Soluble human Suppression of Tumorigenicity 2 is associated with endoscopic activity in patients with moderate-to-severe ulcerative colitis treated with golimumab

Fernando Magro, Susana Lopes, Marco Silva, Rosa Coelho, Francisco Portela, Diogo Branquinho, Luís Correia, Samuel Fernandes, Marília Cravo, Paulo Caldeira, Helena Tavares de Sousa, Marta Patita, Paula Lago, Jaime Ramos, Joana Afonso, Isabel Redondo, Patrícia Machado, George Philip, Joanne Lopes, Fátima Carneiro, Fernando Magro, Susana Lopes, Marco Silva, Rosa Coelho, Francisco Portela, Diogo Branquinho, Luís Correia, Samuel Fernandes, Marília Cravo, Paulo Caldeira, Helena Tavares de Sousa, Marta Patita, Paula Lago, Jaime Ramos, Joana Afonso, Isabel Redondo, Patrícia Machado, George Philip, Joanne Lopes, Fátima Carneiro

Abstract

Background: Suppressor of Tumorigenicity 2 (ST2) is an IL33 receptor detected in the mucosa and serum of ulcerative colitis (UC) patients. We evaluated soluble ST2 (sST2) as a surrogate biomarker of disease outcome and therapeutic response, in moderate-to-severe UC patients treated with golimumab.

Methods: We conducted an open-label single-arm multicentre prospective study. At screening/baseline, week 6 (W6) and week 16 (W16), clinical and endoscopic activity (total Mayo score), histologic activity (Geboes index) and biomarkers were evaluated.

Results: From 38 patients, 34 (89.5%) completed W6 and 29 (76.3%) completed W16. Mean age (±SD) was 34.6 ± 12.6 years; 55.9% were female. At W16, 62.1% achieved clinical response. Patients with endoscopic activity at W6 (n = 20) had higher baseline sST2 (median, 24.5 versus 18.7 ng/ml, p = 0.026) and no decrease from baseline (median change, 0.8 versus -2.7, p = 0.029). At W6, sST2 levels correlated with endoscopic activity (rs = 0.45, p = 0.007) but not with histological activity (rs = 0.25, p = 0.151). The best cut-offs for endoscopic activity were sST2 = 16.9 ng/ml (sensitivity = 85%; specificity = 71%) and faecal calprotectin (FC) = 353 μg/g (sensitivity = 90%, specificity = 67%). Patients with histological activity at W6 (n = 27) had higher baseline ST2 levels (median, 23.0 versus 13.7 ng/ml, p = 0.035). sST2 did not correlate with FC or serum C-reactive protein. FC levels correlated with histological activity and baseline FC were higher when Geboes ⩾3.1 at W6.

Conclusions: sST2 may be a surrogate biomarker of UC activity and therapeutic response as it correlates with endoscopic and clinical activity at W6 of golimumab treatment, and subjects with endoscopic and histological activity at W6 had higher baseline ST2 levels.

Keywords: endoscopic activity; golimumab; histological activity; serum soluble ST2; ulcerative colitis.

Conflict of interest statement

Conflict of interest statement: Fernando Magro received a fee for presenting from: AbbVie, Ferring, Falk, Hospira, PharmaKern, MSD, Schering, Lab. Vitoria, Vifor, OmPharma. Helena Tavares de Sousa reports expert fees and nonfinancial support from MSD, Abbvie, Ferring, Dr Falk Pharma, PharmaKern, Janssen and Takeda, outside the submitted work. Patrícia Machado is employee of MSD Portugal; Philip G is employee of Merck and Co., USA; and Isabel Redondo was an employee of MSD Portugal at the time the study was conducted. All other authors: none to declare.

Figures

Figure 1.
Figure 1.
Proportion (%) of patients by total Mayo score (A), stool frequency (B), rectal bleeding (C) and endoscopic Mayo subscore (D) during the study.
Figure 2.
Figure 2.
Evolution of CRP (A), FC (B) and sST2 (C) levels during the study: median and interquartile range (grey area). CRP, serum C-reactive protein; FC, faecal calprotectin; sST2, serum soluble Suppression of Tumorigenicity 2.
Figure 3.
Figure 3.
Levels of sST2, FC and CRP at baseline, by endoscopic and histological activity and clinical response at week 6. CRP, serum C-reactive protein; FC, faecal calprotectin; sST2, serum soluble Suppression of Tumorigenicity 2.
Figure 4.
Figure 4.
Levels of sST2, FC and CRP at week 6, by endoscopic and histological activity and clinical response. CRP, serum C-reactive protein; FC, faecal calprotectin; sST2, serum soluble Suppression of Tumorigenicity 2.

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