Introduction/objectives Despite treat-to-target strategies, clinically meaningful limitations in daily life often persist in rheumatoid arthritis (RA). As the Disease Activity Score in 28 joints (DAS28) excludes the foot and ankle, lower extremity symptoms may contribute to this residual burden. We aimed to determine whether foot and ankle pain was independently associated with daily activity limitation (DAL), beyond DAS28-CRP, and to explore the potential mediating role of foot-related quality of life. Methods In this single-centre longitudinal cohort study, adults fulfilling the 2010 ACR/EULAR classification criteria for RA were followed for up to four annual visits. DAL was assessed using a standardised single-item questionnaire. Foot and ankle pain was evaluated by interview and examination. Modified Poisson regression with generalised estimating equations estimated adjusted risk ratios controlling for age, sex, body mass index, visit number, and time-varying DAS28-CRP. Lagged and mediation analyses (SAFE-Q) were performed. Results Among 171 patients (489 observations), the median follow-up duration was 2 years (interquartile range [IQR], 1–3), with a median of 3 visits per patient (IQR, 2–4). Foot and/or ankle pain was independently associated with DAL (risk ratio [RR] 1.86, 95% confidence interval [CI] 1.48–2.35). This association persisted across the DAS28-CRP spectrum, including remission. In lagged analyses, foot and/or ankle pain was associated with DAL at the subsequent visit (RR 1.56, CI 1.20–2.04). Foot-related quality of life was partially mediated by this association (37.2%). Conclusions Foot and ankle pain was independently associated with DAL in RA, even in low disease activity or remission. These findings highlight the importance of systematic foot and ankle assessment beyond conventional disease activity measures.<Table Float="No" ID="Taba"> <tgroup cols="2"> <colspec align="left" colname="c1" colnum="1" /> <colspec align="left" colname="c2" colnum="2" /> <tbody> <row> <entry nameend="c2" namest="c1"> Key Points • Foot and ankle pain is independently associated with participation-level daily activity limitation in rheumatoid arthritis, beyond DAS28-CRP-defined disease activity. • This association persists even in patients within the DAS28-CRP remission range. • Foot-related quality of life may partially account for the association between foot/ankle pain and daily activity limitation. </entry> </row> </tbody> </tgroup> </Table>

Foot and ankle pain is associated with subsequent daily activity limitation independent of DAS28-CRP in rheumatoid arthritis: a longitudinal cohort study

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发表日期：

2026年5月18日

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Akihisa Haraguchi,
Tomomasa Kuga,
Shintaro Kaneda,
Kenta Kamo

摘要

Introduction/objectives

Despite treat-to-target strategies, clinically meaningful limitations in daily life often persist in rheumatoid arthritis (RA). As the Disease Activity Score in 28 joints (DAS28) excludes the foot and ankle, lower extremity symptoms may contribute to this residual burden. We aimed to determine whether foot and ankle pain was independently associated with daily activity limitation (DAL), beyond DAS28-CRP, and to explore the potential mediating role of foot-related quality of life.

Methods

In this single-centre longitudinal cohort study, adults fulfilling the 2010 ACR/EULAR classification criteria for RA were followed for up to four annual visits. DAL was assessed using a standardised single-item questionnaire. Foot and ankle pain was evaluated by interview and examination. Modified Poisson regression with generalised estimating equations estimated adjusted risk ratios controlling for age, sex, body mass index, visit number, and time-varying DAS28-CRP. Lagged and mediation analyses (SAFE-Q) were performed.

Results

Among 171 patients (489 observations), the median follow-up duration was 2 years (interquartile range [IQR], 1–3), with a median of 3 visits per patient (IQR, 2–4). Foot and/or ankle pain was independently associated with DAL (risk ratio [RR] 1.86, 95% confidence interval [CI] 1.48–2.35). This association persisted across the DAS28-CRP spectrum, including remission. In lagged analyses, foot and/or ankle pain was associated with DAL at the subsequent visit (RR 1.56, CI 1.20–2.04). Foot-related quality of life was partially mediated by this association (37.2%).

Conclusions

Foot and ankle pain was independently associated with DAL in RA, even in low disease activity or remission. These findings highlight the importance of systematic foot and ankle assessment beyond conventional disease activity measures.

Key Points

• Foot and ankle pain is independently associated with participation-level daily activity limitation in rheumatoid arthritis, beyond DAS28-CRP-defined disease activity.

• This association persists even in patients within the DAS28-CRP remission range.

• Foot-related quality of life may partially account for the association between foot/ankle pain and daily activity limitation.