Long-term Clinical Remission Research Articles

Transmural Healing Evaluated by Intestinal Ultrasound in Patients with Crohn’s Disease Treated with Infliximab

Background and Aims: Transmural healing (TH) has been recently proposed as a measure of deep remission in Crohn’s disease (CD). This study aimed to explore the rate of TH evaluated by intestinal ultrasound (IUS) in patients with CD treated with infliximab (IFX) and its predictive value for long-time clinical remission. Methods: Sixty-four consecutive active CD patients prescribed IFX were retrospectively recruited and followed for at least 2 years. Patients underwent IUS evaluation including bowel wall thickness, stratification, vascularity and mesenteric fat alteration at baseline and 14 weeks after IFX initiation. TH (normalization of all IUS parameters) was assessed at 14 weeks. Results: Fifteen (23.4%) patients achieved TH at 14 weeks, who were at lower risk of clinical relapse during the maintenance period than patients without TH [relative risk (RR) 0.132, P = 0.020]. The multivariate analysis indicated that TH (RR = 0.076, 95% CI: 0.007 - 0.773, P = 0.029) at 14 weeks were negative independent predictors of clinical relapse for patients who achieved steroid-free CR after the induction period. Patients with serum IFX trough levels >3 ug/ml were more likely to achieve TH at 14 weeks (34.3% vs. 10.7%, P = 0.029). Conclusion: IUS is useful in assessing TH, which predicts long-term clinical remission in patients with CD prescribed infliximab.

Induction of mucosal healing by intensive granulocyte/monocyte adsorptive apheresis (GMA) without use of corticosteroids in patients with ulcerative colitis: long-term remission maintenance after induction by GMA and efficacy of GMA re-treatment upon relapse.

This study examined the long-term maintenance rate after inducing remission by intensive granulocyte/monocyte adsorptive apheresis (GMA) without use of corticosteroids (CS) and GMA re-treatment efficacy in the same patients upon relapse with ulcerative colitis. Patients who achieved clinical remission and mucosal healing (MH) by first-time intensive GMA (first GMA) without CS were enrolled. The cumulative non-relapse survival rate up to week 156 was calculated. Patients with relapse during the maintenance period underwent second-time intensive GMA (second GMA) without CS. Clinical remission and MH rates following second GMA were compared to those following first GMA in the same patients. Of the 84 patients enrolled, 78 were followed until week 156 and 34 demonstrated relapse. The cumulative non-relapse survival rate by week 156 was 56.4%. Clinical remission and MH rates after second GMA did not differ from those after first GMA in the same patients (week 6: clinical remission, 100% vs 88.4%, p = 0.134; MH, 100% vs 84.8%, p = 0.074). In conclusion, MH induction by intensive GMA without use of CS in ulcerative colitis patients contributes to subsequent long-term clinical remission maintenance. GMA re-treatment efficacy was comparable to that of first GMA in the same patients who had relapse.

Early Improvements in Disease Activity Indices Predict Long-Term Clinical Remission Suggested by the Treat-to-Target Strategy in Patients with Ankylosing Spondylitis Receiving TNF-α Inhibitor Treatment.

This study evaluated the possibility of clinical remission suggested by the treat-to-target strategy and identified predictors of clinical remission in 139 patients with ankylosing spondylitis (AS) receiving tumor necrosis factor-α inhibitors (TNFi). Clinical remission criteria selected were AS Disease Activity Score Inactive Disease (ASDAS-ID) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) < 2 with normal C-reactive protein (CRP) levels (BASDAI-CRP). The longitudinal relationship between clinical parameters and clinical remission was assessed using generalized estimating equations (GEEs). Responders to ASDAS-ID and BASDAI-CRP increased from 32.4% to 68.9% and from 39.9% to 75.2% at months 3 and 33, respectively. Responders to ASDAS-ID and BASDAI-CRP almost overlapped. In the univariable GEE model, age and 3-month improvement in BASDAI, ASDAS-CRP, physician and patient global assessments, and spinal pain predicted clinical remission achievement, while the presence of syndesmophytes predicted ASDAS-CRP achievement, and normalized CRP at 3 months was associated with BASDAI-CRP achievement. Multivariable GEE analysis revealed age (odds ratio (OR): 0.67; 95% confidence interval (CI), 0.49–0.93) and 3-month BASDAI improvement (OR: 1.70; CI, 1.19–2.41) as independent predictors of ASDAS-ID achievement and age (OR: 0.69; CI, 0.54–0.89), 3-month BASDAI improvement (OR: 2.00; CI, 1.45–2.76), and normalized CRP at 3 months (OR: 3.72; CI, 1.39–9.95) as independent predictors of BASDAI-CRP achievement.

