The efficacy and safety of thymosin alpha‐1 in Japanese patients with chronic hepatitis B; results from a randomized clinical trial

Abstract

Thymalfasin (thymosin alpha-1; Talpha1) is a 28-amino acid polypeptide that has shown efficacy in the treatment of chronic hepatitis B virus (HBV) infection. The objective of this study was to evaluate the long-term, dose-related efficacy and safety of Talpha1 treatment in chronic hepatitis B patients with positive HBV-DNA and abnormally high alanine aminotransferase (ALT) levels. A total of 316 patients were randomized to receive either 0.8 or 1.6 mg of Talpha1 monotherapy for 24 weeks. At the end of the 72-week observation period (12 months after cessation of therapy), 36.4% of patients in the 1.6-mg treatment group achieved normalization of ALT, 30% achieved clearance of HBV-DNA by branched DNA vs 15% by transcription-mediated amplification, and 22.8% achieved clearance of HBe-antigen. Patients in the 0.8-mg treatment group achieved similar efficacy rates, although patients with advanced fibrosis demonstrated a significantly better response rate when treated with 1.6 mg of Talpha1 monotherapy vs 0.8 mg (as determined by intragroup analysis; patients were not stratified by liver biopsy). All adverse drug reactions were mild and most involved the fluctuation of liver enzymes, which was most likely related to the positive immune effects caused by the response to Talpha1 treatment. Adverse event incidence was similar in the 1.6- and 0.8-mg treatment groups. In conclusion, Talpha1 at doses of 0.8 and 1.6 mg exhibits long-term efficacy against hepatitis B with a good safety profile.

A randomized controlled trial of thymalfasin plus transarterial chemoembolization for unresectable hepatocellular carcinoma

“…Among adverse events possibly or probably related to thymalfasin, most were mild and resolved without sequelae, and only one (nipple pain) occurred in 10% or more of thymalfasin-treated patients. These results are consistent with those of previous clinical studies, in which thymalfasin has been shown to have an excellent safety profile [32,[45][46][47][48]. When evaluating new agents for HCC, it is crucial to determine that they do not worsen outcomes and survival due to associated toxicity, compared with placebo or existing treatments [49,50].…”

Strategies in Preventing Diabetes after Pancreatectomy Using Islet Auto- and Allo-Transplantation

“…It has since been accepted as the best treatment option for patients who have exhausted or are not amenable to more conservative medical or surgical therapies. TP is considered a therapy of last resort because it is associated with significant long-term metabolic effects [19], with all patients becoming dependent on exogenous insulin to maintain glucose homeostasis [31]. A summary of these findings is provided in Table 1.…”

“…However, total pancreatectomy alone has been shown to have significant morbidity and mortality [17]. It results in total pancreatic endocrine and exocrine deficiency associated with a variety of deleterious metabolic complications including those directly related to postsurgical diabetes [18,19]. Gall, et al reported long term follow up in 117 patients who underwent total pancreatectomy for chronic pancreatitis reporting 19.1% mortality at 6.5 years with many late deaths caused by hypoglycemia [20].…”

Reviews for APASL guidelines: immunomodulator therapy of chronic hepatitis B

“…HBV genotype B responded to therapy better than genotype C (52% vs. 24%, P = 0.036) [67]. A study of 316 Japanese patients with HBeAg-positive chronic hepatitis B treated with either 0.8 or 1.6 mg of thymosin a 1 six times a week for the first 2 weeks and then twice a week for a further 22 weeks showed HBeAg seroconversion in 18.8% and 21.5% at 48 weeks after the end of treatment for the 0.8 and 1.6 mg doses, respectively [68]. In this study, 95% of the patients were genotype C and an HBeAg seroconversion rate of 21.5% was similar to 24% in a study of Taiwanese patients infected with genotype C [67,68].…”

“…A study of 316 Japanese patients with HBeAg-positive chronic hepatitis B treated with either 0.8 or 1.6 mg of thymosin a 1 six times a week for the first 2 weeks and then twice a week for a further 22 weeks showed HBeAg seroconversion in 18.8% and 21.5% at 48 weeks after the end of treatment for the 0.8 and 1.6 mg doses, respectively [68]. In this study, 95% of the patients were genotype C and an HBeAg seroconversion rate of 21.5% was similar to 24% in a study of Taiwanese patients infected with genotype C [67,68]. A meta-analysis including 353 patients from five trials showed that the odds ratios for virological response to thymosin a 1 at the end of treatment and 6 and 12 months post-treatment were 0.56 (0.2-1.52), 1.67 (0.83-3.37), and 2.67 (1.25-5.68), respectively, with a significantly increasing virological response over time after thymosin therapy [69].…”