Joint inflammation tends to recur in the same joints during the rheumatoid arthritis disease course

Abstract

ObjectivesWe investigated whether local joint swelling recurs in the same joints over time in patients with rheumatoid arthritis (RA) who are treated to target.MethodsPatients with newly diagnosed RA participating in the Behandel-Strategieën, “treatment strategies” (BeSt) study (n=508) were followed for median 10 years while receiving Disease Activity Score (DAS) ≤2.4 steered treatment. Every 3 months 68 joints were assessed for the presence of swelling. We evaluated whether baseline local joint swelling was predictive for swelling in the same joint during follow-up using a multilevel mixed-effect logistic regression model. Different strategies were used to account for missing data. A permutation test was performed to assess if joint swelling was better predicted by baseline swelling of the joint itself than by baseline swelling of randomly selected other joints.ResultsIn 46% of the joints that were swollen at baseline, joint swelling later recurred at least once during follow-up. Joint swelling at baseline was statistically significantly associated with swelling in the same joint during follow-up (OR 2.37, 95% CI 2.30 to 2.43, p<0.001), and also specifically with recurrent swelling in the same joint (OR 1.73, 95% CI 1.37 to 1.59, p<0.001). Local joint swelling was better predicted by baseline swelling of that particular joint than by baseline swelling of other joints (p<0.001).ConclusionJoint swelling tends to recur locally in the joints swollen at RA onset. This suggests that local factors influence the manifestation of joint inflammation over time.

Joint‐Specific Memory and Sustained Risk for New Joint Accumulation in Autoimmune Arthritis

“…However, since 81% of patients experienced at least 1 flare after achieving inactive disease, our cohort provided an optimal opportunity to characterize patterns of disease recurrence. The generalizability of the conclusions beyond JIA is supported by the broad clinical and biologic similarities between pediatric and adult arthritis and the concordance between our results and those found in studies of RA (2)(3)(4)(5).…”

“…This phenomenon was first described more than 30 years ago by Roberts and colleagues, who found that most joints ever involved in an individual with RA, including all joints needing subsequent joint replacement, were already affected in the first year of disease (2). Consistent with this result, analysis of RA patients in the Behandel Strategieen (BeSt) study showed that joints swollen at baseline were at higher risk of subsequent swelling, with wrists, metacarpophalangeal (MCP) joints, and metatarsophalangeal (MTP) joints reaching recurrence rates of 60% (3). These observations suggest that, in addition to systemic autoimmunity, factors local to individual joints render them susceptible to subsequent inflammation.…”

Insights Into the Concept of Rheumatoid Arthritis Flare

“…The same authors could also demonstrate the central role of CD8+ Trm in the maintenance of joint-specific memory in quiescent joints and in the mechanism of recurrent joint-specific flares ( 50 ). Whilst these data provide a potential immune-biologic explanation of the known trend of arthritis flare to recur preferentially in previously involved districts in human disease ( 51 , 52 ), the mechanistic link between Trm activation in the joint and local homing of circulating PRIME cells remains to be clarified.…”

Understanding the function of the GABAergic system and its potential role in rheumatoid arthritis

“…Early treatment with combined methotrexate and glucocorticoids followed by other DMARDs with the inhibitors of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), or Janus kinase can improve prognosis ( 11 ). Treatment aims to reduce disease activity by at least 50% within three months and achieve remission or reduced disease activity within six months, and can prevent RA-related disability with sequential drug therapy if necessary ( 12 , 13 ). Therefore, understanding and identifying novel targets is important for the clinical management and treatment of RA.…”