Patient-reported outcomes from a randomized phase II study of the deferasirox film-coated tablet in patients with transfusion-dependent anemias

Abstract

Background: Adherence to long-term chelation therapy in transfusion-dependent patients is critical to prevent iron overload-related complications. Once-daily deferasirox dispersible tablets (DT) have proven long-term efficacy and safety in patients ≥2 years old with chronic transfusional iron overload. However, barriers to optimal adherence remain, including palatability, preparation time, and requirements for fasting state. A new film-coated tablet (FCT) formulation was developed, swallowed once daily (whole/crushed) with/without a light meal.

Methods: The open-label, Phase II ECLIPSE study evaluated patient-reported outcomes (PROs) in transfusion-dependent thalassemia or lower-risk myelodysplastic syndromes patients randomized 1:1 to receive deferasirox DT or FCT over 24 weeks as a secondary outcome of the study. Three PRO questionnaires were developed to evaluate both deferasirox formulations: 1) Modified Satisfaction with Iron Chelation Therapy Questionnaire; 2) Palatability Questionnaire; 3) Gastrointestinal (GI) Symptom Diary.

Results: One hundred seventy three patients were enrolled; 87 received the FCT and 86 the DT formulation. FCT recipients consistently reported better adherence (easier to take medication, less bothered by time to prepare medication and waiting time before eating), greater satisfaction/preference (general satisfaction and with administration of medicine), and fewer concerns (less worry about not swallowing enough medication, fewer limitations in daily activities, less concern about side effects). FCT recipients reported no taste or aftertaste and could swallow all their medicine with an acceptable amount of liquid. GI summary scores were low for both formulations.

Conclusions: These findings suggest a preference in favor of the deferasirox FCT formulation regardless of underlying disease or age group. Better patient satisfaction and adherence to chelation therapy may reduce iron overload-related complications.

Trial registration: ClinicalTrials.gov identifier: NCT02125877; registered April 26, 2014.

Keywords: Deferasirox; Iron chelation; Iron overload; Patient-reported outcomes.

Conflict of interest statement

Authors’ information

Not applicable.

Ethics approval and consent to participate

The study was conducted in accordance with Good Clinical Practice guidelines and the Declaration of Helsinki and was approved by independent ethics committees at participating sites. Patients (or parents/guardians) provided written, informed consent prior to enrollment.

Consent for publication

Not applicable.

Competing interests

ATT reports receiving research funding and honoraria from Novartis and research funding from Celgene Corporations; RO reports receiving honoraria from Novartis and Apopharma, and for being part of the Italian advisory board for BlueBird Bio; SP reports receiving research funding and honoraria from Novartis and research funding from Acceleron; AKo reports receiving honoraria from Novartis, Amgen, and Janssen, and consultancy for Gilead, Roche, and Celgene; AKa reports receiving research funding from Novartis and participating in advisory boards and educational forums sponsored from Novartis, Apopharma, and Celgene; JBP reports consultancy, receiving research grant funding and honoraria from Novartis Pharmaceuticals, consultancy and honoraria from Shire, and consultancy for Celgene. JBP is supported by the NIHR University College London Hospitals Biomedical Research Centre; VH, AZ, and RMH were full-time employees of Novartis at the time of these analyses; GBR and A-SG declares that they have no competing interests.

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Figures

Fig. 1

Mean ± 95% CI domain scores for patient-reported outcomes (adherence, satisfaction/preference, and concern) (a–c), mean palatability score (d), and mean gastrointestinal symptom scores (e). For adherence (a; scale 6–30), satisfaction/preference (c; scale 2–10), and GI symptoms (e; scale 0–50), higher scores indicate worse outcomes/symptoms. For concern (c; scale 3–15) and palatability (d; scale 0–11), higher scores indicate fewer concerns and better palatability. a–d, SOT was defined as week 2 assessment. If missing, then the week 3 assessment was considered SOT. e, SOT was defined as week 1 score. If missing, then the week 2 score was considered SOT. CI, confidence interval; DFX, deferasirox; DT, dispersible tablet; EOT, end of treatment; FCT, film-coated tablet; SOT, start of treatment. Figure adapted from Taher AT et al. Am J Hematology 2017;92(5):420–428. Published with kind permission of John Wiley & Sons ©2017 The Authors, American Journal of Hematology, Published by Wiley Periodicals, Inc.

Fig. 2

Response frequencies at week 2 (start of treatment) and end of treatment by treatment arm from the mSICT adherence domains, a Thinking about stopping medication, b How hard/easy to take the medication, c Time to prepare medication, d Waiting time to eat, e Following doctor’s instructions, and f Trouble remembering to take medication. Numbers indicate the number of patients in each response category; *n < 5 patients. DT, dispersible tablet; FCT, film-coated tablet; mSICT, modified Satisfaction with Iron Chelation Therapy

Fig. 3

Response frequencies at week 2 (start of treatment) and end of treatment by treatment arm from the mSICT concerns domains, a Swallowing enough medication, b Medication limiting usual activities, c Feeling upset about side effects. Numbers indicate the number of patients in each response category; *n < 5 patients. DT, dispersible tablet; FCT, film-coated tablet; mSICT, modified Satisfaction with Iron Chelation Therapy

Fig. 4

Response frequencies at week 2 (start of treatment) and end of treatment by treatment arm from the Palatability Questionnaire items, a Whether medication was taken, b Perceived amount of liquid, c Taste, and d Aftertaste. Numbers indicate the number of patients in each response category; *n < 5 patients; DT, dispersible tablet; FCT, film-coated tablet

Fig. 5

Response frequencies for the preferred formulation of deferasirox at week 2 (start of treatment) and end of treatment by treatment arm. Numbers indicate the number of patients in each response category; *n