HBV reactivation in HBsAg-/HBcAb+ rheumatoid arthritis patients receiving biologic/targeted synthetic DMARDs.

BACKGROUND: Rheumatoid arthritis (RA) patients seropositive for hepatitis B core antibody (HBcAb) and negative for hepatitis B surface antigen (HBsAg) are at risk of hepatitis B virus (HBV) reactivation when treated with biologic or targeted synthetic (b/ts) disease-modifying antirheumatic drugs (DMARDs). The study aims to investigate the risk in this population. METHODS: From January 2004 through December 2020, 1068 RA patients undergoing b/tsDMARDs therapy and 416 patients with HBsAg-/HBcAb+ were enrolled. Factors associated with HBV reactivation were analysed. RESULTS: During 2845 person-years of follow-up, 27 of 416 (6.5%,9.5 per 1000 person-years) patients developed HBV reactivation, with a cumulative rate of HBV reactivation of 3.5% at 5 years, 6.1% at 10 years and 24.2% at 17 years. The median interval from beginning b/tsDMARDs to HBV reactivation was 85 months (range: 9-186 months). The risk of HBV reactivation varied by type of b/tsDMARD, with rituximab having the highest risk (incidence rate: 48.3 per 1000 person-years), followed by abatacept (incidence rate: 24.0 per 1000 person-years). In multivariate analysis, rituximab (adjusted hazard ratio [aHR]: 15.77, 95% confidence interval [CI]: 4.12-60.32, p = .001), abatacept (aHR: 9.30, 1.83-47.19, p = .007), adalimumab (aHR: 3.86, 1.05-14.26, p = .04) and negative baseline HBV surface antibody (anti-HBs, <10 mIU/mL) (aHR: 3.89, 1.70-8.92, p < .001) were independent risk factors for HBV reactivation. CONCLUSION: HBsAg-/HBcAb+ RA patients are susceptible to HBV reactivation during b/tsDMARD therapy. Those with negative baseline anti-HBs and those on certain b/tsDMARDs, such as rituximab, abatacept and adalimumab, have high reactivation risks. Risk stratification and management should be based on the patient's baseline anti-HBs titre and type of therapy.

Identification and management of contraindicated drug-drug interactions through pharmaceutical care programs: Experience in direct-acting antivirals therapy.

BACKGROUND/PURPOSE: To investigate the impact of pharmaceutical care programs for the management of contraindicated drug-drug interactions (DDIs) in direct-acting antivirals (DAAs) therapy. METHODS: A prospective observational study was performed at Dalin Tzu Chi Hospital between January 2018 and December 2019. Pharmacists screened DDIs for all hepatitis C patients before DAA therapy. The study outcome included the frequency of contraindicated DDIs, acceptance rate, and cost avoidance of the pharmaceutical care program. RESULTS: A total of 1053 patients were enrolled in the study, with a mean age of 67.1 ± 11.9 years. Most patients received therapy with sofosbuvir/ledipasvir (37.1%; n = 391), elbasvir/grazoprevir (23.8%; n = 251), or glecaprevir/pibrentasvir (21.1%; n = 222). A total of 796 (75.6%) patients received at least one co-medication, with the average number of co-medications being 5.2 per patient (SD: 4.4/patient). In total, 1356 DDIs were identified, with the average DDIs per patient of 1.3 (SD: 1.7). For patients with contraindicated DDIs (2%, n = 102), statins and amiodarone were the most common co-medications. Physicians often accepted pharmacists' recommendations (acceptance rate of 72.5%) or withheld co-medication to avoid severe adverse drug events (ADEs). The estimated cost avoidance of preventable ADEs was USD 14,033 for contraindicated DDIs with pharmaceutical care programs. CONCLUSION: The implementation of pharmaceutical care programs in DAA therapy provides a favorable outcome and substantial cost avoidance.

Risk of Hepatitis B Virus Reactivation in Rheumatoid Arthritis Patients Undergoing Tocilizumab-Containing Treatment.

