Table 1.
Summary of studies investigating fecal biomarkers for the prediction of relapses in inflammatory bowel disease.
| References | Location | Age median or mean* (range) | Disease | N | Time interval | Optimal cut-off | Median/mean* | P-value |
Sensitivity/ specificity % |
PPV/NPV % | Method | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Relapse | Non-relapse | |||||||||||
| Calprotectin | ||||||||||||
| Buisson et al. (53) | US | 25.9* | CD | 112 | 1 yr | 100 μg/g | - | - | - | 76/86 | 77/85 | ELISA (Genova diagnostics) |
| UC | 48 | |||||||||||
| Ferreiro-Iglesias et al. (54) | Spain | 44 (18–78) | CD | 71 | 4 mons | >300 μg/g | 477 μg/g | 65 μg/g | <0.005 | 100/80 | 78.3/100 | Lateral flow assay (Buhlmann) |
| UC | 24 | |||||||||||
| Kittanakom et al. (55) | Canada | CD: 14.6 (11–17)UC: 14.1 (11–17) | IBD | 40 | - | 400 μg/g | - | - | - | 100/75.9 | 58.8/100 | ELISA (PhiCal) |
| - | 800 μg/g | - | - | - | 100/72.4 | 55.6/100 | Fluorescence enzyme immunoassay (Phadia) | |||||
| - | 500 μg/g | - | - | - | 100/72.4 | 55.6/100 | ELISA (Buhlmann) | |||||
| Diederen et al. (56) | Netherlands | 14.9 (all <18) | IBD | 114 | 6 mons | 350 μg/g | 370 μg/g | 122 μg/g | 0.003 | 82/79 | 41/96 | - |
| Roblin et al. (57) | France | 35 | CD | 119 | 6 mons | >250 μg/g and TLI <2 μg/mL | - | - | - | 94/84 | 73/97 | Lateral flow assay (Buhlmann) |
| Theede et al. (58) | Denmark | 39* | UC | 70 | 6 and 12 mons | 321 mg/kg | - | - | - | 46.7/85.5 | 46.7/85.5 | ELISA (Buhlmann) |
| Ferreiro-Iglesias et al. (59) | Spain | 46 (18–68) | IBD | 53 | 2 mons | 160 μg/g | 332 μg/g* | 110 μg/g* | <0.005 | 91.7/82.9 | 68.7/96.1 | Lateral flow assay (Buhlmann) |
| 41 (18–43) | CD | 33 | 160 μg/g | 287 μg/g* | 94 μg/g* | <0.005 | 87.5/84.0 | 66.9/94.8 | ||||
| 51 (19–68) | UC | 20 | 198 μg/g | 420 μg/g* | 136 μg/g* | <0.005 | 100/81.3 | 48.5/100 | ||||
| Ferreiro-Iglesias et al. (60) | Spain | 38 (24–64) | CD | 30 | 4 mons | 204 μg/g | 625 μg/g | 45 μg/g | <0.005 | 100/85.7 | 74.1/100 | Lateral flow assay (Buhlmann) |
| Delefortrie et al. (61) | Belgium | 43 | CD | 29 | 6 mons | 183.5 μg/g | 667 μg/g | 109 μg/g | <0.05 | 100/76.2 | 61/100 | Lateral flow assay (Buhlmann) |
| 124.5 μg/g | 339.5 μg/g | 71.4 μg/g | <0.05 | 87.5/66.66 | 50/93.5 | Chemiluminescent immunoassay (Liaison). Samples extracted with Liaison extraction device | ||||||
| 106.5 μg/g | 261.5 μg/g | 37.6 μg/g | <0.05 | 87.5/95.2 | 87.5/95 | Chemiluminescent immunoassay (Liaison). Samples extracted with weighing protocol | ||||||
| Mooiweer et al. (62) | Netherlands | 50 (19–71) | CD | 20 | 12 mons | 56 μg/g& | 284 μg/g | 37 μg/g | <0.01 | 64/100 | 20/100 | ELISA (Ridascreen) |
