The JAK attack: transforming the management of ulcerative colitis in India.

A Meta-Analysis of the Placebo Rates of Remission and Response in Clinical Trials of Active Ulcerative Colitis

Topical Therapy in Ulcerative Colitis: Always a Bridesmaid but Never a Bride?

AGA Clinical Practice Update on Management of Inflammatory Bowel Disease in Elderly Patients: Expert Review

Inflammatory Bowel Disease Clinical

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon characterized by diffuse mucosal inflammation. Acute severe colitis, a potentially lethal condition requiring hospitalization and intensive medical treatment can develop in 18% to 25% of patients with UC. Although intravenous corticosteroids are the mainstay of conventional medical treatment in this condition, about 30% to 40% of patients are resistant to steroids treatment.1 In the past time when other medical treatments were unavailable for steroid-refractory UC, the only option was an emergency colectomy, which had resulted in about 10% of 3-month mortality rate after surgery. Over the recent past, both cyclosporine and infliximab have been shown to have some benefits for severe UC patients who are refractory to intravenous corticosteroids. Since 1994, through several controlled and noncontrolled clinical trials, intravenous cyclosporine, a calcineurin inhibitor, has been shown to be efficacious in severe attacks of UC patients with 64% to 82% of response rates. The rapid onset of action is a major advantage of cyclosporine therapy, which enables timely colectomy to be performed in patients with nonresponse. However, cyclosporine therapy has been associated with high risk of long-term colectomy (88% of colectomy rate at 7 years). UC patients already exposed to thiopurines prior to acute severe attacks are at increased risk of colectomy. Furthermore, significant risk of toxicity and side effects such as nephrotoxicity, hypertension, seizures and neurotoxicity as well as rigorous drug monitoring limit its use in clinical practice. In contrast, since 2005, several randomized placebo-controlled clinical trials demonstrated that infliximab, a monoclonal antibody against tumor necrosis factor α, was safe and effective in severe steroid-refractory UC patients with 60% to 80% of short-term avoiding rates of colectomy. Infliximab also has a long half-life and intensive drug monitoring is not required. Hence, infliximab has been widely used as a pivotal option in patients with acute severe steroid-refractory UC.2 So, should we discard cyclosporine in favor of infliximab in these patients? Although there have been several data comparing the efficacy of intravenous cyclosporine and infliximab, it is still debated which medication is more effective in steroid-refractory UC.3,4 At present, some guidelines recommend intravenous cyclosporine or infliximab as a medical rescue therapy in acute severe UC patients who is refractory to intravenous steroids. Recent meta-analysis of six retrospective cohort studies compared the clinical outcomes of steroid-refractory UC patients receiving infliximab or cyclosporine as a rescue therapy showed no significant differences in the 3-month and 12-month colectomy rate, in adverse events, and in postoperative complications between two groups.5 In addition, the first prospective randomized controlled trial comparing the efficacy of cyclosporine versus infliximab, recently published in Europe, demonstrated there is no significant difference in the treatment outcomes between two groups.6 However, most of these studies have been performed in Western countries. Compared with Western population, Korean UC patients have distinct genetic and ethnic backgrounds as well as different environmental characteristics such as diet and intestinal microbial change.7,8 To date, there has been no data comparing the efficacy of cyclosporine versus infliximab in steroid-refractory UC patients from Korea. In this issue of Gut and Liver, Kim et al.9 investigated the efficacy of cyclosporine and infliximab in 43 patients with severe steroid-refractory UC in a retrospective manner. They compared clinical outcomes of 10 patients who had received intravenous cyclosporine with those of 33 patients who had received infliximab for acute severe steroid-refractory UC. The authors showed that there was no difference in preventing colectomy during follow-up of 12 months (primary outcome) between cyclosporine-treated group and infliximab-treated group. Meanwhile, in the subgroup analysis, infliximab with azathioprine was superior to cyclosporine for preventing colectomy (hazard ratio of infliximab with azathioprine compared to cyclosporine only, 0.073; 95% confidence interval, 0.008 to 0.629). In terms of secondary outcomes, length of hospital stay after rescue therapy was shorter in the infliximab-treated group, and the rates of adverse events did not differ between two groups. This study, firstly compared the efficacy of rescue therapy in Korean patients with acute severe steroid-refractory UC, provide an essential insight into the treatment options available for these patients in Korea. However, as the authors described, this study performed retrospectively with a small sample size and compared the clinical outcomes between groups enrolled from different periods of time. And, the better outcome for avoiding colectomy in the infliximab group relative to the cyclosporine group might be resulted from a beneficial interaction of infliximab and azathioprine. To validate the results of this study, a prospective multicenter randomized clinical trial comparing the efficacy of cyclosporine versus infliximab in Korean steroid-refractory UC patients is warranted. Acute severe UC patients who are resistant to intravenous steroids continue to be a potentially life threatening condition in clinical practice. At present, it is not clear whether infliximab therapy is more effective in acute severe steroid-refractory UC patients than intravenous cyclosporine therapy. Therefore, in the absence of definite contraindication to a particular therapy, the individual situation of each patient and clinician’s experience should be considered when deciding treatment option for rescue therapy. In addition, clinicians have to consider that even if rescue therapy with either infliximab or intravenous cyclosporine is clinically important in acute severe steroid-refractory UC, medical treatment should not postpone the decision for colectomy in patients with inadequate response to rescue therapy.

