Adalimumab In Ulcerative Colitis Research Articles

Real-World Maintenance Phase Persistence on Ustekinumab and Adalimumab in Ulcerative Colitis.

To describe real-world persistence in bio-naïve and bio-experienced adults with ulcerative colitis (UC) treated with ustekinumab, a recently approved anti-interleukin 12/23 antibody, or adalimumab, an anti-TNF biologic. This is a descriptive, retrospective cohort study. Patients initiating ustekinumab or adalimumab (index date, between 10/21/2019 and 08/13/2021) were selected from the Komodo Health comprehensive dataset and stratified into bio-naïve and bio-experienced subgroups based on biologic use 12 months pre-index date. Endpoints evaluated at 12-months after maintenance phase start using Kaplan-Meier analysis included 1) persistence; 2) persistence while being corticosteroid-free (<14 consecutive days of corticosteroid supply after day 90 post-index); and, 3) persistence while on monotherapy (no immunomodulators/non-index biologics/advanced therapies). Ustekinumab cohort included 778 patients (236 bio-naïve, 542 bio-experienced) and adalimumab cohort included 1693 patients (1517 bio-naive, 176 bio-experienced). At 12 months after maintenance phase start, 75.5% and 50.5% of bio-naïve patients persisted on ustekinumab and adalimumab and 72.3% and 56.9% of bio-experienced patients persisted on ustekinumab and adalimumab, respectively. Further, 55.1% and 38.2% of bio-naïve patients were persistent and corticosteroid-free with ustekinumab and adalimumab; 43.7% and 33.4% of bio-experienced patients were persistent and corticosteroid-free with ustekinumab and adalimumab, respectively. Moreover, 68.1% and 44.5% of bio-naïve patients were persistent and on monotherapy with ustekinumab and adalimumab; 61.6% and 47.9% of bio-experienced patients were persistent and on monotherapy with ustekinumab and adalimumab, respectively. At 12 months after maintenance phase start, patients with UC treated with ustekinumab had numerically higher persistence, including persistence while corticosteroid-free and persistence while on monotherapy, than patients treated with adalimumab.

P870 Effectiveness and safety of adalimumab as first line biological treatment in Ulcerative Colitis

Abstract Background The increase in licensed therapies for ulcerative colitis (UC) is revolutionizing its treatment but making first line choice more challenging. Adalimumab (ADA) is inexpensive but, anecdotally, is sometimes regarded as less effective than other first line advanced therapies. We aimed to evaluate the results of first line ADA in UC. Methods We performed a single centre retrospective analysis of UC patients started on ADA between January 15 and March 2022 in an IBD referral hospital. Clinical remission was defined as SCCAI &amp;lt;2 points, endoscopic remission as a UCEIS &amp;lt;2 points and treatment failure as the need for colectomy or second biological line Results A total of 79 patients were included (Table 1). Median follow-up was 19 months (2-91); 78.5% were followed &amp;gt;6 months. At 6 months, 80.3% (61/76) and 37.3% (22/59) of the patients were in clinical and endoscopic remission, respectively. 54.3% received combination treatment with immunomodulators (50.6% thiopurines, 3.7% methotrexate). Dose intensification to weekly treatment occurred in 27.8% after median 9 months (4-48 months). During follow-up 51% received corticosteroids at some point (26% topically-acting oral corticosteroids, 10% oral corticosteroids, 15% both). Of patients who received steroids, 55% (22/40) were able to continue adalimumab therapy. 2.5% of patients were hospitalised for a disease flare. 5.1% had an infection recorded during follow up, none discontinued the treatment. No other major adverse events were recorded. In 22.8% (18/79) of patients, ADA was stopped due to treatment failure, mean 15 months after starting the drug (4-56 months), (Figure 1). None of these patients underwent colectomy at the time of stopping the drug; in 17/18 a second biological therapy was started (10 tofacitinib, 1 filgotinib, 1 upadacitinib, 2 ustekinumab, 2 vedolizumab, 1 golimumab). TDM was performed using a drug-sensitive ELISA, which is only able to detect antidrug antibodies when drug levels are low or absent. Drug levels at the time of stopping the drug were &amp;lt;5 µg/mL in 22% of patients (in 2 antibodies were detected), 5-8 µg/mL in 11% and &amp;gt;8 µg/mL in 67%. Conclusion In a real-world UC cohort, ADA appears to be an effective well tolerated first-line advanced therapy with the vast majority of patients reaching clinical remission and a significant proportion achieving mucosal healing. Table 1. Cohort characteristics (N 79, frequency and %). Figure 1: Kaplan-Meier survival analysis of time to ADA discontinuation.

