EXPLORE: A Prospective, Multinational, Natural History Study of Patients with Acute Hepatic Porphyria with Recurrent Attacks
Gouya L (1), Ventura P (2), Balwani M (3), Bissell DM (4), Rees DC (5), Stölzel U (6), Phillips JD (7), Kauppinen R (8), Langendonk JG (9), Desnick RJ (3), Deybach JC (1), Bonkovsky HL (10), Parker C (7), Naik H (3), Badminton M (11), Stein PE (5), Minder E (12), Windyga J (13), Bruha R (14), Cappellini MD (15), Sardh E (16), Harper P (16), Sandberg S (17), Aarsand AK (17), Andersen J (17), Alegre F (18), Ivanova A (19), Talbi N (20), Chan A (21), Querbes W (21), Ko J (21), Penz C (21), Liu S (21), Lin T (21), Simon A (21), Anderson KE (22).
(1) Centre de Référence Maladies Rares Porphyries, Colombes, France.
(2) Università degli Studi di Modena e Reggio Emilia, Emilia-Romagna, Italy.
(3) Icahn School of Medicine at Mount Sinai, New York, NY, USA.
(4) University of California, San Francisco, CA, USA.
(5) King's College Hospital, King's College London, London, UK.
(6) Klinikum Chemnitz Porphyria Center, Chemnitz, Germany.
(7) University of Utah, Salt Lake City, UT, USA.
(8) University Hospital of Helsinki, Helsinki, Finland.
(9) Porphyria Center, Center for Lysosomal and Metabolic Disease, Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, The Netherlands.
(10) Section on Gastroenterology & Hepatology, Wake Forest University/NC Baptist Medical Center, Winston-Salem, NC, USA.
(11) University Hospital of Wales, Cardiff, UK.
(12) Stadtspital Triemli, Zentrallabor, Zurich, Switzerland.
(13) Department of Hemostatic Disorders and Internal Medicine, Institute of Hematology and Transfusion Medicine, Warsaw, Poland.
(14) 4th internal clinic, General University Hospital, Charles University, Prague, Czech republic.
(15) University of Milan, Fondazione IRCCS, Ca Granda, Milan, Italy.
(16) Porphyria Centre Sweden, Centre for Inherited Metabolic Diseases, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
(17) Norwegian Porphyria Centre, Haukeland University Hospital, Bergen, Norway.
(18) Clinica Universidad de Navarra, Navarra, Spain.
(19) St. Ivan Rilski U Hospital, Sofia, Bulgaria.
(20) Laboratory of Excellence GR-Ex, University of Paris, Paris, France.
(21) Alnylam Pharmaceuticals, Cambridge, MA, USA.
(22) University of Texas Medical Branch, Galveston, TX, USA
Acute hepatic porphyria comprises a group of rare, genetic diseases caused by mutations in genes involved in heme biosynthesis. Patients can experience acute neurovisceral attacks, debilitating chronic symptoms, and long-term complications.
There is a lack of multinational, prospective data characterizing the disease and current treatment practices in severely affected patients. EXPLORE is a prospective, multinational, natural history study characterizing disease activity and clinical management in patients with acute hepatic porphyria who experience recurrent attacks.
Eligible patients had a confirmed acute hepatic porphyria diagnosis and had experienced ≥3 attacks in the prior 12 months or were receiving prophylactic treatment. A total of 112 patients were enrolled and followed for at least 6 months. In the 12 months prior to the study, patients reported a median (range) of 6 (0-52) acute attacks, with 52 (46%) patients receiving hemin prophylaxis. Chronic symptoms were reported by 73 (65%) patients, with 52 (46%) patients experiencing these daily. During the study, 98 (88%) patients experienced a total of 483 attacks, 77% of which required treatment at a healthcare facility and/or hemin administration (median [range] annualized attack rate 2.0 [0.0-37.0]).
Elevated levels of hepatic δ-aminolevulinic acid synthase 1 messenger ribonucleic acid levels, δ-aminolevulinic acid, and porphobilinogen compared with the upper limit of normal in healthy individuals were observed at baseline and increased further during attacks. Patients had impaired quality of life and increased healthcare utilization.
Conclusions: Patients experienced attacks often requiring treatment in a healthcare facility and/or with hemin, as well as chronic symptoms that adversely influence day-to-day functioning. In this patient group, the high disease burden and diminished quality of life highlight the need for novel therapies.
CITATION Hepatology. 2019 Sep 12. doi: 10.1002/hep.30936.