Comparative effectiveness of a second-line biologic in patients with ulcerative colitis: vedolizumab followed by an anti-TNF versus anti-TNF followed by vedolizumab

2022 ◽  
pp. flgastro-2021-101906
Author(s):  
Charles Miller ◽  
Hanson Kwok ◽  
Paul Harrow ◽  
Roser Vega ◽  
Edward Seward ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Survival Rates ◽  
Composite Endpoint ◽  
Outpatient Setting ◽  
Second Line ◽  
Treatment Persistence ◽  
Free Survival ◽  
Mayo Score ◽  
Tnf Α ◽  
Hospital Utilisation

BackgroundSequential drug treatment with biological agents in ulcerative colitis (UC) is becoming increasingly complex. There are few studies comparing head-to-head outcomes in second-line treatments. The study assesses whether using anti-tumour necrosis factor (anti-TNF)-α therapy following the α4β7 integrin blocker vedolizumab (VDZ) or VDZ after an anti-TNF has more favourable clinical outcomes in UC in a real-world outpatient setting.MethodsPatients with UC who were exposed to first-line anti-TNF (adalimumab or infliximab) or VDZ who subsequently switched to the alternate class between May 2013 and August 2020 were identified by reviewing patient databases at 10 hospitals. Data were collected retrospectively using patient records. Baseline demographics, disease activity indices, biochemical markers, endoscopic Mayo score, colectomy rates, treatment persistence and urgent hospital utilisation composite endpoint (UHUC) rates were examined over a 52-week period.ResultsSecond-line week 52 treatment persistence was higher in the VDZ group (71/81, 89%) versus the anti-TNF group (15/34, 44%; p=0.0001), as were week 52 colectomy-free survival (VDZ: 77/80, 96%, vs anti-TNF: 26/32, 81%; p=0.009), week 52 UHUC survival (VDZ: 68/84, 81%, vs anti-TNF: 20/34, 59%; p=0.002) and week 52 corticosteroid-free clinical remission (CFCR) rates (VDZ: 22/34, 65%, vs anti-TNF: 4/20, 20%; p=0.001).ConclusionCompared with second-line anti TNF usage, the VDZ second-line cohort had significantly higher 52-week treatment persistence, UHUC survival, higher colectomy-free survival rates and higher week 52 CFCR. These data suggest that VDZ is an effective biologic in UC as a second-line therapy after anti-TNF exposure. It highlights the effect of biological order on clinically important outcomes.

P445 Does The Sequence Matter ? Comparative effectiveness of a second line biologic in patients with Ulcerative Colitis: vedolizumab followed by an anti-TNF versus anti-TNF followed by vedolizumab

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S443-S444
Author(s):  
C Miller ◽  
H Kwok ◽  
I Parisi ◽  
P Harrow ◽  
S McCartney ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Remission ◽  
Statistical Significance ◽  
Outpatient Setting ◽  
Rank Test ◽  
Second Line ◽  
Survival Curves ◽  
Treatment Persistence ◽  
Free Survival ◽  
Remission Rates

