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

2019Journal article Open access
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dc.contributor.authorMagro, Fernando
dc.contributor.authorLopes, Susana
dc.contributor.authorSilva, Marco
dc.contributor.authorCoelho, Rosa
dc.contributor.authorPortela, Francisco
dc.contributor.authorBranquinho, Diogo
dc.contributor.authorCorreia, Luís
dc.contributor.authorFernandes, Samuel
dc.contributor.authorCravo, Marília
dc.contributor.authorCaldeira, Paulo
dc.contributor.authorTavares de Sousa, Helena
dc.contributor.authorPatita, Marta
dc.contributor.authorLago, Paula
dc.contributor.authorRamos, Jaime
dc.contributor.authorAfonso, Joana
dc.contributor.authorRedondo, Isabel
dc.contributor.authorMachado, Patrícia
dc.contributor.authorPhilip, George
dc.contributor.authorLopes, Joanne
dc.contributor.authorCarneiro, Fátima
dc.date.accessioned2020-08-27T10:32:03Z
dc.date.available2020-08-27T10:32:03Z
dc.date.issued2019
dc.description.abstractBackground: 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.pt_PT
dc.description.sponsorshipThis work was supported by Merck Sharp and Dohme, Lda, Portugal, which provided drug and financial support for the interventional study (Protocol Nr MK8259-22)pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationMagro F, Lopes S, Silva M, et al. Soluble human Suppression of Tumorigenicity 2 is associated with endoscopic activity in patients with moderate-to-severe ulcerative colitis treated with golimumab. Therap Adv Gastroenterol. 2019;12:1756284819869141. Published 2019 Aug 30. doi:10.1177/1756284819869141pt_PT
dc.identifier.doi10.1177/1756284819869141pt_PT
dc.identifier.issn1756-283X
dc.identifier.issn1756-2848
dc.identifier.urihttp://hdl.handle.net/10400.16/2449
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherSAGE Publicationspt_PT
dc.relation.publisherversionhttps://journals.sagepub.com/doi/pdf/10.1177/1756284819869141pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/pt_PT
dc.subjectendoscopic activitypt_PT
dc.subjectgolimumabpt_PT
dc.subjecthistological activitypt_PT
dc.subjectserum soluble ST2pt_PT
dc.subjectulcerative colitispt_PT
dc.titleSoluble human Suppression of Tumorigenicity 2 is associated with endoscopic activity in patients with moderate-to-severe ulcerative colitis treated with golimumabpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.conferencePlaceEnglandpt_PT
oaire.citation.startPage1756284819869141pt_PT
oaire.citation.titleTherapeutic advances in gastroenterologypt_PT
oaire.citation.volume12pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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