The real-world outcomes of vedolizumab in patients with ulcerative colitis in Korea: a multicenter retrospective study

Aim: This study examined the real-world effectiveness and safety outcomes of vedolizumab in ulcerative colitis (UC) patients who had failed anti-tumor necrosis factor (anti-TNF) therapy in Korea. Methods: A retrospective chart review study was conducted in adults with moderate to severely active UC who had failed anti-TNF agents and subsequently received vedolizumab. Clinical response and clinical remission at week 6 and 14 after vedolizumab initiation was evaluated. Safety outcomes were also reported. Outcome rates were compared with a matched sub-cohort derived from the open-label sub-cohort of the GEMINI 1 trial using the optimal matching method. Results: A total of 105 patients (mean age, 45.3 years; 63.8% male) were included. At week 6, 55.8% ( n = 43/77) achieved a clinical response and 18.2% ( n = 14/77) achieved clinical remission. At week 14, 73.2% ( n = 52/71) achieved a clinical response and 39.4% ( n = 28/71) achieved clinical remission. When non-response imputation was used, the clinical response rate at week 6 and week 14 were 40.1% ( n = 43/105) and 49.5% ( n = 52/105) respectively. Of the 105 patients, 16 (15.2%) experienced at least one adverse event. The matched analysis showed that the clinical response rate at week 6 was higher in the matched sub-cohort of this study (24/47, 51.1%) versus the matched sub-cohort from the GEMINI 1 open-label cohort (12/47, 34.3%, p = 0.019). The clinical remission rates at week 6 were similar (7/47, 14.9% versus 9/47, 19.1%, p = 0.785). Conclusions: In the real-world setting, vedolizumab is effective and well tolerated within the first 14 weeks of use in Korea. The proportion of patients experiencing clinical response and clinical remission at 6 and 14 weeks appeared to be largely consistent with that observed in real-world studies from other regions and populations.

Download Full-text

P419 Clinical effectiveness and safety of first-line biologic vedolizumab as a monotherapy or combination therapy in ulcerative colitis and Crohn’s disease patients: results from the EVOLVE study

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.548 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S381-S382

Author(s):

B Bressler ◽

A Yarur ◽

U Kopylov ◽

M Bassel ◽

N Brett ◽

...

Keyword(s):

Ulcerative Colitis ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Clinical Response ◽

Real World ◽

Clinical Remission ◽

Clinical Effectiveness ◽

First Line ◽

Safety Outcomes

Abstract Background There is little long-term research (≥12 months) in ulcerative colitis (UC) and Crohn’s disease (CD) patients investigating the impact on clinical effectiveness of combined (combo) therapy of vedolizumab (VDZ) plus immunomodulators/immunosuppressants (IMMs) compared with VDZ monotherapy. Research suggests the use of concomitant aminosalicylates [5-ASAs] in UC may not bolster effectiveness. Finally, it is unclear if the safety profile differs between VDZ monotherapy and combo therapy. This study described clinical effectiveness and safety outcomes in patients with UC or CD treated with first-line biologic VDZ as monotherapy or combo therapy with IMMs or 5-ASAs (UC only). Methods This was a real-world, multi-country (Canada, Greece and the USA), retrospective chart review study of biologic-naïve UC and CD patients (≥18 years old) treated with VDZ (initiated Tx May 2014–March 2018). Data were collected from Tx initiation to the earliest of death and chart abstraction date. Cumulative rates of clinical effectiveness outcomes over 24 months (Tx persistence, clinical response and clinical remission) were estimated using the Kaplan-Meier method with unadjusted comparisons conducted using the log-rank test. Clinical response and remission were assessed from standard disease measures reported in medical records. Analyses of unadjusted incidence rates (per 100 person-years [PYs]) of disease exacerbations, disease-related surgeries, serious adverse events (SAEs) and serious infections (SIs) were performed. For these analyses in monotherapy vs. VDZ+IMMs, UC and CD patients were combined due to restrictions of sample size and a number of events. Results This analysis included 318 patients treated with VDZ (monotherapy: UC = 53, CD = 108; VDZ+IMMs: UC = 22, CD = 24; VDZ+5-ASAs: UC = 111). There were no observed differences in age, sex or disease duration between patients on monotherapy vs. VDZ+IMMs or vs. VDZ+5-ASAs. Data trends in effectiveness outcomes were similar in monotherapy vs. VDZ+IMMs over 24 months (Figure 1). Tx persistence (monotherapy: 71.6%; VDZ+5-ASAs: 82.7%; p = 0.40), clinical remission (monotherapy: 54.3%; VDZ+5-ASAs: 87.7%; p = 0.37) and clinical response (monotherapy: 81.7%; VDZ+5-ASAs: 92.2%; p = 0.54) were also similar between monotherapy and VDZ+5-ASAs over 24 months. Safety outcomes were similar between groups (Figure 2). Conclusion Though sample sizes were small, the unadjusted trends in the results of this long-term real-world study suggest that biologic-naïve UC or CD patients treated with VDZ alone may have similar clinical effectiveness outcomes to patients receiving VDZ+IMMs. Trends in data also suggest that in patients with UC, VDZ+5-ASAs may not be more effective than VDZ alone.

