A phase 2 study of the safety and efficacy of rituximab with plasma exchange in acute acquired thrombotic thrombocytopenic purpura

Abstract

The safety and efficacy of weekly rituximab 375 mg/m 2 (؋4), given within 3 days of acute TTP admission, with standard therapy (PEX and steroids) was evaluated. Clinical outcomes were compared to historical controls (n ‫؍‬ 40) who had not received rituximab. Within the trial group, 15 of 40 required ICU admission and 15% of all cases with the highest troponin T levels on admission were ventilated. Before the second rituximab infusion, 68% of cases had a platelet count > 50 ؋ 10 9 /L and 38% > 150 ؋ 10 9 /L. Fewer PEX were required in whites compared to nonwhite in the rituximab group (mean 14 vs 21, P ‫؍‬ .0095). Inpatient stay was reduced by 7 days in the non-ICU trial cases compared to historical controls (P ‫؍‬ .04), especially in whites, with a mean reduction of 7 days (P ‫؍‬ .05). Ten percent of trial cases relapsed, median, 27 months (17-31 months), compared to 57% in historical controls, median 18 months (3-60 months; P ‫؍‬ .0011).There were no excess infections or serious adverse events with rituximab. In conclusion, rituximab appears a safe and effective therapy. Inpatient stay and relapse are significantly reduced in the rituximab cohort. Rituximab should be considered in conjunction with standard therapy on acute presentation of TTP. This study was registered at www.clinicaltrials.gov as NCT009-3713. (Blood. 2011;118(7): 1746-1753)

Treatment of thrombotic thrombocytopenic purpura beyond therapeutic plasma exchange

“…Rituximab was first introduced with encouraging results (Table 1) in the acute phase of autoimmune TTP, [6][7][8] typically in patients with a suboptimal response to conventional first-line treatment (ie, disease exacerbation or refractoriness, as defined by no improvement of the clinical features and/or lack of doubling of the platelet count from baseline after 4 full days of standard treatment). In these trials, TPE was usually continued daily and rituximab was administered immediately after a TPE.…”

“…Moreover, it is unclear whether administration of rituximab in the acute phase of disease decreases the incidence of long-term relapses. 7,8 The rapid identification of severe acquired ADAMTS13 deficiency in a patient with features of thrombotic microangiopathy (TMA) represents the main limitation of the systematic use of rituximab as frontline treatment in these patients, because not all centers can assess ADAMTS13 activity in an emergency. Moreover, it is also important to rule out other associated conditions that may influence the decision to treat or not with rituximab, such as HIV infection or history of hepatitis B virus infection.…”

A dramatic recovery in a patient initially expected to die of TTP & its complications

“…Our patient received Rituximab on Day 2 of her hospitalization which preceded her drastic improvement. When started within three days of admission for acute onset TTP, Rituximab has been shown to reduce the number of required PEX treatments and time to achieve remission in white females [7]. The recommendation to include Rituximab as the standard treatment for TTP is relatively new.…”

Novel therapies in thrombotic thrombocytopenic purpura

“…Three different groups have evaluated its use as addition to PEX and steroids in the acute episode of TTP 5, 8, 52. All three of them reported fewer and later relapses in the rituximab treated patients.…”