RESUMO
ABSTRACT: Fostamatinib, a recently approved Syk inhibitor used in adult primary immune thrombocytopenia (ITP), has been shown to be safe and effective in this disorder. However, clinical trial results may not be similarly reproduced in clinical practice. Here, 138 patients with ITP (both primary and secondary) from 42 Spanish centers who had been treated with fostamatinib were evaluated prospectively and retrospectively. The median age of our cohort (55.8% women) was 66 years (interquartile range [IQR], 56-80). The median time since ITP diagnosis at fostamatinib initiation was 51 months (IQR, 10-166). The median number of therapies before fostamatinib initiation was 4 (IQR, 2-5), including eltrombopag (76.1%), romiplostim (57.2%), and IV immunoglobulins (44.2%). Fifty-eight patients (42.0%) had signs/symptoms of bleeding in the month before treatment initiation. Seventy-nine percent of patients responded to fostamatinib with 53.6% complete responses (platelet count > 100 × 109/L). Eighty-three patients (60.1%) received fostamatinib monotherapy, achieving a high response rate (85.4%). The proportion of time in response during the 27-month period examined was 83.3%. The median time to platelet response was 11 days (IQR, 7-21). Sixty-seven patients (48.5%) experienced adverse events, mainly grade 1 to 2; the commonest of which were diarrhea (n = 28) and hypertension (n = 21). One patient had deep venous thrombosis, and one patient developed acute myocardial infarction. Fostamatinib was shown to be effective with good safety profile in patients with primary and secondary ITP across a wide age spectrum in this real-world study.
Assuntos
Aminopiridinas , Morfolinas , Oxazinas , Púrpura Trombocitopênica Idiopática , Piridinas , Pirimidinas , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Idoso , Oxazinas/uso terapêutico , Oxazinas/efeitos adversos , Idoso de 80 Anos ou mais , Pirimidinas/uso terapêutico , Pirimidinas/efeitos adversos , Morfolinas/uso terapêutico , Morfolinas/efeitos adversos , Piridinas/uso terapêutico , Piridinas/efeitos adversos , Aminopiridinas/uso terapêutico , Aminopiridinas/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Quinase Syk/antagonistas & inibidores , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversos , Contagem de Plaquetas , Estudos ProspectivosRESUMO
Relapsing or occurring de novo autoimmune hemolytic anemia (AIHA) during pregnancy or puerperium is a poorly described condition. Here, we report 45 pregnancies in 33 women evaluated at 12 centers from 1997 to 2022. Among the 20 women diagnosed with AIHA before pregnancy, 10 had a relapse. An additional 13 patients developed de novo AIHA during gestation/puerperium (2 patients had AIHA relapse during a second pregnancy). Among 24 hemolytic events, anemia was uniformly severe (median Hb, 6.4 g/dL; range, 3.1-8.7) and required treatment in all cases (96% steroids ± intravenous immunoglobulin, IVIG, 58% transfusions). Response was achieved in all patients and was complete in 65% of the cases. Antithrombotic prophylaxis was administered to 8 patients (33%). After delivery, rituximab was administered to 4 patients, and cyclosporine was added to 1 patient. The rate of maternal complications, including premature rupture of membranes, placental detachment, and preeclampsia, was 15%. Early miscarriages occurred in 13% of the pregnancies. Fetal adverse events (22% of cases) included respiratory distress, fetal growth restriction, preterm birth, AIHA of the newborn, and 2 perinatal deaths. In conclusion, the occurrence of AIHA does not preclude the ability to carry out a healthy pregnancy, provided close monitoring, prompt therapy, and awareness of potential maternal and fetal complications.
