Summary
Background
Data about thiopurines or anti‐TNF use during pregnancy in women with inflammatory bowel diseases (IBD) are reassuring. However, many studies are based upon small sample sizes.
...Aims
To assess IBD medication safety during pregnancy.
Methods
Using the French national health database, which covers more than 99% of the French population, around 65 000 000 people, we identified pregnancies ending with a birth in IBD patients in France between 2010 and 2018. Pregnancy outcomes (vital status at birth, birth term, and weight for gestational age) were compared according to treatment exposure during pregnancy using propensity score‐weighted marginal logistic regression models.
Results
27 729 pregnancies were included: 3554 were exposed to thiopurines monotherapy, 3525 to anti‐TNF monotherapy, 839 to combination therapy, and 19 811 unexposed. Pregnancies exposed to thiopurines monotherapy compared to unexposed pregnancies more frequently resulted in stillbirths (1.0% vs 0.5%, aOR 2.04; 95%CI: 1.18‐3.55), preterm birth (12.3% vs 7.1%, aOR 1.76; 95%CI: 1.55‐2.00), large for gestational age (10.6% vs 8.4%, aOR 1.32; 95%CI: 1.13‐1.53) and less frequently in small for gestational age (9.6% vs 11.1%, aOR 0.79; 95%CI: 0.67‐0.92). By contrast, pregnancies exposed to anti‐TNF monotherapy were not different from unexposed pregnancies as regards to these outcomes. Compared to unexposed pregnancies, those exposed to combination therapy more frequently resulted in preterm births (aOR 1.55; 95%CI: 1.15‐2.11) and larger for gestational age (aOR 1.61; 95%CI: 1.13‐2.29) but did not differ as regards to stillbirths.
Conclusions
Pregnancies exposed to thiopurines more frequently resulted in stillbirths, preterm births and large for gestational age compared to pregnancies exposed to anti‐TNF or unexposed pregnancies. By contrast, pregnancies exposed to anti‐TNF monotherapy were not associated with these outcomes.
Pregnancies exposed to thiopurines more frequently resulted in stillbirths, preterm births, and large for gestational age compared to pregnancies exposed to anti‐TNF or unexposed pregnancies. By contrast, pregnancies exposed to anti‐TNF monotherapy were not associated with these outcomes
Background The WallFlex.sup.® and Evolution.sup.® stents are the most widely used duodenal stents, but no study has compared them. Aims We aimed to compare the efficacy and safety of WallFlex.sup.® ...and Evolution.sup.® stents for malignant gastric outlet obstruction. Methods We included all consecutive patients who were treated for malignant gastric outlet obstruction with WallFlex.sup.® or Evolution.sup.® self-expandable metal uncovered duodenal stents between 2013 and 2020. Multivariable Cox models were performed to assess duodenal stent failure, as defined by gastric outlet obstruction necessitating another duodenal stent. Results We included 129 patients: 74 received a WallFlex.sup.® stent and 55 received an Evolution.sup.® stent. The non-failure rate was of 68% (95%CI 55-84) and 65% (95%CI 50-84) at 6 months and of 48% (95%CI 32-73) and 45% (95%CI 27-74) at 1 year, with the WallFlex.sup.® and Evolution.sup.® stents, respectively. The median time to duodenal stent failure was 10.5 months in the WallFlex.sup.® group and 9.3 months in the Evolution.sup.® group. The type of duodenal stent was not associated with duodenal stent failure (p logrank = 0.43, adjusted hazard ratio 1.55; 95%CI 0.77-3.14). The overall survival was similar between the two groups (p logrank = 0.92). Three patients had complications due to Evolution.sup.® stents; it consisted in dismantled stents that led to hemorrhage in one patient. Conclusions WallFlex.sup.® and Evolution.sup.® duodenal stents had similar efficacy for malignant gastric outlet obstruction. There were more adverse events with Evolution.sup.® stents.
Background:
Therapeutic monoclonal anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibodies are associated with immune-mediated enterocolitis. The aim of this study was to provide a ...detailed description of this entity.
