Refractory Ulcerative Colitis Research Articles

Laparoscopic Robotic-Assisted Restorative Proctocolectomy and Ileal J-Pouch-Anorectal Anastomosis in Children: Shifting to a Two Stage-Approach.

Background: Restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis (IPAA) is the gold standard surgical treatment for patients with ulcerative colitis (UC) unresponsive to medical therapy and those with familial adenomatous polyposis. Robotic IPAA is a safe and feasible option for the surgical treatment of UC in children. The feasibility of IPAA without ileostomy has been demonstrated in adult in the modified two-stage approach. Aim: The aim of the study was to examine feasibility, outcomes, and complications of robotic modified two-stage approach for RPC with IPAA in pediatric patients comparing it with robotic three-stage approach. Methods: All patients aged 4-18 years who underwent operative treatment for medically refractory UC were included. Demographic and clinical features, age at colectomy and at reconstructive surgery, intraoperative details and complications, and postoperative outcomes were analyzed. Results: Thirteen patients were included in the study (6 males, 7 females). Ileostomy was fashioned in 8 patients at the time of RPC and IPAA (Group 1); in 5 patients the bowel continuity was reintegrated at the time of IPAA (Group 2). No intraoperative complications and no conversions were recorded. One patient of Group 1 had a postoperative pouch complication. The 5 patients who underwent a two-stage procedure did not show short-term complications. No statistical differences were found between the groups in short-term (P = .48) and long-term complications (P = .07). Conclusions: Modified two-stage IPAA is a safe and feasible option in pediatric patients with UC, and RALS offers advantages over other techniques for the precision of rectal dissection and ileo-anal anastomosis.

FMT Combined with Vedolizumab for the Treatment of Refractory Ulcerative Colitis.

FMT Combined with Vedolizumab for the Treatment of Refractory Ulcerative Colitis.

Clinical profiles of leucine-rich alpha-2 glycoprotein for indicating mucosal healing in ulcerative colitis patients under administration of molecular targeted drug.

Leucine-rich alpha-2 glycoprotein (LRG) is a useful serum biomarker for monitoring disease activity during remission in ulcerative colitis (UC). Because LRG levels differ among patients, it is necessary to assess them after profiling patients, especially in patients with refractory UC undergoing treatment with molecular targeted drugs. This study aimed to analyze LRG levels that indicate mucosal healing according to clinical characteristics and molecular targeted drugs. Among 214 patients with UC treated with biologics or Janus kinase (JAK) inhibitors, this study evaluated 111 patients (174 measurements) who achieved mucosal healing based on colonoscopy performed within 2 months before and after LRG measurement and experienced no changes in disease status or treatment during the same period. We analyzed the relationship of LRG with clinical characteristics (including sex, age, body mass index, and disease type and duration) and molecular targeted drugs. Compared with men, women had significantly higher LRG levels (9.5 μg/mL vs. 11.3 μg/mL, P<0.001). In addition, LRG levels were significantly higher in older patients (12.0 μg/mL vs. 9.8 μg/mL, P<0.01). LRG levels were the highest in patients treated with vedolizumab and lower in patients treated with JAK inhibitors (vedolizumab: 12.7 μg/mL; tofacitinib: 8.9 μg/mL; upadacitinib: 8.5 μg/mL; and filgotinib: 9.1 μg/mL; P<0.0001). Among the patients who achieved mucosal healing, LRG levels were significantly higher in women and older patients. LRG levels differed according to the molecular targeted drug used, and were higher with vedolizumab and lower with JAK inhibitors.