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Anemia Hemolítica Autoimune , Nascimento Prematuro , Humanos , Feminino , Recém-Nascido , Gravidez , Anemia Hemolítica Autoimune/epidemiologia , Anemia Hemolítica Autoimune/terapia , Anemia Hemolítica Autoimune/diagnóstico , Placenta , Nascimento Prematuro/tratamento farmacológico , Rituximab/uso terapêutico , Imunoglobulinas Intravenosas/uso terapêutico , Período Pós-PartoRESUMO
Immune thrombocytopenia (ITP) is a common autoimmune hematological disorder. Despite this, diagnosis is still challenging due to clinical heterogeneity and the lack of a specific diagnostic test. New findings in the pathology and the availability of new drugs have led to the development of different guidelines worldwide. In the present study, the Delphi methodology has been used to get a consensus on the management of adult patients with ITP in Spain and to help in decision-making. The Delphi questionnaire has been designed by a scientific ad hoc committee and has been divided into 13 topics, with a total of 127 items, covering the maximum possible scenarios for the management of ITP. As a result of the study, a total consensus of 81% has been reached. It is concluded that this Delphi consensus provides practical recommendations on topics related to diagnosis and management of ITP patients to help doctors to improve outcomes. Some aspects remain unclear, without consensus among the experts. Thus, more advances are needed to optimize ITP management.
What is the context? Immune thrombocytopenia (ITP) is a hematologic autoimmune disease characterized by accelerated destruction and inadequate production of platelets mediated by autoantibodies (platelet count <100 × 109 /L).Despite being a common condition, its heterogeneous clinical course makes its diagnosis and management still a challenge.In recent years, new molecules with different mechanisms of action have emerged for the treatment of ITP.Due to the increasing information about the pathology and its therapies, several international guidelines have recently been established to provide recommendations for the management and treatment of ITP.There are still many patient scenarios and disease aspects which are not addressed in the guidelines.What is new? Our Spanish ITP Expert Group has developed a Delphi consensus study to provide recommendations and promote standardization of the management of adult patients with ITP in Spain.The scientific committee defined 127 statements for consensus, corresponding to 13 chapters: (i) Diagnosis of ITP, (ii) First-line treatment, (iii) Second-line treatment, (iv) Treatment of refractory patients, (v) Follow-up, (vi) Emergency and surgery, (vii) ITP in the elderly, (viii) ITP in pregnancy, (ix) Anticoagulation and antiplatelet, (x) Secondary ITP, (xi) Quality of life, (xii) Discontinuation of TPO-RA, and (xiii) ITP and Covid.The total number of agreed statements achieved was 103, giving a final percentage of consensus in the Delphi questionnaire of 81%.What is the impact? This Delphi consensus provides recommendations based on real clinical practice data, regarding the diagnosis, treatment, and management of patients and scenarios in ITP to assist clinicians in addressing this disease and achieving optimal outcomes for the patient.
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Consenso , Técnica Delphi , Púrpura Trombocitopênica Idiopática , Humanos , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/diagnóstico , Espanha , Inquéritos e QuestionáriosRESUMO
The only way to prevent immune thrombocytopenia (ITP) from becoming refractory would be to restore tolerance to platelets at an early phase of the disease. Numerous immune alterations probably accumulate in chronic ITP; thus, the chances of cure decrease significantly with time. Currently, sustained remission off treatment (SROT) is a clinical definition describing patients who can discontinue their ITP treatment without risk and maintain a state of remission. Different treatment strategies are presently being evaluated with the goal of attaining SROT, mostly combining drugs targeting the innate and/or the adaptive immune system, the inflammation state, so as increasing the platelet load. In this sense, thrombopoietin receptor agonists (TPO-RAs) have shown promising results if used as upfront treatment. TPO-RAs seem to exhibit immunomodulation and immune tolerance properties, increasing not only the platelet antigen mass but also increasing the transforming growth factor-ß concentration, and stimulating regulatory T and B lymphocytes. However, more immunological studies are needed to establish accurate molecular alterations in ITP that are potentially reversed with treatments.
