Effectiveness of Early Intervention in Transfusion Independent Aplastic Anemia: a Retrospective Medical Claims Database Study

This was a retrospective non-interventional cohort study with secondary use of data from the Medical Data Vision (MDV) hospital-based database to evaluate the effectiveness of early drug intervention in preventing transfusion compared to watchful observation among adult transfusion-independent aplastic anemia (AA) patients in Japan.

Study Overview

• Status: Completed
• Conditions: Aplastic Anemia (AA)

• Study Type: Observational
• Enrollment (Actual): 1603

Contacts and Locations

Study Locations

• Japan
  • Tokyo, Japan, 105-6333
    • Novartis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This was a retrospective, noninterventional cohort study.

Description

Inclusion Criteria:

• Having at least one confirmed diagnosis of AA within the selection period (1 inpatient or 2 outpatient claims per the International Statistical Classification of Diseases, 10th Revision [ICD-10] code, without any suspicion flag).
• Being aged 15 to 90 years at the index date.
• Having at least 3 months of continuous enrolment prior to the index date.

Exclusion Criteria:

• Having a blood transfusion recorded any time before the index date.
• Having anti-thymocyte globulin (ATG) treatment recorded within 3 months after the index date.
• Having at least one prescription record for any of the drug treatments of interest any time before the index date.
• Having a diagnosis of acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML) or other leukemia any time before the index date.
• Having an AA diagnosis (without suspicious flag) date earlier than the start of patient's observation in the database.
• Having less than 6 months of continuous follow-up.

Safety Population - Additional Exclusion Criterion:

