Table 3: Q3. In adults with moderate-severe UC with persistent increased stool frequency after induction therapy with a biologic or tofacitinib, how accurate is a fecal calprotectin cut-off of 250 for ruling in moderate to severe endoscopically active disease (Mayo endoscopy score 2/3), obviating the need for routine endoscopic assessment?
Population/Setting: Adults with moderate-severe UC who have persistent stool frequency score of 2 or 3 after biologic or tofacitinib induction therapy –Intermediate pre-test probability of having moderate to severe endoscopically active disease (patients with rectal bleeding score 0 + stool frequency score 2/3) with observed prevalence of moderate to severe endoscopically active disease (Mayo endoscopy score 2/3) of 65%; high pre-test probability of having moderate to severe endoscopically active disease (patients with rectal bleeding score 2/3 + stool frequency score 2/3) with observed prevalence of moderate to severe endoscopically active disease (Mayo endoscopy score 2/3) of 90% Pooled sensitivity fecal calprotectin with cut-off ≥250μg/g: 0.76 (95% CI: 0.65 to 0.84) | Pooled specificity fecal calprotectin with cut-off ≥250μg/g: 0.79 (95% CI: 0.73 to 0.84), 12 studies. Reference Test: Lower endoscopy, locally read
| Test result | Number of results per 1000 patients tested (95% CI) | Number of studies | Quality of the Evidence (GRADE) | Comments | |
|---|---|---|---|---|---|
| Intermediate-likelihood (Prevalence 65%) | High-likelihood (Prevalence 90%) | ||||
| True positives (patients with moderate to severe endoscopically active disease) | 494 (423 to 546) | 684 (585 to 756) | 12 studies, 1228 patients | ⊕⊕⊕○ MODERATE1 (Inconsistency) | TP may lead to diagnostic endoscopy for confirmation and modification/optimization of therapy (if FC used as triage strategy), potentially reducing risk of disease-related complications. TP will have further testing (lower endoscopy) and/or intervention which may lead to side effects. In contrast, if FC is used a test replacement strategy, this may lead to treatment modification. |
| False negatives (patients incorrectly classified as being in endoscopic remission or having mildly active disease) | 156 (104 to 227) | 216 (144 to 315) | FN may lead to inadequate treatment and potentially increased risk of disease-related complications due to delay in detection of moderate to severe endoscopically active disease | ||
| True negatives (patients in endoscopic remission or having mildly active disease) | 276 (256 to 294) | 79 (73 to 84) | TN will likely be reassured, avoid an invasive test but may still be retested with fecal calprotectin periodically | ||
| False positives (patients incorrectly classified as having moderate to severe endoscopically active disease) | 74 (56 to 94) | 21 (16 to 27) | FP will likely have further testing (if fecal calprotectin is used as triage strategy) or may be over-treated (if fecal calprotecin is used a test replacement strategy) and will increase anxiety, complications and resource use. | ||
High unexplained heterogeneity, selective inclusion of studies corresponding to cut-off of ≥250μg/g.