Albumin change predicts failure in ulcerative colitis treated with adalimumab.

Anti-tumor necrosis factor (TNF) -α antibodies, including infliximab (IFX), adalimumab (ADA), and golimumab, which were the first biologic therapeutic agents, have a crucial position in advanced therapy for ulcerative colitis (UC). We aimed to investigate serum albumin (Alb) change as a prognostic factor for the therapeutic effect of ADA in UC. Thirty-four patients with UC treated with ADA were enrolled in this study and were divided into failure and non-failure groups. Biological data, such as Alb were compared between the two groups. Thirteen patients showed failure within six months. Examination of the biological data showed a significant difference between the two groups only in the week 2/week 0 Alb ratio. In receiver-operating characteristic (ROC) curve analysis to predict failure, the cut-off value of week 2/week 0 Alb ratio was 1.00, and the area under the curve was 0.868 (95% confidence interval: 0.738-0.999). In addition, in the sub-group analysis of only clinically active patients, the week 2/week 0 Alb ratio of the non-failure group was significantly higher than that of the failure group, and the cut-off-value in ROC analysis was 1.00. Week 2/week 0 Alb ratio ≤ 1 predicts failure within six months of ADA for UC.

Systematic Review and Meta-analysis: Loss of Response and Need for Dose Escalation of Infliximab and Adalimumab in Ulcerative Colitis.

Loss of response to infliximab or adalimumab in ulcerative colitis occurs frequently, and dose escalation may aid in regaining clinical benefit. This study aimed to systematically assess the annual loss of response and dose escalation rates for infliximab and adalimumab in ulcerative colitis. A systematic search was conducted from August 1999 to July 2021 for studies reporting loss of response and dose escalation during infliximab and/or adalimumab use in ulcerative colitis patients with primary response. Annual loss of response, dose escalation rates, and clinical benefit after dose escalation were calculated. Subgroup analyses were performed for studies with 1-year follow-up or less. We included 50 unique studies assessing loss of response (infliximab, n = 24; adalimumab, n = 21) or dose escalation (infliximab, n = 21; adalimumab, n = 16). The pooled annual loss of response for infliximab was 10.1% (95% confidence interval [CI], 7.1-14.3) and 13.6% (95% CI, 9.3-19.9) for studies with 1-year follow-up. The pooled annual loss of response for adalimumab was 13.4% (95% CI, 8.2-21.8) and 23.3% (95% CI, 15.4-35.1) for studies with 1-year follow-up. Annual pooled dose escalation rates were 13.8% (95% CI, 8.7-21.7) for infliximab and 21.3% (95% CI, 14.4-31.3) for adalimumab, regaining clinical benefit in 72.4% and 52.3%, respectively. Annual loss of response was 10% for infliximab and 13% for adalimumab, with higher rates during the first year. Annual dose escalation rates were 14% (infliximab) and 21% (adalimumab), with clinical benefit in 72% and 52%, respectively. Uniform definitions are needed to facilitate more robust evaluations.

End of induction patient reported outcomes predict clinical remission and endoscopic improvement with vedolizumab and adalimumab in ulcerative colitis

