Mayo Clinic Score Research Articles

P588 Interim results from the randomised VERDICT trial to determine the optimal treatment target in patients with ulcerative colitis

Abstract Background The optimal treatment target for ulcerative colitis (UC) is uncertain. The VERDICT trial in moderate to severe UC aims to determine if a treatment target of corticosteroid (CS)-free symptomatic + endoscopic + histologic remission is superior to CS-free symptomatic remission alone. Trial progress and the study cohort to date are described herein. Methods Our aim is to enrol 660 patients with moderately to severely active UC (Mayo rectal bleeding subscore [RBS] ≥1; Mayo endoscopic score [MES] ≥2). Patients are randomised to 3 treatment targets (2:3:5 ratio): CS-free symptomatic remission (Mayo RBS = 0) (Group 1); CS-free endoscopic remission (MES ≤1) + symptomatic remission (Group 2); or CS-free histologic remission (Geboes score <2B.0) + endoscopic + symptomatic remission (Group 3). Therapy is administered according to a treatment algorithm that is dependent upon each patient’s UC treatment at screening. Early introduction of vedolizumab (VDZ) and dose escalation up to 300 mg every 4 weeks until the target is met are central to each algorithm. Up to 3 opportunities to achieve the assigned target were prespecified in the algorithms (weeks 16, 32, or 48). Patients and central readers for endoscopy/histopathology are blinded to group allocation, and investigators are unblinded. Results As of 2 November 2022, 331 patients were enrolled at 55 sites across 10 North American and European countries. Mean (SD) baseline characteristics (Table) include a UC duration of 8.6 (8.3) years, Mayo Clinic score of 8.7 (1.7), C-reactive protein level of 13.3 (15.6) mg/dL, and a faecal calprotectin level of 1462.3 (1481.3) mg/kg. At baseline, 52% (172/331) and 11% (37/331) of patients were receiving concomitant CS and immunosuppressives, respectively, and 14% (47/331) had current/prior exposure to tumour necrosis factor antagonists. Most patients (85%) were receiving nonbiologic therapy. Of all randomised patients, 43/69 (Group 1), 65/98 (Group 2), and 115/164 patients (Group 3) have reached week 16; and 28 (65%), 25 (39%), and 42 (37%) met their target, respectively. After a median of 35 weeks (IQR 18-53), a total of 30 (Group 1), 32 (Group 2), and 50 patients (Group 3) have met their target and will be followed to relapse or study termination. The serious adverse event rate (8%; 36/483) was similar across groups. Conclusion VERDICT has randomised ~50% of its target enrolment. Enrolled patients represent a typical moderate to severe UC population and are primarily bionaive and receiving early VDZ initiation. Early results suggest the feasibility of achieving each treatment target, specifically histologic remission, and are consistent with expected values. No new VDZ safety signals were identified. Completion of enrolment is anticipated in late 2023.

P713 Proactive therapeutic infliximab monitoring during induction phase in inflammatory bowel disease

Abstract Background Therapeutic drug monitoring (TDM) of infliximab (IFX) in patients with Crohn’s disease (CD) and ulcerative colitis (UC) is increasingly used in clinical routine, although proactive TDM is still controversial. Nevertheless, disease activity and drug clearance are higher at the induction phase leading to an increased risk of inadequate drug exposure and treatment failure. The aim of the study was to evaluate the efficacy of the implementation of an early proactive TDM strategy, comparing clinical remission (CR) and biochemical remission (BR) at week 14 and 52, and endoscopic improvement (EI) between two groups. Methods Retrospective cohort study conducted in an Inflammatory Bowel Disease (IBD) unit of a tertiary care hospital. Biologic-naïve patients diagnosed of CD or UC who initiated IFX from 2019 to 2021 (p-TDM group) and from 2016 to 2019 (no-TDM group) were included. In the p-TDM group, proactive IFX trough levels and antidrug antibodies were measured since week 2 and dose adjustment since week 6 was performed using a previously validated population pharmacokinetic model (Fasanmade et al. Clinical Therapeutics 2011). In the no-TDM group, dose escalation was performed considering symptoms, blood, or stool results. CR was defined as Harvey-Bradshaw Index <5 in CD and partial Mayo clinic score <3 in UC. BR was stablished as fecal calprotectin (FCP) <150 mcg/g or c-reactive protein <0.5 mg/dL. EI was defined as lack of ulcerations in CD and Mayo endoscopic score 0-1 in UC. A combined variable to evaluate objective remission (OR) at week 52 was defined as: FCP <150 mcg/g or EI in UC, and EI or radiologic improvement (MRI) in CD. Moreover, surgery, hospitalization and treatment discontinuation rates were compared between both groups. Results 30 patients were included in each group: 13 UC, 16 CD and 1 IBD unclassified. There were no statistical differences in baseline characteristic between groups (table 1). Outcomes at week 14 and 52 are shown in table 2. At week 14, CR rate was significantly higher in p-TDM than in no-TDM (86.7% vs 56.7%, p=0.01). Although BR rate at week 14 was numerically higher in p-TDM, it did not achieve statistical significance (61.1% in p-TDM vs 50.0% in no-TDM, p=0.59). However, limitations in blood and stool collection were considerable at this timepoint. During first year, hospitalizations tend to be fewer in p-TDM group. There were no statistically differences in CR and BR or in EI between groups at week 52. Although OR rate was higher in p-TDM than in no-TDM, it did not reach statistical significance (60.9% vs 33.3%, p=0.06). Conclusion Proactive TDM during induction phase, especially in naïve patients, could be a useful tool to obtain optimal IFX trough levels and to classify correctly primary failure.

