Colectomy-free Survival Research Articles

Real-world efficacy and safety of tofacitinib treatment in Asian patients with ulcerative colitis.

Real-world data on tofacitinib (TOF) covering a period of more than 1 year for a sufficient number of Asian patients with ulcerative colitis (UC) are scarce. To investigate the long-term efficacy and safety of TOF treatment for UC, including clinical issues. We performed a retrospective single-center observational analysis of 111 UC patients administered TOF at Hyogo Medical University as a tertiary inflammatory bowel disease center. All consecutive UC patients who received TOF between May 2018 and February 2020 were enrolled. Patients were followed up until August 2020. The primary outcome was the clinical response rate at week 8. Secondary outcomes included clinical remission at week 8, cumulative persistence rate of TOF administration, colectomy-free survival, relapse after tapering of TOF and predictors of clinical response at week 8 and week 48. The clinical response and remission rates were 66.3% and 50.5% at week 8, and 47.1% and 43.5% at week 48, respectively. The overall cumulative clinical remission rate was 61.7% at week 48 and history of anti-tumor necrosis factor-alpha (TNF-α) agents use had no influence (P = 0.25). The cumulative TOF persistence rate at week 48 was significantly lower in patients without clinical remission than in those with remission at week 8 (30.9% vs 88.1%; P < 0.001). Baseline partial Mayo Score was significantly lower in responders vs non-responders at week 8 (odds ratio: 0.61, 95% confidence interval: 0.45-0.82, P = 0.001). Relapse occurred in 45.7% of patients after TOF tapering, and 85.7% of patients responded within 4 wk after re-increase. All 6 patients with herpes zoster (HZ) developed the infection after achieving remission by TOF. TOF was more effective in UC patients with mild activity at baseline and its efficacy was not affected by previous treatment with anti-TNF-α agents. Most relapsed patients responded again after re-increase of TOF and nearly half relapsed after tapering off TOF. Special attention is needed for tapering and HZ.

Effectiveness and safety of a third-line rescue treatment for acute severe ulcerative colitis refractory to infliximab or ciclosporin (REASUC study).

The advent of new therapeutic agents and the improvement of supporting care might change the management of acute severe ulcerative colitis (ASUC) and avoid colectomy. To evaluate the colectomy-free survival and safety of a third-line treatment in patients with ASUC refractory to intravenous steroids and who failed either infliximab or ciclosporin. Multicentre retrospective cohortstudy of patients with ASUC refractory to intravenous steroids who had failed infliximab or ciclosporin and received a third-line treatment during the same hospitalisation. Patients who stopped second-line treatment due to disease activity or adverse events (AEs) were eligible. We assessed short-term colectomy-free survival by logistic regression analysis. Kaplan-Meier curves and Cox regression models were used for long-term assessment. Among 78 patients, 32 received infliximab and 46 ciclosporin as second-line rescue treatment. Third-line treatment was infliximab in 45 (58%), ciclosporin in 17 (22%), tofacitinib in 13 (17%) and ustekinumab in 3 (3.8%). Colectomy was performed in 29 patients (37%) during follow-up (median 21 weeks). Of the 78 patients, 32 and 18 were in clinical remission at, respectively, 12 and 52 weeks. At the last visit, 25 patients were still on third-line rescue treatment, while 12 had stopped it due to clinical remission. AEs were reported in 26 (33%) patients. Two patients died (2.6%), including one following colectomy. Third-line rescue treatment avoided colectomy in over half of the patients with ASUC and may be considered a therapeutic strategy.

DOP21 Histo-endoscopic remission (HEMR) Predicts Future Relapse in Patients with Ulcerative Colitis and is Associated with Lower Colectomy Risk

Abstract Background Treating beyond clinical and endoscopic remission, aiming for histological remission, is an aspiring target in ulcerative colitis [UC]. Hence, combined histo-endoscopic endpoints are increasingly being embraced. We assessed different degrees of histologic remission in patients with UC and their association with long-term outcomes. Methods UC patients achieving endoscopic improvement (Mayo endoscopic score [MES] ≤1) were recruited at colonoscopy. Clinical data were retrospectively collected from medical records. Endoscopies were video-recorded and biopsies from the most affected segment were collected for histological assessment and RNAseq (in case of MES 0 rectosigmoid biopsies were collected according to previous disease extent). Geboes Score [GS] and Robarts Histopathology Index [RHI] were determined for each biopsy by two pathologists blinded to the endoscopic scores. Non-histo-endoscopic remission [NHR], histo-endoscopic mucosal remission [HEMR] and histo-endoscopic mucosal normalization [HEMN] were defined as GS ≥2B.1, GS &amp;lt;2B.1 and GS ≤0.1. Clinical relapse was defined as the need for dose optimization, switching therapy or initiation of corticosteroids during follow-up. Long-term outcomes were analysed using log-rank test and Cox regression. Results Between 2016 and 2022, a total of 172 UC patients were included (Table). Endoscopic remission (MES 0) was achieved in 104 (60.4%) patients. NHR, HEMR and HEMN were observed in 15 (14.4%), 69 (85.6%), 51 (49.0%) of MES 0 patients and 32 (47.1%), 36 (52.9%), 18 (26.5%) of MES 1 patients. During a median [IQR] follow-up of 2.8 (1.9-3.9) years, 51 (29.7%) patients relapsed, and 7 (4.0%) patients needed colectomy. Relapse- and colectomy-free survival (Figure) were significantly higher when comparing HEMR to NHR (p&amp;lt;0.001 for both). This difference was not observed for endoscopic score (MES 0 vs. 1) or different degrees of histologic remission (HEMN vs. HEMR). The univariate Cox regression showed that histo-endoscopic activity, clinical activity (i.e., patient reported outcomes (PRO-2) for stool frequency or rectal bleeding &amp;gt; 0) and prior advanced therapy failure were associated with an increased risk of relapse. The multivariate Cox regression identified histo-endoscopic activity as the only risk factor for relapse (adjusted hazard ratio [HR]) = 3.01, 95% confidence interval [1.69-5.34], p&amp;lt;0.001). Conclusion In this cohort of UC patients with endoscopic improvement, 14.4% of MES 0 and 47.1% of MES 1 patients still showed signs of histologic activity (i.e., presence of neutrophils in the lamina propria or epithelium. Histologic remission was a superior predictor of future outcome (relapse, colectomy) when compared to endoscopic remission and showed to be the sole predictor of relapse.