Background Patient-reported outcomes (PROs) are increasingly emphasized as endpoints in clinical trials of ulcerative colitis (UC). However, the prognostic value of early improvement in PROs for long-term outcomes remains unclear. Methods This was a post-hoc analysis of 611 vedolizumab-treated or adalimumab-treated patients in the VARSITY trial (Clinicaltrial.gov: NCT02497469). Stool frequency (SF) and rectal bleeding score (RBS) as reported in the Mayo score at post-induction (week 6 and 14) was assessed for their association with one-year endoscopic improvement (EI), defined as Mayo endoscopic subscore <2; histo-endoscopic mucosal improvement (HEMI), defined as EI and Geboes highest grade <3.2, clinical remission (CR), defined as total Mayo score ≤2; and PRO-2 remission, defined as RBS of 0 and SF ≤1. Multivariable logistic regression models adjusted for confounders assessed the relationships between post-induction PROs and outcomes of interest at one-year. Results Patients with severe SF at week 6 were significantly less likely to achieve one-year EI compared to those with non-severe SF [aOR 0.40 (95% CI: 0.24–0.68), p < .001]. Absence of rectal bleeding at week 6 was associated with greater odds of achieving EI at one-year [aOR 2.21 (95% CI: 1.58–3.09), p < .001]. These findings were consistent across comparisons at week 14. Similar findings were observed for the outcomes of one-year HEMI, CR and PRO-2 remission. No difference was observed between the modified partial Mayo score and modified PRO-2 score. Conclusions Post-induction PROs strongly predict the odds of CR and EI in UC and simplified evaluations can be used to assess early response to UC therapies.

Higher vs Standard Adalimumab Induction and Maintenance Dosing Regimens for Treatment of Ulcerative Colitis: SERENE UC Trial Results

SERENE UC (Study of a Novel Approach to Induction and Maintenance Dosing With Adalimumab in Patients With Moderate to Severe Ulcerative Colitis) evaluated the efficacy of higher adalimumab induction and maintenance dose regimens in patients with ulcerative colitis. This phase 3, double-blind, randomized trial included induction and maintenance studies, with a main study (ex-Japan) and Japan substudy. Eligible patients (18-75 years, full Mayo score 6-12, centrally read endoscopy subscore 2-3) were randomized 3:2 to higher induction regimen (adalimumab 160 mg at weeks 0, 1, 2, and 3) or standard induction regimen (160 mg at week 0 and 80 mg at week 2); all received 40 mg at weeks 4 and 6. At week 8, all patients were rerandomized 2:2:1 (main study) to 40 mg every week (ew), 40 mg every other week (eow), or exploratory therapeutic drug monitoring; or 1:1 (Japan substudy) to 40 mg ew or 40 mg eow maintenance regimens. In the main study, 13.3% vs 10.9% of patients receiving the higher induction regimen vs standard induction regimen achieved clinical remission (full Mayo score ≤2 with no subscore >1) at week 8 (induction primary end point; P= .265); among week-8 responders, 39.5% vs 29.0% receiving 40 mg ew vs 40 mg eow achieved clinical remission at week 52 (maintenance primary end point; P= .069). In the integrated (main+ Japan) population, 41.1% vs 30.1% of week-8 responders receiving 40 mg ew vs 40 mg eow achievedclinical remission at week 52 (nominal P= .045). Safety profiles were comparable between dosing regimens. Although primary end points were not met, a >10% absolute difference in clinical remission was demonstrated with higher adalimumab maintenance dosing. Higher dosing regimens were generally well tolerated and consistent with the known safety profile of adalimumab in ulcerative colitis. gov, Number: NCT002209456.

Translating Results from VARSITY to Real World: Adalimumab vs Vedolizumab as First-line Biological in Moderate to Severe IBD.

Selecting a first-line therapy remains challenging in IBD. Adalimumab (ADM) and vedolizumab (VDZ) effectively lead to endoscopic remission in moderate to severe IBD. The VARSITY trial showed superiority of VDZ over ADM in ulcerative colitis (UC) regarding clinical remission and endoscopic improvement at week 52. We explored these results in a real-world setting of UC and Crohn's disease (CD). This retrospective study followed a cohort of biologic-naïve patients starting ADM or VDZ from 2015-2019. Patients had moderate to severe disease (endoscopic Mayo score ≥2 for UC, presence of ulcerations for CD) prior to therapy initiation. For UC, endoscopic remission (endoscopic Mayo score 0) and improvement (endoscopic Mayo score ≤1) at week 52 were assessed. For CD, endoscopic remission (absence of ulcerations) and improvement (markedly better endoscopy despite ulcerations) at weeks 26-52 were studied. Treatment persistence was also evaluated. In total, 195 biologic-naïve patients (109 UC; 86 CD) were included. In UC, VDZ was superior to ADM regarding endoscopic remission (29% vs 11%, P = .03), endoscopic improvement (51% vs 26%, P = .01) at week 52, and treatment persistence (P = .04). In CD, no differences in endoscopic remission (VDZ 48% vs ADM 60%; P=0.37), improvement (VDZ 76% vs ADM 77%; P = 1.00), or treatment persistence (P=0.43) at weeks 26-52 were seen. Safety profiles were similar in UC and CD. This real-world cohort study of biologic-naïve IBD patients found VDZ to be superior to ADM as first-line treatment for patients with UC-but not CD-regarding endoscopic remission at week 52 and treatment persistence.

