Romiplostim plus danazol as salvage treatment for eltrombopag refractory immune thrombocytopenia: a retrospective pilot study.
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ABSTRACT:
SUBMITTER: Nam CH
PROVIDER: S-EPMC8478612 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Immune thrombocytopenia (ITP) may occur in isolation (primary) or in association with a predisposing condition (secondary ITP [sITP]). Eltrombopag is a well-studied treatment for primary ITP, but evidence is scarce for sITP. We evaluated real-world use of eltrombopag for sITP using electronic health records. Eligible patients had diagnoses of ITP and a qualifying predisposing condition, and eltrombopag treatment. We described patient characteristics, treatment patterns, platelet counts, and thrombotic and bleeding events. We identified 242 eligible patients; the most common predisposing conditions were hepatitis C and systemic lupus erythematosus. Average duration of eltrombopag treatment was 6.1 months. Most (81.4%) patients achieved a platelet count ≥ 30,000/µL at a mean of 0.70 months, 70.2% reached ≥ 50,000/µL at a mean of 0.95 months, and 47.1% achieved a complete response of > 100,000/µL at a mean of 1.43 months after eltrombopag initiation. At eltrombopag discontinuation, 105 patients (43%) experienced a treatment-free period for a mean 3.3 months. Bleeding events occurred with similar frequency before and during eltrombopag treatment whereas thrombotic events were less frequent during eltrombopag treatment. Our results suggest similar rates of platelet response with eltrombopag in patients with sITP as compared with primary ITP. In addition, a treatment-free period is possible for a substantial minority of patients.
| S-EPMC8720735 | biostudies-literature
Project description:Patients with immune thrombocytopenia (ITP) may respond to one thrombopoietin receptor agonist (TPO-RA) but not another. Limited data are available describing outcomes in patients who switched from romiplostim or eltrombopag to avatrombopag, a newer oral TPO-RA. We performed a retrospective observational study of adults with ITP who switched from eltrombopag or romiplostim to avatrombopag at four US tertiary ITP referral centres. Forty-four patients were included, with a mean ITP duration of 8.3 years and a median (range) of four prior ITP treatments. On avatrombopag, 41/44 patients (93%) achieved a platelet response (≥50 × 109 /l) and 38/44 patients (86%) achieved a complete response (≥100 × 109 /l). In all patients, the median platelet count on eltrombopag or romiplostim was 45 × 109 /l vs 114 × 109 /l on avatrombopag (p < 0.0001); in patients switched for ineffectiveness of romiplostim/eltrombopag, it was 28 × 109 /l on romiplostim/eltrombopag vs 88 × 109 /l on avatrombopag (p = 0.025). Fifty-seven percent of patients receiving concomitant ITP medications before switching discontinued them after switching, including 63% of patients receiving chronic corticosteroids. In a heavily pretreated chronic ITP population, avatrombopag was effective following therapy with romiplostim or eltrombopag, with high response rates even in patients with inadequate response to a prior TPO-RA.
| S-EPMC9306832 | biostudies-literature
Project description:In absence of direct comparison randomized controlled trials (RCTs), indirect comparison was conducted to evaluate the efficacy and safety of thrombopoietin-receptor agonists (TPO-RAs) in treatment of adult immune thrombocytopenia (ITP).We searched PubMed, Embase and Cochrane Library, Clinical Trials.gov, China National Knowledge Infrastructure, and Chinese Biomedical Literature Database from their earliest records to May 2017. RCTs comparing the TPO-RAs with placebo in adult ITP were included. Primary outcomes were the overall response rate. Secondary outcomes included safety, durable response, overall or clinically significant bleeding, and the proportion of patients receiving rescue medication.Nine randomized placebo-controlled trials (786 participants) were included in this systematic review. Overall response [Risk Ratio(RR) = 0.59, 95%Confidence Interval(CI): 0.24-1.45], the incidence of adverse events (RR = 0.98, 95%CI: 0.79-1.21), durable response (RR = 0.47, 95%CI: 0.08-2.81), the incidence of overall bleeding (RR = 1.15, 95%CI: 0.52-2.57) and clinically significant bleeding (RR = 1.09, 95%CI: 0.37-3.24), and the proportion of patients receiving rescue treatment (RR = 0.95, 95%CI: 0.47-1.90) were similar between eltrombopag and romiplostim.Eltrombopag and romiplostim might be equivalent in efficacy and safety for adult ITP, however, physicians should still take into account drug cost and comorbidities of the specific patient while making decisions on the treatment of ITP with TPO-RAs.PROSPERO International Prospective Register of Systematic Review (PROSPERO 2017: CRD42017068661).
