Romiplostim safety and efficacy for immune thrombocytopenia in clinical practice: 2-year results of 72 adults in a romiplostim compassionate-use program

Khellaf, Mehdi; Michel, Marc; Quittet, Philippe; Viallard, Jean‐François; Alexis, Magda; Roudot‐Thoraval, Françoise; Chèze, Stéphane; Durand, J.M.; Lefrère, François; Galicier, Lionel; Lambotte, Olivier; Panelatti, G.; Slama, Borhane; Damaj, Gandhi; Sébahoun, G; Gyan, Emmanuel; Delbrel, X.; Dhédin, Nathalie; Royer, Bruno; Schleinitz, N.; Rossi, Jean‐François; Mahévas, Matthieu; Languille, Laetitia; Bierling, Philippe; Godeau, Bertrand

doi:10.1182/blood-2011-03-340166

Cited by 102 publications

(102 citation statements)

References 18 publications

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Section: Discussionsupporting

confidence: 90%

“…However, a French study conducted on unselected patients showed that, after two years of follow up, 35% of the patients had to stop romiplostim, mainly because of inefficacy. 21 In agreement with this, our present results showed that the lack of response was the main reason that led physicians to consider switching the TPO-RA.Romiplostim and eltrombopag stimulate the TPO-R but some differences related to molecular structure and pharmacokinetic characteristics could explain their different response patterns: romiplostim is a peptibody that is injected subcutaneously, 25 while eltrombopag is a small molecule taken orally. 26 To date, no pharmacokinetic studRomiplostim/eltrombopag switching for ITP haematologica | 2013; 98(6) 883 is not yet possible to draw definitive conclusions concerning TPO-RA efficacy or to ascertain if one of the 2 available agonists is superior to the other.…”

supporting

confidence: 85%

“…21 Because romiplostim and eltrombopag bind to different sites on the TPO-R and the 2 molecules have not yet been directly compared, the relevance of switching from one TPO-RA to the other in clinical practice has not been A retrospective pilot evaluation of switching thrombopoietic receptor-agonists in immune thrombocytopenia Mehdi Khellaf, 1 Jean-François Viallard, 2 Mohamed Hamidou, 3 Stéphane Cheze, 4 Françoise Roudot-Thoraval, 5 François Lefrere, 6 Olivier Fain, 7 Sylvain Audia, 8 Jean-François Abgrall, 9 Jean-Marie Michot, 10 Charles Dauriac, 11 Sophie Lefort, 12 Emmanuel Gyan, 13 Mathilde Niault, 14 Jean-Marc Durand, 15 Laetitia Languille, 1 David Boutboul, 16 Philippe Bierling, 17 Marc Michel, 1 and Bertrand Godeau…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, one cannot be certain that these patients were fully resistant to romiplostim. 17,19,21 On the other hand, 4patients who switched to eltrombopag received another treatment line after stopping romiplostim and a synergistic effect with subsequent eltrombopag use cannot be excluded.A matter of concern about use of TPO-RA for both physicians and patients is the occurrence of significant and sometimes unexpected platelet-count fluctuations necessitating recourse to rescue therapy and/or to the reduction, transient withdrawal or increase of the TPO-RA dose, thereby running the risk of rebound thrombocytopenia and bleeding or thrombocytosis. In our study, only romiplostim-treated patients were switched for this reason, suggesting that this problem is mainly observed with this agent.…”

mentioning

confidence: 99%

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A retrospective pilot evaluation of switching thrombopoietic receptor-agonists in immune thrombocytopenia