Download Full-text

A phase II open label, single arm study to evaluate the efficacy of pembrolizumab for leukoplakia.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.tps10606 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. TPS10606-TPS10606

Author(s):

Ashleigh Porter ◽

Audrey J. Zeh ◽

Thu Ly ◽

Alyssa Serna ◽

Arturo Villanueva ◽

...

Keyword(s):

Clinical Response ◽

Phase Ii ◽

Response Rate ◽

Two Dimensions ◽

Premalignant Lesions ◽

Clinical Response Rate ◽

Clinical Impression ◽

Severe Dysplasia ◽

Open Label ◽

Recurrence Rates

TPS10606 Background: The presence of pre-cancerous oral lesions such as leukoplakia or erythroleukoplakia are known risk factors for the development of squamous cell carcinoma of the head and neck (SCCHN), however preventative agents have not yet shown clinical benefit. The risk of malignant transformation varies but has been quoted as high as 36% in some studies. While the primary mode of treatment of these lesions is largely surgical, recurrence rates are high. Pembrolizumab is a potent and selective humanized monoclonal antibody that is designed to directly block the interaction between PD-1 and PD-L1 (as well as PD-L2) that is currently FDA-approved for treatment of SCCHN. We have hypothesized that the treatment of oral premalignant lesions with pembrolizumab would be an effective and well-tolerated strategy to prevent transformation to invasive cancer. Methods: This study is an open-label, phase II study that will accrue 26 patients with leukoplakia, erythroleukoplakia, or proliferative verrucous leukoplakia with documented moderate to severe dysplasia or carcinoma in situ to be treated with pembrolizumab 200mg every 3 weeks for a total of 6 months. Patients must have visible and measurable lesions that will be both photographed and measured in two dimensions at each visit from the start of treatment until 12 months post-enrollment. Biopsies will be required at diagnosis and following the final treatment, with an optional biopsy following cycle 2 and at progression of disease. Major exclusion criteria include patients with mild dysplasia or hyperplasia, prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks of Day 1 of study, or patients with a known additional malignancy that is active. Patients will also be excluded if they have received anti-PD-1, anti-PD-L1 or anti-PD-L2 treatments in the past. The primary objective is clinical response rate at 6 months, and will be quantified as the percentage of patients with a complete response (CR) and partial response (PR) at 6 months. A CR is defined as complete resolution by visual inspection for 4 weeks of more and a PR is defined as 50% or greater reduction of the product of the 2 dimensions of a single lesions or the sum of all lesions. Progressive disease (PD) is defined as unequivocal increase (greater than or equal to 5mm in one dimension and greater than 20% increase) or the development of new lesions. Secondary objectives will include histologic response rate at 6 months, change in clinical impression based on photographs, clinical response rate at 9 and 12 months, and toxicity. Additional exploratory objectives will include PD-L1 expression in leukoplakia lesions as well as p16 expression, presence of tumor infiltrating lymphocytes, and immunohistochemical as well as RNA sequencing gene expression profiling which may allow for the identification of novel biomarkers. Enrollment began in June 2019 and is ongoing. Clinical trial information: NCT03603223 .