Mucosal cytokine expression associated with deep endoscopic mucosal healing in ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammatory disease of unknown cause for which no curative treatments have been developed. Cytokines play an important role in the pathogenesis of UC, and therapies targeting specific cytokines have been successful in treating refractory UC. The purpose of this study was to measure mucosal cytokines in UC and identify those that contribute to non-relapsing mucosal healing diagnosed by endoscopy. This prospective, observational study included 163 patients with UC. The mucosa was evaluated by Mayo Endoscopic Subscore (MES) and linked color imaging (LCI) at the time of endoscopy, and cytokine mRNA expression in biopsy tissue taken from the same site was quantified by real-time PCR and compared with endoscopic findings. The relationship between cytokine mRNA expression and endoscopic findings was investigated. Cytokines such as IFNγ, IL-1β, IL-8, IL-17A, and IL-23 were significantly elevated in proportion to endoscopic severity of MES and LCI classification.Interestingly, we found differences in the expression of cytokines (e.g., IL-22 and IL-33) between MES and LCI classification according to disease severity. Additionally, pathway analysis based on RNA sequencing compared between LCI-A and LCI-B in the patients diagnosed as MES 0 revealed that IL-5 and IL-6 are involved in the finer differences in endoscopic mucosal redness. This study is the first to report the correlation between mucosal cytokine expression and the pathogenesis of mucosal healing (MH) in UC and supports the contribution of specific cytokines as molecular markers of MH or in the pathogenesis of MH in UC.

Massive bleeding and perforation due to post-colectomy pan-enteritis with a significant response to biologic in a patient with ulcerative colitis: a case report

BackgroundPost-colectomy pan-enteritis in ulcerative colitis (UC) is very rare, but it is often severe and fatal. We present a case of massive bleeding and perforation due to post-colectomy pan-enteritis, which showed a significant response to biologics in a UC patient.Case presentationA 30-year-old woman with a 5-month history of pancolitis UC underwent subtotal colectomy with ileostomy and mucosal fistula for refractory UC. She was diagnosed with small bowel obstruction on postoperative day (POD) 8 and bowel bleeding was observed on POD18. Reoperation was performed for bowel obstruction and bleeding on POD20. Intraoperatively, adhesive small bowel obstruction in the ileum and multiple erosions and ulcers with perforation were observed throughout the small bowel. We diagnosed post-colectomy pan-enteritis, and jejunostomy, lavage, adhesiolysis, and a simple closure of the perforated ileum were performed. High-dose steroid therapy for pan-enteritis was administered immediately after reoperation, and infliximab was administered because of worsening bleeding on day 3 after reoperation. Bleeding decreased one day after biologic administration and bleeding completely disappeared on day 10 after biologic administration. Specimens obtained from the terminal ileum at colectomy showed a normal ileum without inflammation and villus atrophy, while specimens from the perforated ileum showed congestion, villous atrophy, epithelial erosion, and mononuclear cell infiltration. No cryptitis, crypt distortion, or basal plasmacytosis (common characteristics in UC) were observed in either specimen.ConclusionAn early diagnosis and intervention are important for post-colectomy pan-enteritis, and infliximab may be effective. Post-colectomy pan-enteritis with a multiple ulcer phenotype has different histological characteristics from UC and may have a different pathogenesis.

Navigating treatment resistance: Janus kinase inhibitors for ulcerative colitis

The management of refractory ulcerative colitis (UC) and acute severe UC (ASUC) is challenging due to the lack of standardized approaches in cases resistant to multiple treatments. In this editorial, I investigate the efficacy and safety of Janus kinase inhibitors, particularly upadacitinib and tofacitinib, in controlling severe and refractory disease. I highlight a notable case report by Xu et al , which explores the case of a patient with primary nonresponse to two classes of biologics and two fecal microbiota transplants who exhibited a remarkable response to upadacitinib. Furthermore, I discuss the use of tofacitinib in refractory UC and ASUC, either as monotherapy or in combination with biologics, which has shown promising response rates. Additionally, emerging evidence of upadacitinib efficacy in ASUC is presented. Overall, these cases emphasize the complex nature of managing refractory ASUC and the potential of small-molecule therapies to achieve remission. Further research is needed to refine treatment strategies for patients with treatment-resistant UC.

Connective tissue disorder is a risk factor for ileoanal pouch failure: A case-control study

