Role of fecal calprotectin testing to predict relapse in teenagers with inflammatory bowel disease who report full disease control

Background: Teenagers with inflammatory bowel disease undergo regular follow-up visits to watch for symptoms that may indicate relapse. Current disease activity is frequently estimated with the use of the Pediatric Ulcerative Colitis Activity Index (PUCAI) and the Pediatric Crohn's Disease Activity Index (PCDAI). We examined the capacity of fecal calprotectin and C-reactive protein (CRP) to predict relapse in teenagers who report no symptoms. Second, we examined whether calprotectin and CRP as an "add-on test" improve the specificity of PUCAI or PCDAI to predict relapse.

Methods: We collected data of 62 consecutive teenagers (31 with Crohn's disease and 31 with ulcerative colitis) who scored their degree of disease control between 90 and 100% on two successive outpatient clinic visits. Calprotectin, PUCAI or PCDAI, and CRP were measured at baseline. Primary outcome was symptomatic relapse within 3 months of baseline, necessitating the introduction of steroids, exclusive enteral nutrition, or an aminosalicylate dose escalation.

Results: Fifteen teenagers (24%) developed symptomatic relapse within 3 months of baseline. Based on the receiver operating characteristic curve, the optimum calprotectin cutpoint to differentiate high from low risk patients was 500 μg/g. The PUCAI or PCDAI predicted relapse in 42% (11/26) of teenagers with a positive result (score ≥ 10 points), while a negative PUCAI or PCDAI result reduced the risk of relapse to 11% (4/36). Teenagers with a positive calprotectin test had a 53% (10/19) risk of progressing to symptomatic relapse within 3 months, whereas a negative calprotectin result gave a 12% (5/43) risk of symptomatic relapse. A positive CRP result (cutoff 10 mg/L) gave a 50% (4/8) risk of relapse, whereas a negative CRP result hardly reduced the risk compared with the pretest probability (from 24% to 21% (11/53)). As an add-on test after PUCAI or PCDAI, the calprotectin test limited the number of false positives and thus increased the specificity to detect gastrointestinal inflammation: 60% (9/15) of teenagers with positive concordant test results progressed to symptomatic relapse. Negative concordance reduced the risk of relapse to 10% (3/32). CRP contributed little as add-on test after PUCAI or PCDAI: two of five teenagers with positive concordant tests progressed to symptomatic relapse (40%).

Conclusions: Unlike CRP, fecal calprotectin as an add-on test after PUCAI or PCDAI facilitates recognition of preclinical relapse. This could help to identify teenagers who require treatment intensification at the time of minimal disease rather than at the time of clinically overt relapse. Further studies are warranted to determine the impact of fecal calprotectin testing on treatment management and outcome.