Medical and financial burden of acute intermittent porphyria

Abstract

Introduction: A small proportion of patients with acute intermittent porphyria (AIP) suffer from recurrent porphyric attacks, with a severely diminished quality of life. In this retrospective case-control study, the burden of disease is quantified and compared among three AIP patient subgroups: cases with recurrent attacks, cases with one or occasional attacks and asymptomatic carriers.

Methods: Data from patient records and questionnaires were collected in patients between 1960 and 2016 at the Erasmus Medical Center, Rotterdam, the Netherlands. We collected symptoms related to porphyria, porphyria related complications, attack frequency, hospitalisation frequency, hospitalisation days related to acute porphyric attacks, frequency of heme infusions and medical healthcare costs based on hospitalisations and heme therapy.

Results: In total 11 recurrent AIP cases, 24 symptomatic AIP cases and 53 AIP carriers as controls were included. All recurrent patients reported porphyria related symptoms, such as pain, neurological and/or psychiatric disorders, and nearly all developed complications, such as hypertension and chronic kidney disease. In the recurrent cases group, the median lifelong number of hospitalisation days related to porphyric attacks was 82 days per patient (range 10-374), and they spent a median of 346 days (range 34-945) at a day-care facility for prophylactic heme therapy; total follow-up time was 243 person-years (PYRS). In the symptomatic non-recurrent group the median lifelong number of hospitalisation days related to porphyric attacks was 7 days per patient (range 1-78), total follow-up time was 528 PYRS. The calculated total medical healthcare cost for recurrent cases group was €5.8 million versus €0.3 million for the symptomatic cases group.

Keywords: Acute intermittent porphyria; Acute porphyrias; Heme arginate; Nervous system diseases; Porphyria, acute intermittent/epidemiology.

Fig. 1

The distribution of first measured urinary porphyrin precursors in the different AIP groups. Subgroups were based on phenotypic characteristics: recurrent cases were defined as having more than four attacks in any year, or on prophylactic heme therapy; symptomatic cases, were defined as having experienced one or more confirmed acute porphyric attack; asymptomatic controls never experienced a proven acute porphyric attack. Abbreviations: A, asymptomatic controls; ALA, delta-aminolevulinic acid; PBG; porphobilinogen; R, recurrent cases; S, symptomatic cases. The grey areas mark increased levels, starting at 4 times the upper limit of normal (ULN) 4xULN ALA ≥ 184 μmol/L 4x ULN PBG ≥ 36 μmol/L

Fig. 2

Schematic information with individual life lines with porphyric attacks of all symptomatic cases, including information regarding prophylactic heme therapy. Subgroups were based on phenotypic characteristics: recurrent cases were defined as having more than four attacks in any year, or on prophylactic heme therapy; symptomatic cases, were defined as having experienced one or more confirmed acute porphyric attack; asymptomatic controls never experienced a proven acute porphyric attack. On the left there are 11 lines derived from patients with recurrent attacks, and on the right 24 lines derived from symptomatic cases. Each line starts at 15 years of age and ends at the end of the observation period or death. Each segment on the line represents one year. The red blocks represent one attack during that year. The green bars under the timelines represent years in which patients received prophylactic heme. A cross represents death. Abbreviations. LTF, lost to follow-up; HCC, hepatocellular carcinoma; LTx, liver transplant. *not included in study analysis