Severe Hypogammaglobulinemia (IgG) During Efgartigimod Therapy in Neurological Practice: A Real-World Case Series.

Background Efgartigimod is a neonatal Fc receptor (FcRn) antagonist approved for adults with generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor antibody-positive, and for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). By blocking FcRn-mediated IgG recycling, efgartigimod lowers circulating IgG and reduces pathogenic autoantibodies. Clinical trials have demonstrated efficacy and an overall acceptable safety profile, but patients with low baseline IgG were generally not well represented. Objective The main objective of this study is to describe severe reductions in serum IgG observed in routine neurologic practice during efgartigimod therapy, and to explore their potential clinical implications, including infection risk and management considerations. Methods We performed a retrospective case series of 10 patients treated with efgartigimod in our practice between 2025 and 2026 for CIDP and MG. Available clinical data were reviewed, including diagnosis, prior immunotherapy exposure, baseline IgG (when available), serial IgG measurements, nadir IgG, and any documented infectious complications.  Results Several patients developed marked hypogammaglobulinemia during treatment, including profound reductions to levels below 100 mg/dL in selected cases. Several patients reached IgG levels within ranges associated with increased susceptibility to infection (<500 mg/dL, particularly <400 mg/dL), although no severe infections were observed. One patient with CIDP and prior rituximab exposure had a baseline IgG of approximately 800 mg/dL, and later developed an IgG level of 66 mg/dL. Another patient without prior B-cell-depleting therapy also developed an IgG level below 100 mg/dL. No major infectious complication was documented during the observation period, but the degree of IgG suppression raised concern for clinically meaningful vulnerability to severe infection. Conclusions Efgartigimod therapy was associated with significant reductions in IgG in this real-world cohort. Because trial populations excluded or underrepresented patients with low baseline IgG, and did not meaningfully study extreme hypogammaglobulinemia, baseline and serial IgG monitoring should be strongly considered in all patients starting therapy, especially during the first six months. These findings highlight the potential for clinically meaningful IgG decline in certain patients, and support consideration of individualized monitoring strategies. These observations are hypothesis-generating and warrant further study.