Vedolizumab as first-line biological therapy in elderly patients and those with contraindications for anti-TNF therapy: a real-world, nationwide cohort of patients with inflammatory bowel diseases

Background Data from real-life populations about vedolizumab as first-line biological therapy for ulcerative colitis (UC) and Crohn’s disease (CD) are emerging. Objective To investigate the efficacy and safety of vedolizumab in bio-naïve patients with UC and CD. Methods A Danish nationwide cohort study was conducted between November 2014 and November 2019. Primary outcomes were clinical remission, steroid-free clinical remission, and sustained clinical remission from weeks 14 through 52. Results The study included 56 patients (UC:31, CD:25) who initiated treatment with vedolizumab mainly because of contraindications to anti-TNFs, of whom 54.8 and 24.0%, respectively received systemic steroids at the initiation. Rates of clinical remission at weeks 6, 14, and 52 were 32.0, 48.0, and 40.0%, respectively, in UC, and 36.8, 36.8, and 47.4% in CD. Steroid-free clinical remission at week 52 was achieved among 36.0 and 47.4% of UC and CD patients, while sustained clinical remission was achieved in 32.0 and 36.8%. Lack of remission was associated with being female (68.8 vs. 11.1%, p = .01) in UC and non‐structuring, non‐penetrating behavior in CD (90.0 vs. 44.4%, p = .03); however, this was not confirmed in multivariate analysis. Discontinuation due to primary non-response occurred in 20.0 and 5.3% of UC and CD patients, respectively, while rates of secondary loss of response were 12.0 and 5.3% after 52 weeks of follow-up. Vedolizumab was well-tolerated as only one UC patient experienced a serious adverse event. Conclusion Vedolizumab is effective in the achievement of short-term, long-term, and steroid-free clinical remission in bio-naïve UC and CD patients.

Short and long-term effectiveness and safety of vedolizumab in treatment-refractory patients with ulcerative colitis and Crohn’s disease – a real-world two-center cohort study

Real-world data about sustained clinical remission (SCR) and treatment optimization with vedolizumab for ulcerative colitis (UC) and Crohn's disease (CD) are scarce. We aimed to investigate the short and long-term effectiveness and safety of vedolizumab in a real-world cohort in Denmark. A retrospective two-center cohort study was conducted between November 2014 and November 2019 with the primary outcomes of clinical remission (CR) at weeks 14, 30, 52 and 104 and SCR defined as CR at week 14 through week 52. The study included 182 patients (UC: 97, CD: 85), all previously exposed to at least one biological therapy. Rates of CR at weeks 14, 30, 52 and 104 were 36.6, 35.1, 34.0 and 27.8%, respectively, in UC, and 31.7, 30.1, 26.5 and 22.4% in CD. SCR was achieved in 19.6 and 20.0%, respectively. In UC and CD, optional dosing of vedolizumab at week 10 (odds ratio [OR] = 0.23 (95% confidence interval [CI], 0.03-1.17), and OR = 0.68 (95% CI, 0.22-2.04)), as well as increase of frequency (OR = .26 (95% CI, 0.01-2.86), and OR = 0.19 (95% CI, 0.01-1.45)), were not associated with CR at week 52. Furthermore, combination treatment with azathioprine was not associated with long-term outcomes. However, dose intensification of vedolizumab successfully restored CR in 65.2 and 57.1% of patients with UC and CD experiencing loss of response. Vedolizumab is effective in achieving and restoring short and long-term CR and SCR in patients with treatment-refractory UC and CD. This study emphasizes that supplementary dosing at week 10, and simultaneous treatment with azathioprine, did not improve long-term outcomes.

P421 Treatment optimization with vedolizumab in treatment-refractory patients with ulcerative colitis and Crohn’s disease – a real-world two-center cohort study