| UC/IBD-U | 52 | |||||||||||
| Yamamoto et al. (63) | Japan | 35 (18–74) | UC | 80 | 40 wks | Elevated level ≥55 μg/g | 76.5 μg/g | 15.5 μg/g | <0.0001 | 88/80 | 66/94 | ELISA (Cell sciences) |
| Scaioli et al. (64) | Italy | 40 (16–89) | UC | 74 | 1 yr | 193 μg/g | 218 μg/g | 48 μg/g | <0.01 | 65/98 | 92/88 | ELISA (Calprest) |
| Yamamoto et al. (65) | Japan | 35.1* (20–75) | UC | 80 | 12 mons | 170 μg/g | 173.7 μg/g* | 135.5 μg/g* | 0.02 | 76/76 | -/- | ELISA (Cell sciences) |
| Jauregui-Amezaga et al. (66) | Spain | 46* | UC | 64 | 1 yr | 250 μg/g | 200 μg/g | 75 μg/g | 0.75 | 41/85 | -/80 | ELISA (Cerba internacional) |
| Naismith et al. (67) | UK | 47* (>18) | CD | 92 | 12 mons | 240 μg/g | 414 μg/g | 96 μg/g | 0.005 | 80.8/74.4 | 28/97 | ELISA (Buhlmann) |
| Vos et al. (68) | Belgium and Norway | 48* (19–79) | UC | 87 | 52 wks | 300 μg/g | 125 μg/g* | 27 μg/g* | <0.001 | 58.3/93.3 | -/- | ELISA (PhiCal) |
| Two consecutive measurements of >300 μg/g within 1 mon | 61.5/100 | -/- | ||||||||||
| Lasson et al. (69) | Sweden | 33 (18–74) | UC | 69 | 1 yr | 169 μg/g | 263 μg/g | 102 μg/g | 0.009 | 64.4/70.8 | 80.6/51.5 | ELISA (Buhlmann) |
| 67 | 2 yrs | 262 μg/g | 263 μg/g | 124 μg/g | <0.05 | 51.1/81.8 | 85.2/45.0 | |||||
| 67 | 3 yrs | 262 μg/g | 280 μg/g | 118 μg/g | 0.01 | 52.2/85.7 | 88.9/45.0 | |||||
| Meuwis et al. (70) | France and Belgium | 32 | CD | 79 | 28 mons | 250 μg/g | - | - | - | -/- | -/- | ELISA (PhiCal) |
| van Rheenen et al. (71) | Netherlands | 14.1* (<18) | CD | 31 | 3 mons | 500 μg/g | - | - | - | 67/81 | -/- | ELISA (Calpro) |
| 13* (<18) | UC | 31 | ||||||||||
| Louis et al. (72) | France and Belgium | 32 (>17) | CD | 115 | 1 yr | 300 μg/g | - | - | - | -/- | -/- | ELISA (PhiCal) |
| Laharie et al. (73) | France | 30.4 (15–69) | CD | 65 | 14 wks | 130 μg/g | 200 μg/g | 150 μg/g | Ns | 61/48 | -/- | ELISA (Buhlmann) |
| 250 μg/g | 43/57 | -/- | ||||||||||
| García-Sánchez et al. (74) | Spain | 36.9* | CD | 66 | 1 yr | 200 μg/g | 524 μg/g | 123 μg/g | <0.01 | 80/65 | 46/88 | ELISA (Calprest) |
| 40.4* | UC | 69 | 120 μg/g | 298 μg/g | 105 μg/g | <0.01 | 81/63 | 49/88 | ||||
| Kallel et al. (75) | Tunisia | 33 (15–66) | CD | 53 | 12 mons | 340 μg/g | 380.5 μg/g | 155 μg/g | <0.001 | 80/90.7 | -/- | ELISA (Calprest) |
| Sipponen et al. (76) | Finland | 12.9 (2–17) | IBD | 72 | 12 mons | 108.5 μg/g | 409 μg/g | 282 μg/g | 0.44 | 38/72 | -/- | ELISA (PhiCal) |
| 100 μg/g | -/- | 39.6/75 | ||||||||||
