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. 2024 Sep 1;63(9):2336-2344.
doi: 10.1093/rheumatology/keae044.

Patient burden and joint inflammation during development of RA from arthralgia: is it similar in ACPA-positive and ACPA-negative disease?

Sarah J H Khidir  1 , Doortje I Krijbolder  1 , Herman K Glas  2 , Elise van Mulligen  1   3 , Annette H M van der Helm-van Mil  1   3
Affiliations

Patient burden and joint inflammation during development of RA from arthralgia: is it similar in ACPA-positive and ACPA-negative disease?

Sarah J H Khidir et al. Rheumatology (Oxford). .

Abstract

Objectives: ACPA-positive and ACPA-negative RA differ in underlying risk factors but have a similar clinical presentation at RA diagnosis. It is unknown what the ACPA-associated differences or similarities are during the symptomatic at-risk stage of RA, i.e. clinically suspect arthralgia (CSA). To deepen insights into these differences/similarities, we compared the course of symptoms/impairments and subclinical joint inflammation in the CSA phase during progression to inflammatory arthritis (IA) or to CSA resolution.

Methods: A total of 845 CSA patients were followed for a median of 24 months; 136 patients developed IA and an additional 355/505 patients had resolution of CSA according to rheumatologists. Patient burden (pain, morning stiffness, fatigue, functional disabilities, presenteeism) was assessed at baseline and 4, 12 and 24 months and at IA development. Subclinical joint inflammation in the hands and feet was assessed over time with 1.5T MRI. Linear and Poisson mixed models were used.

Results: In both ACPA-positive and ACPA-negative patients, patient burden increased towards IA development and decreased towards CSA resolution. However, patient burden was lower in ACPA-positive vs ACPA-negative disease at all timepoints. Conversely, subclinical joint inflammation tended to increase more rapidly during development of ACPA-positive IA [incidence rate ratio (IRR) 1.52 (95% CI 0.94, 2.47), P = 0.089] and remained higher over time in ACPA-positive CSA patients achieving resolution compared with ACPA-negative patients [IRR 1.52 (95% CI 1.07, 2.15), P = 0.018]. Although correlation coefficients between changes in patient burden and subclinical joint inflammation during progression to IA were weak, they were consistently higher in ACPA-positive than ACPA-negative disease, e.g. ρ = 0.29 vs 0.12 for functional disabilities.

Conclusion: During RA development and CSA resolution, ACPA-positive CSA patients have lower patient burden but more subclinical joint inflammation than ACPA-negative CSA patients. These data strengthen the notion that the development of ACPA-positive and ACPA-negative RA is pathophysiologically different and encourage further research on these differences.

Keywords: anti-citrullinated protein antibody; clinically suspect arthralgia; joint inflammation; patient burden; rheumatoid arthritis.

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Figures

Figure 1.
Figure 1.
The course of patient burden in CSA over time during progression to IA and resolution of CSA, stratified for ACPA
Figure 2.
Figure 2.
The course of subclinical joint inflammation over time in CSA patients during progression to IA and resolution of CSA, stratified for ACPA
Figure 3.
Figure 3.
Correlation between change in patient burden with simultaneous change in subclinical joint inflammation during 12 months before IA development in ACPA-positive and ACPA-negative CSA
See this image and copyright information in PMC

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