DAS28-ESR Scores Higher in Female Patients With Rheumatoid Arthritis in Remission

Of the disease activity indicators, a significant difference between sexes was observed in Disease Activity Score-28 for Rheumatoid Arthritis with erythrocyte sedimentation rate (DAS28-ESR) was reported in female patients with rheumatoid arthritis (RA) in remission, with women demonstrating higher values of DAS28-ESR in remission compared with male patients, according to a study published in BMC Rheumaotology.¹ However, investigators noted that the degree of misclassification in DAS28-ESR remission was unignorable.

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Evaluating the disease activity is an important aspect of the “Treat to Target” (T2T) approach, which includes setting a goal and formulating an appropriate treatment strategy. It is usually assessed via scoring systems including DAS-28 ESR, Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI), and DAS28-C-reactive protein (CRP). Disease activity is historically influenced by factors including sex, age, and body mass index (BMI).²

“It is unclear whether previous studies accurately evaluated the effects of sex differences on disease activity indices, or the results were obtained due to differences in disease activity between the groups,” wrote a group of Japanese investigators. “For the aforementioned reasons, the effects of sex differences on disease activity indices, while taking into account the different drugs used, require a comprehensive evaluation.”

A large, observational study evaluated the influence of sex on disease activity indices of Japanese patients with RA using data from the National Database of Rheumatic Diseases in Japan (NinJa) in 2017. A total of 14,958 patients were analyzed regarding DAS28-CRP, SDAI, and CDAI by disease activity category using Cliff’s delta and regression analysis. Patients were categorized as having low disease activity (LDA), moderate disease activity (MDA), or high disease activity (HDA) based on these evaluations.

Differences were assessed using permutational multivariate analysis of variance. Additionally, correction equations were constructed to determine the number of misclassifications in male patients who achieved DAS28-ESR remission.

Most patients were female (79.7%, n = 11,916) and females exhibited higher values of disease activity indices, a longer disease duration, and had a higher Health Assessment Questionnaire-Disability Index (HAQ-DI) score.

The DAS28-ESR reported higher values in female patients when compared with male patients in remission, although they had no obvious difference in other indices or disease activity categories. Of the different components of DAS28-ESR, only ESR was higher in female patients compared with male patients in remission. The DAS28-CRP and SDAI 28-tender joint count was higher in females and CRP was lower. Further, the profiles among those with high disease activity were different among sexes. Using correction equations, almost 12% of male patients with DAS28-ESR remission were determined to be misclassified due to differences in ESR.

Investigators stated that they did not evaluate all the factors that may have affected ESR and the other components of the indices, including alcohol consumption, ethnicity and race, comorbidities, and a history of fibromyalgia. Further, the correction equations were not confirmed using an independent dataset. However, the study is the first to determine the impact of bias due to sex difference on remission using correction equations.

“This sex difference in the components indicated that the profiles of male and female patients were different, especially in those with high disease activity,” investigators concluded. “Furthermore, almost 12% of male patients with DAS28-ESR remission were considered to be equivalent to LDA using equations to correct the effects of sex and age differences on ESR. Our results will help to understand the properties of composite measures of disease activity and allow the appropriate selection of indices based on the sex differences.”

References

1. ^{Nishino, T., Hashimoto, A., Tohma, S. et al. Comprehensive evaluation of the influence of sex differences on composite disease activity indices for rheumatoid arthritis: results from a nationwide observational cohort study. BMC Rheumatol 7, 4 (2023). https://doi.org/10.1186/s41927-023-00328-9}
2. ^{Rintelen B, Haindl PM, Maktari A, et al. SDAI/CDAI levels in rheumatoid arthritis patients are highly dependent on patient’s pain perception and gender. Scand J Rheumatol. 2008;37:410–3.}