CO:09:1 | The impact of sex and gender on fibromyalgia syndrome: data from the Italian Fibromyalgia Registry

Martina Favretti¹, Cristina Iannuccelli², Giulio Dolcini¹, Sonia Farah³, Marco Di Carlo³, Giuseppina Tramontano⁴, Giorgia Ferrari⁴, Fabiola Atzeni⁵, Greta Pellegrino^6|7, Piercarlo Sarzi-Puttini^6|7, Fausto Salaffi³, Manuela Di Franco⁸. | ¹Dipartimento di Medicina Molecolare, Sapienza Università di Roma; ²UOC Reumatologia, Policlinico Umberto I, Roma; ³Unità di Reumatologia, Dipartimento di Scienze Cliniche e Molecolari, Università Politecnica delle Marche, Jesi (AN); ⁴Unità di Reumatologia, Dipartimento di Specialità Mediche, Regional Health Trust 3, Genova; ⁵Unità di Reumatologia, Dipartimento di Medicina Interna, Università di Messina; ⁶Unità di Reumatologia, IRCCS Ospedale Galeazzi - Sant'Ambrogio, Milano; ⁷Dipartimento di Scienze Biomediche e Cliniche, Università degli studi di Milano; ⁸UOC Reumatologia, Dipartimento di Scienze Cliniche Internistiche Anestesiologiche e Cardiovascolari, La Sapienza, Roma, Italy

Background. Studies have shown that the majority of fibromyalgia (FM) patients are women, with an average global female-to-male ratio of 3:1. Although differences in the perception, description, and expression of pain between sexes have been documented, the impact of sex and gender on FM disease severity and burden remains controversial. Moreover, despite the availability of various disease severity measures, the potential occurrence of gender-related differential item functioning (DIF) within these questionnaires has not been explored. Consequently, it is unclear whether these tools are equally sensitive in both men and women with FM. The primary aim of this study was to assess potential sex differences in disease severity using data from a web-based FM patient registry. The secondary aim was to investigate the presence of gender-related DIF in three disease-specific questionnaires: the Polysymptomatic Distress Scale (PDS), the modified Fibromyalgia Assessment Status (ModFAS), and the revised Fibromyalgia Impact Questionnaire (FIQR).

Methods. The study population comprised male and female patients, pair-matched for age and body mass index (BMI), diagnosed with FM according to the 2010/2011 American College of Rheumatology (ACR) criteria, and recruited from five Italian rheumatology centers. Data collected for each patient included sociodemographic characteristics (age, sex, marital status, education level, and BMI) as well as scores from the three FM-specific questionnaires. Multiple linear regression models were used to examine associations between sex and disease activity measures. Further analyses stratified by sex assessed how sociodemographic factors differentially impacted FM outcomes. DIF was analyzed using a hybrid Ordinal Logistic Regression/Item Response Theory (OLR/IRT) approach.

Results. Data from 331 male and 331 female patients were retrospectively analyzed. Demographic characteristics are shown in Table 1. Multivariate analysis revealed that female sex was significantly associated with greater physical disability (FIQR physical function beta=1.686, p<0.001), but not with overall disease severity (PDS beta=0.304, p=0.5) (Table 2). In sex-stratified analyses, being married was significantly associated with both disease severity (PDS beta=1.730, p=0.04) and disease impact (FIQR total beta=-7.658, p<0.001) among women, whereas BMI was significantly associated with disease impact (FIQR total beta=0.962, p<0.001), disease and symptoms severity (ModFAS beta=-0.19, p=0.02; SSS beta=-0.090, p=0.02) among men (Figure 1). Significant gender-related DIF was observed for only one item in the Symptoms Severity subscale of the PDS.

Conclusions. These findings suggest that women with FM experience greater physical impairment than men, despite similar overall disease severity. Additionally, the study highlights a complex interplay between sociodemographic factors and FM severity and impact, with differing effects across sexes. Finally, the minimal gender-related DIF observed supports the validity of the three FM-specific questionnaires for use in both male and female patients.