P543 Better response rates to anti-TNFa than cyclosporin in steroid refractory acute severe colitis: data from the UK IBD audit

P544 Does measuring IFX and human anti-chimeric antibody concentrations in patients with inflammatory bowel disease impact clinical management? A Canadian experience

Tofacitinib Is Safe and Effective When Used in Combination With Infliximab for the Management of Refractory Ulcerative Colitis

After a new look at the history of the Marchioness del Valles conspiracy as part of the tensions that queen Margaret and her ladies caused at the Court of Philip III, the essay stresses the doubts, questions poned and interest that these circumstances aroused in the Spanish political and popular media in the early 17th century. Special attention is given to the information media which prepared and passed on these facts: rumours and oral narrations, announcements, historical and literary texts, relations of ambassadors, all in the framework of a budding public opinion structure.

P1242 Incidence of Acute Severe Ulcerative Colitis in a Changing Landscape of Increased Disease Prevalence and More Effective Therapies

Defining Endpoints and Biomarkers in Inflammatory Bowel Disease: Moving the Needle Through Clinical Trial Design

Introduction: Elderly-onset inflammatory bowel disease (IBD) composes up to 20% of new cases of IBD, and ulcerative colitis (UC) is up to twice as common as Crohn's disease (CD) among the elderly. Some, but not all, studies have shown a modest increase in mortality among all patients with IBD. To our knowledge, no studies have evaluated the long-term mortality among patients with elderly-onset UC in the United States. Methods: We conducted a retrospective cohort study to evaluate the all-cause mortality and survival among patients with elderly-onset UC vs. non-IBD patients in the US National VA health care system from January 1, 2000 to June 30, 2016 using data from the VA Informatics and Computing Infrastructure. We included individuals with new-onset UC in the exposure group (UC group) if they met the following conditions: 1) ≥2 UC diagnoses and no diagnoses of CD or other diseases of the anus/rectum; 2) age>60 at the time of first UC diagnosis; 3) ≥1 year of pre-diagnosis VA care; 4) ≥5 VA visits prior to UC diagnosis 5) ≥ 4 pharmacy claims for aminosalicylates. For each elderly-onset UC patient, up to 4 non-IBD veterans were selected, matching on: 1) date of birth; 2) first VA visit; 3) VA location and 4) gender. Time to death was the outcome of interest. We estimated the incidence rate of death in the exposed and unexposed groups, respectively. Cox regression was used to determine the hazard ratio for time to death associated with elderly-onset UC. Results: The mean age was 70.7 (SD 7.4) years among the UC group and 70.3 (SD 7.4) in the non-IBD group. As expected, there was male predominance in the groups (97.6%). Elderly-onset UC patients had worse survival compared to matched non-IBD patients (Figure, log-rank test p value<0.0001). The incidence rate of death after UC diagnosis among the exposed group (N= 4,327) was 106.8 deaths per 1000 patient-years (95% CI 106.7 - 106.9) compared with 74.5 (95% CI 74.5- 74.6) in the matched non-IBD comparison group (N= 17,164). Compared with the non-IBD group, the hazard ratio for death associated with elderly-onset UC was 1.49 (95% CI: 1.42 - 1.55). Conclusion: We report a novel population-based mortality rate among elderly-onset UC patients. In addition, we observed that elderly-onset UC is associated with significantly increased risk of mortality compared to an age and sex matched non-IBD population. These prognostic data would be of great interest to patients and health policy makers.576 Figure 1. Death after UC Diagnosis vs. Matched Date in UC and non-IBD cohorts.

