scholarly journals P368 Tofacitinib induction efficiency and intracellular cytokine dynamics in ulcerative colitis: Results from clinical practice

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S348-S348 ◽  
Author(s):  
M Kolar ◽  
M Lukas ◽  
K Malickova ◽  
L Prochazkova ◽  
M Bortlik ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Practice ◽  
Oral Candidiasis ◽  
Mucosal Healing ◽  
Faecal Calprotectin ◽  
Mayo Score ◽  
Systemic Corticosteroids ◽  
Potential Biomarker ◽  
Insufficient Response ◽  
Baseline Predictor

Abstract Background Tofacitinib is an oral JAK inhibitor approved for the treatment of ulcerative colitis (UC). Its efficiency was proven in registration trials; however, data from clinical practice are insufficient. Our aim was to evaluate response to tofacitinib after 8 weeks in UC patients, and to assess potential predictors of response including early cytokine production shifts. Methods Data from consecutive UC patients who started tofacitinib 10 mg b.i.d. were evaluated. Disease activity was assessed by Mayo score at baseline and week 8 together with C-reactive protein (CRP) and faecal calprotectin (FC). Production of IL-4, IL-10, IL-17, TNFα and IFNγ in T-helper cells was determined at baseline and week 4. At week 8, patients with total Mayo 0–5 with endoscopic subscores 0–1 were considered responders. Adverse events were registered at every visit. Results Twenty-four patients (41.7% males, 58.3% females), mean age 35.3 ± 11.8 years were included. Mean disease duration was 8.3 ± 5.2 years. In median, the patients were previously treated with two biologic agents; however, 25% of the patients were naive to any biologic therapy. Systemic corticosteroids were present in 41.7% patients at baseline and no patient had concomitant biologic or other immunosuppressive therapy. At week 8, 52.9% of patients responded to therapy. Total Mayo decreased in responders from mean 5.9 ± 3.5 to 1.1 ± 1.3 (p = 0.01), while in nonresponders it changed from 8.0 ± 2.5 to 8.9 ± 2.1 (p = 0.86). Endoscopic subscore decreased from 2.0 ± 1.0 to 0.6 ± 0.7 (p = 0.02) in responders, however, remained stationary in nonresponders (2.9). CRP and FC dropped significantly in responders (6.7 ± 6.2 vs. 2.0 ± 2.2 mg/l, p = 0.04; 1195 ± 1189 vs. 578 ± 654 μg/g, p = 0.05), but not in nonresponders. The responding and nonresponding groups differed significantly in baseline triglycerides, which were higher in nonresponders. Other baseline parameters were comparable. In responders, there was a significant decrease in IL-4 and no change in IL-10, while in nonresponders, there was no change in IL-4 and a significant decrease in IL-10. Tofacitinib was stopped in 23.5% of patients at week 8 due to insufficient response. Two patients reported headaches after treatment initiation and single events of CMV colitis, C. diff. colitis and oral candidiasis occurred. Conclusion Tofacitinib was efficient in inducing clinical response with mucosal healing in about 50% of UC patients after 8 weeks of therapy. There was no clear baseline predictor of response, however, considering limited sample, there was also no indication of even multiple biologics failure negatively affecting the response. Preliminary results of cytokine dynamics suggest early IL-4 decrease as a potential biomarker of response, warranting further investigation.

scholarly journals P494 The efficacy and safety of adalimumab for patients with moderately to severely active ulcerative colitis and predictors of response in Korea

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S432-S432
Author(s):  
S Shin Shin ◽  
S J Park ◽  
Y Kim ◽  
J P Im ◽  
H J Kim ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Response ◽  
Clinical Remission ◽  
Drug Level ◽  
Mucosal Healing ◽  
Efficacy And Safety ◽  
Faecal Calprotectin ◽  
Mayo Score ◽  
Predictors Of Response ◽  
Tnf Α

