THU0286 The Efficacy and The Long-Term Prognosis of Rituximab for Refractory Thrombotic Microangiopathy Associated with Connective Tissue Diseases
Authors: A. Kondo, H. Dobashi, Y. Takeuchi, T. Kameda, M. Izumikawa, S. Nakashima, H. Ozaki, R. Wakiya, N. Kadowaki
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Recently, it has been described in many reports that B cell has important roles in connective tissue disease (CTD). Rituximab (RTX), anti-CD20 monoclonal antibody is widely known as effective for patients with several autoimmune hematological disorders including thrombotic microangiopathy (TMA) through not only B cell depletion but reducing antigen-presenting cell function, complement hyperactivation, release of inflammatory cytokines and abnormal auto-reactive T cell response through co-stimulatory signals.<sup>1)</sup> TMA is developed in CTD occasionally. CTD-TMA especially with normal activity of von Willebrand factor cleaving protease, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member-13 (ADAMTS-13) is often resistant for plasma exchange (PE) conducted for thrombotic thrombocytopenic purpura with ADAMTS-13 inhibitor and lack of ADAMTS-13 activity as a first-line treatment.<sup>2)</sup> It has been reported that the autoantibodies other than ADAMTS-13 inhibitor, complement hyperactivation, and excessive inflammatory cytokines production associated with refractory TMA.<sup>3)</sup> <h3>Objectives</h3> We investigate the efficacy and the long-term prognosis of RTX treatment for refractory TMA associated with CTD. <h3>Methods</h3> We enrolled 7 CTD-TMA patients (SLE; 3, SS; 2, MCTD; 1, DM; 1) with refractory to PE treatment between 2006 and 2015. We examined the ADAMTS-13 activity, its inhibitor and ultra-large von Willebrand factor multimers (UL-VWFMs) at TMA onset. RTX was given 375mg/m<sup>2</sup> per a dose. We defined complete response (CR) as platelet counts &gt;150×10<sup>9</sup>/l for more than 3 consecutive days, with normal levels of serum LDH and an absence of TMA-related symptoms. We considered CR continued more than 30 days after RTX treatment as remission. In addition, we investigated as follow subjects; duration from initial RTX treatment to CR, duration of sustained CR, relapse and adverse events. <h3>Results</h3> No abnormality of ADAMTS-13 activity was observed 6 patients. The thrombocytopenia was improved immediately within 2–3 weeks after the initiation of RTX and hemolytic anemia and neuropsychiatric manifestations were improved following after the recovery of thrombocytopenia, respectively. 6 patients could achieve CR. They who achieved CR all have sustained long-term remission by only 1 or 2 doses of RTX administration and there was no relapse. RTX was partial response for 1 patient with insufficient recovery of thrombocytopenia but detectable serum haptoglobin and she was reported with controllable bacterial pneumonia. <h3>Conclusions</h3> We suggest that RTX treatment has efficacy with high response rate and long-term remission for the refractory CTD-TMA patients. Moreover, RTX treatment can be the first-line treatment for CTD-TMA. <h3>References</h3> Roberto Stasi. Rituximab in autoimmune hematologic disease: not just a matter of B cells. Semin Hematol. 2010; 47: 170–179. Tomomi Matsuyama, Masataka Kuwana, Masanori Matsumoto, et.al. Heterogeneous pathogenic processes of thrombotic microangiopathies in patients with connective tissue diseases. Thromb Haemost. 2009; 102: 371–378. Marina Noris, Federica Mescia, Giuseppe Remuzzi. STEC-HUS, atypical HUS and TTP are all diseases of complement activation. Nat. Rev. Nephrol. 2012; 8: 622–633. <h3>Disclosure of Interest</h3> None declared