scholarly journals P348 Clinical outcomes and response predictors of vedolizumab treatment for anti-TNF-failed patients with IBD in Korea: A prospective multicenter cohort study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S333-S334
Author(s):  
J Kim ◽  
H Yoon ◽  
K M Lee ◽  
S A Jung ◽  
D I Park ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Response ◽  
Clinical Outcomes ◽  
Induction Therapy ◽  
Clinical Remission ◽  
Response Rates ◽  
Faecal Calprotectin ◽  
Korean Patients ◽  
Response Predictors ◽  
Endoscopic Remission

Abstract Background Vedolizumab (VDZ) inhibits gut lymphocyte trafficking by binding to α4β7 integrin, which can be effective for patients with Crohn’s disease (CD) or ulcerative colitis (UC). We aimed to investigate the clinical outcomes and response predictors of VDZ treatment for Korean patients with CD or UC, who were previously failed to anti-tumour necrosis factor (TNF) therapy. Methods Between August 2017 and November 2019, a total of 159 patients with CD (n = 81) or UC (n = 78) received a VDZ induction therapy from 16 centres and were prospectively enrolled. Of those, patients who were evaluated at week 14 after three induction doses of VDZ (week 0, 2, and 6) were analysed. The co-primary endpoints were corticosteroid-free clinical remission and endoscopic remission/response (for UC) at week 14. We also analysed predictors of corticosteroid-free clinical remission, persistence of vedolizumab and safety. Results A total of 153 patients were analysed (CD, 77 [50.3%]; male, 94 [61.4%]; median age, 40 years [range, 17–80]; median disease duration, 8.0 years [range, 0.1–38.0]). All patients had previously experienced failures to at least one anti-TNF agent (one, 105 [68.6%]; two, 44 [28.8%]; three, 4 [2.6%]). Corticosteroid-free clinical remission/response rates in CD and UC patients were 44.6%/51.8% and 39.4%/62.0%, respectively. In patients with UC, endoscopic remission and response rates defined by Mayo endoscopic subscore/ulcerative colitis endoscopic index of severity were 33.8%/14.1% and 55.4%/39.1%, respectively. Multivariate analysis revealed that a clinical response at week 6 were associated with a corticosteroid-free clinical remission at week 14 in both CD (Odds ratio [OR] 33.84, 95% confidence interval [CI] 6.25–183.31, p < 0.001) and UC (OR 12.22, 95% CI 1.30–115.28, p = 0.029). In addition, UC patients with higher baseline levels of C-reactive protein (CRP) and faecal calprotectin were less likely to be in corticosteroid-free clinical remission (CRP > 0.31 mg/dl: OR 0.05, 95% CI 0.00–0.60, p = 0.019; faecal calprotectin > 2,000 μg/g: OR 0.04, 95% CI 0.00–0.93, p = 0.045). The cumulative probabilities of continuing VDZ after one year were 48.7% for CD and 65.7% for UC, respectively. During median 10 months of follow-up periods (range, 3–26 months), disease exacerbation was the most common adverse event (n = 73, 47.7%), followed by nasopharyngitis (n = 23, 15.0%) and arthralgia (n = 19, 12.4%). Conclusion In anti-TNF-failed Korean patients with CD and UC, VDZ induction therapy was effective with an acceptable safety profile. Early clinical response and higher inflammatory burden at baseline were associated with corticosteroid-free clinical remission after VDZ induction therapy.

scholarly journals OP24 Efficacy and safety of upadacitinib induction therapy in patients with Moderately to Severely Active Ulcerative Colitis: Results from the phase 3 U-ACHIEVE study

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S022-S024
Author(s):  
S Danese ◽  
S Vermeire ◽  
W Zhou ◽  
A Pangan ◽  
J Siffledeen ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Response ◽  
Induction Therapy ◽  
Clinical Remission ◽  
Janus Kinase ◽  
Phase 3 ◽  
Mayo Score ◽  
Significant Difference ◽  
Endoscopic Remission ◽  
Secondary Endpoints

