Thymosin Alpha-1

• Randomised controlled trial2012n = 552

  Thymosin alpha-1 added to peginterferon alfa-2a and ribavirin in hepatitis C non-responders

  Finding. Negative on the headline comparison. Sustained viral response in the intention-to-treat population was 12.7% with thymosin alpha-1 versus 10.5% with placebo (P = 0.407). The authors separately report that adding it to standard of care "did not increase the on-treatment HCV viral response", and conclude that thymosin alpha-1 "seems to play no role in the primary therapy of the disease". Among the minority of patients who completed all 48 weeks of therapy, response favoured thymosin alpha-1 — 41.0% (34 of 83) versus 26.3% (26 of 99), P = 0.048 — which the authors offer only as a hypothesis that the drug "may have a secondary therapeutic role as an adjuvant in the prevention of relapses in patients achieving a virologic response during therapy", not as a demonstrated benefit. No significant difference was observed between treatment groups in the incidence of adverse events.

  Limitation. Retreatment of patients whose infection had already failed peginterferon plus ribavirin, 88% of them genotype 1 — it is not a test of thymosin alpha-1 in untreated hepatitis C or in hepatitis B. The favourable 41.0% versus 26.3% figure rests on 182 of the 552 randomised patients: completers are a group defined after randomisation rather than by it, and roughly two thirds of each arm did not finish the course. This is one multicentre trial, published in a journal supplement; the abstract states no phase designation and says nothing about the fate of the development programme.

• Systematic review2026n = 1,349

  Cochrane review of randomised trials in chronic hepatitis B

  Finding. Pooled 10 randomised trials of thymosin-α1 in chronic hepatitis B, conducted in Bangladesh, China, Italy, Korea, Singapore and Taiwan, with the drug given alone or with interferon, pegylated interferon, lamivudine, entecavir, or standard medical therapy (entecavir or tenofovir). Certainty was low for serious adverse events and very low for every other outcome, so every estimate below is uncertain. Thymosin-α1 "may reduce all-cause mortality" (RR 0.53, 95% CI 0.29 to 0.96; I² = 0%; 3 studies, 907 participants; very low certainty), HBV-related mortality (RR 0.53, 95% CI 0.29 to 0.96; 3 studies, 907 participants; very low certainty), serious adverse events (RR 0.72, 95% CI 0.53 to 0.99; 5 studies, 1056 participants; low certainty) and non-serious adverse events (RR 0.47, 95% CI 0.27 to 0.83; 5 studies, 300 participants; very low certainty), but "may have little to no effect on health-related quality of life" (MD 0.70, 95% CI -2.55 to 3.95; 1 study, 161 participants) or on histological improvement (RR 0.51, 95% CI 0.13 to 2.06; I² = 74%; 2 studies, 702 participants), and the evidence is "very uncertain about the effect of thymosin-α1 on hepatitis B-related morbidity" (RR 0.86, 95% CI 0.54 to 1.40; 3 studies, 854 participants). Subgroup testing gave "no evidence of differences in effect" between trials with and without co-interventions.

  Limitation. The review's own conclusion is that "we are not sure whether" thymosin-α1 reduces all-cause mortality, serious adverse events, HBV-related mortality or non-serious adverse events, nor whether it has any effect on quality of life or histological improvement. Certainty was downgraded for risk of bias, for imprecision — "wide or very wide confidence intervals crossing the line of no effect, and small participant numbers" — and for inconsistency (I² = 74% for histological improvement). No pooled estimate draws on all 1349 randomised participants: both mortality results rest on 3 trials and 907 participants, the non-serious adverse event result on 300, and the quality-of-life estimate on a single trial of 161. Trials were published between 1991 and 2018, 1045 of 1349 participants (77.5%) were male, and among the trials reporting age none included anyone younger than 17. Four of the 10 trials were industry-funded, five were funded by research grants and one reported no funding information. Sixteen further studies await assessment because of incomplete reporting, with no responses to the authors' enquiries.

No preclinical studies catalogued.