P381 Intestinal ultrasound in newly diagnosed Ulcerative Colitis predicts the need for colectomy

Abstract Background Upon diagnosis of ulcerative colitis (UC), it remains challenging to predict who will have a severe disease course, ultimately necessitating colectomy. Predictive tools capable of risk-stratifying patients and individualize treatment are warranted. The aim of this study was to assess whether Intestinal ultrasound (IUS), performed at the onset of UC, could help predict the need for colectomy within the first year of diagnosis. Methods In a Danish prospective inception cohort, all new-onset adult patients with UC (including unclassified IBD) with left-sided or extensive colitis underwent IUS near the diagnostic endoscopy. The assessment included the International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) and the bowel wall thickness (BWT) of the most inflamed segment. Besides IUS, we recorded age, gender, smoking, BMI, the Mayo endoscopic score (MES), the Simple Clinical Colitis Activity Index (SCCAI), and biomarkers hemoglobin (hgb), C-reactive protein (CRP), albumin and fecal calprotectin. Results During inclusion (May 2021 – April 2023), we included 193 UC patients with Montreal classification E2 or E3. In total, 12/193 (6%) underwent colectomy within the first year or during follow-up (min. 6 months). Baseline characteristics are presented in Table 1. Univariable analyses identified high MES, CRP, SCCAI, IBUS-SAS, and BWT, along with low Hgb and albumin, as significantly associated with an increased colectomy risk. Multivariable analysis with stepwise reduction identified only SCCAI (OR: 2.0, CI 1.2–3.3, p&amp;lt;0.005) and BWT (OR: 1.6, CI 1.1–2.3, p=0.01) as independent predictors. Through ROC analysis, BWT presented the highest accuracy (AUC: 0.89), and the optimal cut-off by Youden Index for colectomy prediction was &amp;gt; 6.1 mm. Combining all the significant non-IUS predictors, CRP, MES, SCCAI, hgb, and albumin yielded an AUC of 0.88. The highest accuracy was found by combining SCCAI and BWT, with an AUC of 0.94. Kaplan-Meier curve for colectomy-free survival is presented in Figure 1. Among patients with BWT&amp;gt;6.1mm, 18/21 (86%) started systemic steroids within the first week, compared to 43/125 (34%) of patients with BWT ≤ 6.1, p=0.007. Among patients with BWT &amp;gt; 6.1mm, 11/21 (52%) started biologics within the first 31 days, compared to 5/125 (4%) of patients with BWT≤6.1mm, p&amp;lt;0.001. Despite more aggressive treatment, 8/21 (38%) with BWT&amp;gt;6.1mm had a colectomy compared to 2/125 (2%) with BWT≤6.1mm.Conclusion IUS at UC onset, specifically BWT, is a robust predictor of colectomy risk within the first year of diagnosis. Combining clinical symptom scores with IUS enhances predictive accuracy. It can accurately identify patients at an increased risk of colectomy, guiding early treatment decisions for improved patient outcomes.

Impact of cytomegalovirus on outcomes in acute severe ulcerative colitis: a retrospective observational study.

Concomitant cytomegalovirus (CMV) is highly prevalent in acute severe ulcerative colitis (ASUC) but data for outcomes of CMV positivity in ASUC and the benefit of antiviral therapy remain unclear. We aim to determine the impact of CMV positivity, and antiviral therapy, on outcomes such as colectomy-free survival, length of hospital stay and readmission rate, among hospitalized patients with ASUC. This is a retrospective, multicentre study of patients admitted with ASUC. CMV positivity was diagnosed from blood CMV DNA and inpatient colonic biopsies. Background demographics and disease characteristics, clinical characteristics and outcomes during admission and long-term outcomes were obtained from electronic medical records and compared according to the presence of CMV and the use of antiviral therapy. CMV was detected in 40 (24%) of 167 ASUC admissions. Previous steroid exposure was the only clinical predictor of CMV positivity on multivariate analysis. Outcomes of greater requirement for rescue therapy (60% versus 33%), longer hospital stay (14.3 versus 9.9 days) and higher readmission rates at 3 and 12 months were associated with CMV positivity. No difference was found in the rate of colectomy or colectomy-free survival. Antiviral therapy was not associated with a lower risk of colectomy but did extend the time to colectomy (126 versus 36 days). CMV positivity was associated with worse outcomes of need for rescue therapy, hospital stay and readmissions. Antiviral therapy was not found to reduce the risk of colectomy but did extend the time to colectomy. Further prospective studies will be required to more clearly determine its benefit in patients with concomitant CMV and ASUC.

