Efficacy of TOcilizumab in Mitigating Inflammatory Cascade in Patients with Predicted Severe Acute Pancreatitis: A Multicenter Randomized, Double-Blind, Placebo-Controlled Trial

Aims Progression of acute pancreatitis to moderate to severe disease was associated with as high as 42% mortality rate. Despite this debilitating outcome, there is currently no specific pharmacotherapy for the disease. With better understanding of its pathogenesis, promising pharmacological agents targeting the key detrimental pro-inflammatory cytokines, such as interleukine(IL)-6, have been developed. Tocilizumab, a humanized anti-human IL-6R antibody has been proven to be effective in preventing catastrophic complications of acute pancreatitis in animal studies by inhibiting IL-6 receptor as evidenced by an increase in free IL-6 level. This study aimed to evaluate the efficacy of Tocilizumab in mitigating initial inflammatory cascade in patients with predicted severe acute pancreatitis using pro-inflammatory cytokine as surrogate markers.

Methods Adult patients who were diagnosed with acute pancreatitis and were predicted to develop severe pancreatitis, defined as BISAP score≥3 or Modified Marshall score≥2, between January 2021 and October 2023 were randomly assigned to two groups within 12 hours of presentation. Tocilizumab group received Tocilizumab 4 mg/kg intravenous and standard of care. The placebo group received normal saline intravenous and standard of care. IL-6, CRP, and procalcitonin were collected longitudinally on the date of admission, at 24, and 48-hour.

Results 20 patients with a mean age of 59.5±18.5 years were enrolled. 10 patients were randomized to the Tocilizumab group and 10 patients were to the placebo group. Baseline characteristic of the patients were not different between two groups. Alcohol and gallstone were the majority of the etiology of pancreatitis in both groups (45% and 40%, respectively). There were no statistical differences in the duration of the onset of the symptom onset (16.6±14.3 vs 16.4±14.1 hours; p=0.98), the BISAP score (2.6±0.7 vs 2.3±0.8; p=0.39) or the modified Marshall score (2.7±1.8 vs 2.7±1.9; p=1.00) between the Tocilizumab and placebo groups, respectively. At 48 hours, there was a significantly higher reduction in CRP (-41.9% vs+31.7%; p<0.01) and increase in IL-6 level (+74.2% vs -44.75; p<0.01) in Tocilizumab group compared to placebo, respectively. Although there was a trend toward an increase in procalcitonin level, but there was no statistically difference between both group at 48 hours (12.89+25.71 vs 11.24±18.47; p=0.88). There was no adverse event from medication in both groups [1] [2].

Conclusions Tocilizumab can reduce inflammatory cytokine response in patients with predicted severe pancreatitis at 48 hours, particularly CRP, when administered within the first 12 hours of presentation.

Conflicts of interest

Authors do not have any conflict of interest to disclose.

• References

• 1 Pooran N. et al. &quot;Cytokines (IL-6, IL-8, TNF): early and reliable predictors of severe acute pancreatitis.&quot;. Journal of clinical gastroenterology 2003; 37 (03) 263-266
• 2 Tocilizumab can reduce inflammatory cytokine response in patients with predicted severe pancreatitis at 48 hours, particularly CRP, when administered within the first 12 hours of presentation.

Publication History

Article published online:
15 April 2024