Reviewing Disease Activity Indices in Spondyloarthritis From the Sex Perspective: A Systematic Review and Metaanalysis

Abstract

Objective To determine whether the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Ankylosing Spondylitis Disease Activity Score (ASDAS) exhibited differences between women and men. Methods We systematically searched MEDLINE, Embase, Web of Science and other sources in English or Spanish from 01 January 1995 to 31 July 2020, to assess the differences according to sex in BASDAI and ASDAS. We performed a comparative analysis by sex using t-student test and mean difference by sex meta-analyses for BASDAI and ASDAS, using a random-effects model via the inverse-variance method. Results Forty-one studies included BASDAI (6,785 women/12,929 men) and 16 of them included ASDAS (2,046 women/4,403 men). Disease activity detected through BASDAI was significantly higher in women than in men (mean: 4.9 vs. 4.2, p=0.02), whereas ASDAS did not detect differences between sexes (mean: 2.8 women vs. 2.8 men). In the meta-analyses, BASDAI detected significant differences between women and men [mean difference= 0.55 (95% confidence intervals (95%CI): 0.46, 0.65), p<0.00001], but ASDAS did not identify significant mean difference between sexes [0.04 (95%CI: -0.05, 0.12), p=0.38]. Conclusion The two most widely used indexes of disease activity in spondyloarthritis discriminate differently according to sex by their different evaluation of peripheral disease. Their different components and weights influence BASDAI and ASDAS values. BASDAI may be influenced by fatigue, but in predominantly peripheral manifestations like enthesitis, ASDAS may not be sensitive enough to detect activity. This may represent a gender bias unfavourable to women, because peripheral spondyloarthritis is more common in women than in men.

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

“…Differences in disease activity between sexes have been reported in patients with axSpA. Previous studies have also reported significant differences in BASDAI between males and females, similar to this study, whereas no significant differences were observed in ASDAS [ 12 , 27 , 28 ]. The specific reasons for variations in disease activity between men and women are not completely understood.…”

“…In BASDAI, the weight of the questions for both peripheral arthritis and enthesitis is set at 20%. However, in ASDAS, the weight for peripheral arthritis (tender and swollen joints) was set to approximately 10.4%, and there was no independent question for enthesitis [ 28 ]. Therefore, it is possible that BASDAI is more sensitive in distinguishing differences in peripheral manifestations than ASDAS.…”

“…Therefore, it is possible that BASDAI is more sensitive in distinguishing differences in peripheral manifestations than ASDAS. In a previous study, BASDAI was able to identify more peripheral manifestations in women, whereas ASDAS was unable to detect this difference [ 28 ]. In this study, both peripheral arthritis and enthesitis were significantly more frequent in women than in men, which may explain why there was a sex difference in the BASDAI at baseline but not in the ASDAS.…”

Disease activity indexes might not capture the same disease aspects in males and females with ankylosing spondylitis: A real-world nationwide analysis

“…In this regard, a recent systematic review and metanalysis showed that BASDAI was higher in females, but no differences in the ASDAS were detected, suggesting that the two most widely used indices of disease activity in axSpA discriminate differently according to gender ( 14 ), as we disclosed in our study. The authors proposed that this is most likely because of their differences in their components and the relative weight of them in the final score, which would result in different BASDAI and ASDAS scores depending on the presence/absence of different disease manifestations ( 14 ). Females in our study had more peripheral manifestations and significatively higher scores for fatigue, spinal pain, joint pain/swelling and localized tenderness than males.…”

“…Regarding peripheral manifestations, the question about joint pain/swelling has a lower weight in the ASDAS score than in the BASDAI index and the presence of enthesitis, more frequent and severe in females, is not included in ASDAS, but it is in BASDAI, as the fourth question of BASDAI is considered as a proxy for enthesitis ( 15 ). All these clinical differences could at least partially explain why ASDAS may not be sensitive enough to detect gender differences in disease activity ( 14 , 16 ). We acknowledge that ASDAS is the preferred and most recommended index to evaluate disease activity nowadays, for different reasons ( 17 ).…”