IntroductionIleal-pouch anal anastomosis (IPAA) is a widely preferred surgical intervention in patients with medically refractory ulcerative colitis, familial adenomatous polyposis, and indeterminate colitis. Concerns have been raised regarding the impact of connective tissue disorders on the outcomes of IPAA owing to potential alterations in collagen metabolism. To date, there is a lack of studies assessing the feasibility, long-term viability, and pouch function of IPAA in patients with connective tissue disorders. We hypothesized that the presence of a connective tissue disorder was associated with an increased risk of pouch failure. MethodsData were collected from a prospectively maintained pouch database and chart review. Patients with connective tissue disorders were propensity score matched in a 1:5 ratio with control pouch patients without connective tissue disorders. A comparative analysis of the demographics, long-term complications, functional outcomes, and QoL was conducted. ResultsNineteen patients with connective tissue disorders were matched with 95 control pouch patients. Postoperative diagnoses included ulcerative colitis (82.5%), indeterminate colitis (7%), constipation (5.3%), Crohn's disease (4.4%), and familial adenomatous polyposis (1%). The connective tissue disorders identified included unspecified diffuse connective tissue disorders (26.3%), Ehlers-Danlos syndrome (15.7%), Sjögren's syndrome (15.7%), and others (31.2%). Patients with connective tissue disorders were more likely to have pouch leaks (OR 4.8, 95% CI: 1.54,15, p=0.007), pouchitis (OR 3.02, 95% CI: 1.09, 8.37, p=0.034), pouch revisions (OR 3.83, 95% CI: 1.31,11.2, p=0.014), and pouch failure (OR 3.55, 95% CI: 1.25, 10.1, p=0.017). When questioned, patients with connective tissue diseases were more likely to have work restrictions (OR 4.68, 95% CI: 0.74, 6.38, p=0.005) and a worse quality of life (std. estimate -0.15, 95% CI: -0.28,-0.19, p=0.025). ConclusionPatients with connective tissue diseases are more likely to be affected by pouch-related complications and pouch failure and report worse quality of life. Physicians treating patients with these disorders should counsel patients appropriately and be aware of the elevated risks of leaks, pouchitis, and pouch failure.

Combination of granulocyte–monocyte apheresis and tofacitinib: Multicentre and retrospective study

ObjectiveGranulocyte–monocyte apheresis (GMA) has shown to be safe and effective in treating ulcerative colitis (UC), also in combination with biologics. The objective of this study is to evaluate the efficacy and safety of combining GMA after primary non-response (PNR) or loss of response (LOR) to tofacitinib (TOFA) in patients with UC. Patients and methodsRetrospective study including all patients with refractory UC who received GMA plus TOFA. Efficacy was assessed 1 and 6 months after finishing GMA by partial Mayo score, C-reactive protein (CRP) and fecal calprotectin (FC). Descriptive statistics and non-parametric tests were used in the statistical analysis. ResultsTwelve patients were included (median 46 years [IQR, 37–58]; 67% female; 67% E3). Patients were mostly receiving TOFA 10mg bid (75%), and 33% also concomitant steroids at baseline. Median partial Mayo score at baseline was 7 (IQR, 5–7), and it decreased to a median of 2 (IQR, 0–3) and 0 (IQR, 0–3) after 1 and 6 months (p=0.027 and 0.020, respectively), while no differences were found in CRP and FC. Clinical remission was achieved by 6 patients both at 1 (50%) and 6 months (67%). CF values<250mg/kg were achieved by 2 and 4 patients at 1 and 6 months (data available in 5 and 7 patients, respectively). No patient required dose-escalation of TOFA, and one patient was able to de-escalate the drug. No patient required colectomy and all patients under steroids were able to stop them. ConclusionThe combination of GMA and TOFA can be effective in selected cases of UC after PNR or LOR to this drug.

Long-term efficacy and safety of tofacitinib in patients with ulcerative colitis: 3-year results from a real-world study.

The efficacy and safety of tofacitinib for the treatment of refractory ulcerative colitis (UC) has been demonstrated in clinical trials. Although, a series of reports with real-world evidence of its short-term efficacy and safety profiles have already been published, reports of long-term real-world data have been limited. We aimed to show our 3-year evidence on the clinical use of tofacitinib for the treatment of UC, focusing on its efficacy and safety profiles. A retrospective observational study was conducted on patients who started tofacitinib for active refractory UC at our hospital. The primary outcome was the retention rate until 156 weeks after initiating tofacitinib. The secondary outcomes were short-term efficacy at 4, 8, and 12 weeks; long-term efficacy at 52, 104, and 156 weeks; prognostic factors related to the cumulative retention rate; loss of response; and safety profile, including adverse events. Forty-six patients who were able to be monitored for up to 156 weeks after tofacitinib initiation, were enrolled in this study. Continuation of tofacitinib was possible until 156 weeks in 54.3%, with > 50% response rates and > 40% remission rates. Among patients in whom response or remission was achieved and tofacitinib was deescalated after 8 weeks of induction treatment, 54.3% experienced relapse but were successfully rescued by and retained on reinduction treatment, except for 1 patient. No serious AEs were observed in the study. Tofacitinib is effective and safe as long-term treatment in a refractory cohort of UC patients in real-world clinical practice.