Abstract Background Drug choice and order in Inflammatory Bowel Disease (IBD) is an important challenge and is becoming increasingly complex. There are few studies comparing head-to-head outcomes in second line treatments in Ulcerative Colitis (UC). It is unclear if using anti-Tumour Necrosis Factor-a (anti-TNF) therapy following vedolizumab (VDZ) or VDZ after anti-TNF has a more favourable outcome in UC in a real-world outpatient setting. Methods Patients with UC who were exposed to first-line anti-TNF (adalimumab/ADA or infliximab/IFX) or VDZ who subsequently switched to the alternate class between May 2013-August 2020 were identified following a review of databases at 10 hospitals. 88 VDZ and 39 anti-TNF (12 ADA,27 IFX) second line patients were eligible. Data was collected retrospectively. Baseline demographics, disease activity indices, colectomy rates, treatment persistence and healthcare resource utilisation composite endpoint (HRUC) were examined over a 52 week period for the second line biologic. HRUC included unplanned emergency hospital attendance or hospital admission. The primary endpoints of 52 week treatment persistence, HRUC survival and colectomy free survival were analysed with Kaplan Meier method, statistical significance between the survival curves was assessed with Log Rank test. Propensity score matching (PSM) was applied to survival curves (tolerance level 0.1). For a subset where SCCAI scores available, week 52 corticosteroid free clinical response/remission rates were calculated (response: reduction of SCCAI ≥3 and remission: SCCAI ≤2).: Results The second line anti-TNF group had a significantly higher baseline endoscopic Mayo score (p=0.035) and lower concomitant immunomodulator use (p=0.001). Second line week 52 treatment persistence was higher in the VDZ group 71/80 (89%) vs. Anti-TNF 15/36 (42%) ,p<0.0001 (Figure 1). Second line week 52 HRUC survival was higher in the VDZ group 68/81 (84%) vs. anti-TNF 20/33 (61%), p=0.003 (Figure 2). Week 52 colectomy free survival VDZ 77/80 (96%) vs. anti-TNF 26/32 (81%), p= <0.011 (Figure 3). For treatment persistence and colectomy free survival statistical significance was maintained with PSM. Week 52 corticosteroid free clinical remission rates VDZ 22/32 (69%) vs. anti-TNF 5/19 (25%) p=0.004 (Figure 4). Conclusion The VDZ second line cohort had significantly higher 52-week treatment persistence, lower HRUC and lower colectomy rates and higher corticosteroid free clinical remission rates. This data suggests that VDZ is an effective biologic in UC in a second line therapy after anti-TNF exposure. It highlights the effect of biologic sequencing on clinically important outcomes in an outpatient setting. Larger prospective studies are required to confirm these findings.

scholarly journals Intravenous tacrolimus is a superior induction therapy for acute severe ulcerative colitis compared to oral tacrolimus

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hiromichi Shimizu ◽  
Toshimitsu Fujii ◽  
Kenji Kinoshita ◽  
Ami Kawamoto ◽  
Shuji Hibiya ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Cohort Study ◽  
Primary Outcome ◽  
Remission Rate ◽  
Survival Rates ◽  
Efficacy And Safety ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Severe Ulcerative Colitis ◽  
Intravenous Corticosteroid

Abstract Background Intravenous corticosteroid is the mainstay for managing acute severe ulcerative colitis, but one-third of patients do not respond to intravenous corticosteroid. Tacrolimus, a salvage therapy before colectomy, is usually orally administered, though its bioavailability is low compared intravenous administration. The efficacy of intravenous tacrolimus has not been widely studied. Aim To determine the efficacy and safety of intravenous tacrolimus for the treatment of acute severe ulcerative colitis. Methods Eighty-seven hospitalized acute severe ulcerative colitis patients were enrolled for a prospective cohort study between 2009 and 2017. Sixty-five patients received intravenous tacrolimus and 22 received oral tacrolimus. The primary outcome was the achievement of clinical remission within 2 weeks. Relapse and colectomy incidence and adverse events were assessed at 24 weeks. Results Response rates of both treatments exceeded 50% but were not significantly different. The remission rate was higher in intravenous tacrolimus compared with oral tacrolimus. At 24 weeks, oral and intravenous tacrolimus showed similar relapse-free survival rates; however, colectomy-free survival rates were higher in intravenous tacrolimus compared with oral tacrolimus. Conclusions Patients receiving intravenous tacrolimus achieved superior remission and colectomy-free survival rates compared with patients receiving oral tacrolimus. Safety was similar between the two treatments.

scholarly journals P690 A propensity score weighted comparison of vedolizumab, adalimumab, and golimumab in patients with ulcerative colitis: Real-life data from the Sicilian Network for Inflammatory Bowel Disease (SN-IBD)

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S561-S562
Author(s):  
F S Macaluso ◽  
M Ventimiglia ◽  
W Fries ◽  
A Viola ◽  
M Cappello ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Propensity Score ◽  
Clinical Benefit ◽  
Real Life ◽  
Mucosal Healing ◽  
Treatment Persistence ◽  
Mayo Score ◽  
Inflammatory Bowel