Abstract Background An unmet therapeutic need remains in patients with ulcerative colitis (UC). U-ACHIEVE is one of two phase 3 induction trials evaluating the safety and efficacy of the selective Janus kinase–1 inhibitor upadacitinib (UPA) 45 mg once daily (QD) in adults with UC. Methods U-ACHIEVE is a multicentre, double-blind, placebo (PBO)–controlled trial (NCT02819635) that randomized patients with moderately to severely active UC 2:1 to UPA 45 mg QD or PBO for 8 weeks. Patients were stratified by response to biologic therapy (inadequate vs non–inadequate responder), baseline corticosteroid use (yes or no), and baseline adapted Mayo score (≤7 or >7). The primary endpoint was proportion of patients achieving clinical remission (per adapted Mayo Score) at week 8.Ranked secondary endpoints included endoscopic improvement, endoscopic remission, and clinical response per adapted Mayo Score at week 8; clinical response per partial adapted Mayo Score at week 2; and histologic-endoscopic mucosal improvement at week 8. Non-responder imputation incorporating multiple imputations for missing data due to COVID-19 are reported. Safety was assessed through week 8. Results 474 patients were randomized (UPA, n=319; PBO, n=155). Baseline characteristics were well balanced between groups (Table 1). A significantly higher proportion of patients receiving UPA (26.1%) vs PBO (4.8%) achieved clinical remission at week 8 (adjusted treatment difference [95% CI], 21.6% [15.8, 27.4]; P<0.001; Figure 1). For all ranked secondary endpoints, UPA was superior to PBO (P<0.001; Figure 1). A significant difference in clinical response favouring UPA vs PBO was seen as early as week 2 (60.1% vs 27.3%) and was sustained over 8 weeks (79.0% vs 41.6%; Figure 2). There were more serious adverse events (AEs), severe AEs, and AEs leading to study drug discontinuation with PBO (Table 2). The most common AEs were acne, creatine phosphokinase elevation, and nasopharyngitis with UPA and worsening of UC and anaemia with PBO. Incidence of serious infection was similar between UPA and PBO. Neutropenia and lymphopenia were reported more frequently with UPA vs PBO (Table 2).No adjudicated gastrointestinal perforation, major cardiovascular AEs, or thrombotic events and no active tuberculosis, malignancy, or deaths were reported. Conclusion In patients with moderately to severely active UC, UPA 45 mg QD induction therapy was superior to PBO in inducing clinical remission/response, and endoscopic remission/response over 8 weeks; responses were significant and rapid. UPA 45 mg QD was well tolerated; safety was comparable with the known safety profile of UPA, and no new safety signals were identified.

Clinical Outcomes and Response Predictors of Vedolizumab Induction Treatment for Korean Patients With Inflammatory Bowel Diseases Who Failed Anti-TNF Therapy: A KASID Prospective Multicenter Cohort Study

2021 ◽  
Author(s):  
Jeongseok Kim ◽  
Hyuk Yoon ◽  
Nayoung Kim ◽  
Kang-Moon Lee ◽  
Sung-Ae Jung ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Clinical Response ◽  
Induction Therapy ◽  
Clinical Remission ◽  
Tumor Necrosis ◽  
Korean Patients ◽  
Endoscopic Remission ◽  
Remission Rates ◽  
Factor Therapy ◽  
Necrosis Factor

Abstract Background We investigated the real-life effectiveness and safety of vedolizumab (VDZ) induction therapy among Korean patients with Crohn disease (CD) or ulcerative colitis (UC) for whom anti-tumor necrosis factor therapy previously failed. Methods Adult patients who started VDZ induction therapy at 16 centers were prospectively enrolled in the Korean VDZ nationwide registry. The coprimary outcomes were clinical remission, defined as a Crohn’s Disease Activity Index score <150 points and a partial Mayo score ≤2 points with a combined rectal bleeding and stool frequency subscore ≤1 point at week 14 and endoscopic remission defined as a Mayo endoscopic subscore ≤1 point. We also analyzed predictors of clinical remission. Results Between August 2017 and November 2019, a total of 158 patients (80 with CD and 78 with UC) received VDZ induction therapy. Clinical remission rates among patients with CD and patients with UC were 44.1% and 44.0%, respectively. Among patients with UC, the endoscopic remission rate was 32.4%. Clinical response and remission rates showed increasing trends during induction therapy. Multivariable analysis revealed that clinical response at week 6 was the only predictor of clinical remission at week 14 for both patients with CD and patients with UC. Among patients who experienced 1 or more adverse events (n = 71; 44.9%), disease exacerbation (n = 28; 17.7%) was the most common adverse event. Conclusions Among Korean patients with CD or UC for whom anti-tumor necrosis factor therapy failed, VDZ induction therapy was effective and safe. The early clinical response was associated with clinical remission after VDZ induction therapy.