Vedolizumab cost effective versus adalimumab for ulcerative colitis

Vedolizumab cost effective versus adalimumab for ulcerative colitis

Histologic Outcomes With Vedolizumab Versus Adalimumab in Ulcerative Colitis: Results From An Efficacy and Safety Study of Vedolizumab Intravenous Compared to Adalimumab Subcutaneous in Participants With Ulcerative Colitis (VARSITY)

VARSITY (An Efficacy and Safety Study of Vedolizumab Intravenous [IV] Compared to Adalimumab Subcutaneous [SC] in Participants With Ulcerative Colitis) showed superior clinical remission and endoscopic improvement in ulcerative colitis with vedolizumab vs adalimumab. This analysis compared histologic outcomes. Patients in VARSITY were randomized 1:1 to maintenance with vedolizumab IV 300 mg every 8 weeks or adalimumab SC 40 mg every 2 weeks (both following standard induction). Geboes Index and Robarts Histopathology Index (RHI) scores were used to assess prespecified histologic exploratory end points of histologic remission (Geboes <2 or RHI ≤2) and minimal histologic disease activity (Geboes ≤3.1 or RHI ≤4) at weeks 14 and52. In total, 769 patients received vedolizumab (n= 383) or adalimumab (n= 386). Mean baseline histologic disease activity was similar between vedolizumab and adalimumab groups. Vedolizumab induced greater histologic remission than adalimumab at week 14 (Geboes: 16.7% vs 7.3%, Δ9.4% [95% confidence interval {CI}, 4.9%-13.9%], P < .0001; RHI: 25.6% vs 16.1%, Δ9.5% [95% CI, 3.8%-15.2%], P= .0011) and week 52 (Geboes: 29.2% vs 8.3%, Δ20.9% [95% CI, 15.6%-26.2%], P < .0001; RHI: 37.6% vs 19.9%, Δ17.6% [95% CI, 11.3%-23.8%], P<.0001) overall and in both anti-tumor necrosis factor (TNF)-naïve and -failure subgroups. Results were similar for minimal histologic disease activity. Histologic outcomes were generally better in anti-TNF-naïve vs -failure patients. At week 52, rates of mucosal healing (composite end point of histologic plus endoscopic improvement) were also higher with vedolizumab than adalimumab (Geboes: 25.6% vs 6.7%; RHI: 30.5% vs 14.5%). Higher rates of histologic remission, minimal histologic disease activity, and combined histologic plus endoscopic outcomes were observed with vedolizumab than with adalimumab in ulcerative colitis in both anti-TNF-naïve and -failure subgroups. ClinicalTrials.gov NCT02497469; EudraCT 2015-000939-33.

Mucosal microbiota and gene expression are associated with long-term remission after discontinuation of adalimumab in ulcerative colitis

Given that sustained remission is the ultimate treatment goal in the management of patients with ulcerative colitis (UC), the decision to stop anti-tumor necrosis factor (anti-TNF) treatment in UC patients is difficult. The aim of this study was to evaluate mucosal microbiota and gene expression profiles associated with long-term remission after discontinuation of anti-TNF therapy. In nine UC patients who received anti-TNF therapy for 6 months, microbiota isolated from uninflamed mucosae and gene expression in inflamed and uninflamed mucosae were investigated at week 0 and at week 24. At treatment initiation, Fusobacterium sp. and Veillonella dispar were over-represented in the relapse group compared with the non-relapse group. After treatment, Dorea sp. and Lachnospira sp. were over-represented in the non-relapse group. In the relapse group only, a significant shift in gut bacterial community composition was found between week 0 and week 24. Gene expression of ALIX (PDCD6IP) and SLC9A3 was significantly higher in the non-relapse group than in the relapse group. Lastly, we used machine learning methods to identify relevant gene signatures associated with sustained remission. Statistical analyses of microbiota and expression profiles revealed differences between UC patients who did or did not keep remission after the discontinuation of TNF inhibitors.Trial registration: UMIN000020785: Evaluation of adalimumab therapy in mesalazine-resistant or -intolerant ulcerative colitis; an observational study (EARLY study).