Download Full-text

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

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.810 ◽

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.

Download Full-text

DOP55 A real-world comparison of the effectiveness and safety of vedolizumab and anti-TNF therapies in early treatment initiation with first-line biologic therapy in ulcerative colitis: Results from EVOLVE

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.094 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S092-S094

Author(s):

G Mantzaris ◽

B Bressler ◽

U Kopylov ◽

M Bassel ◽

N Brett ◽

...

Keyword(s):

Ulcerative Colitis ◽

Clinical Response ◽

Real World ◽

Early Treatment ◽

Clinical Remission ◽

Treatment Initiation ◽

Clinical Effectiveness ◽

Mucosal Healing ◽

First Line

Abstract Background Evidence suggests that early treatment (Tx) with biologic agents in Crohn’s disease improves long-term clinical outcomes. However, there is less evidence in ulcerative colitis (UC), and data comparing early Tx with first-line biologic vedolizumab (VDZ) to anti-tumour necrosis factor (anti-TNF) in real-world settings is needed. This study compared the clinical effectiveness and safety of UC patients who initiated VDZ or an anti-TNF as a first-line biologic within 2 years following diagnosis. Methods This was a real-world, multi-country, retrospective chart review study in Canada, Greece and the United States where biologic-naïve UC patients (≥18 years old) were treated with VDZ or an anti-TNF (adalimumab, infliximab, golimumab) agent within 2 years following diagnosis (initiated Tx May 2014–March 2018). Clinical effectiveness and safety data were collected from Tx initiation to earliest of chart abstraction date, death, or 6 months post-Tx discontinuation (Canada only). Tx persistence was defined as the duration of time from treatment initiation to discontinuation. Analyses of cumulative rates of Tx persistence, clinical response, clinical remission and mucosal healing over 24 months were estimated using Kaplan–Meier analyses. Clinical response, remission and mucosal healing were assessed using pre-defined hierarchical algorithms of standard disease measures reported in the medical records. Analyses of incidence rates (per 100 person-years [PYs]) of disease exacerbations, disease-related surgeries, serious adverse events (SAEs) and serious infections (SIs) were performed. Adjusted analyses used inverse probability weighting to balance cohorts. Results This analysis included 176 UC patients (VDZ: 86; anti-TNF: 90) from 37 sites. Mean (SD) age at index date: VDZ, 41.4 (18.9); anti-TNF, 36.8 (15.6) years (p = 0.20) and the proportion male: VDZ, 58.1%; anti-TNF, 56.7% (p = 0.84). At 12 months, 72.9% and 58.1% continued VDZ and anti-TNF respectively (p = 0.03) (Figure 1A). Though there were no differences in clinical response, clinical remission or mucosal healing between VDZ and anti-TNF groups; VDZ patients were significantly less likely to experience disease exacerbations (HR = 0.47 [95% CI: 0.32–0.69]) and SAEs (HR = 0.37 [95% CI: 0.19–0.72]) (Figure 2). Adjusted outcomes (Figures 1C and D, and 2B) were similar to unadjusted outcomes. Conclusion EVOLVE is one of the first studies that compared early VDZ Tx to early anti-TNF Tx in biologic-naïve UC patients. Results showed VDZ was associated with higher persistence, lower likelihood of experiencing disease exacerbations and a more favourable safety profile. Thus, in early UC, Tx with VDZ may improve long-term clinical outcomes. Sample size limitations warrant further study.

Download Full-text

Mucosal Biomarker of Innate Immune Activation Predicts Response to Vedolizumab in Crohn’s Disease

Inflammatory Bowel Diseases ◽

10.1093/ibd/izz222 ◽

2019 ◽

Cited By ~ 1

Author(s):

Mark T Osterman ◽

Ilyssa O Gordon ◽

Elisabeth M Davis ◽

Matthew Ciorba ◽

Sarah C Glover ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Clinical Response ◽

