Less common etiologies of exocrine pancreatic insufficiency

Table 5 Pancreatic enzyme replacement therapy clinical trials

Study	Study design, duration (when given), and number of patients	Disease	Results	Adverse effects
Bruno et al[66]	DBRPC, 8 wk, 24 adults (21 analyzed)	Pancreatic cancer	The mean absolute difference for PERT vs placebo in percentage change in body weight was 4.9% (P = 0.02); other outcomes were numerically improved with PERT vs placebo [fat absorption coefficient, 12% increase vs 8% decrease (P = 0.13); stool frequency, decrease of 1/d vs increase of 2/d (P = 0.07)]	No treatment-related AEs
Woo et al[70]	DBRPC, 8 wk, 67 adults	Pancreatic cancer	The mean change in body weight at 8 wk was similar with PERT vs placebo (-1.49% vs -2.99%; P = 0.381), but the mean change in nutritional status was superior with PERT vs placebo in the subset of patients with cancer of the pancreatic head (PG-SGA score, -42.65% vs 32.93%; P = 0.039)	Three patients died [PERT group, 2/34 (6%); placebo group, 1/33 (3%)]
				There were no PERT-related serious AEs
Perez et al[60]	Open-label, 12 adults	Pancreatic cancer	Most patients with moderate to severe fat (6/7) or protein (3/3) malabsorption improved, but no patients with mild fat or protein (0/8) malabsorption improved	No descriptions regarding TEAEs
Ewald et al[49]	DBRPC, 16 wk, 80 adults	Type 1 diabetes	No significant change in HbA1c, fasting glucose, or postprandial glucose; increase in mean vitamin D from baseline to week 16 (PERT, from 54.1 to 59.4 nmol/L; placebo, 60.2 to 62.7 nmol/L)	TEAEs occurred in 33 patients (84.6%) in PERT group and in 35 (85.4%) in PBO group; most frequent AEs were headache, infection, pain, diarrhea, and dyspepsia
Carroccio et al[150]	DBRPC, 2 mo, 40 children	Celiac disease	Significant mean ± SD weight gain in first 30 d (1131 ± 461 g with PERT vs 732 ± 399 g with placebo; P < 0.006), not significant at 60 d	No undesired side effects were reported
Evans et al[141]	Open-label, up to 4 yr, 20 adults	Celiac disease	Significant increase in fecal elastase from median of 90 μg/g to 365 μg/g (P < 0.0001) and improvement in chronic diarrhea with reduction in median stool frequency from 4/d to 1/d (P ≤ 0.0001), but no weight increase (P = 0.3)	No descriptions regarding TEAEs
Leeds et al[135]	Open-label, up to 2 yr, 20 adults	Celiac disease	Significant improvement in chronic diarrhea with reduction in median stool frequency from 4/d to 1/d (P ≤ 0.0001), but no weight increase (P = 0.3)	No descriptions regarding TEAEs
Huddy et al[181]	Open-label, 10 adults	Esophagectomy	Improvement in diarrhea and steatorrhea (9/10), increased weight (7/10)	Nausea in 1 patient
Armbrecht et al[183]	DBRPC crossover trial, 2 wk (plus 1-wk washout), 15 adults	Total gastrectomy	Improved stool consistency (score, 7.6 with PERT vs 9.3 with placebo; P < 0.05), but not the number of bowel movements or abdominal symptoms	No descriptions regarding TEAEs
Hillman et al[166]	Open-label, 6 mo, 30 adults	Partial gastrectomy	Mean ± SE weight gain of 6.73 ± 0.77 (P < 0.001), mean ± SE decrease in steatorrhea of 49.7% ± 7.7% (P < 0.001)	No descriptions regarding TEAEs
Brägelmann et al[184]	DBRPC, 14 d, 52 adults	Total gastrectomy	Improvement of overall well-being (15/23 with PERT vs 6/24 with placebo; P = 0.006), but no improvement of specific symptom	No descriptions regarding TEAEs

AE: Adverse event; DBRPC: Double-blind, randomized, placebo-controlled; GIP: Gastric inhibitory polypeptide; GLP-1: Glucagon-like peptide-1; HbA_1c: Glycated hemoglobin A_1c; PBO: Placebo; PERT: Pancreatic enzyme replacement therapy; PG-SGA: Patient-generated subjective global assessment; TEAE: Treatment-emergent AE.