S0664 Disease Control and Changes in Individual Treatment Outcomes From Week 14 to Week 52 With Vedolizumab or Adalimumab in Ulcerative Colitis: A VARSITY Trial Post Hoc Analysis

INTRODUCTION: In VARSITY, vedolizumab (VDZ), an anti-α4β7 integrin antibody, achieved superior clinical, endoscopic and histologic outcomes vs adalimumab (ADA), an anti-tumor necrosis factor (TNF) agent, in patients with moderate-to-severe ulcerative colitis (UC) (1). In recent years, the therapeutic goal for UC has evolved from symptom relief to disease control across multiple outcomes. METHODS: This VARSITY post hoc analysis evaluated the trajectory of UC key endpoints and disease control with intravenous VDZ vs subcutaneous ADA between early (Week [W]14) and late (W52) time points. Evolution in disease control over time was assessed based on the proportion of patients who maintained, improved or lost treatment benefit from W14 to W52 for the efficacy endpoints clinical remission, endoscopic and histologic improvement (defined in Figure 1). Data were analyzed within treatment arms in the full analysis population and by prior anti-TNF use (anti-TNF naïve or experienced). Observed data were reported without imputation. RESULTS: The study included 769 patients with UC (386 ADA, 383 VDZ). Most patients (56.0% ADA vs 60.8% VDZ) were male, were not using a corticosteroid at baseline (63.7% vs 63.9%) and were anti-TNF naïve (79.0% vs 79.2%). Median UC duration was 4.5 (ADA) and 4.8 (VDZ) years. At W14 and W52, clinical remission, endoscopic and histologic improvement, and disease control were all achieved more frequently with VDZ vs ADA (Table 1). More patients maintained each efficacy outcome and disease control from W14 to W52 with VDZ vs ADA, in both anti-TNF subgroups (Figure 1). In both arms, more anti-TNF naïve than anti-TNF experienced patients maintained efficacy (Figure 1). The numbers of patients who gained efficacy at W52 were more comparable between anti-TNF naïve and experienced. At W52, the overall rate of disease control was higher with VDZ (47.3% anti-TNF naïve vs 39.0% anti-TNF experienced) than ADA (32.7% vs 24.2%) (Table 1). Further analyses of early predictors of late disease control will be presented. CONCLUSION: VDZ treatment maintains greater early disease control than ADA in moderate-to-severe UC from W14 to W52, especially in anti-TNF naïve patients. These data suggest that VDZ is superior to ADA during both induction treatment evaluated at W14 and maintenance treatment evaluated at W52. Most of the observed treatment differences in anti-TNF naïve patients at W52 were established with early response to treatment between W0 and W14.Table 1.: Clinical Efficacy Outcomes and Disease Control at Weeks 14 and 52 by Anti-TNF Status With Adalimumab and Vedolizumab Treatment in Patients With UCFigure 1.: Changes in Clinical Efficacy Outcomes and Disease Control From Week 14 to Week 52 by Anti-TNF Status (Naïve/Experienced) With Adalimumab (N=305/N=81) and Vedolizumab (N=304/N=79) Treatment in Patients With UC.

Short and long-term efficacy of adalimumab in ulcerative colitis: a real-life study

