Thymosin alpha-1 · research summary

Association between pretreatment lymphocyte count and efficacy of immune-enhancing therapy in acute necrotising pancreatitis: a post-hoc analysis of the multicentre, randomised, placebo-controlled TRACE trial.

EClinicalMedicine · 2023. Summary drawn from the study's full text. Each statement is followed by the exact sentence it comes from. This is a research summary, not medical advice.

Study type

Post-hoc analysis of a multicentre, double-blind, randomised, placebo-controlled trial
“A post-hoc analysis of data from a multicentre, double-blind, randomised, placebo-controlled trial testing the efficacy of Tα1 therapy in patients with predicted severe ANP was performed.”

Subjects

Patients with predicted severe acute necrotising pancreatitis
“The TRACE trial recruited patients with predicted severe ANP (APACHE II (acute physiology and chronic health evaluation II) ≥ 8) admitted within seven days of the advent of abdominal pain.”

Sample size

502 patients involved in the analysis
“Between March 18, 2017, and December 10, 2020, a total of 508 patients were randomised in the original trial, and 502 were involved in this analysis, with 248 in the Tα1 group and 254 in the placebo group.”

Duration

90 days follow-up for primary outcome
“The primary outcome was the incidence of IPN 90 days after randomisation.”

Reported findings

Tα1 therapy significantly reduced the risk of infected pancreatic necrosis in patients with baseline absolute lymphocyte count ≥0.8 × 10^9/L
“Within the subgroup of patients with baseline ALC≥0.8 × 10ˆ9/L (n = 290), the Tα1 therapy significantly reduced the risk of IPN (covariate adjusted risk difference, −0.12; 95% CI, −0.21,-0.02; p = 0.015).”
Patients with baseline absolute lymphocyte count between 0.79 and 2.00 × 10^9/L benefited most from Tα1 therapy
“Patients with baseline ALC between 0.79 and 2.00 × 10ˆ9/L benefited most from the Tα1 therapy in reducing IPN (n = 263).”
No significant difference in mortality or other secondary clinical outcomes was observed between groups
“Mortality and other clinical outcomes during the 90 days after randomisation was comparable between groups.”

Limitations stated by the authors

Subgroup analysis was not pre-specified, interaction strength was inconsistent, and generalisability may be affected by high proportion of hypertriglyceridemia cases
“Some limitations must be acknowledged: (1) the subgroup analysis and the "direction" of the treatment effect were not pre-defined; (2) the strength of interaction was inconsistent among multiple subgroups defined by using different definitions of 'lymphopenia'; (3) other measures of immune suppression such as IL-10, in addition to baseline ALC, were not used; (4) approximately half of the study patients were caused by hypertriglyceridemia, which may affect the generalisability of the results; and (5) Due to the difficulties in multisite lab standardisation, the mHLA-DR expression was only obtained in less than half of the study individuals, making the comparison likely underpowered.”

Source: PubMed 37007743 · DOI 10.1016/j.eclinm.2023.101915 · all study summaries

Reported findings

Tα1 therapy significantly reduced the risk of infected pancreatic necrosis in patients with baseline absolute lymphocyte count ≥0.8 × 10^9/L

“Within the subgroup of patients with baseline ALC≥0.8 × 10ˆ9/L (n = 290), the Tα1 therapy significantly reduced the risk of IPN (covariate adjusted risk difference, −0.12; 95% CI, −0.21,-0.02; p = 0.015).”

Patients with baseline absolute lymphocyte count between 0.79 and 2.00 × 10^9/L benefited most from Tα1 therapy

“Patients with baseline ALC between 0.79 and 2.00 × 10ˆ9/L benefited most from the Tα1 therapy in reducing IPN (n = 263).”

No significant difference in mortality or other secondary clinical outcomes was observed between groups

“Mortality and other clinical outcomes during the 90 days after randomisation was comparable between groups.”

Limitations stated by the authors

Subgroup analysis was not pre-specified, interaction strength was inconsistent, and generalisability may be affected by high proportion of hypertriglyceridemia cases

“Some limitations must be acknowledged: (1) the subgroup analysis and the "direction" of the treatment effect were not pre-defined; (2) the strength of interaction was inconsistent among multiple subgroups defined by using different definitions of 'lymphopenia'; (3) other measures of immune suppression such as IL-10, in addition to baseline ALC, were not used; (4) approximately half of the study patients were caused by hypertriglyceridemia, which may affect the generalisability of the results; and (5) Due to the difficulties in multisite lab standardisation, the mHLA-DR expression was only obtained in less than half of the study individuals, making the comparison likely underpowered.”