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

Abstract

BackgroundAdherence 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.MethodsThe 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.ResultsOne 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.ConclusionsThese 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 registrationClinicalTrials.gov identifier: NCT02125877; registered April 26, 2014.Electronic supplementary materialThe online version of this article (10.1186/s12955-018-1041-5) contains supplementary material, which is available to authorized users.

Pharmacological and clinical evaluation of deferasirox formulations for treatment tailoring

“…Compliance to DFX DT was already close to optimal in the considered series and was slightly but consistently higher for FCT, confirming what was expected from previous reports about the acceptability of this formulation 21 , 23 , 32 , 33 . The evaluation of the impact of DFX FCT on compliance for patients with non-optimal adherence to therapy or a possible psychological role of novelty itself in long-term treatment is beyond the scope of this work.…”

Comparison of Compliance of Different Iron Chelators Including Original and Bioequivalents of Deferasirox

“…Film-coated tablets recipients reported better compliance and greater satisfaction in comparison to dispersable DFX tablets. Moreover, film-coated tablet recipients noted no taste or aftertaste of the drug [3]. The limitations of this study majorly come from its cross-sectional nature, which is based on patient-oriented responses.…”

“…As these patients are transfusion-dependent, chelation therapy should be administered for a lifetime. Safety, tolerability, and convenience of these drugs are essential for compliance, the wellbeing and the support of the patients are other accompanying factors [3]. The choice of the chelator or combination therapies are the most significant factors in preventing disease-related complications [2].…”

Improving outcomes and quality of life for patients with transfusion-dependent β-thalassemia: recommendations for best clinical practice and the use of novel treatment strategies

“…In a recent metaanalysis (2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015)(2016) that included 2961 patients with TD βthalassemia, those receiving deferoxamine and combination therapy had poorer HRQoL status across all eight domains of the 36-item Short Form (SF-36) health survey than those receiving deferasirox [48]. In addition, a new film-coated formulation of deferasirox that can be taken with a meal, rather than on an empty stomach, has advantages in adherence, satisfaction/preference, and patient concerns compared to the dispersible formulation [51]. The dose of ICT must be adjusted for each patient and careful regular monitoring is required to manage the adverse effects, such as nausea, joint pain, kidney injury, and agranulocytosis, which may be associated with treatment and may compromise adherence [8,9,17,52,53].…”