Background drugs targeting tumor necrosis factor-α (TNF) biological activity deal with an increased risk of infections. Few papers address whether TNF blockers in rheumatic patients with potential HBV occult infection are safe (1–9).
Objectives to evaluate the safety of anti-TNF agents in cases of spondyloarthritis with resolved hepatitis B (HBsAg negative, HBcAb±anti-HBs positive) through a close monitoring of a possible HBV reactivation and/or rise in the aminotransferase levels.
Methods the medical records for 992 outpatients with rheumatic inflammatory diseases attending two Italian Rheumatology Units between 2007–2015 were retrospectively reviewed for diagnosis of spondyloarthritis, current treatment with anti-TNF agents and seropositivity for past HBV infection. 131 patients (70 men, 61 women; mean age:60,63±9,59 years) were included in the study: 55 with ankylosing spondylitis, 65 psoriatic arthritis, 9 inflammatory bowel disease-associated arthritis, 2 non-radiographic axial spondyloarthritis. Mean disease duration was 98,64±42,60 months. 64 patients were currently in treatment with Etanercept (29 in monotherapy, 31 with MTX, 3 with SSZ, 1 with CsA); 32 with Infliximab (18 as monotherapy, 10 with MTX, 3 with SSZ, 1 with CsA); 31 with Adalimumab (16 in monotherapy, 12 with MTX, 2 with LEF, 1 with CsA); 4 with Golimumab (3 with MTX, 1 as monotherapy). 101 patients received only 1 TNF inhibitor (54 Etanercept, 27 Infliximab, 20 Adalimumab); 23 patients switched to a second and 7 patients switched to a third anti-TNF agent. 51 patients had concomitant prednisone <12,5 mg/die. All 131 patients were anti-HBc+, of which 109 were anti-HBc and anti-HBs+. No patient was positive for HBV-DNA at baseline, none received antiviral therapy prior to or during anti-TNF treatment.
Results at the end of the follow-up (mean of 75,50±33,37 months of anti-TNF therapy), no case of viral reactivation was observed in anti-HBc+ patients, no matter anti-HBs positivity. HBV-DNA remained undetectable, HBsAg negative, aminotransferases normal, nor it was necessary to stop biologic therapy because of viral infection.
Conclusions our retrospective analysis supports the safety of TNF inhibitors for spondyloarthritis patients with a serological pattern of previous HBV infection during a follow-up >6 years. Pre-emptive antiviral prophylaxis is not necessary routinely, but strict monitoring for AST/ALT increase, as well as for changes in HBV serology and HBV-DNA, is necessary and seems a cost-effective approach to identify early viral reactivation, whose occurrence is low, but not negligible, and consequently start antiviral therapy.
Kim et al. J Rheumatol 2010;2)Vassilopoulos et al. ARD 2010;3)Caporali et al. Arthritis Care Res 2010;4)Giannitti et al. J Rheumatol 2011;5)Lan et al. ARD 2011;6)Lee et al. Clin Exp Rheumatol 2013;7)Cantini et al. Int J Rheumatol 2014;8)Biondo et al. Eur J Intern Med 2014;9)Barone et al. Hepatology 2015
Disclosure of Interest None declared