Abstract Background Real-world data about treatment optimization of vedolizumab in ulcerative colitis (UC) and Crohn’s disease (CD) are scarce. Therefore, we aimed to investigate the influence of administration of a supplementary dose of vedolizumab at week ten on short and long-term outcomes. Methods A retrospective two-center cohort study was conducted between November 2014 and November 2019. The primary outcomes were clinical remission (CR) at weeks 14, 30, 52, and 104 and Sustained CR (SCR) defined as CR at week 14 through week 52. Results The study included 182 patients (UC: 97, CD: 85), all previously exposed to at least one biological therapy. As shown in Table 1, patients with CD receiving or not receiving the additional dosing at week ten were comparable in terms of disease activity at weeks 0 and 6, while patients with UC receiving the dosing at week 10 experienced higher disease activity at week 0 but not week 6. The overall efficacy of vedolizumab in UC and CD stratified according to treatment with the optional dosing at week ten is summarized in Figures 1 and 2, demonstrating no statistically significant difference among patients receiving or not receiving vedolizumab at week 10. Furthermore, the optional dosing of vedolizumab at week 10 (odds ratio (OR)=0.23 (95%CI 0.03-1.17), and OR=0.68 (95%CI 0.22-2.04)), was not associated with CR at week 52 among patients with UC and CD, respectively. Conclusion Vedolizumab is effective in achieving short and long-term CR and SCR in patients with treatment-refractory UC and CD. This study emphasizes that supplementary dosing at week 10 did not improve long-term outcomes.

P304 Rational infliximab induction dosing to achieve long-term deep remission in children with Inflammatory Bowel Diseases

Abstract Background Adequate infliximab (IFX) trough concentrations (TCs) during induction treatment are predictive for long-term clinical and endoscopic remission in paediatric patients with inflammatory bowel diseases (IBD). However, under the approved weight-based dosing (5 mg/kg), children often have low IFX TCs, since the relationship between bodyweight and the IFX pharmacokinetic (PK) parameters is nonlinear. Therefore, there is a need to optimise paediatric dosing to engage optimal IFX TCs during induction treatment. Methods Fifty-two paediatric patients with IBD (34 Crohn’s disease (CD), 18 ulcerative colitis (UC)) contributed IFX samples (246 intermediate and 150 trough samples) during either induction treatment (n=32) or maintenance treatment (n=20). A population PK (popPK) model was developed to describe the relationship between IFX dose and exposure. The previously published IFX popPK model based on data of 112 children with CD in the Phase 3 REACH trial was used as a frequentist prior to inform parameter estimation using NONMEM. Our popPK model was used to simulate IFX TCs during induction treatment under different induction dosing regimens (5 mg/kg, 7.5 mg/kg, and 10 mg/kg IFX at weeks 0, 2, and 6). Probabilities of TC target attainment (PTA) were compared. The TC target, associated with a 75% probability of achieving deep remission (DR) at six months after initiating IFX treatment, was identified using a logistic regression model and a ROC analysis. DR was defined as combined endoscopic remission (Simple Endoscopic Score for CD &amp;lt;3 or Mayo endoscopic sub-score 0) and corticosteroid-free clinical remission (Paediatric CD or UC Activity Index &amp;lt;10). Results The median boyweight was 44 kg (range 15-92 kg). A 2-compartment popPK model with first-order elimination described IFX concentrations well (Table 1). The IFX clearance by weight increased with decreasing bodyweight, decreasing serum albumin and absence of immunomodulator combo-therapy. Also, the IFX volume of distribution in the central and peripheral compartment by weight increased with decreasing bodyweight. A total of 18/32 (56%) patients in the induction treatment achieved DR at six months. An IFX TC of 23.0 mg/L at week 6 was identified as the TC target (100% sen, 33% spe, 100% npv, and 50% ppv). Children with a bodyweight less than 30 kg could only reach a 50% PTA when receiving 10 mg/kg IFX combo-therapy during induction (Figure 1). While children with a bodyweight above 30 kg had more than 50% PTA when receiving either 10 mg/kg IFX monotherapy or 7.5 mg/kg IFX combo-therapy (Table 2). Conclusion IFX doses higher than 5 mg/kg are needed during induction in children with IBD to facilitate the attainment of the TC target, thereby increasing the chance of long-term DR.

P347 Vedolizumab as first line biologic therapy in elderly patients with contraindications against anti-TNF therapy - A real-world nationwide cohort of patients with inflammatory bowel diseases

