Safety of disease modifying anti-rheumatic agents in rheumatoid arthritis patients with chronic viral hepatitis

Objective To examine the safety of the use of disease modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients with chronic viral hepatitis (CVH) Methods Records of 600 Chinese patients satisfying the ARA criteria for RA in two r heumatology centers were reviewed. Patients with CVH were studied. Liver en zymes were checked before (baseline) and during DMARD use at 3-month interv als or more frequently if necessary. Drug-episodes (D-Ep), defined as the c ontinuous use of DMARD, singly or in combination, for more than 6 months in a patient, were analysed. Changes in serum liver alanine transaminase (ALT ) levels as multiples of the upper range of normal were taken to reflect th e severity of hepatotoxicity. Changes of ALT to greater than or equal to 1. 5 times the upper range of normal if they were measured at baseline or grea ter than or equal to 2 times the upper range of normal if they were measure d during and after the use of DMARD were considered as abnormal. Control pa tients included those with CVH alone (n = 623) or RA without CVH (n = 62) m atched for age, sex and D-Ep. Results 30 RA patients were found to have concomitant CVH. One patient was excluded because of use of NSAID alone (n = 2). Among the 29 patients, 23 were HBsA g +ve and 6 were anti-HCV Ab +ve. A total of 47 D-Ep were analysed. 20/47 ( 42.6%) of D-Ep in 16/29 (55.2%) RA+CVH patients developed abnormal ALT leve ls after a mean 1.9-year duration of DMARD use. This was statistically sign ificant when compared with 13/94 (13.8%) of D-Ep which ended with abnormal ALT levels in 13/62 (21%) patients with RA alone (p < 0.0001 for D-Ep which ended Lcp with abnormal ALT, and p < 0.02 for the number of patients who d eveloped abnormal ALT) and 128/623 (20.5%) patients with CVH alone (p < 0.0 05). 53% (9/17) of hydroxychloroquine (HCQ) D-Ep were associated with an ab normal outcome. Corresponding figures for sulphasalazine (SAZP) and oral or intramuscular gold preparations were 55.6% (5/9) and 0% (0/3) respectively . Two patients on methotrexate, used either singly or in combination, had n ormal ALT levels throughout the study period. One patient on azathioprine d eveloped reactivation of hepatitis B infection. When D-Ep of the RA+CVH gro up were further analysed, 16/43 (37.2%) and 4/4 (100%) D-Ep which started w ith normal and abnormal baseline ALT respectively developed further liver e nzyme derangement. Conclusion The use of DMARD in RA+CVH patients is associated with a high incidence of hepatotoxicity. The effect is likely to be synergistic. This includes drugs such as HCQ, which is generally believed to be less hepatotoxic.