Intralesional Steroid Injection Versus Extracorporeal Shockwave Therapy in the Treatment of Plantar Fasciitis: A Comparative, Prospective, Case Series Study.

Background This study aimed to compare and evaluate the outcomes of intralesional steroid injections (ultrasound-guided) versus extracorporeal shockwave therapy in the treatment of plantar fasciitis. Methodology Between January 2021 and March 2022, 120 (84 male, 36 female) patients with a confirmed diagnosis of plantar fasciitis were identified. Subjective assessment was done using Mayo Clinical Score, and objective evaluation was done by measuring plantar fascia thickness using ultrasonography. For this study, two groups were made, wherein group A was administered a high dose of extracorporeal shockwave therapy, and group B was administered ultrasound-guided intralesional or local steroid injections. Results Plantar fascia thickness was considerably reduced after therapy in both groups; however, the difference in thickness reduction was not statistically significant between both groups. Mayo Clinic Scores showed statistically significant improvement in pain; however, the difference in pain reduction was not statistically significant between both groups. Conclusions A considerable clinical and radiological improvement was noted in both groups; however, we did not record statistically significant and superior results in either group. Intralesional steroid injections provided faster clinical improvement and better patient compliance.

Assessing the Clinical and Endoscopic Efficacy of Extended Treatment Duration with Different Doses of Mesalazine for Mild-to-Moderate Ulcerative Colitis beyond 8 Weeks of Induction

Introduction: High-strength mesalazine formulations play an important role in providing a convenient option to increase the dose in ulcerative colitis (UC) patients and therefore avoiding the switch to another therapeutic class. Higher doses of mesalazine may be required during periods of remission in order to prevent relapse. Aim: The aim of the study was to investigate clinical outcomes of three mesalazine maintenance doses adapted for post induction response. Methods: In this post hoc analysis, 675 UC patients entered an open-label extension study for a total of 38 weeks (including 8–12 week induction period with 3.2 g/day mesalazine). After the induction period, they were separated into three groups: remitters (in clinical and endoscopic remission), responders (decrease in Partial Mayo Clinic Score of ≥2 points and ≥30% from week 0), and nonresponders (failed to achieve endoscopic or clinical response at week 8) and received 1.6 g/day, 3.2 g/day, or 4.8 g/day of mesalazine (using a new 1,600 mg mesalazine tablet), respectively. Results: 133/202 (65.8%), 108/274 (39.4%), and 59/199 (29.6%) patients achieved clinical and endoscopic remission at week 38 with 1.6 g/day, 3.2 g/day, and 4.8 g/day, respectively. At week 38, 142/202 (70.3%), 93/274 (33.9%), and 61/199 (30.7%) patients achieved clinical remission (stool score of 0 and rectal bleeding score of 0) with 1.6 g/day, 3.2 g/day, and 4.8 g/day, respectively. Conclusions: Patients partially responding or not responding to an initial induction dose of 3.2 g/day mesalazine could benefit from an extended treatment period at the same dose, or an increase to 4.8 g/day in an attempt to achieve combined clinical and endoscopic remission.

Lateral elbow ligament reconstruction for posterolateral rotatory instability: 10 years follow-up in 32 patients

Posterolateral rotatory instability (PLRI) is the most frequent form of both acute and chronic elbow instability. It is due to mechanical incompetence of the lateral collateral ligament. O'Driscoll etal described treatment of this instability by autologous reconstruction of the lateral ulnar collateral ligament. The aim of our study was to evaluate the medium and long-term clinical, functional and radiological results of patients who were surgically treated for PLRI by this technique. We hypothesized that such ligament reconstruction restores a functional joint complex and durably stabilizes the elbow and limits the long-term risk of osteoarthritis. All patients treated for symptomatic PLRI by ligament reconstruction since January 1995 and who had a minimum follow-up of 36 months were retrospectively included. Thirty-two patients (32 elbows) underwent clinical and radiological evaluation with a mean follow-up of 112 months (range, 36-265 months). The success rate of the procedure was 97% with one patient requiring revision reconstruction. Twenty-four patients (75%) were free from pain. Pain was significantly greater in patients with associated lesions (P=.03) and those with morbid obesity (body mass index ≥40) (P=.03). Twenty-nine (91%) patients had resumed their previous activities. Twenty-eight patients (87%) were satisfied or very satisfied. The mean Mayo Clinic score was 96/100 and the QuickDash 14.7/100. Two patients (6%) with accompanying lesions developed severe osteoarthritis. Elbow ligament reconstruction by the technique of O'Driscoll etal effectively restores stability and limits progression to osteoarthritis in the long term. The only failure in our series was due to several technical errors. Patients who had dislocation with associated lesions or morbid obesity are at risk of poorer functional results.

