Introduction: IVIG+rituximab is an acceptable approach for DES with good outcomes. Despite this, ∼30% of patients fail DES, thus other approaches are needed. Options include addition of PLEX, eculizumab and bortezomib, however the most difficult HS patients fail to respond. IL-6/IL-6R interactions are critical for B-cell differentiation and plasmablast growth and plasma cell IgG production. Thus, we hypothesized that interruption of IL-6/IL-6R interactions would reduce HLA antibodies and improve DES. Here we investigated Tocilizumab (TCZ), a humanized antibody directed at the IL-6R as a DES agent. Patients & Methods: From 7/2012-11/2013, 10 HS patients unresponsive to DES with IVIG+rituximab ±plasma exchange were treated with IVIG+TCZ. Patients received IVIG 2gm/kg on days 0 & 30; TCZ (8mg/kg) on days 15, 45, 75, 105, 119, 135 and 149. Post transplant, patients received IVIG on day 0; TCZ on day 2 and then TCZ monthly x6M. All patients received induction with alemtuzumab x1 and were maintained on tacrolimus/cellcept/prednisone taper. All patients had immunologic parameters assessed and underwent protocol biopsy @6M. Results: During the study period, 8/10 patients completed the TCZ DES phase. Two patients were withdrawn d/t compliance issues. Five patients (4DD/1LD) remaining in the study were transplanted. The mean time to transplant from initial DES was 25±10.5M but after TCZ DES was 7.8±9M. Another patient had frequent offers with negative CMXs but did not receive transplant d/t allocation priority. Four of 5 patients were DSA+ at transplant, however, only 1 patient remained DSA+ @12M (A2 & A29, MFI 1500). No patient showed ABMR on protocol biopsy @6M while 1 patient showed mild ABMR @12M with DSA- but AT1R antibody+. Renal function was acceptable @12M post-transplant (mean SCr 1.3±0.4 mg/dl and cGFR 60±25 ml/min). Immunologic analysis showed elevated IL-6 and IL-6R levels and a trend to decreased CRP levels during TCZ therapy, findings c/w effective IL-6R blockade. Long term TCZ therapy did not result in hypogammaglobulinemia or significant infection risk (IgG levels @baseline v. 6M post-TCZ therapy (928±275 v. 859±226, p=0.78). Conclusions: IVIG+TCZ appears to offer benefits as a DES strategy that can be maintained post-transplant. However, larger studies are required to substantiate these observations.

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