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1.
Artigo em Inglês | MEDLINE | ID: mdl-38908734

RESUMO

BACKGROUND & AIMS: Because transmural healing (TH) could be the best therapeutic target in Crohn's disease (CD), we aimed to build and validate a score to assess TH and transmural response (TR), and to confirm their association with favorable CD outcomes. METHODS: DEVISE-CD project encompassed 2 retrospective cohorts (274 and 224 patients with CD for development and validation phase, retrospectively) and 1 multicenter prospective validation cohort (N = 46 patients). A step-by-step process was used to build the modified Clermont score (C-score). The primary end points were time to bowel damage progression, and steroid-free clinical remission with fecal calprotectin <250 at 1 year for retrospective and prospective validation cohorts, respectively. RESULTS: Edema, ulcer, contrast enhancement, diffusion-weighted hyperintensity, fat wrapping, bowel thickening (>3 mm), and enlarged lymph nodes were associated to higher risk of bowel damage progression (P < .01). Edema, diffusion-weighted hyperintensity, post-gadolinium contrast enhancement, and bowel thickening were highly coexistent (>95%) and collinear (P < .0001). Bowel thickness had the highest sensitivity to change after treatment (standardized mean difference = 0.30 ± 1.0; P = .001). C-score was calculated as 0.2x(bowel thickness-3mm) + 1.5x enlarged lymph nodes + 2x ulcer. TH (C-score <0.5; hazard ratio [HR], 0.28 [0.13-0.63]; P = .002; adjusted HR [aHR], 0.15 [0.04-0.53]; P = .003), TR50 (50% decrease of C-score; HR, 0.30 [0.15-0.63]; P = .001; aHR, 0.36 [0.14-0.88]; P = .025), or TR25 (25% decrease of C-score; HR, 0.37 [0.19-0.71]; P = .003; aHR, 0.46 [0.23-0.94]; P = .034) prevented bowel damage progression in development and validation cohorts, respectively. In the prospective validation cohort, achieving TH (OR, 4.6 [1.3-15.6]; P = .016), TR50 (OR, 6.9 [1.8-26.0]; P = .008), or TR25 (OR, 6.0 [1.6-22.3]; P = .008) after 12 weeks of anti-tumor necrosis factor therapy led to higher rate of corticosteroid-free remission at 1 year. CONCLUSIONS: C-score is a validated, reliable, and easy-to-use tool to assess TH and TR in patients with CD.

2.
J Crohns Colitis ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38742654

RESUMO

BACKGROUND: Both vedolizumab and ustekinumab can be considered for the treatment of ulcerative colitis (UC) but head-to-head trials are lacking. AIM: We aimed to compare the effectiveness of vedolizumab and ustekinumab after anti-TNF failure in UC patients. PATIENTS AND METHODS: In this multicenter study, we included consecutive adult patients with UC, with partial Mayo score >2 and prior anti-TNF exposure, treated with vedolizumab or ustekinumab between January 2019 and August 2022. Comparisons were performed using propensity score analyses (inverse probability of treatment weighting). RESULTS: Among a total of 293 patients included, 151 and 142 received vedolizumab and ustekinumab, respectively. After propensity-score analysis, steroid-free clinical remission (SFCR) (Mayo score partial ≤ 2) was achieved at week 16 in 38.0% and 40.3%, of patients treated with vedolizumab and ustekinumab, respectively (aOR = 1.11 [0.39-3.13], p = 0.85). Rate of SFCR in patients exposed to one line, 2 lines and 3 lines of biologics/small molecules among patients treated with vedolizumab and ustekinumab were respectively 53.3% vs 62.1% (p=0.52), 44.4% vs 33.8% (p=0.52) and 2.6% vs 19.1% (p=0.027). Endoscopic remission (SFCR and endoscopic Mayo score ≤1) and histological remission (SFCR, endoscopic remission and Nancy histological index ≤1) at W16 were achieved in respectively, 5.3% vs 17.5% (aOR = 3.77 [1.25-11.36], p=0.018) and 2.1% vs 11.1% (aOR = 5.85 [1.47-23.30], p=0.012) in vedolizumab and ustekinumab groups. No difference regarding the risk of drug discontinuation between the two groups (aHR = 1.03 [0.51-2.08], p = 0.92) were observed. While no factor was identified for vedolizumab, primary failure to at least one biologic/small molecule (OR=0.31, 95%CI [0.11-0.82], p=0.018) was significantly associated with decreased rate of SFCR among patients treated with ustekinumab. CONCLUSION: While no difference in terms of short-term clinical remission was observed, ustekinumab appears to be more effective than vedolizumab to induce endoscopic and histological remission at week 16 after failure of anti-TNFs in UC.

3.
PLoS One ; 19(4): e0298313, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38564601

RESUMO

AIMS: In patients with ulcerative colitis (UC), no biomarker is available to help the physician to choose the most suitable biotherapy. The primary objective of this pilot study was to assess the feasibility of identification of α4ß7- and TNF-expressing cells, to predict the response to vedolizumab using confocal laser endoscopy (CLE). METHODS: Patients with moderate-to-severe UC, naïve of biotherapy, received vedolizumab. Clinical evaluation was performed at each infusion. Endoscopic evaluation was performed before inclusion and at week 22. Fresh colonic biopsies were stained using FITC-labelled vedolizumab and Alexa fluor-labelled adalimumab and ex vivo dual-band CLE images were acquired. Blood samples were collected to measure trough concentrations of vedolizumab and to determine absolute counts of T and B cells subpopulations, NK cells and monocytes. RESULTS: Nineteen patients were enrolled in the study and received at least one dose of vedolizumab. Clinical remission and endoscopic improvement were observed in 58% of whom 5 patients (45%) had an endoscopic subscore of 0. In terms of clinical response and remission, endoscopic improvement and histologic response, FITC-conjugated vedolizumab staining tended to be higher in responder patients compared to non-responders at week 22. A threshold value of 6 positive FITC-vedolizumab staining areas detected by CLE seemed informative to discriminate the responders and non-responders. The results were similar in terms of clinical remission and endoscopic improvement with a sensitivity of 78% and a specificity of 85% (p = 0.05). Trough concentrations and blood immune cells were not associated with responses to vedolizumab. CONCLUSION: This pilot study demonstrate that dual-band CLE is feasible to detect α4ß7- and TNF-expressing cells. Positive α4ß7 staining seems to be associated with clinical and endoscopic remission in UC patients treated by anti-α4ß7-integrin, subject to validation by larger-scale studies. Clinical-trial.gov: NCT02878083.


Assuntos
Anticorpos Monoclonais Humanizados , Colite Ulcerativa , Humanos , Projetos Piloto , Fluoresceína-5-Isotiocianato , Biomarcadores , Endoscopia Gastrointestinal , Fármacos Gastrointestinais/uso terapêutico , Resultado do Tratamento , Indução de Remissão
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