Safety and Pregnancy Outcomes in Thrombocythemia Patients Exposed to XAGRID® (Anagrelide Hydrochloride) Compared to Other Treatments

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants who were newly diagnosed (received no treatment at the time of study registration) or previously diagnosed with essential thrombocythemia (ET), receiving or continuing previous cytoreductive therapy were recruited in the study

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Due to the non-interventional nature of the study, participants could be receiving XAGRID, XAGRID+Other (Cytoreductives), other (cytoreductives) and no essential thrombocythemia (ET) therapy. During the study participants could change the treatments.

Reporting Groups

	Description
XAGRID Only	Participants who received XAGRID at a dose and mode of administration managed as per investigator's discretion and the relevant Summary of Product Characteristics (SmPC) at the time of registering into the study for a 5 year observation period, during which participants were able to switch treatments per investigator's discretion
XAGRID+Other (Cytoreductives)	Participants who received XAGRID+Other (Cytoreductives) at a dose and mode of administration managed as per investigator's discretion and the relevant SmPC at the time of registering into the study for a 5 year observation period, during which participants were able to switch treatments per investigator's discretion. Other Cytoreductives included Hydroxyurea, Interferon- alpha, Pegylated interferon, Busulphan, Pipobroman, Sodium phosphate P32.
Other (Cytoreductives)	Participants who received other (Cytoreductives) at a dose and mode of administration managed as per investigator's discretion and the relevant SmPC at the time of registering into the study for a 5 year observation period, during which participants were able to switch treatments per investigator's discretion. Other Cytoreductives included Hydroxyurea, Interferon- alpha, Pegylated interferon, Busulphan, Pipobroman, Sodium phosphate P32.
No Essential Thrombocythemia (ET) Therapy	Participants who were not receiving any cytoreductive treatment for at least 28 consecutive days at the time of registering into the study for a 5 year observation period, during which participants were able to switch treatments per investigator’s discretion.

Participant Flow:   Overall Study

	XAGRID Only	XAGRID+Other (Cytoreductives)	Other (Cytoreductives)	No Essential Thrombocythemia (ET) Therapy
STARTED	804	141	2666	110
Initiated Treatment	804	141	2666	38
COMPLETED	563	108	1758	23
NOT COMPLETED	241	33	908	87
Lost to Follow-up	91	14	351	2
Death	65	16	360	5
Unspecified	64	2	134	6
Participant request	12	1	33	1
Sponsor request	9	0	30	1
Never Initiated Treatment	0	0	0	72

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
First Treatment Safety Population included all participants who received at least 1 dose of cytoreductive treatment. Data of 2 participants were missing in the Other (Cytoreductives) treatment arm.

Reporting Groups

	Description
XAGRID Only	Participants who received XAGRID at a dose and mode of administration managed as per investigator's discretion and the relevant Summary of Product Characteristics (SmPC) at the time of registering into the study for a 5 year observation period, during which participants were able to switch treatments per investigator's discretion.
XAGRID+Other (Cytoreductives)	Participants who received XAGRID along with Other cytoreductives drugs at a dose and mode of administration managed as per investigator's discretion and the relevant SmPC at the time of registering into the study for a 5 year observation period, during which participants were able to switch treatments per investigator's discretion. Other Cytoreductives included Hydroxyurea, Interferon- alpha, Pegylated interferon, Busulphan, Pipobroman, Sodium phosphate P32.
Other (Cytoreductives)	Participants who received other (Cytoreductives) at a dose and mode of administration managed as per investigator's discretion and the relevant SmPC at the time of registering into the study for a 5 year observation period, during which participants were able to switch treatments per investigator's discretion. Other Cytoreductives included Hydroxyurea, Interferon- alpha, Pegylated interferon, Busulphan, Pipobroman, Sodium phosphate P32.
No Essential Thrombocythemia (ET) Therapy	Participants who were not receiving any cytoreductive treatment for at least 28 consecutive days at the time of registering into the study for a 5 year observation period, during which participants were able to switch treatments per investigator's discretion.
Total	Total of all reporting groups

Baseline Measures

	XAGRID Only	XAGRID+Other (Cytoreductives)	Other (Cytoreductives)	No Essential Thrombocythemia (ET) Therapy	Total
Overall Participants Analyzed  [Units: Participants]	804	141	2664	38	3647
Age  [Units: Years] Mean (Standard Deviation)	55.4  (14.99)	59.9  (13.74)	67.4  (13.05)	64.3  (14.26)	64.4  (14.43)
Age, Customized  [Units: Participants]
Less than (<) 65 years	575	89	913	14	1591
65-<75 years	133	30	897	13	1073
Greater than equal to (>=)75 years	96	22	854	11	983
Gender  [Units: Participants]
Female	501	80	1632	25	2238
Male	303	61	1032	13	1409

1.  Primary:

Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies   [ Time Frame: Up to 5 years ]

2.  Primary:

Number of Participants With Suspected Serious Adverse Reaction (SSAR) Events   [ Time Frame: Up to 5 years ]

3.  Secondary:

Event Rate of Thrombohaemorrhagic Events   [ Time Frame: Up to 5 years ]

4.  Secondary:

Platelet Count   [ Time Frame: Baseline, Month 6,12,18, 24, 30, 36, 42, 48, 54, 60 ]

5.  Secondary:

Duration of Exposure for Each Essential Thrombocythemia (ET) Therapy   [ Time Frame: Up to 5 years ]

6.  Secondary:

Cumulative Dose for Each Essential Thrombocythemia (ET) Therapy   [ Time Frame: Up to 5 years ]

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Results for other adverse events (excluding SAEs) was reported under OM 1 due to limitation in basic result’s format, as SAEs and non-SAEs were not planned to be reported separately.