Outcome of Biological Therapies and Small Molecules in Ulcerative Proctitis: A Belgian Multicenter Cohort Study

Several advanced therapies (biologic therapies and small molecules) have been approved for the treatment of moderate-to-severe ulcerative colitis. The registration trials for these agents typically excluded patients with isolated proctitis, leaving an evidence gap. We evaluated efficacy and safety of advanced therapies in patients with ulcerative proctitis (UP). This multicenter retrospective cohort study included consecutive patients with active UP (Mayo endoscopy subscore of ≥2, rectal inflammation up to 15 cm) initiating advanced therapy, after failing conventional therapy. The primary end point was short-term steroid-free clinical remission (total Mayo score ≤2 with no individual subscore >1). In addition, drug persistence and relapse-free and colectomy-free survival were assessed. Both binary logistic and Cox regression analyses were performed. In total, 167 consecutive patients (52.0% female; median age 41.0 years; 82.0% bionaive) underwent 223 courses of therapy for UP (38 adalimumab, 14 golimumab, 54 infliximab, 9 ustekinumab, 99 vedolizumab, 9 tofacitinib). The primary end point was achieved with 36.3% of the treatment courses, and based on multivariate analysis, more commonly attained in bionaive patients (P= .001), patients treated with vedolizumab (P= .001), patients with moderate endoscopic disease activity (P= .002), and a body mass index <25 kg/m2 (P= .018). Drug persistence was significantly higher in patients treated with vedolizumab (P < .001) and patients with a shorter disease duration (P= .006). No new safety signals were observed. Advanced therapies are also efficacious and safe in patients with ulcerative colitis limited to the rectum. Therefore, the inclusion of patients with UP in future randomized-controlled trials should be considered.

Oral Tacrolimus in Steroid Refractory and Dependent Pediatric Ulcerative Colitis-A Systematic Review and Meta-Analysis.

There are limited treatment options for children with steroid-refractory or dependent ulcerative colitis (UC). A few observational studies suggest efficacy of oral tacrolimus. We performed a systematic review and meta-analysis to assess the efficacy of tacrolimus in pediatric UC. PubMed and Scopus were searched for publications related to the use of oral tacrolimus in pediatric UC. Data regarding the clinical response and colectomy-free survival were extracted from studies that met the selection criteria. The search strategy yielded 492 articles of which 7 studies were included in the final review. They included 166 children (111 steroid-refractory, 52 steroid-dependent, 3 no steroids). Majority of cases (150/166 [90%]) were naïve to biologics. An initial response to tacrolimus therapy was seen in 84% (95% CI: 73%-93%) (n = 7 studies). No difference was observed between children with high (>10 ng/mL) or low tacrolimus levels (127/150 [85%] vs 12/16 [75%], P = 0.3). No difference in initial response between the children who were steroid refractory or dependent (92/111 [83%] vs 46/52 [88%], P = 0.36). The response in the biologic-exposed group (n = 10) was 70%. At 1-year follow-up, 15.2% (95% CI: 7%-21%) (n = 2 studies, 85 patients) had a sustained response on only tacrolimus. The pooled frequency of 1-year colectomy-free survival in children treated with initial oral tacrolimus was 64% (95% CI: 53%-75%). Twelve (7.2%) patients required cessation of therapy because of side effects. Tacrolimus has a high initial response in biologic naïve UC children. It can be effectively used as a bridge to other therapies with a 1-year colectomy-free survival of 64%.

P778 Effectiveness and safety of a second-line rescue therapy for acute severe ulcerative colitis refractory to infliximab or ciclosporin (REASUC study)

Abstract Background The advent of new therapeutic agents and the improvement of supporting care might change the management of acute severe ulcerative colitis (ASUC) to avoid colectomy and change the natural history of the disease. The effectiveness and safety of sequential treatment should be evaluated in this scenario. Main aim To evaluate colectomy-free survival in patients with ASUC refractory to intravenous steroids who had failed infliximab (IFX) or ciclosporin (CyA) and received a second salvage therapy. Secondary aims: To evaluate the short-term and long-term effectiveness and to assess the safety of this strategy. Methods Multicentre study of patients admitted with ASUC refractory to corticosteroids who failed CyA or IFX and had received a second salvage therapy during the same hospital stay. Clinical activity was classified based on partial Mayo score and Lichtiger activity index. Patients who stopped second-line therapy due to disease activity or adverse events were considered as failures. Short-term colectomy-free survival was assessed by logistic regression analysis while long-term colectomy-free survival was evaluated by Kaplan-Meier curves and Cox regression models. Results Results: A total of 78 patients from 24 centres were included. As first-line therapy, IFX was administered to 32 patients, and CyA to 46. Baseline characteristics are detailed in table 1. The prescribed salvage therapy was IFX in 45 patients, CyA in 17, tofacitinib in 13, and ustekinumab in 3 (Figure 1). Colectomy was required in 29 patients (37%) during the follow-up (median 14 days, IQR 3-23). Colectomy-free survival curves are shown in figure 2-A and 2-B. Second-line salvage therapy with CyA was associated with a higher rate of colectomy (Figure 2-C). A total of 39 patients (55%) at week 12 and 20 patients (33%) at month 12 had clinical response; 31 patients (44%) at week 12 and 18 (30%) at month 12 were in clinical remission. At the last visit of the study, 26 patients (33%) were still under the second-line therapy. Adverse events (AE) were recorded in 26 patients (33%), being serious in 15. Resolution with no sequelae was observed in 20 patients (77%). No differences in AE between the second-line therapies prescribed were observed. There were two deaths: one due to cerebral thrombophlebitis and another due to bacteriemia after colectomy, both when CyA was the salvage therapy prescribed (Table 2). Conclusion A second-line salvage therapy avoids colectomy in a considerable percentage of patients admitted by ASUC and therefore it could be considered after IFX or CyA failure. The individual therapeutic approach must be discussed with patients due to the risk of serious adverse events.

