Deferasirox (ICL670) is a once-daily oral iron chelator developed for the treatment of chronic iron overload from blood transfusions. A comparative phase 3 trial was conducted to demonstrate the efficacy of deferasirox in regularly transfused patients with ␤-thalassemia aged 2 years or older. Patients were randomized and received treatment with deferasirox (n ‫؍‬ 296) or deferoxamine (n ‫؍‬ 290), with dosing of each according to baseline liver iron concentration (LIC). The primary endpoint was maintenance or reduction of LIC; secondary endpoints included safety and tolerability, change in serum ferritin level, and net body iron balance. In both arms, patients with LIC values of 7 mg Fe/g dry weight (dw) or higher had significant and similar dose-dependent reductions in LIC and serum ferritin, and effects on net body iron balance. However, the primary endpoint was not met in the overall population, possibly due to the fact that proportionally lower doses of deferasirox relative to deferoxamine were administered to patients with LIC values less than 7 mg Fe/g dw. The most common adverse events included rash, gastrointestinal disturbances, and mild nonprogressive increases in serum creatinine. No agranulocytosis, arthropathy, or growth failure was associated with deferasirox administration. Deferasirox is a promising once-daily oral therapy for the treatment of transfusional iron overload. (Blood. 2006;107:3455-3462)

This prospective study assessed the quality of life of patients with homozygous transfusion-dependent beta-thalassemia in Greece receiving three different iron chelation treatments. Patients enrolled were receiving one of the following chelation therapies: deferoxamine (n = 21), deferasirox (n = 75), or deferoxamine in combination with deferiprone (n = 39). The three groups were compared in terms of their quality of life, satisfaction and adherence to treatment, control of their health, and self-esteem through the completion of five questionnaires. A higher percentage of patients receiving deferoxamine felt that their treatment negatively influenced their body and skin appearance and limited their ability to work, attend school, and perform daily tasks (P = 0.0066). The adherence to treatment rate and self-esteem were the lowest in the deferoxamine group (P < 0.05). The deferoxamine group also had the lowest physical component summary score in the SF-36 questionnaire (P = 0.014). This study suggests that the quality of life of beta-thalassemia patients receiving chelation therapy is dependent on the type of iron chelation treatment they receive. The study provides insight into important factors associated with the quality of life of these patients, which are essential for developing a more suitable clinical support team and counseling in order to maximize the treatment benefits for these patients in daily clinical practice.

Anemia is a frequent manifestation of rheumatoid arthritis, with a probably multifactorial etiology. We investigated the effect of peripheral blood mononuclear cell supernatants (PBMCS) from rheumatoid arthritis (RA) patients on hematopoietic colony formation in vitro, by using a methylcellulose assay. PBMCS from patients suppress in vitro erythroid (BFU‐E), mixed‐lineage (CFU‐GEMM) and to a lesser degree granulocyte‐macrophage (CFU‐GM) progenitors. PBMCS from anemic RA patients were more suppressive for BFU‐E than those from non‐anemic patients. Addition of antibodies to tumor‐necrosis factor alpha (TNFα) almost completely reversed the inhibition of BFU‐E and CFU‐GEMM, but had little effect on the CFU‐GM colony formation. Antibodies to interferon‐gamma (IFNγ) and interleukin‐1 (IL‐1) were not effective. The above data suggest that PBMCS from RA patients suppress in vitro erythropoiesis via the production of TNFα; a pathogenetic role for TNFα in the anemia of RA can be implied.

Background:Background: NTDT is characterized by an imbalanced α /β -globin chain ratio, ineffective erythropoiesis, increased intestinal iron absorption and iron overload. Vamifeport inhibits ferroportin-mediated iron export into plasma and has been shown to decrease serum iron and transferrin saturation (TSAT) levels in relevant animal disease models and healthy volunteers. Aims:Aims: The primary objective of this multicenter, Phase 2a, double-blind, randomized, placebo-controlled study (NCT04364269) was to assess the safety and tolerability of vamifeport (given once [QD] or twice [BID] daily) versus placebo in patients with NTDT over a 12-week treatment period. A secondary objective was to assess preliminary efficacy of vamifeport versus placebo with respect to pharmacodynamic effects on iron parameters (serum iron, ferritin, hepcidin and TSAT) in these patients.Methods: Methods: Adults (18-65 years) with documented NTDT (including β -thalassemia intermedia) who provided informed consent, were included. NTDT was defined as receipt of <5 units of red blood cells during the 24 weeks prior to randomization. Patients also required a mean baseline hemoglobin of ≤11 g/dL on two consecutive measurements ≥1 week apart within 6 weeks prior to randomization. Use of iron chelation therapy (ICT) within 4 weeks prior to randomization was not permitted; patients with TSAT <30%, serum ferritin <150 ng/mL and/or liver iron content ≤1 mg/g (<300 ng/mL/3 mg/g, respectively, for those recently on ICT) were also excluded. Patients received vamifeport at a dose of 60 mg if their body weight was 40-59 kg or 120 mg if their weight was 60-100 kg. Results:Results: Twenty-five patients were included (vamifeport QD n=9, BID n=12, placebo n=4; median age 42.0, 31.0 and 40.5 [range 18-61] years, respectively). Overall, 64% were male, 56% had a body weight <60 kg and 16% had received prior ICT. At baseline, mean (standard deviation [SD]) serum iron concentrations were 27.2 (11.6) µmol/L and mean TSAT was 76.2 (27.6)% for the population as a whole. Mean (SD) serum ferritin concentrations were 746.7 (1431.7) µg/L. There were no differences between groups in treatment-emergent adverse event (TEAE) rates (vamifeport QD 66%, BID 58%; placebo 75%). All TEAEs were mild or moderate intensity, and each was reported only once. There were no deaths or serious AEs (1 patient receiving vamifeport QD had an acute hemolytic event); one TEAE (increased creatine kinase and transaminase levels, not drug-related) led to drug discontinuation in the vamifeport BID group. There were also no clinically relevant changes in any assessed safety parameter. Serum iron concentrations decreased 3 h after first vamifeport dose (Day 1) in all vamifeport-treated patients (mean [SD] decrease: QD -11.3 [7.2] µmol/L; BID -17.0 [9.6] µmol/L) and were maintained below baseline levels at 3-4 h post vamifeport administration at each visit throughout the remaining treatment period. Mean (SD) TSAT also decreased at Day 1 (3 h post dose; QD -32.6 [19.6]%; ]%) and were below baselin...