Effectiveness and Safety of Vedolizumab Induction Therapy for Patients With Inflammatory Bowel Disease.

BACKGROUND & AIMS: Phase 3 trials have shown the efficacy of vedolizumab, which binds to integrin α4ß7, in patients with Crohn's disease (CD) or ulcerative colitis (UC). We investigated the effectiveness and safety of vedolizumab in patients who failed anti-tumor necrosis factor therapy. METHODS: From June through December 2014, there were 173 patients with CD and 121 patients with UC who were included in a multicenter nominative compassionate early access program granted by French regulatory agencies. This program provided patients with access to vedolizumab before it was authorized for marketing. Vedolizumab (300 mg) was administered intravenously at weeks 0, 2, and 6, and then every 8 weeks. Disease activity was assessed using the Harvey-Bradshaw Index for CD and the partial Mayo Clinic score for UC. We report results obtained after the 14-week induction phase. RESULTS: Among the 294 patients treated with vedolizumab (mean age, 39.5 ± 14.0 y; mean disease duration, 10.8 ± 7.6 y; concomitant steroids, 44% of cases), 276 completed the induction period, however, 18 discontinued vedolizumab because of a lack of response (n = 14), infusion-related reaction (n = 2), or infections (n = 2). At week 14, 31% of patients with CD were in steroid-free clinical remission and 51% had a response; among patients with UC, 36% were in steroid-free clinical remission and 50% had a response. No deaths were reported. Severe adverse events occurred in 24 patients (8.2%), including 15 (5.1%) that led to vedolizumab discontinuation (1 case of pulmonary tuberculosis and 1 rectal adenocarcinoma). CONCLUSIONS: In a cohort of patients with CD or UC who failed previous anti-tumor necrosis factor therapy, approximately one third of patients achieved steroid-free clinical remission after 14 weeks of induction therapy with vedolizumab. This agent had an acceptable safety profile in these patients.

Laparoscopic vs. open surgery for T4 colon cancer: A propensity score analysis.

PURPOSE: The study aimed to compare, using propensity score matching (PSM) analyses, the short- and long-term results of laparoscopic colectomy (LC) versus open colectomy (OC) in a bicentric cohort of patients with T4 colon cancer. METHODS: This is a retrospective PSM analysis of consecutive patients undergoing elective LC or OC for pT4 colon cancer (TNM stage II/III) between 2005 and 2014. RESULTS: Overall, 237 patients were selected. After PSM, 106 LC-and 106 OC-matched patients were compared. LC was associated with longer operative time and lower blood loss than OC (220 vs. 190 min, p < 0.0001; 116 vs. 150 mL, p = 0.002, respectively). LC patients showed a faster recovery, which translated into a shorter hospital stay compared to OC (10.5 vs. 15.3 days, p < 0.0001). Conversion was required in 13 (12.2 %) LC patients. No group difference was observed for 30- and 90-day mortality. R0 resection was achieved in the majority of LC and OC patients (93.9 %). The 1-, 3-, and 5-year overall survival was 99, 76.8, and 58.6 %, respectively, for the LC group and 98, 70.1, and 59.9 %, respectively, for the OC group (p = 0.864). The 1-, 3-, and 5-year disease-free survival was 86.3, 66, 57.6 %, respectively, for the LC group and 79.1, 55.1, and 50.2 % for the OC group (p = 0.261). CONCLUSION: With an acceptable conversion rate, laparoscopy can achieve complete oncologic resections of T4 colon cancer similar to open surgery and can be considered a safe and feasible alternative approach that confers the advantage of a faster recovery.

Risk of SARS-CoV-2 infection in healthcare workers with inflammatory bowel disease: a case-control study.

Background: Whether healthcare workers with inflammatory bowel disease (IBD) are at increased risk of Novel coronavirus disease (COVID-19) due to occupational exposure is unknown. Aim: To assess the risk of COVID-19 in healthcare workers with IBD. Methods: A case control study enrolled 326 healthcare workers with IBD from 17 GETAID centres and matched non-healthcare workers with IBD controls (1:1) for gender, age, disease subtype and year of diagnosis. The study period was year 2020 during the COVID-19 outbreak. Results: In total, 59 COVID-19 were recorded among cases (n = 32) and controls (n = 27), including 2 severe COVID-19 (requiring hospitalization, mechanic ventilation) but no death. No difference was observed between healthcare workers and controls regarding the overall incidence rates of COVID-19 4.9 ± 2.2 vs. 3.8 ± 1.9 per 100 patient-semesters, P = 0.34) and the overall incidence rates of severe COVID-19 (0.6 ± 7.8 vs. 0.3 ± 5.5 per 100 patient-semesters, P = 0.42). In multivariate analysis in the entire study population, COVID-19 was associated with patients with body mass index > 30 kg/m2 (HR = 2.48, 95%CI [1.13-5.44], P = 0.02). Conclusion: Healthcare workers with IBD do not have an increased risk of COVID-19 compared with other patients with IBD.

