Patients with rheumatoid arthritis (RA) and resolved hepatitis B virus (HBV) infection receiving immunosuppressive therapy were at an elevated risk of viral reactivation, according to research published in the Annals of Rheumatic Disease.
Wataru Fukuda, MD, of the Center for Rheumatic Disease at the Japanese Red Cross Daiichi Hospital in Kyoto, Japan, and colleagues conducted a multicenter, observational, prospective study over 2 years to investigate the incidence and risk factors of HBV reactivation.
Patients eligible for study inclusion were ≥18 years old with a diagnosis of RA or other rheumatic disease who were being evaluated at several specialty rheumatic disease clinics in Japan. Researchers collected demographic information, rheumatic disease duration, and data related to hepatitis medical history including HBV surface antigen (HBsAg), anti-HBV surface antibody (HBsAb), and anti-HBV core antibody (HBcAb) titers, and immunological data.
Primary study end point was frequency of HBV reactivation in HBsAg negative, HBsAb-positive and HBcAb –positive patients with comorbid rheumatic disease. Secondary end points were the clinical and serological assessments after HBV reactivation.
Just over 1040 patients were included for analysis; 959 of those patients were diagnosed with RA. A majority of patients with RA were treated with methotrexate (MTX), and almost one-third used a biologic—73% of which were tumor necrosis factor inhibitors (TNFis).
Investigators detected HBV DNA in 35 patients—32 with RA and 3 with other rheumatic diseases. Positivity >2.1 log copies/mL was seen in 10 patients (8 with RA, 2 with other rheumatic diseases). Researchers calculated HBV reactivation frequency to be 1.93 per 100 person-years and found that quantitative positivity (defined as ≥2.1 log copies/mL) was 0.55 per 100 person-years. Patients with negative HBsAb had higher incidence rates of reactivation than patients with negative HBcAb or positive antibodies.
Poisson regression analyses found that risk ratio (RR) of a low HBsAb titer was 2.8 (95% confidence interval [CI], 1.3-6.8) below the median (71.4) and 3.1 (95% CI, 1.4-6.4) below the cut-off (titer <10.0).
Age >69 years increased patient’s RR for HBV reactivation to 3.3 (95% CI, 1.5-8.4), while patients treated with MTX had lower risk ratios—especially compared to those treated with prednisolone (RR: 0.4; 95% CI, 0.2-0.7 vs RR: 2.2; 95% CI, 1.0-4.6, respectively).
The interval between the start of patient’s immunosuppressant drug regimen and HBV reactivation was between 3 and 182 months (mean: 66.2 months, median: 66 months; interquartile range [IQR]: 60).
Summary and Clinical Applicability
“Although a low HBsAb titer has been considered a candidate risk factor for HBV reactivation, we had no direct evidence to support this idea,” wrote Dr Fukuda and colleagues. “However, our results show that low HBsAb titers at baseline were significant risk factors for HBV reactivation.”
Additionally, Dr Fukuda and colleagues pointed out that biologics, steroids, MTX, and other synthetic disease-modifying antirheumatic drugs (DMARDs) used to treat rheumatic disorders can all cause HBV reactivation; as such, evaluation of reactivation risk in each drug is important when starting therapy.
Limitations and Disclosures
Risk and latency of immunosuppression could not accurately be estimated
The dosage and combination of immunosuppressive drug regimens were modified in many patients
Fukuda W, Hanyu T, Katayama M, et al. Incidence of hepatitis B virus reactivation in patients with resolved infection on immunosuppressive therapy for rheumatic disease: a multicentre, prospective, observational study in Japan. Ann Rheum Dis. 2016. doi: 10.1136/annrheumdis-2016-209973 [ePub ahead of print]