Combined Dopaminergic Drugs with Supplemental Progesterone to Treat Recurrent Miscarriage and Ulcerative Colitis despite Diminished Egg Reserve

Rationale: Chronic inflammation of pelvic tissues related to increased cellular permeability may not only be responsible for diminished oocyte reserve (DOR) but may also contribute to recurrent miscarriage and other comorbidities. Objective: To determine if treatment with dextroamphetamine sulfate to release more dopamine from sympathetic nerve fibers to decrease excessive cellular permeability, and thus reduce excessive cellular immune activity, coupled with progesterone supplementation from luteal phase throughout the first trimester to increase the amount of the immunomodulatory protein the progesterone induced blocking factor (PIBF) could prevent another miscarriage in a 37-year-old woman with recurrent pregnancy losses. Findings: With this treatment, not only did she conceive in her first treatment cycle and delivered a full-term healthy baby, but the dextroamphetamine markedly improved her ulcerative colitis. Proof that the improvement of the ulcerative colitis was medication related and not merely fortuitous was determined by proving Koch’s postulates. The improvement was found to be long-lasting in that she has not had any symptoms of inflammatory bowel disease for 1 ½ years post-partum. Conclusions: Dopaminergic drugs plus progesterone should be considered first in women with DOR and a manifestation of potential excessive inflammation as evidenced in this case by inflammatory bowel disease. This is the second case report of improving treatment refractory ulcerative colitis with dextroamphetamine, which is considerably safer to the patient and more efficacious than the standard immune suppressants.

A Propensity Score-Matched Analysis of Single-Port Vs Multiport Laparoscopic Total Abdominal Colectomy With End Ileostomy for Medically Refractory Ulcerative Colitis.

