AB0419 Frequency of disease flare and study of the cd4+cd25+highcd127low/- cell populations after discontinuation of anti-tnfΑ therapy in patients with rheumatoid arthritisin persistent remission
Authors: A. Lo Monaco, C.A. Scirè, F. Casciano, V. Tisato, P. Secchiero, M. Govoni
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Rheumatoid arthritis (RA) patients in a prolonged remission status represent a population whose future management has yet to be established. Treg cell function in patients with active RA is assumed to be impaired, a trend that seems to be reversed by TNFalpha antagonist therapy (aTNF). Theoretically a deeper remission may be represented by an immunological resetting of immune system, a condition which could enable to consider the possibility of a drug-free remission. <h3>Objectives</h3> To evaluate the incidence of disease flare after cessation of aTNF in pts in remission together with reconstitution of the CD4 +CD25highCD127low/- Tcell subset respect to those patients in the same remission status with persistent low CD4 +CD25highCD127low/-Tcell population, assuming the Treg populations as a markers of deep remission allowing a better selection of those patients at low-risk of flare after aTNF withdrawal. <h3>Methods</h3> inclusion criteria: patients with RA (&gt;18 years) fulfilling the 1987 ACR classification criteria treated with aTNF and synthetic DMARDs for at least 12 months, in remission (DAS28 &lt;2.6/DAS44 &lt;1.6)&gt;6 months, without glucocorticosteroid. Exclusion criteria:&lt;18 years, glucocorticosteroids within the three months before; another inflammatory disease other than RA; ongoing infections. Intervention: aTNF drug withdrawal with continuation of DMARDs previously associated (MTX or LFN); a 24 months of follow up was performed. Serial clinical and instrumental evaluation, blood sampling and radiographs have been performed according to the scheduled protocol. Treg population and several cytokines/chemokines/growth factors were analysed (Human Cytokine/Chemokine Panel I, Millipore). <h3>Results</h3> 23 patients were included, mean age 53 years (SD 12.3), 68% RF +, 52% ACPA +, DAS28 medium 1.41 (SD 0.48); average duration of illness 9.62 years (SD ±5.73). During the 24 month post-suspension follow-up, for a total of 267 person-months, 11 patients presented a flare, for a flare rate of 3.74/100 person-months (CI95% 1.79–6.88). The average observed exacerbation time from aTNF withdrawal was 14.6 months (SD ±9.32). None statistical predictive value of Treg levels regarding disease outcome after aTNF withdrawal was observed IIR (95% CI) 1.38 (0.82–2.30). None significant correlation among cytokines concentrations and disease status/Treg levels was observed. A correlation was observed between the presence of a synovitis with PD1+* at the baseline and the loss of remission [HR 7.062 (1.64–30.41, p 0.009);*higher values were exclusion criteria]. All 3 patients with positive US (PD1) who had flare-up were asymptomatic at baseline. <h3>Conclusions</h3> 47.8% of pts maintained aTNF-induced remission at 24 months continuing only sDMARDs therapy (MTX). Only in 1 case reintroduction of Adalimumab did not allow to regain clinical remission, which was obtained using another therapeutic target (anti-CTL4). The presence of a residual synovitis, although mild (PD1), was correlated with the risk of exacerbation. Further results will be discussed. <h3>Reference</h3> [1] Kawashiri, et al. J Rheumatol2011;38(12):2517–21. <h3>Acknowledgements</h3> Study financed with funds from the Emilia-Romagna Region deriving from the "Alessandro Liberati" young researchers in the framework of the. Region-University research program 2013 <h3>Disclosure of Interest</h3> None declared