Dataset Information

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

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.

SUBMITTER: Gouya L

PROVIDER: S-EPMC7255459 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAcute hepatic porphyria (AHP) is a rare, debilitating disease characterized by potentially life-threatening attacks often resulting in chronic symptoms that negatively impact daily functioning and quality of life. Symptoms of AHP prevent many individuals from working and achieving lifetime work averages. The aim of this study was to apply a public economic framework to evaluate AHP in Belgium, taking into consideration a broad range of costs that are relevant to government in relation to social benefit payments and lifetime taxes paid.MethodologyA public economic framework was developed exploring lifetime costs for government attributed to an individual with AHP and recurrent attacks in Belgium. Work-activity and lifetime direct taxes paid, indirect consumption taxes and requirements for public benefits were estimated based on established clinical pathways for AHP and compared to the general population (GP). The model includes AHP-related healthcare costs and non-AHP healthcare costs for the GP.ResultsLifetime earnings are reduced in an individual with AHP by €347,802 per person (p.p.), translating to reduced lifetime taxes paid of €183,187 for an AHP individual compared to the GP. We estimate increased lifetime disability benefit support of €247,242 for an AHP individual compared to GP. Lifetime healthcare costs for a person with AHP were estimated to be €3,030,316 due to frequent hospitalisations associated with porphyria attacks compared to the GP. The lifetime costs for a person with 12 attacks per annum factoring in transfers, taxes and healthcare costs are estimated to be €3,460,745 p.p. Eliminating AHP attacks after 10 years of active disease, thus, enabling a person to return to work increases lifetime earnings by €224,575 p.p. Increased work activity in such individuals would generate an estimated €118,284 p.p. over their lifetime. The elimination of AHP attacks could also lead to reductions in disability payments of €179,184 p.p. and healthcare cost savings of €1,511,027 p.p.ConclusionsDue to severe disability resulting from constant attacks, AHP patients with recurrent attacks incur significant public costs. Lifetime taxes paid are reduced as these attacks occur during peak earning and working years. In those patients, reducing AHP attacks can confer significant fiscal benefits for government, including reduced healthcare costs, reduced disability payments and improved tax revenue.

Project description:IntroductionAcute hepatic porphyria (AHP) is a family of rare metabolic diseases characterized by potentially life-threatening acute attacks and, in some patients, chronic debilitating symptoms. While patients with frequent or recurrent attacks (three or more attacks annually) are known to have reduced health-related quality of life (HRQoL) as most aspects of daily living are impacted, limited data exist in patients with sporadic attacks. This research aims to identify porphyria-related symptoms between attacks, characterize the frequency, severity, and bothersomeness of these symptoms, and more generally understand the burden of this disease in patients who experience attacks sporadically.MethodsPatients with AHP with sporadic attacks (AHP-SA) (at least one porphyria attack in the past 2 years, but no more than two attacks per year in the previous 2 years) were recruited, via outreach performed by patient advocacy groups, for participation in qualitative telephone interviews. Interviews were conducted using a semi-structured guide and were audio-recorded, transcribed, anonymized, coded, and analyzed to determine if saturation was reached.ResultsA total of 14 participants with AHP-SA were interviewed (mean age 45 years, 100% female). The most frequently reported chronic symptoms were fatigue, pain, heartburn, and constipation. The most frequently experienced chronic impacts were difficulty performing daily activities, difficulty exercising, negative impact on work, need for a special diet, anxiety, and depression. Beyond these chronic symptoms and impacts, participants also frequently described flares in their porphyria that were severe, did not qualify in their minds as an acute attack, but were nonetheless more severe than their typical chronic experience.ConclusionPatients with acute hepatic porphyria who experience sporadic attacks face significant chronic symptoms and impacts that frequently require significant pharmacological and clinical treatment. The reported severity of these symptoms and impacts suggests that the humanistic burden of AHP-SA is substantial and may lead to a significant decrease in health-related quality of life in these patients between acute attacks. The presence of flares that do not reach the level of what is considered an acute attack by patients is a unique finding of this study not reported elsewhere and requires additional investigation.

Project description:Acute hepatic porphyria (AHP) is a family of rare genetic diseases, including acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and delta-aminolevulinic acid dehydratase-deficient porphyria. The objective of this retrospective cohort study was to provide information on the clinical features of AHP in Japan-including acute attacks, chronic symptoms, and long-term complications. Patients with AHP between April 2008 and June 2020 were selected from Japan's Medical Data Vision claims database. Patients with AHP were matched 1:10, by sex and age, to patients without AHP. The outcomes were evaluated overall, for patients age ≥ 55 years, and for the matched population. A total of 391 patients with AHP were included from the Japanese Medical Data Vision database. During the observation period (April 2008-June 2020), 18.2% (71/391) of patients experienced 1 acute attack and 10.5% (41/391) experienced ≥ 2 attacks. Chronic symptoms with rates ~ 10% or higher in the AHP population compared with the matched population included neurotic, stress-related, and somatoform disorders (21.7% vs. 6.7% [15.0% difference]); sleep disorders (23.0% vs. 9.9% [13.1% difference]); other and unspecified abdominal pain (13.6% vs. 3.7% [9.9% difference]); and nausea and vomiting, excluding chemotherapy-induced emesis (17.9% vs. 8.1% [9.8% difference]). Long-term complications with higher incidence rates in the AHP population compared with the matched population included fibrosis and cirrhosis of liver (15.9% vs. 3.0% [12.9% difference]), polyneuropathies and other disorders of the peripheral nervous system (20.5% vs. 7.9% [12.6% difference]), liver cancer (16.9% vs. 4.7% [12.2% difference]), renal failure (16.4% vs. 4.3% [12.1% difference]), and hypertension (26.1% vs. 18.8% [7.3% difference]). Among AHP patients age ≥ 55 years, the most common long-term complications were hypertension, kidney failure, and liver cancer. In Japan, patients with AHP experience a high clinical burden in terms of acute attacks, chronic symptoms, and long-term complications. The clinical burden related to chronic symptoms and long-term complications was substantially higher in Japanese patients with AHP compared with a matched population without AHP. Recognizing these signs and symptoms of AHP may aid physicians in making an earlier diagnosis, which may help patients avoid attack triggers, implement disease management, and reduce lifetime disease burden.