Abstract Background The aim of this study to assess the efficacy and safety of adalimumab (ADA), a monoclonal antibody against tumour necrosis factor α (TNF-α), and to explore predictors of response in Korean patients with ulcerative colitis (UC). Methods We conducted a prospective observational multicenter study over 56 weeks in adult patients with moderately to severely active UC. Clinical response and remission were assessed by Mayo score. Mucosal healing was defined as Mayo subscore 0 or 1. Faecal calprotectin (FC) were assessed at baseline, week 8 and 56. Adalimumab drug levels were checked at week 8 and at loss of response. Missing or incomplete data were handled using the nonresponder imputation method. Results A total of 146 patients were enrolled and included in the analysis. Clinical response rates were 52.1% (76/146) and 37.7% (55/146) at week 8 and 56, respectively. Clinical remission was achieved in 24.0% (35/146) and 21.9% (32/146) of patients at week 8 and 56. Steroid-free remission rates were 21.2% (31/146) at week 56. Mucosal healing rates were 39.0% (57/146) and 30.1% (44/146) at week 8 and 56. Prior use of anti-TNF-α did not affect the clinical and endoscopic responses. Treatment persistence was achieved in 57.5% (84/146) of patients at week 56. Adalimumab drug level was significantly higher in patients with clinical response (10.8 vs. 8.0, p = 0.004), clinical remission (11.7 vs. 8.8, p = 0.007) and mucosal healing (11.0 vs. 8.5, p = 0.010) at week 8. Adalimumab dose was escalated to 40 mg weekly in 25 (17.1%) patients, and clinical response and remission were achieved in 40% and 20% of patients at week 56, respectively. Mean faecal calprotectin levels were significantly more decreased in clinical responders compared with non-responders at week 8 (336.3 mg/kg vs. 628.8 mg/kg, p < 0.001). The Fecal calprotectin levels are well correlated with endoscopic severity, and the best cut-off value to predict mucosal healing was 274 mg/kg. The lower endoscopic severity, higher body mass index and higher serum albumin level at baseline were associated with a clinical response at week 8. The lower Mayo score, lower C-reactive protein level, clinical response (74.5% vs. 38.5%, p < 0.001) and mucosal healing (52.7% vs. 30.8%, p = 0.008) at week 8 were associated with clinical response at week 56. Serious adverse drug reactions were identified in 2.7% (4/146) of patients including 1 case of pulmonary tuberculosis. Conclusion Adalimumab is safe and effective for induction and maintenance in Korean patients with UC, regardless of prior anti-TNF therapy. Adalimumab drug level is associated with the efficacy of induction therapy. A better response to induction therapy can predict a better long-term response.

scholarly journals Effectiveness of treatment of moderate ulcerative colitis with prolonged mesalazine in real clinical practice

2021 ◽  
pp. 144-151
Author(s):  
O. V. Knyazev ◽  
A. V. Kagramanova ◽  
A. A. Lishchinskaya
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Remission ◽  
Topical Therapy ◽  
Fecal Calprotectin ◽  
Mucosal Healing ◽  
Prolonged Release ◽  
Mayo Score ◽  
Endoscopic Remission ◽  
Oral Mesalazine ◽  
High Doses

Introduction. Ulcerative colitis (UC) is one of the severe therapeutic diseases. High doses of oral granular mesalazine are required to maintain clinical and endoscopic remission of UC, which may be sufficient and supposedly more acceptable for patients, as some studies showed that adherence to topical therapy is significantly lower than to oral 5-ASA drugs.Objective of the study. To evaluate the efficacy of therapy of patients with moderate left-sided ulcerative colitis (UC) and pancolitis receiving prolonged-release ethylcellulose-coated mesalazine.Materials and methods. The evaluation of the outcomes of treatment of UC patients who received prolonged-release mesalazine was carried out. We examined 87 patients with UC who received granular ethylcellulose-coated mesalazine, of those 38 (43.7%) men and 49 (56.3%) women. The average age of the enrolled patients was 38.3 ± 12.6 years.Results and discussion. After 2 weeks from the beginning of therapy with prolonged-release mesalazine, the majority of patients – 71 (81.6%) responded to the therapy. After 12 weeks, 71 (81.6%) of 87 UC patients, who responded to therapy with prolongedrelease mesalazine, remained in clinical remission. On average, the Mayo score in the group decreased from 7.6 ± 0.99 to 2.6 ± 0.25 points. There was a significant decrease in CRP, ESR, leukocytosis, and fecal calprotectin. After 26 weeks, Mayo score in the group of patients remained on average at the level of 2.2–2.3 points. The number of UC patients with colon mucosal healing was 32 (36.8%) patients. A year after the start of therapy with prolonged-release mesalazine, 69 (79.3%) UC patients who responded to therapy had a clinical remission, of those 32 (36.8%) patients had a clinical and endoscopic remission. During the year of observation, no case of surgical intervention or re-hospitalization due to exacerbation of the disease was recorded in patients with UC who achieved remission.Conclusions. Treatment of moderate active UC should begin with oral mesalazine ≥ 3 g per day in combination with topical mesalazine. The prolonged-release mesalazines are the most preferred

scholarly journals P227 Defining faecal calprotectin thresholds to predict endoscopic and histological healing in ulcerative colitis (UC) by using advanced optical enhancement techniques