MM-219 Smoldering Multiple Myeloma: A Demographic and Survival Analysis of a Retrospective Cohort Study in a University Hospital of Buenos Aires

Smoldering multiple myeloma (SMM) is a heterogeneous asymptomatic precursor to multiple myeloma (MM). It is the intermediate stage between monoclonal gammopathy of undetermined significance (MGUS) and MM, where there is a subset of patients with an indolent disease and a subset with progressive disease. The Mayo Clinic published a risk stratification model to help to differentiate these patients into 3 groups. To describe the demographic features of patients with SMM treated at the Italian Hospital of Buenos Aires. Retrospective cohort study, between 01/2005 and 05/2022. Consecutive patients with a confirmed diagnosis of SMM were included. Patients were followed from diagnosis until death, progression or loss to follow-up. Thirty-nine patients with SMM were included, of whom 16 (41%) were men. The median age at diagnosis was 69 years (95% CI: 55-77). 25 (64%) had a previous MGUS; the median time to progression (TTP) from MGUS to SMM was 6.4 months. 19 (49%) of patients had progression to MM. Eight (20%) of patients died, 3 (37%) secondary to myeloma. The most common type of band was IgG kappa with 55%. The median of monoclonal band was 1.5 (CI: 1.2-2), the median of plasma cells in bone marrow biopsy was 15% (CI: 12-20), 29 patients (74.36%) presented evaluation of lytic lesions, 6 patients (15%) presented risk assessment by FISH, of which 2 were positive for del(17p). The median follow-up of the cohort was 92 months (95% CI: 72.4-127.2). The estimated median TTP for the entire cohort was 71 months (95% CI, 55-94). Eight (21%) patients presented a high risk of progression according to the Mayo clinic score. The median TTP according to the Mayo Clinic score was 44 months (CI: 27-62) for high-risk patients, 86.5 months (CI: 69-94) for intermediate-risk patients, and 75 months for low risk. Of the patients who presented del(17p) all progressed to myeloma during follow-up with a median TTP of 49 months (CI: 35-64). 1 patient entered the research protocol. Our cohort demonstrated characteristics similar to those published. Patients with high-risk Mayo score and del(17p) by FISH showed faster progression, which emphasizes the need to include them in research protocols.

Rapid and Sustained Symptom Relief in Patients With Ulcerative Colitis Treated With Filgotinib: Data From the Phase 2b/3 SELECTION Trial.

Patients with ulcerative colitis (UC) regard rapid onset of action among the most important aspects of their treatment. We used the partial Mayo Clinic Score (pMCS) and component patient-reported subscores to assess the rapidity and sustainability of response to filgotinib, a once-daily, oral Janus kinase 1 preferential inhibitor, in adults with moderately to severely active UC in the phase 2b/3 SELECTION trial. The association between early symptomatic improvements and health-related quality of life (HRQoL) outcomes was also assessed. In these post hoc analyses of the double-blinded, randomized, placebo-controlled 58-week SELECTION trial (NCT02914522), rectal bleeding and stool frequency diary data on days 1-15 and pMCS remission and response at multiple time points including weeks 10 and 58 were evaluated. HRQoL was assessed using the Inflammatory Bowel Disease Questionnaire at weeks 10 and 58. Filgotinib 200 mg relative to placebo improved rectal bleeding and stool frequency within 7 days ( P < 0.05). By week 2, greater proportions of filgotinib 200 mg-treated patients than placebo-treated patients achieved pMCS remission (biologic-naive, 15.1% vs 8.0%, P = 0.0410; biologic-experienced, 10.3% vs 4.2%, P = 0.0274). A similar treatment effect was observed at week 58 ( P < 0.0001). Day 7 rectal bleeding and stool frequency subscores were associated with the Mayo Clinic Score response at weeks 10 and 58. Patients in pMCS remission at weeks 10 and 58 had greater improvements in the Inflammatory Bowel Disease Questionnaire score than those not in pMCS remission. Filgotinib 200 mg daily resulted in rapid and sustained improvements in both UC symptoms and HRQoL.

Early fecal microbiome transfer after donor defecation determines response in patients with moderate to severe ulcerative colitis.

Fecal microbiome transfer (FMT) targeting gut microbiome dysbiosis is an emerging therapy for ulcerative colitis (UC). There is however no consensus on protocols for performing FMT in UC, especially in relation to time after donor feces defecation. This is a single-center retrospective analysis of patients with moderate-severe UC (total Mayo Clinic score ≥6 and endoscopic Mayo Clinic subscore of ≥2) treated with FMT between September 2017 and December 2019 at Dayanand Medical College and Hospital, Ludhiana,India. Fresh fecal samples from unrelated healthy voluntary donors were administered through colonoscopy at weeks 0, 2, 6, 10, 14, 18, and 22. Time interval between donor feces defecation and FMT procedure was recorded for each FMT session and the mean time of seven sessions was designated aika. Impact of aika on clinical response and safety of FMT was evaluated. During the study period, 123 adult patients (mean age 33.75±11.97 years, 61.8% [n=76] males) with moderate-severe UC (mean total Mayo Clinic and endoscopic Mayo Clinic scores 7.49±1.60 and 2.50±0.50, respectively) were treated with FMT. The mean aika was 2.29±0.75 h. The aika was smaller in patients who responded to FMT as compared to non-responders (2.13±0.75h vs. 2.71±0.76 h, p=0.0002) as well as in patients achieving clinical remission (2.15±0.76 h vs. 2.42±0.76 h, p=0.05). There was no significant impact of aika on adverse effects except forthe incidence of borborygmi after FMT, which was higher in patients with aika ≤2 h. Early FMT after donor feces defecation favorably impacts the clinical response rates in patients with active UC.