Immune Activation ◽

Clinical Remission ◽

Response Rate ◽

Intestinal Inflammation ◽

Innate Immune ◽

Clinical Response Rate ◽

Innate Immune Activation

Abstract Objective Mucosal barrier dysfunction plays a crucial role in intestinal inflammation in Crohn’s disease (CD). Intestinal epithelial cell (IEC) death resulting from innate immune activation, termed pyroptosis, was recently found to be a cause of this barrier defect. The aim of this study was to determine the predictive value of pretreatment ileal biopsy pyroptosis as a biomarker for clinical response to vedolizumab in CD. Design Crohn’s disease patients ranging 18 to 80 years old from 5 IBD centers with pre-vedolizumab ileal biopsies during colonoscopy were enrolled. Biopsies were stained for activated caspases, and levels of ileal IEC pyroptosis levels were quantified. The primary outcome was clinical response 6 months after therapy, defined as a reduction of Harvey-Bradshaw Index (HBI) of ≥5 points from baseline. Secondary outcomes included clinical remission, defined as HBI <5, and endoscopic improvement, as measured by the Simple Endoscopic Score for Crohn’s Disease (SES-CD). Results One hundred CD patients (45 male, 55 female), median age 47 (19, 78) years, were included; clinical response rate was 60%, and clinical remission was 36%. The response rate in patients with ileal pyroptosis <14 positive cells per 1000 IECs was significantly higher than those above the threshold: 89% (25 of 28) vs 49% (35 of 72), odds ratio (OR) 8.8 (95% CI, 2.3–48.6; P < 0.001). Corresponding remission rates were 54% (15 of 28) vs 29% (21 of 72; OR 2.8 [1.03–7.59; P = 0.036]). For endoscopic improvement, ileal pyroptosis of 22 positive cells per 1000 IECs was the optimal threshold that determines the magnitude SES-CD change. Conclusions Ileal biopsy IEC pyroptosis was predictive of clinical response and endoscopic improvement to vedolizmab in CD patients.

Download Full-text

Tofacitinib in Treatment-Refractory Moderate to Severe Ulcerative Colitis: Real-World Experience from a Retrospective Multicenter Observational Study

Journal of Clinical Medicine ◽

10.3390/jcm9072177 ◽

2020 ◽

Vol 9 (7) ◽

pp. 2177

Author(s):

Peter Hoffmann ◽

Anna-Maria Globig ◽

Anne K. Thomann ◽

Maximilian Grigorian ◽

Johannes Krisam ◽

...

Keyword(s):

Ulcerative Colitis ◽

Adverse Events ◽

Clinical Response ◽

Real World ◽

Clinical Remission ◽

Safety Data ◽

Colon Perforation ◽

Severe Ulcerative Colitis ◽

Emergency Colectomy

(1) Background: Tofacitinib is approved in Europe for the treatment of adults with moderately to severely active ulcerative colitis since 2018. Real-world efficacy and safety data are currently scarce. (2) Methods: We performed a retrospective multicenter study at three German tertiary outpatient clinics for inflammatory bowel diseases and included all patients who started tofacitinib therapy between August 2018 and March 2020. The primary endpoint was a combined endpoint of steroid-free clinical remission, steroid-free clinical response, or clinical response at week 8. Secondary endpoints were biochemical response at week 8, as well as steroid-free clinical remission, steroid-free clinical response or clinical response at week 24, respectively, adverse events by week 24, and need for colectomy by the end of follow-up. (3) Results: Thirty-eight patients with moderate-to-severe ulcerative colitis were included. Eleven patients (28.9%) achieved steroid-free clinical remission at week 8. Fifty-three percent of the patients were primary non-responders at week 8. Three severe adverse events (pneumonia, hospitalization for aggravation of ulcerative colitis, emergency colectomy due to colon perforation), and 12 adverse events were documented by week 8 of therapy. By the end of follow-up, seven patients (18.4%) had undergone colectomy.

Download Full-text

Real-world effectiveness of vedolizumab in inflammatory bowel disease: week 52 results from the Swedish prospective multicentre SVEAH study

Therapeutic Advances in Gastroenterology ◽

10.1177/17562848211023386 ◽

2021 ◽

Vol 14 ◽

pp. 175628482110233

Author(s):

Carl Eriksson ◽

Sara Rundquist ◽

Vyron Lykiardopoulos ◽

Ruzan Udumyan ◽

Per Karlén ◽

...