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S255-S256
Author(s):  
R Cannatelli ◽  
D Zardo ◽  
O Nardone ◽  
A Bazarova ◽  
U Shivaji ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Surrogate Marker ◽  
Scoring Systems ◽  
Roc Curves ◽  
Mucosal Healing ◽  
Faecal Calprotectin ◽  
Area Under Roc Curve ◽  
Index Of Severity ◽  
Sensitivity Specificity ◽  
A Prospective Study

Abstract Background Faecal calprotectin (FC) is the most common surrogate marker of mucosal healing (MH) in UC. A number of endoscopic and histologic scoring systems in UC have been developed for defining MH. We report the optimum FC thresholds for defining MH using all the assessment methods. Methods In a prospective study we collected all clinical, endoscopic and histologic data and FC from 76 UC patients (mean age 44.2y, 50.0% male) who attended endoscopy unit for colitis assessment or surveillance. Endoscopic scores were determined by the same endoscopist (MI) and included Mayo Endoscopic Score (MES), Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and PICaSSO (Paddington International virtual ChromoendoScopy ScOre). Histological activity was scored by the Robarts Histology Index (RHI) and Nancy Index by the same pathologist (DZ). Faecal calprotectin was assayed using Buhlmann faecal turbo test, particle enhanced turbidimetric immunoassay. ROC curves were performed to evaluate sensitivity, specificity and accuracy of the optimum cut-off of FC to predict endoscopic and histological healing. Results The best cut-off for FC to predict endoscopic healing calculated as Picasso≤3 was 161 μg/g with Area Under ROC curve (AUROC) of 85.3% (95% CI 76.2, 94.4). Sensitivity, specificity and accuracy were 87.9% (95% CI 57.6, 100), 76.7% (95% CI 53.5, 90.7) and 81.6% (95% CI 68.4, 89.5), respectively. While, the best threshold of FC to predict UCEIS≤1 was 148 μg/g with AUROC of 89.2 (95% CI 81.9, 96.5). Sensitivity was 93.5% (95% CI 50.5, 100), specificity 82.2% (95% CI 53.3, 91.1) and accuracy 86.8% (95% CI 69.7, 92.1). The best threshold for FC to predict MES equal to 0, was 112 μg/g, with AUROC of 89.6 μg/g, (95% CI 82.5, 96.7). Sensitivity, specificity and accuracy were 89.7%ww (95% CI 39.2, 100), 85.1% (95% CI 55.3, 93.6) and 86.9% (95% CI 68.4, 92.1), respectively. The best value of FC to predict histological healing with RHI≤3 was 112μg/g with AUROC of 88.0% (95% CI 80.6, 95.4). Sensitivity, specificity and accuracy were 88.5% (95% CI 53.8, 100), 80.0% (95% CI 62.0, 90.0) and 82.9% (95% CI 72.5, 89.5), respectively. When used Nancy≤1 FC cut-off to predict healing was 172 μg/g with AUROC of 87.1% (95% CI 78.6, 95.6). Sensitivity was 96.4% (95% CI 60.7, 100), specificity 72.9% (54.2, 85.4) and accuracy 81.6% (69.7, 89.5). Conclusion Advanced enhancement technologies can accurately define the level of FC to predict endoscopic and histological healing in UC. The optimum FC threshold for MH by PICaSSO and by Nancy was similar (161 and 172 μg/g respectively), while the FC threshold for mucosal healing by MES and by RHI was 112 μg/g. The FC threshold for determining MH in clinical practice should be lower than at least 200 μg/g.

scholarly journals P270 Ulcerative colitis disease extent and inflammatory burden assessment: DUBLIN and modified Nancy score

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S285-S286
Author(s):  
J C Rocha Silva ◽  
J Rodrigues ◽  
A Rodrigues ◽  
A Silva ◽  
C Fernades ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Score ◽  
Mucosal Inflammation ◽  
Clinical Relapse ◽  
Disease Extent ◽  
Faecal Calprotectin ◽  
Protein Levels ◽  
Mayo Score ◽  
Disease Extension ◽  
Inflammatory Burden