scholarly journals A15 EFFICACY AND SAFETY OF FILGOTINIB AS INDUCTION THERAPY FOR PATIENTS WITH MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS: RESULTS FROM THE PHASE 2B/3 SELECTION STUDY

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 18-20
Author(s):  
B G Feagan ◽  
E V Loftus ◽  
S Danese ◽  
S Vermeire ◽  
W J Sandborn ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Induction Therapy ◽  
Clinical Remission ◽  
Active Ulcerative Colitis ◽  
Treatment Groups ◽  
Disease Characteristics ◽  
Serious Infections ◽  
Endoscopic Remission ◽  
Induction Study ◽  
Secondary Endpoints

Abstract Aims The SELECTION (NCT02914522) Induction Studies evaluated the efficacy/safety of filgotinib (FIL), a preferential JAK1 inhibitor, as induction therapy for patients (pts) with moderately to severely active ulcerative colitis (UC) who were biologic-naïve but failed conventional therapy (Induction Study A) or failed prior biologics (Induction Study B). Methods Pts were randomized 2:2:1 to once–daily FIL 200mg, FIL 100mg or placebo (PBO). The primary (clinical remission), key secondary (Mayo Clinic Score [MCS] remission, endoscopic remission, and histologic remission), and exploratory endpoints (MCS response and endoscopic improvement) were assessed at Week 10. Results In both studies, baseline demographics and disease characteristics were similar across treatment groups. In Study A, 659 pts were randomized and treated. Baseline mean MCS was 8.6 and 56% had a Mayo endoscopic subscore (ES)=3. A significantly higher proportion of biologic-naïve pts on FIL 200mg achieved clinical remission vs PBO and all key secondary endpoints (Table). In Study B, 689 pts were randomized and treated. Baseline mean MCS was 9.3 and 78% had ES=3. Prior treatment failures were: anti-TNF (86%), vedolizumab (52%) and both (dual-refractory; 43%). A significantly higher proportion of biologic-experienced pts on FIL 200mg achieved clinical remission vs PBO. In Studies A and B, a greater proportion of pts on FIL 200 mg achieved an MCS response and endoscopic improvement vs PBO. The rates of AEs, serious AEs and discontinuations due to AEs were similar across FIL and PBO groups during induction. In the PBO, FIL 100mg and FIL 200mg groups, serious infections occurred in 0.7%, 0.7% and 0.4% pts in Study A and 1.4%, 1.4% and 0.8% pts in Study B; H Zoster occurred in <1% in both groups for both cohorts. Conclusions SELECTION included a high proportion of dual-refractory pts, and pts with severe endoscopic disease. Both doses of FIL were well tolerated. Filgotinib 200mg was effective induction therapy for both biologic-naïve/-experienced pts with moderately to severely active UC. Funding Agencies None

scholarly journals P471 What is the appropriate cut-off value of CRP to predict endoscopic remission in ulcerative colitis patients with clinical remission?