| Gisbert et al. (77) | Spain | 43* | IBD | 163 | 12 mons | 150 μg/g | 239 μg/g | 136 μg/g | <0.001 | 69/69 | 30/92 | ELISA (PhiCal) |
| CD | 89 | 150 μg/g | 266 μg/g | 145 μg/g | 0.002 | 28/93 | -/- | |||||
| UC | 74 | 150 μg/g | 213 μg/g | 126 μg/g | 0.03 | 31/91 | -/- | |||||
| D'incà et al. (78) | Italy | - | IBD | 162 | 1 yr | 130 μg/g | - | - | - | 68/67 | 52/79 | ELISA (Calprest) |
| 43 (18–77) | CD | 65 | 130 μg/g | 207 μg/g | 88 μg/g | 0.055 | 65/62 | 44/80 | ||||
| 46 (15–80) | UC | 97 | 130 μg/g | 190 μg/g | 49 μg/g | 0.02 | 70/70 | 60/79 | ||||
| Diamanti et al. (79) | Italy | - | IBD | 73 | 3 yrs | 275 μg/g | - | - | - | 97/85 | 85/97 | ELISA (Calprest) |
| 16 (1.5–18) | CD | 32 | 462 μg/g | - | - | - | 100/71 | 78/100 | ||||
| 12 (6–18) | UC | 41 | 275 μg/g | - | - | - | 94/95 | 94/95 | ||||
| Costa et al. (80) | Italy | 35.7* | CD | 38 | 12 mons | 150 μg/g | 220.1 μg/g | 220.5 μg/g | 0.395 | 87/43 | 50/83 | ELISA (Calprest) |
| 41.2* | UC | 41 | 150 μg/g | 220.6 μg/g | 67 μg/g | <0.0001 | 89/82 | 81/90 | ||||
| Tibble et al. (81) | UK | 33 | CD | 43 | 12 mons | 100 μg/g | 244 μg/g | 84 μg/g | <0.0001 | 90/83 | -/- | ELISA (In-house) |
| 49 | UC | 37 | 246 μg/g | 58 μg/g | <0.0001 | |||||||
| Lactoferrin | ||||||||||||
| Yamamoto et al. (65) | Japan | 35.1* (20–75) | UC | 80 | 12 mons | 140 μg/g | 161.5 μg/g* | 130.7 μg/g* | 0.03 | 67/68 | -/- | Colloidal gold agglutination assay (Alfresa Pharma Corp.) |
| Gisbert et al. (77) | Spain | 43* | IBD | 163 | 12 mons | - | 62%∧ | 35%∧ | <0.05 | 62/65 | 25/90 | ELISA (TechLab) |
| Walker et al. (82) | US | 13.4* (2–21) | IBD | 55 | 2 mons | - | 845 μg/g* | 190 μg/g* | 0.003 | -/- | -/- | ELISA (TechLab) |
| S100A12 | ||||||||||||
| Däbritz et al. (83) | Germany | 37.4 (3.5–74.6) | IBD | 181 | Predicting relapse 8–12 wks earlier | 0.43 μg/g | - | - | - | 70/83 | -/- | ELISA (In-house) |
| CD | 61 | |||||||||||
| UC | 120 | |||||||||||
Time interval: cut-off values for predicting relapse within a specified period. Concentrations of fecal markers in relapsers and non-relapsers are expressed as mean
(*)
or median. Age of patients are presented as mean (*) or median. Studies on pediatric patients are in italic.
&
Cut-off value for prediction of absence of relapse.
∧
Positive lactoferrin test was more frequent in relapsing than in non-relapsing patients. TLI, trough level of infliximab; IBD, inflammatory bowel disease; CD, Crohn's disease; UC, ulcerative colitis; IBD-U, inflammatory bowel disease-unclassified; PPV, positive predictive value; NPV, negative predictive value; Ns, Not statistically significant; Wk, week. Mon, month; Yr, year. -, information not available.