Abstract Background Current endoscopic activity scores for ulcerative colitis (UC) do not take into account the extent of mucosal inflammation. The DUBLIN score (Degree of Ulcerative Colitis Burden of Luminal Inflammation) is a simple bedside clinical score that estimates inflammatory burden using both disease severity and extent, which correlates with objective inflammatory markers and is associated with clinical outcomes. The validated Nancy score is used to evaluate histological activity; nonetheless, it does not take in consideration disease extension. We aimed to evaluate the relation of both Mayo and Dublin scores with disease activity and as predictive factors of clinical relapse. Also, we developed a modified Nancy score in order to assess histologic activity considering disease extension. Methods A retrospective cohort study, which consecutively included all UC patients submitted to colonoscopy with biopsies between 2016 and 2019 in our unit. Mayo and DUBLIN scores were calculated. Modified Nancy score was calculated as a product of Nancy Score and disease extent (E1-E3). Correlation of both endoscopic and histologic scores with biomarkers, relapse (in a 6months) and relapse-free time as performed. Results 107 patients were selected, 52.3% (n = 56) male, mean age = 48.4 ± 13.9 years. Mean Dublin score was 2.65 ± 2.75. Mayo and DUBLIN scores presented good correlation (r = 0.880, p < 0.001). Also Dublin score correlated with modified Nancy score (p < 0.001). Both Dublin score (p = 0.009) and modified Nancy score (p = 0.026) correlated with C-reactive protein levels. Nancy score correlated with faecal calprotectin (p = 0,025). Relapse occurred in 26.2% (n = 28) of patients with a mean time for the event of 13 ± 7 weeks. Mayo Score (p < 0.001), Dublin score (p < 0.001), Nancy score (p < 0.001) and modified Nancy score (p < 0.001) presented a significant association with relapse. Areas under the ROC curve were 0.786 for Dublin score, 0.751 for Mayo score, 0.84 for Nancy score and 0.79 for modified Nancy score. Conclusion DUBLIN and modified Nancy scores correlate with each other and with biomarkers and are independent predictors of relapse. Dublin score was superior to Mayo score in the prediction of relapse.

scholarly journals MODERATE TO SEVERE ENDOSCOPIC INFLAMMATION IS FREQUENT AFTER ACHIEVING CLINICAL REMISSION IN PEDIATRIC ULCERATIVE COLITIS

2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S13-S13
Author(s):  
Chen Sarbagili-Shabat ◽  
Dror Weiner ◽  
Joram Wardi ◽  
Lee Abramas ◽  
Michal Yaakov ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Remission ◽  
Residual Disease ◽  
Activity Index ◽  
Final Analysis ◽  
Mucosal Healing ◽  
Sustained Remission ◽  
High Relapse Rate ◽  
Mayo Score

Abstract Background Pediatric ulcerative colitis (UC) is characterized by low sustained remission rates and frequent extension of disease even if clinical remission is obtained with therapy. Moderate to severe endoscopic activity is a risk factor for relapse while evidence regarding early mucosal healing or persistence of inflammation after remission in children is not available. Our aim was to evaluate if persistence of significant inflammation is common and could explain the high relapse rate in pediatric UC. Methods Pediatric UC patients with clinical remission, defined as pediatric UC activity index (PUCAI) scores < 10, were prospectively assessed for mucosal healing by endoscopy 3–5 months after remission was documented. Mayo score was assessed for each segment by a blinded adult gastroenterologist using central reading. Symptomatic patients prior to sigmoidoscopy were excluded Sustained remission was assessed retrospectively at 18 months follow-up. Results Forty-six children were enrolled, 28 children in continuous clinical remission at time of sigmoidoscopy were included in the final analysis. Mayo 0 was present in 12/28 (42.86%), Mayo 1 in 2/28 (7.1%) and Mayo 2–3 in 14/28 (50.0%) endoscopies. Among 23/28 patients with follow-up through 18 months, remission was sustained in 2/11 (18.18%) of patients with Mayo 2 and 3 versus 6/12 (50.0%) with Mayo score 0–1. Conclusion Over 50% of children assessed for mucosal healing 3–5 months after clinical remission is obtained have residual disease activity, primarily moderate to severe inflammation which was associated with lower sustained remission. Early sigmoidoscopy after clinical remission for assessment of mucosal disease should be considered in pediatric UC.

