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.Agência financiadora
Merck Sharp and Dohme, Lda, Portugal 	
MK8259-22info:eu-repo/semantics/publishedVersio

Diogo Branquinho

Fernando Magro

Francisco Portela

Fátima Carneiro

George Philip

Gisbert JP

Helena Tavares de Sousa

Isabel Redondo

Jaime Ramos

Joana Afonso

Joanne Lopes

Kim DB

Luís Correia

Magro F

Marco Silva

Marta Patita

Marília Cravo

Patrícia Machado

Paula Lago

Paulo Caldeira

Rosa Coelho

Samuel Fernandes

Susana Lopes

Therapeutic Advances in Gastroenterology

English

Crossref

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

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.This work was supported by Merck Sharp and Dohme, Lda, Portugal, which provided drug and financial support for the interventional study (Protocol Nr MK8259-22)info:eu-repo/semantics/publishedVersio

Magro, Fernando

Lopes, Susana

Silva, Marco

Coelho, Rosa

Portela, Francisco

Branquinho, Diogo

Correia, Luís

Fernandes, Samuel

Cravo, Marília

Caldeira, Paulo

Tavares de Sousa, Helena

Patita, Marta

Lago, Paula

Ramos, Jaime

Afonso, Joana

Redondo, Isabel

Machado, Patrícia

Philip, George

Lopes, Joanne

Carneiro, Fátima

Repositório Científico da Unidade Local de Saúde de Santo António

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.info:eu-repo/semantics/publishedVersio

Magro, F

Lopes, S

Silva, M

Coelho, R

Portela, F

Branquinho, D

Correia, L

Fernandes, S

Cravo, M

Caldeira, P

Tavares de Sousa, H

Patita, M

Lago, P

Ramos, J

Afonso, J

Redondo, I

Machado, P

Philip, G

Lopes, J

Carneiro, F

Repositório da Unidade Local de Saúde São José

Soluble Human Suppression of Tumorigenicity 2 Is Associated with Endoscopic Activity in Patients with Moderate-to-Severe Ulcerative Colitis Treated with Golimumab

Sousa, Helena Tavares

Sapientia (Univ. do Algarve)

https://sapientia.ualg.pt/bitstream/10400.1/12800/1/10.1177_1756284819869141.pdf

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

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Repositório Científico da Unidade Local de Saúde de Santo António

Repositório da Unidade Local de Saúde São José

Sapientia (Univ. do Algarve)