Background Rheumatoid arthritis (RA) patients with chronic hepatitis B virus infection (HBV) are at risk for HBV reactivation during TNF inhibitor (TNFi) therapy. Recent data in patients with hematologic diseases have shown an increased risk for HBV reactivation after rituximab (RTX)-based therapies, even in past HBV infection. Similar data are sparse in RA patients especially with the newer non-TNFi biologics (abatacept-ABA, tocilizumab-TCZ).
Objectives To evaluate the long term safety of non-TNFi biologics in RA patients with chronic or past HBV infection and in HBV vaccinated patients.
Methods A retrospective systematic chart review of the 346 RA patients treated with biologics in our Rheumatology Unit from 1/1/2003 to 31/12/2015 was performed. All patients were followed regularly with appropriate clinical and laboratory monitoring (ALT, HBV DNA levels). We identified 44 patients; 8 with chronic HBV infection (HBsAg+), 25 with past infection (anti-HBc+/anti-HBs+ n=12, anti-HBc+ only n=10, anti-HBs+ only n=3) and 11 HBV vaccinated patients (anti-HBs+) who were treated with IV non-TNFi biologics (ABA, RTX, TCZ). Patient's files were reviewed for biochemical or virological reactivation and anti-HBs titers (before and during therapy) were measured in stored patients' sera.
Results 38/44 (86%) of patients were women with a mean age of 64 ± 16.8 years and a mean disease duration of 14.4 ± 11.3 years. 28/44 (65%) were seropositive (RF and/or anti-CCP) and 80% had been previously treated with TNFi (median: 14 months). Eight patients with chronic HBV infection (all HBV DNA negative at baseline) received 9 courses of non-TNFi (RTX: n=4, ABA: n=4, TCZ n=1) under appropriate antiviral prophylaxis (tenofovir: n=5, lamivudine: n=2, entecavir: n=2, median treatment period: 19 months). During follow-up, no evidence of biochemical or virological reactivation was observed. Similarly, there were no cases of HBV reactivation among 25 patients with past HBV infection treated with 33 courses of non-TNFi (RTX: n=21, TCZ n=7, ABA: n=5, median treatment period: 18 months). Anti-HBs titers were measured during non-TNFi treatment in 26 anti-HBs+ patients (past infection: n=15, vaccinated: n=11, median interval between testing: 28 months) who had received 32 treatment courses (RTX: n=15, TCZ: n=12, ABA: n=5). Although anti-HBs titers decreased with all non-TNFi, this was statistically significant only for TCZ (from 436 ± 388 iu/L to 323 ± 368 IU/L, p=0.021) and not for RTX (from 394 ± 396 iu/L to 381 ± 417 IU/L, p=0.213) or ABA (from 362 ± 413 IU/L to 279 ± 410 iu/L, p=0.144). Anti-HBs titers dropped <10 IU/L in only 3 patients (10%, 2 with past infection on RTX, 1 vaccinated on TCZ); all had low anti-HBs titers before treatment (26 ± 9 IU/L) and none exhibited HBV reactivation.
Conclusions In this long term study, non-TNFi biologics proved to be safe for patients with chronic HBV infection on oral antivirals as well as in patients with resolved HBV infection. Despite a small decrease in anti-HBs titers during treatment, only 10% of anti-HBs+ patients exhibited levels below the protective cut-off and this was not associated with HBV reactivation.
Acknowledgement Supported by research grants from the Special Account for Research Grants (S.A.R.G.), National and Kapodistrian University of Athens, Athens, Greece.
Disclosure of Interest None declared