Abstract Background Data regarding the efficacy and safety of vedolizumab as the first line of biologic therapy for elderly patients with ulcerative colitis (UC) and Crohn’s disease (CD) or patients with contraindications against anti-tumor necrosis factor antagonists (anti-TNFs) are scarce. Therefore, we aimed to investigate the short and long-term efficacy and safety of vedolizumab in patients with bio-naïve UC and CD stratified according to age. Methods A Danish nationwide cohort study was conducted between November 2014 and November 2019, including all bio-naïve patients receiving vedolizumab. The primary outcomes were clinical remission, steroid-free clinical remission, and sustained clinical remission defined as clinical remission at week 14 through week 52. Elderly patients were defined as patients aged 60 years or older at initiation of vedolizumab. Results The study included 56 patients (UC: 31 (55.4%), CD: 25 (44.6%)) with 15 (60.0%) and nine (47.4%) elderly patients with UC and CD, respectively. Elderly patients with UC and CD experienced higher rates of early response, remission, and steroid-free clinical remission, which, however, did not reach statistical significance (Figures 1 and 2). However, elderly patients with CD had similar long-term response as compared with younger patients. In the overall study population, lack of remission at week 52 was associated with female gender (p=0.01) in UC and ileal CD (p=0.03). Discontinuation due to primary non-response occurred in 20.0% and 5.3%, while rates of secondary loss of response were 12.0% and 5.3% after 26 weeks and 52 weeks, respectively. Only one UC patient, who developed a serious infection, experienced a serious adverse event during treatment with vedolizumab. However, mild adverse events were experienced by 35.5% and 8.0% of patients with UC and CD, respectively. As shown in Table 1, elderly patients experienced adverse events similar to the corresponding younger patients. Conclusion Vedolizumab is effective for induction of short and long-term sustained clinical remission in bio-naïve elderly and younger UC and CD patients with contraindications to anti-TNFs.

Clinical Analysis of Eight Cases of Pemphigus with High Titers of Anti-desmoglein Antibodies in Remission

Objective To investigate the clinical manifestations,diagnosis,treatment,and laboratory examination characteristics of 8 pemphigus patients with high titers of anti-desmoglein antibodies in remission. Methods A retrospective study was conducted for the pemphigus patients diagnosed and treated in the department of dermatology from January 2013 to September 2020.The patients should have the serum anti-desmoglein antibodies ≥150 U/ml in remission or the antibody levels dropped less than 20%(calculated based on the maximum detection limit of 150 U/ml)of their initial ones detected before treatment,and the clinical and laboratory data of patients eligible for the inclusion criteria were collected. Results Among the 134 pemphigus patients with available follow-up data during this period,a total of 8 patients met the criteria,with the follow-up period of 21-85 months and the remission duration of 18-70 months.They all received less than or equal to 10 mg/d prednisone and had high titers of anti-desmoglein antibodies.At their first visit,the number of patients with positive anti-desmoglein 1/desmoglein 3 antibodies was 7.Two patients still had high titers of anti-desmoglein 1 antibodies 19 months and 21 months after they achieved remission,and 5 patients had high titers of anti-desmoglein 3 antibodies in 18-70 months.There was one patient showing high titers of both antibodies,especially for anti-desmoglein 1 antibodies.This patient relapsed after 19 months' remission while other patients were still in clinical remission. Conclusions Some pemphigus patients showed persistent high titers of anti-desmoglein antibodies in remission.Anti-desmoglein 3 antibodies were more common to keep positive,while high titer of anti-desmoglein 1 antibodies was less observed.The high titer of anti-desmoglein 1 antibodies had a correlation with recurrence.For the pemphigus patients with long-term clinical remission but high antibody titer,the dosages of corticosteroids should be adjusted carefully according to their actual clinical manifestations and the positive antibody type.For the patients with high titer of anti-desmoglein 1 antibodies,the dosage reduction of corticosteroids should be appropriately slower.

End of Induction Patient-reported Outcomes Predict Clinical Remission but Not Endoscopic Remission in Crohn's Disease.

It is unclear whether early symptom improvement in Crohn's disease [CD] provides any prognostic information for patients long-term. This paper aims to investigate the relationship between early patient-reported outcomes [PROs] after completion of induction of infliximab, and their relationship with long-term clinical remission [CR] and endoscopic remission [ER]. This post-hoc analysis [Clinicaltrials.gov: NCT02096861] used data from 220 CD patients to evaluate the relationship of Weeks 6 and 14 PRO variables and Week 54 clinical remission (Crohn's Disease Activity Index [CDAI <150), PRO2 remission (mean score abdominal pain [AP] ≤1 and stool frequency [SF] ≤1.5), and endoscopic remission (Simple Endoscopic Score-CD [SES-CD <3). Multivariable logistic regression models adjusted for confounders were used to assess the relationships between post-induction PROs and outcomes of interest. Patients with moderate or severe AP after induction had reduced odds of achieving 1-year CR and PRO2 remission compared with those with mild AP (adjusted odds ratio [aOR] for CR 0.31, 95% confidence interval [CI] 0.17-0.57, p = 0.0002). Similarly, patients with moderately to severely elevated SF after induction had reduced odds of 1-year CR and PRO2 remission compared with patients with less SF [aOR for CR 0.31, 95% CI 0.16-0.58, p = 0.0003]. No significant differences were found when comparing higher Weeks 6 or 14 PRO scores of AP and/or SF with lower PRO scores in the odds of achieving 1-year ER. Post-induction PROs of AP and SF strongly predict likelihood of 1-year CR but are not associated with 1-year ER. Clinical symptoms alone should not be relied upon when assessing response to therapies for CD.