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Púrpura Trombocitopênica Idiopática , Trombocitopenia , Humanos , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Suíça , Imunomodulação , PlaquetasRESUMO
To establish pan-European consensus on tapering and discontinuing thrombopoietin receptor agonists (TPO-RAs) in patients with immune thrombocytopenia (ITP), we applied a three-step Delphi technique consisting of a one-to-one interview round and two online survey rounds. Three healthcare professionals (HCPs) from Italy, Spain, and the United Kingdom formed the Steering Committee (SC), which advised on study design, panelist selection, and survey development. A literature review also informed the development of the consensus statements. Likert scales were used to collect quantitative data on panelists' level of agreement. Twelve hematologists representing nine European countries assessed 121 statements spanning three categories: (1) patient selection; (2) tapering and discontinuation strategies; (3) post-discontinuation management. Consensus was reached on approximately half of the statements in each category (32.2%; 44.6%; 66%). Panelists agreed on patients' main selection criteria, patients' involvement in decision-making, tapering strategies, and follow-up criteria. Areas not reaching consensus were risk factors and predictors of successful discontinuation, monitoring intervals, and rates of successful discontinuation or relapse. This lack of consensus signals knowledge and practice gaps among European countries and suggests the need for the development of clinical practice guidelines that outline a pan-European, evidence-based approach to tapering and discontinuing TPO-RAs.
Immune thrombocytopenia (ITP) is a condition that may cause extensive bruising and excessive bleeding. Another sign is a pattern of small reddish-purple dots resembling a rash. ITP is treated with a class of medications known as thrombopoietin receptor agonists (TPO-RAs), which include eltrombopag, avatrombopag, and romiplostim. Sometimes the beneficial effects of the medication last even after the patient stops taking it, which means that some patients can be tapered off it. This paper presents the results of a Delphi panela method of research that gathers insights from expertsabout tapering and discontinuing TPO-RAs. There were 12 physicians from nine European countries on the Delphi panel, all practicing hematologists with expertise in tapering and discontinuing TPO-RAs in patients with ITP. Panelists were presented with a total of 130 statements over three survey rounds. At the end of Round Three, 52 statements (40%) achieved consensus (response pattern of ≥80% "Agree"), and six statements (4.6%) achieved dissensus (response pattern of ≥80% "Disagree"). Consensus was achieved on the appropriateness of tapering the dose of the TPO-RA for two to three months prior to attempting discontinuation. The panel also reached consensus on considering tapering in a slower fashion (six to 12 months) for patients showing suboptimal response to TPO-RAs. More than half the survey's statements did not achieve consensus or dissensus. This signals that knowledge gaps exist and highlights the importance of conducting prospective, real-world evidence studies to identify best practices and develop pan-European guidelines for tapering and discontinuing TPO-RAs.
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Púrpura Trombocitopênica Idiopática , Trombocitopenia , Humanos , Púrpura Trombocitopênica Idiopática/etiologia , Receptores de Trombopoetina/agonistas , Trombopoetina , Receptores Fc , Trombocitopenia/etiologia , Benzoatos , Hidrazinas , Proteínas Recombinantes de FusãoRESUMO
Background and Objectives: TPO-RAs (romiplostim/eltrombopag/avatrombopag) have broadly demonstrated high efficacy rates (59-88%), durable responses (up to three years) and a satisfactory safety profile in clinical trials. The effect of TPO-RAs is classically considered to be transient because platelet numbers usually dropped rapidly to baseline unless therapy was maintained. However, several groups have reported the possibility of successfully discontinuing TPO-RAs in some patients without further need for concomitant treatments. This concept is usually referred as sustained remission off-treatment (SROT). Materials and Methods: Unfortunately, we still lack predictors of the response to discontinuation even after the numerous biological, clinical and in vitro studies performed to study this phenomenon. The frequency of successful discontinuation is matter of controversy, although a percentage in the range of 25-40% may probably be considered a consensus. Here, we describe all major routine clinical practice studies and reviews that report the current position on this topic and compare them with our own results in Burgos. Results: We report our Burgos ten-step eltrombopag tapering scheme with which we have achieved an elevated percentage rate of success (70.3%) in discontinuing treatment. Conclusions: We hope this protocol may help successfully taper and discontinue TPO-RAs in daily clinical practice.
