Management of Acute Intermittent Porphyria with Monoclonal Antibodies

Rationale for Safety

The American Association for the Study of Liver Diseases recommends avoiding medications that induce hepatic ALAS1, which increases production of neurotoxic porphyrin precursors ALA and PBG, in patients with acute intermittent porphyria 1, 2
Drugs that precipitate attacks in acute intermittent porphyria typically do so by inducing hepatic cytochrome P450 enzymes, which increases heme demand, or depleting hepatic free heme pools 1

The European Association for the Study of the Liver recommends avoiding drugs that induce hepatic enzymes, such as barbiturates, sulfonamides, and certain anticonvulsants, in patients with acute intermittent porphyria 4
The American College of Gastroenterology recommends preferring drugs with minimal hepatic metabolism or those metabolized through non-P450 pathways in patients with acute intermittent porphyria 3

Monoclonal antibodies, such as fremanezumab, are catabolized into amino acids through proteolytic degradation, not hepatic metabolism, and do not induce cytochrome P450 enzymes or affect heme biosynthesis pathways 4, 1
The International Association for the Study of Pain recommends using monoclonal antibodies, which do not deplete hepatic heme pools, in patients with acute intermittent porphyria 4

The American Academy of Neurology recommends ensuring proper AIP diagnosis with elevated urinary PBG (>10 times upper limit of normal during attacks) and counseling patients on avoiding known triggers, such as fasting, alcohol, smoking, and hormonal changes, in patients with acute intermittent porphyria 2, 1
The National Institute of Diabetes and Digestive and Kidney Diseases recommends monitoring for chronic complications, including hypertension and renal dysfunction, which occur in AIP patients, and maintaining baseline monitoring with CBC, ferritin, metabolic panel, and liver function tests 3, 4