Abstract Background No real-life study aiming at comparing at the same time the effectiveness of vedolizumab (VDZ), adalimumab (ADA), and golimumab (GOL) in Ulcerative colitis (UC) is currently available. Methods Data of consecutive patients with UC treated with VDZ, ADA, and GOL from June 2015 to December 2018 were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Disease (SN-IBD). A three-arms propensity score-adjusted analysis was performed to reduce bias caused by imbalanced covariates at baseline, including the proportion of TNF-α inhibitor naïve and non-naïve patients, using the Inverse Probability of Treatment Weighting (IPTW) method. The effectiveness was evaluated at 8 weeks, 52 weeks, and as treatment persistence at the end of follow-up. The clinical endpoints were steroid-free clinical remission (partial Mayo score <2 without steroid use) and clinical response (reduction of the partial Mayo score ≥2 points with a concomitant decrease of steroid dosage compared with baseline). The sum of the two outcomes was defined as a clinical benefit. The achievement of mucosal healing (endoscopic Mayo score 0–1) was assessed after at least 6 months of biological treatment. Results A total of 463 treatments (VDZ: n = 187; ADA: n = 168; GOL: n = 108) were included, with a median follow-up of 47.6 weeks (IQR 20.0–85.9). At 8 weeks, a clinical benefit was achieved in 70.6% patients treated with VDZ, in 68.5% patients treated with ADA, and in 67.6% patients treated with GOL (p = n.s. for all comparisons). After 52 weeks, VDZ showed better rates of clinical benefit compared with both ADA (71.6% vs. 47.5; OR: 2.79, 95% CI 1.63–4.79, p < 0.001) and GOL (71.6% vs. 40.2%; OR: 3.77, 95% CI 2.08–6.80, p < 0.001), while the difference between ADA and GOL was not significant. Cox survival analysis demonstrated that patients treated with VDZ had a reduced probability of treatment discontinuation compared with those treated with ADA (HR: 0.42, 95% CI 0.28–0.64, p < 0.001) and GOL (HR: 0.30, 95% CI 0.19–0.46, p < 0.001), while patients treated with ADA had a reduced risk of treatment discontinuation compared with those treated with GOL (HR: 0.71, 95% CI 0.50–1.00, p = 0.048). Post-treatment mucosal healing rates showed a numerical but non-significant difference in favour of VDZ (48.1%) compared with ADA and GOL (38.0% and 34.6%, respectively). Conclusion In the first study comparing at the same time the clinical effectiveness of VDZ, ADA, and GOL in UC patients via propensity score-adjusted analysis, VDZ was superior to both subcutaneous agents at 52 weeks and as treatment persistence, while ADA showed a superior treatment persistence compared with GOL.

scholarly journals Treatment persistence and colectomy-free outcomes in patients with ulcerative colitis receiving golimumab or adalimumab: a UK experience

2020 ◽  
Vol 7 (1) ◽  
pp. e000476
Author(s):  
Sami Hoque ◽  
Amy Puenpatom ◽  
Simona Boccaletti ◽  
Chloe Green ◽  
Christopher M Black ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Real World ◽  
Clinical Characteristics ◽  
Treatment Initiation ◽  
Post Treatment ◽  
Categorical Variables ◽  
Treatment Persistence ◽  
Free Survival ◽  
Treatment Switching ◽  
Persistence Rates

ObjectiveTo examine real-world treatment persistence, colectomy-free survival and treatment switching patterns in UK patients with ulcerative colitis (UC) prescribed golimumab or adalimumab.DesignThis was a retrospective chart review study in adult patients diagnosed with UC using data from 16 National Health Service sites in the UK. Patient records were included in the study if they had initiated first or second-line adalimumab or golimumab between 1 March 2016 and 30 September 2017 (index date). Subjects were required for ≥6 months post treatment initiation. Demographics, clinical characteristics, treatment-related data and colectomy data were extracted over a follow-up period of 6–12 months. Treatment persistence rate was the primary outcome. Colectomy-free survival and treatment switching were secondary outcomes. Outcomes were compared between treatments using χ2 tests and Fisher’s exact test for categorical variables. The t-tests were used for continuous variables. Time-to-event variables were evaluated using Kaplan-Meier curves and log-rank tests.ResultsThe study included a total of 183 patients (96 (52.5%) prescribed adalimumab; 87 (47.5%) golimumab), and patients were mostly first line (79.8%). Demographic and clinical characteristics were generally similar between treatment groups. Persistence rates within 12 months were 64.6% for adalimumab and 64.4% for golimumab (p=0.681). Overall, 20.2% switched to other therapy within 1 year, with 8.2% golimumab and 12.0% adalimumab switching to another biologic. Of patients prescribed adalimumab, 14.6% had ≥1 dose change, mainly dose escalations. In the 12 months post treatment initiation, 8.2% of patients underwent colectomy, with no significant difference in colectomy-free survival by treatment, p=0.73.ConclusionThis study provides evidence of clinical outcomes and real-world persistence for adalimumab and golimumab in UC. The persistence rates of both therapies were above 64.0% at 12 months following treatment initiation. In addition, the 1-year colectomy-free survival was relatively similar between the two treatments.