Long-Term Results of Endoscopic Metal Stenting for Biliary Anastomotic Stricture after Liver Transplantation.

(1) Background: Anastomotic biliary stricture (ABS) is a well-known complication of liver transplantation which can lead to secondary biliary cirrhosis and graft dysfunction. The goal of this study was to evaluate the long-term outcomes of endoscopic metal stenting of ABS in the setting of deceased donor liver transplantation (DDLT). (2) Methods: Consecutive DDLT patients with endoscopic metal stenting for ABS between 2010 and 2015 were screened. Data on diagnosis, treatment and follow-up (until June 2022) were collected. The primary outcome was endoscopic treatment failure defined as the need for surgical refection. (3) Results: Among the 465 patients who underwent LT, 41 developed ABS. It was diagnosed after a mean period of 7.4 months (+/-10.6) following LT. Endoscopic treatment was technically successful in 95.1% of cases. The mean duration of endoscopic treatment was 12.8 months (+/-9.1) and 53.7% of patients completed a 1-year treatment. After a mean follow-up of 6.9 years (+/-2.3), endoscopic treatment failed in nine patients (22%) who required surgical refection. Conclusions: Endoscopic management with metal stenting of ABS after DDLT was technically successful in most cases, and half of the patients had at least one year of indwelling stent. Endoscopic treatment long-term failure rate occurred in one fifth of the patients.

Outcomes after double switching from originator Infliximab to biosimilar CT-P13 and biosimilar SB2 in patients with inflammatory bowel disease: a 12-month prospective cohort study.

BACKGROUND: There are few data regarding multiple switching from the originator Infliximab to its biosimilars. AIM: To assess outcomes and patient perspectives in a prospective manner after double switching from Infliximab to the biosimilars CT-P13 and SB2. METHODS: A total of 158 consecutive patients with inflammatory bowel disease (IBD) receiving CT-P13 maintenance therapy were switched to SB2 and followed for 54 weeks. Patients were stratified according to previous switch from the originator Infliximab to CT-P13 (double switch group) or not (single switch group). RESULTS: The drug persistence was high (94.9%) after 54 weeks. In total, 17 (10.8%) patients experienced loss of response to SB2, including 10 patients who were managed through dose optimisation and continued treatment. No changes were observed in clinical activity scores, fatigue, biological activity and pharmacokinetical parameters after the switch. The safety profile was in line with the current knowledge of Infliximab. According to the Beliefs about Medicines Questionnaire, the patients' perspectives did not change after switching from CT-P13 to SB2. The primary patient concerns remained after the switch, which were focused on effectiveness and safety rather than on the molecular differences between originator and biosimilars or socioeconomic benefits. There were also no differences in the concerns and beliefs between the double and single switch groups. CONCLUSION: Double switching from the originator Infliximab to CT-P13 and then to SB2 was not associated with an impairment in patient beliefs, while the effectiveness, immunogeniity and safety of anti-TNF therapy remained stable after 54 weeks of follow-up.

Effectiveness and Safety of Subcutaneous Rituximab for Patients With Gastric MALT Lymphoma: A Case-Control Comparison With Intravenous Rituximab.

