Lack of dose–response with Pancrease MT for the treatment of exocrine pancreatic insufficiency in adults

Abstract

Background Choosing the optimum pancreatic enzyme replacement therapy for patients with exocrine insufficiency remains a problem. An enteric coated enzyme microsphere pancreatic enzyme preparation (Pancrease) has been marketed with several levels of lipase activity, implying that there is a dose–response relationship between dose and effectiveness such that the high potency form appears to be the most cost effective. Methods In a randomized, single‐blind, cross‐over study, we evaluated the effectiveness of a commercial enzyme preparation with different amounts of lipase per dosage unit in adults with exocrine pancreatic insufficiency. Patients received a diet comprising 100 g fat each day for 6 days. With each meal (three per day) they received two capsules of either Pancrease MT4 (8000 unit lipase), Pancrease MT10 (20 000 units lipase), Pancrease MT16 (32 000 units lipase) or placebo. A 72‐h quantitative faecal collection was carried out for the last 3 days of the 6‐day period. Results There was a reduction in faecal fat excretion with each of the preparations compared to placebo. The difference failed to reach significance with the 8000 units lipase preparation (P>0.05) but was significant (P=0.02) with the 20 000 units lipase and the 32 000 units lipase preparations (faecal fat excretion: placebo=42.1±29 g, lipase 8000 =22.1 ± 7.3 g, lipase 20 000 =10.2±4.5 g and lipase 32 000 = 15.8±12.5 g, P < for 20 000 units and 32 000 units lipase compared to placebo). Conclusion A dose–response relationship between the amount of lipase administered with each meal and a reduction in faecal fat was not evident. The most potent preparation did not provide additional benefits compared to the less expensive lower potency dosage form.

ESPEN guideline on clinical nutrition in acute and chronic pancreatitis

“…The results of several RCTs have proven the efficacy of pancreatic enzyme replacement therapy with enteric-coated mini-microspheres at a dose ranging from 40,000e80,000 PhU of lipase per main meal, and half dose per snack [165,166,170,172e174]. Studies evaluating enteric-coated microspheres have shown a similar efficacy for doses ranging from 10,000e40,000 PhU of lipase per meal, indicating the lack of a dose-response relationship with these preparations [175,176]. Dose escalation may be warranted according to response.…”

Systematic review: efficacy and safety of pancreatic enzyme supplements for exocrine pancreatic insufficiency

“…Twenty‐nine relevant studies were identified, retrieved and completely reviewed. Seventeen studies 6–22 did not meet study selection criteria because of a variety of exclusion criteria, including inappropriate or incomplete reporting about changes in fat absorption, non‐use of cross‐over design, or use of inappropriate patient populations. Twelve studies 23–34 met all inclusion criteria and were available in full manuscript form for inclusion in this systematic review (Table 1).…”

Efficacy and safety of pancreatic enzyme replacement therapy on exocrine pancreatic insufficiency: a meta-analysis

“…Higher dose than usually used might obtain more fat and nitrogen absorption, and consequently improve nutritional parameters in more severe CP patients [ 43 , 44 ]. However, high strength PERT is demonstrated unimproved evident effectiveness but high expense and more adverse events, such as fibrosing colonopathy, hyperuricemia or potential for viral transmission [ 45 – 50 ]. Therefore, Cystic Fibrosis Consensus Committee provides a guideline that the upper limit of daily dosage of PERT in patients with cystic fibrosis: 10,000 IU lipase per kg body weight [ 51 ].…”