Temporal prescribing trends in AIH: exploring the influence of early thiopurine use on corticosteroid dependency and biochemical response

Abstract

Objective: patients with autoimmune hepatitis (AIH) receive variable corticosteroid and thiopurine regimens. Our aim was to undertake a cohort study to determine whether earlier introduction of azathioprine allowed reduction in cumulative corticosteroid burden. We also determined temporal trends in treatment choices and outcomes. 

Method: 226 adults with AIH treated from 1970 to 2020 at Kings College Hospital were divided into two groups: patients who received azathioprine therapy within 8 weeks of initiation of corticosteroid therapy (early group, n=106) and patients who had received azathioprine more than 8 weeks after corticosteroid initiation (late group, n=120). 

Results: cumulative exposure to corticosteroid was not significantly different between each group. 80% of patients achieved normalisation of aspartate aminotransferase within 6 months of corticosteroid induction compared with 64.5% in the late group (p=0.013). When evaluated by decade, the cumulative corticosteroid exposure and dose declined over time (p<0.001). Azathioprine initiation fell from a mean of 80 weeks from corticosteroid induction in the 1970s to 10 weeks in the 2010s (p=0.026). Biochemical remission occurred at a faster rate in more recent cohorts (p=0.001). 

Conclusion: earlier introduction of azathioprine after corticosteroid therapy resulted in a higher rate of transaminase normalisation at 6 months but did not significantly reduce the cumulative prednisolone exposure over 5 years. Temporal effects in the management of AIH are evident, whereby earlier introduction of thiopurines in recent decades facilitated more rapid reduction in corticosteroid dose while achieving a higher rate of biochemical response.

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