Striving towards Normality in Daily Life: A Qualitative Study of Patients Living with Metastatic Gastrointestinal Stromal Tumour in Long-Term Clinical Remission.

Background This study explored how patients with metastatic gastrointestinal stromal tumour (GIST) experience the psychosocial challenges associated with their disease and its treatment, as well as how that experience influenced their practical, relational, vocational, and existential life. Methods This qualitative study has an explorative design and applied a phenomenological and hermeneutical approach. We conducted in-depth, semistructured interviews with 20 patients with metastatic GIST in long-term clinical remission. The gathered data were interpreted using a thematic analysis. Results Living with metastatic GIST, as well as the side effects of the required medication, led to changes that limited the participants' daily life. They expressed how tiredness, impaired memory, and physical challenges were among the detrimental impacts of the disease on their family life, vocational life, social life, and leisure time. Adjustments were necessary to ensure they had sufficient energy to cope with the practical and relational aspects of everyday life. Feelings of uncertainty stemming from drug resistance, disease progression, and the possibility of early death were also experienced as challenging. Half the participants stated that it was difficult to keep negative mental health issues at bay, and all of them considered the time spent waiting for their scheduled follow-up scan to be burdensome. Conclusions It is important to focus increased attention on how the daily practical and psychosocial life of patients with chronic cancer, including metastatic GIST, is affected by their disease. Doing so might provide health-care workers with clues regarding how best to guide and support such patients throughout their emotional journey and, therefore, to improve their quality of life. As new medical treatments can also prolong survival and induce long-term clinical remission in relation to several other forms of metastatic cancer, the findings concerning GIST reported in this study might have widespread implications.

Fecal Microbiota Transplantation for Ulcerative Colitis: The Optimum Timing and Gut Microbiota as Predictors for Long-Term Clinical Outcomes.

INTRODUCTION:The previous researches aimed to evaluate the efficacy and safety of fecal microbiota transplantation (FMT) for ulcerative colitis (UC) in a short-term observation. The present study aimed to explore the optimum timing of FMT for maintaining the long-term clinical benefits and to target the gut microbiota that may help to predict the long-term success or failure of FMT in UC.METHODS:Two hundred two patients with UC were recruited from November 2012 to September 2018. The primary endpoint of this study was the maintaining time of the first and second courses of FMT. Relapse was defined as partial Mayo score ≥2 after achieving clinical remission and an increase of partial Mayo score ≥1 after achieving clinical response. The stool samples were analyzed by 16S rRNA gene sequencing.RESULTS:The median maintaining time of the efficacy was 120 days (IQR, 45–180) and 182.5 days (IQR, 105–311.25) from the first course and second course of FMT, respectively. No FMT-related serious adverse events were observed. The differences of the relative abundance in Eggerthella, Lactobacillus, and Ruminococcus between pre-FMT and 5 days post-FMT were remarkably correlated with the long-term clinical remission (P < 0.05).DISCUSSION:This study demonstrated that patients with UC should undergo the second course of FMT within 4 months after the first course of FMT for maintaining the long-term clinical benefits. The short-term alterations of microbiota after FMT may be conducive to predicting the long-term efficacy of FMT in UC (see Visual , Supplementary Digital Content, http://links.lww.com/CTG/A363).

Deficiency of CFHR plasma proteins and autoantibody positive hemolytic uremic syndrome: treatment rationale, outcomes, and monitoring.

Deficiency of Complement Factor H Related (CFHR) plasma proteins and Autoantibody Positive Hemolytic Uremic Syndrome (DEAP-HUS) is a subtype of atypical hemolytic uremic syndrome, known to be associated with significant morbidity. Its pathogenesis is linked to the production of IgG autoantibodies against complement factor H, a regulator of the alternative complement pathway. The binding of the autoantibodies to the C terminal of complement factor H interferes with its regulatory function, leading to increased activation of the alternative complement pathway and consequent endothelial cellular damage. Early diagnosis and initiation of appropriate therapy is reported to lead to favorable outcomes. Institution of plasma exchange therapy within 24h of diagnosis has been shown to rapidly lower antibody levels, leading to clinical improvement. Adjunctive immunosuppression therapy suppresses antibody production and helps in maintaining long-term clinical remission of the disease. Available data advocates a treatment regimen that combines plasma therapy (preferably plasma exchange) and immunosuppression to halt disease process and sustain long-term disease remission.