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S415-S415
Author(s):  
J Shin ◽  
G Seong ◽  
J H Song ◽  
S M Kong ◽  
T J Kim ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Sensitivity And Specificity ◽  
Clinical Remission ◽  
Activity Index ◽  
Area Under The Curve ◽  
Endoscopic Evaluation ◽  
Faecal Calprotectin ◽  
Reactive Protein ◽  
Endoscopic Remission ◽  
Low Sensitivity

Abstract Background A noninvasive and reliable markers for predicting endoscopic remission (ER) in ulcerative colitis (UC) patients with clinical remission (CR) provide important information in predicting disease progression and in determining treatment. Faecal calprotectin test is known to be the most accurate to predict ER, but patients are reluctant to handle faecal materials. C-reactive protein (CRP) is one of the surrogate markers for assessing disease activity, but it is known to have low sensitivity and specificity of normal CRP value (<0.3 mg/dl). The sensitivity of the CRP test has been improved, and even fine values within the normal range can be measured. The aim of this study was to determine appropriate CRP cut-off values for the prediction of ER in UC patients with CR even though within normal CRP range. Methods A total of 132 UC patients who underwent endoscopic evaluation in CR were retrospectively reviewed. Serum biomarkers including haemoglobin, leukocytes, platelets, erythrocyte sedimentation rate, and CRP were evaluated within 1 week period from endoscopic evaluation. The clinical and endoscopic activity was measured by simple clinical colitis activity index and endoscopic Mayo subscore. Results In UC patient with CR, CRP level was significantly lower in ER (median 0.05, 0.03–2.57) vs. non-ER (median 0.11 0.03-2.81). (p < 0.005) The proportion of males in non-ER was slightly higher than in ER (24, 72.7% vs. 52, 52.5 %; p = 0.042), and only gender and CRP showed statistical differences in baseline clinical characteristics. CRP had predictive value of ER [Area under the curve (AUC = 0.760)] and the sensitivity was 71.4%, specificity was 71.7 % at cut-off value of 0.09mg/dl. In contrast, the sensitivity and specificity of normal CRP (0.3mg/dl) were low. (sensitivity 27.3%, specificity 90.9%). Conclusion Norma CRP cut-off values are not sufficient to reflect ER. It may be helpful to change the CRP cut-off value that predicts ER in CR to value other than 0.3 mg/dl.

scholarly journals P682 Faecal calprotectin and C-reactive protein levels are associated with long-term clinical and endoscopic outcomes: Analysis of the OASIS open-label extension trial of etrasimod for ulcerative colitis

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S555-S556
Author(s):  
A Yarur ◽  
M Chiorean ◽  
J Zhang ◽  
W Reinisch ◽  
S Vermeire ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Disease Activity ◽  
Clinical Response ◽  
Clinical Remission ◽  
C Reactive Protein ◽  
Open Label ◽  
Faecal Calprotectin ◽  
Reactive Protein ◽  
Open Label Extension

Abstract Background Reliable biomarkers of ulcerative colitis (UC) disease activity may be useful in clinical trials and practice. Etrasimod is an oral, selective, sphingosine 1-phosphate receptor modulator with efficacy in a 12-week, phase 2, double-blind (DB), randomised, controlled trial in adult patients with moderately-to-severely active UC (OASIS; NCT02447302). Patients who completed the DB study were eligible to enrol in an open-label extension (OLE; NCT02536404) and receive etrasimod 2 mg once daily for up to an additional 34 weeks. The aim of this post-hoc analysis was to assess the correlation of sequential faecal calprotectin (FC) and C-reactive protein (CRP) levels throughout the DB study and OLE with clinical and endoscopic outcomes at end of treatment (EOT) in the OLE. Methods In the DB study, patients received etrasimod 1 mg, etrasimod 2 mg or placebo. The OLE evaluable cohort comprised patients who received etrasimod 2 mg throughout the OLE. The modified intention-to-treat (mITT) population comprised patients with non-missing assessments. EOT was the last observation for each patient, occurring at week 46 (OLE week 34) for study completers or at last visit for patients who discontinued or had missing data. Endpoints were modified Mayo Clinic score (mMCS; range 0–9; including endoscopy, rectal bleeding [RB], and stool frequency [SF]); clinical remission (endoscopic subscore ≤1 [with absence of friability], RB ≤1, and SF score ≤1 with ≥1 point decrease from DB baseline); clinical response (clinical remission or decrease in mMCS of ≥2 points and ≥30% decrease from DB baseline, with either a RB decrease of ≥1 or RB score of ≤1); and endoscopic improvement (subscore ≤1). FC and CRP were measured longitudinally to EOT. Comparisons between subgroups were assessed with a Wilcoxon rank-sum test (2-sided P values). Analysis of correlation between variables was conducted using the Spearman’s rank coefficient. Results The evaluable cohort included 105 patients, 31 of whom received etrasimod 2 mg throughout both DB and OLE periods. At EOT 70%, 35% and 45% of patients in the mITT evaluable cohort had clinical response, clinical remission and endoscopic improvement, respectively. Differences in FC and CRP levels between patients with and without clinical remission at EOT are shown in Figures 1 and 2, respectively for patients who received etrasimod 2 mg throughout both the DB and OLE periods. Correlation analyses of FC and CRP with clinical (mMCS) and endoscopic disease activity and with each other are shown in Table 1. Conclusion FC and CRP appear to correlate with clinical and endoscopic outcomes over long-term treatment with etrasimod. Additional validation is needed to determine their utility in treat-to-target management strategies.

