There is a marked heterogeneity in AMR patients' prognosis after SOC treatment including plasma exchange (PE) and intravenous immunoglobulins (IVIG). We investigated whether a composite prognostic score might identify high-risk patients after AMR SOC therapy, who would be eligible for second-line intervention.

We prospectively included kidney recipients diagnosed with active AMR between 2012 and 2014 who received standardized SOC therapy (PE x4 and IVIG 2 g/kg x3) in 2 Paris centers. Patients were stratified according to their risk of allograft loss after AMR SOC therapy based on a prognostic score. High-risk patients received second-line complement inhibition therapy (C5-inhibitor Eculizumab or C1-inhibitor Berinert) and IVIG for 6 months. The AMR prognostic score was defined in a prospective cohort of 284 kidney recipients with active AMR who received SOC therapy with PE and IVIG (abstract N[deg]252028), and integrated GFR and IF/TA at diagnosis, and change in GFR, ptc score and anti-HLA DSA MFI after treatment. Optimal cut-off values for risk stratification were identified by recursive partitioning.

83 patients with active AMR diagnosed at a median time of 4.3 months after transplantation were enrolled. All patients received the SOC therapy, after which they were stratified in 3 risk groups according to the AMR prognostic score: 0-5.96: low-risk group, 5.96-6.76 intermediate-risk group, 6.76-10: high-risk group. 15 (18%), 11 (13%) and 57 (69%) patients were stratified in the high-risk, intermediate-risk and low-risk groups, respectively. Predicted 3-year allograft survivals were 94% (95%CI, 89-96) in the low-risk group, 64% (95%CI, 43-79) in the intermediate-risk group and 32% (95%CI, 17-48) in the high-risk group (P<0.001). The prognostic characteristics of high-risk patients were: GFR: 37.1±10.5 mL/min, g+ptc score: 3.5±1.4 and DSA MFImax: 10319±646 before AMR SOC treatment and 27.4±8.9 mL/min, 4.1±1.2 and 14482±485 after AMR treatment, respectively. The high-risk patients receiving second-line therapy showed a 3-year allograft survival of 84%.

Risk stratification for kidney allograft loss by a composite prognostic score based on clinical, histological and immunological parameters allows to identify high-risk patients for allograft loss after SOC treatment of AMR. Risk-based second-line strategies might improve outcomes in high-risk patients. Controlled studies are needed to determine the nature and the efficacy of second-line strategies.

CITATION INFORMATION: Viglietti D, Loupy A, Aubert O, Pillebout E, Legendre C, Glotz D, Lefaucheur C. Second-Line Therapy After Standard of Care in Antibody-Mediated Rejection: A Prospective Study. Am J Transplant. 2017;17 (suppl 3).

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