Showing papers by "Raffaella Origa published in 2018"

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

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

Quality of life in Sardinian patients with transfusion-dependent Thalassemia: a cross-sectional study

Abstract: The aim of this study has been to evaluate the physical, psychological, and social well-being in a large group of Sardinian adult patients with transfusion-dependent beta-Thalassemia when compared with a group of healthy subjects of the same age and geographical extraction. Male or female patients ≥ 18 years of age with Thalassemia major on regular transfusion at Thalassemia Center in Cagliari (Italy) were requested to complete the World Health Organization Quality of life-BREF (WHOQOL-BREF) questionnaire. The WHOQOL-BREF was also made available online to age- and sex-matched non-thalassemic adult subjects living in Sardinia. Two hundred and seven subjects with Thalassemia were invited to participate in the study. The questionnaire was also completed by 211 age- and sex-matched non-thalassemic subjects living in Sardinia. Scores suggestive of a good quality of life were obtained in all the areas investigated. Thalassemia patients had scores at least as good as those of non-thalassemic subjects in all items and the percentage of those with a score ≥ 60 was higher among patients. The analysis of demographic actually highlights that the disease has a little effect on their personal and social lives. There was a positive association between subjective well-being and effective clinical conditions. Moreover, the association between health perception and adherence to treatment suggests that compliance with treatment contributes to the well-being of the patient, both physically and psychologically. Adult subjects with Thalassemia who live in Western countries have a good quality of life in accordance with the advances in the management of the disease.

Renal safety under long-course deferasirox therapy in iron overloaded transfusion-dependent β-thalassemia and other anemias.

Abstract: To the Editor: Renal adverse events (AE) and increases in serum creatinine (SCr) have been reported in patients with transfusional hemosiderosis treated with deferasirox. Since the core registration trials, various extension and long-term observational studies have been conducted in pediatric and adult populations. These studies have described the reversible, non-progressive nature of SCr increases and confirmed the overall acceptable renal safety profile of deferasirox. Given the chronic nature of treatment, especially in children with congenital anemias, a longer follow-up was thought opportune to demonstrate the absence of late or cumulative effects of deferasirox in real treatment practice. Italian sites enrolled 34% of the patients across the registration studies, and many of these patients have since then been followed up by the same physicians. This allowed us to conduct a retrospective chart review of SCr values, other renal parameters, and renal AEs in patients on iron chelation therapy for up to 13 years. To minimize selection bias, the study set out to enroll all patients who were treated with at least one dose of deferasirox during the registration trials and had at least one post-baseline assessment of SCr. All available charts had an equal chance of selection but the first SCr, urinary protein, and urinary creatinine values available at the same visit were collected quarterly. Of the 282 patients analyzed, more than 90% were observed for at least seven years following the registration studies. At quarter 1, 65 patients (23%) were less than 18 years of age and 217 patients (76%) were 18 years or older. b-Thalassemia was by far the most common underlying disease (n5264), followed by myelodysplastic syndromes (n59), sickle cell disease (n57), and other anemias (n52). As commonly occurs in real world practice, most patients were not treated with the same chelator since the registration studies but were exposed to various chelating agents including deferasirox. Baseline and worst value of SCr recorded during the registration studies, as well as the quarterly trend over the retrospective period are shown in Figure 1. Mean baseline value was 53.39613.45 lmol/L (range 20.35–87.96 lmol/L), while the worst value was on average 79.73620.19 lmol/L (range 35.40–156.50 lmol/L). During the retrospective period, mean/median SCr values were slightly higher than baseline but lower than worst value, with a stable quarterly trend (around 60 lmol/L in mean) until quarter 43, when the number of patients began to drop considerably and mean/median values started fluctuating. A subgroup analysis assessed SCr in patients (n598) treated with only deferasirox during the retrospective period. Mean value was 50.05613.69 mmol/L at baseline and stable throughout the retrospective period, with mean values between 60 and 65 mmol/L, corresponding to a 15%-20% increase from baseline at most quarters. The SCr trend was traced in a subgroup made up of patients (n5197) with renal AEs or confirmed, notable renal laboratory values during the registration studies. Mean SCr at baseline was 53.236 13.72 lmol/L (range 26.10–87.96 lmol/L), and mean worst value 82.95621.11 lmol/L (range 41.50–156.50 lmol/L). Mean/median values were then steady over time, higher than baseline but lower than worst value, and about the same as values for the full Safety Set (around 62 lmol/L vs. 60 lmol/L), indicating that renal AEs occurring during the registration studies did not provoke irreversible or progressive long-term effects on renal function. Although data for urinary protein, urinary creatinine, and creatinine clearance were often missing, these renal parameters also appeared to remain steady over the retrospective period, with values below the worst value reported in the registration studies. During the retrospective period, renal AEs regardless of treatment relations were reported in 86/282 (30.5%) patients. The most common were nephrolithiasis (10.99% of patients) and renal colics (9.93%), followed by abnormal urine protein/creatinine (UPCR) ratio, abnormal/ increased SCr, and proteinuria. At least one serious adverse event (SAE) was reported for eight patients (2.84%) (increased SCr, acute kidney injury, hematuria, hydronephrosis, renal colic, renal failure, and urethral stenosis). No causal relationship was suspected between the events and treatment with deferasirox. Suspected deferasirox-related renal AEs were reported in 33 patients (11.70%). Proteinuria, abnormal/increased UPCR, and increased blood creatinine were the most frequently reported drug-related events. None of these events was serious but four were considered of severe intensity: increase of UPCR (n52), proteinuria, and glycosuria. In most cases, deferasirox was temporarily interrupted or dosage was adjusted and no further action was required. Five (5) patients (1.77%) did however discontinue treatment permanently. No cases of acute renal failure or of end stage renal disease were reported during the retrospective period. The one case of “acute kidney injury” mentioned previously as an SAE occurred during acute pancreatitis.