving diagnosis, approaching treatment decisions, and improving outcomes for individuals with this condition

●

Women with axSpA experience diagnostic delays and poorer treatment outcomes, creating an urgent need for increased awareness and education surrounding the recognition and early diagnosis of axSpA in women, as well as other underdiagnosed populations.

●

Randomized

Declaration of competing interest

The authors have nothing to disclose.

Acknowledgements

Role of the funding source:

HM-O is supported by the National Institute for Health Research (NIHR) Leeds Biomedical Research Centre (LBRC). The views expressed are those of the authors and not necessarily those of the (UK) National Health Service (NHS), the NIHR, or the (UK) Department of Health.

JWL is supported by the Rheumatology Research Foundation Investigator Award, the Spondyloarthritis Research and Treatment Network (SPARTAN) seed grant, and the Spondylitis Association of America Bruckel

References (107)A.S. Pinto et al.Predictors of remission in people with axial spondyloarthritis: a systematic literature review

Semin Arthritis Rheum

(2022 Oct)

H.F. Polley et al.Rheumatoid spondylitis: a study of 1,035 cases

Ann Intern Med

(1947 Feb 1)

H.F. WestAetiology of ankylosing spondylitis

Ann Rheum Dis

(1949 Jun)

S. Thornton et al.Towards statistical best practices for gender and Sex Data

Significance

(2022 Jan 25)

M. van Onna et al.General practitioners' perceptions of their ability to identify and refer patients with suspected axial spondyloarthritis: a qualitative study

J Rheumatol

(2014 May)

R. van den Berg et al.Agreement between clinical practice and trained central reading in reading of sacroiliac joints on plain pelvic radiographs: results from the Desir cohort

Arthritis Rheumatol

(2014 Sept)

A. van Tubergen et al.Radiographic assessment of Sacroiliitis by radiologists and rheumatologists: does training improve quality?

Ann Rheum Dis

(2003 Jun)

M. Rudwaleit et al.The development of assessment of Spondyloarthritis International Society classification criteria for Axial Spondyloarthritis (part I): classification of paper patients by expert opinion including uncertainty appraisal

Ann Rheum Dis

(2009 Jun)

M.L. Marques et al.Measuring spinal mobility in early axial spondyloarthritis: does it matter?

Rheumatology

(2019 Sept)

J.D. Reveille et al.The prevalence of HLA-B27 in the US: data from the US national health and nutrition examination survey, 2009

Arthritis Rheum

(2012 May)

J.A. Walsh et al.Clinical manifestations and diagnosis of axial spondyloarthritis

J Clin Rheumatol

(2021 Dec)

P.J. Mease et al.Comparative disease burden in patients with rheumatoid arthritis, psoriatic arthritis, or axial spondyloarthritis: data from two Corrona registries

Rheumatol Ther

(2019 Dec)

D. van der Heijde et al.Referral patterns, diagnosis, and disease management of patients with axial spondyloarthritis

J Clin Rheumatol

(2014 Dec)

V. Jovaní et al.Understanding how the diagnostic delay of spondyloarthritis differs between women and men: a systematic review and metaanalysis

J Rheumatol

(2017 Feb)

H. Baumberger et al.Gradual progressive change to equal prevalence of ankylosing spondylitis among males and females in Switzerland: data from the Swiss ankylosing spondylitis society (SVMB)

(2017)

J. Sieper et al.Review: nonradiographic axial spondyloarthritis: new definition of an old disease?

Arthritis Rheum

(2013 Mar)

J.F. Simard et al.Are we missing lupus in males? Evidence of cognitive bias from a randomized experiment in the United States

Am J Epidemiol

(2022 Jan 1)

M. Garrido-Cumbrera et al.Gender differences in patient journey to diagnosis and disease outcomes: results from the European Map of Axial spondyloarthritis (EMAS)

Clin Rheumatol

(2021 Jul)

G. Slobodin et al.Recently diagnosed axial spondyloarthritis: gender differences and factors related to delay in diagnosis

Clin Rheumatol

(2011 Aug)