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Benzoatos , Receptores de Trombopoetina , Humanos , Contagem de Plaquetas , Benzoatos/uso terapêutico , Hidrazinas/uso terapêuticoRESUMO
Primary immune thrombocytopenia (ITP) is an acquired blood disorder that causes a reduction in circulating platelets with the potential for bleeding. The incidence of ITP is slightly higher in adults and affects more women than men until 60 years, when males are more affected. Despite advances in basic science, primary ITP remains a diagnosis of exclusion. The disease is heterogeneous in its clinical behavior and response to treatment. This reflects the complex underlying pathophysiology, which remains ill-understood. Platelet destruction plays a role in thrombocytopenia, but underproduction is also a major contributing factor. Active ITP is a proinflammatory autoimmune disease involving abnormalities within the T and B regulatory cell compartments, along with several other immunological abnormalities. Over the last several years, there has been a shift from using immunosuppressive therapies for ITP towards approved treatments, such as thrombopoietin receptor agonists. The recent COVID-19 pandemic has hastened this management shift, with thrombopoietin receptor agonists becoming the predominant second-line treatment. A greater understanding of the underlying mechanisms has led to the development of several targeted therapies, some of which have been approved, with others still undergoing clinical development. Here we outline our view of the disease, including our opinion about the major diagnostic and therapeutic challenges. We also discuss our management of adult ITP and our placement of the various available therapies.
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COVID-19 , Púrpura Trombocitopênica Idiopática , Adulto , Feminino , Humanos , Púrpura Trombocitopênica Idiopática/terapia , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Receptores de Trombopoetina/agonistas , Receptores de Trombopoetina/uso terapêutico , Pandemias , Plaquetas , Teste para COVID-19RESUMO
Management of immune thrombocytopenia (ITP) during pregnancy can be challenging because treatment choices are limited. Thrombopoietin receptor agonists (Tpo-RAs), which likely cross the placenta, are not recommended during pregnancy. To better assess the safety and efficacy of off-label use of Tpo-RAs during pregnancy, a multicenter observational and retrospective study was conducted. Results from 15 pregnant women with ITP (pregnancies, n = 17; neonates, n = 18) treated with either eltrombopag (n = 8) or romiplostim (n = 7) during pregnancy, including 2 patients with secondary ITP, were analyzed. Median time of Tpo-RA exposure during pregnancy was 4.4 weeks (range, 1-39 weeks); the indication for starting Tpo-RAs was preparation for delivery in 10 (58%) of 17 pregnancies, whereas 4 had chronic refractory symptomatic ITP and 3 were receiving eltrombopag when pregnancy started. Regarding safety, neither thromboembolic events among mothers nor Tpo-RA-related fetal or neonatal complications were observed, except for 1 case of neonatal thrombocytosis. Response to Tpo-RAs was achieved in 77% of cases, mostly in combination with concomitant ITP therapy (70% of responders). On the basis of these preliminary findings, temporary off-label use of Tpo-RAs for severe and/or refractory ITP during pregnancy seems safe for both mother and neonate and is likely to be helpful, especially before delivery.
