Comparison of Rituximab originator (MabThera) to biosimilar (Truxima) in patients with immune-mediated thrombotic thrombocytopenic purpura.

Immune thrombotic thrombocytopenic purpura (iTTP) is an acute, multisystem thrombotic microangiopathy mediated by ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) autoantibodies. Immunosuppression with anti-CD20 therapy is the mainstay of treatment. MabThera's patent has now expired and biosimilars have been approved. Eighty-four consecutive patient episodes over 2 years, prior to and following our switch to Truxima are presented. Day 1 (D1), Day 28 (D28) and 3-month platelet counts, ADAMTS13 activity, and CD19 levels, adverse reactions and infective complications were recorded. Platelet counts were not significantly different between acute MabThera and Truxima treatment (D1 P = 0.085, D28 P = 0.77, 3 months P = 0.71) and electively (D1 P = 0.79, D28 P = 0.68, 3 months P = 0.99). ADAMTS13 recovery also was not significantly different acutely (D1 P = 0.99, D28 P = 0.27, 3 months P = 0.26) and electively (D1 P = 0.59, D28 P = 0.61, 3 months P = 0.34). CD19% depletion at D1 and 3 months was not significantly different acutely (D1 P = 0.52, 3 months P = 0.56) and electively (D1 P = 0.22, 3 months P = 0.19). Infusion reactions and infective complications were comparable with both therapies. This is the first series of the Rituximab biosimilar Truxima to be reported in iTTP, demonstrating equivalence to MabThera in terms of ADAMTS13 recovery, CD19 depletion, and platelet count at D28 and 3 months post-administration, with comparable infusion and infective complications. The financial benefit of the biosimilar anti-CD20 is considerable.

Bortezomib in the treatment of refractory thrombotic thrombocytopenic purpura.

Acquired thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening condition caused by autoantibody-mediated inhibition of ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type-1 motif, 13). Therapeutic plasma exchange (TPE) improves survival, but disease may be refractory despite therapy. Management and treatment response of refractory TTP is variable, with rituximab and other immunosuppression often being used. Case reports have suggested a benefit of the proteasome inhibitor, bortezomib, possibly due to elimination of the autoreactive plasma cells producing anti-ADAMTS13 antibodies. We evaluated the effect of bortezomib in a series of primary refractory TTP patients unresponsive to intensive therapy. Bortezomib-treated patients were identified from consecutive cases managed at two UK referral centres. Demographic and clinical data were extracted from hospital records. ADAMTS13 activity was measured using a fluorescence resonance energy transfer VWF73 assay, and anti-ADAMTS13 IgG using enzyme-linked immunosorbent asssay. We identified six bortezomib-treated patients out of 51 consecutive cases of acute, acquired TTP. All patients received TPE, methylprednisolone and rituximab. Five of the six achieved complete remission with bortezomib, and one died of cardiac arrest due to underlying disease. No treatment-related adverse events were observed. Mean follow-up time after hospital discharge was 17 months (range: 3-33). Bortezomib appears effective in the treatment of a subgroup of cases with severe, refractory TTP. Prospective trials are required to further investigate this effect.