| S-EPMC5983520 | biostudies-other
Project description:Immune thrombocytopenia (ITP) is a bleeding disorder caused by a decrease in platelet count resulting from increased destruction and insufficient production of platelets. Although impaired regulatory T-lymphocyte activity plays a critical role in platelet destruction, many other immunologic abnormalities are also likely to be involved. Importantly, patients with ITP appear to have defects in a thrombopoietin-mediated physiological mechanism that compensates for a decrease in platelet count by increasing platelet production. Thus, simultaneous treatment of multiple pathogenic pathways involved in ITP could potentially result in synergistic efficacy. While conventional treatments for ITP suppress or modulate the immune system to reduce platelet destruction, a unique class of ITP therapy, namely thrombopoietin receptor agonists (TPO-RAs), improves platelet production by activating the thrombopoietin pathway. As hypothesized, preliminary studies show that combinations of eltrombopag, an oral TPO-RA, with conventional treatments improve outcomes in both newly diagnosed and refractory patients. In this review, the clinical experience with eltrombopag-based combinations in patients with ITP is summarized and the implications of the available data are discussed.
| S-EPMC6187430 | biostudies-literature
Project description:In absence of direct comparison, we conducted an indirect-comparison meta-analysis to evaluate the efficacy and safety of thrombopoietin-receptor agonists(TPO-RAs) in treatment of pediatric persistent or chronic immune thrombocytopenia(ITP). PubMed, Embase, Cochrane Library, Clinical Trials.gov, China National Knowledge Infrastructure, and Chinese Biomedical Literature Database were searched from their earliest records to May 2017. Randomized controlled trials comparing the TPO-RAs with placebo in pediatric ITP were included. Outcomes included overall response rate(primary), durable response, overall or clinically significant bleeding, the proportion of patients receiving rescue medication, and safety. Five randomized placebo-controlled studies(N = 261) were analyzed. The overall response[Risk Ratio(RR) 0.57, 95% confidence interval(CI) 0.21-1.56], the incidence of adverse events (RR 0.96, 95%CI 0.66-1.39), durable response(RR 2.48, 95%CI 0.31-19.97), and the proportion of patients receiving rescue treatment(RR 0.73, 95%CI 0.20-2.73) were similar between eltrombopag and romiplostim group. Nevertheless, eltrombopag might have lower risk of overall bleeding(RR 0.43, 95%CI 0.23-0.80) and clinically significant bleeding(RR 0.33, 95%CI 0.12-0.89) than romiplostim. This meta-analysis suggests that eltrombopag might be similar to romiplostim in efficacy and safety, but seems to reduce the risk of bleeding compared to romiplostim. Furthermore, cost of the treatment, comorbidity of patients and drug compliance should also be considered in clinical decision making.
| S-EPMC5766584 | biostudies-literature
Project description:"Immune thrombocytopenia" (ITP) is an autoimmune disorder that leads to peripheral destruction, as well as a decreased production of platelets. ITP most commonly presents as mild mucocutaneous bleeding. Though it is rare, the leading cause of mortality in persons with ITP is intracranial hemorrhage and those that do not respond to therapy are at increased risk. Our understanding of the pathophysiology of ITP has evolved immensely, especially over the last 60 years. The discovery of the platelet-production stimulator, thrombopoietin (TPO), lent clarity to an earlier hypothesis that inhibition of platelet production at the level of the megakaryocyte, at least in part, accounts for thrombocytopenia in adults with ITP. This facilitated the development of TPO-based therapies to treat ITP. Thrombopoietin receptor agonists are one of the most recent treatments to enter the landscape. Original production of a recombinant human TPO was halted after clinical trials revealed the untoward effect of autoantibodies to the recombinant human TPO with cross-reactivity to endogenous TPO. Next-step development focused on stimulation of the TPO receptor with fewer immunogenic agents. Currently, two such thrombopoietin receptor agonists, romiplostim and eltrombopag, are licensed in the USA to treat thrombocytopenia in adults with persistent or chronic ITP. Ongoing research will assess their efficacy in other immune-mediated and nonimmune-mediated primary and secondary thrombocytopenias.
| S-EPMC4304598 | biostudies-other
Project description:Immune thrombocytopenia (ITP) in dogs is analogous to that in humans. Romiplostim, a novel thrombopoietin receptor (TPO-R) agonist, is currently used for the treatment of refractory ITP in humans, but not in dogs. Here, we describe the response to romiplostim in five dogs with refractory ITP. Five dogs with severe and refractory ITP (three primary and two secondary) received romiplostim subcutaneously. Four dogs were administered 3-5 ?g/kg and one dog received 10-13 ?g/kg body weight once weekly.Romiplostim was well-tolerated and administration was associated with an increase in platelet counts in all five dogs. Four of the five dogs entered remission and relapses were not observed over a follow-up period of 3-10 months.Romiplostim is effective in the treatment of ITP in dogs at least as well as in humans. This finding may help to develop and use new therapeutics for ITP in dogs and humans.
