Intermittent loss of anti-HBc antibodies in people with multiple sclerosis undergoing disease-modifying therapies

Background: Disease-modifying therapies (DMTs) are widely used in the treatment of multiple sclerosis (MS). A mounting body of evidence suggests that the risk of hepatitis B virus (HBV) reactivation is primary associated with anti-CD20 therapies. HBV infection leads to the development of anti-HBc antibodies, which typically persist for life. However, the existing literature also highlights the intermittent loss of anti-HBc antibodies in certain immunocompromised individuals. The present study aims to gather real-world evidence on the risk of infection in people with MS (pwMS) prior to the initiation or modification of DMTs, with a particular focus on HBV reactivation and the dynamics of anti-HBc antibody levels in this population. Materials and methods: At the Neuroinfectious Unit, pwMS were longitudinally evaluated for infectious risk before starting, switching, or during DMTs, with a particular focus on the course of anti-HBc antibodies over time during anti-CD20 treatment. Results: A seven-year retrospective and observational study was conducted, with 318 pwMS enrolled (183 females and 135 males, with a median age [interquartile range, IQR] of 51 [41-60] years). Among 110 anti-CD20 treated pwMS, 15 were anti-HBc positive, with negative or positive HBsAg, and positive or negative anti-HBs antibodies. In 2/15 of pwMS HBsAg was positive, detectable HBV-DNA was found in blood and start specific antiviral therapy before DMT. During anti-CD20 therapy, four out of the fifteen pwMS showed a transient loss of anti-HBc following the start of anti-CD20 treatment. Moreover, during this seven-year retrospective and observational study, two pwMS showed HBV reactivation. Conclusions: The findings of this observational cohort study demonstrated the intermittent loss of anti-HBc antibodies in pwMS during anti-CD20 therapy. It is imperative that infectious disease screening is performed on pwMS before starting DMTs to define the serological profile and to mitigate the risk of infection, allowing for the avoidance of discontinuing MS therapy and guaranteeing a higher degree of safety. Trial registration: Clinical trial number: not applicable.