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Clinical Response ◽

Real World ◽

Bowel Disease ◽

Clinical Remission ◽

Real World Data ◽

Inflammatory Bowel

Background: Prospectively and systematically collected real-world data on vedolizumab are scarce. We aimed to assess the long-term clinical effectiveness of vedolizumab in inflammatory bowel disease (IBD). Methods: This study was a prospective, observational, multicentre study. Overall, 286 patients with active IBD were included (Crohn’s disease, n = 169; ulcerative colitis, n = 117). The primary outcomes were clinical response at week 12 and clinical remission at week 52, based on the Harvey Bradshaw Index and the partial Mayo Clinic score. Secondary outcomes included clinical remission at week 12, clinical response at week 52, corticosteroid-free clinical remission at week 52, changes in biochemical measures, and health-related quality of life (HRQoL). Results: At baseline, 88% of the patients were exposed to anti-TNF and 41% of the patients with Crohn’s disease had undergone ⩾1 surgical resection. At week 12, clinical response was 27% and remission 47% in Crohn’s disease; corresponding figures in ulcerative colitis were 52% and 34%. Clinical response, remission and corticosteroid-free remission at week 52 were 22%, 41% and 40% in Crohn’s disease and 49%, 47% and 46% in ulcerative colitis, respectively. A statistically significant decrease in median faecal-calprotectin and C-reactive protein was observed at 12 and 52 weeks in patients with Crohn’s disease and ulcerative colitis. The HRQoL measures Short Health Scale and EuroQol 5-Dimensions improved in both Crohn’s disease and ulcerative colitis patients ( p < 0.001). Clinical disease activity at baseline was inversely associated with clinical remission at week 52. Conclusion: Vedolizumab proved effective for the treatment of refractory IBD in clinical practice.

Download Full-text

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

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.562 ◽

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.

Download Full-text

P714 Real-world effectiveness of vedolizumab in ulcerative colitis: Week 52 results from the Swedish multi-centre, prospective, observational SVEAH UC study

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.842 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S576-S577

Author(s):

C ERIKSSON ◽

S Rundquist ◽

V Lykiardopoulos ◽

R Udumyan ◽

P Karlén ◽

...

Keyword(s):

Quality Of Life ◽

Ulcerative Colitis ◽

Clinical Response ◽

Rectal Bleeding ◽

Real World ◽

Clinical Remission ◽

Mayo Score ◽

National Quality ◽

Bleeding Score

Abstract Background Clinical trials may not readily reflect clinical practice. We aimed to assess the clinical effectiveness of vedolizumab in a real-world cohort of patients with ulcerative colitis (UC). Methods This is a prospective, observational, multi-centre cohort study. Eligible patients had active UC confirmed by a Mayo endoscopic subscore ≥2 at initiation of vedolizumab and had started treatment from 1/6/2015. Exclusion criteria included concurrent participation in a clinical trial in which UC treatment is dictated and contraindications to vedolizumab. All patients provided a written consent. Data on clinical characteristics, treatment patterns, disease activity and the short health scale were recorded at baseline and prospectively, using an electronic Case Record Form, integrated with the Swedish National Quality Registry for IBD (SWIBREG). The primary outcomes were A) clinical response, defined as a decrease in partial Mayo score of ≥2 and a reduction of ≥25 % from baseline, with a decrease ≥1 on the rectal bleeding score or an absolute rectal bleeding score of 0 or 1, at week 12 and B) clinical remission, defined as a partial Mayo score <2, at week 52. Continuous data are presented as median (interquartile range). Differences between baseline and follow-up visits were assessed by the Wilcoxon-signed rank test. Results In total, 117 eligible UC patients were included during the study period 1/6/2015 to 2/6/2018. Clinical and demographical characteristics of patients are shown in Table 1; 101/117 (86%) patients had failed prior anti-TNF therapy. The drug persistence rate was 106/117 (91%) at 12 weeks and 79/117 (68%) at 52 weeks. The clinical response rate at 12 weeks was 59/117 (50%) and the clinical remission rate at 52 weeks was 57/117 (49%). Altogether, 35/117 (30%) had an endoscopic Mayo score ≤1 at 12 weeks and 41/117 (35%) at 52 weeks. However, data on endoscopy were not available for 42 vedolizumab treated patients at 12 weeks and 30 at 52 weeks. Among patients who continued vedolizumab, the median partial Mayo score decreased from 4 (3–5) at baseline to 1 (0–2) at 52 weeks (p < 0.0001). Correspondingly, the median faecal calprotectin decreased from 646 (333–1130) µg/g to 162 (42–382) µg/g (p = 0.0002) and the median C-reactive protein from 5.0 (2.1–8.0) mg/L to 3.5 (1.6–5.0) mg/L (p = 0.008). Consistently, quality of life improved in vedolizumab treated patients, with a significant reduction of the overall short health scale score at 52 weeks (p < 0.0001). Conclusion Vedolizumab treated patients with UC represented a treatment-refractory group. Long-term (52 weeks) effectiveness of vedolizumab can be achieved, in terms of clinical- and inflammatory activity as well as in quality of life. The study was financially supported by Takeda.

