Anemia, Aplastic
Conditions
Keywords
Eltrombopag, Effectiveness, Safety, Treatment patterns
Brief summary
The main goal of this study was to investigate the effectiveness and safety of eltrombopag (ETB) when compared to other treatments in Japanese aplastic anemia (AA) patients using data from the Medical Data Vision (MDV) hospital-based database.
Interventions
None listed
Sponsors
Novartis Pharmaceuticals
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
15 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
Inclusion and
Exclusion criteria
for the safety population: Inclusion criteria: * Patients with: * At least one confirmed diagnosis of AA registered during the baseline period, or * At least one confirmed diagnosis of idiopathic thrombocytopenic purpura (International Classification of Diseases, 10th Revision \[ICD10\] code: D69.3) registered before the index date and at least one confirmed diagnosis of AA during the follow-up period. * Had at least 6 months of continuous enrolment prior to the index date. Confirmed diagnosis was defined as having ≥1 inpatient or ≥2 outpatient claims with a relevant ICD-10 code and without any doubtful flag. Continuous enrolment (being continuously followed in the database) was defined as having at least one claim every semester.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Probability of Achieving Hematologic Response by AA Treatment Category | Month 6, Years 1, 2, and up to approximately 3 years | The Kaplan-Meier analysis technique was used to estimate probability. Hematologic response was defined as the first occurrence of an 8-week period without any transfusion procedure. Treatment categories included: * CSA alone * CSA + ETB * ETB alone * ATG + CSA * ATG + CSA + ETB |
| Probability of Achieving Hematologic Response by ETB Dose Density | Month 6, Years 1, 2, and up to approximately 3 years | The Kaplan-Meier analysis technique was used to estimate probability. Hematologic response was defined as the first occurrence of an 8-week period without any transfusion procedure. ETB dose density was defined as the dosage of ETB divided by the duration to maximum dose: * Optimal dose-density: 62.5 milligrams (mg) or more mg/8 weeks, * Suboptimal dose-density: 25.1-62.4 mg/8 weeks, * Minimum dose: 25 mg or less/8weeks. |
| Time to Achieve First Hematologic Response by AA Treatment Category | Up to approximately 3 years | Time to hematologic response was defined as the number of days from the index date + 28 days to the first hematologic response. The index date was defined as the date of the first prescription of the following AA treatments: ATG, CSA, ETB or ROM. Event-free patients were censored at the earliest record of any of the following: death, end of the database registration, or end of the study. Treatment categories included: * CSA alone * CSA + ETB * ETB alone * ATG + CSA * ATG + CSA + ETB |
| Time to Achieve First Hematologic Response by ETB Dose Density | Up to approximately 3 years | Time to hematologic response was defined as the number of days from the index date + 28 days to the first hematologic response. The index date was defined as the date of the first prescription of the following AA treatments: ATG, CSA, ETB or ROM. Event-free patients were censored at the earliest record of any of the following: death, end of the database registration, end of the study. ETB dose density was defined as the dosage of ETB divided by the duration to maximum dose: * Optimal dose-density: 62.5 mg or more mg/8 weeks, * Suboptimal dose-density: 25.1-62.4 mg/8 weeks, * Minimum dose: 25 mg or less/8weeks. |
| Percentage of Patients who Achieved Hematologic Response by Treatment Category | Months 3 and 6 | Hematologic response was defined as the first occurrence of an 8-week period without any transfusion procedure. Treatment categories included: * CSA alone * CSA + ETB * ETB alone * ATG + CSA * ATG + CSA + ETB |
| Cox Proportional Hazard Ratio for the Association Between Hematologic Response and Patient Characteristics | Up to approximately 3 years | Patient characteristics included age, body mass index (BMI), treatment category (CSA+ETB vs CSA and ETB vs CSA), gender, comorbidity, medications received (antibiotics, anti-inflammatory drugs, anticonvulsants, antipsychotics), and bone marrow conditioning received before bone marrow transplant (BMT). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Amount of Blood and Plasma Transfused | Up to approximately 7 months | — |
| Percentage of Patients With at Least One Transfusion of 400 Milliliters (mL) or More of red Blood Cells | Up to approximately 8 weeks | — |
| Percentage of Patients who Achieved Complete Response (CR) | Month 6 | CR was defined as hemoglobin \>100 grams per liter (g/L) and neutrophils \>1.0x10\^9/L and platelets \>100x10\^9/L. |
| Percentage of Patients who Achieved Partial Response (PR) | Month 6 | PR was defined as no longer meeting severe AA criteria, transfusion independence, hemoglobin \>8 grams per deciliter (gr/dL) and neutrophils \>0.5x10\^9/L and platelets \>20x10\^9/L. |
