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

BackgroundIn 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.MethodsForty-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.ResultsSelected 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.ConclusionsUS evaluation using PD signalling allows the identification of patients with RA in clinical and histological remission after tapering and discontinuing biologics.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-0927-z) contains supplementary material, which is available to authorized users.

Tapering biologic and conventional DMARD therapy in rheumatoid arthritis: current evidence and future directions

“…Iwamoto et al reached similar conclusions about the likelihood of relapse when stopping TNF inhibitors in 42 patients with RA in sustained remission 51. In addition, a recent study by Alivernini et al showed that synovial hypertrophy is associated with higher risk of flares after tapering and withdrawing TNF inhibitors 52. Of particular interest, the authors also showed that absence of ultrasound hypertrophy is associated with only minimal synovial changes in the histology, supporting the accuracy of ultrasound examination to detect residual disease activity.…”

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

“…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]. GS synovial hypertrophy alone seems to be linked to fibrotic intraarticular tissue in old disease and was not linked to histologic inflammatory activity in a recent validity study [31]. Only PD subclinical synovitis is significant for disease progression.…”

“…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].…”

How should a patient with rheumatoid arthritis behave after achievement of remission?

“…[33], включавшем 42 больных РА со стойкой клиниче-ской ремиссией (DAS <1,6) на фоне терапии МТ + ГИБП (АДА 40 мг/2 нед либо ЭТЦ 50 мг/нед). Всем больным про-водилось УЗИ суставов кистей и стоп, 5 -пункционная биопсия синовиальной оболочки коленного сустава, под-твердившая отсутствие активного синовита.…”