Medically refractory ulcerative colitis necessitates surgical intervention, with total abdominal colectomy with end ileostomy being a definitive treatment. The comparison between single-port and multiport laparoscopic surgery outcomes remains underexplored. To compare the surgical outcomes of single-port versus multiport laparoscopic surgery in patients undergoing total abdominal colectomy with end ileostomy for medically refractory ulcerative colitis. A retrospective analysis comparing single-port to multiport surgery in patients with ulcerative colitis from 2010 to 2020. Patients were propensity score-matched 3:1 (multiport to single-port) on baseline characteristics. Single-center academic hospital. A total of 756 patients with medically refractory ulcerative colitis who underwent multiport vs single-port total abdominal colectomy with end ileostomy from 2010 to 2020 were included. Binary outcomes were compared using a multivariable logistic regression model, and a subset analysis was conducted for postoperative stump leak based on stump implantation during surgery. These metrics were compared between the single-port and multiport groups to assess the differences in surgical outcomes. The multiport and single-port groups included 642 and 114 patients, respectively. The matched cohort included 342 multiports and 114 single ports. We observed a statistically significant difference in mean operation time, with the single-port procedure taking 43 minutes less than the multiport laparoscopy. There were no significant differences between the 2 groups in postoperative stump leaks, postoperative ileus, stoma site complications, postoperative readmission within 30 days, postoperative reoperation within 30 days, and subsequent IPAA surgery. In the subset analysis, stump implantation was associated with a higher risk of stump leak in the multiport group. The single-port group had a shorter hospital stay. Retrospective nature and being conducted at a single center. Single-incision laparoscopic total abdominal colectomy in the treatment of mucosal ulcerative colitis is a safe, effective, and efficient approach. In our cohort, single-incision laparoscopy has had shorter operation times and better overall length of stay compared with the multiport approach. Taking into account a less invasive approach, decreased abdominal trauma, and faster recovery, single-port surgery is a viable alternative to multiport surgery. See Video Abstract . ANTECEDENTES:La colitis ulcerosa (CU) médicamente refractaria requiere una intervención quirúrgica, siendo la colectomía abdominal total con ileostomía terminal un tratamiento definitivo. La comparación entre los resultados de la cirugía laparoscópica con puerto único y con puerto múltiple aún no se ha explorado lo suficiente.OBJETIVO:Comparar los resultados quirúrgicos de la cirugía laparoscópica con puerto único versus con puerto múltiple en pacientes sometidos a colectomía abdominal total con ileostomía terminal para CU médicamente refractaria.DISEÑO:Un análisis retrospectivo que comparó la cirugía de puerto único con la de puerto múltiple en pacientes con CU de 2010 a 2020. Los pacientes fueron emparejados por puntuación de propensión 3:1 (puerto múltiple a puerto único) según las características iniciales.AJUSTES:Hospital académico unicentrico.PRINCIPALES MEDIDAS DE RESULTADO:Los resultados binarios se compararon utilizando un modelo de regresión logística multivariable y se realizó un análisis de subconjunto para la fuga postoperatoria del muñón basado en la implantación del muñón durante la cirugía. Estas métricas se compararon entre los grupos de puerto único y de puerto múltiple para evaluar las diferencias en los resultados quirúrgicos.RESULTADOS:Los grupos de puerto único y multipuerto incluyeron 642 y 114 pacientes, respectivamente. La cohorte emparejada incluyó 342 puertos múltiples y 114 puertos únicos. Observamos una diferencia estadísticamente significativa en el tiempo medio de operación, ya que el procedimiento de puerto único duró 43 minutos menos que la laparoscopia de puerto múltiple. No hubo diferencias significativas entre los dos grupos en las fugas del muñón posoperatorio, el íleo posoperatorio, las complicaciones del sitio del estoma, el reingreso posoperatorio dentro de los 30 días, la reoperación posoperatoria dentro de los 30 días y la cirugía IPAA posterior. En el análisis de subconjunto, la implantación del muñón se asoció con un mayor riesgo de fuga del muñón en el grupo multipuerto. El grupo de puerto único tuvo una estancia hospitalaria más corta.LIMITACIONES:Carácter retrospectivo, realizándose en un único centro.CONCLUSIÓN:La colectomía abdominal total laparoscópica de incisión única en el tratamiento de la colitis ulcerosa mucosa es un enfoque seguro, eficaz y eficiente. En nuestra cohorte, en comparación con el abordaje multipuerto, la laparoscopia de incisión única ha mostrado tiempos de operación más cortos y una mejor duración total de la estancia hospitalaria. Teniendo en cuenta un enfoque menos invasivo, un menor traumatismo abdominal y una recuperación más rápida, la cirugía con puerto único es una alternativa viable a la cirugía con puertos múltiples. (Traducción-Dr. Mauricio Santamaria ).

Tofacitinib in Pediatric Ulcerative Colitis: A Retrospective Multicenter Experience.

Tofacitinib has recently been approved for treatment of moderate-to-severe ulcerative colitis (UC) in adults, yet pediatric data are limited. This international multicenter study describes the effectiveness and safety of tofacitinib in pediatric UC. This is a retrospective review of children diagnosed with UC treated with tofacitinib from 16 pediatric centers internationally. The primary outcome was week 8 corticosteroid-free clinical remission (Pediatric Ulcerative Colitis Activity Index <10). Secondary outcomes were clinical response (≥20-point decrease in Pediatric Ulcerative Colitis Activity Index) at week 8, corticosteroid-free clinical remission at week 24, and colectomy rate and adverse safety events through to last follow-up. The primary outcome was calculated by the intention-to-treat principle. We included 101 children with a mean age at diagnosis of 12.8 ± 2.8 years and a median disease duration of 20 months (interquartile range [IQR], 10-39 months). All had treatment failure with at least 1 biologic agent, and 36 (36%) had treatment failure with 3 agents. Median follow-up was 24 weeks (IQR, 16-54 weeks). Sixteen (16%) children achieved corticosteroid-free clinical remission at week 8, and an additional 30 (30%) demonstrated clinical response. Twenty (23%) of 88 children achieved corticosteroid-free clinical remission at week 24. A total of 25 (25%) children underwent colectomy by median 86 days (IQR, 36-130 days). No serious drug-related adverse events were reported; there was 1 case of herpes zoster and 2 cases of minor blood test perturbations. In this largest real-life pediatric cohort to date, tofacitinib was effective in at least 16% of patients with highly refractory UC by week 8. Adverse events were minor and largely consistent with adult data.

