Progression from symptom onset to rheumatoid arthritis: is the trajectory similar in anticitrullinated protein antibody-positive and -negative disease? A comparative longitudinal study
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Mitra Hosseini Malekroudi1, Stijn Claassen1, Hanna W van Steenbergen1
1Department of Rheumatology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands.
Objectives:
The period between symptom onset and the development of rheumatoid arthritis (RA) is a putative window for disease modification. It is insufficiently known whether anticitrullinated protein antibody (ACPA)-positive and ACPA-negative disease develop similarly in this symptomatic pre-RA period. We therefore studied this trajectory in developing ACPA-positive and ACPA-negative RA and compared timelines and inflammation-related markers.
Methods:
We studied 173 (n = 87 ACPA-negative and n = 86 ACPA-positive) patients with clinically suspected arthralgia (CSA) who all developed RA. Time from symptom onset to presentation with CSA, and from CSA presentation to RA development were compared. Longitudinal inflammatory trajectories were assessed by studying clinical measures (morning stiffness and tender joints), laboratory (C-reactive protein [CRP]), and imaging (hand/foot-magnetic resonance imaging) markers.
Results:
ACPA-positive patients had a longer time between symptom onset and presentation with CSA, but a shorter time from CSA presentation until RA development (p = 0.006 and p = 0.014, respectively). ACPA-negative patients had more morning stiffness at symptom onset (p = 0.024), at CSA presentation (p = 0.006) and until RA development (p = 0.017). Likewise, ACPA-negative patients had more hand pain at symptom onset, more tender hand joints at CSA presentation (p < 0.001) and until RA development (p < 0.001). In contrast, ACPA-positive patients showed a faster increase in CRP level (p = 0.006) and subclinical joint inflammation the year before developing RA, which was due to a significantly greater increase in forefoot inflammation (p = 0.043).
Conclusions:
From symptom onset to RA development, ACPA-negative and ACPA-positive disease differ in timelines, morning stiffness severity, and location of inflammation in hands/feet. These differences may reflect differences in underlying inflammatory mechanisms and may suggest that different preventive strategies are required to intervene in the development of ACPA-positive and ACPA-negative RA.
