Intravenous immunoglobulin or high-dose methylprednisolone, with or without oral prednisone, for adults with untreated severe autoimmune thrombocytopenic purpura: a randomised, multicentre trial
ABSTRACT Treatment of adults with autoimmune thrombocytopenic purpura (AITP) is based more on individual experience than on results of controlled studies. We compared intravenous immunoglobulin with high-dose methylprednisolone in untreated adults with severe AITP and assessed efficacy of subsequent oral steroids compared with placebo. Primary outcome was number of days with platelet count greater than 50 x 10(9)/L within the first 21 days.
We did a randomised multicentre trial based on a 232 design. 122 adults with severe AITP (platelet count < or =20 x 10(9)/L) were randomly assigned to receive either intravenous immunoglobulin or high-dose methylprednisolone on days 1-3 (randomisation A), and then to receive either oral prednisone or placebo (randomisation B) on days 4-21. Analysis was by intention to treat.
Six patients were excluded from the analysis. The number of days on which platelet counts were above 50 x 10(9)/L was 18 in 56 patients receiving intravenous immunoglobulin and 14 in 60 receiving high-dose methylprednisolone (p=0.02). Percentage of patients who had platelet counts over 50 x 10(9)/L on days 2 and 5 was 7% and 79%, respectively, in the intravenous immunoglobulin group compared with 2% and 60%, respectively, in the high-dose methylprednisolone group (p=0.04). During the second treatment period, prednisone was more effective than placebo for all short-term endpoints. Patients who received intravenous immunoglobulin and prednisone had platelet count greater than 50 x 10(9)/L for 18.5 days (p=0.005), and those treated with high-dose methylprednisolone and prednisone had this count for 17.5 days.
Intravenous immunoglobulin and oral prednisone seems to be more effective than high-dose methylprednisolone and oral prednisone in adults with severe AITP, although the latter treatment is effective and well tolerated.
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ABSTRACT: Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder in which platelets are opsonised by autoantibodies and destroyed by macrophages. Therefore, ITP represents a prototype of a B-cell-mediated autoimmune disorder. B-cell activating factor (BAFF) is a member of the tumour necrosis factor family and an important regulator of B-cell development. BAFF levels were determined in serum samples from 53 patients with ITP. Serum BAFF levels in patients with an active ITP were increased when compared with the healthy control group (median 1620 pg/ml vs. 977 pg/ml; P < 0.001). Moreover, immunosuppressive treatment was associated with strongly suppressed BAFF levels (median 629 pg/ml; P < 0.01). In addition, a polymorphic site was detected in the BAFF promoter region (-871) that appeared to occur more frequently in ITP patients than in healthy persons. This promoter variant was associated with very high BAFF levels in ITP patients. Our data suggest that BAFF is an important pathogenetic factor in the development of ITP.British Journal of Haematology 01/2007; 136(2):309-14. DOI:10.1111/j.1365-2141.2006.06431.x · 4.96 Impact Factor
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ABSTRACT: The true incidence and prognosis of autoimmune thrombocytopenic purpura (ITP) in adults is unknown. We present the results of a prospective study in a population-based cohort of newly presenting adults (> or = 16 years) with ITP and platelet count of < 50 x 109/l, which took place between 1 January 1993 and 31 December 1999 in the former Northern Health Region in the UK (population 3.08 million). A total of 245 cases were confirmed by bone marrow examination with a median follow-up of 60 months (range 6-78 months). There were 134 females/111 males (1.2:1). Overall incidence was 1.6 per 105 per annum. Absolute incidence was similar for both sexes, with highest age-specific incidence in those aged > 60 years. Thirty patients (12%) presented with frank bleeding, and 28% were asymptomatic. Forty-five patients (18%) received no treatment, and 135 (55%) received first-line treatment only. Thirty patients (12%) underwent splenectomy. There were four deaths (1.6%) from bleeding and/or the complications of therapy in this cohort, but only one was in the acute phase of the illness. The majority of patients (155 out of 245) achieved remission (platelet count > 100 x 109/l), with a further 59 (24%) in partial remission with no symptoms (platelet count 30-100 x 109/l). This population-based study suggests that the traditional view of adult ITP as being a predominantly chronic disease that preferentially affects females needs to be modified.British Journal of Haematology 09/2003; 122(6):966-74. DOI:10.1046/j.1365-2141.2003.04547.x · 4.96 Impact Factor
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ABSTRACT: Splenectomy remains the most effective treatment of chronic autoimmune idiopathic thrombocytopenia (ITP) (i.e. of > 6 months duration). Treatment of patients refractory to splenectomy (with absence of response or relapse after initial response) is difficult, and their long-term outcome is not well known. Over a 10-year period, 183 patients with chronic ITP were splenectomized including 158 adults and 25 children (</= 15 years). Forty-seven of them, who were refractory to this treatment, were prospectively followed up for 5-15 years (median 7.5 years). Twelve of them, with moderate thrombocytopenia, remained untreated, and 35 were treated by a median of two regimens (range 1--6), to which 27 responded. Thirty-six (77%) of the refractory cases reached platelet counts durably > 100 x 10(9)/l, nine of them without treatment and 27 of them with low-dose steroids or azathioprine; six (13%) remained moderately thrombocytopenic (35 x 10(9)/l to 100 x 10(9)/l platelets); the last five patients, without response to any treatment (up to six regimens), remained severely thrombocytopenic (platelets < 20 x 10(9)/l), and three of them died from bleeding. Twenty-seven (57%) of the 47 refractory cases required at least one hospitalization, in the majority of cases for intravenous immunoglobulin (IVIg) infusions. Seven of the refractory cases occurred in children. Six of them subsequently reached platelet counts > 100 x 10(9)/l, but one died from bleeding. Our findings confirm the overall favourable long-term prognosis of chronic ITP refractory to splenectomy.British Journal of Haematology 03/2003; 120(6):1079-88. DOI:10.1046/j.1365-2141.2003.04211.x · 4.96 Impact Factor