Conference Coverage

BSR: Subclinical synovitis common in RA remission




MANCHESTER, U.K. – Subclinical synovitis on ultrasound was apparent in almost half of patients with early rheumatoid arthritis deemed to be in clinical remission and in two-thirds of those with low-disease activity in an observational study.

Power Doppler ultrasound changes were seen in 43% of patients in remission and in 65% of those with LDA. Grey-scale ultrasound changes also were found in 78% of the cohort studied, suggesting synovial hypertrophy. The changes correlated with disease activity. Alterations in synovial T-cell populations also were observed.

Attaining and maintaining clinical remission is a long-established primary treatment goal in rheumatoid arthritis (RA), but current criteria used to determine if this is being achieved are largely subjective, noted Dr. Hanna Gul, who presented the research at the for Rheumatology annual conference.

“Over the years there have been many attempts to define clinical remission criteria using disease activity indices,” said Dr. Gul, a clinical research fellow and specialist registrar at the Leeds Institute of Rheumatic and Musculoskeletal Medicine at the University of Leeds (England).

However, current criteria used in clinical practice and in clinical trials – most commonly the DAS28 – tend to be based on composite scores of disease, can vary in their interpretation, and do not include objective imaging or immunological assessments, she said.

While patients do seem to be increasingly achieving remission, this is not always associated with good outcomes as structural and functional progression still occurs, Dr. Gul said.

“This raises the question regarding the validity of clinical criteria,” she suggested. “Subsequently, the concept of ‘true remission’ has arisen, which is described as the absence of intra- and extra-articular inflammation, immunologic activity, and structural and functional progression.”

To look at the true remission state in more depth using disease activity criteria, imaging, and immunologic markers, Dr. Gul and her colleagues conducted a retrospective, cross-sectional study of 632 patients with early inflammatory arthritis who were considered to be in clinical remission.

Clinical remission was defined as a DAS28-CRP of less than 3.2. A total of 512 patients had a score of less than 2.6, considered as being in ‘strict’ remission, and the remaining 120 had a score of 2.6 to 3.2, having low disease activity (LDA).

The mean age of patients in the strict remission group was 58 years, and in the LDA group it was 57 years. Most of study subjects were female (70% vs. 67%), had anti-citrullinated antibodies (70% and 68%), and were rheumatoid factor positive (59% and 67%).

The median duration of disease was 6.7 months longer in the patients achieving clinical remission, at 12.9 months versus 6.2 months in the LDA group, and patients in the strict remission group had been in remission for an average of 7.6 months (in the LDA group no patient was in strict remission by definition).

The majority (75% in both groups) had been or was being treated with conventional disease-modifying drugs (csDMARDs) either alone (40%-45%) or in combination (30%-34%). About 12.5% of patients in the remission group, and 7.5% of those in the LDA group were being treated with biologics, mostly in combination with a csDMARD.

“In terms of clinical characteristics, the levels of CRP and swollen and tender joints were generally low,” Dr. Gul reported. “There was also overlap between remission and low disease activity states.”

Various patient-reported outcomes were assessed and showed that the levels of disability and functional impairment were generally low, but that there were differences between the remission and LDA states, with the best outcomes reported in patients with a CRP, tender and swollen joint count of zero.

Flow cytometry was used to analyze T-cell populations in 51 patients compared to 120 healthy controls. Results showed that there was a 9% decrease from the normal range in the percentage of naive CD4+ T-cells, a 26% increase in inflammation-related cells, and a 50% decrease in regulatory T-cells.

“This is the most extensive examination of T-cell abnormalities in RA and confirms T-regulatory abnormalities in patients with clinical remission,” Dr. Gul observed.

“Further research is required for understanding the implications, specifically with regard to T-cell abnormalities as predictors of flare,” she said.

The research was supported by the U.K. National Institute for Health Research. Dr. Gul had no disclosures.

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