Anemia in Patients with Ulcerative Colitis in Remission: A Cross-Sectional Study from Pakistan

Background and Aim: Anemia is an extra intestinal manifestation of inflammatory bowel disease that frequently causes complications. In inflammatory bowel disease (IBD) such as ulcerative colitis and Crohn’s disease, anemia is mostly caused by iron deficiency which impacts the patient's quality of life [1, 2]. The present study aimed to assess the anemia in ulcerative colitis patients in remission. Methodology: A cross-sectional study was conducted on 82 ulcerative colitis patients at the Department of Medicine and Gastroenterology, Jinnah hospital, Lahore from February 2021 to January 2022. All the patients were assessed for anemia based on Mayo clinical score &lt;3 for at least three months. Hemogram tests such as CBC, vitamin B12 serum levels, ferritin, folic acid levels, concentration of C - reactive protein (CRP), and transferrin were performed for the initial screening. Further, patients were evaluated for the determination of different causes of anemia. Patients were categorized into mild, moderate, and severe anemia cases. Oral iron, intravenous iron, and blood transfusion were given to mild, moderate, and severe anemia patients respectively. SPSS version 25 was used for data analysis. Results: Of the total 82 ulcerative colitis patients, there were 48 (58.5%) male and 34 (41.5%) females. The prevalence of anemia in ulcerative colitis patients and control was 51.2% (n=42) and 11.9% (n=5) respectively. The hemoglobin mean values in UC patients and control was 11.95 g/dL and 13.21 g/dL respectively. Out of 42 ulcerative colitis patients, the prevalence of mild, moderate, and severe anemia was 52.4% (n=22), 35.7% (n=15), and 11.9% (n=5) respectively. Iron deficiency was the prevalent etiology of anemia found in 22 (52.4%) patients followed by chronic anemia disease with iron deficiency found in 8 (21.9%). Hemoglobin level has no association with ferritin level. Hemoglobin level has no association with ferritin level. The hemoglobin level was increased with oral iron and intravenous iron by 1.6 g/dL and 2.3 g/dL respectively. Conclusion: The present study concluded that prevalence of anemia was higher in ulcerative colitis patients. The most common etiology of anemia was iron deficiency in both groups. Increased CRP and moderate activity associated to anemia disease was significantly related with comorbid anemia. Oral iron and intravenous iron could increase hemoglobin levels in ulcerative colitis associated anemia patients. Keywords: Anemia, Ulcerative Colitis, Iron deficiency

Exposure-response relationships of etrolizumab in patients with moderately-to-severely active ulcerative colitis.

Etrolizumab is an IgG1‐humanized monoclonal anti‐β7 integrin antibody. Phase III trials with induction and/or maintenance phases were conducted in patients with moderately‐to‐severely active ulcerative colitis (UC) who were either previously treated with tumor necrosis factor (TNF) inhibitors (HICKORY) or were TNF inhibitor naïve (HIBISCUS I/II, LAUREL, and GARDENIA). A total of eight exposure‐response analyses were conducted for two clinical outcomes (remission and endoscopic improvement) at the end of induction for studies HIBISCUS I/II (combined) and HICKORY and at the end of maintenance for studies HICKORY and LAUREL. Trough concentration at week 4 (C trough,wk4) of induction was selected as the exposure metric. Exposure‐response (ER) modeling was conducted using logistic regression. A full covariate model was used to examine the impact of covariates on clinical outcomes. Linear models with a single intercept for placebo and active treatments adequately described the data for all eight analyses. The etrolizumab exposure‐response slope was significant (p < 0.05) for seven of the eight analyses. Baseline Mayo Clinic Score (MCS) was the only statistically significant covariate that impacted induction remission and endoscopic improvement. No statistically significant covariate was identified to impact maintenance outcomes except for baseline fecal calprotectin on endoscopic improvement for LAUREL study. A statistically significant positive ER relationship was identified for most of the clinical outcomes tested, reflecting a better treatment effect in patients with UC with higher etrolizumab C trough,wk4 of induction. Baseline MCS was the only other significant covariate impacting induction efficacy. Besides C trough,wk4 of induction, no consistent covariate was identified to impact maintenance efficacy.

CORE-IBD: A Multidisciplinary International Consensus Initiative to Develop a Core Outcome Set for Randomized Controlled Trials in Inflammatory Bowel Disease

End points to determine the efficacy and safety of medical therapies for Crohn's disease (CD) and ulcerative colitis (UC) are evolving. Given the heterogeneity in current outcome measures, harmonizing end points in a core outcome set for randomized controlled trials is a priority for drug development in inflammatory bowel disease. Candidate outcome domains and outcome measures were generated from systematic literature reviews and patient engagement surveys and interviews. An iterative Delphi process was conducted to establish consensus: panelists anonymously voted on items using a 9-point Likert scale, and feedback was incorporated between rounds to refine statements. Consensus meetings were held to ratify the outcome domains and core outcome measures. Stakeholders were recruited internationally, and included gastroenterologists, colorectal surgeons, methodologists, and clinical trialists. A total of 235 patients and 53 experts participated. Patient-reported outcomes, quality of life, endoscopy, biomarkers, and safety were considered core domains; histopathology was an additional domain for UC. In CD, there was consensus to use the 2-item patient-reported outcome (ie, abdominal pain and stool frequency), Crohn's Disease Activity Index, Simple Endoscopic Score for Crohn's Disease, C-reactive protein, fecal calprotectin, and co-primary end points of symptomatic remission and endoscopic response. In UC, there was consensus to use the 9-point Mayo Clinic Score, fecal urgency, Robarts Histopathology Index or Geboes Score, fecal calprotectin, and a composite primary end point including both symptomatic and endoscopic remission. Safety outcomes should be reported using the Medical Dictionary for Regulatory Activities. This multidisciplinary collaboration involving patients and clinical experts has produced the first core outcome set that can be applied to randomized controlled trials of CD and UC.