S. Maguire et al.Worse scores but similar patterns of disease activity: interpreting outcomes in women with axial spondyloarthropathy

Scand J Rheumatol

(2023 Mar)

C. Fernández‐Carballido et al.Female sex, age, and unfavorable response to tumor necrosis factor inhibitors in patients with axial spondyloarthritis: results of statistical and artificial intelligence–based data analyses of a national multicenter prospective registry

Arthritis Care Res

(2023 Jan)

R.N. Cunha et al.Sex differences in axial spondyloarthritis: data from a Portuguese spondyloarthritis cohort

ARP Rheumatol

(2022 Jan-Mar)

R.A. Andreasen et al.The impact of sex and disease classification on patient-reported outcome measures in axial spondyloarthritis: a descriptive prospective cross-sectional study

Arthritis Res Ther

(2019 Oct 29)

N. Vastesaeger et al.Predicting the outcome of ankylosing spondylitis therapy

Ann Rheum Dis

(2011 Jun 1)

M. Arévalo et al.Influence of HLA-B27 on the ankylosing spondylitis phenotype: results from the REGISPONSER database

Arthritis Res Ther

(2018)

K. Ziegeler et al.Anatomical variation of the sacroiliac joint carries an increased risk for erosion and bone marrow oedema in axial spondyloarthritis

Rheumatology

(2023 Mar 1)

K. Ziegeler et al.Joint anatomy in axial spondyloarthritis: strong associations between sacroiliac joint form variation and symptomatic disease

Rheumatology

(2021 Dec 24)

K. Aouad et al.Influence of sex on early axial spondyloarthritis: a six‐year longitudinal analysis from a large national cohort

Arthritis Care Res

(2023 Feb 14)

M. Lorenzin et al.Relationship between sex and clinical and imaging features of early axial spondyloarthritis: results from a 48 month follow-up (Italian arm of the SPondyloArthritis Caught Early (SPACE) study)

Scand J Rheumatol

(2023 Feb 27)

W.P. Maksymowych et al.Data-driven definitions for active and structural MRI lesions in the sacroiliac joint in spondyloarthritis and their predictive utility

Rheumatology

(2021 Oct 2)

U. Weber et al.Imaging in axial spondyloarthritis: what is relevant for diagnosis in daily practice?

Curr Rheumatol Rep

(2021 Jul 3)

S.T. Ulas et al.New perspectives in axial spondyloarthritis - first results of gender-specific assessment of MRI imaging criteria [abstract]

Ann Rheum Dis

(2022 May 23)

H. Marzo-Ortega et al.The impact of gender and sex on diagnosis, treatment outcomes and health-related quality of life in patients with axial spondyloarthritis

Clin Rheumatol

(2022)

V. Jovani et al.Challenges to conquer from the gender perspective in medicine: the case of spondyloarthritis

PLoS One

(2018 Oct 12)

K.L. Lapane et al.Patient perspectives on health care provider practices leading to an axial spondyloarthritis diagnosis: an exploratory qualitative research study

BMC Fam Pract

(2021 Dec 20)

C.A. Hay et al.Diagnostic delay in axial spondyloarthritis: a systematic review

Clin Rheumatol

(2022 Jul)

E. Yi et al.Clinical, economic, and humanistic burden associated with delayed diagnosis of axial spondyloarthritis: a systematic review

Rheumatol Ther

(2020 Mar)

R. Stovall et al.Sexual dimorphism in the prevalence, manifestation and outcomes of axial spondyloarthritis

Nat Rev Rheumatol

(2022 Nov)

M. Benhamou et al.Clinical relevance of C-reactive protein in ankylosing spondylitis and evaluation of the NSAIDs/coxibs' treatment effect on C-reactive protein

Rheumatology

(2010 Mar)

F.P. Kroon et al.Non-steroidal anti-inflammatory drugs (NSAIDs) for axial spondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis)

Cochrane Database Syst Rev

(2015 Jul 17)

View full text

© 2023 Elsevier Ltd. All rights reserved.