scholarly journals P476 Effectiveness and safety of ustekinumab in ulcerative colitis: Real-world evidence from the ENEIDA registry

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S465-S466
Author(s):  
M Chaparro ◽  
A Garre ◽  
M Iborra ◽  
M Sierra ◽  
M Barreiro-de Acosta ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Practice ◽  
Elevated Serum ◽  
Real Life ◽  
Development Program ◽  
Lower Probability ◽  
Clinical Activity ◽  
Mayo Score

Abstract Background The development program (UNIFI) has shown promising results of ustekinumab in ulcerative colitis (UC) treatment that should be confirmed in clinical practice. Aims Primary: to evaluate the durability of ustekinumab treatment in UC patients in clinical practice. Secondary: to assess the short-term response (at week 16) and the long-term effectiveness (at maximum follow-up) and to assess the safety of ustekinumab in clinical practice. Methods Patients included in the prospectively maintained ENEIDA registry who received at least one intravenous dose of ustekinumab due to active UC [Partial Mayo Score (PMS) >2] were included. Clinical activity and effectiveness were defined based on PMS. Results 95 patients were included (table 1). At week 16, 53% of patients had clinical response (including 35% of patients in remission) (figure 1). In the multivariate analysis, elevated serum C-reactive protein was the only variable significantly associated with clinical remission. Long-term remission is represented in figure 2. 36% of patients discontinued the treatment with ustekinumab during a median follow-up of 31 weeks. The probability of maintaining ustekinumab treatment was 87% at week 16, 63% at week 56, and 59% at week 72 (figure 3); primary failure was the main reason for ustekinumab discontinuation. No variable was associated with risk of discontinuation. Three patients reported adverse events; one of them had a fatal severe SARS-CoV-2 infection. Conclusion Ustekinumab is effective both in the short and the long-term in real-life, even in a highly refractory cohort. Higher inflammatory burden at baseline correlated with lower probability of achieving remission. Safety was consistent with the known profile of ustekinumab.

scholarly journals The level of faecal calprotectin as a noninvasive biomarker of mucosal healing in children with ulcerative colitis

2020 ◽  
Vol 15 (4) ◽  
pp. 343-348
Author(s):  
Edyta Szymańska ◽  
Monika Meglicka ◽  
Maciej Dądalski ◽  
Marcin Osiecki ◽  
Marta Kotkowicz-Szczur ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Mucosal Healing ◽  
Faecal Calprotectin ◽  
Noninvasive Biomarker

scholarly journals Long-term, Real-life, Observational Study in Treating Outpatient Ulcerative Colitis with Golimumab

2021 ◽  
Author(s):  
Antonio Tursi ◽  
Giammarco Mocci ◽  
Walter Elisei ◽  
Leonardo Allegretta ◽  
Raffaele Colucci ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Response ◽  
Clinical Remission ◽  
Real Life ◽  
Mucosal Healing ◽  
Term Treatment ◽  
Short Term Treatment ◽  
Mayo Score

Background and Aims: Several studies have found Golimumab (GOL) effective and safe in the short-term treatment of ulcerative colitis (UC), but few long-term data are currently available from real world. Our aim was to assess the long-term real-life efficacy and safety of GOL in managing UC outpatients in Italy. Methods: A retrospective multicenter study assessing consecutive UC outpatients treated with GOL for at least 3-month of follow-up was made. Primary endpoints were the induction and maintenance of remission in UC, defined as Mayo score ≤2. Several secondary endpoints, including clinical response, colectomy rate, steroid free remission and mucosal healing, were also assessed during the follow-up. Results: One hundred and seventy-eight patients were enrolled and followed up for a median (IQR) time of 9 (3-18) months (mean time follow-up: 33.1±13 months). Clinical remission was achieved in 57 (32.1%) patients: these patients continued with GOL, but only 6 patients (3.4%) were still under clinical remission with GOL at the 42nd month of follow-up. Clinical response occurred in 64 (36.4%) patients; colectomy was performed in 8 (7.8%) patients, all of them having primary failure. Steroid-free remission occurred in 23 (12.9%) patients, and mucosal healing was achieved in 29/89 (32.6%) patients. Adverse events occurred in 14 (7.9%) patients. Conclusions: Golimumab does not seem able to maintain long-term remission in UC in real life. The safety profile was good.

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