Abatacept is second to rituximab at risk of HBsAg reverse seroconversion in patients with rheumatic disease

Abstract

BackgroundHepatitis 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.MethodsFrom 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.ResultsDuring 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.ConclusionsNot 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.

Risk of hepatitis B virus reactivation following treatment with abatacept: A retrospective study of international pharmacovigilance databases

“…A recent retrospective cohort study including 489 Chinese patients with rheumatoid arthritis and resolved hepatitis B also showed that abatacept is second to rituximab at risk of HBVr, followed by TNF inhibitors. 27 The incidence rates of HBVr for rituximab, abatacept, and TNF inhibitors were 17·72, 9·38, and 0·99 per 1000 patient-years, respectively. 27 Although abatacept and TNF inhibitors are currently classified as the same risk group that is moderate-risk group for HBVr by AGA, 6 more concern may need to be given to abatacept as the above data suggested.…”

“… 27 The incidence rates of HBVr for rituximab, abatacept, and TNF inhibitors were 17·72, 9·38, and 0·99 per 1000 patient-years, respectively. 27 Although abatacept and TNF inhibitors are currently classified as the same risk group that is moderate-risk group for HBVr by AGA, 6 more concern may need to be given to abatacept as the above data suggested.…”

“… 24 , 25 , 26 Recently, a study from China with longer treatment follow-up (median 12·7 years) showed that six out of 69 cases experienced HBVr during abatacept treatment, with an HBVr incidence of 9·38 per 1000 person-years. 27 Abatacept use was found to be independently associated with increased risk of HBVr (adjusted hazard ratio: 60·57, 95% CI 6·99–525·15). 27 This study supports our findings based on international pharmacovigilance databases.…”

“… 27 Abatacept use was found to be independently associated with increased risk of HBVr (adjusted hazard ratio: 60·57, 95% CI 6·99–525·15). 27 This study supports our findings based on international pharmacovigilance databases. Since HBVr relatively rarely happens, studies with longer follow-ups or using extensive population-based databases are more likely to detect a positive association between HBVr and abatacept use, while studies with shorter follow-ups are less likely to detect the association.…”

Average corticosteroid dose and risk for HBV reactivation and hepatitis flare in patients with resolved hepatitis B infection

“…Most of existing studies concerning HBV reactivation focused on novel biological drugs, such as rituximab, abatacept and anti-TNF agents 5 6. Due to the lack of systemically collected data, there is difficulty in estimating the precise risk of HBV reactivation in corticosteroid users with resolved HBV infection.…”