Underutilization of pancreatic enzyme replacement therapy in pancreatic cancer and chronic pancreatitis

Exocrine pancreatic insufficiency (EPI) is a major complication associated with several conditions, such as chronic pancreatitis (CP), pancreatic cancer, and cystic fibrosis [1]. It is characterized by reduced/abnormal secretion or activity of the pancreatic enzymes resulting in chronic malabsorption and malnutrition. EPI presents clinically with abdominal pain, steatorrhea, and unintentional weight loss along with clinical signs of deficiency of fat-soluble vitamins such as vitamin D. CP has been identified as the most common cause of EPI, with an estimated prevalence of 60%–90% within 10–12 years from diagnosis [2].


Underutilization of pancreatic enzyme replacement therapy in pancreatic cancer and chronic pancreatitis
Dear Editor, Exocrine pancreatic insufficiency (EPI) is a major complication associated with several conditions, such as chronic pancreatitis (CP), pancreatic cancer, and cystic fibrosis [1].It is characterized by reduced/abnormal secretion or activity of the pancreatic enzymes resulting in chronic malabsorption and malnutrition.EPI presents clinically with abdominal pain, steatorrhea, and unintentional weight loss along with clinical signs of deficiency of fat-soluble vitamins such as vitamin D. CP has been identified as the most common cause of EPI, with an estimated prevalence of 60%-90% within 10-12 years from diagnosis [2].
Pancreatic enzyme replacement therapy (PERT), involving supplementation with fixed dose formulations of pancreatic enzymes, is the mainstay of treatment for patients with EPI.
PERT has been shown to be associated with improvement in overall nutritional status, quality of life measures, and EPI-related symptoms [3].According to the United European Gastroenterology guidelines on the diagnosis and therapy of CP, PERT is indicated for all patients with CP and PEI in the presence of clinical symptoms or laboratory signs of malabsorption [4].Similarly, the American College of Gastroenterology endorses the use of PERT in the management of EPI, aimed at reduction in symptoms, gain of weight, improvement in fat absorption, improvement in fat-soluble vitamin and trace element levels, reduction in consequences of maldigestion (e.g., risk of bone fracture due to osteoporosis), improvement in quality of life, or reduction in mortality [5].However, despite known benefits, infrequent prescription and underuse of PERT are common [6].Existing studies also show that adherence to evidence-based guidelines in the medical management of EPI remains suboptimal [7][8][9].Therefore, we sought to analyze various factors associated with the use of PERT in patients with EPI.
We used TriNetX, a national database comprising approximately 74 million patients across 54 health care organizations in the United States.We retrospectively identified patients who were prescribed PERT for patients with an ICD10 diagnosis of CP or pancreatic cancer with a concomitant diagnosis of EPI.We then performed a comparative analysis between patients who were prescribed PERT and those who were not.The odds ratio and 95% confidence interval were calculated for differences between cases and the comparison groups.
Out of 73,992,263 patients, 20,754 had a diagnosis of CP or pancreatic cancer and EPI, but only 5672 (27.3%) received PERT.A comparative analysis between patients who received PERT and those who did not are presented in Table 1.
The current analysis highlights the underutilization of PERT for the management of EPI.
Patients who were not prescribed PERT were significantly older and more likely to be Asian, which demonstrates key disparities in the use of PERT.Patients with certain comorbidities, such as type 2 diabetes, celiac disease, and class III obesity with prior bariatric surgery, were more likely to be prescribed PERT.It is possible that the presence of comorbidities prompts these patients to seek medical care, allowing the initiation of PERT.Severe EPI results in complications, such as progressive protein calorie malnutrition and vitamin D deficiency.This could explain the higher odds of PERT prescription noted among these groups in our analysis and highlights relative delays in the initiation of PERT.In the current analysis, patients with substance use disorders had higher odds of being prescribed PERT; perhaps due to severe disease and chronic malabsorption commonly noted among these patients [10,11].EPI is a major complication of surgical resection in patients with pancreatic cancer, which may explain the higher odds of PERT prescription in patients who underwent pancreatectomy for pancreatic cancer [12].PERT is a cost-effective therapy that curtails health care burden and significantly improves outcomes among patients with EPI.Provider and patient education along with robust nutritional surveillance are crucial to mitigate underutilization of PERT among patients with EPI.
Most patients appear to be initiated on therapy after they have developed complications such as malnutrition and nutritional deficiencies.Although the current analysis is limited by lack of insurance information, patients with financial needs may need special assistance to allow unrestricted access to therapy.Focused efforts to target groups at greater risk of undertreatment may help bridge disparities in PERT prescription.Further large prospectives are needed to investigate the impact of targeted interventions aimed at the amelioration of under-prescription of PERT for the treatment of EPI.

Table 1 .
Comparative analysis between patients who did and did not receive pancreatic enzyme replacement therapy (PERT).