High versus standard dose methylprednisolone in the acute phase of idiopathic thrombotic thrombocytopenic purpura: a randomized study

Abstract

Order of Authors: Carlo L Balduini; Luigi Gugliotta; Mario Luppi; Luca Laurenti; Catherine Klersy; Carla Pieresca; Gerlando Quintini; Francesco Iuliano; Rossana Re; Pierangelo Spedini; Nicola Vianelli; Alfonso Zaccaria; Enrico M Pogliani; Roberto Musso; Enrico Bobbio Pallavicini; Giovanni Quarta; Piero Galieni; Alberto Fragasso; Gianluca Casella; Patrizia Noris; Edoardo Ascari Abstract: Therapeutic plasma exchange (PE) is the accepted therapy for thrombotic thrombocytopenic purpura (TTP). Because not all patients obtain remission, other treatment modalities have been used in addition to PE, but no randomized clinical trial evaluated their efficacy. The aim of this multicentric study was to compare the effectiveness of standard-versus high-dose methylprednisolone as an adjunctive treatment to PE in the acute phase of TTP. Sixty patients with idiopathic TTP were randomized to receive standard-dose (1 mg/kg/die i.v.) or high-dose methylprednisolone (10 mg/kg/die for three days, thereafter 2.5 mg/kg/die) in addition to PE. Both dosages of steroids were well tolerated. At the end of induction therapy (day 23), the percentage of patients failing to obtain complete remission was significantly higher in the standard-dose (16/30) than in the high-dose group (7/30). Also the number of cases without a good response at day 9 and the number of deaths were higher in the standard-dose arm, but the differences did not reach the statistical significance. Results of present study indicate that the association of PE with high-dose instead of standard-dose steroids reduces the percentage of TTP patients that fail to achieve complete remission.Response to Reviewers: Reviewer #1: The authors have proved that the association of plasma exchanged with high-dose methylprednisolone instead of standard-dose reduces the percentage of TTP patients that failed to achieve complete remission. This observation has important clinical implication. I have no major remarksMinor remarks: Activity of ADAMTS 13 and autoantibodies against ADAMTS 13 were not tested. In my opinion this paper can be published in Annals Of Hematology in the present form.Reviewer #2: General:In this randomized clinical trial Balduini and colleagues compared low-dose vs. high dose steroids as an adjunctive treatment to plasma exchange with fresh frozen plasma / cryosupernatant in 60 patients suffering from acute TTP. In the low-dose arm more patients (13/30 vs. 7/30, p= 0.17) failed to achieve a good response at day 9 (primary endpoint of the study) and also more patients failed to achieve complete remission (16/30 vs. 7/30; p= 0.03). Also the number of death (4 vs. 1) was higher, this was however not statistically significant. The authors conclude that plasma exchange in combination with high dose steroids is superior to low-dose steroids. Over the years the Italian TTP study group has been able to conduct several randomized clinical trials in the setting of acute TTP addressing open questions in the field where many other groups have failed to do likewise due to lack of sui...

Treatment of thrombotic thrombocytopenic purpura beyond therapeutic plasma exchange

“…Although this study did not answer the question of whether steroids increase the likelihood of remission compared to treatment without steroids, it suggests that high-dose steroid therapy improves the management of TTP. 5 Together, these results indicate that steroids might have a place in the management of TTP in association with TPE, provided there is no obvious contra-indication. However, the modality of administration remains debatable.…”

Thrombotic thrombocytopenic purpura and neurologic manifestations – Case report and integrative review

“…[8,9] It is important to note that various diseases are part of the differential diagnosis and may present similarly to TTP, the Hemolytic Uremic Syndrome is the main condition described [16]. Other conditions that can mimic TTP are disseminated intravascular coagulation, Evans Syndrome, Antibody antiphospholipid syndrome, severe vasculitis, malignant hypertension, disseminated metastatic cancer.…”

“…Some studies show cases of death as a complication of plasmapheresis, which makes it clear that, although it is a good treatment option, does not come without risks and new therapies need to be developed. [8,[19][20][21][22][23][24][25][26][27] …”

Thrombotic Thrombocytopenic Purpura and Hemolytic Uremic Syndrome in 2014—Current Knowledge and Outcomes with Plasma Exchange

“…54 There is no robust evidence for use of corticosteroid in conjunction with plasma exchange and its use is largely dictated by center-specific practices; however, a recent small RCT of highdose therapy does suggest benefit. [55][56][57] Registry data show that the number of plasma exchange treatments to achieve remission is lower in relapsed cases then in first episodes of acquired idiopathic TTP.…”