Inpatient Infliximab Biosimilar Cost-Savings: Cost Analysis of Inpatient Treatment with Originator Infliximab (Remicade™) versus Biosimilar Infliximab (Renflexis™) for Acute Severe Ulcerative Colitis

Introduction: Infliximab (IFX) is a standard, inpatient salvage therapy for the treatment of refractory acute severe ulcerative colitis (ASUC). Remicade™ is the originator IFX. Its biosimilar Renflexis™ offers a reduced cost structure. We performed a cost-minimization analysis to compare costs with Remicade™ and Renflexis™ for the inpatient treatment of ASUC. Methods: Retrospective clinical and financial data were obtained from 34 inpatients with refractory ASUC who received Renflexis™ (n = 17) or Remicade™ (n = 17) between 2019 and 2021. Clinical data included admission and discharge laboratory values. Financial data included a decision support drug cost (DSDC), constituting the total cost associated with inpatient IFX administration, and total inpatient cost of care. The following equation generated a ratio (rDSDC) representing the percentage of drug cost (or DSDC) of the total inpatient cost of care, after controlling for IFX dose and length of stay: [DSDC of IFX/Number of Units of IFX] ÷ [Total Inpatient Cost of Care/Length of Stay in Days]. Median and non-parametric Wilcoxon ranked sum test were used for analyzing patient demographics, clinical, and financial data. Results: No differences were found in baseline or discharge clinical parameters. The median unadjusted ratio of DSDC to total inpatient cost of care was 0.387 versus 0.241 in the Remicade™ versus Renflexis™ groups (p = 0.0025), respectively, representing an absolute difference of ∼14%. Median adjusted rDSDC were 0.04 versus 0.024 in the Remicade™ versus Renflexis™ groups, respectively, representing a relative cost reduction of ∼40% (p = 0.0001). Discussion: The unadjusted absolute cost reduction and adjusted relative cost reduction were, respectively, 14% and 40% in the Renflexis™ group as compared to Remicade™, when treating inpatient ASUC. Our calculation included median DSDC as a percentage of the total inpatient cost of care, controlling for IFX dose and length of stay. This reduced cost structure promotes use of Renflexis™ for ASUC inpatients and may reduce costs systemically.

Effectiveness and Safety of Ustekinumab in Pediatric Ulcerative Colitis: A Multi-center Retrospective Study from the Pediatric IBD Porto Group of ESPGHAN.

Current data on ustekinumab therapy in children with ulcerative colitis (UC) or unclassified inflammatory bowel disease (IBDU) are limited. We aimed to evaluate the effectiveness and safety of ustekinumab in pediatric UC and IBDU. This multicenter retrospective study included 16 centers affiliated with the IBD Interest and Porto groups of ESPGHAN. Children with UC or IBDU treated with ustekinumab were enrolled. Demographic, clinical, laboratory, endoscopic, and imaging data as well as adverse events were recorded. Analyses were all based on the intention-to-treat principle. Fifty-eight children (39 UC and 19 IBDU, median age 14.5 [IQR 11.5-16.5] years) were included. All had failed biologic therapies, and 38 (66%) had failed two or more biologics. Corticosteroid-free clinical remission (CFR) was observed in 27 (47%), 33 (57%), and 37 (64%) children at 16, 26, and 52 weeks, respectively. Normalization of C-reactive protein and calprotectin <150μg/g were achieved in 60% and 52%, respectively, by 52 weeks. Endoscopic and radiologic remissions were reached in 8% and 23%, respectively. The main predictors of CFR were diagnosis of UC compared with IBDU (hazard ratio [HR] 2.2, 95% CI 1.03-4.85; p=0.041) and no prior vedolizumab therapy (HR 2.1, 95% CI 1.11-4.27; p=0.023). Ustekinumab serum levels were not associated with disease activity. Adverse events were recorded in six (10%) children, leading to discontinuation of the drug in three. Based on these findings, ustekinumab appears as an effective therapy for pediatric refractory UC and IBDU. The potential efficacy should be weighed against the risks of serious adverse events.

Severe Disease Activity May Predispose Patients to Post-colectomy Duodenitis Associated with Ulcerative Colitis.