- Having a diagnosis of hepatotoxicity, kidney dysfunction, hypertension, or diabetes mellitus any time before the index date.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Early drug intervention group; Patients who had at least one prescription record associated with any of the drug treatments of interest (cyclosporine A, eltrombopag, romiplostin, danazol, or methenolone) during each period of interest before the first transfusion record during the follow-up period.
Watchful observation group; Patients with no prescription record associated with any of the drug treatments of interest (cyclosporine A, eltrombopag, romiplostin, danazol, or methenolone) during the follow-up period and before the first transfusion record, if any.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Probability of Having Blood Transfusion in the Matched Effectiveness Population	The Kaplan-Meier survival analysis technique was used to estimate probability.	Baseline, at 6 and 9 months, and at 1, 2, 5, and 10 years
Crude Hazard Ratios of Having Blood Transfusion After 6 Months of Follow-up in the Matched Effectiveness Population		Baseline, 6 months
Adjusted Hazard Ratios of Having Blood Transfusion After 6 Months of Follow-up in the Matched Effectiveness Population		6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight		Baseline
Age		Baseline
Sex		Baseline
Hemoglobin Level		Baseline
Body Mass Index (BMI)		Baseline
Number of Patients With Aplastic Anemia, per Severity Level		Baseline
Number of Patients With Immune Thrombocytopenia (ITP) Diagnosis Before Index Date		Baseline
Number of Patients With Myelodysplastic Syndrome (MDS) Diagnosis Before Index Date		Baseline
Number of Patients With Pre-index Comorbidities		Baseline
Number of Patients With Pre-index Use of Chloramphenicol		Baseline
Platelet Count		Baseline
Neutrophil Count		Baseline
Number of Patients Per Treatment Therapy in the Matched Effectiveness Population		Baseline
Number of Patients With Aplastic Anemia in the Matched Effectiveness Population, per Severity Level		Baseline
Number of Patients in the Matched Effectiveness Population Who Discontinued		Baseline, at 6 and 9 months, and at 1 and 2 years
Probability of Having Blood Transfusion in Early Drug Intervention and Watchful Observation Matched Patients From the Effectiveness Population	The Kaplan-Meier survival analysis technique was used to estimate probability.	Baseline, at 6 and 9 months, and at 1, 2, 5, and 10 years
Probability of Having Stem-Cell Transplantation (SCT) in Early Drug Intervention and Watchful Observation Matched Patients From the Effectiveness Population	The Kaplan-Meier survival analysis technique was used to estimate probability.	Baseline, at 6 and 9 months, and at 1, 2, 5, and 10 years
Probability of Having Anti-Thymocyte Globulin (ATG) in Early Drug Intervention and Watchful Observation Matched Patients From the Effectiveness Population	The Kaplan-Meier survival analysis technique was used to estimate probability.	Baseline, at 6 and 9 months, and at 1, 2, 5, and 10 years
Probability of Having Blood Transfusion at Different Timepoints by Drug Categories in the Matched Effectiveness Population	The Kaplan-Meier survival analysis technique was used to estimate probability.	Baseline, at 6 and 9 months, and at 1, 2, 5, and 10 years
Probability of Having SCT at Different Timepoints by Drug Categories in the Matched Effectiveness Population	The Kaplan-Meier survival analysis technique was used to estimate probability.	Baseline, at 6 and 9 months, and at 1, 2, 5, and 10 years
Probability of Having ATG at Different Timepoints by Drug Categories in the Matched Effectiveness Population	The Kaplan-Meier survival analysis technique was used to estimate probability.	Baseline, at 6 and 9 months, and at 1, 2, 5, and 10 years
Probability of Having a Bleeding Event in Early Drug Intervention and Watchful Observation Matched Patients From the Safety Population	The Kaplan-Meier survival analysis technique was used to estimate probability.	Baseline, at 6 and 9 months, and at 1, 2, 5, and 10 years
Probability of Having Cataract in Early Drug Intervention and Watchful Observation Matched Patients From the Safety Population	The Kaplan-Meier survival analysis technique was used to estimate probability.	Baseline, at 6 and 9 months, and at 1, 2, 5, and 10 years
Probability of Having Diabetes in Early Drug Intervention and Watchful Observation Matched Patients From the Safety Population	The Kaplan-Meier survival analysis technique was used to estimate probability.	Baseline, at 6 and 9 months, and at 1, 2, 5, and 10 years
Probability of Having Hepatotoxicity in Early Drug Intervention and Watchful Observation Matched Patients From the Safety Population	The Kaplan-Meier survival analysis technique was used to estimate probability.	Baseline, at 6 and 9 months, and at 1, 2, 5, and 10 years
Probability of Having Hypertension in Early Drug Intervention and Watchful Observation Matched Patients From the Safety Population	The Kaplan-Meier survival analysis technique was used to estimate probability.	Baseline, at 6 and 9 months, and at 1, 2, 5, and 10 years
Probability of Having an Infection in Early Drug Intervention and Watchful Observation Matched Patients From the Safety Population	The Kaplan-Meier survival analysis technique was used to estimate probability.	Baseline, at 6 and 9 months, and at 1, 2, 5, and 10 years
Probability of Having Kidney Dysfunction in Early Drug Intervention and Watchful Observation Matched Patients From the Safety Population	The Kaplan-Meier survival analysis technique was used to estimate probability.	Baseline, at 6 and 9 months, and at 1, 2, 5, and 10 years
Probability of Having Acute Myeloid Leukemia (AML), Chronic Myelomonocytic Leukemia (CMML) or Another Leukemia in Early Drug Intervention and Watchful Observation Matched Patients From the Safety Population	The Kaplan-Meier survival analysis technique was used to estimate probability.	Baseline, at 6 and 9 months, and at 1, 2, 5, and 10 years
Probability of Having MDS in Early Drug Intervention and Watchful Observation Matched Patients From the Safety Population	The Kaplan-Meier survival analysis technique was used to estimate probability.	Baseline, at 6 and 9 months, and at 1, 2, 5, and 10 years
Probability of Having Paroxysmal Nocturnal Hemoglobinuria (PNH) in Early Drug Intervention and Watchful Observation Matched Patients From the Safety Population	The Kaplan-Meier survival analysis technique was used to estimate probability.	Baseline, at 6 and 9 months, and at 1, 2, 5, and 10 years
Probability of Having a Thromboembolic Event in Early Drug Intervention and Watchful Observation Matched Patients From the Safety Population	The Kaplan-Meier survival analysis technique was used to estimate probability.	Baseline, at 6 and 9 months, and at 1, 2, 5, and 10 years
Probability of Having Myelofibrosis in Early Drug Intervention and Watchful Observation Matched Patients From the Safety Population	The Kaplan-Meier survival analysis technique was used to estimate probability.	Baseline, at 6 and 9 months, and at 1, 2, 5, and 10 years
Probability of Having a Bleeding Event by Drug Categories in the Matched Safety Population	The Kaplan-Meier survival analysis technique was used to estimate probability.	Baseline, at 6 and 9 months, and at 1, 2, 5, and 10 years
Probability of Having Cataract by Drug Categories in the Matched Safety Population	The Kaplan-Meier survival analysis technique was used to estimate probability.	Baseline, at 6 and 9 months, and at 1, 2, 5, and 10 years
Probability of Having Diabetes by Drug Categories in the Matched Safety Population	The Kaplan-Meier survival analysis technique was used to estimate probability.	Baseline, at 6 and 9 months, and at 1, 2, 5, and 10 years
Probability of Having Hepatotoxicity by Drug Categories in the Matched Safety Population	The Kaplan-Meier survival analysis technique was used to estimate probability.	Baseline, at 6 and 9 months, and at 1, 2, 5, and 10 years
Probability of Having an Infection by Drug Categories in the Matched Safety Population	The Kaplan-Meier survival analysis technique was used to estimate probability.	Baseline, at 6 and 9 months, and at 1, 2, 5, and 10 years
Probability of Having Kidney Dysfunction by Drug Categories in the Matched Safety Population	The Kaplan-Meier survival analysis technique was used to estimate probability.	Baseline, at 6 and 9 months, and at 1, 2, 5, and 10 years
Probability of Having AML, CMML or Another Leukemia by Drug Categories in the Matched Safety Population	The Kaplan-Meier survival analysis technique was used to estimate probability.	Baseline, at 6 and 9 months, and at 1, 2, 5, and 10 years
Probability of Having MDS by Drug Categories in the Matched Safety Population	The Kaplan-Meier survival analysis technique was used to estimate probability.	Baseline, at 6 and 9 months, and at 1, 2, 5, and 10 years
Probability of Having PNH by Drug Categories in the Matched Safety Population	The Kaplan-Meier survival analysis technique was used to estimate probability.	Baseline, at 6 and 9 months, and at 1, 2, 5, and 10 years
Probability of Having a Thromboembolic Event by Drug Categories in the Matched Safety Population	The Kaplan-Meier survival analysis technique was used to estimate probability.	Baseline, at 6 and 9 months, and at 1, 2, 5, and 10 years
Probability of Having Myelofibrosis by Drug Categories in the Matched Safety Population	The Kaplan-Meier survival analysis technique was used to estimate probability.	Baseline, at 6 and 9 months, and at 1, 2, 5, and 10 years

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2022
• Primary Completion (Actual): November 3, 2023
• Study Completion (Actual): November 3, 2023

Study Registration Dates

• First Submitted: October 30, 2024
• First Submitted That Met QC Criteria: October 30, 2024
• First Posted (Estimated): November 1, 2024

Study Record Updates

• Last Update Posted (Estimated): November 1, 2024
• Last Update Submitted That Met QC Criteria: October 30, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bone Marrow Failure Disorders; Hematologic Diseases; Bone Marrow Diseases; Anemia; Anemia, Aplastic
• Other Study ID Numbers: CETB115EJP05