Bladder neck stenosis surgery in interstitial cystitis / bladder pain syndrome treatment

Introduction. Current methods of interstitial cystitis / bladder pain syndrome (IC/BPS) treatment dont allow to achieve long-term clinical remission.&#x0D; Aim of the study was to investigate the clinical efficacy of bladder neck transurethral incision (TUI) in women with IC/BPS, who had bladder outlet obstruction signs.&#x0D; Materials and methods. TUI was performed to patients with IC/BPS and proven bladder neck stenosis (n = 29). Assessment of the results of this operation was provided after 1, 3 and 6 months after surgical treatment. Treatment efficacy was evaluated by using Global Response Assessment (GRA) Scale, Pelvic Pain and Urgency / Frequency (PUF) Patient Symptom Scale, urination diaries, analysis of which allowed to determine functional bladder capacity, urinary frequency and nocturia. Pain assessment was made with 10-point Visual Analogue Pain Scale (VAS). Functional efficacy was evaluated with urodynamic examination, which included cystometric bladder capacity, maximal urinary flow rate and residual volume rate. Treatment results were compared with such in 39 patients with IC/BPS without signs of bladder neck stenosis.&#x0D; Results. GRA score 2 had 96.5% and 72.4% in 1 and 3 months after bladder neck TUI, respectively. VAS, PUF Scale parameters, cystometric bladder capacity, maximal urinary flow rate, residual volume rate, urinary frequency and nocturia values also significantly improved after surgery.&#x0D; Conclusions. This prospective clinical study is the first, in which IC/BPS course in women with bladder neck stenosis was investigated. It was noticed, that in 1 month after bladder TUI in 96.5% of patients decreased severity of IC/BPS symptoms, there were no urinary tract infection and local complications. In addition, this effect lasted for 3 months after surgery in 72.4% of patients and for 6 months in 68.9% of patients.

Lengthening adalimumab dosing interval in quiescent Crohn’s disease patients: protocol for the pragmatic randomised non-inferiority LADI study

IntroductionAdalimumab is effective for maintenance of remission in patients with Crohn’s disease (CD) at a dose of 40 mg subcutaneously every 2 weeks. However, adalimumab is associated with (long-term) adverse...

A71 MESOCAVAL SHUNT EMBOLIZATION AS A TREATMENT FOR MEDICALLY REFRACTORY HEPATIC ENCEPHALOPATHY IN A PATIENT WITH NON-DECOMPENSATED CIRRHOSIS

Abstract Background Hepatic encephalopathy (HE) is a common complication of cirrhosis with a spectrum of neuropsychiatric manifestations. In patients with medically refractory HE (i.e. after a trial of Lactulose with or without Rifaximin), it is warranted to investigate and manage underlying spontaneous portosystemic shunts (SPS) as a cause of chronic or recurrent HE in the absence of precipitants. Aims Here we present a case report of a patient with non-decompensated cirrhosis who underwent mesocaval shunt embolization as a treatment for medically refractory HE (grade III) in the absence of underlying precipitants. Methods The patient’s chart was reviewed and radiological images pre- and post- shunt embolization were obtained. A literature review was performed on the treatment of SPS for HE in cirrhosis. Results Mr. H is a 56-year-old man with alcohol-related cirrhosis who was admitted to the hospital with a reduced level of consciousness. On examination he was arousable but nonverbal. Asterixis was observed with no focal neurologic findings. Laboratory, infectious and toxicology results were negative. His MELD-Na score was 11. Computed tomography (CT) of his head and ultrasound of his abdomen were normal. The patient did not improve with lactulose and rifaximin. A CT of his abdomen/pelvis revealed a large SPS arising from the superior mesenteric vein (SMV) to the infrarenal inferior vena cava (IVC). A decision was made to attempt partial occlusion of the shunt. A 22-mm Amplatzer™ Vascular Plug II and two 8mm x 59mm Atrium balloon expandable covered stents were deployed in the right gonadal vein. Partial occlusion was subsequently demonstrated with contrast injection. The patient had gradual improvement of his HE and became independent for his ADLs six months post-procedure. Conclusions Between 45–70% of patients with cirrhosis and medically refractory HE have SPS as a result of chronic liver injury and increased portal venous pressures. AASLD guidelines recommend screening for SPS in cirrhotic patients with medically refractory HE or in HE with compensated liver disease. Shunt embolization in patients with MELD &amp;lt; 11 has been shown to reverse chronic or recurrent HE as well as improve hepatic outcomes for at least a two-year follow-up, as shown by a recent multicentre survey done by Laleman et al. Further studies have shown that portosystemic shunt embolization can result in reversal of HE in over 75% of cases. The most frequently encountered shunt in these studies is the splenorenal shunt. Our case, however, offers insight into the less commonly experienced mesocaval shunt, which accounts for only 5% of large SPS. We have shown that mesocaval shunts, when discovered, have the potential for successful treatment with embolization that can lead to reversal and long-term clinical remission of HE. Funding Agencies None

P467 Can induction and maintenance serum vedolizumab levels predict long-term clinical outcome in inflammatory bowel disease (IBD)?

