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Poster 14
04153 Clinical and biochemical evolution of eight acute hepatic porphyria patients under givosiran treatment
  1. C Puente Fernández1,
  2. I Solares1,
  3. FJ Castelbón1,
  4. I Liria Fernandez2,
  5. S Diaz-Diaz2,
  6. D Bellido3,
  7. J Ros3,
  8. PM Alcazar-Carmona4,
  9. R Enríquez de Salamanca1,
  10. A Fontanellas5,
  11. M Morales-Conejo1
  1. 1Department of Internal Medicine, Hospital Universitario 12 de Octubre, Madrid, Spain; CIBERER
  2. 2Biochemistry service, Hospital Universitario 12 de Octubre, Madrid, Spain; CIBERER
  3. 3Department of Internal Medicine, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain
  4. 4Department of Internal Medicine, Hospital La Mancha Centro, Albacete, Spain
  5. 5Center for Applied Medical Research (CIMA)-University of Navarra, Pamplona, Spain. CIBERehd

Abstract

Acute hepatic porphyrias (AHPs) are rare inherited disorders characterized by enzyme dysfunctions in the hepatic pathway of heme biosynthesis, leading to recurrent life-threatening neurovisceral attacks due to the accumulation of neurotoxic porphyrin precursors, including delta-aminolevulinic acid (ALA) and porphobilinogen (PBG). Givosiran (Givlaari®), a subcutaneously administered small interfering RNA, targets hepatic aminolevulinate synthase 1 (ALAS1) activity, thereby reducing porphyrin precursor levels and mitigating attack frequency.

This study conducted a comprehensive clinical and analytical follow-up of eight AHP patients treated with Givosiran for at least 17 months. Analyzed parameters encompassed urinary ALA and PBG excretion, plasma levels of homocysteine (HCy), transaminases, glomerular filtration rate (GFR), lipase, amylase, vitamin B12, folic acid, vitamin B6, plasma cystathionine-β-synthase (CBS) activity, methylenetetrahydrofolate reductase (MTHFR) and hemopexin mutations.

The majority of patients exhibited notable improvements in quality of life and a sustained reduction in hemin and opiate usage. Treatment discontinuation occurred in two patients: one due to nausea and fatigue (resulting in increased opiate use and the occurrence of moderate porphyric crises) and another due to pregnancy. Plasma homocysteine elevation was frequent and managed by supplementing the treatment with vitamins B6, B12, and folate. Although elevated pancreatic enzyme levels were observed in 50% of patients, clinical pancreatitis was not evident. Individualized dosing adjustments were implemented based on clinical evolution and precursor excretion profiles.

Long-term Givosiran treatment in severe AHP patients demonstrated favorable clinical and biochemical outcomes. Elevated homocysteine levels and pancreatic enzyme elevation were effectively managed through vitamin supplementation and dose adjustments respectively. Close monitoring for adverse effects remains paramount for optimizing patient outcomes, while tailored treatment approaches may further enhance therapeutic efficacy in acute hepatic porphyria.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/bmjgast-2024-ICPP.43

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