Opposing effects of efgartigimod and rozanolixizumab on serum albumin levels in patients with generalized myasthenia gravis

Although efgartigimod and rozanolixizumab are both neonatal Fc receptor (FcRn) inhibitors for generalized myasthenia gravis (MG), they possess distinct molecular structures: efgartigimod is an engineered immunoglobulin G1 (IgG1) Fc fragment, whereas rozanolixizumab is an IgG4 monoclonal antibody. This study aimed to investigate whether these distinct molecular structures induce differential effects on serum albumin in a real-world setting. We conducted a single-center observational study in patients with generalized MG who newly initiated efgartigimod or rozanolixizumab, measuring serum IgG and albumin levels at baseline and the end of the first treatment cycle. We analyzed 21 treatment cycles (efgartigimod, n = 16; rozanolixizumab, n = 5) from 20 patients, including one who received both therapies. Both drugs induced comparable reductions in serum IgG (median: efgartigimod 671.5 mg/dL vs. rozanolixizumab 734.0 mg/dL, p = 0.59). In contrast, their effects on serum albumin levels were diametrically opposed. In the efgartigimod group, albumin levels increased in 15 (94%) cases (median: + 0.45 g/dL), whereas in the rozanolixizumab group, levels decreased in 5 (100%) cases (median: − 0.40 g/dL). The between-group difference in median albumin change was substantial (p = 0.001). Efgartigimod and rozanolixizumab exert opposing effects on serum albumin levels despite similar IgG-lowering efficacy. This modality-specific pattern suggests distinct pharmacological interactions with the FcRn–albumin recycling pathway, potentially influencing treatment selection in specific patient populations.