Risk factors for losing hepatitis B virus surface antibody in patients with HBV surface antigen negative/surface antibody positive serostatus receiving biologic disease-modifying anti-rheumatic drugs: a nested case-control study

Abstract Background: Hepatitis B virus (HBV) reactivation consequent to immunosuppressive therapy is an increasingly prevalent problem with serious clinical implications. Treatment with biologic agents conduces to the loss of protective antibody to HBV surface antigen (anti-HBs), which significantly increases the risk of HBV reactivation. Hence, we investigated the risk factors for losing anti-HBs in patients with rheumatic diseases and HBV surface antigen negative/anti-HBs positive (HBsAg-/anti-HBs+) serostatus during treatment with biologic disease-modifying anti-rheumatic drugs (DMARDs). Methods: Using a nested case-control design, we prospectively enrolled patients with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis/psoriasis, or juvenile idiopathic arthritis, who were treated with biologic DMARDs at Changhua Christian Hospital, Taiwan, from January 2013 to June 2019 and had HBsAg-/anti-HBs+ serostatus; the analytic sample excluded all patients with HBsAg+ or anti-HBs- serostatus. Anti-HBs titers were monitored 6-monthly and cases were defined as anti-HBs < 10 mIU/ml during follow-up. Cases were matched one- to-all with controls with anti-HBs ≥ 10 mIU/ml on the same ascertainment date and equivalent durations of biologic DMARDs treatment (control patients could be resampled and could also become cases during follow-up). Between-group characteristics were compared and risk factors for anti-HBs loss were investigated by conditional logistic regression analyses. Results: Among 294 eligible patients, 23 cases were matched with 311 controls. The incidence of anti-HBs loss was ∼ 2.7%/person-year during biologic DMARDs treatment. Besides lower baseline anti-HBs titer (risk ratio 0.93, 95% CI 0.89-0.97), cases were significantly more likely than controls to have diabetes mellitus (risk ratio 4.76, 95% CI 1.48-15.30) and chronic kidney disease (risk ratio 14.00, 95% CI 2.22-88.23) in univariate analysis. Risk factors remaining significantly associated with anti-HBs loss in multivariate analysis were lower baseline anti-HBs titer (adjusted risk ratio 0.93, 95% CI 0.88-0.97) and chronic kidney disease (adjusted risk ratio 45.68, 95% CI 2.39-871.5). Conclusions: Besides lower baseline anti-HBs titer, chronic kidney disease also strongly predicts future anti-HBs negativity in patients with HBsAg-/anti-HBs+ serostatus who receive biologic DMARDs to treat rheumatic diseases. Patients with low anti-HBs titer (≤ 100 mIU/ml) and/or chronic kidney disease should be monitored during biologic DMARDs therapy, to enable timely prophylaxis to preempt potential HBV reactivation.

Gender differences in ankylosing spondylitis-associated cumulative healthcare utilization: a population-based cohort study.

BACKGROUND: Ankylosing spondylitis (AS) is one of the most common rheumatic diseases with gender differences in prevalence and clinical presentation. This study aimed to examine whether such gender differences are correlated with cumulative healthcare utilization in Taiwan. METHODS: The National Health Insurance Research Database supplied claim records of one million individuals from 1996 to 2007. Selected cases included patients aged >16 years. Certified rheumatologists diagnosed the patients in three or more visits and gave prescriptions for AS. Multivariate adjusted logistic regression analyses were used to calculate the influence of gender on cumulative healthcare utilization associated with AS. RESULTS: The study included 228 women and 636 men. After adjustment for potential confounding factors, men had more cumulative outpatient visits associated with AS (odds ratio, 1.59; 95% confidence interval, 1.13 -2.23; p = 0.008). Men also exhibited a trend for higher frequency of AS-related hospitalization (p = 0.054). CONCLUSION: Men are more likely to have high cumulative AS-associated healthcare utilization than women. Further investigation of the causal factors is warranted.

Gender differences in ankylosing spondylitis-associated cumulative healthcare utilization: a population-based cohort study

BACKGROUND: Ankylosing spondylitis (AS) is one of the most common rheumatic diseases with gender differences in prevalence and clinical presentation. This study aimed to examine whether such gender differences are correlated with cumulative healthcare utilization in Taiwan. METHODS: The National Health Insurance Research Database supplied claim records of one million individuals from 1996 to 2007. Selected cases included patients aged >16 years. Certified rheumatologists diagnosed the patients in three or more visits and gave prescriptions for AS. Multivariate adjusted logistic regression analyses were used to calculate the influence of gender on cumulative healthcare utilization associated with AS. RESULTS: The study included 228 women and 636 men. After adjustment for potential confounding factors, men had more cumulative outpatient visits associated with AS (odds ratio, 1.59; 95 percent confidence interval, 1.13 -2.23; p = 0.008). Men also exhibited a trend for higher frequency of AS-related hospitalization (p = 0.054). CONCLUSION: Men are more likely to have high cumulative AS-associated healthcare utilization than women. Further investigation of the causal factors is warranted.