This multi-centre, phase II non-randomised trial, using Rituximab, in conjunction with standard therapy, plasma exchange (PEX) and pulsed methylprednisolone (MP), to include 40 adult patients with acute idiopathic thrombotic thrombocytopenic purpura (TTP). Rituximab 375mg/m2 was given once a week for 4 weeks, following plasma exchange, started within 3 days of admission, having excluded secondary TTP causes such as pregnancy/retroviral infection. ADAMTS 13 activity/IgG antibody levels guided further therapy to a maximum of 8 treatments. Historical cases were used as comparisons to determine if Rituximab therapy on admission was associated with improved time to remission, defined by platelet count and number of PEX. Secondary outcomes were relapse rate, mortality at 3 months, safety/toxicity of Rituximab, effect on B-lymphocytes, ADAMTS 13 activity and IgG antibodies to ADAMTS 13. Results from the first 20 patients (15 females and 5 males), median age 43 years with 5 females presenting with an acute relapse TTP, none previously receiving Rituximab. All received 4 weekly Rituximab treatments and 2 continued to 8. Eight were afro-Caribbean (A/C), 9 Caucasian and 3 SE Asian. Historical controls: 17 females and 3 males, 5 with relapsed acute TTP, median age 42 years. 14 were Caucasian, 5 A/C and 1 Asian. There were comparable presenting features in both groups. The median number of PEX to remission in the trial group was 13.5 and 19 in the historical group. Platelet counts on admission were 12 (8–31) x109/L for trial cases and 14 (4–78) x109/L in historical controls. Pre 1st Rituximab therapy, median platelet count was 23x 109/L. By day 7 platelet counts were 211 x109/L for the historic controls but 9/20 had platelets< 150 x109/L. Pre 2nd Rituximab (day 8) for trial cases, median platelet counts were 91 x109/L and 10/20 had platelets <150x109/L. However, by day 15 (pre 3rd Rituximab) median platelet counts were 228 x109/L and was sustained. In the trial group, 2 patients received other immunosuppressive therapies (vincristine in 2 and ciclosporin (CSA) in 1). In the historical group, 5 received CSA, 4 defibrotide, 2 cyclophosphamide and 4 vincristine. In both groups, median ADAMTS 13 activity was <5% on admission. In the Rituximab cases, activity was 33% at 4 weeks and 51% at 3 months (normal range >66%). Median IgG ADAMTS 13 on admission was 34% (7–162%), reducing to a median of 9% pre the 4th Rituximab (normal range <4.2%). CD19 pre 1st Rituximab was 31% and pre 2nd, 4.5% (normal range 5–15%); specifically, there have been no increased infectious episodes. There was no deaths or serious adverse events in the patients receiving Rituximab. One patient in the historical group died. There have been no relapses in the trial group, follow-up 3–15 months. Over 15 months in the historical group, 10/20 had relapsed. In conclusion, Rituximab appears to be safe in patients with acute idiopathic TTP. The trial group have a greater proportion of A/C cases with a trend for more PEX to remission. However the trial group have had no episodes of relapse compared to the historical group, in which 50% of patients had further TTP episodes.

Author notes

Disclosure: Research Funding: Baxter UK. Honoraria Information: Baxter UK. Off Label Use: Rituximab in thrombotic thrombocytopenic purpura.