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    Oral Communication

    Hemophilia and Rare Bleeding Disorders

    Hemophilia Gene Therapy for Hemophilia A

    OC 20.4 - The impact of gene therapy on the musculoskeletal health of patients with severe hemophilia A

    Sunday, June 25, 2023
    15:30 – 15:45 ET
    Room: 517
    Session Available As: Live-Stream and On-Demand

      Presenting Author(s)

    • Gabriela G. Yamaguti-Hayakawa, MD, PhD (she/her/hers)

      Hematologist
      Hemocentro UNICAMP, University of Campinas, Campinas, SP, Brazil
      Campinas, Sao Paulo, Brazil

      • Co-Author(s)

    • JR

      Janaina B. S. Ricciardi

      Physiotherapist
      Hemocentro UNICAMP, University of Campinas, Campinas, SP, Brazil
      Campinas, Sao Paulo, Brazil

    • Jessica O. Frade-Guanaes, MsC

      Graduate student
      Hemocentro UNICAMP, University of Campinas, Campinas, SP, Brazil
      Campinas, Sao Paulo, Brazil

    • VF

      Vanessa B. Faiotto

      Study coordinator
      Hemocentro UNICAMP, University of Campinas, Campinas, SP, Brazil
      Campinas, Sao Paulo, Brazil

    • LD

      Luiz G. R. R. De Lima

      Undergraduate student
      Hemocentro UNICAMP, University of Campinas, Campinas, SP, Brazil
      Campinas, Sao Paulo, Brazil

    • GF

      Glenda Feldberg

      Physiotherapist
      Hemocentro UNICAMP, University of Campinas, Campinas, SP, Brazil
      Campinas, Sao Paulo, Brazil

    • ES

      Emerson T. I. Sakuma

      Radiologist
      Department of Anesthesiology, Oncology and Radiology, School of Medical Sciences, University of Campinas, UNICAMP, Campinas, SP, Brazil
      Campinas, Sao Paulo, Brazil

    • DD

      Daniela M. De Paulo

      Study Coordinator
      Hemocentro UNICAMP, University of Campinas, Campinas, SP, Brazil
      Campinas, Sao Paulo, Brazil

    • AS

      Andrea L. A. Sambo

      Registered Nurse
      Hemocentro UNICAMP, University of Campinas, Campinas, SP, Brazil
      Campinas, Sao Paulo, Brazil

    • MH

      Mariana M. T. Hosokawa

      Registered Nurse
      Hemocentro UNICAMP, University of Campinas, Campinas, SP, Brazil
      Campinas, Sao Paulo, Brazil

    • VS

      Valdirene C. F. Stahl

      Nurse
      Hemocentro UNICAMP, University of Campinas, Campinas, SP, Brazil
      Campinas, Sao Paulo, Brazil

    • SM

      Samuel S. Medina

      Hematologist
      Hemocentro UNICAMP, University of Campinas, Campinas, SP, Brazil
      Campinas, Sao Paulo, Brazil

    • MC

      Marina P. P. Colella

      Hematologist
      Hemocentro UNICAMP, University of Campinas, Campinas, SP, Brazil
      Campinas, Sao Paulo, Brazil

    • NF

      Nivia M. Foschi

      Hematologist
      Hemocentro UNICAMP, University of Campinas, Campinas, SP, Brazil
      Campinas, Sao Paulo, Brazil

    • Carolina Costa-Lima, Master's degree and PHD student (she/her/hers)

      Hematologist
      Hemocentro UNICAMP, University of Campinas, Campinas, SP, Brazil
      Campinas, Sao Paulo, Brazil

    • Margareth C. Ozelo, MD, PhD (she/her/hers)

      Professor
      Hemocentro UNICAMP, Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil
      Campinas, Sao Paulo, Brazil

    Background: Patients with severe hemophilia A (HA) (factor[F] VIII < 1%) have recurrent joint bleeds, which lead to progressive arthropathy. Once present, arthropathy will progress even in individuals with no reported bleeds and under intense FVIII prophylaxis.

    Aims: This prospective study aims to evaluate the impact of gene therapy with valoctogene roxaparvovec on the musculoskeletal (MSK) health of patients with HA.

    Methods: MSK health was evaluated with HJHS, FISH, HAL, and HEAD-US at baseline (before infusion) and at the end of the second year (Y2) after infusion. The concentration of MSK-related biomarkers (inflammation, cartilage degradation/repair, and bone absorption/formation) was measured in plasma samples at baseline and at Y2.

    Results: Twelve patients with severe HA, who underwent gene therapy with valoctocogene roxaparvovec at the dose of 6e13 vg/kg, were included in this study. Two years after gene therapy, participants presented with better HJHS scores than at baseline (median of 41 vs. 47.5 respectively, p= 0.022), with no difference in FISH and HAL scores. Joint ultrasound assessment yielded a higher HEAD-US score at Y2 than at baseline (median score 26.5 vs. 23.5; p= 0,018). In this period, median annualized bleeding and joint bleeding rates were 0, with 66.7% of the cohort with no joint bleeds (n= 8) (table 1). The median change in HJHS was -4 (range= -16 to +6), while the median change in HEAD-US was 5 (range= 0 to +6). MSK biomarkers evaluation at Y2 showed a significant decrease in plasma levels of IL17a, IL1β, IL6, LOX1, MMP3, MMP13, and TNFa, along with an increase in plasma levels of OC and Dkk1 (table 2).

    Conclusion(s): After 2 years of gene therapy, we observed a clinical improvement in MSK health, despite the imaging progression of arthropathy. Biomarkers suggested a decrease in inflammatory state, damage to the cartilaginous matrix, and greater production of bone mass.

    Learning Objectives:

    • Understand the main scores used to assess MSK health in hemophilia
    • Identify possible plasma biomarkers for musculoskeletal health in people with hemophilia A and chronic arthropathy
    • Understand the impact of gene therapy for severe hemophilia A on hemophilic arthropathy