TY - JOUR
T1 - EXPLORE
T2 - A Prospective, Multinational, Natural History Study of Patients with Acute Hepatic Porphyria with Recurrent Attacks
AU - Gouya, Laurent
AU - Ventura, Paolo
AU - Balwani, Manisha
AU - Bissell, D. Montgomery
AU - Rees, David C.
AU - Stölzel, Ulrich
AU - Phillips, John D.
AU - Kauppinen, Raili
AU - Langendonk, Janneke G.
AU - Desnick, Robert J.
AU - Deybach, Jean Charles
AU - Bonkovsky, Herbert L.
AU - Parker, Charles
AU - Naik, Hetanshi
AU - Badminton, Michael
AU - Stein, Penelope E.
AU - Minder, Elisabeth
AU - Windyga, Jerzy
AU - Bruha, Radan
AU - Cappellini, Maria Domenica
AU - Sardh, Eliane
AU - Harper, Pauline
AU - Sandberg, Sverre
AU - Aarsand, Aasne K.
AU - Andersen, Janice
AU - Alegre, Félix
AU - Ivanova, Aneta
AU - Talbi, Neila
AU - Chan, Amy
AU - Querbes, William
AU - Ko, John
AU - Penz, Craig
AU - Liu, Shangbin
AU - Lin, Tim
AU - Simon, Amy
AU - Anderson, Karl E.
N1 - Publisher Copyright:
© 2019 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of American Association for the Study of Liver Diseases.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - Background and Aims: 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. Approach and Results: 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 before 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 health care 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 health care utilization. Conclusions: Patients experienced attacks often requiring treatment in a health care facility and/or with hemin, as well as chronic symptoms that adversely influenced day-to-day functioning. In this patient group, the high disease burden and diminished quality of life highlight the need for novel therapies.
AB - Background and Aims: 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. Approach and Results: 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 before 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 health care 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 health care utilization. Conclusions: Patients experienced attacks often requiring treatment in a health care facility and/or with hemin, as well as chronic symptoms that adversely influenced day-to-day functioning. In this patient group, the high disease burden and diminished quality of life highlight the need for novel therapies.
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U2 - 10.1002/hep.30936
DO - 10.1002/hep.30936
M3 - Article
C2 - 31512765
AN - SCOPUS:85074800104
SN - 0270-9139
VL - 71
SP - 1546
EP - 1558
JO - Hepatology
JF - Hepatology
IS - 5
ER -