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Benzoatos/administração & dosagem , Hidrazinas/administração & dosagem , Complicações Hematológicas na Gravidez/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Pirazóis/administração & dosagem , Receptores Fc/administração & dosagem , Receptores de Trombopoetina , Proteínas Recombinantes de Fusão/administração & dosagem , Trombopoetina/administração & dosagem , Adulto , Benzoatos/efeitos adversos , Feminino , Seguimentos , Humanos , Hidrazinas/efeitos adversos , Gravidez , Pirazóis/efeitos adversos , Proteínas Recombinantes de Fusão/efeitos adversos , Estudos Retrospectivos , Trombopoetina/efeitos adversosRESUMO
BACKGROUND: Eltrombopag is useful for immune thrombocytopenia (ITP). However, results of clinical trials may not accurately mirror clinical practice reality. Here we evaluated eltrombopag for primary and secondary ITP in our ≥65-year-old population. METHODS: A total of 106 primary ITP patients (16 with newly diagnosed ITP, 16 with persistent ITP, and 74 with chronic ITP) and 39 secondary ITP patients (20 with ITP secondary to immune disorders, 7 with ITP secondary to infectious diseases, and 12 with ITP secondary to lymphoproliferative disorders [LPD]) were retrospectively evaluated. RESULTS: Median age of our cohort was 76 (interquartile range, IQR, 70-81) years. 75.9% of patients yielded a platelet response including 66.2% complete responders. Median time to platelet response was 14 (IQR, 8-21) days. Median time on response was 320 (IQR, 147-526) days. Sixty-three adverse events (AEs), mainly grade 1-2, occurred. The most common were hepatobiliary laboratory abnormalities (HBLAs) and headaches. One transient ischemic attack in a newly diagnosed ITP and two self-limited pulmonary embolisms in secondary ITP were the only thrombotic events observed. CONCLUSION: Eltrombopag showed efficacy and safety in ITP patients aged ≥65 years with primary and secondary ITP. However, efficacy results in LPD-ITP were poor. A relatively high number of deaths were observed.
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Benzoatos/uso terapêutico , Hidrazinas/uso terapêutico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Pirazóis/uso terapêutico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Benzoatos/administração & dosagem , Benzoatos/efeitos adversos , Biomarcadores , Terapia Combinada , Comorbidade , Quimioterapia Combinada , Feminino , Humanos , Hidrazinas/administração & dosagem , Hidrazinas/efeitos adversos , Masculino , Prognóstico , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/diagnóstico , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Estudos Retrospectivos , Resultado do TratamentoAssuntos
Anemia Hemolítica Autoimune , Púrpura Trombocitopênica Idiopática , Trombocitopenia , Adulto , Anemia Hemolítica Autoimune/tratamento farmacológico , Benzoatos , Humanos , Hidrazinas , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Receptores Fc , Receptores de Trombopoetina/agonistas , Proteínas Recombinantes de Fusão , Trombocitopenia/tratamento farmacológico , TrombopoetinaAssuntos
Vacina de mRNA-1273 contra 2019-nCoV/administração & dosagem , Vacina BNT162/administração & dosagem , COVID-19 , Neoplasias Hematológicas , SARS-CoV-2/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/imunologia , COVID-19/mortalidade , COVID-19/prevenção & controle , Feminino , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/mortalidade , Humanos , Masculino , Pessoa de Meia-IdadeAssuntos
Tratamento Farmacológico da COVID-19 , COVID-19 , Dexametasona , Neoplasias Hematológicas , Sistema de Registros , SARS-CoV-2 , Humanos , Dexametasona/uso terapêutico , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/tratamento farmacológico , COVID-19/mortalidade , COVID-19/complicações , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , SARS-CoV-2/isolamento & purificação , Adulto , Idoso de 80 Anos ou maisRESUMO
Patients with multirefractory immune thrombocytopenia (ITP) have limited treatment options. Recent data suggest that specific anti-platelet antibodies may cause destruction of platelets by favoring platelet loss of sialic acid. In this multicenter study 35 patients with ITP, including 16 with multirefractory disease, were analyzed for antiplatelet-antibodies, thrombopoietin (TPO) levels, and platelet desialylation. In selected cases, responses to a novel treatment strategy using oseltamivir were tested. We found that antibodies against GPIbα were overrepresented in multirefractory patients compared to responders (n = 19). In contrast to conventional ITP patients, multirefractory patients exhibited a significant increased platelet activation state (granule secretion) and desialylation (RCA-1 binding) (p < 0.05), and a trend toward higher plasma TPO concentrations. The decreased sialic acid content seemed to be restricted to platelet glycoproteins, since other plasma proteins were not hypoglycosylated. A total of 10 patients with multirefractory ITP having remarkable loss of platelet terminal sialic acids were given oseltamivir phosphate. When the antiviral drug was combined with TPO receptor agonists (TPO-RAs) or with immunosuppressant drugs, platelet responses were observed in 66.7% of patients. All responding patients presented with antibodies reactive only against GPIbα. These findings suggest that desialylation may play a key pathogenic role in some multirefractory ITP patients, and provide diagnostic tools for the identification of such patients. Furthermore, we show that sialidase inhibitor treatment in combination with therapies that help to increase platelet production can induce sustained platelet responses in some patients with anti-GPIbα -mediated thrombocytopenia that have failed previous therapies.