P739 Sequential treatment is effective to achieve remission and avoid colectomy in moderate-to-severe Ulcerative Colitis refractory to anti-TNF therapy

Abstract Background The development of anti-TNF agents has brought advances in the treatment of ulcerative colitis (UC). However, many patients require biological treatment sequencing. We aimed to evaluate clinical outcomes, the rate of treatment persistence and colectomy-free survival at second-, third-, and fourth-line therapy after switching from TNF-inhibitor to another treatment and to identify factors predicting the need for colectomy. Methods In this retrospective study, we included active UC patients refractory to at least one anti-TNF agent and needed treatment sequencing. The efficacy of therapies of the different lines was assessed by endoscopic or clinical scoring systems and laboratory markers. Kaplan-Meier analysis was performed to investigate the colectomy-free survival. Possible predictive factors were examined by logistic regression. Results Data of 90 UC patients were analyzed. The most frequently used first-line biologic therapy was infliximab (83.3%), which was discontinued after an average of 21.3 months. In the second-line vedolizumab (VDZ) was administered in 48.9% of cases, adalimumab in 36.7%. Average time between initiation and discontinuation was 15.7 months. In the third line, VDZ was used in 50%, tofacitinib in 29% of the patients, until an average of 8.7 months. In the fourth line, 53.1% of patients received tofacitinib and it was terminated after an average of 8.9 months. Loss of response, as a reason for treatment discontinuation was more common in the first-, and second-line therapies (58.9% and 46.2%), while primary non-response was more often observed in third-, and fourth-line therapies (52.6% and 63.6%). Fifteen patients underwent colectomy (16.7%). There was a significant increase in the probability of having surgery within 2 years after therapy initiation (p=0.0239) independently from treatment lines. Presence of deep ulcer showed inverse correlation with colectomy-free survival (p=0.0189; OR: 10.414 (95% CI: (1.472; 73.669)). Patients with high partial Mayo score at therapy initiation were more likely to undergo colectomy (p=0.0436, OR: 1.463 (95% CI: (1.011; 2.118)). In contrast, gender, age and disease extent at the time of the diagnosis, and the use of concomitant immunmodulators were not shown to be significant in predicting the subsequent surgical need. Conclusion Our results suggest that the remission rate does not decrease considerably as the sequential treatment progresses, more than half of the patients receiving fourth-line therapy were still in sustained remission. The more severe disease activity and deep ulcerations proved to be predictive for colectomy. Further studies in a larger patient population would be required to confirm our data and reveal predictive markers.

P583 Tofacitinib for acute severe ulcerative colitis: a systematic review

Abstract Background Treatment of acute severe ulcerative colitis (ASUC) comprising iv steroids, second line infliximab or cyclosporin, and finally colectomy, has remained unchanged for nearly two decades and without improvements in colectomy rates. Tofacitinib (TOFA), a pan JAK-inhibitor, has emerged as a potential new treatment option for ASUC. We conducted a systematic review to assess efficacy, safety, and integration in current ASUC algorithms. Methods Systematic search in MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and Clinicaltrials.gov until August 17, 2022, including all studies reporting original observations on JAK-inhibitor use, notably tofacitinib, for ASUC defined according to Truelove and Witts criteria. Primary outcome was colectomy-free survival. Individual patient data from case reports were pooled and collectively analyzed. Results Of 853 publications identified, 20 studies (seven single case reports and eight case series resulting in data from 42 patients; one combined retrospective and prospective GETAID cohort study of 55 patients; one retrospective study of 40 cases and 113 matched controls; one pediatric retrospective cohort study of 11 patients; two ongoing trials) involving 148 patients (female 44-60%, age median 28-34 years, disease duration 5-10 years) treated with second- or third line tofacitinib for ASUC were included. Colectomy-free survival was 78% from 90-day onwards in the pooled cohort of individual cases (Figure); GETAID cohort 85% 30-day, 79% 90-day, 74% 180-day; and 63% in the pediatric cohort. The case-control study observed lower 90-day colectomy risk among TOFA treated (HR 0.28 [0.10-0.28], p=0.018). The majority received second line TOFA rescue therapy after initial failure to iv steroids (n=65), and with previous failure to one or more biologics, notable infliximab (n=62, 95%). There was no difference in colectomy rates between patients treated with second or third line TOFA (n=15 (23%) vs. n=1 (8%), p=0.44). Tofacitinib persistence at follow-up was 68-91%, clinical remission 35-69%, endoscopic remission 55%, and without reports of novel or severe safety signals (Table). Conclusion Tofacitinib appears to result in high short-term colectomy-free survival among refractory ASUC patients and may have potential in the future treatment of patients otherwise deemed for colectomy. Efficacy was comparable to first line ASUC therapy with iv steroids, but observations are limited, uncontrolled and with short follow-up. High-quality studies are needed.