Epstein-Barr Virus and Human Cytomegalovirus Infection in Intestinal Mucosa of Chinese Patients With Inflammatory Bowel Disease.

ObjectiveThis study aimed to determine the frequency of Epstein–Barr virus (EBV), cytomegalovirus (CMV) in mucosa and blood of inflammatory bowel disease (IBD) patients in China and evaluate their correlation with the clinical disease activities.MethodsPeripheral blood and endoscopic fresh colonic mucosal samples were collected from a cohort of 287 IBD patients and 50 controls. Viral DNA load was analyzed through quantitative real-time PCR. The clinical disease activity of ulcerative colitis (UC) and Crohn’s disease (CD) was assessed by the Mayo Clinic Score and Crohn’s disease activity index, respectively.ResultsAmong 287 IBD patients, 228 (79.4%) were positive for EBV and 99 (34.5%) were positive for CMV. EBV and CMV infection rates are significantly higher than those in the control group (28.0%, p < 0.05; 4.0%, p < 0.05). In addition, EBV/CMV prevalence increases as clinical activities progress [For EBV infection, the prevalence was 53.93% (48/89) in the mild group, 87.00% (87/100) in the moderate group, and 94.90% (93/98) in the severe group; and for CMV infection, the prevalence was 3.37% (3/89) in the mild group, 27.00% (27/100) in the moderate group, and 70.41% (69/98) in the severe group]. EBV and CMV loads are related to clinical disease activities (p < 0.05). In addition, viral load in the intestinal mucosa of patients with acute exacerbation of IBD is higher than that of patients in remission.ConclusionHigh prevalence of EBV and CMV is found in patients with IBD, and their prevalence is related to clinical disease activities. In addition, the viral load in the intestinal mucosa is associated with the status of mucosa in the same patients (active phase versus remission phase). Detection of viral load on mucosal specimens with quantitative real-time PCR is a feasible method to monitor EBV and CMV infection in IBD patients.

Predictive value of faecal calprotectin in ulcerative colitis – single centre experience

Objectives Faecal calprotectin is an important biomarker used in the evaluation of inflammatory bowel disease. The aim of this study was to establish the value of faecal calprotectin concentration as a predictor of remission in ulcerative colitis and its correlation with laboratory, endoscopic and clinical findings. Methods The single centre study included 126 adult patients with established diagnosis of ulcerative colitis consecutively visiting our Day clinic from March 2017 to March 2019. We measured serum biomarkers- CRP, haemoglobin, leukocytes and platelets. Faecal calprotectin was determined from stool, and endoscopy was performed with calculation of MAYO endoscopic subscore system (MES 0–1: remission, and MES 2–3: active disease). Clinical assessment was done by using Mayo score for ulcerative colitis (clinical Mayo score <2:remission, >5: active disease).The statistical analysis was performed using an univariate and multivariate model of disease remission prediction using logistic regression. Results According to univariate analysis the increase of faecal calprotectin concentration by 10 ug/g is associated with an 8% decrease in probability of disease remission (OR 0.9921, p < .05). In the multivariate analysis, faecal calprotectin remained a significant predictor of disease remission (OR 0.9948, 95% CI 0.9914–0.9982, p = .0028), however, with a significant contribution of C-reactive protein (OR 0.8340, 95% CI 0.7085–0.9818, p = .0292). According to our model the cut off value for faecal calprotectin was 154 ug/g. Conclusion Our results have shown that faecal calprotectin is an independent predictor of remission in UC patients. The results of our study represent real-life data from a single university centre dealing with FC as a prognostic marker in patients with UC. KEY MESSAGES Faecal calprotectin is an independent predictor of remission in UC patients. Recent studies have suggested that calprotectin correlates well with endoscopic activity of inflammation but correlation of faecal calprotectin in a phase of remission hasn’t been evaluated yet. We have found that other inflammatory biomarkers do not correlate well with either endoscopic or clinical activity in ulcerative colitis.

Efficacy, safety, and predictors of response to infliximab therapy for ulcerative colitis

Background Using infliximab (IFX), an antitumor necrosis factors antibody, has dramatically increased therapeutic choices for ulcerative colitis (UC). This study assessed IFX therapy’s efficacy, safety, and action predictor variables for UC. Patients and methods This prospective interventional study was done on 50 patients with UC. Patients underwent colonoscopy, biopsy, complete blood count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) before start of IFX and after 8 weeks. Patients started 5 mg/kg IFX infusion at 0, 2, and 6 weeks and then every eight weeks. After 6 months, cases were subjected to colonoscopy, biopsy, CRP, complete blood count, and ESR to assess IFX therapy. Results After therapy, hemoglobin and inactive UC cases (90%) increased significantly and white blood cell, ESR, and CRP decreased significantly than before treatment, without significant difference in platelet count. IFX treatment was associated with improvement in 90% of cases. There was a significant relation between improvement and colonoscopy, histopathology finding, and CRP after treatment (P&lt;0.001) as the majority of cases had inactive UC, UC chronic phase with mild inflammation, and negative CRP after therapy. There was a nonsignificant relation between improvement and disease extension and severity (mayo clinic score) after the period. Conclusions Active UC cases treated by IFX had a better mucosal healing and clinical responses, corrected of anemia and thrombocytopenia and normalized acute-phase reaction.