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Ácido N-Acetilneuramínico/metabolismo , Púrpura Trombocitopênica Idiopática , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
OBJECTIVE: To develop a new questionnaire with good psychometric properties to measure satisfaction with medical care in patients with non-valvular atrial fibrillation. METHOD: The initial instrument was composed of 37 items, arranged in 6 dimensions: efficacy, ease and convenience, impact on daily activities, satisfaction with medical care, undesired effects of medication, and overall satisfaction. Items and dimensions were extracted from reviewing existing instruments, 3 focus groups with chronic patients, and a panel of 8 experts. Additionally, 3 visual analog scales measuring quality of life, effectiveness, and overall satisfaction were administered. A convenience sample of 119 patients was used for item reduction. Classic psychometric theory and item analysis techniques were used (exploratory factor and confirmatory factor analysis, test-retest, and correlation with visual scales). A validation sample of 230 patients was used to assess convergent validity, and an additional 220 patients sample was used to discriminate between treatment and compliance groups. RESULTS: The questionnaire was reduced in length to 25 items, but the impact dimension had split in treatment inconvenience and treatment control. Overall reliability was high (α = 0.861) with acceptable dimensional reliabilities (α = 0.764-0.908). Individual dimensions correlated to varying degrees. Test-retest correlations were high (r = 0.784-0.965), and correlations with visual and already validated scales were substantial. Differences were detected between antivitamin K and new-oral-anticoagulant treatments in several dimensions (p < 0.05). Treatment satisfaction was related with compliance. CONCLUSION: This new 25-item questionnaire has good psychometric properties for measuring satisfaction with medical care in patients with this condition. It is capable of detecting differences between different treatments.
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Fibrilação Atrial/psicologia , Cooperação do Paciente , Qualidade de Vida , Idoso , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Análise Fatorial , Feminino , Humanos , Masculino , Satisfação Pessoal , Reprodutibilidade dos Testes , Espanha , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Eltrombopag is effective and safe in chronic immune thrombocytopenia (ITP). However, clinical trials may not accurately reflect what happens in clinical practice. We evaluated the efficacy and safety of eltrombopag in primary chronic ITP in a real-world setting. METHODS: A total of 164 primary patients with chronic ITP from 40 Spanish centers, who had been treated with eltrombopag, were retrospectively evaluated. RESULTS: The median age of our cohort (72% women) was 63 yr (interquartile range, IQR, 45-75 yr). The median time with ITP diagnosis was 81 months (IQR, 30-192 months). The median number of therapies prior to eltrombopag was 3 (IQR, 2-4). At the time of eltrombopag start, 45 patients (30%) were receiving concomitant treatment for ITP. Forty-six patients (30%) had bleeding signs/symptoms the month before the treatment started. The median platelet count at eltrombopag initiation was 22 × 10(9) /L (IQR, 8-39 × 10(9) /L). A total of 135 patients (88.8%) achieved a platelet response. The median time to platelet response was 12 d (95% CI, 9-13 d). Maintained platelet response rate during the 15-month period under examination was 75.2%. Twenty-eight patients (18.4%) experienced adverse events, mainly grades 1-2. CONCLUSION: Eltrombopag is highly effective and well tolerated in unselected patients with primary chronic ITP.