scholarly journals P433 A real-world observational study assessing treatment persistence in ulcerative colitis patients receiving anti-TNF treatment (golimumab or adalimumab)

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S394-S394
Author(s):  
S Hoque ◽  
S Boccaletti ◽  
A Puenpatom ◽  
C Brown ◽  
C Black ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Real World ◽  
Treatment Initiation ◽  
Retrospective Chart Review ◽  
Real World Data ◽  
Biologic Treatment ◽  
Treatment Persistence ◽  
Free Survival ◽  
The Real ◽  
The Uk

Abstract Background There are limited published observational data describing both clinical outcomes and treatment persistence rates for anti-TNFs used to treat ulcerative colitis (UC), particularly for golimumab. Based on published literature the outcomes demonstrated in clinical trials do not necessarily translate into clinical practice, highlighting the importance of real-world studies. In this study, we evaluated treatment persistence, switching patterns, and colectomy outcomes between golimumab and adalimumab in the real-world setting. Methods A retrospective chart review was conducted across 16 NHS sites in the UK. Data describing demographics, treatment history and colectomy were collected for UC patients treated with either golimumab or adalimumab. Patients were receiving golimumab or adalimumab as first or second-line therapy and initiating treatment between 1 March 2016 and 30 September 2017. Patients enrolled were required to have at least 6 months of data for analyses, and were followed within 12 months where the data were available. Kaplan–Meier analysis was conducted to assess time to discontinuation and also time to colectomy; log-rank tests were used to compare the two treatment arms. Results A total of 183 patients, (87 golimumab, 96 adalimumab), mean age was 45.6 years (46.8 years golimumab; 44.4 years adalimumab) and 59.6% were male (71.3% golimumab; 49.0% adalimumab), were included. Overall, 79.8% (78.2% golimumab; 81.3% adalimumab) of patients were receiving their first-line biologic. Treatment persistence with golimumab or adalimumab were relatively similar; 64.4% of golimumab and 64.6% of adalimumab patients remaining on treatment at 12 months (p = 0.7, Figure 1). Of the 65 patients who discontinued treatment within 12 months, 48.4% golimumab and 64.7% adalimumab switched to another biologic. Of those patients who switched, vedolizumab was the most commonly prescribed drug (56.8%), followed by infliximab biosimilar (Inflectra/Remsima) (29.7%) and infliximab (Remicade) (13.5%). Colectomy-free survival was demonstrated by 92.0% golimumab and 91.7% of adalimumab patients 12 months post-treatment initiation (p = 0.7). Conclusion The real-world data collected in this study demonstrate comparable treatment persistence for golimumab compared with adalimumab 12 months following treatment initiation. Colectomy-free survival was relatively similar within 1 year.

scholarly journals Serum PR3-ANCA Is a Predictor of Primary Nonresponse to Anti-TNF-α Agents in Patients with Ulcerative Colitis

2021 ◽  
pp. 1-6
Author(s):  
Atsushi Yoshida ◽  
Katsuyoshi Matsuoka ◽  
Fumiaki Ueno ◽  
Toshio Morizane ◽  
Yutaka Endo ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Odds Ratio ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Study Data ◽  
Mayo Score ◽  
Tnf Α ◽  
Factor Α ◽  
First Time ◽  
Necrosis Factor