AJM300 (carotegrast methyl), an oral antagonist of α4-integrin, as induction therapy for patients with moderately active ulcerative colitis: a multicentre, randomised, double-blind, placebo-controlled, phase 3 study

AJM300 is an oral, small-molecule α4-integrin antagonist. We assessed the efficacy and safety of AJM300 in patients with moderately active ulcerative colitis. This multicentre, randomised, double-blind, placebo-controlled, phase 3 study consisted of two phases: a treatment phase and an open-label re-treatment phase. The study was done at 82 hospitals and clinics in Japan. Patients with a Mayo Clinic score of 6-10, endoscopic subscore of 2 or more, rectal bleeding subscore of 1 or more, and an inadequate response or intolerance to mesalazine were enrolled. Patients were randomly allocated (1:1) via a website to either AJM300 (960 mg) or placebo by the minimisation method, which was adjusted centrally by dynamic assignment against the Mayo Clinic score (≥6 to ≤7, ≥8 to ≤10 points), any use of corticosteroid, anti-TNFα antibody, or immunosuppressants during the disease-active period (yes vs no), duration of induction therapy until randomisation (<4 weeks vs ≥4 weeks) as the minimisation factors. Patients, investigators, site staff, assessors, and the sponsor were masked to treatment assignments. The study drug was administered orally, three times daily, for 8 weeks, and continued for up to 24 weeks if endoscopic remission was not achieved or rectal bleeding did not stop. The primary endpoint was the proportion of patients with a clinical response at week 8, and was analysed in the full analysis set. Clinical response was defined as a reduction in Mayo Clinic score of 30% or more and 3 or more, a reduction in rectal bleeding score of 1 or more or rectal bleeding subscore of 1 or less, and an endoscopic subscore of 1 or less at week 8. The study is registered with ClinicalTrials.gov, NCT03531892, and is closed to recruitment. Between June 6, 2018, and July 22, 2020, 203 patients were randomly assigned to AJM300 (n=102) or placebo (n=101). At week 8, 46 (45%) patients in the AJM300 group and 21 (21%) patients in the placebo group had a clinical response (odds ratio 3·30, 95% CI 1·73-6·29; p=0·00028). During the 8-week treatment and 16-week extension treatment periods, adverse events occurred in 39 (39%) of 101 patients in the placebo group and 39 (38%) of 102 patients in the AJM300 group. We found no difference in the incidence of adverse events between groups or after repeated administration of AJM300. The most common adverse event was nasopharyngitis (11 [11%] of 101 patients in the placebo group and ten [10%] of 102 patients in the AJM300 group). The most common treatment-related adverse event was also nasopharyngitis (four [4%] of 101 patients in the placebo group and three [3%] of 102 patients in the AJM300 group). Most adverse events were mild-to-moderate in severity. No deaths were reported. A serious adverse event was reported in the AJM300 group (one patient with anal abscess), but this was judged to be unrelated to study drug. AJM300 was well tolerated and induced a clinical response in patients with moderately active ulcerative colitis who had an inadequate response or intolerance to mesalazine. AJM300 could be a novel induction therapy for the treatment of patients with moderately active ulcerative colitis. EA Pharma and Kissei Pharmaceutical. For the Japanese translation of the abstract see Supplementary Materials section.

Efficacy and safety of filgotinib as induction and maintenance therapy for Japanese patients with moderately to severely active ulcerative colitis: a post-hoc analysis of the phase 2b/3 SELECTION trial.

The safety and efficacy of filgotinib, a once-daily oral Janus kinase 1 preferential inhibitor, were evaluated in Japanese patients with ulcerative colitis (UC) in the phase 2b/3 SELECTION trial. SELECTION (NCT02914522) was a randomized, placebo-controlled trial comprising 2 induction studies and a maintenance study. Adults with moderately to severely active UC were randomized in induction study A (biologic-naïve) or B (biologic-experienced) to receive filgotinib 200 mg, 100 mg, or placebo once daily for 11 weeks. Patients in clinical remission or Mayo Clinic score response at week 10 entered the 47-week maintenance study. Efficacy and safety outcomes were assessed in Japanese patients enrolled in Japan. Overall, 37 and 72 Japanese patients were enrolled in Japan in induction studies A and B, respectively, and 54 entered the maintenance study. Numerically higher proportions of filgotinib 200 mg-treated than placebo-treated patients achieved clinical remission in induction study A (4/15 [26.7%] vs. 0/6 [0%]) and the maintenance study (5/20 [25.0%] vs. 0/9 [0%]), but not induction study B (1/29 [3.4%] vs. 1/14 [7.1%]). Both doses were well tolerated, and no new safety signals were noted. Herpes zoster was reported in 1 filgotinib 200 mg-treated patient in each of induction study A (2.3%, 1/44) and the maintenance study (5.0%, 1/20). These data, alongside those of the overall SELECTION population, suggest the potential of filgotinib 200 mg as a viable treatment option for Japanese patients with UC. Owing to small patient numbers, data should be interpreted cautiously.