Abstract Background Vedolizumab (VDZ) is an established IBD therapy, however, the role of therapeutic drug levels (TDM) is not fully established.1 Our aim was to assess whether week 6 and maintenance serum trough VDZ levels predict the clinical outcome at week 52. Methods A retrospective review of patients with Crohn’s disease (CD) or ulcerative colitis (UC) on VDZ was performed. Twenty-one IBD patients with serum VDZ trough level monitoring between January 2016 and December 2017 were identified. All patients received VDZ induction and maintenance as per standard protocol. Patients were excluded if complete dataset of VDZ levels was not available. Clinical remission was defined as a partial Mayo score &amp;lt; 2 for patients with UC or a Harvey–Bradshaw index (HBI) score &amp;lt; 4 for those with CD. A trough VDZ level ≥ 27 μg/ml cut-off was used to evaluate remission outcomes for both induction and average maintenance VDZ levels. Statistically, analysis was carried out using the Fisher exact test. Key demographics are 57% CD, 43% UC; Baseline HBI score: 11; Baseline Partial Mayo score: 9; Concurrent Immunomodulator: 55% Results: ( 1) Week 6 induction levels: At week 52, 69% of patients were in clinical remission. Those patients in remission had a higher mean and median trough VDZ levels (Figure A). When the induction serum trough VDZ level ≥ 27 μg/ml 30% more patients were in clinical remission at week 52, although this failed to reach statistical significance (p = 0.40) (Figure C). (2) Average maintenance VDZ levels: At week 52, 63% of patients were in clinical remission. Those patients in remission had a higher mean and median average maintenance trough VDZ levels (Figure B). When the average maintenance trough VDZ level was ≥ 27 μg/ml 17% more patients were in clinical remission, this failed to reach statistical significance (p = .0.39) (Figure D). Conclusion High levels of clinical remission in both CD and UC were seen. In our study, we could use a similar cut-off for induction trough VDZ levels to those used in the literature that correlated with positive outcomes.1 Although the observed levels used to predict remission did not reach statistical significance, this may represent a type 2 error in view of the small numbers of patient. Furthermore, it was not possible to assess whether there is a difference between CD and UC. For maintenance levels, our cut-off of 27 μg/ml was higher than that used in the literature that correlated with positive outcomes.1 Our data suggest there is some correlation between trough VDZ levels for both induction and average maintenance levels and long-term clinical remission. Our induction cut-off was similar to currently available data associated with positive outcomes.1 Further studies are required to fully establish the role of TDM. References

Normalization of long-term quality of life in Crohn's disease patients receiving ustekinumab.

ustekinumab is a fully human monoclonal antibody against IL-12/23, approved for induction and maintenance treatment of Crohn's disease (CD). Real-life data shows its true effectiveness in terms of clinical and endoscopic response. However, there is little information regarding health-related quality of life (HRQoL) in CD patients receiving ustekinumab. The main aim of this study was to define long-term clinical remission and HRQoL normalization. The clinical predictive factors of clinical remission were investigated as a secondary aim. a retrospective, observational study was performed in CD patients under ustekinumab treatment in the Hospital Vall d'Hebron, between January 2009 and January 2019. Clinical remission was defined using the Crohn's Disease Activity Index (CDAI) and HRQoL normalization was defined by the 36-item Inflammatory Bowel Disease Questionnaire (IBDQ). thirty-three patients were included. The average disease evolution was eleven years (standard deviation [SD]: 8), perianal disease was present in 13 patients (39 %), 30 patients (91 %) had previously been treated with alfa tumor necrosis factor antagonists (anti-TNF) agents and 22 patients (67 %) had a history of intestinal resection. Twenty-four patients (73 %) had undergone one year of treatment. Seventeen patients (51 %) reached clinical remission and six (18 %) restored the HRQoL. No predictors of clinical remission were identified. ustekinumab shows clinical effectiveness in real-life conditions similar to previous data. Normalization of HRQoL is low compared to clinical remission, which may be due to the inaccuracy of the indicator and the severe disease course. Such normalization is a challenge for physicians dealing with inflammatory bowel diseases.

