Long-term risk of relapse in immune-mediated Thrombotic Thrombocytopenic Purpura and the role of anti-CD20 therapy.

Disease relapse is recognised as a risk in immune-mediated Thrombotic Thrombocytopenic Purpura (iTTP) after treatment of the acute presenting episode. Identification of patients at risk of relapse and its patterns are yet to be clearly established. We reviewed patients with iTTP having >3 years follow-up over 10-years in the United Kingdom to identify patient characteristics for relapse, assess relapse rates and patterns, and response to anti-CD20 therapy in those with ADAMTS13 relapses (ADAMTS13 activity <20% without thrombocytopenia). We identified 443 patients demonstrating relapse rates of 40% at 5-year follow-up. At 10-years follow-up, no difference in relapse was observed irrespective of whether rituximab was used at acute presentation or not (p=0.39). Black-Caribbean ethnicity increased the risk of disease relapse in the British population (odds ratio 2.66, 95% CI 1.42 - 5.00). There was a distinct population of patients (6%) that relapsed early with subsequent frequent relapses occurring on average within 2 years (average time to relapse in subgroup: 1.7 years). Overall, nearly 60% of relapses described were ADAMTS13 relapses, with subsequent treatment reducing the risk of progression to clinical relapses. We demonstrate that iTTP diagnosed in the latter part of the study period had lower rates of clinical relapses (22.6 vs 11.1%, p=0.0004) with the advent of regular monitoring and pre-emptive rituximab. In ADAMTS13 relapses, 96% responded to anti-CD20 therapy achieving ADAMTS13 activity >20%. Anti-CD20 therapy was demonstrated to be an effective long-term treatment regardless of relapse pattern and there was no loss of this treatment response following subsequent treatment episodes.