<b><i>Background:</i></b> Anti-tumor necrosis factor-α (TNF-α) agents are effective for moderately to severely active ulcerative colitis (UC). Nonetheless, a proportion of patients fail to respond to these agents as therapy for induction of remission. Recent studies indicated that perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) may predict response to anti-TNF-α agents in UC patients. However, whether PR3-ANCA can predict primary nonresponse (PNR) to anti-TNF-α agents has not yet been evaluated. The aim of this study was to examine whether PR3-ANCA can predict PNR to anti-TNF-α in UC patients. <b><i>Methods:</i></b> This was a single-center retrospective study. Data were extracted from 50 patients with UC who had measurements of PR3-ANCA and received anti-TNF-α agents for the first time as induction therapy. The primary endpoint of this study was a proportion of patients with PNR stratified by PR3-ANCA positivity. PNR to anti-TNF-α agents was defined as failure to achieve reduction in partial Mayo score by 2 or more points and change to other therapeutics within 6 weeks. <b><i>Results:</i></b> Fourteen (28%) of the 50 patients were PR3-ANCA positive. Seventeen (34%) of the 50 patients demonstrated PNR. Eleven (78.6%) of the 14 PR3-ANCA-positive patients demonstrated PNR, while 6 (16.7%) of the 36 PR3-ANCA-negative patients demonstrated PNR. Multivariate analysis demonstrated that PR3-ANCA positivity was associated with PNR to anti-TNF-α agents (odds ratio 19.29, 95% CI: 3.30–172.67; <i>p</i> = 0.002). <b><i>Conclusion:</i></b> PR3-ANCA positivity can predict PNR to anti-TNF-α agents in UC patients.

scholarly journals Combination chemotherapy consisting of irinotecan, etoposide, and carboplatin (IREC) for refractory or relapsed neuroblastoma

2020 ◽  
Author(s):  
Masayuki Imaya ◽  
Hideki Muramatsu ◽  
Atsushi Narita ◽  
Ayako Yamamori ◽  
Manabu Wakamatsu ◽  
...  
Keyword(s):  
Gene Polymorphisms ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Second Line ◽  
Free Survival ◽  
Ugt1a1 Gene ◽  
One Year ◽  
The One ◽  
The Impact ◽  
Related Mortality

Background: Patients with relapsed or refractory neuroblastoma have a poor prognosis; there are limited effective and safe rescue chemotherapies for these patients. Development of new chemotherapy regimens for these patients is a key imperative. Procedure: We retrospectively analyzed patients with refractory or relapsed neuroblastoma who received irinotecan, etoposide, and carboplatin (IREC) as a second-line treatment for neuroblastoma. We evaluated the therapeutic response, toxicity, and survival outcomes. We also assessed the impact of UGT1A1 gene polymorphisms, which are involved in irinotecan metabolism, on the outcomes and toxicity. Results: A total of 131 cycles of IREC were administered to 43 patients with a median of two cycles per patient (range, 1–10). All patients were classified as high-risk (International Neuroblastoma Risk Group). Seven patients had relapsed before IREC. One patient (2%) showed partial response and 37 patients (86%) developed stable disease (disease control rate: 88%). Grade IV neutropenia was observed in 127 cycles (97%), while ≥ grade III gastrointestinal toxicity was observed in 3 cycles (2%). There was no IREC-related mortality. The one-year overall survival and progression-free survival rates were 65% and 52%, respectively. Patients with UGT1A1 polymorphisms showed a higher frequency of grade IV neutropenia; however, there was no increase in treatment-related mortality or nonhematological toxicity in these patients. Patients with UGT1A1 gene polymorphisms showed better one-year survival rate than the wild type (80% vs. 44%, p = 0.012). Conclusions: This study suggests that IREC is well-tolerated by patients with UGT1A1 polymorphisms and is a promising second-line chemotherapy for refractory/relapsed neuroblastoma.

P627 Acute severe ulcerative colitis in pregnancy: A retrospective cohort study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S518-S519
Author(s):  
J Ollech ◽  
I Avni-Biron ◽  
S Dalal ◽  
L Glick ◽  
S Schafer ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Gestational Age ◽  
Survival Rates ◽  
Incidence Rates ◽  
Low Birth Weight Infants ◽  
Free Survival ◽  
Severe Ulcerative Colitis ◽  
Chronic Inflammatory Condition ◽  
Adverse Pregnancy ◽  
Intravenous Steroids

