Early change in faecal calprotectin predicts primary non-response to anti-TNFα therapy in Crohn’s disease

Abstract

Objective: The early identification of primary non-response to anti-TNFα therapy facilitates the timely management of patients with Crohn’s disease (CD). A recent, pilot study to detect prognostic markers of early response to anti-TNFα therapy identified the two genes coding for the calprotectin subunits (S100A8, S100A9) to be among the most highly expressed gene transcripts in non-responders. This study tests the hypothesis that measurements of faecal calprotectin (FCAL) pre- and post-anti-TNFα induction can predict primary non-response.

Methods: Retrospective study of 32 CD patients treated over a two-year period. Outcomes were assessed at 6 months based on clinical activity scores and the use of corticosteroids: (a) remission: Harvey–Bradshaw index (HBI) < 5, off corticosteroids >2 months; (b) response: drop in HBI >3, off corticosteroids; (c) non-response: ΔFCAL (and ΔCRP, respectively) was calculated as (FCAL post-induction – FCAL pre-induction) × 100/FCAL pre induction.

Results: At 6 months, 23 (72%) patients had responded (median (interquartile range) HBI: 4 (3–5), FCAL: 55 (27–146)), 17 (73%) of whom were in remission [HBI: 3 (2.5–4) and FCAL: 42 (16–115)]. There was a significant difference in the ΔFCAL from baseline to post-induction in the three groups (p < 0.0001). Comparing non-responders to combined response and remission groups, the AUC of ΔFCAL to predict outcome at 6 months was 0.97. Using ROC analysis, a Δ70% returned a sensitivity and specificity of 99% and 96%, respectively (likelihood ratio, LR= 23). ΔCRP did not predict 6 months outcomes.

Conclusions: A drop in FCAL <70% after induction predicts primary non-response to anti-TNFα in CD.

keywords:

• Anti-TNFα
• Crohn’s
• faecal calprotectin
• primary non-response

Acknowledgements

Polychronis Pavlidis conceived the idea for the study, collected the data, performed the analysis, prepared the first and final draft of this manuscript. Shraddha Gulati, Patrick Dubois, Guy Chung-Faye, Roy Sherwood, Ingvar Bjarnason provided clinical data and reviewed final version of the manuscript, BHH is the guarantor of the presented work, had input in the analysis of the data and critically reviewed the manuscript. All authors approved the final version of the article, including the authorship list. Polychronis Pavlidis would like to thank Dr Nick Powell for his input and critical review of the early versions of this manuscript.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.