et al. 2013

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Romiplostim and eltrombopag, the first thrombopoietic receptor-agonists with demonstrated efficacy against immune thrombocytopenia in prospective controlled studies, were recently authorized in most countries for adults with chronic immune thrombocytopenia. So far, no data are available about the potential contribution of switching from romiplostim to eltrombopag or vice versa in terms of efficacy or tolerance. Efficacies and tolerance profiles were evaluated for 46 patients who sequentially received both drugs, switching from one to the other. The reasons for switching were: lack of efficacy for 23 patients, platelet-count fluctuations for 11, side effects for 4, and 8 patients' preferences. For 50-80% of the patients, switching from romiplostim to eltrombopag or eltrombopag to romiplostim effectively impacted the platelet count, with fluctuations disappearing in 54% and side effects resolved in 100%. In 80% of the patients, the 2 thrombopoietic receptor-agonists achieved similar response patterns. Our results confirmed that switching from one thrombopoietic receptor-agonist to the other could be beneficial in clinical practice for patients with severe chronic immune thrombopenia who failed to respond or experienced adverse events to the first. (Clinical Trials.gov identifier: NCT01618734). A retrospective pilot evaluation of switching thrombopoietic receptor-agonists in immune thrombocytopenia Design and Methods PatientsAll patients followed by specialists in the network of National ITP Referral Centers who have been sequentially treated with the TPO-RAs, romiplostim and eltrombopag, were enrolled. Inclusion criteria were: 1) age 18 years or over; 2) primary ITP diagnosed according to the current definitions; 4,22 3) previous romiplostim and eltrombopag treatment, regardless of the switching sequence, with at least three months of follow up with each molecule. Patients treated for secondary ITP were excluded.The trial protocol was approved by the Henri-Mondor University Hospital Institutional Review Board and Ethics Committee; all patients received a written information form before screening and data analysis. Treatment designAccording to the European Medicines Agency authorization of the 2 TPO-RAs, patients received a weekly subcutaneous injection of romiplostim, usually started at 1 mg/kg/week, or daily oral eltrombopag, at a starting dose of 50 mg/day; the dose was then adjusted, as needed (up to a maximum 10 mg/kg/week and 75 mg/day, respectively) based on the patient's platelet count.Patients could continue to receive concurrent ITP therapies, including rescue interventions, defined as any agent administered to transiently increase the platelet count, e.g. IVIg, corticosteroids, anti-IgD and/or platelet transfusions. The need to increase the dose of concurrent ITP medication to levels above those used at baseline was also considered a rescue intervention. Assessments and outcome measuresThe following characteristics were recorded on a standardized form by the same investigator (MK): age, gender; and ITP ...

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Section: Discussionsupporting

confidence: 90%

supporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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A retrospective pilot evaluation of switching thrombopoietic receptor-agonists in immune thrombocytopenia

et al. 2013

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“…In a single retrospective, nationwide, open access, compassionate use study of romiplostim in France in 72 adults with primary ITP , 54% splenectomized, after a follow-up up to 2 years in 45/72 (62%) only 2 patients (2.8%) aged greater than 70 years with cardiovascular risk factors had transient ischemic attack without sequelae at platelet count less than 100 3 10 9 /L [37]. A disproportionality analysis to compare adverse drug reaction of romiplostim and eltrombopag conducted by Moulis et al using the French PharmacoVigilance Database failed to show any signal for an excess risk of thrombosis of one TPO-ra versus the other (odds ratio of romiplostim vs. eltrombopag: 1.45; 95% CI: 0.48-4.45) [38].…”

Section: Thrombotic Risk and Tpomentioning

confidence: 99%

Is ITP a thrombophilic disorder?

2015

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Immune thrombocytopenia (ITP) represents the epitome of acquired bleeding diseases for the hematologist. Stemming from the interest for the safety of thrombopoietin‐receptor agonists (TPO‐ra) romiplostim and eltrombopag, recent data have investigated if thrombotic risk is also increased in this disorder. In patients not treated with TPO‐ra, a slightly higher risk of venous thrombosis (VTE) is consistently found in ITP, but not to a rate demanding special attention in the generality of cases. No significant increase of arterial thrombosis (AT) is apparent. However, age, splenectomy, and personal risk factors may put some ITP patient to a particularly higher risk of venous and arterial thrombosis (three to four times higher than the average subject). Patients exposed to TPO‐ra present indirect evidence of a much higher risk of both AT and VTE. Unfortunately, no matched control population is available and the prospective and registrative nature of these studies may have emphasized the incidence of thrombosis, which was recorded as adverse event. The clinician should be able to individualize the best treatment for the patient, taking also into account the thrombotic risk, limiting active treatment of ITP to those patients really at risk of bleeding. Am. J. Hematol. 91:39–45, 2016. © 2015 Wiley Periodicals, Inc.

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Thrombopoietin receptor agonists in the treatment of immune thrombocytopenia: A clinician's perspective

Ruggeri

2012

American J Hematol

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Romiplostim safety and efficacy for immune thrombocytopenia in clinical practice: 2-year results of 72 adults in a romiplostim compassionate-use program

Cited by 102 publications

References 18 publications

A retrospective pilot evaluation of switching thrombopoietic receptor-agonists in immune thrombocytopenia

A retrospective pilot evaluation of switching thrombopoietic receptor-agonists in immune thrombocytopenia

Is ITP a thrombophilic disorder?

Thrombopoietin receptor agonists in the treatment of immune thrombocytopenia: A clinician's perspective

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