Abstract Background Ulcerative colitis is a chronic inflammatory condition of the colon with peak incidence rates between the ages of 15 and 35 years. Consequently, women with ulcerative colitis are often diagnosed during childbearing years, which makes the effect of the disease on pregnant patients an important clinical question. Acute severe ulcerative colitis will affect up to 25% of patients. There are limited studies that describe the medical treatment, colectomy rates, and birth outcomes of women hospitalised with acute severe ulcerative colitis during pregnancy. Methods We performed a retrospective observational study of pregnant ulcerative colitis patients hospitalised at two large tertiary medical centres between January 2003 and December 2018. The primary endpoint was colectomy-free survival. Secondary endpoints included details of disease management and fetal outcomes. Results Twenty patients met the inclusion criteria. At admission, the median age was 30.3 years (IQR 23.4–32), and the median gestational age was 21 weeks (IQR 14–28). All patients met Truelove and Witts criteria for acute severe ulcerative colitis. The median follow-up time was 48 months (IQR 20.7–80). Colectomy free survival rates from admission were 90% at six months, 84% at one year, and 64% at four years (Figure 1). Only one patient (5%) underwent colectomy at her index admission. All patients were treated with intravenous steroids, and half received anti-tumour necrosis factor agents as inpatients (7 received infliximab and 3 received adalimumab). Following discharge, seven (35%) patients were maintained on infliximab, four (20%) were maintained on adalimumab, vedolizumab and azathioprine were used as the maintenance drug in one patient each, and another seven (35%) patients were transitioned to mesalamine preparations. Live birth occurred in 18 patients (90%), and the median gestational age at birth was 37 weeks (IQR 34.5–38). Adverse pregnancy outcomes included two spontaneous abortions (10%), six premature births (30%), and four low birth weight infants (20%). There were no stillbirths, and no major congenital abnormalities were noted. Conclusion We report on the largest cohort of pregnant patients hospitalised for acute severe ulcerative colitis and have shown that these patients have good response rates to standard treatments and comparable colectomy rates to studies of non-pregnant patients. In our cohort, there were relatively high rates of preterm and low weight births.

scholarly journals P272 Tofacitinib as salvage therapy for patients hospitalized with refractory severe active ulcerative colitis: a GETAID multicenter prospective/retrospective cohort

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S305-S306
Author(s):  
M Uzzan ◽  
C Bresteau ◽  
D Laharie ◽  
C Stefanescu ◽  
F Carbonnel ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Response ◽  
Clinical Remission ◽  
Thrombotic Event ◽  
Survival Rates ◽  
Primary Objective ◽  
Multiple Drug ◽  
Biologic Treatment ◽  
Mayo Score

Abstract Background Up to 25% of patients with ulcerative colitis (UC) will require hospitalization for severe flare. In UC patients admitted who have already experienced multiple drug failures, including steroids and anti-TNF agents, new quick-acting medical options are needed. Tofacitinib is effective in refractory UC and has a rapid mechanism of action. It could be considered in this setting. We aimed to evaluate the efficacy and safety of tofacitinib in patients hospitalized for an acute UC flare. Methods We conducted an observational and multicenter study with both retrospective and prospective collections in 14 GETAID tertiary IBD centers. The primary objective was to assess the survival without colectomy following tofacitinib initiation. We determined rates of clinical response, clinical remission, and clinical steroid-free remission at week 6 and week 14 and safety. Results Fifty-eight patients were included. All but one patient with active lupus were exposed to antiTNF. 50 (86.2%) patients have received infliximab and 18 (31%) to ciclosporin. Patients were previously exposed to a median of 2.5 lines of biologic treatment before tofacitinib.Median Lichtiger at inclusion was 11.5 (interquartile range IQR[9 - 13]), median CRP was 17 mg/l (IQR[6.5 - 67]) and total Mayo score was 10 (IQR[9.3 - 11]). Deep ulcerations were observed in 10 patients (17.2%).With a median follow-up of 6.5 months (IQR [2.9-12.4]), colectomy-free survival rates were estimated at 80.1% (95CI [70.1-91.4]) at 3 months and at 75.1% (95CI[64.1-88.1]) at 6 months. Rates of clinical response, clinical remission and clinical steroid-free remission were 60.3%, 46.6% and 37.9% at week 6 an, 48.1%, 37% and 35.2% at week 14, respectively. At the end of follow-up, 29 patients (50%) were still treated with tofacitinib. The survival without tofacitinib discontinuation was estimated at 82.8% (95CI[73.6-93.1), 67.8% (95CI[56.6-81.4]) and 46.2% (95CI[34.2-62.4]) at 1, 3, and 6 months (Figure 3).Regarding safety, no death was observed, three patients withdrew tofacitinib due to adverse events. Two herpes zosters occurred in patients aged over 60 years old. No thrombotic event occurred. Conclusion Tofacitinib appears as a promising option in patients hospitalized with a severe UC flare that needs further validation in prospective and controlled trials.

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 &lt; 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 &lt; 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.

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