INTRODUCTION: Rituximab is a standard treatment for gastric mucosa-associated lymphoid tissue (MALT) lymphoma (GML). We sought to compare the effectiveness and safety of subcutaneous and intravenous rituximab in a retrospective case-control study. PATIENTS AND METHODS: All consecutive patients with GML treated with subcutaneous rituximab between January 2017 and December 2018 were included and compared to 3 matched control patients (based on Ann Arbor classification, presence of t(11;18) translocation, history of treatment, and type of current treatment) treated with intravenous rituximab between January 2000 and December 2018. Patients with t(11;18) translocation were treated with rituximab in combination with chlorambucil; the other patients were treated with rituximab alone. Effectiveness was assessed at week 52, and safety was assessed through weeks 0 to 52 and compared by the chi-square test. RESULTS: Twenty-five patients were included in the subcutaneous rituximab group and 75 in the intravenous group. There was no difference between the groups in complete remission (78% vs. 76%, P = .99) or overall response rates (91% vs. 89%, P = .99) at week 52. Safety profiles were similar in both groups, with a significant decrease in postinduction grade 2 injection-related reactions and outpatient hospital length of stay in the subcutaneous rituximab group. CONCLUSION: In a small case-control study, we did not find any difference in the effectiveness or safety profiles between subcutaneously and intravenously delivered rituximab for the treatment of patients with GML. We found a decrease in postinduction grade 2 injection-related reactions and outpatient hospital length of stay in the subcutaneous rituximab group.

Colonic mucosa-associated lymphoid tissue lymphoma: a case series.

Primary colonic mucosa-associated lymphoid tissue (MALT) lymphoma accounts for less than 0.5% of all colon cancers. We report 9 cases of colonic MALT lymphomas (median follow up: 9 [IQR 1-26] years). The disease was multi-focal in 4 patients: the most frequent sites were the cecum in 4 and the rectum in 3 patients. The main endoscopic finding was a polypoid lesion. The treatment modalities were rituximab +/- an alkylating agent (n = 5), an alkylating agent alone (n = 2), surgical resection (n = 1), and endoscopic resection (n = 1). Remission was achieved in 8 cases. Three patients relapsed, and 2 were re-treated. At the end of the study period, 67% of the patients were in remission. All patients were symptom-free. This current series of colonic MALT lymphomas shows the indolent nature of the disease, which may be treated with various modalities.

Patients' perspectives after switching from infliximab to biosimilar CT-P13 in patients with inflammatory bowel disease: A 12-month prospective cohort study.

BACKGROUND: Patients' perspectives after switching from infliximab to a biosimilar have yet to be assessed. AIM: To assess patients' perspectives in a prospective manner after switching from infliximab to CT-P13. METHODS: 113 consecutive patients with inflammatory bowel disease (IBD) on maintenance therapy with infliximab were switched to CT-P13. Patients' perspectives were assessed by questionnaires, including the Beliefs about Medicines Questionnaire (BMQ) and FACIT-F (questionnaire regarding fatigue), and patient-reported outcomes (IBD disability index) at the inclusion and after the fourth CT-P13 infusion. RESULTS: After one year, the patients' perspectives did not change after the switch according to BMQ-general, BMQ-specific necessity and BMQ-specific concerns subscales. No difference was observed in the mean IBD-DI score, while a significant improvement in fatigue was observed according to the FACIT-F questionnaire. Patients' concerns were raised about the use of biosimilars and the risks of switching with a significant improvement after switching (65% vs. 42%, respectively, p = 0.01). Fourteen (12.4%) patients experienced loss of response to CT-P13, including 12 with restoration of steroid-free clinical remission after CT-P13 dose optimization. CONCLUSION: Although some concerns were reported, no difference was observed in patients' perspectives after switching from infliximab to CT-P13.

Three-year effectiveness and safety of vedolizumab therapy for inflammatory bowel disease: a prospective multi-centre cohort study.

BACKGROUND: Cohort studies have described the short-term effectiveness and safety of vedolizumab in treating patients with Crohn's disease (CD) and ulcerative colitis (UC), but data beyond 1 year are lacking. AIM: To assess the effectiveness and safety of vedolizumab after 162 weeks in patients with UC and CD. METHODS: Between June and December 2014, 294 patients including 173 patients with CD and 121 with UC were treated with vedolizumab induction therapy. Among them, 149 continued to be treated with vedolizumab beyond week 54 (78 patients with CD and 71 with UC). Disease activity was assessed using the Harvey-Bradshaw Index for CD and the partial Mayo Clinic score for UC. The primary outcome was steroid-free clinical remission at week 162, computed for the whole population included at week 0. RESULTS: Steroid-free clinical remission rates at week 162 were 19.9% and 36.1% in patients with CD and UC respectively. Vedolizumab dose optimisation to 300 mg every 4 weeks instead of 300 mg every 8 weeks was at investigator's discretion and occurred in 58.7% and 52.1% of patients with CD and UC respectively. The 1-, 2- and 3-year persistence rates of vedolizumab were 48.5%, 31.4% and 26.3% respectively, in patients with CD and 61.0%, 49.9% and 42.9% respectively, in patients with UC. No new safety signal was identified. CONCLUSION: Vedolizumab is able to maintain steroid-free clinical remission in patients with UC and CD up to week 162. Loss of response resulting in discontinuation of vedolizumab occurred in 10% of patients per year.