Objective: Randomized controlled trials have shown the effectiveness of Adalimumab in ulcerative colitis. However, real-life data is scarce. We aimed to assess the effectiveness and predictive factors of effectiveness in a large Swedish cohort.Methods: Retrospective capture of data from local registries at five Swedish IBD centers. Clinical response and remission rates were assessed at three months after starting adalimumab treatment and patients were followed until colectomy or need for another biological. Bio-naive patients were compared to bio experienced patients. Factors associated with short term responses were assessed using logistic regression model. Failure on drug was assessed using a Cox proportional hazards regression model.Results: 118 patients (59 males, 59 females) with median age 34.4 years (IQR 27.0–51.4) were included. Median disease duration was 4.3 years (IQR 2.0–9.0) and follow-up 1.27 years (IQR 0.33–4.1). A clinical corticosteroid-free remission was achieved by 38/118 (32.2%) and response by 91/118 (77%) after three months. CRP >3 mg/l at baseline was predictive of short-term failure to reach corticosteroid-free remission. Factors associated with survival on the drug were male gender, CRP <3 mg/l and absence of primary sclerosing cholangitis. Patients >42 years of age at diagnosis were more likely to respond to adalimumab and remain on treatment compared to patients <20 years.Conclusions: An elevated CRP-level, primary sclerosing cholangitis and female gender were predictors of treatment failure. In contrast older age at diagnosis was a predictor of short-term clinical response and drug survival. Prior infliximab failure, regardless of cause, did not influence the outcome of adalimumab treatment.

P361 The effect of immunomodulators and other factors on the persistence of biological agents for Crohn’s disease and ulcerative colitis: data from the Australian population-based registry

Abstract Background Treatment persistence (duration of medication use) provides real-world evidence on therapeutic effectiveness, tolerability and prescriber and patient preferences. Biological agent persistence in Crohn’s disease (CD) and ulcerative colitis (UC) was compared from a national population-based registry with no hierarchical prescribing order. We hypothesised immunotherapy co-therapy would increase persistence for anti-TNF agents, but not for non-anti-TNF agents due to reduced immunogenicity. Methods A randomly selected ten per cent subgroup of the prospectively collected population-based registry from the Australian Pharmaceutical Benefits Scheme between June 2005 and June 2019 was analysed. Treatment persistence of adalimumab (ADA), infliximab (IFX), vedolizumab (VDZ) and ustekinumab (UST) was compared. Factors affecting discontinuation were evaluated using multivariate proportional hazard regression. Results 886 patients consisting of 1294 lines of therapy (992 CD, 302 UC, 2778 person-years of follow-up) were included. In CD, UST had the highest overall persistence rate (median persistence rate was &amp;gt; 74.6% where 24.6 months is the maximum follow-up time recorded), followed by VDZ, IFX and ADA (p = 0.03) (Figure 1). UST had the highest persistence as first, second and third-line therapies (p &amp;lt; 0.05). In UC, VDZ had the highest persistence rate (median persistence rate was &amp;gt;50.3% where 47.4 months is the maximum follow-up time recorded), followed by IFX and ADA (p &amp;lt; 0.001) (Figure 2). VDZ had the highest persistence rates as first-line therapy (p &amp;lt; 0.001), while second and third-line therapies did not demonstrate significant differences. Persistence of biological agents correlated with immunomodulator co-therapy in CD (R2: 0.65 p &amp;lt; 0.001) and UC (R2: 0.50 p &amp;lt; 0.001). Thiopurine co-therapy significantly increased persistence for IFX and ADA in CD and UC (p &amp;lt; 0.001) (Figures 3 and 4) but was not significant for UST and VDZ. Methotrexate decreased persistence for VDZ in UC and had no effects on UST, IFX and ADA in UC and CD. In acute-severe UC, there were no significant differences between IFX as monotherapy vs. co-therapy. On multivariate analysis, higher persistence was seen in males (HR: 0.75 95% CI: 0.59–0.94) and with immunomodulator co-therapy (HR 0.77 95% CI: 0.61–0.97, p = 0.03). Conclusion This real-world data reflecting treatment effectiveness, tolerability and patient and prescriber preferences supports the use of UST and VDZ over anti-TNF agents in CD and UC, respectively, to achieve high treatment persistence which is independent of immunomodulator co-therapy, possibly secondary to differing immunogenicity rates. It also highlights the substantial increase in anti-TNF therapy persistence with thiopurine co-therapy, but not with methotrexate.