BACKGROUND AND AIM: To investigate the risk of hepatitis B virus reactivation in patients undergoing long-term tocilizumab therapy for rheumatoid arthritis. METHOD: From January 2011 through August 2019, a total of 97 patients were enrolled in this retrospective study. Clinical data, comedications, and the occurrence of HBV reactivation were recorded. RESULTS: Seven patients were HBsAg+ (7.2%), 64 were HBsAg-/HBcAb+ (65.9%), and 26 were HBsAg-/HBcAb- (26.8%). The median disease follow-up time was 9 years. TCZ was administered for a median of 29 months. Four patients (4.1%) experienced HBV reactivation after tocilizumab therapy. Of the 7 HBsAg+ patients, 4 received antiviral prophylaxis and had no HBV reactivation; the remaining 3 patients did not receive antiviral prophylaxis, and all 3 (100%) experienced HBV reactivation and hepatitis flare-up. Hyperbilirubinemia occurred in 2 of these 3 patients, with mild prothrombin time prolongation in one. After salvage entecavir treatment, all patients had a favorable outcome. Of the 64 HBsAg-/HBcAb+ patients, only one became positive for serum HBV DNA (2.5 × 107 IU/mL) after 18 months of tocilizumab treatment (1.6%; 1/64). This patient was immediately treated with entecavir, which prevented hepatitis flare-up. CONCLUSIONS: Tocilizumab is widely used in treating rheumatoid arthritis and has the potential to reduce the mortality rate among severe COVID-19 patients. However, HBV reactivation needs to be considered. HBsAg+ patients have a high risk of HBV reactivation, which could be prevented by antiviral prophylaxis. Although the risk of reactivation is low in HBsAg-/HBcAb+ patients, strict monitoring is necessary.

Drug-drug interactions between direct-acting antivirals and statins in the treatment of chronic hepatitis C.

As the first line of treatment for hepatitis C virus (HCV) infection, direct-acting antivirals (DAAs) have greater efficacy and fewer adverse effects than other treatments; however, drug-drug interactions (DDIs) must be avoided when used in combination with other medications, such as statins. HCV patients are mostly in the need for polypharmacy, particularly the comedication of DAAs and cardiovascular drugs such as statins. This poses a risk of pharmacokinetic interactions between the two classes of drugs that may lead to severe myopathy or even rhabdomyolysis. Therefore, evaluating the severity of the DDIs and managing them is important. A multidisciplinary team-based model of care for HCV patients receiving DAAs can review the pharmacology profiles of other drugs for relevant DDIs with the DAAs, before prescription. Such a model can also follow the patients through the therapeutic cycle to make sure that their medical regimen is safe and effective. This article reviews the comedication rate and DDI-prevalence in HCV patients receiving statins along with the DAAs, details the mechanisms involved, gives recommendations for management, and shares our experience with a multidisciplinary team-based care program for the treatment of HCV patients.

Moderate Risk of Hepatitis B Virus Reactivation in HBsAg-/HBcAb+ Carriers Receiving Rituximab for Rheumatoid Arthritis.

To investigate the incidence and risk factors of hepatitis B virus (HBV) reactivation in HBV surface antigen (HBsAg)-/ HBV core antibody (HBcAb)+ patients who underwent rituximab (RTX) therapy for rheumatoid arthritis (RA). From January 2000 through December 2017, a total of 134 RA patients with various HBV serostatuses who received RTX at Dalin Tzu Chi Hospital were screened. Finally, 50 HBsAg-/HBcAb+ patients were enrolled in this retrospective study. Baseline characteristics, comedications, and the occurrence of HBV reactivation were recorded. Four HBsAg-/HBcAb+ RA patients (8%; 4/50) experienced HBV reactivation after treatment with RTX. Hepatitis flare-up occurred in 2 of these 4 patients, with a fatal outcome in one. HBV reactivation occurred approximately 1-4 years after the first dose of RTX and 0.5-1.5 years after the last one. In HBsAg-/HBcAb+ patients, HBV reactivation was significantly more common in those who were HBV surface antibody (HBsAb)- at baseline than in those who were HBsAb+ (30% vs 4%; p = 0.02). A history of adalimumab use was associated with HBV reactivation (100% vs 39%; p = 0.02). A moderate risk of HBV reactivation was observed in HBsAg-/HBcAb+ RA patients receiving RTX therapy. The reactivation may induce acute hepatitis and even death. To reduce the risk of HBV reactivation, regular monitoring of liver function is insufficient; monitoring of viral load and HBsAg or prophylaxis with antiviral therapy should be considered.