We need a new approach to clinical trials in alcohol‐associated hepatitis: Is there a lesson in RECOVERY?

Abstract

If it were done when 'tis done, then 'twere well It were done quickly.

Letter to the Editor: Survival in placebo-treated patients with severe alcohol-associated hepatitis

“…In conclusion, the shown survival figures of placebo-treated sAH patients have major implications for the required sample size of future trials in sAH, questioning the feasibility of demonstrating superiority over placebo in a classical RCT design. Therefore, we fully agree with the conclusion of Lucey and Thursz that alternative trial designs should be explored to identify effective new treatments for this extremely vulnerable patient population 2…”

“…To the editor, With great interest, we read the recent article of Szabo et al, [1] reporting a negative randomized controlled trial (RCT) in patients with severe alcoholic hepatitis (sAH) and the accompanying editorial of Lucey and Thursz. [2] We share the concern for future trial design in sAH regarding the sample size needed to demonstrate the survival benefit of a specific therapy. Insight into the survival of placebo-treated patients, as a surrogate for the natural history of the disease, is crucial herein.…”

“…Therefore, we fully agree with the conclusion of Lucey and Thursz that alternative trial designs should be explored to identify effective new treatments for this extremely vulnerable patient population. [2]…”

Therapeutic modulation of the liver immune microenvironment

“…Importantly, in a later follow-up analysis, patients with AH treated with anakinra+zinc showed a worse outcome compared with the prednisone group as anakinra-treated patients had a significantly lower 90-day survival and a higher rate of acute kidney injury 172,173 . Treatment of AH is rather frustrating since decades, and as discussed by Lucey and Thursz in an accompanying Editorial to the Szabo study, 171 a new “RECOVERY-like” approach will be needed to advance therapies in AH 174 . Anakinra or other anti-IL-1 treatments have so far not been tested in other liver diseases.…”

“…[172,173] Treatment of AH is rather frustrating since decades, and as discussed by Lucey and Thursz in an accompanying Editorial to the Szabo study, [171] a new "RECOVERY-like" approach will be needed to advance therapies in AH. [174] Anakinra or other anti-IL-1 treatments have so far not been tested in other liver diseases.…”