| S-EPMC4901510 | biostudies-literature
Project description:Thrombocytopenia, anasarca, fever, reticulin fibrosis, organomegaly (TAFRO) syndrome is a unique clinicopathologic subtype of multicentric Castleman's disease that has recently been identified in Japan. However, little is known about its renal histological changes and the optimal treatment for TAFRO syndrome. An 80-year-old Japanese woman was admitted to our hospital for evaluation of severe anasarca and weight gain (10 kg in a month). She had polyneuropathy, monoclonal plasma cell proliferative disorder with positive kappa M-protein, a sclerotic bone lesion, elevation of vascular endothelial growth factor (VEGF), skin changes, and extravascular volume overload, which fulfilled the diagnostic criteria for POEMS (polyneuropathy, organomegaly, endocrinopathy, and monoclonal protein, skin changes) syndrome. However, kappa-type M-protein and thrombocytopenia with positivity of platelet-associated immunoglobulin G antibody were unusual, and fitted the diagnostic criteria for TAFRO syndrome. Renal biopsy showed diffuse endocapillary proliferative glomerulonephritis with endothelial swelling and the infiltration of monocytes and neutrophils without specific immunoglobulin deposits. Her systemic symptoms were refractory to initial treatment with high-dose melphalan and glucocorticoids. Alternative therapy with an anti-interleukin-6 (IL-6) receptor antibody (tocilizumab) effectively controlled the symptoms, while a thrombopoietin receptor agonist (romiplostim) was effective for her thrombocytopenia. Results suggest that IL-6-VEGF axis and an autoimmune mechanism may be responsible for TAFRO syndrome with clinical features of POEMS and refractory thrombocytopenia, which can be successfully treated with combination of tocilizumab and romiplostim.
| S-EPMC5886949 | biostudies-literature
Project description:There are no standard treatments to prevent or hasten the recovery from severe conditioning-regimen-induced thrombocytopenia occurring after autologous hematopoietic cell transplantation (auto-HCT). We conducted an open-label, single-arm pilot study of romiplostim, a thrombopoietin receptor agonist, to enhance platelet recovery in patients with multiple myeloma or lymphoma undergoing auto-HCT. All patients were treated weekly with romiplostim starting day +1 after auto-HCT until the platelet count was >50 × 109/L without transfusion. Compared with contemporary retrospective data from romiplostim-naïve patients (N = 853), romiplostim-treated patients (N = 59) had a similar median number of days of grade 4 thrombocytopenia or days requiring transfusions, time to platelet engraftment, and number of platelets transfusions during the auto-HCT. However, romiplostim-treated patients had enhanced platelet recovery to normal values beginning at approximately day +15. In matched cohort multivariable analyses, romiplostim treatment was associated with higher platelet counts by an average of 40 × 109/L (95% confidence interval (CI) (14, 67), P = .003) and 118 × 109/L (95% CI [84, 152], P<.001) at days +21 and +30, respectively, compared with those of no romiplostim. Only 1 adverse event was deemed possibly attributable to romiplostim: a low-risk pulmonary embolism in a patient with multiple myeloma. In conclusion, romiplostim showed promising activity and safety after auto-HCT, but the improvement in platelet counts occurred later than the goal of shortening the duration and depth of the platelet nadir. This trial was registered at www.clinicaltrials.gov (#NCT04478123).
| S-EPMC10130608 | biostudies-literature
Project description:Immune thrombocytopenia (ITP) is an autoimmune disorder that induces a decrease in the number of circulating platelets due to spleen destruction and inability of megakaryocytes to restore normal counts. Immunosuppressive therapy with glucocorticoid drugs constitutes the first line of treatment. However, lack of response to these agents is not uncommon, and the management of refractory patients is a matter of controversy. In fact, day-to-day clinical practice shows that, in spite of the current guidelines, splenectomy, which is currently considered a suitable second-choice therapy, is being replaced by treatment with thrombopoietin receptor agonists. These boost platelet production by megakaryocytes. The use of one of these, namely eltrombopag, has been permitted for ITP patients refractory to first-line drugs or splenectomy, for the last 10 years. This review summarizes the experience reported using eltrombopag in ITP, paying attention to efficacy and safety. Results from clinical trials will be discussed, and studies performed in the course of daily clinical practice will also be reviewed, as these are useful to assess the potential of the drug in real-world settings. The management of adverse events and the use of eltrombopag in particular situations will also be covered. The experience reported so far permits us to suggest that eltrombopag efficiently induces recovery of platelet counts. Furthermore, recent papers have demonstrated that a sustained response after discontinuation, initially thought to be problematic, may be possible in a nonnegligible number of cases. The safety profile is satisfactory, although patients presenting with thromboembolism risk factors should be treated with caution until the eltrombopag-associated prothrombotic risk is fully established. In summary, although larger studies are still needed to clarify some issues, eltrombopag may be a useful alternative tool for ITP patients refractory to conventional medical management or splenectomy.
| S-EPMC5971401 | biostudies-literature