716 Early Clinical Response and Remission With Vedolizumab Versus Adalimumab in Ulcerative Colitis: Results From VARSITY

INTRODUCTION: VARSITY is the first head-to-head trial comparing the efficacy and safety of 2 biologic therapies, vedolizumab (VDZ) and adalimumab (ADA), in patients with moderately to severely active ulcerative colitis (UC). We previously reported significantly higher rates of clinical remission (31.3% vs 22.5%; P = 0.0061) and endoscopic improvement (39.7% vs 27.7%; P = 0.0005) at Week (Wk) 52 with VDZ vs ADA. 1 METHODS: VARSITY was a phase 3b, randomized, double-blind, double-dummy, active-controlled study (NCT02497469; EudraCT 2015-000939-33). Here we report the predefined, exploratory endpoints of early clinical response and clinical remission (defined in the Table 1) within the first 14 wks, as well as durable clinical remission (patients in clinical remission at Wk 14 and Wk 52). RESULTS: A total of 769 patients received ≥1 dose of VDZ (n = 383) or ADA (n = 386). Baseline characteristics were comparable between the 2 groups. A trend for separation in clinical response started to emerge at Wk 6 favoring VDZ vs ADA. Clinical response at Wk 14 favored VDZ vs ADA (257 [67.1%] vs 177 [45.9%]; treatment difference 21.2%). More patients achieved clinical remission at Wk 14 on VDZ vs ADA (102 [26.6%] vs 82 [21.2%]; treatment difference 5.3%). Patients on VDZ achieved higher rates of durable clinical remission (70 [18.3%] vs 46 [11.9%]); laboratory results correlated with these findings. Post hoc analyses showed a larger mean (standard deviation) change of C-reactive protein (CRP) from baseline to Wk 14 (−32.88 [155.77] nmol/L VDZ vs −3.35 [260.81] nmol/L ADA) and to Wk 52 (−50.87 [174.76] nmol/L VDZ vs −37.21 [169.17] nmol/L ADA) in favor of VDZ. Greater mean declines in fecal calprotectin (FCP) levels were seen in patients on VDZ compared with ADA (Wk 14: −1,551.3 [6,236.70] mg/kg VDZ vs −1,167.6 [4,647.67] mg/kg ADA; Wk 52: −2,187.3 [7,440.42] mg/kg VDZ vs −1,846.6 [4,560.55] mg/kg ADA). CONCLUSION: Patients on VDZ had numerically higher rates of both clinical response and clinical remission by Wk 14 compared with ADA. Patients on VDZ also achieved higher rates of durable clinical remission compared with ADA. CRP and FCP results correlated with these findings. These data on early clinical response and clinical remission, as well as durable remission, further support the use of VDZ over ADA in patients with moderately to severely active UC.

757 Histologic Improvement With Vedolizumab vs. Adalimumab in Ulcerative Colitis: Results From VARSITY

INTRODUCTION: Histologic remission is associated with superior long-term clinical outcomes in ulcerative colitis (UC). VARSITY, the first head-to-head comparison of biologic agents in UC (NCT02497469; EudraCT 2015-000939-33), showed superior clinical remission and endoscopic improvement at Week 52 with vedolizumab (VDZ), a gut-selective, humanized, α4β7 integrin monoclonal antibody, vs adalimumab (ADA), a systemic, human, anti-tumor necrosis factor (anti-TNF) monoclonal antibody. 1 Both VDZ and ADA were generally safe and well-tolerated. 1 This analysis compared histologic improvements with VDZ vs ADA in VARSITY. METHODS: Patients with moderately to severely active UC were randomized 1:1 to active VDZ intravenous (IV) infusions (300 mg)/placebo subcutaneous (SC) injections or placebo IV/active ADA SC (160/80/40 mg). Prespecified histologic exploratory endpoints included histologic remission (Geboes score &lt; 2 or Robarts Histopathology Index [RHI] score &lt; 3) and minimal histologic disease activity (Geboes score &lt; 3.2 or RHI score &lt; 5) at Week 14 and Week 52. Histologic remission was also assessed based on previous anti-TNF use. RESULTS: A total of 769 patients received ≥1 dose of VDZ (n = 383) or ADA (n = 386). Median (range) duration of exposure was 477 (127, 630) days for VDZ and 420 (71, 454) days for ADA. Mean (standard deviation) baseline histologic disease activity was similar between groups (Geboes: VDZ, 15.0 [4.92]; ADA, 15.1 [5.03]; RHI: VDZ, 19.5 [8.74]; ADA, 19.6 [8.89]). Histologic remission induced by VDZ at Week 52 was greater than with ADA in the overall (Geboes or RHI), anti-TNF naïve (Geboes or RHI), and anti-TNF failure (RHI only) groups (Table 1). Histologic remission at Week 14 favored VDZ over ADA, with larger differentiation when using RHI (Table 1). VDZ also outperformed ADA in achieving minimal histologic disease activity at Weeks 14 and 52 (Table 1). CONCLUSION: VARSITY showed that use of VDZ, compared with ADA, achieved higher rates of histologic remission and minimal histologic disease activity at Weeks 14 and 52 in patients with moderately to severely active UC. These data support the use of VDZ over ADA in UC.

