Maria Ling Lundström [1], Christer Peterson [2], Maria Lampinen [1], Charlotte R. H. Hedin [3],[4], Åsa V Keita [5], Robert Kruse [6], Maria K Magnusson [7], Carl Mårten Lindqvist [8], Dirk Repsilber [8], Mauro D’Amato [9-12], Henrik Hjortswang [13], Hans Strid [14], Anders Rönnblom [15], BIOIBD consortium, Johan D Söderholm [5], [16], Lena Öhman [7], Per Venge [2], Jonas Halfvarson [17] and Marie Carlson [1]

Affiliates

[1] Department of Medical Sciences, Gastroenterology Research Group, Uppsala University, Uppsala, Sweden [2] Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden [3] Karolinska Institute, Department of Medicine Solna, Stockholm, Sweden [4] Karolinska University Hospital, Gastroenterology Unit, Department of Gastroenterology, Dermatovenereology and Rheumatology, Stockholm, Sweden [5] Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden [6] iRiSC – Inflammatory Response and Infection Susceptibility Centre and Department of Clinical Research Laboratory, Faculty of Medicine and Health, Örebro University, Örebro, Sweden [7] Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden [8] School of Medical Sciences, Örebro University, Örebro, Sweden. [9] Clinical Epidemiology Unit, Department of Medicine, Karolinska Institute, Solna, Sweden [10] Department of Medicine and Surgery, LUM University, Casamassima, Italy [11] Gastrointestinal Genetics Lab, CIC bioGUNE – BRTA, Derio, Spain [12] Ikerbasque, Basque Foundation for Science, Bilbao, Spain [13] Division of Gastroenterology and Hepatology, Department of Clinical and Experimental Science, Linköping University, Linköping, Sweden [14] Department of Internal Medicine, Södra Älvsborgs Hospital, Borås, Sweden [15] Department of Medical Sciences, Uppsala University, Uppsala, Sweden [16] Department of Surgery, Linköping University, Linköping, Sweden [17] Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden

Abstract

Background:
Faecal calprotectin (FC) is a non-invasive tool for examining response to biologics in inflammatory bowel disease (IBD), but its performance in relation to other novel faecal markers of various cellular origins is unknown. In the present study, we aimed to examine the association between different faecal markers and treatment outcomes of biological therapy.

Methods:
We performed a prospective multicentre cohort study and included patients with active IBD who provided a faecal sample at initiation of biological therapy. Levels of FC, myeloperoxidase (MPO), human neutrophil lipocalin (HNL), and eosinophil-derived neurotoxin (EDN) were analysed and related to clinical remission status at 3 months. Changes in levels of markers at 3 months were calculated and the impact of concomitant use of corticosteroids at baseline was estimated.

Results:
In patients achieving clinical remission (n=27), a decrease in levels of FC (p=0.005), MPO (p<0.001), HNL (p<0.001) and EDN (p<0.001) was observed, whereas no significant decrease was seen in patients not achieving remission (n=39) (Figure 1). There was a significant difference in the change in the level of MPO (p=0.01) and HNL (p=0.02) between patients achieving clinical remission compared with those who did not, but changes in FC (p=0.25) and EDN (p=0.09) could not differentiate between these groups. Patients with concomitant systemic corticosteroids at inclusion had lower levels of HNL (p=0.01) and EDN (p<0.001) but not FC and MPO at baseline, compared with patients without corticosteroids.

Conclusion:
Faecal MPO, HNL, and EDN are all promising biomarkers for assessing treatment outcome of biologics in patients with IBD. Faecal levels of EDN and HNL are significantly affected by corticosteroids indicating a greater sensitivity to the effects of corticosteroids compared with FC and MPO. MPO showed the strongest association with remission and may be the most suitable faecal marker for treatment evaluation of biologics.