Long-term course of precancerous lesions arising in patients with gastric MALT lymphoma.

BACKGROUND AND AIMS: To evaluate the prevalence and the long-term course of gastric precancerous lesions in patients with GML. PATIENTS AND METHODS: In this retrospective single-centre study, we included 179 patients with GML, 70 with gastric diffuse large B-cell lymphoma (GDLBCL) and 152 with Helicobacter pylori-associated gastritis (HpG), from January 1995 to January 2014. The presence of atrophic gastritis, intestinal metaplasia and neoplastic lesion has been assessed at baseline and during follow-up. RESULTS: Atrophic gastritis was more frequent in the GML group whereas there was also a trend for intestinal metaplasia and gastric dysplasia. In patients with GML, atrophic gastritis, intestinal metaplasia and gastric dysplasia were more frequent in the GML area than in other part of the stomach. During follow-up, the prevalence of atrophic gastritis remained stable overtime whereas intestinal metaplasia and dysplasia tend to increase overtime. In multivariate analysis, the occurrence of dysplasia or carcinoma was associated with the presence of intestinal metaplasia at baseline and male gender. CONCLUSION: GML is associated with gastric precancerous lesion to a higher extent than GDLBCL and HpG. Those precancerous lesions do not regress despite achievement of complete remission of GML and tend to increase overtime.

Risk of serious infection in healthcare workers with inflammatory bowel disease: a case-control study of the Groupe d'Etude Thérapeutique des Affections Inflammatoires du tube Digestif (GETAID).

BACKGROUND: Whether healthcare workers with inflammatory bowel disease (IBD) are at increased risk of severe infection due to daily pathogen exposure is controversial. AIM: To assess the risk of severe infection in healthcare workers with IBD in a large multicentre case-control study. METHODS: The study population comprised 482 healthcare workers with IBD from 17 centres who were matched for gender, age, disease subtype and year of diagnosis to 482 controls (non-healthcare workers with IBD). The study period was between the date of diagnosis of IBD and June 2016. Severe infection was defined as any community-acquired infection that required hospitalisation. RESULTS: With a median follow-up of 9.3 years, 139 severe infections were recorded among cases and controls, including 30 Clostridium difficile infections, 33 severe viral infections, nine tuberculosis infections, 21 community-acquired pneumonia and 46 others. No difference was observed between healthcare workers and controls regarding the overall incidence rates of severe infection. An increased risk of tuberculosis was noted in healthcare workers. In multivariate analysis in the entire study population, severe infection was associated with current exposure to corticosteroids (OR = 3.05, 95% CI [2.06-4.52], P < 0.001), immunosuppressants (OR = 1.98, 95% CI [1.38-2.84], P < 0.001) and anti-TNF agents (OR = 2.93, 95% CI [2.02-4.27], P < 0.001) and reduced with Crohn's disease (OR = 0.63, 95% CI [0.43-0.91], P = 0.01). CONCLUSIONS: Healthcare workers with IBD do not have an increased risk of severe infection compared with other patients with IBD, except for tuberculosis. Screening for tuberculosis exposure should be assessed in this high-risk population when treated with anti-TNF agents.

Second primary malignancies in patients treated for gastric mucosa-associated lymphoid tissue lymphoma.

To assess the risk of second primary malignancy (SPM) in patients with gastric mucosa-associated lymphoid tissue (MALT) Lymphoma (GML), we included 175 patients with GML in the present study. The incidence of SPM in the general population, used for reference, was determined from the French network of cancer registries. During the 1442.9 patient-years of follow-up, 29 patients were diagnosed with incident SPM, including five patients diagnosed with gastric cancer (20.1/1000 patient-years). An increased incidence of SPM was observed in patients with GML (standardized incidence ratios [SIR]: 1.71 [1.14-2.45]) compared to the general French population especially for gastric cancer (SIR: 16.1 [5.19-37.56]). This elevated risk of SPM was significantly increased only in patients treated with immuno/chemotherapy but not in patients treated with Helicobacter pylori eradication alone. Long-term follow-up of patients with GML is mandatory even in patients who have achieved complete remission.