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Benzoatos/uso terapêutico , Hidrazinas/uso terapêutico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Pirazóis/uso terapêutico , Idoso , Benzoatos/administração & dosagem , Benzoatos/efeitos adversos , Doença Crônica , Feminino , Humanos , Hidrazinas/administração & dosagem , Hidrazinas/efeitos adversos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/imunologia , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Retratamento , Estudos Retrospectivos , Espanha , Resultado do TratamentoRESUMO
The thrombopoietin receptor agonists (THPO-RAs), romiplostim and eltrombopag, are effective and safe in immune thrombocytopenia (ITP). However, the value of their sequential use when no response is achieved or when adverse events occur with one THPO-RA has not been clearly established. Here we retrospectively evaluated 51 primary ITP adult patients treated with romiplostim followed by eltrombopag. The median age of our cohort was 49 (range, 18-83) years. There were 32 women and 19 men. The median duration of romiplostim use before switching to eltrombopag was 12 (interquartile range 5-21) months. The reasons for switching were: lack of efficacy (n = 25), patient preference (n = 16), platelet-count fluctuation (n = 6) and side-effects (n = 4). The response rate to eltrombopag was 80% (41/51), including 67% (n = 35) complete responses. After a median follow-up of 14 months, 31 patients maintained their response. Efficacy was maintained after switching in all patients in the patient preference, platelet-count fluctuation and side-effect groups. 33% of patients experienced one or more adverse events during treatment with eltrombopag. We consider the use of eltrombopag after romiplostim for treating ITP to be effective and safe. Response to eltrombopag was related to the cause of romiplostim discontinuation.
Assuntos
Benzoatos/administração & dosagem , Benzoatos/efeitos adversos , Hidrazinas/administração & dosagem , Hidrazinas/efeitos adversos , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Receptores Fc/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/efeitos adversos , Trombopoetina/administração & dosagem , Trombopoetina/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Púrpura Trombocitopênica Idiopática/sangue , Receptores de Trombopoetina/agonistas , Estudos RetrospectivosRESUMO
Eltrombopag is effective and safe in immune thrombocytopenia (ITP). Some patients may sustain their platelet response when treatment is withdrawn but the frequency of this phenomenon is unknown. We retrospectively evaluated 260 adult primary ITP patients (165 women and 95 men; median age, 62 years) treated with eltrombopag after a median time from diagnosis of 24 months. Among the 201 patients who achieved a complete remission (platelet count >100 × 10(9) /l), eltrombopag was discontinued in 80 patients. Reasons for eltrombopag discontinuation were: persistent response despite a reduction in dose over time (n = 33), platelet count >400 × 10(9) /l (n = 29), patient's request (n = 5), elevated aspartate aminotransferase (n = 3), diarrhea (n = 3), thrombosis (n = 3), and other reasons (n = 4). Of the 49 evaluable patients, 26 patients showed sustained response after discontinuing eltrombopag without additional ITP therapy, with a median follow-up of 9 (range, 6-25) months. These patients were characterized by a median time since ITP diagnosis of 46.5 months, with 4/26 having ITP < 1 year. Eleven patients were male and their median age was 59 years. They received a median of 4 previous treatment lines and 42% were splenectomized. No predictive factors of sustained response after eltrombopag withdrawal were identified. Platelet response following eltrombopag cessation may be sustained in an important percentage of adult primary ITP patients who achieved CR with eltrombopag. However, reliable markers for predicting which patients will have this response are needed.
