Hypogammaglobulinemia in MS Patients on Anti-CD20 Therapy: When to Act

This episode discusses "Hypogammaglobulinemia in MS Patients on Anti-CD20 Therapy: When to Act." Dr. Williams identifies hypogammaglobulinemia — low IgG levels resulting from prolonged B-cell depletion — as one of the most clinically consequential long-term complications of anti-CD20 therapy, and asks the panel how they identify high-risk patients and manage this finding.

Dr. Greenberg notes that risk stratification is imprecise: patients who start with lower baseline IgG or who are older are at greatest risk, but it is not a foregone conclusion. The prevalence of hypogammaglobulinemia in treated populations ranges from 8–20% depending on the study. He shares that after initially referring all patients with below-normal IgG to immunology — and being counseled by his immunology colleagues to stop — he now monitors routinely (to capture trends) but acts only on clinical correlation, not numbers alone.

The panel agrees: IgG level alone does not reliably predict infection risk. Patients with recurrent bacterial sinusitis or pneumonia warrant further workup; patients with recurrent UTIs — the most common infection in this population — may have neurogenic bladder as the primary driver, rather than low antibody levels. IVIg has not proven broadly effective for UTI reduction in this setting.

An emerging concern raised by panelist is non-infectious pulmonary pathology: bronchiectasis and other structural lung changes have been identified in some patients, and pulmonology consultation is now warranted for patients with chronic cough — even when infection seems probable. The panel concludes that the overall safety profile of long-term B-cell depletion remains reassuring, as demonstrated by the Covid-19 experience, but vigilance and collaborative management are essential.

In the next episode, "Extended Interval Dosing of Anti-CD20 Therapies: Benefits, Risks, and Real-World Experience," the panel debates whether spacing out dosing is a viable strategy and what evidence supports or cautions against it.