Rituximab reduces risk for relapse in patients with thrombotic thrombocytopenic purpura.

Recent systematic reviews assessing the role of rituximab in the management of patients with acquired thrombotic thrombocytopenic purpura (TTP) identified 2 major observational studies describing relapse after rituximab treatment. One report described a significantly decreased frequency of relapse in 40 patients who, in addition to plasma exchange (PEX) and high-dose corticosteroids, were treated with rituximabwithin 3 days of diagnosis as comparedwith historical control patients who had not received rituximab. The other report compared 22 patients who were treated with rituximab for an inadequate response after initial treatment with PEX and corticosteroids with historical control patients who had not received rituximab; the researchers reported no significant difference in relapse frequency related to rituximab treatment. Both studies had important limitations. Control patientswere retrospectively selected froma time period preceding the patient group receiving rituximab. Some patients had a history of previous episodes of TTP. Not all patients had ADAMTS13 activity ,10%. The frequency of corticosteroid use and other treatments for TTPwas not controlled. A shorter duration of follow-up of rituximabtreated patients compared with control patients potentially biased the results to observe fewer relapses in the treatment group. We updated our previous systematic review to February 23, 2016, and identified no additional comparable studies of rituximab treatment of TTP. We report the experience of the Oklahoma TTP Registry with rituximab treatment of initial episodes of acquired TTP. The Registry is an inception cohort of all consecutive patients for whom the Oklahoma Blood Institute (OBI) is requested to provide PEX for patients with a clinical diagnosis ofTTP.Because theOBI is the soleprovider ofPEX for all hospitals in our region, the Registry includes all patients without selection or referral bias. All identified patients have been enrolled; no patients were excluded. The Registry is approved by the institutional review boards of the University of Oklahoma Health Sciences Center and each participating hospital. Our report describes all 41 consecutive patients enrolled in the Registry with their first episode of acquired TTP in December 2003 through December 2014. The diagnosis of TTP was documented by ADAMTS13 activity ,10%. Four (10%) of the 41 patients died with their initial episode:2werenot treatedwith rituximab (1diedbeforePEX began and 1 died during her first PEX) and 2 were treated with rituximab (1 died of Staphylococcus aureus sepsis and 1 died after failure of multiple agents). Follow-up of 36 of the 37 surviving patients is complete through 2015; 1 patient who was not treated with rituximab relapsed at 6 months and then was lost to follow-up. Sixteen (43%) of the 37 surviving patients were treated with rituximab for their initial episode. Fourteen were treated because they were unresponsive to PEX and corticosteroids or they had recurrent thrombocytopeniawhenPEXwas stopped.One patientwas treatedwith rituximab because she could not return for evaluations. One patient was treated with rituximab (once) and corticosteroids for a diagnosis of primary immune thrombocytopenia 5 days before TTP was diagnosed and PEXwas begun; she then had 3moreweekly infusions. Fourteen of the 16 patients received 4 weekly infusions of 375mg/m. Two patients received only 1 infusion: 1 because she developed bacteremia and 1 because of no insurance. Comparison of the 16 rituximab-treated patients to the 21 patients not treated with rituximab demonstrated no significant differences in demographic features, initial clinical data, or the year of their initial episode (Table 1). The only significant differenceswere that rituximabtreated patients had more PEX treatments over a longer duration and received a greater total dose of corticosteroids, reflecting their inadequate response to initial treatment. Two of the 37 patients subsequently died (16 and 30 months) after TTP; neither had been treated with rituximab for the TTP initial episode and neither had relapsed. Both deaths were related to systemic lupus erythematosus that preceded TTP. The frequency of relapse among the rituximab-treated patients was significantly less than that among patients not treated with rituximab (P5 .009, Figure 1). Two rituximab-treated patients relapsed at 2.5 and 9.9 years after the initial episode. Both patients had received 4 infusions of rituximab for their initial episode; they had ADAMTS13 activity ,10% at the time of their relapse and were re-treated with rituximab. Nine patients not treated with rituximab relapsed at 0.4 to 5.9 years (median, 3.1 years) after their initial episode. Two of 6 patients who received rituximab for their initial relapses relapsed again after 3.0 and 8.6 years; they were again treated with rituximab. One of 3 patients who had not received rituximab for their initial relapses relapsed again after 10 months; she was then treated with rituximab. ADAMTS13 activity was ,10% in 11 of 12 relapses (it was not measured in 1 patient). All 11 relapsing patients have survived. Patients treated with rituximab for their initial TTP episode had significantly fewer relapses than patients not treated with rituximab, even though their initial episodes were complicated by inadequate response to initial treatment with PEX and corticosteroids. Compared with the previous reports, our 2 groups of patients were concurrent. Only patients with their first episode of TTPwere included. All patients had ADAMTS13 activity ,10% at the time of their initial episodes. The patients’ demographics, initial clinical data, and the durations of follow-up were not different. The greater total dose of corticosteroids given to rituximab-treated patients may have confounded our interpretation that rituximabwas associatedwith the decreased frequency of relapses. Other limitations of our data are that there was no standard treatment protocol and only selected patients received rituximab. Although these patients were treated in 9 different Oklahoma City hospitals, 1 of the authors (J.N.G.) saw each of these 37 patients and participated in treatment decisions.