Ocrelizumab (OCR) is a humanized anti-CD20 monoclonal antibody approved for the treatment of relapsing remitting (RRMS) and primary progressive multiple sclerosis (PPMS). Immunoglobulin levels were monitored during the phase III trials, and 1.5% of patients developed low immunoglobulin G (IgG) values after 2-3 years of OCR treatment, potentially increasing the risk of infections. The JCV antibody index used to stratify PML risk in patients treated with natalizumab was not studied and the impact of long-term B-cell suppression on JCV and IgG titers is unknown.
As part of the ACAPELLA trial, a prospective study with a primary objective of assessing OCR-associated adverse events (AEs) in a real-world MS population, we sought to evaluate the impact of OCR treatment on immunoglobulin levels and JCV titers over time.
The study includes all subjects receiving OCR at the Elliot Lewis Center followed prospectively since March 2017. Subjects are monitored for occurrence of infections and other serious adverse events (SAEs) and have biannual assessments of serum immunoglobulin levels and JCV antibody titers.
As of December 2019, 291 patients have been treated with OCR and enrolled in ACAPELLA: 181 have been treated for at least 12 months, 131 have been treated for 18 months, and 84 subjects have reached 24 months. Two hundred eighty-one of the total 291 subjects had IgG levels drawn at baseline. Twenty-seven subjects (10%) had IgG levels below the lower limit of normal (LLN) at baseline. Of the 27 patients with low IgG at baseline, 19 have received treatment for at least 12 months. Of those 19, 4 patients were seen to have a >10% drop in IgG level after 12 months. Ten patients developed at least one low IgG level after 12-24 months of treatment exposure, although many returned to normal.
Two hundred eighty-one of the 291 patients had a baseline JCV index. Ninety-three (33%) had titers <0.4, 73 (26%) between 0.4-1.5, and 115 (41% >1.5. In our two-year data, three patients had a change in JCV status from positive to negative between 12 and 24 months of treatment duration. Year three data is characterized in the poster.
The frequency of persistent hypogammaglobulinemia was low in this cohort of patients and thus far has not been associated with an increased risk of infection. Three patients had a change in JCV status from positive to negative, and the effect of JCV index in the remaining subjects is further characterized.