Synovial features of patients with rheumatoid arthritis and psoriatic arthritis in clinical and ultrasound remission differ under anti-TNF therapy: a clue to interpret different chances of relapse after clinical remission?

Abstract

ObjectiveTo define the synovial characteristics of patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) in clinical and ultrasound remission achieved by combination therapy with methotrexate (MTX) and tumour necrosis factor (TNF) blockers.MethodsPatients with RA in remission (n=25) (disease activity score (DAS)<1.6 for at least 6 months), patients with RA in low disease activity (LDA) (n=10) (1.6<DAS<2.4 for at least 6 months) and patients with PsA in remission (n=18) (DAS<1.6 and Psoriasis Area Severity Index (PASI)=0 for at least 6 months) achieved by MTX+anti-TNF (adalimumab 40 mg or etanercept 50 mg) with power Doppler (PDUS)-negative synovial hypertrophy underwent synovial tissue biopsy. Patients with RA with high/moderate disease naïve to treatment (n=50) were included as a comparison group. Immunostaining for cluster designation (CD)68, CD21, CD20, CD3, CD31 and collagen was performed.ResultsPDUS-negative patients with RA in remission showed lower histological scores for synovial CD68+, CD20+, CD3+ cells and CD31+ vessels and collagen deposition (p<0.05 for both lining and sublining) compared with PDUS-positive patients with RA with high/moderate disease. In addition, there was no significant difference in terms of lining and sublining CD68+, CD20+, CD3+, CD31+ cells and collagen comparing PDUS-negative patients with RA in remission and in LDA, respectively. On the contrary, PDUS-negative patients with PsA in remission showed higher histological scores for sublining CD68+ (p=0.02) and CD3+ cells (p=0.04) as well as CD31+ vessels (p<0.001) than PDUS-negative patients with RA in remission.ConclusionsPDUS-negative patients with RA in remission have comparable synovial histological features than PDUS-negative patients with RA in LDA. However, patients with PsA in remission are characterised by a higher degree of residual synovial inflammation than patients with RA in remission, despite PDUS negativity under TNF inhibition.

Synovial tissue macrophages: friend or foe?

“…These therapies are life-long, expensive and offer inadequate responses in 30%–50% of patients with RA 7 10. Furthermore, of those who respond, approximately half will relapse within months of treatment cessation and few achieve long-term remission with restoration of joint function 10 11. Remission of RA is defined by sustained resolution of swollen and painful joints and by normalised biomarkers of inflammation.…”

Does patients’ opinion of remission in rheumatoid arthritis overlap ultrasound “true” remission? – a pilot study

“…Subclinical US findings, especially PD activity, were pointed out as the possible main cause for perpetuating joint destruction in patients considered as having achieved remission [8]. PD activity evaluation alone could identify patients with RA in clinical and histologic remission [30,31]. The proportion of subclinical synovitis found with US in various cohorts of patients in remission according to usual indices varied between 20-50% for moderate PD activity (grade 2) to over 80% for GS synovitis which is constantly the most encountered finding in remission patients [3,7,32].…”

“…US is known to better depict intraarticular pathology than clinical examination [35]. PDUS negative patients in clinical RA remission developed significantly fewer flares during the 12 months of follow-up than PDUS positive patients [30]. PDUS positive tenosynovitis showed a significant association with the flare questionnaire and further predicts an unstable remission [15].…”

The safety and optimal dosage of an interleukin-17A inhibitor (secukinumab) in the treatment of psoriatic arthritis in a patient with concomitant hepatitis C virus infection

“…[21] показали, что наличие у пациентов, достигших клинической ремиссии, субклинического синовита по данным УЗИ явилось предиктором обострения ПсА, которое в ближайшие 6 мес развивалось у таких больных в 11 раз чаще, по сравнению с теми, у кого воспалительные изменения при УЗИ не выявлялись. Более того, оказалось, что морфологические признаки воспаления в синовиальной оболочке (повышенное содержание CD68+, CD3+ и CD31+ клеток) ранее пораженных суставов у больных ПсА сохраняются даже при стойкой (6 мес) клинической и УЗИ-ремиссии [23]. Не исключено, что именно остаточный активный синовит (по данным гистологического исследования) у этих пациентов является причиной высокой частоты обострений ПсА после отмены ГИБТ.…”