Patients' comorbidities reduce the clinical value of emergency colonoscopy: results of a retrospective cohort study.

BACKGROUND AND STUDY AIMS: Urgent endoscopy is often used to diagnose and sometimes treat acute upper gastrointestinal syndromes (hemorrhage, toxic ingestion, and occlusion). However, its suitability concerning the management of lower gastrointestinal conditions in emergency circumstances is controversial. PATIENTS AND METHODS: We studied the role of emergency colonoscopy in diagnosis and treatment of all consecutive patients presenting with acute lower gastrointestinal symptoms referred to our hospital on an emergency basis. All patients were first managed by physicians from the emergency room and/or the intensive care unit (ICU); the treatments included fluid resuscitation, blood transfusion, and antibiotic or cardiotonic as needed. Bowel cleansing was performed to purge the colon of clots, stool, and blood when clinically possible; alternatively, a bowel enema was used. Patients only underwent a computed tomography (CT) scan prior to the colonoscopy in clinically relevant situations. Colonoscopy was performed within 6 - 36 hours after hospitalization or the beginning of the clinical symptoms (hemorrhage, sepsis, colon distension) or occlusion, as assessed by abdominal CT scan. RESULTS: From 2010 to 2015, 603 patients underwent urgent colonoscopy; among them, 214 (36 %) presented with lower GI bleeding, while 264 (44 %) had symptoms suggestive of intestinal ischemia; almost half (49 %, n = 295) of the patients were hospitalized in the ICU. Patients received therapies, such as clips (15 %), epinephrine injections (5 %), bipolar coagulation (7 %), or devolvulation (3 %) using colonoscopy or antibiotic therapy when needed. No perforation was observed after colonoscopy and only three cases of hemorrhage recurrence were documented as complications after the procedure. Overall, 192 patients died within 1 month after colonoscopy due to four independent risk situations, as follows: septic shock, heart transplantation, multiorgan failure, and ischemic colitis. Only 67 (35 %) underwent urgent intestinal surgery when ischemic colitis was identified, and this did not have a significant effect on the mortality rate. CONCLUSIONS: Urgent bedside colonoscopy is feasible and safe for routine use. The highest advantage was observed in patients with red blood hemorrhage, diarrhea, and colon distension when symptoms were not associated with multiorgane failure, heart transplantation, or septic shock. As revealed by colonoscopy and pathological features, ischemic colitis is associated with a bad prognosis, and patients experience a higher rate of early mortality regardless of whether they undergo urgent colon surgery.

Therapeutic drug monitoring is predictive of loss of response after de-escalation of infliximab therapy in patients with inflammatory bowel disease in clinical remission.

BACKGROUND: There is no evidence that therapeutic drug monitoring is helpful in patients with inflammatory bowel disease patients in clinical remission with infliximab therapy. METHODS: Eighty consecutive inflammatory bowel disease patients in clinical remission on infliximab maintenance therapy were included and followed-up for at least one year. Infliximab trough level and antibody to infliximab concentration were measured prior to enrollment. At the time of enrollment, physicians in charge were free to alleviate infliximab therapy. Discrepancies between blind and therapeutic drug monitoring-based adjustments were assessed at the end of the follow-up period. Relapse-free survival was analyzed using univariate and multivariate analyses. RESULTS: The mean infliximab trough level was 3.1 µg/mL. Antibody to infliximab was found in 15 (19%) patients. At the end of the follow-up period, 18 (22.5%) patients experienced a relapse. The 3, 6, 9 and 12-month relapse-free rates were 98%, 87%, 86% and 80%, respectively. In our multivariate analysis, relapse-free survival was negatively associated with discrepancies between therapeutic drug monitoring-based and blind adjustments of infliximab therapy, absence of concomitant immunomodulator, the absence of mucosal healing, prior use of infliximab, infliximab therapy duration>2 years and C-reactive protein levels>5mg/L at the time of enrollment. CONCLUSION: In patients with inflammatory bowel disease in clinical remission on infliximab therapy, de-escalation of infliximab therapy should be considered based on therapeutic drug monitoring rather than according to symptoms and CRP.