P547 Rate of Colectomy Increases within Twelve Months of Sequential Therapy for Ulcerative Colitis

Abstract Background Even the best medical treatments for ulcerative colitis (UC) are often ineffective, with up to 15% of patients requiring a colectomy within the first 10 years of diagnosis. In the current era, patients have access to an increasing number of medical therapies that may prevent and/or delay surgery. To evaluate the relative effectiveness of sequential therapies for UC, we evaluated the 12-month colectomy rate among patients switching to a second, third, or fourth-line biologic or small molecule therapy for UC. Methods We conducted a retrospective cohort study, using a new-user design, evaluating patients with commercial insurance in the MarketScan database between 2000 and 2019. The index date for the study was defined as the date of the first claim for a second, third, or fourth biologic or small molecule therapy. The primary outcome was defined as colectomy-free survival at 12 months after the index date. Significance of 12-month colectomy rates over time was evaluated using the Cochran-Armitage test of trend and a Generalized Estimating Equation (GEE) model adjusting for age (18-35, 36-55, &amp;gt;55), sex and index year (year 2007-2014 and 2015-2019). Results We identified 3,325 patients with UC that made at least 1 switch in biologic or small molecule therapy during the study period. Among these, 50% were female and the median age was 41 years (interquartile range 31-52 years, Table 1). The most frequent initial biologic switches were from an anti-tumor necrosis factor alpha (TNF) to an anti-TNF (1895 patients [57%]) and anti-TNF to vedolizumab (980 patients [30%]) were the most common sequences of therapies (Table 2). Overall, 392 (12%) patients underwent colectomy within 12 months of the first switch while 116 of 695 (17%) patients underwent colectomy within 12 months of the second switch. Among 161 patients that underwent 3 switches, 30 (19%) underwent colectomy within 12 months of the third switch (p&amp;lt;0.001, Table 3). The rate of UC-related hospitalizations in the 12 months after switch also increased significantly with each subsequent switch (11% vs. 15% vs. 19% for first, second and third switches respectively, p&amp;lt;0.001). The colectomy rate per switch in therapy appeared stable when stratifying by index date and age at index date (Figure 1). Conclusion Despite increases in the number of available mechanisms for the treatment of UC, a substantial proportion of patients will still require colectomy for UC. The absolute risk of colectomy within 12 months and other negative outcomes increase with each subsequent treatment. These data can help inform complex decisions regarding the timing of surgery relative to initiation of subsequent therapy in patients with medically-refractory disease.

P780 Prognosis and optimal treatment for 5-aminosalicylic acid-intolerant patients with Ulcerative Colitis

Abstract Background 5-aminosalicylic acid (5-ASA) is widely used as a first-line treatment for ulcerative colitis (UC), but intolerance sometimes occurs. 5-ASA-intolerance was considered a risk factor for colectomy in UC patients, but no reports have examined which treatment is suitable to avoid colectomy in 5-ASA-intolerant UC patients. This is the first report describing a treatment strategy for 5-ASA-intolerant UC. The aims of this study were to determine the optimal therapeutic strategy in 5-ASA-intolerant UC patients. Methods This retrospective cohort study involved patients who were newly diagnosed as having UC after January 2010 and who received oral 5-ASA agents. Patients were considered 5-ASA-intolerant when they fulfilled two or more of the following conditions: (1) paradoxical aggravation of colitis on introducing oral 5-ASA agents or allergic reactions to the agents; (2) obvious improvement of abdominal symptoms after discontinuation of 5-ASA agents; (3) positive drug-induced lymphocyte stimulation test (DLST) for at least two formulations of 5-ASA; (4) adverse events following re-challenge with 5-ASA agents; and (5) severe adverse events owing to 5-ASA agents. Results Of 950 UC patients with a history of 5-ASA administration, 213 (22.4%) were considered 5-ASA-intolerant. Five-year colectomy-free survival was significantly lower in 5-ASA-intolerant patients compared with 5-ASA-tolerant patients (73% vs. 84%, respectively). From the multivariate Cox proportional hazards model analysis in the 5-ASA-intolerant patient cohort, thiopurine use was shown to contribute to avoidance of colectomy in 5-ASA-intolerant patients (hazard ratio = 0.25; 95% confidence interval, 0.13–0.47; P &amp;lt; 0.001); however, 5-ASA-intolerant patients were also likely to be thiopurine-intolerant compared with 5-ASA-tolerant patients (27% vs. 15%, respectively; P = 0.04). Calcineurin inhibitor use was associated with an increased risk of colectomy (hazard ratio = 4.80; 95% confidence interval, 2.24–10.3; P &amp;lt; 0.001), while treatment with systemic corticosteroids and biologics did not affect the colectomy rate (hazard ratio = 1.07; 95% confidence interval, 0.60–1.91; P = 0.81). Conclusion Treatment with thiopurines demonstrated the potential to improve the prognosis in 5-ASA-intolerant patients. However, it should be noted that thiopurine intolerance was more frequent in 5-ASA-intolerant patients. Compared to biologics, calcineurin inhibitors may not contribute to avoidance of colectomy, and biologics may be preferred for intractable patients with 5-ASA intolerance. This is the first report describing a treatment strategy for 5-ASA-intolerant UC, and we believe it will have many implications in clinical practice.