Outcomes of Arthroscopic-Assisted Distal Radius Fracture Volar Plating: A Meta-Analysis

The use of wrist arthroscopy to assist fixation of distal radius fractures with volar locking plates (VLPs) has been gaining popularity in recent years; however, there is no consensus on its benefits. This meta-analysis compares outcomes of arthroscopic-assisted VLP to fluoroscopic-assisted VLP in distal radius fractures through a systematic review of the published literature. A systematic search of publications from databases (Medline, EMBASE, Scopus, and Cochrane) was obtained from inception to May 2020. A random-effects meta-analysis was used to calculate effect sizes. Outcomes included postoperative radiographic reduction (gap, stepoff, radial inclination, volar tilt, and ulnar variance), procedural outcomes (operative time, additional soft tissue injuries and complications), and functional outcomes (range of motion; visual analog scale score; Disabilities of the Arm, Shoulder, and Hand score; Patient-Rated Wrist Evaluation score; Mayo clinic score; and grip strength). Six studies, involving 280 patients, met the final inclusion criteria. The meta-analysis for postoperative stepoff was statistically significant, favoring arthroscopic-assisted VLP. In addition, there was greater identification of associated soft tissue injuries, increased wrist extension, and a longer operative duration when performing arthroscopic-assisted VLP fixation. There were no differences in other postoperative radiographic outcomes, complications, or functional outcomes. The current literature suggests that arthroscopic-assisted VLP is a useful adjunct to intra-articular reduction and treatment of associated soft tissue injuries in distal radius fractures. Considerations should include operative time, costs, and the additional training required. Further studies are needed to assess functional outcomes. Therapeutic II.

WITHDRAWN: EFFICACY, SAFETY, AND TOLERABILITY OF OMILANCOR IN A PHASE 2 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL OF PATIENTS WITH ULCERATIVE COLITIS.

Omilancor is an oral, once-daily, gut-restricted, small molecule, first-in-class therapeutic for Crohn's disease (CD) and ulcerative colitis (UC) that targets the novel LANCL2 pathway. Through LANCL2 activation, omilancor increases the suppressive capacity of regulatory immune cells, including regulatory CD4+ T cells (Tregs), locally within the intestinal mucosa. In a Phase I study in normal healthy volunteers no changes in AEs or trends in safety laboratory trends were observed up to daily oral doses of 7500 mg/day. In a Phase 2, proof of concept, double blind, parallel-group study, adult patients with Mayo Clinic scores (MCS) of 4 - 10 and endoscopic subscores of 2 or more were randomly assigned to groups given omilancor 440 mg QD (n=66), omilancor 880 mg QD (n=66) or placebo (n=66) for 12 weeks. The primary endpoint was clinical remission after 12 weeks as defined by rectal bleeding (RB) equal to 0, stool frequency (SF) equal to 0 or 1 and endoscopic appearance (MES) equal to 0 or 1. A modified intent to treat (mITT) population was defined by patients with RB > 0, histological activity and elevated fecal calprotectin (FCP) at baseline. Secondary endpoints included histological remission as defined by a Geboes score < 3.1 with absence of neutrophils in the lamina propria, endoscopic remission as defined by a MES < 2, normalization of FCP and pharmacokinetics (PK) of omilancor in stool, tissue and plasma. Oral omilancor was well tolerated with no trends in AE profile observed and most AEs of mild severity and no dose-limiting toxicities. In the mITT population, clinical remission was induced in 30.4% of omilancor treated patients relative to 3.7% of patients given placebo (Δ = 26.7, p = 0.01), thereby meeting the primary endpoint. Endoscopic remission was induced in 41.7% of patients treated with omilancor relative to 18.6% of patients given placebo (Δ = 23.1, p = 0.07). Histological remission was induced in 41.7% of patients treated with omilancor relative to 22.2% of patients given placebo (Δ = 19.5, p = 0.14). In patients with elevated baseline FCP, normalization occurred in 43.8% of the omilancor 880 mg group and 40.6% of the omilancor 440 mg group relative to 21.4% of the placebo group after 2 weeks (p = 0.048). PK analysis validated a gut-restricted profile with stable drug levels in stool over the 12-week treatment period and penetration into colonic biopsy tissue with limited systemic exposure. Reduction of patient reported outcomes occurred during the OLE with nearly 90% of patients reaching SF ≤ 1 and RB = 0 after 36 weeks of open-label treatment. Once a day oral dosing with omilancor was well-tolerated and induced clinical remission in a Phase II mild to moderate UC population. A Phase II study in CD and a Phase III program in UC (PACIFY) were initiated in 2021 and are currently recruiting.

