Efficacy of pancreatic enzyme replacement therapy in chronic pancreatitis: systematic review and meta-analysis

Daniel de la Iglesia-García, Wei Huang, Peter Szatmary, Iria Baston-Rey, Jaime Gonzalez-Lopez, Guillermo Prada-Ramallal, Rajarshi Mukherjee, Quentin M Nunes, J Enrique Domínguez-Muñoz, Robert Sutton, NIHR Pancreas Biomedical Research Unit Patient Advisory Group, Graham Cameron, Kirsty Donaldson, Georgia Jones, John Lancaster, Amy Lucas, Karen Manby, Tor McLaren, Catherine Rodgers, Jason Rodgers, William Swindlehurst, Neil Symon, Douglas Warrington, Mary Whitby, Daniel de la Iglesia-García, Wei Huang, Peter Szatmary, Iria Baston-Rey, Jaime Gonzalez-Lopez, Guillermo Prada-Ramallal, Rajarshi Mukherjee, Quentin M Nunes, J Enrique Domínguez-Muñoz, Robert Sutton, NIHR Pancreas Biomedical Research Unit Patient Advisory Group, Graham Cameron, Kirsty Donaldson, Georgia Jones, John Lancaster, Amy Lucas, Karen Manby, Tor McLaren, Catherine Rodgers, Jason Rodgers, William Swindlehurst, Neil Symon, Douglas Warrington, Mary Whitby

Abstract

Objective: The benefits of pancreatic enzyme replacement therapy (PERT) in chronic pancreatitis (CP) are inadequately defined. We have undertaken a systematic review and meta-analysis of randomised controlled trials of PERT to determine the efficacy of PERT in exocrine pancreatic insufficiency (EPI) from CP.

Design: Major databases were searched from 1966 to 2015 inclusive. The primary outcome was coefficient of fat absorption (CFA). Effects of PERT versus baseline and versus placebo, and of different doses, formulations and schedules were determined.

Results: A total of 17 studies (511 patients with CP) were included and assessed qualitatively (Jadad score). Quantitative data were synthesised from 14 studies. PERT improved CFA compared with baseline (83.7±6.0 vs 63.1±15.0, p<0.00001; I2=89%) and placebo (83.2±5.5 vs 67.4±7.0, p=0.0001; I2=86%). PERT improved coefficient of nitrogen absorption, reduced faecal fat excretion, faecal nitrogen excretion, faecal weight and abdominal pain, without significant adverse events. Follow-up studies demonstrated that PERT increased serum nutritional parameters, improved GI symptoms and quality of life without significant adverse events. High-dose or enteric-coated enzymes showed a trend to greater effectiveness than low-dose or non-coated comparisons, respectively. Subgroup, sensitive and meta-regression analyses revealed that sample size, CP diagnostic criteria, study design and enzyme dose contributed to heterogeneity; data on health inequalities were lacking.

Conclusions: PERT is indicated to correct EPI and malnutrition in CP and may be improved by higher doses, enteric coating, administration during food and acid suppression. Further studies are required to determine optimal regimens, the impact of health inequalities and long-term effects on nutrition.

Keywords: EXOCRINE PANCREATIC FUNCTION; NUTRIENT ABSORPTION; PANCREATIC ENZYMES; PANCREATITIS.

Conflict of interest statement

Competing interests: JED-M has provided consultancy to and received financial support from Abbott (Mylan) for lecture fees and travel expenses; RS has provided consultancy to Abbott (Mylan).

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Figures

Figure 1
Figure 1
Preferred Reporting Items for Systematic Reviews and Meta-analyses flow chart of study selection process. CP, chronic pancreatitis.
Figure 2
Figure 2
Daily lipase dose of pancreatic enzymes in the reported studies. Black, non-EC microspheres; blue, minimicrospheres; cyan, EC microspheres; EC, enteric-coated; grey, EC microtablets; USP, United States Pharmacopoeia; white, non-EC microtablets; yellow, EC granules.
Figure 3
Figure 3
The pooled clinical outcomes of pancreatic enzyme replacement therapy (PERT) versus baseline. (A) coefficient of fat absorption (CFA), (B) coefficient of nitrogen absorption (CNA), (C) faecal fat excretion (FFE), (D) faecal nitrogen excretion (FNE) and (E) faecal weight.
Figure 4
Figure 4
The pooled clinical outcomes of pancreatic enzyme replacement therapy (PERT) versus placebo. (A) coefficient of fat absorption (CFA), (B) coefficient of nitrogen absorption (CNA), (C) faecal fat excretion (FFE), (D) faecal nitrogen excretion (FNE), (E) faecal weight and (F) adverse events.
Figure 5
Figure 5
The pooled clinical outcomes of pancreatic enzyme replacement therapy (PERT) versus PERT. (A) coefficient of fat absorption (CFA) and faecal fat excretion (FFE) for high dose versus low dose and (B) CFA and FFE for enteric-coated versus non-coated.

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