Background/Purpose: Remission is the key treatment
goal in rheumatoid arthritis (RA).  Although clinical remission is increasingly
achieved, many patients progress both structurally and functionally. We currently
do not routinely assess immunological markers or perform ultrasound imaging to
define remission.

 We aimed to document the variability of clinical,
patient-reported, imaging and immunological characteristics of RA patients in
clinical remission and to correlate these with outcomes.

Methods: In a retrospective, observational study patients
with an RA diagnosis (1987 or 2010 ACR/EULAR criteria) were selected from our
early inflammatory arthritis database; the lowest observation of 3-variable DAS28CRP≤3.2
after diagnosis was chosen as the index visit. We defined flare as loss of
index visit state [remission (<2.6) or low disease activity (LDA; 2.6-3.2)].
We collected clinical data, patient-reported outcomes and ultrasound Power Doppler
(PD) and Grey Scale (GS) findings. Frequencies of naïve CD4⁺T-cells,
Inflammation related cells (IRC), regulatory T-cells (Treg) measured and
analysed by advanced 8-colour flow-cytometry were compared with reference range
values obtained from 120 healthy controls.

Results: We included 633 patients (69% female; mean
age 57.6 years) with a minimum DAS28CRP≤3.2 (mean 1.87/SD 0.68). Of
these, 513 were in DAS-defined clinical remission. The majority (75%) were
taking conventional synthetic DMARD therapy only, 45% as monotherapy. Inflammatory
markers, joint counts and levels of disability/function and life impairment
were generally low, as expected.

Positive PD signal was present in 43% (141/326) of patients
in remission; 76% (248/326) had evidence of GS changes >1 in ≥1 joint.
In LDA, PD and GS changes were 64% (46/72) and 85% (61/72) respectively.

In remission, abnormal T-cell numbers were seen in 9%
(4/46), 26% (12/46) and 50% (23/46) for naïve, IRC and Treg’s respectively. For
LDA, the figures were 40% (2/5), 60% (3/5) and 100% (5/5).

15% (85/559) of patients flared within 6 months of the index
visit. Odds of flare were higher in females, those with higher DAS28, longer
disease and/or remission duration and evidence of PD synovitis (Table 1).

Conclusion: Despite being in DAS-defined clinical
remission, a substantial proportion of patients exhibit PD synovitis on
ultrasound and have evidence of T-cell abnormalities. Current remission
criteria are composite scores and do not measure inflammation directly.  Validation
of imaging techniques and identification of remission biomarkers could lead to
a better understanding of what constitutes true remission, with relevance for
disease stability. Further work is required to assess the predictive value of
T-cell abnormalities for flare.

Table 1: Associations between clinical and imaging
findings at the index visit and the unadjusted odds of flare within 6 months.