P793 Infliximab and prevention of colectomy in acute severe ulcerative colitis: an individual patient data meta-analysis

Abstract Background Infliximab (IFX) is used to treat patients with acute severe ulcerative colitis (ASUC) who fail to respond to intravenous corticosteroid therapy. Yet, a significant proportion of patients does not respond adequately and requires colectomy. Our aim was to explore baseline predictors of colectomy-free survival during IFX rescue therapy in patients with steroid-refractory ASUC. Methods We performed an individual patient data meta-analysis (IPDMA) with data retrospectively collected from hospitalised, corticosteroid-refractory patients diagnosed with ASUC (based on Truelove and Witts’ criteria) who received IFX rescue therapy. Baseline characteristics including sex, smoking status, disease extent, disease duration, Mayo endoscopic subscore, serum albumin, C-reactive protein, haemoglobin, and white blood count were evaluated as predictors of colectomy-free survival at three and twelve months after start of IFX therapy. Data were analysed using R software (v4.2.0). Results Data were collected from six centres contributing a total of 140 patients (Table 1). Fifteen patients (10.7%) required colectomy within three months and another eight patients underwent colectomy by one year (total colectomy rate after one year 16.4%) (Figure 1). No baseline predictors of colectomy-free survival were identified (log-rank P&amp;gt;0.05). Patients who received intensified IFX induction therapy (n=64, &amp;gt;5 mg/kg), in contrast to patients on regular induction doses of 5 mg/kg at weeks 0-2-6 (n=49), did not have lower rates of colectomy. A total of 53 IFX serum trough concentrations (TC) were measured in 31 patients. The median IFX TC during weeks (w)1-2 of therapy was 13.5 mg/L (interquartile range [IQR] 9.3-16.3 mg/L), and 7.0 (IQR 1.9-12.0) mg/L during w3-6. Target attainment rates were 8.3% (1/12 patients) and 18.2% (2/11 patients), respectively, towards the previously reported IFX TC targets of 28.3 mg/L at w2 and 15.0 mg/L at w6 for achieving endoscopic remission at w12.1 IFX TCs during induction were not significantly different between patients who received standard and intensified induction therapy. Conclusion Colectomy rates remain a significant burden of ASUC even for patients receiving IFX. In our interim IPDMA, we did not identify baseline predictors of colectomy-free survival. Poor target attainments of the previously established concentration targets demand dose optimisation. Pharmacometrics modelling of the IFX dose-exposure-biomarker/measure-response relationship within the spECTRUM consortium (DEFINE study) will facilitate dose-finding simulations to demonstrate the value of model-informed therapeutic drug monitoring.

S990 Cost Analysis of Inpatient Originator Infliximab (Remicade) vs Biosimilar Infliximab (Renflexis) for Acute Severe Ulcerative Colitis: A Cost Minimization Study

Introduction: Infliximab (IFX) is a standard, inpatient salvage therapy for treatment of refractory acute severe ulcerative colitis (ASUC). Inpatient IFX, as the originator Remicade, significantly increases colectomy-free survival in this population. The biosimilar Renflexis offers reduced cost as compared to Remicade. We performed a cost-minimization analysis to compare costs with Remicade and Renflexis for inpatient treatment of ASUC. Methods: Retrospective clinical and financial data was obtained from 34 inpatients with refractory ASUC who had received treatment with Renflexis (17) or Remicade (17) between 2019-2021. Clinical data included admission and discharge serum albumin (alb), hemoglobin (Hgb), C-reactive protein (CRP), and colectomy rate within 30 days of treatment (CR-30). Financial data included a decision support drug cost (DSDC), depicting the total cost associated with inpatient infliximab administration, and total inpatient care cost, depicting the full cost of the inpatient admission. The following equation generated a ratio (rDSDC) which represents the percentage of how much the DSDC accounts for the total inpatient care cost, after controlling for dose of infliximab and length of stay. [DSDC of IFX/Number of Units of IFX] ÷ [Total Inpatient Cost of Care/Length of Stay in Days] Mean and unpaired T-test (parametric test) were used for clinical data analysis. Median and non-parametric test called Wilcoxon ranked sum test were used for financial data analysis. (Figure) Results: No differences were found in baseline or discharge clinical parameters including baseline CRP (P=0.64), alb (P=0.1294), Hgb (P=0.5051), discharge CRP (P=0.1244), alb (P=0.8728), Hgb (P=0.4875), or CR-30 (23.53% vs. 29.41%, p=0.6975) (Table). Median rDSDC was 0.387 vs. 0.241 in the Remicade vs. Renflexis groups, respectively (Figure, p = 0.0025) representing a difference of ∼14%. Conclusion: A 14% reduction in cost attributed to DSDC was found using Renflexis, as compared to Remicade, treating inpatient ASUC. Our calculation included median decision support drug cost as a percentage of the total inpatient care cost, controlling for dose of infliximab and length of stay. Such a reduced cost structure promotes use of Renflexis for ASUC inpatients, which may result in improved utilization, improved health outcomes, and reduced costs for patients and hospitals. Further studies may confirm non-inferiority and demonstrate cost-effectiveness.Figure 1 Table 1. - Remicade (n=17) Renflexis (n=17) P- Value Admission C-reactive protein 117.73 mg/L 103.98 mg/L 0.6400 Albumin 2.74 g/dL 2.45 g/dL 0.1294 Hgb 11.34 g/dL 10.82 g/dL 0.5051 Discharge C-reactive protein 17.18 mg/L 30.99 mg/L 0.1244 Albumin 2.36 g/dL 2.4 g/dL 0.8728 Hgb 10.11 g/dL 9.71 g/dL 0.4875 Colectomy rate within 30 days of Treatment 23.53% (n=4) 29.41% (n=5) 0.6975 Median ratio of decision support drug cost to total inpatient cost of care after accounting for number of units of IFX administered and length of inpatient stay in days 0.387 0.241 0.0025

Tofacitinib Salvage Therapy for Children Hospitalized for Corticosteroid- and Biologic-Refractory Ulcerative Colitis.