Download Full-text

P087 REAL-WORLD EFFECTIVENESS OF USTEKINUMAB IN ULCERATIVE COLITIS

Inflammatory Bowel Diseases ◽

10.1093/ibd/zaa010.185 ◽

2020 ◽

Vol 26 (Supplement_1) ◽

pp. S73-S74

Author(s):

Simon Hong ◽

Samantha Zullow ◽

Jordan Axelrad ◽

Shannon Chang ◽

David Hudesman

Keyword(s):

Ulcerative Colitis ◽

Clinical Response ◽

Real World ◽

Clinical Remission ◽

Treatment Options ◽

Interleukin 12 ◽

World Population ◽

Tnf Antagonists ◽

Mayo Score ◽

Chronic Inflammatory Condition

Abstract Introduction Ulcerative colitis (UC) is a chronic inflammatory condition of the colon. Ustekinumab is a monoclonal antibody to the p40 subunit of interleukin-12 and interleukin-23 FDA approved for use in Crohn’s disease. A recent randomized control trial UNIFI [Sands et al, NEJM 2019] demonstrated the efficacy of ustekinumab in patients with moderate-to-severe UC. The goal of this study was to describe the real-world effectiveness of ustekinumab in patients with UC. Methods A retrospective, single-center, chart review was performed of all patients with UC who received ustekinumab between January 2017 and October 2019. As ustekinumab is not yet FDA approved for UC, for patients who have exhausted other treatment options its use is considered “off-label”. Patient demographics, disease characteristics and prior treatment history were recorded. The primary outcome was clinical remission at 12 months after initiation of ustekinumab. Secondary outcomes were clinical response and remission at 3 months, and endoscopic response, corticosteroid-free remission, and deep remission (combined clinical and endoscopic remission) at 12 months (all outcomes defined in Figure 1). Results 19 pts received ustekinumab for moderate-to-severe UC. They were 47.4% male with a mean age of 42.7 ±17.0 years. Mean total Mayo score was 7.6 ± 1.5 and 47.4% of pts had disease limited to the left colon. 18/19 pts received a weight-based IV induction dose (520 mg, 390 mg or 260 mg for > 85 kg, >55 to 85 kg or ≤55 kg respectively) and 1/19 received 90mg subcutaneous injection as induction. All pts received 90mg subcutaneous injections every 8 weeks initially for maintenance, and 9/19 eventually needed dose escalation to every 4 weeks. All pts had prior exposure to a TNF antagonist, 26.3% had exposure to two or more TNF antagonists, 89.5% had prior failure of vedolizumab and 10.5% had prior failure of tofacitinib (Table 1). At 12 months, 38.5% had a clinical response, 30.8% were in clinical remission, 38.5% had an endoscopic response, and 30.8% were in deep remission (Figure 1). Two infectious adverse events (shigellosis, Escherichia coli enterocolitis) were reported in follow-up. Conclusions Ustekinumab is effective in patients with UC. The efficacy of ustekinumab in the UNIFI trial translated to our real-world population, despite higher rates of prior biologic failure with TNF antagonists and vedolizumab in our cohort. Further studies of large, real-world cohorts are needed to assess the long-term effectiveness and safety of ustekinumab in UC.

Download Full-text