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We read with great interest the study by Gaujoux et al, who described a whole blood marker for anti-tumour necrosis factor (TNF) responsiveness in patients with Crohn’s disease (CD). The availability of anti-TNF agents dramatically changed therapeutic strategies for patients with CD. However, an overall non-response rate of 30% has been observed, and, together with the approval of new classes of biological agents with a different mode of action, clearly indicates the need for predictive biomarkers. Gaujoux et al identified triggering receptor expressed on myeloid cells 1 (TREM1) expression in whole blood as a biomarker for anti-TNF (non)response (higher expression in responders).1 In inflamed colonic tissue, TREM1 expression is also decreased in future infliximab responders.1 2 TREM-1 is known to amplify inflammation, whereas TREM-1 inhibition in vivo attenuates colitis by modulating autophagy and endoplasmic reticulum (ER) stress.3
We first measured serum TREM-1 (sTREM-1) (Human sTREM-1 ELISA (HK348), Hycult Biotech, Uden, the Netherlands) in 85 patients with CD with active disease prior to anti-TNF therapy (table 1). To reduce the risk of including treatment failures secondary to immunogenicity (and not drug mechanistic failure) or non-drug-related healers, all included patients had to have a good drug exposure, defined as a maintenance trough level >3.0 µg/mL for infliximab or >5.0 µg/mL for adalimumab. Interestingly, patients who achieved mucosal healing (complete absence of ulcerations and erosions4) after 6 months of anti-TNF therapy (adalimumab and infliximab) had significantly lower baseline sTREM-1 levels compared with non-responders (50.8 pg/mL …
Contributors BV: study design, data acquisition and interpretation, statistical analysis and drafting of the manuscript. SaV: technical assistance qPCR and critical revision of the manuscript. HB: technical assistance ELISA. IC, MdB and GVA: critical revision of the manuscript. SV and MF: study design, data interpretation, supervision and critical revision of the manuscript. All authors agreed with the final version of the manuscript prior to submission.
Funding B Verstockt is a doctoral fellow and G Van Assche, S Vermeire and M Ferrante are Senior Clinical Investigators of the Research Foundation Flanders (FWO), Belgium. B Verstockt has also received research grants by the Belgium Week of Gastroenterology, the Belgian IBD Research and Development (BIRD), the European Crohn’s and Colitis Organization (ECCO) and the IBD Patient’s Association Flanders (CCV VZW).
Disclaimer The authors have no other relevant affiliations or financial involvement with any organisation or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclose.
Competing interests B Verstockt received lecture fees from Ferring and Takeda Pharmaceuticals. G Van Assche received financial support for research from Abbott and Ferring Pharmaceuticals; lecture fees from Janssen, MSD and Abbott; consultancy fees from PDL BioPharma, UCB Pharma, Sanofi-Aventis, Abbott, Abbvie, Ferring, Novartis, Biogen Idec, Janssen Biologics, NovoNordisk, Zealand Pharma A/S, Millenium/Takeda, Shire, Novartis and Bristol Mayer Squibb. S Vermeire received financial support for research from MSD, Abbvie, Janssen and UCB Pharma; lecture fees from Abbott,Abbvie, Merck Sharpe & Dohme, Ferring Pharmaceuticals and UCB Pharma; consultancy fees from Pfizer, Ferring Pharmaceuticals, Shire Pharmaceuticals Group, Merck Sharpe & Dohme, and AstraZeneca Pharmaceuticals. M Ferrante received financial support for research from Takeda and Janssen; lecture fees from Ferring, Boehringer- Ingelheim,Chiesi, Merck Sharpe & Dohme, Tillotts, Janssen Biologics, AbbvieTakeda, Mitsubishi Tanabe, Zeria; consultancy fees from Abbvie, Boehringer-Ingelheim, Ferring, Merck Sharpe & Dohme, and Janssen Biologics. SaV, HB, IC and MdB declare no conflicts of interest.
Patient consent Obtained.
Ethics approval All patients included in the analysis had given written consent to participate in the Institutional Review Board-approved IBD Biobank (B322201213950/S53684), collecting serum and clinical characteristics among other items.
Provenance and peer review Not commissioned; externally peer reviewed.