Background The increasing number of patients treated with biologic therapies, the extending duration and costs of these treatments necessitate the development of strategies to the tapering or discontinuation of biologics in rheumatoid arthritis (RA) patients with long-standing remission on these agents. As flares occur frequently in patients in whom biologics are stopped, the identification of predictive markers for the preservation of long-standing remission after discontinuation is an important need. Several microRNA-s (miRNA) and SuPar (soluble urokinase plasminogen activator receptor) have been found to correlate with disease activity, and to be sensitive biomarkers of treatment response.
Objectives The authors' aim was to prospectively follow the disease course after the permanent cessation of biologics, and to identify clinical and biochemical predictors of sustained biologic-free remission.
Methods In this prospective, multicentre, controlled trial, eligible RA patients were treated with anti-TNF or IL6R-blocker, had a minimum of one-year remission (DAS-28<2.6), and no corticosteroid therapy. After discontinuation of the biologics, DAS28, HAQ, ESR and CRP were recorded at baseline, month 1, 3 and every 3 months thereafter. SuPar and soluble miRNA146a, miRNA16, miRNA155, miRNA223 and miRNA346 levels were measured by ELISA or QRT-PCR, respectively at baseline, month 1, 3, 6 and at relapse, if occurred. In the control group (n=5), patients had sustained remission on biologics, and had similar demographic and serological parameters, but the biologic therapy was not stopped.
Results At present 23 patients with RA have been enrolled (average age: 59,95/35–79/ years).The mean duration of biologic therapy was 54,04 (25–84) months, and was started an average of 62,3 months (1–240 months) after the diagnosis. After the discontinuation, 14 patients are in biologic-free remission for an average of 5,21 (1–16 months). Relapse occurred in 9 cases an average of 5,20 (2–12) months after the discontinuation. miRNA146a levels at stop were higher in relapsers than in those with sustained remission (relative expression to cel miR39: -3,08 vs -7,87, p=0.009) (n=8 stopped patients, n=1 control). Circulating miRNA223, miRNA16, miRNA155 and miRNA346 levels were comparable in the two drug-cessation groups. SuPar levels were not different in the 12 patients in remission and 7 relapsers, in whom the measurements have been performed so far.
Conclusions In RA patients with long-term remission on anti-TNF or IL6R-blocker, elevated level of miRNA146a may indicate a higher risk of relapse after stopping biologics. Further follow-up and the involvement of more patients are currently underway, and this may identify further predictive markers.
Toldi G, Kádár G et al. Soluble urokinase plasminogen activator receptor (suPAR) in the asessment of inflammatory activity of rheumatoid arthritis in patients in remission. ClinChem Lab Med 51(2):327–332. 2013
Disclosure of Interest None declared
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