Heterogeneity of clinical management of low-grade gastric lymphoma of mucosa-associated lymphoid tissue. An audit of 198 patients in Spain

IntroductionCure of Helicobacter pylori infection in patients with gastric lymphoma of mucosa-associated lymphoid tissue (MALT) leads to long-term clinical remission in the initial stages. As it is a rare disease, its management in clinical practice remains largely unknown and heterogeneity of care remains a concern.The aim was to audit the management and evolution of a large series of low-grade gastric MALT lymphomas from thirteen Spanish hospitals. Materials and methodsMulticentre retrospective study including data on the diagnosis and follow-up of patients with gastric low-grade MALT lymphoma from January 1998 to December 2013. Clinical, biological and pathological data were analyzed and survival curves were drawn. ResultsOne-hundred and ninety-eight patients were included. Helicobacter pylori was present in 132 (69%) patients and 103 (82%) in tumors confined to the stomach (stage EI) and was eradicated in 92% of patients. Chemotherapy was given in 90 (45%) patients and 43 (33%) with stage EI. Marked heterogeneity in the use of diagnostic methods and chemotherapy was observed. Five-year overall survival was 86% (89% in EI). Survival was similar in EI patients receiving aggressive treatment and in those receiving only antibiotics (p=0.577). DiscussionGastric MALT lymphoma has an excellent prognosis. We observed, however, a marked heterogeneity in the use of diagnostic methods or chemotherapy in early-stage patients.

772 Long-Term Mucosal Healing, Clinical Response and Clinical Remission in Patients With Ulcerative Colitis Treated With the Anti-MAdCAM-1 Antibody Ontamalimab: Results From the Open-Label Extension Study TURANDOT II

INTRODUCTION: Ontamalimab (SHP647), a human monoclonal IgG2 antibody, targets mucosal addressin cell adhesion molecule-1 (MAdCAM-1), to reduce lymphocyte homing to the gastrointestinal (GI) tract. In the TURANDOT II trial, ontamalimab was well-tolerated and clinical benefit was seen up to 144 wks in patients with ulcerative colitis (UC). Here we report long-term mucosal healing, response and remission in a subset of patients in TURANDOT II. METHODS: TURANDOT II (NCT01771809) is a phase 2, 2-part open-label (OL) extension study of ontamalimab in patients with UC who received placebo or ontamalimab 7.5, 22.5, 75 or 225 mg in the feeder study (TURANDOT). At TURANDOT II baseline (TURANDOT wk 12), patients were randomized to ontamalimab 75 or 225 mg every 4 wks for 72 wks (OL1). In cases of clinical exacerbation or no response, escalation from 75 to 225 mg was permitted from wk 8. In OL2, patients received 75 mg every 4 wks for 72 wks. Endoscopies were carried out at wk 16, and a subset of patients undergoing routine cancer surveillance had at least one follow-up endoscopy between wks 40 and 72 of OL1: all endoscopies were centrally-read. Mucosal healing (Mayo endoscopy subscore ≤1), clinical remission (total Mayo score ≤2, no subscore &gt;1) and clinical response (≥3-point decrease in total Mayo score from TURANDOT baseline, ≥30% change; ≥1-point decrease in or ≤1 rectal bleed absolute score) were measured. RESULTS: Of 330 patients in TURANDOT II, 101 had follow-up endoscopies (Table 1), 25.7% (n = 26) of whom had mucosal healing at TURANDOT II baseline. At wk 16, 43.6% (n = 44) had mucosal healing, and 33 of these patients (75%) maintained mucosal healing up to wk 40–72. Of 65 responders in TURANDOT, 37 (56.9%) had mucosal healing at both wk 16 and wk 40–72. Of 36 non-responders, 7 (19.4%) and 9 (25%) achieved mucosal healing at wk 16 and wk 40–72, respectively (Figure 1). Of the responders, 58 (89.2%) maintained response and 27 (41.5%) were in remission at wk 16; at wk 40–72, 53 (81.5%) maintained response and 33 (50.8%) were in remission. Of non-responders, 22 (61.1%) achieved response and 5 (13.9%) achieved remission by wk 16; by wk 40–72, 17 (47.2%) had responded and 8 (22.2%) were in remission. Overall, the mean Mayo endoscopic subscore of 2 (SD, 0.1) was maintained to wk 40–72. CONCLUSION: Mucosal healing, response and remission persisted in a subset of patients who continued ontamalimab treatment up to 72 wks and underwent surveillance endoscopies between wks 40 and 72.