Rituximab chimeric anti-CD20 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenic purpura
ABSTRACT The role of rituximab, a chimeric monoclonal antibody directed against the CD20 antigen, in the treatment of patients with chronic idiopathic thrombocytopenic purpura (ITP) has not been determined. The effectiveness and side effects of this therapeutic modality were investigated in a cohort of 25 individuals with chronic ITP. All patients had ITP that had been resistant to between 2 and 5 different therapeutic regimens, including 8 patients who had already failed splenectomy. Patients were scheduled to receive intravenous rituximab at the dose of 375 mg/m(2) once weekly for 4 weeks. Rituximab infusion-related side effects were observed in 18 patients, but were of modest intensity and did not require discontinuation of treatment. A complete response (platelet count greater than 100 x 10(9)/L) was observed in 5 cases, a partial response (platelet count between 50 and 100 x 10(9)/L) in 5 cases, and a minor response (platelet count below 50 x 10(9)/L, with no need for continued treatment) in 3 cases, with an overall response rate of 52%. In 7 cases, responses were sustained (6 months or longer). In 2 patients with relapsed disease, repeat challenge with rituximab induced a new response. In patients with a complete or partial response, a significant rise in platelet concentrations was observed early during the course of treatment, usually 1 week after the first rituximab infusion. No clinical or laboratory parameter was found to predict treatment outcome, although there was a suggestion that women and younger patients have a better chance of response. In conclusion, rituximab therapy has a limited but valuable effect in patients with chronic ITP. In view of its mild toxicity and the lack of effective alternative treatments, its use in the setting of chronic refractory ITP is warranted. (Blood. 2001;98:952-957)
- SourceAvailable from: Sophie Auger
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- "Early anti-CD20 data outcome is also inferior to outcomes seen after splenectomy. However, all but two published studies (Stasi et al, 2001; Cooper et al, 2004) have reported only a small number of patients, and most cohorts have included a mix of splenectomized and/or non-splenectomized patients. Although a recent French pilot study assessed rituximab efficacy and safety in non-splenectomized adults with chronic ITP (Godeau et al, 2008), it remains important to determine whether rituximab is an effective treatment for delaying or avoiding splenectomy in chronic ITP. "
ABSTRACT: Primary immune thrombocytopenia (ITP) is an acquired immune-mediated disorder with absence of any underlying cause. Corticosteroids are the standard initial treatment. Splenectomy is the main second-line treatment. A trend to delay or avoid splenectomy has developed thanks to new agents like rituximab. Few studies have assessed the response rate to rituximab in chronic ITP. We performed the first meta-analysis of randomized clinical trials and observational studies on rituximab as an effective splenectomy-avoiding option in adult chronic ITP. Overall methods were adapted from published guidelines for meta-analysis (meta-analysis of observational studies in epidemiology and preferred reporting items for systematic reviews and meta-analyses). Two haematologist investigators carried out study selection and data extraction independently, recording overall response rate (ORR) and complete response (CR) as primary assessment criteria. Of 364 records were identified through electronic databases. Of 19 retrospective or prospective observational studies were retained after removing duplicate studies and full-text analyses. The ORR was 57% (95% confidence interval [CI]: 48-65), for 368 non-splenectomized patients after rituximab; CR was 41% (95% CI: 0·33-0·51) for 346 patients. Results were stable for ORR and CR in all sub-analyses. In univariate or multivariate mixed-effect meta-regression, age was the most relevant effect. According to our results, rituximab should be used in earlier in non-splenectomized patients.British Journal of Haematology 05/2012; 158(3):386-98. DOI:10.1111/j.1365-2141.2012.09169.x · 4.96 Impact Factor
- "However, the most consistent results with monoclonal antibody therapy have been obtained with rituximab, an anti- CD20 chimeric antibody inducing B cell depletion. At the dawn of the new millennium rituximab was reported an efficacious therapy for a significant proportion of adults with chronic ITP (Saleh et al, 2000; Stasi et al, 2001) and this agent soon became the standard (albeit unlicensed) treatment for patients with this condition in many countries. There is no doubt that the major breakthrough in the treatment of chronic ITP has been witnessed in the last few years, with the publication of the results of randomized clinical trials with the TPO receptor agonists, more specifically romiplostim (Kuter et al, 2008, 2010) and eltrombopag (Bussel et al, 2009a; Cheng et al, 2010). "
Article: ITP: A historical perspective[Show abstract] [Hide abstract]
ABSTRACT: A clinical syndrome of bleeding and purpura consistent with a diagnosis of immune thrombocytopenia (ITP) was described by Werlhof long before platelets were identified as the cellular component of blood playing an essential role in primary haemostasis. Although a role for the spleen was suggested nearly a century ago, the pathophysiology of ITP has remained elusive for many decades. During this time Werlhof's disease was renamed idiopathic thrombocytopenic purpura, from which the acronym ITP originally derives. The second half of the 20th century brought recognition of the autoimmune components of ITP, and hence the need for a new standard nomenclature, which has recently been accepted. ITP currently stands for Immune Thrombocytopenia, a name that more appropriately reflects the low platelet count rather than purpura as the main feature of the disease, as well as to defining its underlying nature. Advances in our knowledge of the disease have paralleled the availability of new therapeutic agents, and we are now entering an era of pathophysiologically-based treatment options.British Journal of Haematology 04/2011; 153(4):437-50. DOI:10.1111/j.1365-2141.2010.08562.x · 4.96 Impact Factor
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- "Alternatively, pathogenic autoantibodies may be produced by short-lived plasma cells or plasmablasts that are not replenished after B-cell depletion (Stasi, 2010). These hypotheses remain speculative: While rapid and profound B-cell depletion has been well documented following rituximab treatment (Stasi et al, 2001; Roll et al, 2006), the correlation with platelet autoantibody levels or with clinical response have not yet been demonstrated. Besides its effect on autoantibody production, rituximab might improve ITP through its effect on T-cells. "
ABSTRACT: Immune thrombocytopenia (ITP) is a common autoimmune disease characterized by low platelet counts and an increased risk of bleeding. Antibody-mediated platelet destruction has been the prevailing hypothesis to explain ITP pathogenesis, supported by the efficacy of B-cell depletion therapy; however, the recent success of thrombopoietin receptor agonists lends support to the notion that platelet production is also insufficient. Best practice for the management of chronic ITP has not yet been established because data from comparative trials are lacking. Despite renewed interest in novel drugs capable of increasing platelet counts, ultimate treatment goals for ITP patients must be kept in mind: to improve patients' health and well-being. In this article, the pathophysiology of ITP is reviewed and key remaining questions about mechanism are explored. A rational approach to the management of ITP in adults is outlined, acknowledging evidence and evidence gaps, and highlighting the need for clinically important endpoints in future clinical trials.British Journal of Haematology 11/2010; 152(1):52-60. DOI:10.1111/j.1365-2141.2010.08412.x · 4.96 Impact Factor