Tapering and discontinuation of TNF-α blockers without disease relapse using ultrasonography as a tool to identify patients with rheumatoid arthritis in clinical and histological remission

Abstract

Background: In this study, we assessed whether clinical and ultrasonography (US)-based remission could be used to select patients with rheumatoid arthritis (RA) eligible to taper and discontinue anti-TNF-α therapy after achievement of remission, looking at disease relapse.

Methods: Forty-two patients with RA in sustained remission who were receiving anti-TNF-α treatment (Disease Activity Score <1.6 at three visits 3 months apart) underwent US evaluation of synovial hypertrophy (SH) and power Doppler (PD) signal presence. Five SH+/PD- patients with RA underwent US-guided knee synovial tissue biopsy to assess histological features of residual synovitis (CD68, CD3 and CD20 immunostaining) after sustained clinical remission was achieved. All patients were enrolled to taper first then discontinue anti-TNF-α. They were followed every 3 months afterwards, and the relapse rate was recorded.

Results: Selected SH+/PD- patients showed low-grade synovitis as demonstrated by the presence of CD68+ cells in the lining layer and few infiltrating CD3+ and CD20+ cells at the time sustained clinical remission was achieved. After anti-TNF-α tapering, 13 patients (30.9 %) relapsed and 29 (69.1 %) SH+/PD- patients maintained disease remission after 3 months and discontinued anti-TNF-α treatment. Among them, 26 patients (89.7 %) maintained disease remission status after 6 months of follow-up. All patients who relapsed were retreated with the previous biologic, following the last effective therapeutic regimen, again reaching a good European League Against Rheumatism response within 3 months.

Conclusions: US evaluation using PD signalling allows the identification of patients with RA in clinical and histological remission after tapering and discontinuing biologics.

Fig. 1

Cluster of differentiation 68 (CD68), CD20 and CD3 immunohistochemical staining of synovial tissue (ST) of patients with rheumatoid arthritis (RA) in clinical remission after undergoing therapy with tumour necrosis factor-α blockers. Five synovial hypertrophy–positive/power Doppler–negative patients with RA underwent ultrasonography-guided knee ST biopsy at study entry. a CD68 immunohistochemical staining of ST (original magnification, ×40). b CD20/CD3 double immunohistochemical staining of ST [CD20 diaminobenzidine (brown) and CD3 (red); original magnification, ×40]

Fig. 2

Changes in Disease Activity Score (DAS) values over time during the tapering and discontinuation of biologic treatment in synovial hypertrophy–positive (SH+)/power Doppler–negative (PD−) patients with rheumatoid arthritis (RA). Forty-two SH+/PD− patients with RA were tapered on anti-tumour necrosis factor (TNF)-α therapy for 3 months. Among them, 29 SH+/PD− patients with RA (69.1 %) maintained disease remission 3 months after anti-TNF-α tapering. All SH+/PD− patients still in disease remission after anti-TNF-α tapering discontinued anti-TNF-α treatment and were followed every 3 months afterwards. Among them, 26 (89.7 %) maintained disease remission for 6 months, whereas 3 (10.3 %) had disease relapse within 6 months. Among patients with RA who completed the 12-month follow-up, 16 SH+/PD− patients (38.1 %) had a chance of disease relapse after anti-TNF-α tapering and discontinuation. US ultrasonography