Introduction

Burosumab is a human monoclonal antibody to fibroblast growth factor 23 (FGF23) which is used in the treatment of X-linked hypophosphatemia. Burosumab therapy has not been associated with serum enzyme elevations during therapy nor has it been implicated in cases of clinically apparent drug induced liver injury with jaundice.

Background

Burosumab (bur oh' sue mab) is a recombinant, human IgG1 monoclonal antibody to fibroblast growth factor 23 (FGF23) which is used in the treatment of X-linked hypophosphatemia which is associated with excessive FGF23 production. X-linked hypophosphatemia is the most common cause of congenital rickets and is caused by mutations in genes that regulate FGF23 production which result in excessive circulating levels that cause phosphate wasting and poor bone mineralization. Patients have limb deformities, frequent fractures, short stature and musculoskeletal pain and stiffness. Binding of the monoclonal antibody to circulating FGF23 blocks its activity and results in increases in serum phosphate, decreases in alkaline phosphatase and improvements in clinical symptoms and rickets severity. Burosumab was approved for use in the United States in 2018, and current indications are for adults and children above 1 year of age with X-linked hypophosphatemia. Burosumab is available in single use vials of 10, 20 or 30 mg/mL under the brand name Crysvita. It is given subcutaneously and the dose and frequency of administration (every 2 or 4 weeks) varies by age and body weight. Side effects of are uncommon but can include injection site reactions, headache and back and leg pains. Rare, potentially severe side effects include severe hypersensitivity reactions and hyperphosphatemia.

Hepatotoxicity

In prelicensure clinical trials, burosumab was not associated with changes in serum aminotransferase levels during therapy and rates of most adverse reactions were similar in patients who received burosumab as placebo. There have been no published reports of clinically apparent acute liver injury attributed to burosumab therapy.

Likelihood score: E (unlikely cause of clinically apparent liver injury).

Mechanism of Liver Injury

Burosumab is a human monoclonal antibody and is unlikely to be inherently hepatotoxic. While most recombinant proteins are metabolized by the liver, the metabolism leads largely to small peptides and amino acids which may be reused to synthesize proteins and are unlikely to be toxic or immunogenic. Inhibition of FGF23 does not appear to have an adverse effect on liver function.

Drug Class: Genetic Disorder Agents, Monoclonal Antibodies