BACKGROUND:
A known complication of delandistrogene moxeparvovec-rokl (Elevidys) treatment Duchenne Muscular Dystrophy (DMD) is acute liver injury, typically occurring in the second and third months post-infusion. The pathophysiology is considered immune-mediated, and some patients have required non-steroidal immunosuppressants. Currently, there is no standardized protocol for managing acute liver injury in the post-infusion period.
RESULTS:
A 10 year old ambulatory male with genetically confirmed DMD (exons 48-54 deletion) was treated with vamorolone. He tested negative for AAVrh74 antibodies, started prednisone 1 mg/kg/day, and was dosed with delandistrogene moxeparvovec-rokl. Four weeks post-infusion, he developed signs and symptoms of acute liver injury: scleral icterus, fatigue, clay-colored stools, AST and ALT 4x baseline, gamma-glutamyl transferase (GGT) 3x upper limit of normal, and total and direct hyperbilirubinemia. Oral prednisone was increased to 2 mg/kg/day. With worsening lab values one week later, seven days of daily intravenous methylprednisolone was added. GGT, bilirubin, and INR peaked six weeks post-infusion: GGT 4x upper limit of normal, total bilirubin 7.3, direct bilirubin 5.8, and INR 1.34. Liver ultrasound demonstrated increased echogenicity and no bile duct dilatation. Viral, autoimmune, and toxic hepatitis were ruled out. Enzyme-linked immunosorbent spot (ELISpot) assay showed a positive T cell response to the AAVrh74 vector, but a negative response to the micro-dystrophin protein. Ursodiol was initiated at 250 mg twice daily to treat hepatobiliary dysfunction and reduce serum bilirubin levels. By ten weeks, AST and ALT returned to baseline, bilirubin normalized, and prednisone was reduced to 1 mg/kg/day. Ursodiol was discontinued. Interestingly, serum creatine kinase levels reduced to <1000 U/L during treatment with IV methylprednisolone. Muscle strength improved seven weeks post-infusion and maintained through week 12.
CONCLUSION:
This case highlights successful liver injury and hyperbilirubinemia management with corticosteroids and ursodiol, avoiding additional immunosuppressants. It is not yet known if this experience will be generalizable, but it establishes benefit from corticosteroids without other immunosuppressive treatments.