Summary 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.
Anti-beta-2 glycoprotein I antibodies (anti-B2GPI) are often cited as the major pathogenically relevant antibody in antiphospholipid syndrome (APS), but it is unclear if there is clinical evidence to support this theory. We performed a systematic review to determine if IgG anti-B2GPI positivity was independently associated with thrombotic and/or obstetric manifestations of APS. We searched MEDLINE, EMBASE, The Cochrane Library, and ClinicalTrials.gov electronic databases through April 2020 for prospective studies that met pre-specified design criteria. Of 4758 articles identified through computer-assisted search, 4 studies examining obstetric outcomes and 2 studies examining thrombotic outcomes were included for qualitative assessment. The presence of anti-B2GPI had only a weak independent association with thrombosis and was, at best, inconsistently associated with obstetric complications. A quantitative assessment could not be performed due to study heterogeneity. The overall quality of the evidence was very low. Although anti-B2GPI are commonly thought to mediate APS manifestations, clinical evidence is lacking with very low-quality data to support a weak association with thrombosis.
BACKGROUND : Thrombopoietin receptor agonists (TPO-RAs) are widely utilized second-line treatments for immune thrombocytopenia (ITP). The TPO-RAs eltrombopag and romiplostim have been FDA approved for over a decade with established efficacy and safety profiles. Avatrombopag is a newer oral TPO-RA approved in 2019 for ITP. Avatrombopag was efficacious in raising platelet counts in clinical trials, and it has an exposure-adjusted safety profile generally comparable to placebo with no boxed warning for hepatotoxicity as does eltrombopag. Also unlike eltrombopag, avatrombopag does not chelate polyvalent cations; therefore, it is administered with food and without restrictions regarding meal composition. A high proportion of patients (~90%) respond to avatrombopag; however, data describing the durability of platelet response on avatrombopag following treatment with other TPO-RAs is limited. AIMS : Understand the time until patients treated with avatrombopag experienced their first loss of response, if any, and their percent of time with a response following switch from eltrombopag or romiplostim. METHODS : We retrospectively evaluated all adults with ITP who switched from eltrombopag or romiplostim to avatrombopag at four U.S. tertiary ITP referral centers from July 2019 through December 2020. Reason for switching from eltrombopag or romiplostim (ineffectiveness, adverse event, convenience) was collected. Patients were treated with avatrombopag for at least two months to evaluate effectiveness. Response was defined as a platelet count ≥30,000/uL. Loss of response was defined as two consecutive platelet counts at least 7 days apart <30,000/uL. In these analyses, platelet counts were disqualified if <8 weeks from receipt of rescue corticosteroids or <4 weeks from intravenous immunoglobulin. RESULTS: 44 patients were included, with a median (range) age of 60 (21-87) years; 55% were female. At avatrombopag initiation, patients had an ITP diagnosis for a mean of 8.1 years with a mean of 4.8 unique prior ITP therapies. 42/44 (95%) of patients responded to avatrombopag at least once and 36/44 (81.8%) responded without the need for rescue therapy. 6/44 (13.6%) responded to avatrombopag and required at least one rescue therapy during exposure. 31/42 (73.8%) of patients never experienced a loss of response. All patients who responded to avatrombopag maintained response for 88.7% of their time on treatment. Patients who responded without the need for rescue therapy maintained their response for 93.6% of their time on avatrombopag. Patients who switched for convenience maintained a response for 96.5% of the time on avatrombopag. Patients who switched for adverse events maintained a response for 90.2% of the time. Patients who switched for efficacy maintained a response for 68.2% of the time. Overall, the median platelet count for all avatrombopag exposure was 107×10 9/L. The median platelet count for convenience switchers was 129×10 9/L, efficacy switchers was 60×10 9/L, and adverse event switchers was 93×10 9/L. CONCLUSION: In a heavily pretreated chronic ITP population who switched from another TPO-RA to avatrombopag, the initial response to avatrombopag was both durable (with up to 74% of patients never experiencing a loss of response) and stable (with patients maintaining a response on average for up to 89% of the time). Figure 1 Figure 1. Disclosures Al-Samkari: Argenx: Consultancy; Dova/Sobi: Consultancy, Research Funding; Novartis: Consultancy; Amgen: Research Funding; Rigel: Consultancy; Agios: Consultancy, Research Funding; Moderna: Consultancy. Gernsheimer: Principia: Research Funding; Rigel: Research Funding; Amgen: Honoraria; Novartis: Honoraria; Cellphire: Consultancy; Dova: Consultancy; Sanofi: Consultancy. Liebman: Pfizer: Consultancy; Dova: Consultancy, Honoraria; Argenx: Research Funding; Amgen: Consultancy; Sanofi/Genzyme: Research Funding; Novartis: Consultancy, Research Funding. Lee: Dova: Honoraria. Bernheisel: Sobi, Inc.: Current Employment. Kolodny: Sobi, Inc.: Current Employment. Wojdyla: Sobi, Inc.: Current Employment. Vredenburg: Sobi, Inc.: Current Employment. Jamieson: Sobi, Inc.: Current Employment. Cuker: Takeda: Research Funding; Sanofi: Research Funding; Spark Therapeutics: Research Funding; Pfizer: Research Funding; Novo Nordisk: Research Funding; Novartis: Research Funding; Bayer: Research Funding; Alexion: Research Funding; UpToDate: Patents & Royalties; Synergy: Consultancy.
LEARNING OBJECTIVES• Recognize the dif fer ent strat e gies to pre vent and man age severe alloimmune plate let refrac to ri ness • Understand when to sus pect and how to diag nose alloimmune plate let refrac to ri ness CLINICAL CASEA 35 -year -old woman from Mexico with idi o pathic aplastic ane mia receives leu ko cyte -reduced apher e sis plate lets for a plate let count of 8 × 10 9 / L. A 30 -min ute post trans fusion plate let count is 9 × 10 9 / L. There is no change after a sec ond unit of apher e sis plate lets. Recent abdom i nal imag ing shows no spleno meg aly. The patient has been preg nant 4 times and has received non -leukoreduced blood prod ucts in her home coun try. She dem on strates no signs or symp toms of bleed ing. A human leu ko cyte anti gen (HLA) anti body screen reveals a cal cu lated panelreac tive anti body (cPRA) of 100 % . The blood bank is notifi ed and low -res o lu tion HLA typ ing is requested.
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