Baseline urinary ALA and PBG as criteria for starting pharmacologic prophylactic treatment in acute intermittent porphyria treated with givosiran.

Introduction: For patients with acute intermittent porphyria (AIP), a true attack could be difficult to distinguish from chronic abdominal pain. This study focused on treatment responses from two patients with confirmed elevated biochemical data (delta-aminolevulinic acid (ALA), porphobilinogen (PBG)) and clinical evidence for acute attacks before starting givosiran. Methods: Data from patients who participated in the phase III givosiran trial in Taiwan between May 2018 and May 2021 were reviewed. The pre-trial and post-trial biochemical data (urinary ALA/PBG), annualized attack rate (AAR), for two participants were obtained from our hospital record. Results: Two patients had detailed records of biochemical evidence of acute attacks pre-trial (ALA:11.66-79.8 mg/24-h urine collection, PBG:75.45-160.11 mg/24-h). Patient Pb/Gn#1 with a disease duration of 1.6-years, had zero AAR during givosiran treatment. Patient Pb/Gn#2 had received prior hemin prophylaxis, had AIP for 6.7-years, had an AAR of 17.0 before givosiran, and an AAR of 12 at the post-trial compassionate-use period. The change in SF-12 PCS score from baseline was marginally clinical-meaningful (2.8 for Patient Pb/Gn#1 and 2.0 for Patient Pb/Gn#2). Conclusion: Our data from 2 AIP patients with biochemical and clinical evidence of acute attacks suggested that patient with a shorter disease duration may respond better in terms of AAR. Further studies are necessary to understand the association between disease characteristics, treatment history, and optimal treatment response for patients with recurrent AIP in terms of both attack frequency and quality of life.