International sentinel site surveillance of patients with transfusional hemosiderosis treated with deferasirox in actual practice setting

Funding: This study was funded by Novartis Pharma AGObjective:The study evaluates the long-term deferasirox treatment of adult and pediatricpatients with chronic transfusional iron overload in clinical practice.Methods:In this non-interventional study, patients were observed for up to 3 years frominitiation of deferasirox treatment both prospectively and retrospectively for up to 1 yearprior to enrollment. The primary end points were the proportion of patients with≥1 notableincrease in serum creatinine (SCr), and≥1 notable increase in alanine aminotransferase (ALT).Results:Overall, 120 patients were enrolled and 51 completed the study, with a limited 3-yeardropout rate of 12.5% due to adverse events (AEs). Increase in SCr > 33% above baseline and theage-adjusted ULN (upper limit of normal) was observed in 14 patients (95%CI, 7.1-19.2). The ALTlevels >5 × ULN was observed in 1 patient. Most frequent AEs reported during treatment withdeferasirox include gastrointestinal disturbances.Conclusions:The long-term treatment with deferasirox was manageable in most transfusion-dependent patients with no unexpected safetyfindings. Regular monitoring and an adjusteddeferasirox dosing strategy per local labels allowed continued iron chelation treatment andcontrol of transfusional iron in the majority of patients on study

Effect of crizanlizumab on pain crises in subgroups of patients with sickle cell disease: A SUSTAIN study analysis

The cell adhesion molecule P-selectin plays a key role in the pathogenesis of a vaso-occlusive crisis (VOC) in patients with sickle cell disease (SCD). In the double-blind, placebo-controlled phase 2 SUSTAIN study, crizanlizumab (humanized, anti-P-selectin monoclonal antibody) 5 mg/kg significantly lowered the rate of VOC in patients with SCD by 45% vs placebo. In SUSTAIN, patients with SCD were randomized to crizanlizumab 2.5 mg/kg, crizanlizumab 5 mg/kg, or placebo intravenously 14 times over 52 weeks. The primary endpoint was the annual rate of VOC with crizanlizumab vs placebo. This post hoc descriptive analysis evaluated the proportion of patients who did not experience a VOC during the study in the following subgroups: VOCs in the year prior to study entry (2-4/5-10), SCD genotype (HbSS/non-HbSS), and concomitant hydroxyurea use (yes/no). More patients were VOC event-free in the crizanlizumab 5 mg/kg arm than in the placebo arm, including those with more frequent prior VOCs (ie, 5-10; 28.0% vs 4.2%), the HbSS genotype (31.9% vs 17.0%) and/or using concomitant hydroxyurea (33.3% vs 17.5%). Further analyses of secondary endpoints demonstrated that crizanlizumab treatment significantly increased time-to-first VOC vs placebo in these subgroups. The rates of treatment-emergent adverse events were similar between treatment arms across all subgroups. This post hoc analysis of SUSTAIN shows that in patients with a high number of prior VOCs, on concomitant hydroxyurea and/or with the HbSS genotype, crizanlizumab treatment increases the likelihood of patients being VOC event-free and delays time-to-first VOC