Use of Avatrombopag in Patients with Immune Thrombocytopenia: Interim Analysis of the Phase 4 Adopt Study

Introduction: Avatrombopag (AVA) is an oral thrombopoietin receptor agonist (TPO-RA) approved for the treatment of adults with chronic immune thrombocytopenia (ITP). Both the disease and the treatment strategies can have a significant impact on ITP patients' health-related quality of life (HRQoL). Therefore, patient-reported outcomes (PROs) play a crucial role in evaluating patients' perspectives on their condition, treatments, and healthcare journey. Previously we reported an interim analysis of the ADOPT study designed to evaluate the real-world effectiveness and safety of AVA in routine clinical practice in Europe (Álvarez Román, et al. HemaSphere 2024;8[S1]:P2235). Here we report an interim analysis of the ADOPT study that focuses on PROs and provides an update on effectiveness and safety.

Methods: Retrospective data were collected from patients' medical records for up to 12 months prior to initiation of AVA treatment, and prospective data were collected at routine clinical visits over a 12-month period. Eligible patients were aged ≥18 years with an established and well-documented ITP diagnosis and were being treated with or had initiated treatment with AVA at enrollment. Patients provided informed consent. The primary endpoint was the cumulative number of weeks with a platelet count (PC) ≥30 × 10⁹/L. The following secondary endpoints were assessed: HRQoL, assessed by change from enrollment in the 13-item Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) score, which evaluates patient-reported fatigue and its impact upon daily function over the past 7 days (a 3-point change indicates clinically important change); patient satisfaction with treatment, assessed by the 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9); physician satisfaction with treatment outcome, assessed by a 5-point scale; treatment adherence, assessed by the self-administered 8-item Morisky Medication Adherence Scale (MMAS-8); and safety.

Results: The study completed enrollment in January 2024 and, at the interim data cut-off (May 02, 2024), the full analysis set (FAS) consisted of 190 patients, recruited at 51 centers in nine European countries. Mean (standard deviation [SD]) age of patients was 55.6 (18.1) years, 56.8% were female, mean (SD) time from ITP diagnosis to enrollment was 9.7 (11.4) years, and 53.7% had been treated with another TPO-RA in the 12 months prior to enrollment. In 18 patients who completed the 12-month study period, the median cumulative number of weeks with a PC ≥30 × 10⁹/L was 50.4 (range 5.9-51.4) weeks. In patients who initiated AVA at enrollment, the mean (SD) FACIT-F score improved from 29.8 (14.0) at enrollment (n=9) to 40.0 (9.3) at 6 months (n=9) (mean [SD] change 7.7 [9.6]; n=3). Patient treatment satisfaction improved across all three domains of the TSQM-9 (effectiveness [n=3], convenience [n=3], and global satisfaction [n=3]) at 6 months in patients who initiated AVA at enrollment. At 6 months since enrollment, 68.4% (13/19) of patients who initiated AVA at enrollment and 69.0% (107/155) of patients in the FAS, which also included patients who initiated AVA before enrollment, had satisfactory or highly satisfactory treatment, as judged by physicians. At 6 months since enrollment, 88.9% (8/9) of patients who initiated AVA at enrollment and 86.5% (45/52) of patients in the FAS, which also included patients who initiated AVA before enrollment, had medium or high adherence (as assessed by MMAS-8). A total of 49 adverse events (AEs) were reported in 29/190 patients (15.3%) in the FAS, with 15 AEs in ten patients (5.3%) considered AVA-related. Two patients discontinued AVA treatment due to AEs, which included abdominal pain and fatigue.

Conclusion: This interim analysis of the ADOPT study supports that treatment with AVA is effective and safe, may improve HRQoL, is associated with patient and physician treatment satisfaction, and offers medium to high treatment adherence in routine clinical practice. Comparable physician satisfaction and adherence between the FAS and patients who initiated AVA at enrollment suggest both are stable over longer treatment periods. Improvements in clinical outcomes, treatment satisfaction, and adherence suggest that AVA may reduce the overall treatment burden for people with ITP.

Mingot-Castellano:Grifols: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Sobi: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Novonordisk: Honoraria, Speakers Bureau; Sanofi: Honoraria, Speakers Bureau. Alvarez-Román:Sobi: Membership on an entity's Board of Directors or advisory committees, Other: Sponsored symposia , Speakers Bureau; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees, Other: Sponsored symposia , Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Other: Sponsored symposia , Speakers Bureau; Octapharma: Membership on an entity's Board of Directors or advisory committees, Other: Sponsored symposia , Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Sponsored symposia , Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Other: Sponsored symposia , Speakers Bureau; CSL Behring: Membership on an entity's Board of Directors or advisory committees, Other: Sponsored symposia , Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Sponsored symposia , Speakers Bureau; Grifols: Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees, Other: Sponsored symposia , Research Funding, Speakers Bureau. Lozano:UCB: Consultancy; Sobi: Consultancy; Grifols: Consultancy; Novartis: Consultancy; Argenx: Consultancy; Amgen: Consultancy, Research Funding. Miesbach:Bayer: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau; Biotest: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau; CSL Behring: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau; LFB: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau; Octapharma: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau; Sanofi: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sobi: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau; Takeda/Shire: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau; Biomarin: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau; uniQure: Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Chugai: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Grifols: Speakers Bureau; Freeline: Membership on an entity's Board of Directors or advisory committees; Regeneron: Membership on an entity's Board of Directors or advisory committees. McDonald:Sobi: Honoraria; Novartis: Honoraria; Grifols: Research Funding; Amgen: Honoraria; AbbVie: Honoraria; Argenx: Honoraria. Putnik:Sobi: Current Employment. Zhang:Sobi: Current Employment. Skuban:Sobi: Current Employment. Cano Garcia:Sobi: Current Employment. Lethagen:Sobi: Current Employment.