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  1. Cappellini MD, Viprakasit V, Georgiev P, Coates TD, Origa R, Khelif A, et al.
    Lancet Haematol, 2025 Mar;12(3):e180-e189.
    PMID: 39947215 DOI: 10.1016/S2352-3026(24)00376-4
    BACKGROUND: Treatments to reduce red blood cell (RBC) transfusion burden among patients with transfusion-dependent β-thalassaemia remain limited. Here, we report long-term follow-up data from the phase 3 BELIEVE trial of luspatercept for transfusion-dependent β-thalassaemia.

    METHODS: BELIEVE was a phase 3, randomised, double-blind, placebo-controlled study performed at 65 sites in 15 countries. The trial included adults with transfusion-dependent β-thalassaemia or haemoglobin E/β-thalassaemia and Eastern Cooperative Oncology Group score of 0-1. Patients were randomly assigned (2:1) using integrated response technology stratified by region to luspatercept (1·0-1·25 mg/kg) or placebo administered subcutaneously once every 21 days. After study unblinding, patients could receive luspatercept in the open-label extension phase (crossover allowed). The primary endpoint results (proportion of patients with reduction in transfusion burden of ≥33% and ≥2 RBC units during weeks 13-24) are described elsewhere; herein we present an update to the primary endpoint analysis consequent to late-reported transfusion events. We also report long-term efficacy (intention-to-treat population) and safety data (safety population) for patients followed up for approximately 3 years. This trial is registered on ClinicalTrials.gov (NCT02604433) and is completed.

    FINDINGS: Between May 2, 2016, and May 16, 2017, 336 patients were randomly assigned to luspatercept (n=224) or placebo (n=112). The median age of patients was 30 years (IQR 23-40); 195 (58%) were female and 141 (42%) male. As of Jan 5, 2021, the median duration of treatment in the luspatercept group was 153·6 weeks (IQR 81·0-171·0) and median study follow-up was 163·1 weeks (140·5-176·2). Due to the difference in treatment duration between the luspatercept and placebo groups, no comparative analyses between the two groups were performed after week 96. Patients in the luspatercept group showed a sustained reduction in RBC transfusion burden from baseline through week 192, with mean decreases of 6·2 RBC units (SD 5·7) during weeks 97-144 and 6·4 RBC units (4·3) during weeks 145-192. In the luspatercept group, a 33% or greater reduction in transfusion burden from baseline was observed in 173 (77%) patients over any 12-week interval and in 116 (52%) patients over any 24-week interval. The median total duration of 33% or greater transfusion burden reduction response during any period of at least 12 weeks was 586·0 days (IQR 264·0-1010·0). The most common grade 3 or worse treatment-emergent adverse events (TEAEs) among all patients who received luspatercept (n=315, including 92 patients who crossed over after study unblinding) were anaemia (nine [3%]), increased liver iron concentration (seven [2%]), and bone pain (seven [2%]); serious TEAEs occurred in 71 (23%) patients. No treatment-related deaths occurred in any group during the study.

    INTERPRETATION: These long-term results affirm luspatercept's efficacy in addressing key unmet needs of patients with transfusion-dependent β-thalassaemia with a manageable safety profile.

    FUNDING: Celgene and Acceleron Pharma.

  2. Burton AC, Beirne C, Gaynor KM, Sun C, Granados A, Allen ML, et al.
    Nat Ecol Evol, 2024 May;8(5):924-935.
    PMID: 38499871 DOI: 10.1038/s41559-024-02363-2
    Wildlife must adapt to human presence to survive in the Anthropocene, so it is critical to understand species responses to humans in different contexts. We used camera trapping as a lens to view mammal responses to changes in human activity during the COVID-19 pandemic. Across 163 species sampled in 102 projects around the world, changes in the amount and timing of animal activity varied widely. Under higher human activity, mammals were less active in undeveloped areas but unexpectedly more active in developed areas while exhibiting greater nocturnality. Carnivores were most sensitive, showing the strongest decreases in activity and greatest increases in nocturnality. Wildlife managers must consider how habituation and uneven sensitivity across species may cause fundamental differences in human-wildlife interactions along gradients of human influence.
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