P492 A comparison of treatment effects for clinical, endoscopic and histological remission in ulcerative colitis clinical trials

Abstract Background Clinical remission, defined by the Mayo Clinic Score (MCS) or modified MCS, is the accepted regulatory endpoint in drug development for ulcerative colitis (UC). Whilst histologic remission is a more stringent outcome, recent trials have reported numerically higher rates compared to endoscopic or clinical remission rates at the same timepoint, suggesting that histologic remission may be a more sensitive endpoint for detecting treatment response Methods A systematic review was performed from inception to December 2020, including all placebo-controlled drug trials for adults with UC. Clinical, endoscopic, and histologic induction remission rates for active treatment and placebo arms were pooled on the logit scale using a random-effects model to account for both between- and within-study variability. Risk ratios (RR) and risk differences comparing the rate of remission in active treatment arms to the rate of remission in placebo arms were also pooled using a random-effects model. Results For induction trials, 15/84 reported clinical, endoscopic, and histologic remission rates at the same timepoint. Clinical remission was mostly defined as a MCS≤2 with no individual subscore&amp;gt;1 (10/15;66.6%), and endoscopic remission as MES=0 (6/15; 40%) or MES≤1 (9/15; 60%). Histologic remission was defined using Geboes score in 10/15(66.7%) trials, with a score≤1.0 in 4/10(40%), score=0 in 3/10(30%), and score&amp;lt;3.0 in 3/10(30%) trials. For placebo/active treatment arms, the pooled clinical, endoscopic, and histologic remission rates were 11.3%(95% CI 7.4–16.9%) /17.8%(95% CI 13.7–22.8%), 13.4%(95% CI 8.5–20.5%) /18.7% (95% CI 12.2–27.5%), and 18.2%(95% CI 13.8–23.6%) /27%(95% CI 20.6–34.7%), respectively(Figure 1). The differences in pooled clinical, endoscopic, and histologic remission rates between active treatment and placebo were 7.2%(95% CI 4.3%–10.1%), 6.6% (95% CI 2.5%–10.7%), and 8.4% (95% CI 4.3%–12.4%), respectively(Figure 2A), and the pooled RR comparing clinical, endoscopic, and histologic remission rates in the active treatment and placebo arms were 1.59 (95%CI 1.19–2.13), 1.49 (95%CI 1.16–1.90), and 1.47 (95%CI 1.20–1.81), respectively(Figure 2B) Conclusion Histologic remission has been proposed as a treatment target for patients with UC, given an association between this outcome and lower rates of clinical relapse.1 Although we found numerically higher pooled histologic remission rates for active treatment and placebo arms, compared to pooled clinical and endoscopic remission rates, we found no difference in the pooled RR for clinical, endoscopic, and histologic remission rates in the active treatment and placebo arms. Whilst histology has the potential to serve as a more efficient endpoint for drug development, more studies are needed.

P517 Re-treatment with filgotinib in patients with Ulcerative Colitis following treatment interruption: Analysis of the SELECTION and SELECTIONLTE studies

Abstract Background Long-term treatment regimens for ulcerative colitis (UC) present challenges for patients who may need to interrupt therapy for various reasons.1 Filgotinib (FIL) is an oral Janus kinase 1 preferential inhibitor. We performed a post hoc analysis of data collected from patients with UC treated with FIL in the phase 2b/3 SELECTION programme to assess the efficacy and safety of re-treatment following treatment interruption. Methods The SELECTION programme comprises two Induction Studies and a Maintenance Study (NCT02914522) and a long-term extension (LTE) study (NCT02914535). Adults aged 18–75 years with moderately to severely active UC, who had clinical remission or Mayo Clinic Score (MCS) response to FIL 200 mg or 100 mg at week 10 of SELECTION were re-randomized 2:1 to continue assigned FIL treatment or placebo (PBO) from week 11 to week 58. Patients with disease worsening (DW) in the Maintenance Study could enter the LTE study to receive open-label FIL 200 mg once daily. We assessed the efficacy of FIL in patients treated with induction FIL 200 mg or 100 mg who were randomized to PBO in the Maintenance Study and were re-treated with open-label FIL in the LTE study. Efficacy endpoints included partial MCS (pMCS) response and remission at LTE baseline and weeks 2, 4, 12 and 24. Non-responder imputation was used to analyse efficacy results. Results This analysis evaluated 50 patients treated with FIL 200 mg and 35 treated with FIL 100 mg in the Induction Study, who were withdrawn and re-treated upon DW. Baseline characteristics were similar among patients in the 200 mg and 100 mg treatment groups, with a median time to DW of 16.9 and 13.3 weeks, respectively. Mean pMCS declined rapidly in both groups from LTE baseline to week 2, reaching pMCS &amp;lt;2 at week 24 (Figure 1). By as early as week 2 of re-treatment, over 60% of patients in both groups had achieved pMCS response (Figure 2). By week 12, 78% of the 200 mg group and 94% of the 100 mg group achieved a pMCS response. Median time to response was 2.4 and 2.1 weeks in the 200 mg and 100 mg groups, respectively. Figure 3 shows that pMCS remission was achieved in 42% of the 200 mg group and 45% of the 100 mg group by week 24. Median time to pMCS remission was 23.6 and 12.1 weeks in the 200 mg and 100 mg groups, respectively. The number of adverse events upon re-treatment in the LTE was consistent with that reported in SELECTION (Table 1). Conclusion The majority of patients re-treated with FIL achieved pMCS response and remission within 12 weeks, with onset as early as week 2. Good disease control was maintained over the course of 24 weeks. Re-treatment was well tolerated, with no new safety signals observed among these patients. Reference 1. Rubin DT. Gastroenterol Hepatol 2019;15:612–5.