To compare the efficacy of strategies to manage hypogammaglobulinemia in neuroimmunology patients on anti-CD20 agents, including the effect of anti-CD20 dose reduction and reduced dosing frequency, IVIG/SCIG, anti-CD20 cessation, and DMT switches.

Anti-CD20 monoclonal agents are increasingly used as therapies for multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Few studies have compared strategies to address hypogammaglobulinemia.

All MS, NMOSD, and MOGAD patients at our institution with hypogammaglobulinemia on anti-CD20 agents from 2001-2022 were analyzed. The median change in IgG, infection frequency, and infection severity before and after the treatment was calculated.

In total, 257 patients were screened, and 30 had a treatment for hypogammaglobulinemia. IVIG/SCIG yielded the largest increase in IgG per year (674.0 mg/dL), followed by B-cell therapy cessation (34.7 mg/dL), and DMT switch (5.9 mg/dL). Dose reduction had the largest decrease in yearly infection frequency (2.7 fewer infections), followed by IVIG/SCIG (2.5 fewer), DMT switch (2 fewer), and reduced dosing frequency (0.5 fewer). Infection grade decreased by 1.9 for reduced dosing frequency (less severe infections), by 1.3 for IVIG/SCIG, and by 0.6 for DMT switch. 

This data suggests that IVIG/SCIG may yield the greatest recovery in IgG while also reducing infection frequency and severity. Stopping anti-CD20 therapy and/or switching DMTs also increase IgG and may lower infection risk. Overall, longer follow-up is needed to assess IgG recovery and infection risk with these interventions.