| Percentage of Patients who Achieved Overall Response | Month 6 | Overall response was defined as having CR or PR. CR was defined as hemoglobin \>100 g/L and neutrophils \>1.0x10\^9/L and platelets \>100x10\^9/L. PR was defined as no longer meeting severe AA criteria, transfusion independence, hemoglobin \>8 gr/dL and neutrophils \>0.5x10\^9/L and platelets \>20x10\^9/L. |
| Probability of Achieving an Effectiveness Event by Treatment Category | Month 6, Years 1, 2, and up to approximately 3 years | The Kaplan-Meier analysis technique was used to estimate probability. Effectiveness events included death, treatment discontinuation, relapse, BMT, bleeding, bleeding requiring transfusion, bleeding requiring a treatment, and infection. Treatment categories included: * CSA alone * CSA + ETB * ETB alone * ATG + CSA * ATG + CSA + ETB |
| Probability of Achieving an Effectiveness Event by ETB Dose Density | Month 6, Years 1, 2, and up to approximately 3 years | The Kaplan-Meier analysis technique was used to estimate probability. Effectiveness events included death, treatment discontinuation, relapse, BMT, bleeding, bleeding requiring transfusion, bleeding requiring a treatment, and infection. ETB dose density was defined as the dosage of ETB divided by the duration to maximum dose: * Optimal dose-density: 62.5 mg or more mg/8 weeks, * Suboptimal dose-density: 25.1-62.4 mg/8 weeks, * Minimum dose: 25 mg or less/8weeks. |
| Number of Patients per Demographic Category | Baseline | Demographics included: * Age category * Gender * BMI * Most frequent comorbidities * Most frequent medications received |
| Time to Achieve an Effectiveness Event by ETB Dose Density | Up to approximately 3 years | Time to an effectiveness event was defined as the number of days from the index date + 28 days until the earliest record of an event of interest. The index date was defined as the date of the first prescription of the following AA treatments: ATG, CSA, ETB or ROM. Event-free patients were censored at the earliest record of any of the following: death, end of follow-up, or end of the study. Effectiveness events included death, treatment discontinuation, relapse, BMT, bleeding, bleeding requiring transfusion, bleeding requiring a treatment, and infection. ETB dose density was defined as the dosage of ETB divided by the duration to maximum dose: * Optimal dose-density: 62.5 mg or more mg/8 weeks, * Suboptimal dose-density: 25.1-62.4 mg/8 weeks, * Minimum dose: 25 mg or less/8weeks. |
| Number of Patients who Received First Line Treatment by Type of Treatment Received | Up to approximately 3 years | — |
| Number of Patients who Received Second Line Treatment by Type of Treatment Received | Up to approximately 3 years | — |
| Number of Patients who Received Third Line Treatment by Type of Treatment Received | Up to approximately 3 years | — |
| Probability of Having a Safety Event by Treatment Category | Month 6, and Years 1, 2, and 5 | The Kaplan-Meier analysis technique was used to estimate probability. Safety events included diabetes, hepatotoxicity event, hypertension event, thromboembolic event, transformation to myelodysplastic syndrome (MDS), AML, CMML or other leukemia, and transformation to paroxysmal nocturnal hemoglobinuria (PNH). Treatment categories included: * CSA alone * CSA + ETB * ETB alone * ATG + CSA * ATG + CSA + ETB |
| Time to Having a Safety Event by Treatment Category | Up to approximately 9 years | Time to each safety event was defined as the number of days from the index date until the earliest record of the event of interest. The index date was defined as the date of the first prescription of the following AA treatments: ATG, CSA, ETB or ROM. Event-free patients were censored at the earliest record of any of the following: death, end of follow-up, or end of the study. Safety events included diabetes, hepatotoxicity event, hypertension event, thromboembolic event, transformation to MDS, AML, CMML or other leukemia, and transformation to PNH. Treatment categories included: * CSA alone * CSA + ETB * ETB alone * ATG + CSA * ATG + CSA + ETB |
| Time to Achieve an Effectiveness Event by Treatment Category | Up to approximately 3 years | Time to an effectiveness event was defined as the number of days from the index date + 28 days until the earliest record of an event of interest. The index date was defined as the date of the first prescription of the following AA treatments: ATG, CSA, ETB or ROM. Event-free patients were censored at the earliest record of any of the following: death, end of follow-up, or end of the study. Effectiveness events included death, treatment discontinuation, relapse, BMT, bleeding, bleeding requiring transfusion, bleeding requiring a treatment, and infection. Treatment categories included: * CSA alone * CSA + ETB * ETB alone * ATG + CSA * ATG + CSA + ETB |
| Hemoglobin Level | Baseline | — |
| Platelets Count | Baseline | — |
| Neutrophil Level | Baseline | — |
| Number of Blood Transfusions | Up to approximately 7 months | — |
| Total Units of Blood Transfusions | Up to approximately 7 months | — |
Countries
United States
Outcome results
None listed