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. 2021 Feb 15;12(2):e00298.
doi: 10.14309/ctg.0000000000000298.

Prospective Validation of CD-62L (L-Selectin) as Marker of Durable Response to Infliximab Treatment in Patients With Inflammatory Bowel Disease: A 5-Year Clinical Follow-up

Francisco Bravo  1   2 , Jamie A Macpherson  1 , Emma Slack  1 , Nicolas Patuto  2 , Julia Cahenzli  1 , Kathy D McCoy  1 , Andrew J Macpherson  1   2 , Pascal Juillerat  1   2 ; SATICC (Sensitivity to Anti-TNF Inhibition in Crohn's disease and ulcerative Colitis) study group
Affiliations

Prospective Validation of CD-62L (L-Selectin) as Marker of Durable Response to Infliximab Treatment in Patients With Inflammatory Bowel Disease: A 5-Year Clinical Follow-up

Francisco Bravo et al. Clin Transl Gastroenterol. .

Abstract

Introduction: The development of biomarkers to guide management of anti-tumor necrosis factor (TNF) agents in patients with inflammatory bowel disease (IBD) is an unmet need. We developed an in vitro blood assay to predict patient long-term outcome with the anti-TNFα agent infliximab (IFX).

Methods: Patients with IBD were classified according to the shedding of an L-selectin (CD62L) from the surface of their granulocytes in whole blood. CD62L shedding was quantified by flow cytometry before and after drug administration. A clinical data collection from June 2012 to August 2017 with blinded IFX management was aimed at validating the long-term predictive value of this test.

Results: Among 33 patients with IBD (17 Crohn's disease and 5 ulcerative colitis), 22 were predicted functional responders (PFR) and 11 were predicted as nonresponders (NR) according to the in vitro test. Five years after study initiation, 72% of PFR were still treated with IFX (vs 27% in the NR group; P < 0.05), with a median time spent under IFX of 45 vs 12 months (P = 0.019), respectively. Thirty-five medicosurgical events occurred with a median time to first event of 3 vs 30 months (P = 0.023), respectively. Our assay was the best independent predictor of staying long term on IFX (P = 0.056).

Discussion: An assay-based in vitro test for functional blockade of TNFα (CD62L shedding) provides an excellent long-term (at 3-5 years) independent predictor of durable use of IFX in patients with IBD. Testing patients could personalize decision making to significantly reduce costs and risk of adverse events and complications.

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Conflict of interest statement

Guarantor of the article: Pascal Juillerat, MD, MSc.

Specific author contributions: J.C., K.D.M., A.J.M., and P.J.: the original concept (aims, hypothesis, and experimental design) of the project, the supervision, and technical assistance. J.A.M., E.S.: established the setting up and optimization of the initial assay and running patient samples from June to December 2012. P.J.: recruited patients for this study, prepared the ethical guidelines, and was responsible for the clinical data collection, founding, and writing the draft of the manuscript. F.B.: was responsible for the long-term follow-up clinical data collection and processing and writing the draft of the manuscript. All authors had access to the study data, reviewed, and approved the final manuscript and improved its scientific and clinical content.

Financial support: This work was supported by a grant from the Ruth and Arthur Scherbarth Foundation, as well as a research grant from Bern University Hospital.

Potential competing interests: None to declare.

Previous presentations: Part of this work was presented at Digestive Disease Week (DDW) 2018, 2015, and 2014, United European Gastroenterology Week (UEGW) 2015, and the European Crohn's and Colitis Organization (ECCO) congresses 2018 and 2014.

Figures

Figure 1.
Figure 1.
CD 62L granulocyte shedding in 2 different patients as measured by mean fluorescence intensity after incubation of citrate blood with different infliximab (IFX) concentrations. (a) Predicted functional responder (PFR). (b) nonresponder (NR). TNF, tumor necrosis factor.
Figure 2.
Figure 2.
Infliximab treatment duration after inclusion. Dots represent individual patients and the duration of infliximab (IFX) therapy in months, from inclusion to treatment cessation or end of follow-up period. Data are represented as medians ± interquartile ranges (Wilcoxon test). TNF, tumor necrosis factor.
Figure 3.
Figure 3.
Kaplan-Meier curves of time to first event in months, stratified by response prediction through the anti–tumor necrosis factor assay. P value calculated using the log-rank test. NR, nonresponders; PFR, predicted functional responders.
Figure 4.
Figure 4.
Therapeutic outcomes per patient at the end of each follow-up year, stratified by predicted response groups. IFX, infliximab; NR, predicted nonresponders; PFR, predicted functional responders.
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