Mo1920 – Results of Interim Analysis of a Retrospective Igibd Study on Adalimumab Use in Real Practice in Italy: the Real-Life Clinical Effectiveness of Adalimumab in Ulcerative Colitis (REALADA-UC) Study

Mo1920 – Results of Interim Analysis of a Retrospective Igibd Study on Adalimumab Use in Real Practice in Italy: the Real-Life Clinical Effectiveness of Adalimumab in Ulcerative Colitis (REALADA-UC) Study

P512 Results of interim analysis of a retrospective IGIBD study on adalimumab use in real practice in Italy: the REAL-life clinical effectiveness of ADAlimumab in ulcerative colitis

P512 Results of interim analysis of a retrospective IGIBD study on adalimumab use in real practice in Italy: the REAL-life clinical effectiveness of ADAlimumab in ulcerative colitis

Assessment of Long-Term Efficacy and Safety of Adalimumab in Patients with Ulcerative Colitis: Results from a 6-Year Real-World Clinical Practice

Background: Although evidence for the short- to medium-term efficacy of adalimumab in ulcerative colitis (UC) patients is emerging, there are a limited number of reports on the long-term efficacy of adalimumab. This study was to understand baseline demographic features, which potentially could be risk factors for relapse or colectomy following induction of remission by adalimumab in UC patients. Additionally, factors affecting long-term outcomes were to be identified. Methods: Twenty-one patients with UC who had been treated with adalimumab were reviewed retrospectively. Comparative analyses were undertaken by factoring steroid withdrawal versus non-withdrawal, long-term remission versus relapse following remission, and requiring surgical intervention for UC versus surgery-free. Results: Adalimumab treatment was associated with steroid tapering in steroid-dependent cases in the long term. Of the 14 patients in whom clinical remission was achieved, the cumulative nonrelapse survival rate at 350 weeks was 43.8% and the cumulative nonoperative survival rate was 85.7%. Risk factors for surgery included intolerance to salicylates (p = 0.005) and past treatment with tacrolimus (p = 0.023). Conclusions: Adalimumab treatment was associated with long-term efficacy in patients with mild UC – patients achieved a high cumulative nonoperative survival rate over a long period of time, beyond 6 years.

Adalimumab in ulcerative colitis – efficacy, safety and optimization in the era of treat-to target

ABSTRACTIntroduction: Active ulcerative colitis is associated with significant morbidity and impairment to quality of life. Adalimumab is a welcome addition to the therapeutic armamentarium for clinicians treating patients with moderate-severe ulcerative colitis refractory to conventional therapies, an indication with few prior treatment options. It offers the convenience of self-injection and is most appropriate for outpatients with moderate disease activity.Areas covered: This review briefly summarizes data from well-designed clinical trials and observational real-life studies that demonstrate the safety and efficacy of adalimumab in UC. Particular attention is paid to newer studies, including those with objective treatment endpoints and pharmacokinetic outcomes that incorporate a treat to target approach in inflammatory bowel disease.Expert opinion: Adalimumab is effective for the induction and maintenance of remission in patients with moderate-severe ulcerative colitis refractory to conventional therapies. At currently approved doses, it is most suitable for use in outpatients with moderate disease activity; higher doses may be required for patients with more severe disease. The convenience of self-injection will make it popular for remote patients and it may be an appropriate option in patients in whom monotherapy, rather than combination therapy with an immunomodulator, is preferred.

P395. Real-life prospective experience with adalimumab in ulcerative colitis in Italy: preliminary results of a pilot study

P395. Real-life prospective experience with adalimumab in ulcerative colitis in Italy: preliminary results of a pilot study