Objective Diffuse mucosal inflammation in the duodenum, distinct from peptic ulcer disease, has been repeatedly reported in patients with ulcerative colitis (UC). The pathogenesis of this complication remains uncertain; however, colectomy for medically refractory UC appears to trigger duodenitis. Cases in which colectomy was performed for UC were analyzed to characterize UC-related duodenitis after colectomy. Methods A retrospective case-control study of UC-related duodenitis that developed after colectomy in medically refractory UC between January 2011 and June 2020 was conducted. UC-related duodenitis was diagnosed based on typical clinical, endoscopic, and histological findings, and no duodenitis was endoscopically defined by the normal duodenal mucosa. Clinical and laboratory data, disease severity, and medications used were collected and compared between the UC-related and non-duodenitis cases. Results Ten UC-related duodenitis and 35 non-duodenitis cases were identified among 45 patients with UC who underwent esophagogastroduodenoscopy after colectomy. Disease severity, defined by the C-reactive protein level and partial Mayo score prior to colectomy, was significantly higher in duodenitis patients than in non-duodenitis patients. In comparison to non-duodenitis patients, duodenitis patients more frequently received rescue therapies with calcineurin inhibitors or anti-TNF-α agents at the time of colectomy (100% vs. 65.7%). Conclusion Patients with UC with higher disease activity, especially those who require rescue therapies with calcineurin inhibitors and anti-TNF-α agents, may be prone to developing UC-related duodenitis after colectomy.

Combination of granulocyte–monocyte apheresis and ustekinumab: Multicentre and retrospective study

ObjectiveGranulocyte–monocyte apheresis (GMA) has shown to be safe and effective in ulcerative colitis (UC), also in combination with biologics, mainly with anti-TNF. The aim of this study was to evaluate the efficacy and safety of combining GMA after primary non-response (PNR) or loss of response (LOR) to ustekinumab (UST) in patients with UC. Patients and methodsA retrospective study was performed in 12 IBD Units, including all patients with refractory UC or unclassified IBD (IBD-U) who received combined GMA plus UST. The number and frequency of GMA sessions, filtered blood volume and time of each session were registered. Efficacy was assessed 1 and 6 months after finishing GMA by partial Mayo score, C-reactive protein (CRP) and fecal calprotectin (FC). Descriptive statistics and non-parametric tests were used in the statistical analysis. ResultsSeventeen patients were included (15 UC, 2 IBD-U; median age 47 years [IQR, 35–61]; 59% male; 53% E3). Most patients (89%) had prior exposure to anti-TNF agents and 53% to vedolizumab; 65% were also receiving steroids at baseline. Median partial Mayo score at baseline was 6 (IQR, 5–7) and it significantly decreased after 1 and 6 months (p=0.042 and 0.007, respectively). Baseline FC significantly decreased after 6 months (p=0.028) while no differences were found in CRP. During follow-up, 18% patients started a new biologic therapy and 12% required surgery; 64% of patients under steroids were able to discontinue them. Adverse events were reported in one patient. ConclusionGMA can recapture the response to UST in selected cases of UC after PNR or LOR to this drug.

The GIPP Never Lies: A Case of Refractory Ulcerative Colitis

The GIPP Never Lies: A Case of Refractory Ulcerative Colitis

Real-World Effectiveness of Ustekinumab in Ulcerative Colitis in a United States Multicenter Cohort Consortium.

Pivotal trials have shown that ustekinumab is effective in ulcerative colitis (UC). However, the population included in these trials do not represent the cohort of patients treated in the real world. In this study, we aimed to describe the effectiveness and safety of ustekinumab in a clinical cohort of patients with UC. We performed a multicenter retrospective cohort study and included patients with active UC starting ustekinumab. Variables collected included demographics, clinical data, and disease activity (measured using partial Mayo score [PMS] and endoscopic Mayo score) at follow-up. The primary outcomes were cumulative rates of steroid-free clinical and biochemical remission (SFCBR), defined as a PMS <2 while off steroids and a normal C-reactive protein and/or fecal calprotectin. A total of 245 patients met inclusion criteria. The median time of follow-up was 33 (interquartile range, 17-53) weeks, and 214 (87.3%) had previous exposure to a biologic and/or tofacitinib. Rates of SFCBR, clinical remission, and endoscopic remission at 6 and 12 months were 12.0% (n = 16 of 139), 29.0% (n = 71 of 175), and 18.0% (n = 7 of 39), and 23.8% (n = 15 of 63), 54.3% (n = 57 of 105), and 31.0% (n = 9 of 29), respectively. Non-Hispanic White race, higher baseline PMS, and the use of concomitant corticosteroids were independently associated with failure to achieve SFCBR. Of the 73 that were dose escalated, 28.4% did not respond, 49.3% experienced a benefit, and 21.6% achieved remission. In a population enriched with refractory UC, ustekinumab was well tolerated and induced remission in a significant number of patients. Larger studies with a longer follow-up are warranted.

