Chronic Pancreatitis: Enzyme Replacement Effective

Ricki Lewis, PhD

December 20, 2016

Pancreatic enzyme replacement therapy (PERT) successfully treats exocrine pancreatic insufficiency (EPI) due to chronic pancreatitis (CP), according to results of a meta-analysis of controlled clinical trials published online December 9 in Gut.

The analysis found that PERT reduces pain, fecal fat excretion, fecal nitrogen excretion, and fecal weight; improves nitrogen and fat absorption and quality of life; and counters nutritional deficiencies.

EPI decreases absorption of fat-soluble vitamins, essential fatty acids, folic acid, thiamine, calcium, zinc, and magnesium, and contributes to the decreased median survival following CP diagnosis. The symptoms of severe abdominal pain, diarrhea, weight loss, and steatorrhea adversely affect quality of life, and the associated malnutrition increases the risk for osteoporosis, infection, and cardiovascular disease. EPI affects more than half of patients diagnosed with CP and becomes severe within 5 to 10 years of diagnosis.

PERT uses porcine digestive enzymes (pancreatic amylase, protease, and lipase), with lipase the most important. The drugs differ by whether or not they have enteric coating and composition (granules, microtablets, microspheres, or mini-microspheres).

Daniel de la Iglesia-García, MD, from the NIHR Liverpool Pancreas Biomedical Research Unit at the University of Liverpool, United Kingdom, and the Department of Gastroenterology and Hepatology at University Hospital of Santiago de Compostela in Spain, and colleagues searched databases covering 1966 to 2015. They identified 511 patients with CP treated in 17 studies, of which 14 were analyzed quantitatively.

The primary outcome for the meta-analysis was coefficient of fat absorption, calculated from fat intake and excretion in feces. Secondary outcomes were coefficient of nitrogen absorption; fecal fat excretion and nitrogen excretion; fecal weight, consistency, and frequency; abdominal pain and gastrointestinal symptoms; body weight; quality of life; and adverse events.

The investigators evaluated PERT compared with baseline, placebo, and each other and considered different formulations, doses, and schedules of the products.

Pooled results of the 11 studies that assessed coefficient of fat absorption indicated improvement with PERT compared with baseline (83.7 ± 6.0 vs 63.1 ± 15.0; P < .00001). Four studies evaluated coefficient of nitrogen absorption, which also improved compared with baseline, as did fecal fat excretion, fecal nitrogen excretion , and fecal weight in 13 studies. PERT also improved fecal consistency, abdominal pain, and flatulence, with no effect on fecal frequency. Findings were similar for placebo (83.2 ± 5.5 vs 67.4 ± 7.0; P = .0001).

Comparison of the PERTs revealed higher efficacy with higher dose, enteric coating, acid suppression, and administration during meals. Subgroup analyses accounted for the differences among the products, with findings similar to those of the overall evaluation. Adverse effects were not significant.

"Unlike in the previous Cochrane review with meta-analysis of only two studies, our meta-analysis of 14 [randomized controlled trials] demonstrates that PERT is clearly indicated in CP for EPI," the researchers concluded.

Limitations of the study reflect limitations in the evaluated investigations: short-term (less than 2 months) study period and no consideration of health inequality indicators, such as alcoholism and smoking. Health inequality is an independent risk factor for EPI.

"The article pulls together a number of studies using various agents and various dosages to provide more precise estimates of effect and benefit. The combined data provide additional reassurance that the agents have at least reasonable effectiveness," Chris E. Forsmark, MD, chief of the Division of Gastroenterology, Hepatology, and Nutrition at the University of Florida, Gainesville, told Medscape Medical News.

Dr Forsmark added that the analysis shows that PERT improves fat and protein digestion and absorption, but not to the levels of patients without CP and EPI. He also pointed out what the meta-analysis did not address. "Does PERT prevent important nutritional complications, specifically osteoporosis and metabolic bone disease? Does PERT prolong life? What is the minimum dosage or optimal dosage for these agents? So all in all a very nice quantitative analysis — but still lots of unknowns in terms of hard outcomes and effective utilization."

Coauthors Dr Domínguez-Muñoz and Dr Sutton have consulted for Abbott (Mylan).

Gut. Published online December 9, 2016. Full text

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