scholarly journals P510 Dose escalation of subcutaneous vedolizumab in patients with ulcerative colitis: A post hoc analysis of the VISIBLE trial data

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S442-S443
Author(s):  
W Sandborn ◽  
D Wolf ◽  
G D’haens ◽  
J Jansson ◽  
J Chen ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Treatment Failure ◽  
Clinical Response ◽  
Dose Escalation ◽  
Clinical Remission ◽  
Severe Disease ◽  
Response Rates ◽  
Response To Treatment ◽  
Dosing Regimen ◽  
Open Label

Abstract Background Vedolizumab (VDZ), a gut-selective, α 4β7 integrin monoclonal antibody, is approved for intravenous (IV) administration to patients with moderate-severe ulcerative colitis (UC). Subcutaneous (SC) VDZ was evaluated for maintenance therapy for UC in VISIBLE 1, a double-blind, placebo-controlled, Phase 3 study, and its open-label extension (OLE). We evaluated the efficacy of increasing dose frequency of VDZ SC from every-2-weeks (Q2W) to weekly administration (QW) after treatment failure (disease worsening or need for rescue medication). Methods In VISIBLE 1 (NCT02611830; EudraCT 2015-000480-14), a Q2W dosing regimen was used for patients with UC who achieved clinical response at week 6 (after open-label IV VDZ inductions at weeks 0 and 2) and were randomised to maintenance treatment with VDZ SC. Patients who did not respond at week 6 but responded by week 14 rolled over to the VISIBLE OLE (NCT02620046; EudraCT: 2015-000482-31) and received Q2W VDZ SC dosing. In VISIBLE 1 and the OLE, 2 groups of patients experienced dose escalation: (1) patients who entered the VISIBLE OLE study on a Q2W VDZ dosing regimen but experienced disease worsening and were escalated to QW dosing (OLE Q2W/QW); and (2) patients who experienced treatment failure during Q2W VDZ treatment in VISIBLE 1, rolled over to OLE, and were escalated to a QW dosing regimen (VISIBLE 1 treatment failure). Efficacy was evaluated by clinical remission and response rates after dose escalation using partial Mayo scores at the visits in the Visible OLE study. In this interim analysis, not all patients continuing in the trial had not completed all study visits. Only patients who had completed a given visit (evaluable patients) were included in the analyses for that visit. Results Of the 54 patients who received dose escalation 52% were male. Mean age was 39 years, mean UC duration was 7.4 years; 76% had severe disease activity (Mayo 9–12) at baseline, and 43% had prior anti-TNF therapy failure (Table 1). Of the patients with dose escalation, 27.1% (13/48 evaluable patients) recaptured clinical remission 16 weeks after dose escalation and 10.8% (4/37 evaluable patients) were in clinical remission after 48 weeks (Table 2). A similar trend was observed for clinical response rates in this patient population. Conclusion Increasing the frequency of VDZ SC dosing to QW recaptured lost response to treatment for some patients. These are interim results of the OLE study; further follow-up during the ongoing OLE will provide more insight into the long-term efficacy and safety of dose escalation with VDZ SC.