Effect of Tofacitinib on One-Year Colectomy Risk in Anti-TNF Refractory Ulcerative Colitis: A Prospective Multicenter Italian Study.

Tofacitinib is an oral Janus kinase inhibitor recently approved to induce and maintain remission in ulcerative colitis (UC). Considering the number of anti-TNF non-responders, this study aims to assess the effectiveness and safety of tofacitinib in a cohort of multi-failure patients with moderate-to-severe UC at 52weeks. From January 2021 to March 2023, we performed a prospective multicenter study observing adult patients with moderate-to-severe UC starting tofacitinib after an anti-TNF failure for a 52-week-long period. Effectiveness and safety were assessed in terms of colectomy rate, clinical remission and response, endoscopic remission, steroid-free clinical remission, and rate of adverse events. We included 58 patients with UC with an age of 42 ± 14.4years, 59% males, 96.6% left-sided or pancolitis, who were failure to a single (65.5%) or more than one anti-TNF (34.5%). Only 6 (10.3%) patients underwent colectomy. Colectomy was clinically associated with the necessity and the number of extra cycles of tofacitinib 10mg bid at W8 (p = 0.023) and W24 (p = 0.004), and with a higher partial Mayo score at W8 (p = 0.025). At W52, clinical remission, clinical response, and steroid-free clinical remission were 53.4%, 43.1%, and 48.3%, respectively. Of 22 performed colonoscopies at W52, 11 (50%) showed endoscopic remission. Adverse events occurred in 14 (24.1%) patients, but only 2 (3.4%) led to tofacitinib discontinuation. In a real-life setting of patients with anti-TNF refractory UC, tofacitinib has proved to be effective in preventing colectomy and inducing clinical and endoscopic remission at 52weeks with a good safety profile.

Real-world effectiveness of ustekinumab and vedolizumab in TNF-exposed pediatric patients with ulcerative colitis.

Vedolizumab (VDZ) and ustekinumab (UST) are second-line treatments in pediatric patients with ulcerative colitis (UC) refractory to antitumor necrosis factor (anti-TNF) therapy. Pediatric studies comparing the effectiveness of these medications are lacking. Using a registry from ImproveCareNow (ICN), a global research network in pediatric inflammatory bowel disease, we compared the effectiveness of UST and VDZ in anti-TNF refractory UC. We performed a propensity-score weighted regression analysis to compare corticosteroid-free clinical remission (CFCR) at 6 months from starting second-line therapy. Sensitivity analyses tested the robustness of our findings to different ways of handling missing outcome data. Secondary analyses evaluated alternative proxies of response and infection risk. Our cohort included 262 patients on VDZ and 74 patients on UST. At baseline, the two groups differed on their mean pediatric UC activity index (PUCAI) (p = 0.03) but were otherwise similar. At Month 6, 28.3% of patients on VDZ and 25.8% of those on UST achieved CFCR (p = 0.76). Our primary model showed no difference in CFCR (odds ratio: 0.81; 95% confidence interval [CI]: 0.41-1.59) (p = 0.54). The time to biologic discontinuation was similar in both groups (hazard ratio: 1.26; 95% CI: 0.76-2.08) (p = 0.36), with the reference group being VDZ, and we found no differences in clinical response, growth parameters, hospitalizations, surgeries, infections, or malignancy risk. Sensitivity analyses supported these findings of similar effectiveness. UST and VDZ are similarly effective for inducing clinical remission in anti-TNF refractory UC in pediatric patients. Providers should consider safety, tolerability, cost, and comorbidities when deciding between these therapies.