Clinical Characteristics and Outcomes of Acute Intermittent Porphyria: Insights From the European Porphyria Registry.

BACKGROUND AND AIMS: Acute intermittent porphyria (AIP) is a rare disorder with diverse clinical presentations, ranging from latent at-risk individuals to recurrent acute attacks with severe complications. Differences between clinical states and risk factors for severe outcomes remain incompletely defined.

APPROACH AND

RESULTS

In this cross-sectional study, personal, biochemical and clinical data were recorded for non-givosiran treated AIP patients across all clinical states by European porphyria expert centres into the European Porphyria Registry during 2012-2018. Logistic regression models assessed associations between clinical factors and outcomes, with disease states defined according to clinical practice at study initiation. Urinary δ-aminolevulinic acid (u-ALA) and porphobilinogen (u-PBG) were normalized to each centre's upper reference limits. Data from 239 participants were included and patients were classified as sporadic attack(s) (n = 61), recurrent (n = 49), in-remission (n = 58), asymptomatic high excreters (n = 23) and latent at-risk (n = 48). Hospitalization for an acute attack was associated with ≥ 10-fold u-PBG increase (adjusted Odds Ratios [aOR] = 22.40, 95% CI = 5.34-94.03), 4-9-fold (6.35 [2.87-14.02]) and ≥ 10-fold (177.50 [8.03-3923]) u-ALA increase, BMI < 18.5 (12.68 [2.86-56.23]) and age 20-39 (4.35 [1.82-10.42]). A 10-fold u-PBG increase (8.22 [2.31-29.28]) and a positive family history at diagnosis (0.30 [0.14-0.64]) were associated with recurrent classification. Recurrent AIP (7.28 [2.77-19.14]) and sporadic heme-treated acute attacks (5.30 [1.89-14.91]) were associated with reduced work capacity and unemployment. Chronic hypertension, chronic kidney disease and primary liver cancer were observed across all clinical groups.

CONCLUSIONS

In this multicentre European study, we describe disease burden across all clinical AIP states including non-givosiran treated recurrent patients and identify risk factors associated with hospitalization and recurrent disease.