scholarly journals DOP01 Efficacy and safety of the IL-6 trans-signalling inhibitor olamkicept: a phase 2 randomized, placebo-controlled trial in moderately to severely active Ulcerative Colitis

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S041-S042
Author(s):  
B Chen ◽  
S Zhang ◽  
B Wang ◽  
H Chen ◽  
Y Li ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Adverse Events ◽  
Clinical Response ◽  
Induction Therapy ◽  
Clinical Remission ◽  
Mucosal Healing ◽  
Active Ulcerative Colitis ◽  
Phase 2 ◽  
Efficacy And Safety ◽  
Mayo Score

Abstract Background Total inhibition of IL-6 or its receptor represents a potent anti-inflammatory therapy with considerable side effects. Selective targeting IL-6 trans-signalling may have safety advantages that differentiates it from current pan-IL-6 inhibitors. We evaluated the efficacy and safety of olamkicept, a soluble gp130-Fc fusion protein that binds to the IL-6 and soluble IL-6 receptor complex, as induction therapy for active ulcerative colitis (UC). Methods This multi-national, randomized, double-blind, placebo-controlled phase 2 trial (NCT03235752) enrolled patients with active UC (full Mayo score ≥5, rectal bleeding (RB) score ≥1, endoscopy score (ES) ≥2) with an inadequate response to at least conventional therapy, in a 1:1:1 ratio to receive either placebo, olamkicept 300 mg or 600 mg biweekly for 12 weeks. Primary efficacy endpoint was clinical response (decrease in Mayo score from baseline ≥3 and ≥30%, including RB ≤1 or RB decrease ≥1) at week 12. Secondary endpoints were mucosal healing (ES 0 or 1) and clinical remission (Mayo score ≤2, with no subscore >1 and RB=0). The efficacy endpoints were analysed by logistic regression. All p-values were 2-sided without adjustment for multiplicity. Results Of 91 treated patients (30 in placebo, 31 in olamkicept 300 mg group and 30 in 600 mg group), 88 patients (29:30:29) were evaluable for efficacy. Baseline disease and demographic characteristics were similar among the groups (Table 1). Most patients (94.5%) were bio-naïve. The percentage of patients achieving clinical response at week 12 was significantly greater for olamkicept 600 mg than placebo (58.6% vs 34.5%, P=0.032). Clinical remission at week 12 occurred in 0% (placebo), 6.7% (olamkicept 300 mg) and 20.7% (olamkicept 600 mg, P<0.001) of patients. Mucosal healing at week 12 occurred in 3.4%, 10% and 34.5% (P<0.001) of patients, respectively (Figure 1). Incidence of treatment emergent adverse events (TEAEs) was similar across the groups. The most common TEAEs included upper respiratory tract infection, increased AST levels, and increased urine bilirubin levels, which were mild to moderate and mostly transient. Serious adverse events (SAEs) were reported in 6.7%, 3.2% and 3.3% of patients, respectively. There were no deaths, or other severe AEs associated with current IL-6 inhibitors, such as perforations, severe infections, neutropenia or thrombocytopenia. Conclusion Biweekly 600 mg olamkicept induction therapy demonstrated clinical efficacy with respect to achieving clinical response, clinical remission and mucosal healing in patients with active UC. Olamkicept was well tolerated with a favourable safety profile. The positive results of this phase 2 study support further development of olamkicept in IBD.

scholarly journals P308 Effectiveness and Safety of tofacitinib for the Treatment of Ulcerative Colitis: A Single-Arm Meta-analysis of Observational Studies

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S336-S336
Author(s):  
F S Macaluso ◽  
M Maida ◽  
M Ventimiglia ◽  
A Orlando
Keyword(s):  
Ulcerative Colitis ◽  
Adverse Events ◽  
Clinical Response ◽  
Incidence Rate ◽  
Real World ◽  
Clinical Remission ◽  
Observational Studies ◽  
Meta Analysis ◽  
Endoscopic Remission ◽  
Almost All

