Article Text
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.
- EXOCRINE PANCREATIC FUNCTION
- NUTRIENT ABSORPTION
- PANCREATIC ENZYMES
- PANCREATITIS
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Footnotes
Collaborators The Members of the NIHR Pancreas Biomedical Research Unit Patient Advisory Group: Graham Cameron, Kirsty Donaldson, Georgia Jones, John Lancaster, Amy Lucas, Karen Manby, Tor McLaren (BRU Steering Committee), Catherine Rodgers, Jason Rodgers, William Swindlehurst (Chair), Neil Symon, Douglas Warrington, Mary Whitby.
Contributors DdlI-G and WH are co-first authors. RS and JED-M conceived, designed and supervised the study, and obtained funding. DdlI-G, WH, PS, IB-R, JG-L, GP-R, RM and QMN acquired, analysed and interpreted the data. DdlI-G, WH and RS wrote the paper; JED-M and NIHR BRU PAG undertook critical revision of the manuscript for important intellectual content.
Funding This work was funded by the University Hospital of Santiago de Compostela, Spain (DdlI-G, IB-R, JG-L, GP-R, JED-M), Royal College of Surgeons of England (PS) and the Biomedical Research Unit funding scheme of the National Institute for Health Research (WH, RM, QMN, RS). RS is an NIHR Senior Investigator.
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).
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement Upon publication raw data from individual studies will be made available by the corresponding author to interested researchers requesting data for bona fide scientific purposes.