Colectomy rates following acute severe ulcerative colitis have plateaued around 20% despite intravenous corticosteroid and intensified anti-tumor necrosis factor (TNF) biologic dosing. Recent studies have shown tofacitinib to provide additional benefit in further decreasing colectomy rates among hospitalized adult patients with corticosteroid- and anti-TNF-nonresponsive ulcerative colitis. Pediatric data describing the effectiveness of tofacitinib for this indication does not yet exist. We aimed to describe the treatment courses and colectomy-free survival among pediatric patients treated with tofacitinib while hospitalized for refractory ulcerative colitis. We performed a retrospective single-center cohort study of consecutive hospitalized pediatric patients initiating tofacitinib for refractory ulcerative colitis from 2018 to 2021. The primary outcome was 90-day colectomy-free survival. Secondary outcomes included colectomy-free clinical remission, corticosteroid independence, colectomy-free tofacitinib drug-persistence, tofacitinib-related adverse events, and postoperative complications. Baseline characteristics and details of the timing and positioning of therapies utilized during hospitalization were described. Outcomes were described using counts, percentages, and Kaplan-Meier curves. Eleven patients met inclusion criteria. All patients demonstrated nonresponse to both intravenous corticosteroids and anti-TNF therapy prior to tofacitinib initiation. Median hospitalization length was 22 days and mean maximum pediatric ulcerative colitis activity index during hospitalization was 68. Eight of 11 patients remained colectomy-free at 90 days following hospital admission and 6 remained colectomy-free over median 182-day follow-up, including 4 of whom remained on tofacitinib. Tofacitinib may represent a new treatment option for hospitalized pediatric patients with corticosteroid- and anti-TNF-nonresponsive ulcerative colitis. Future research is essential in determining the optimal positioning of these therapies.

Multicenter Cohort Study of Infliximab Pharmacokinetics and Therapy Response in Pediatric Acute Severe Ulcerative Colitis

We aimed to model infliximab (IFX) pharmacokinetics (PK) in pediatric acute severe ulcerative colitis (ASUC) and assess the association between PK parameters, including drug exposure, and clinical response. We studied a multicenter prospective cohort of hospitalized children initiating IFX for ASUC or IBD-unclassified. Serial IFX serum concentrations over 26 weeks were used to develop a PK model. We tested the association of PK parameter estimates with day 7 clinical response, week 8 clinical remission, week 26 corticosteroid-free clinical remission (CSF-CR) (using the Pediatric Ulcerative Colitis Activity Index), and colectomy-free survival. Thirty-eight participants received IFX (median initial dose, 9.9 mg/kg). Day 7 clinical response, week 8 clinical remission, and week 26 CSF-CR occurred in 71%, 55%, and 43%, respectively. Albumin, C-reactive protein, white blood cell count, platelets, weight, and antibodies to IFX were significant covariates incorporated into a PK model. Week 26 non-remitters exhibited faster IFX clearance than remitters (P= .013). However, cumulative IFX exposure did not differ between clinical response groups. One (2.7%) and 4 (10.8%) participants underwent colectomy by week 26 and 2 years, respectively. Day 3 IFX clearance >0.02 L/h was associated with colectomy (hazard ratio, 58.2; 95% confidence interval, 6.0-568.6; P < .001). At median higher-than-label IFX dosing for pediatric ASUC, baseline faster IFX CL was associated with colectomy and at week 26 with lack of CSF-CR. IFX exposure was not predictive of clinical outcomes. Higher IFX dosing may sufficiently optimize early outcomes in pediatric ASUC. Larger studies are warranted to determine whether sustained intensification can overcome rapid clearance and improve later outcomes. gov identifier: NCT02799615.

DOP17 Evaluating segmental healing with the modified Mayo endoscopic score (MMES) has a clear additional value in predicting long-term outcome in patients with Ulcerative Colitis: Results from a prospective cohort study