Real-time use of artificial intelligence at colonoscopy predicts relapse in ulcerative colitis: predicting with “intelligence”

Background and AimsTofacitinib (TFB) appears to be effective in the treatment of ulcerative colitis (UC); however, available real-world studies are limited by cohort size. TFB could be an option in the treatment of acute severe ulcerative colitis (ASUC). We aimed to investigate efficacy and safety of TFB in moderate-to-severe colitis and ASUC.MethodsThis retrospective, international cohort study enrolling UC patients with ≥6-week follow-up period was conducted from February 1 to July 31, 2022. Indications were categorized as ASUC and chronic activity (CA). Baseline demographic and clinical data were obtained. Steroid-free remission (SFR), colectomy, and safety data were analyzed.ResultsA total of 391 UC patients (median age 38 [interquartile range, 28-47] years; follow-up period 26 [interquartile range, 14-52] weeks) were included. A total of 27.1% received TFB in ASUC. SFR rates were 23.7% (ASUC: 26.0%, CA: 22.8%) at week 12 and 41.1% (ASUC: 34.2%, CA: 43.5%) at week 52. The baseline partial Mayo score (odds ratio [OR], 0.850; P = .006) was negatively associated with week 12 SFR, while biologic-naïve patients (OR, 2.078; P = .04) more likely achieved week 52 SFR. The colectomy rate at week 52 was higher in ASUC group (17.6% vs 5.7%; P < .001) and decreased with age (OR, 0.94; P = .013). A total of 67 adverse events were reported, and 17.9% resulted in cessation of TFB. One case of thromboembolic event was reported.ConclusionsTFB is effective in both studied indications. TFB treatment resulted in high rates of SFR in the short and long terms. Higher baseline disease activity and previous biological therapies decreased efficacy. No new adverse event signals were found.

In recent years, cases of elderly-onset ulcerative colitis (UC) have been increasing in number and are currently reported to account for 10–15% of all cases of UC. Although the treatment of UC is essentially similar between older and younger patients, evidence of the therapeutic efficacy of tacrolimus in elderly-onset UC patients is still limited. Herein, we report our attempt to induce remission using tacrolimus in three patients with elderly-onset UC. A 75-year-old Japanese woman, a 71-year-old Japanese man and a 76-year-old Japanese woman with severe elderly-onset UC of the pancolitis type were treated with tacrolimus. Although all three patients showed response to the drug, the eventual outcome was poor in the first patient, who developed toxic megacolon, underwent surgery, and suffered from recurrent infections and hemorrhage after the surgery. However, clinical remission was successfully achieved in the second and third patient. Tacrolimus shows some indication of effectiveness in the treatment of elderly-onset UC. However, in elderly-onset UC patients, it is necessary to keep in mind the higher risk of adverse effects of medical therapy and postoperative complications because of the high comorbidity rates. Moreover, in situations where surgery needs to be considered, it is important to ensure appropriate timing of the surgery.