Methods: Using 1997-2011 national data from the U.S. Veteran’s Health Administration, we identified a cohort of 38,453 rheumatologist-diagnosed RA patients.  Patients who had hepatitis B infection (defined by detectable hepatitis B surface antigen, hepatitis B core antibody or hepatitis B DNA), initiated a new biologic (anti-TNF: infliximab, adalimumab, etanercept; vs. rituximab) that they had never been on previously and had a baseline ALT < 1.5x the upper limit of laboratory normal within 90 days prior to starting biologic therapy were eligible for analysis.  Patients could contribute more than one biologic treatment episode provided they switched to a new biologic they had not previously used, or switched to a previously used biologic they had not used in the past year. The main outcome of interest was hepatotoxicity, defined as ALT elevation > 100 IU/L (corresponding to 3x ULN for women and 2.5 ULN for men).  Hepatotoxicity was examined within the first year of biologic use.  Current exposure was defined as-treated based on day supply (injection biologics) or usual dosing intervals (infused biologics).  Results were reported as the cumulative incidence of patients achieving pre-defined hepatotoxicity at 3, 6 and 12-months post biologic exposure.

Results: 248 RA patients with hepatitis B were identified and contributed 322 new biologic treatment episodes.  Mean age was 60.2 years and 91.7% were male. Overall, ALT elevations were uncommon, with 10 hepatotoxicity events (ALT > 100 IU/L) occurring among 322 episodes (3.1%) within 12-months.  Most hepatotoxicity events (7/10, 70%) occurred within 90 days of initiation of biologic. The highest proportion of hepatotoxicity occurred in patients receiving rituximab (4/35, 11.4%) (p = 0.013 vs. anti-TNF).

Table:  RA patients with Hepatitis B and hepatotoxicity within 12 months of initiating biologics