Abstract Background Most endoscopic scoring systems (including the Mayo endoscopic subscore, MES) do not consider the extent of inflammation and can therefore not pick up segmental endoscopic improvement. The modified Mayo endoscopic score (MMES) was developed to overcome this limitation. We examined the predictive value of the MMES in addition to the MES on long-term clinical outcome in ulcerative colitis (UC). Methods Between 2014 and 2017, patients initiating biologic therapy for active UC (baseline MES ≥2) were recruited. Patients without assessment of the upper margin of inflammation or with a clinical follow-up &amp;lt;12 months were excluded. We conducted a clinical and endoscopic assessment at baseline and week 8 (adalimumab, ADM) or 14 (golimumab, GOL; infliximab, IFX; vedolizumab, VDZ). Clinical response was defined as a decrease in the adapted Mayo score (excluding physician global assessment) with ≥2 points and ≥30%, plus a decrease in rectal bleeding score ≥1 or an absolute rectal bleeding score ≤1. We classified patients by evolution of endoscopic activity at week 8/14 in group A (endoscopic healing, MES ≤1), group B (segmental healing, MES &amp;gt;1 but decrease in MMES ≥30%) and group C (MES &amp;gt;1 and no drop in MMES ≥30%). Clinical relapse-free, discontinuation-free and colectomy-free survival was estimated by Kaplan-Meier analysis with log-rank test. Results A total of 150 UC patients were included (52% male, median age 42 years, median disease duration 7 years) with a median (IQR) follow-up of 61 (48–68) months. An anti-TNF was initiated in 74 (35 IFX, 23 ADM, 16 GOL), and VDZ in 76 patients. A significant reduction in MES and MMES was observed at week 8/14 (cf. table). In group A 67/69 (97%) patients achieved clinical response compared to 15/27 (55%) in group B and 11/54 (20%) in group C. During follow-up 60/93 (65%) patients maintained clinical response, 83/150 (55%) patients discontinued treatment due to primary non-response or loss of response and 33/150 (22%) patients underwent colectomy. The ΔMMES demonstrated to be of additional predictive value: there was a significant difference between groups B and C regarding clinical relapse, drug persistence and need for colectomy (cf. figure). Conclusion Although MES ≤1 remains the best predictor of long-term outcome, the MMES - identifying a subgroup with a segmental endoscopic response - demonstrated a clear additional value predicting long-term outcome in UC. These promising results merit inclusion of the MMES in future clinical trials. Table The MMES is calculated by multiplying the Mayo endoscopic subscore for the different colon segments with the maximal extent of inflammation (in decimeters) divided by the number of segments with active inflammation (Lobatón T, et al. JCC 2015; 9:846–52.) Figure

Comparative effectiveness of a second-line biologic in patients with ulcerative colitis: vedolizumab followed by an anti-TNF versus anti-TNF followed by vedolizumab

BackgroundSequential drug treatment with biological agents in ulcerative colitis (UC) is becoming increasingly complex. There are few studies comparing head-to-head outcomes in second-line treatments. The study assesses whether using anti-tumour...

Intravenous tacrolimus is a superior induction therapy for acute severe ulcerative colitis compared to oral tacrolimus

BackgroundIntravenous corticosteroid is the mainstay for managing acute severe ulcerative colitis, but one-third of patients do not respond to intravenous corticosteroid. Tacrolimus, a salvage therapy before colectomy, is usually orally administered, though its bioavailability is low compared intravenous administration. The efficacy of intravenous tacrolimus has not been widely studied.AimTo determine the efficacy and safety of intravenous tacrolimus for the treatment of acute severe ulcerative colitis.MethodsEighty-seven hospitalized acute severe ulcerative colitis patients were enrolled for a prospective cohort study between 2009 and 2017. Sixty-five patients received intravenous tacrolimus and 22 received oral tacrolimus. The primary outcome was the achievement of clinical remission within 2 weeks. Relapse and colectomy incidence and adverse events were assessed at 24 weeks.ResultsResponse rates of both treatments exceeded 50% but were not significantly different. The remission rate was higher in intravenous tacrolimus compared with oral tacrolimus. At 24 weeks, oral and intravenous tacrolimus showed similar relapse-free survival rates; however, colectomy-free survival rates were higher in intravenous tacrolimus compared with oral tacrolimus.ConclusionsPatients receiving intravenous tacrolimus achieved superior remission and colectomy-free survival rates compared with patients receiving oral tacrolimus. Safety was similar between the two treatments.

Tofacitinib as salvage therapy for 55 patients hospitalised with refractory severe ulcerative colitis: A GETAID cohort.

Up to 25% of patients with ulcerative colitis (UC) will require hospitalization for severe flare. In patients hospitalised for severe flare, who previously experienced multiple drug failures, including steroids and anti-TNF agents, new quick-acting medical options are needed. Tofacitinib is effective in refractory UC and has a rapid onset of action. To evaluate effectiveness and safety of tofacitinib as rescue therapy in patients hospitalised for UC flare. We conducted an observational and multicentre study with both retrospective and prospective collections in 14 GETAID centres. The primary objective was to assess the survival without colectomy following tofacitinib initiation in patients hospitalised for a UC flare. We determined rates of clinical response, clinical remission, and steroid-free clinical remission at week 6 and week 14 and safety. Fifty-five patients were included (49 with prior infliximab failure and 19 previously exposed to ciclosporin). With a median follow-up of 6.5months (interquartile range [IQR] [3-12.3]), rate of colectomy-free survival was estimated at 78.9% (95 CI [68.5-90.9]) and 73.6% (95 CI [61.9-87.3]) at 3 and 6months, respectively. Rates of clinical response, clinical remission and steroid-free clinical remission were 60%, 45.5% and 37.5% at week 6 and 41.8%, 34.5% and 32.7% at week 14. Regarding safety, no death was observed, three patients withdrew tofacitinib due to adverse events. Two herpes zoster infections occurred in patients aged over 60years old. No venous thrombotic or major adverse cardiovascular events occurred. Tofacitinib appears as a promising option in patients hospitalised with a UC flare but needs further validation in controlled trials.