ORLANDO – Adding celecoxib to octreotide within 48 hours of onset of acute pancreatitis may reduce the risk of progression to severe acute disease and its consequences, based on data from a randomized controlled trial of more than 300 patients.
The findings were presented at the annual Digestive Disease Week.
Overall, 25.6% of patients predicted to progress to severe acute pancreatitis (SAP) who were assigned to octreotide (Sandostatin) alone had organ failure at day 8, compared with 12.9% who received both octreotide and celecoxib (Celebrex), reported Dr. Rui Wang of West China Hospital, Sichuan University, in Chengdu, China.
In addition, 36.7% of patients on octreotide-only had CT severity index (CTSI) scores of 6 or greater at day 8, compared with 15.1% of patients on octreotide and celecoxib combined.
"Celecoxib exerted special effects on reducing incidences of pulmonary failure, acute respiratory distress syndrome, and encephalopathy," Dr. Wang said.
Dr. Wang and colleagues hypothesized that celecoxib may decrease serum levels of the inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor–alpha (TNF-alpha), and increase levels of the anti-inflammatory interleukin-10 (IL-10).
To see whether celecoxib could augment the anti-inflammatory action of octreotide, an analogue of the endogenous anti-inflammatory peptide somatostatin, the investigators conducted a study of high-dose octreotide and somatostatin in patients with predicted or actual SAP.
They enrolled 195 patients with predicted SAP, defined as an Acute Physiology and Chronic Health Evaluation II (APACHE II) score greater than 8, and a multiorgan failure (MOF) score lower than 2; and 159 patients with SAP, defined as an APACHE II score greater than 8 and a MOF score of 2 or greater.
Patients in each disease category were randomized within 48 hours to receive either octreotide alone in an IV infusion at 50 mcg/hour for 3 days, and then 25 mcg/hour for 4 days, or to the same 7-day octreotide regimen plus 200 mg of oral celecoxib twice daily.
Patients with predicted SAP who received the combination had less than half the rate of progression to SAP (P = .001) and half the rate of organ failure (P = .030).
Among patients with frank SAP, there were no significant differences between octreotide alone and octreotide/celecoxib for organ failure, local complications, CTSI or MOF scores, or length of hospital stay, the researchers noted.
Compared with octreotide alone, the addition of celecoxib significantly reduced day 8 rates of acute respiratory distress syndrome (ARDS) (24% vs. 11%, respectively; P = .037), and encephalopathy (16% vs. 5.5%; P = .039).
With regard to the secondary outcome of plasma cytokine levels, the researchers found that octreotide alone or combined with celecoxib similarly restored somatostatin levels to normal by day 8.
The investigators also found that the combination therapy, but not octreotide alone, normalized plasma levels of both IL-6 and TNF-alpha (P less than .05 over baseline), and that IL-10 levels were markedly increased in both groups, although the combination treatment significantly outperformed octreotide-only (P less than .05).
The findings suggest that early treatment with a combination of octreotide and celecoxib may prevent progression to SAP and also ameliorate both ARDS and encephalopathy through simultaneous down-regulation of inflammatory cytokines and promotion of the anti-inflammatory IL-10, the researchers noted.
The funding source was not disclosed. Dr. Wang and colleagues reported having no financial disclosures.
