EXPLORE: A Prospective, Multinational, Natural History Study of Patients with Acute Hepatic Porphyria with Recurrent Attacks

Laurent Gouya, Paolo Ventura, Manisha Balwani, D. Montgomery Bissell, David C. Rees, Ulrich Stölzel, John D. Phillips, Raili Kauppinen, Janneke G. Langendonk, Robert J. Desnick, Jean Charles Deybach, Herbert L. Bonkovsky, Charles Parker, Hetanshi Naik, Michael Badminton, Penelope E. Stein, Elisabeth Minder, Jerzy Windyga, Radan Bruha, Maria Domenica CappelliniEliane Sardh, Pauline Harper, Sverre Sandberg, Aasne K. Aarsand, Janice Andersen, Félix Alegre, Aneta Ivanova, Neila Talbi, Amy Chan, William Querbes, John Ko, Craig Penz, Shangbin Liu, Tim Lin, Amy Simon, Karl E. Anderson

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
JournalHepatology
DOIs
Publication statusAccepted/In press - Jan 1 2019

Fingerprint

Natural History
Hemin
Aminolevulinic Acid
Health Facilities
Acute Hepatic Porphyria
Porphobilinogen
Patient Acceptance of Health Care
Quality of Life
Delivery of Health Care
Therapeutics
Inborn Genetic Diseases
Rare Diseases
Heme
RNA

ASJC Scopus subject areas

  • Hepatology

Cite this

Gouya, L., Ventura, P., Balwani, M., Bissell, D. M., Rees, D. C., Stölzel, U., ... Anderson, K. E. (Accepted/In press). EXPLORE: A Prospective, Multinational, Natural History Study of Patients with Acute Hepatic Porphyria with Recurrent Attacks. Hepatology. https://doi.org/10.1002/hep.30936

EXPLORE : A Prospective, Multinational, Natural History Study of Patients with Acute Hepatic Porphyria with Recurrent Attacks. / Gouya, Laurent; Ventura, Paolo; Balwani, Manisha; Bissell, D. Montgomery; Rees, David C.; Stölzel, Ulrich; Phillips, John D.; Kauppinen, Raili; Langendonk, Janneke G.; Desnick, Robert J.; Deybach, Jean Charles; Bonkovsky, Herbert L.; Parker, Charles; Naik, Hetanshi; Badminton, Michael; Stein, Penelope E.; Minder, Elisabeth; Windyga, Jerzy; Bruha, Radan; Cappellini, Maria Domenica; Sardh, Eliane; Harper, Pauline; Sandberg, Sverre; Aarsand, Aasne K.; Andersen, Janice; Alegre, Félix; Ivanova, Aneta; Talbi, Neila; Chan, Amy; Querbes, William; Ko, John; Penz, Craig; Liu, Shangbin; Lin, Tim; Simon, Amy; Anderson, Karl E.

In: Hepatology, 01.01.2019.

Research output: Contribution to journalArticle

Gouya, L, Ventura, P, Balwani, M, Bissell, DM, Rees, DC, Stölzel, U, Phillips, JD, Kauppinen, R, Langendonk, JG, Desnick, RJ, Deybach, JC, Bonkovsky, HL, Parker, C, Naik, H, Badminton, M, Stein, PE, Minder, E, Windyga, J, Bruha, R, Cappellini, MD, Sardh, E, Harper, P, Sandberg, S, Aarsand, AK, Andersen, J, Alegre, F, Ivanova, A, Talbi, N, Chan, A, Querbes, W, Ko, J, Penz, C, Liu, S, Lin, T, Simon, A & Anderson, KE 2019, 'EXPLORE: A Prospective, Multinational, Natural History Study of Patients with Acute Hepatic Porphyria with Recurrent Attacks', Hepatology. https://doi.org/10.1002/hep.30936
Gouya, Laurent ; Ventura, Paolo ; Balwani, Manisha ; Bissell, D. Montgomery ; Rees, David C. ; Stölzel, Ulrich ; Phillips, John D. ; Kauppinen, Raili ; Langendonk, Janneke G. ; Desnick, Robert J. ; Deybach, Jean Charles ; Bonkovsky, Herbert L. ; Parker, Charles ; Naik, Hetanshi ; Badminton, Michael ; Stein, Penelope E. ; Minder, Elisabeth ; Windyga, Jerzy ; Bruha, Radan ; Cappellini, Maria Domenica ; Sardh, Eliane ; Harper, Pauline ; Sandberg, Sverre ; Aarsand, Aasne K. ; Andersen, Janice ; Alegre, Félix ; Ivanova, Aneta ; Talbi, Neila ; Chan, Amy ; Querbes, William ; Ko, John ; Penz, Craig ; Liu, Shangbin ; Lin, Tim ; Simon, Amy ; Anderson, Karl E. / EXPLORE : A Prospective, Multinational, Natural History Study of Patients with Acute Hepatic Porphyria with Recurrent Attacks. In: Hepatology. 2019.
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abstract = "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.",
author = "Laurent Gouya and Paolo Ventura and Manisha Balwani and Bissell, {D. Montgomery} and Rees, {David C.} and Ulrich St{\"o}lzel and Phillips, {John D.} and Raili Kauppinen and Langendonk, {Janneke G.} and Desnick, {Robert J.} and Deybach, {Jean Charles} and Bonkovsky, {Herbert L.} and Charles Parker and Hetanshi Naik and Michael Badminton and Stein, {Penelope E.} and Elisabeth Minder and Jerzy Windyga and Radan Bruha and Cappellini, {Maria Domenica} and Eliane Sardh and Pauline Harper and Sverre Sandberg and Aarsand, {Aasne K.} and Janice Andersen and F{\'e}lix Alegre and Aneta Ivanova and Neila Talbi and Amy Chan and William Querbes and John Ko and Craig Penz and Shangbin Liu and Tim Lin and Amy Simon and Anderson, {Karl E.}",
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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.

PY - 2019/1/1

Y1 - 2019/1/1

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

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