Abstract Background Several observational studies on Tofacitinib (TOFA) for the treatment of ulcerative colitis (UC) have been published over the last 2 years. The aim of this single-arm meta-analysis was to estimate the effectiveness and safety of TOFA arising from real-world observational studies. Methods PubMed Central/Medline and Embase, as well as reference lists of articles, were systematically searched for real-world observational studies of TOFA for the treatment of UC through November 2020. Results Seven studies comprising 759 patients met the inclusion criteria. Almost all patients (range: 76.5-100%) had been previously exposed to anti-TNFs, and a variable proportion (range: 38.8-100%) had been previously treated with Vedolizumab The pooled estimate rates were 49% for clinical response, 40% for clinical remission, and 34% for corticosteroid-free clinical remission at induction, while the rates of endoscopic response and endoscopic remission were 37% and 19%, respectively. At maintenance, the pooled estimate rates of clinical response, clinical remission, and corticosteroid-free clinical remission were 36%, 35%, and 24%, respectively. The pooled estimate of incidence rate of total adverse events was 53.0 per 100 person-years (PY), while the pooled estimate of incidence rate of withdrawal of TOFA due to adverse events was 9.3 per 100 PY, with a pooled rate of infections of 17.6 per 100 PY. Conclusion Cumulative analysis of data from real-world studies confirmed the good efficacy of TOFA in UC shown by randomized controlled trials for both induction and maintenance, while the safety profile was consistent with previous reports.

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 OP34 AJM300, an Oral Antagonist of α4-Integrin, as induction therapy for patients with Moderately Active Ulcerative Colitis: A Phase 3, randomized, double-blind, placebo-controlled induction study

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S031-S032
Author(s):  
M Watanabe ◽  
K Matsuoka ◽  
T Ohmori ◽  
K Nakajima ◽  
T Ishida ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Response ◽  
Induction Therapy ◽  
Primary Endpoint ◽  
Similar Response ◽  
Inadequate Response ◽  
Active Ulcerative Colitis ◽  
Phase 3 ◽  
Endoscopic Remission ◽  
To Receive

Abstract Background AJM300 (INN; carotegrast methyl), an orally active small molecule antagonist of the α4 subunit of α4β1/α4β7 integrins, demonstrated the efficacy and safety in patients with moderately active ulcerative colitis (UC) in a phase 2 study. The phase 3 study (NCT 03531892) of AJM300 as induction therapy was conducted in patients with moderately active UC. Methods Eligible patients were moderately active Japanese UC, defined as total Mayo Clinic scores (MCS) of 6–10, endoscopic subscores (ES) ≥2, and rectal bleeding subscores (RBS) ≥1, who had inadequate response or intolerance to oral 5-ASA. Followed by a 2-week single-blind placebo (PBO) run-in phase, patients were randomized 1:1 to receive AJM300 960 mg or PBO 3 times daily for 8 weeks. Responders or remitters were allowed to receive AJM300 960 mg again at the subsequent relapse (open-label). The primary endpoint was clinical response at week 8, defined as reduction of the MCS of ≥3-pts and ≥30%, reduction in RBS of ≥1-pt or RBS of ≤1, and ES ≤1. Results The randomized 203 patients had moderately active endoscopic evidence at baseline with median UC duration of 6.1 years and MCS of 7.8. For the primary endpoint, 45.1% (46/102) and 20.8% (21/101) of patients in the AJM300 and PBO groups, respectively, achieved clinical response at week 8 (OR=3.30 [95% CI, 1.73–6.29]; p=0.0003). Symptomatic remission, endoscopic improvement and endoscopic remission were also statistically significant for AJM300 vs PBO (Table). In case of episodic AJM300 treatment, AJM300 exhibited similar response to initial treatment. Overall, the incidence of AEs and serious AEs were similar between AJM300 and PBO. There were no deaths or cases of progressive multifocal leukoencephalopathy. Conclusion AJM300 induced clinical response as well as endoscopic remission with good tolerability. AJM300 may become a novel therapeutic option for patients who had inadequate response or intolerance to oral 5-ASA.

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