Hypogammaglobulinemia and infection rates in patients with multiple sclerosis treated with ocrelizumab for up to six years: A real-world single-center study.

Objectives and aims: Ocrelizumab (OCR) is disease-modifying therapy that depletes B cells for the treatment of patients with relapsing and progressive multiple sclerosis (MS). The aim of this study was to evaluate occurrence of hypogammaglobulinemia and infection rates in patients with MS treated with OCR for up to 5.9 years in a real-world, single-center study. Methods: We assessed immunoglobulins IgG, IgM, IgA; CD19, CD4, CD8 cell counts, anti-JCV antibodies, at baseline and every six months prior to each OCR infusion. Mixed effects regression models controlling for random patient intercept were used to analyze immunological trends. Infections requiring oral or intravenous antibiotics were also recorded and analyzed. Results: A total of 238 patients were followed for up to 5.9 years and received a mean of 7.6 (range, 2-13) OCR infusions. IgG declined on average by 3.7% (p < .001) and IgM by 11.8% (p < .001) annually. At last follow-up, 14.6% of patients had IgG < 600 mg/dL and 51.1% had IgM M < 40 mg/dL. Patients with IgG < 600 mg/dL experienced higher rates of infections requiring oral antibiotics (1.17 vs 0.99 per year, p = .004) and IV antibiotics (0.147 vs 0.066 per year, p = .009) compared to those with normal IgG. White race was associated with reduced IgG (p = .008) and IgA (p < .001) levels, while female sex was associated with increased CD4 (p < .001) and CD8 (p = .015) counts. Anti-JCV antibody index declined by 1.9% annually (p < .001). Linear trend analysis predicted that 14.9 years of treatment would be required for at least 50% of patients to have IgG levels <600 mg/dL. Conclusions: Continuous OCR treatment results in increasing hypogammaglobulinemia associated with increasing risk of moderate and severe infections. The clinical significance of these immunological findings and the influences of demographic characteristics highlight the importance of regular, personalized immunoglobulin monitoring during long-term OCR therapy.