Assuntos
Benzoatos/administração & dosagem , Eritropoese/efeitos dos fármacos , Hematínicos/administração & dosagem , Hidrazinas/administração & dosagem , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Pirazóis/administração & dosagem , Adulto , Idoso , Plaquetas/efeitos dos fármacos , Plaquetas/patologia , Doença Crônica , Esquema de Medicação , Monitoramento de Medicamentos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Púrpura Trombocitopênica Idiopática/patologia , Púrpura Trombocitopênica Idiopática/cirurgia , Receptores de Trombopoetina/agonistas , Receptores de Trombopoetina/genética , Receptores de Trombopoetina/metabolismo , Recidiva , Indução de Remissão , Estudos Retrospectivos , Esplenectomia , Resultado do TratamentoRESUMO
Eltrombopag is effective and safe in chronic immune thrombocytopenia (ITP) patients not responding to previous therapy. However, when eltrombopag is discontinued, platelet counts usually return to baseline within 2 weeks. Here, we describe the clinical characteristics of the, to the best of our knowledge, largest case series of patients with ITP, who presented sustained responses after discontinuing eltrombopag (n = 12). The median time from diagnosis to eltrombopag initiation was 24 months (range, 1-480). The median number of prior therapies was 5 (range, 1-7), and the median duration of eltrombopag treatment was 5 months (range, 1-13). Three patients received eltrombopag for only 1 month. The treatment was well-tolerated. The median (range) follow-up of this case series was of 7 months (6-20), during which all patients maintained a safe platelet count without the need for anti-ITP treatment. The communication of such cases may support the conduction of new studies to investigate which predictive factors could identify ITP patients with sustained responses after discontinuing eltrombopag without additional therapy. The need of long-term use of eltrombopag should be re-examined.
Assuntos
Benzoatos/administração & dosagem , Hidrazinas/administração & dosagem , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Pirazóis/administração & dosagem , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/diagnóstico , Receptores de Trombopoetina/agonistas , Resultado do TratamentoRESUMO
Thrombopoietin receptor agonists (TPO-Ras; romiplostim/eltrombopag/avatrombopag) have demonstrated high efficacy rates (59-88%) and a good safety profile in clinical trials with adult patients with immune thrombocytopenia (ITP). Similar efficacy and safety results have been observed with romiplostim and eltrombopag in paediatric cohorts. Continuous treatment with TPO-RAs has shown durable responses with long-term use, up to 3 years. The effect of TPO-RAs was generally considered transient, as platelet counts tended to drop to baseline values after a short period of time (about 2 weeks), unless treatment was maintained. Several groups have reported successful discontinuation of TPO-RAs without the need for concomitant treatments. This is referred to as sustained remission off treatment (SROT). Both short- and medium-term treatment with TPO-RAs may reduce costs to our healthcare systems and, more importantly, may reduce the potential side effects that may be associated with continuous TPO-RA treatment. The issue of tapering and discontinuation of TPO-RAs in paediatric patients with ITP has received little attention to date. Given that paediatric ITP has much higher rates of spontaneous remission than ITP in adults, we consider that the possibility of SROT of TPO-RAs in paediatric patients with ITP is a neglected but very relevant issue in this subtype of the disease.
RESUMO
BACKGROUND: Clarkson's disease is a very rare entity characterised by acute episodes of systemic oedema and severe hypotension associated with paraproteinaemia. Its classical treatment relies on methylxanthine combined with terbutaline. Although this prophylactic therapy reduces the mortality rate, relapses are frequent. Eighty percent of patients with Clarkson's disease present with monoclonal gammopathy of unknown significance (MGUS). The risk of progression to multiple myeloma is 1% per year. CASE DESCRIPTION: Here, we present a 49-year-old woman who suffered multiple such episodes requiring treatment in the intensive care unit. Treatment with terbutaline and theophylline was ineffective. She was diagnosed with multiple myeloma (MM) 8 years after the first of these acute episodes. Antimyeloma treatment with bortezomib and dexamethasone was started, followed by autologous haemopoietic transplantation, with no further acute episodes since then. CONCLUSION: Our case is, to our knowledge, unique because eradication of MM was followed by complete disappearance of acute episodes of capillary leakage. Our case report is also the first to support the use of bortezomib and dexamethasone in this setting. Furthermore, autologous peripheral blood progenitor cell transplantation consolidated the MM stringent complete remission achieving a very long progression-free survival (> 11 years) of both MM and Clarkson's disease.