Hepatitis B surface antigen (HBsAg) reverse seroconversion (RS) can happen in patients with rheumatoid arthritis (RA) with resolved hepatitis B (RHB) undergoing biological disease-modifying antirheumatic drugs (bDMARDs). But the incidence and risk factors need to be delineated.
From 2003 to 2019, 1937 patients with RA with available HBsAg and antibody to hepatitis B virus (HBV) core antigen data were retrospectively reviewed, and 489 patients with RHB undergoing bDMARDs treatment were identified. Factors associated with HBsAg RS were analysed.
During 67 828 person-months of follow-up, 27 (5.5%) patients developed HBsAg RS after bDMARD treatment. As compared with those without HBsAg RS, patients with HBsAg RS were older, had lower frequency of antibody to HBsAg (anti-HBs), and lower baseline anti-HBs levels. In multivariate analysis, rituximab, abatacept and baseline negative for anti-HBs were the independent risk factors for HBsAg RS (adjusted HR: 87.76, 95% CI: 11.50 to 669.73, p<0.001; adjusted HR: 60.57, 95% CI: 6.99 to 525.15, p<0.001; adjusted HR: 5.15, 95% CI: 2.21 to 12.02, p<0.001, respectively). The risk of HBsAg RS was inversely related to the level of anti-HBs. Both rituximab and abatacept might result in anti-HBs loss, and abatacept had a cumulative incidence of HBsAg RS of 35.4%-62.5% in patients with low titers or negative of anti-HBs.
Not only rituximab, but also abatacept has a high risk of HBV reactivation in patient with RA with RHB. Anti-HBs positivity cannot confer HBV reactivation-free status if the anti-HBs levels are not high enough for patients with RHB on rituximab and abatacept treatment.