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Eltrombopag provides long-term disease control in immune thrombocytopenia
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Adults with chronic or persistent immune thrombocytopenia maintained ideal platelet counts and decreased bleeding rate after treatment with eltrombopag, according to long-term efficacy data from the EXTEND trial.
“[The data] validate [eltrombopag] as an important oral treatment option that, by often increasing platelet counts, significantly decreased bleeding rates and reduced the need for concurrent therapies [among] certain patients with chronic/persistent immune thrombocytopenia,” James B. Bussel, MD, professor emeritus of pediatrics at Weill Cornell Medicine, said in a press release. “With this information, physicians can better optimize long-term disease management for appropriate patients living with this chronic disease.”
Treatment for immune thrombocytopenia is individualized based upon platelet count and bleeding frequency. Eltrombopag (Promacta, Novartis) — an oral thrombopoietin receptor — is approved for patients aged older than 1 year.
Previous 6-week and 6-month placebo-controlled studies showed eltrombopag decreased bleeding and increased platelets for up to 80% of previously treated patients with thrombocytopenia. However, serious adverse events can occur.
The EXTEND trial — an open-label extension study of four trials investigating eltrombopag for the treatment of immune thrombocytopenia — evaluated long-term safety and efficacy.
Researchers enrolled 302 patients who had thrombocytopenia for at least 6 months, demonstrated insufficient response to at least one prior therapy, and had platelet counts less than 30 × 109/L.
Investigators conducted the study in four stages.
In the first stage, patients received 50 mg once daily. Doses later were adjusted to levels that increased platelet counts to 100 × 109/L or more.
In the second stage, patients reduced use of or stopped concomitant immune thrombocytopenia medications while maintaining platelet count of at least 50 × 109/L or more with eltrombopag.
In the third stage, patients adjusted the dose of eltrombopag to find the minimal amount necessary to maintain platelet counts of at least 50 × 109/L in conjunction with minimal concomitant immune thrombocytopenia medication.
In the fourth stage, researchers assessed efficacy and safety of eltrombopag at the minimal effective dose, with or without the minimal dose of any concomitant medication, that maintained platelet counts of at least 50 × 109/L.
Results of clinical laboratory tests, ocular examinations and frequency of adverse events served as the primary endpoints.
Secondary endpoints included:
The number of patients with platelet count thresholds of 50 × 109/L and 30 × 109/L during therapy;
Maximum continuous duration of elevated platelet count of 50 × 109/L or 30 × 109/L;
Reduced or sparing of concomitant therapies while maintaining platelet count of 50 × 109/L; and
Incidence and severity of symptoms associated with disease using WHO bleeding scale and ITP Bleeding Score.
Forty-five percent of enrolled patients (n = 135) completed the study; of these patients, 59% received treatment for at least 2 years and 35% received treatment for at least 3 years. Fourteen percent of patients withdrew from the study due to adverse events and 11% withdrew due to lack of efficacy.
Median duration of eltrombopag treatment was 2.37 years (range, 2 days-8.76 years).
At 2 weeks, median platelet counts increased to 50 × 109/L or more and were sustained throughout the treatment period.
Overall, 259 patients achieved a platelet count of 50 × 109/L at least once without rescue treatment. Further, 133 of 257 patients achieved a continuous platelet count for 25 weeks or longer.
Patients who had platelet counts lower than 15 × 109/L, those who underwent more previous therapies and those who underwent splenectomy tended to have lower response rates.
Thirty-four of 101 patients who received concomitant immune thrombocytopenia medication discontinued one or more medications.
Bleeding symptoms according to WHO, bleeding scale decreased from 57% at baseline to 16% at 1 year. Bleeding rates decreased among splenectomized and nonsplenectomized patients. Researchers observed grade 3 bleeding among 19 patients and grade 4 bleeding among one patient.
Approximately one-quarter of patients (26%) reported grade 3 adverse events and 6% reported grade 4 adverse events.
The most common adverse events included hepatobiliary adverse events (n = 7), cataracts (n = 4), deep vein thrombosis (n = 3), cerebral infarction (n = 2), headache (n = 2) and myelofibrosis (n = 2).
Thromboembolic events (6%) and hepatobiliary events (15%) did not increase with treatment duration past 1 year. – by Melinda Stevens
Disclosures: Bussell reports consultant, advisory or speakers bureau roles with Amgen, GlaxoSmithKline, Momenta Pharmaceuticals, Novartis, Physicians Education Resource, Prophylix Pharma, Protalex and Rigel Pharmaceuticals; research funding from Amgen, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Prophylix Pharma, Protalex and Rigel Pharmaceuticals; and royalty fees from UpToDate. Please see the full study for a list of all other authors’ relevant financial disclosures.
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