Methods:
We included patients with endoscopic signs of inflammation after anti-CTLA-4 infusions for cancer treatment. Other causes of enterocolitis were excluded. Clinical, biological and endoscopic data were recorded. A single pathologist reviewed endoscopic biopsies and colectomy specimens from 27 patients. Patients with and without enterocolitis after ipilimumab-treated melanoma were compared, to identify clinical factors associated with enterocolitis.
Results:
Thirty-nine patients with anti-CTLA-4 enterocolitis were included (ipilimumab n = 37; tremelimumab n = 2). The most frequent symptom was diarrhoea. Ten patients had extra-intestinal manifestations. Most colonoscopies showed ulcerations involving the rectum and sigmoid, 66% of patients had extensive colitis, 55% had patchy distribution and 20% had ileal inflammation. Endoscopic colonic biopsies showed acute colitis in most patients, while half of the patients had chronic duodenitis. Thirty-five patients received steroids that led to complete clinical remission in 13 patients (37%). Twelve patients required infliximab, of whom 10 (83%) responded. Six patients underwent colectomy (perforation n = 5; toxic megacolon n = 1); one of them died postoperatively. Four patients had a persistent enterocolitis at follow-up colonoscopy. Patients with enterocolitis were more frequently prescribed NSAIDs compared with patients without enterocolitis (31 vs 5%, p = 0.003).
Conclusions:
Ipilimumab and tremelimumab may induce a severe and extensive form of inflammatory bowel disease. Rapid escalation to infliximab should be advocated in patients who do not respond to steroids. Patients treated with anti-CTLA-4 should be advised to avoid NSAIDs.
SB5 is an EMA-approved adalimumab biosimilar, having demonstrated bioequivalence, equivalent efficacy, and similar safety and immunogenicity to the reference product.
Describe patient training and ...satisfaction using patient-reported outcome measures (PROMs) and assess their impact on 12-month persistence on SB5.
The observational PERFUSE study included 318 Crohn's disease (CD) patients and 88 ulcerative colitis (UC) patients in 27 sites across France between October 2018 and December 2020. PROMs were collected at 1-month post-baseline using an online questionnaire (ePRO) designed with patient associations. Treatment persistence was collected during routine visits (up to 15 months post-initiation). Results are presented by prior experience with subcutaneous biologics and training in proper use of the injection device.
57.1% (n = 145) and 44.1% (n = 67) of naïve and pre-treated patients, respectively, answered the ePRO. Naïve patients were offered training more often (86.9% vs 31.3% respectively, p < 0.05), with disparities between sites. All subgroups’ satisfaction scores were high. 12-month persistence on SB5 was significantly higher for respondents than for non-respondents (68.0% 60.9; 74.1 vs 52.3% 44.5; 59.6; p < 0.05) and in patients with a better perception of their illness (OR=1.02, 1.0; 1.05; p < 0.05).
Early patient questionnaires may be useful to identify patients at higher risk of treatment discontinuation.
We investigated perforations, bleeding, and splenic injuries after screening or diagnostic colonoscopies to identify patient-, procedure-, endoscopist-, and facility-associated risk factors.
We ...analyzed data from the SNIIRAM-PMSI national claims databases in France. A total of 4,088,799 patients, 30 years or older, undergoing a first screening or diagnostic colonoscopy from 2010 through 2015 were identified. Rates of severe adverse events (SAEs) were estimated using stringent and broad definitions. Risk factors associated with perforations and major bleeding were estimated using multilevel logistic regression models, adjusted for patient, colonoscopy, and endoscopist characteristics.
Perforation rates ranged from 3.5 (stringent definition) to 7.3 (broad definition) per 10,000 procedures, bleeding rates ranged from 6.5 to 23.1 per 10,000 procedures, and splenic injury rates ranged from 0.20 to 0.34 per 10,000 procedures. Rates of 30-day mortality were 13.2 per 1000 bleeds, 29.2 per 1000 perforations, and 36.1 per 1000 splenic injuries (stringent definitions). Patient characteristics associated with SAEs were increasing age (especially for perforation), cancer, and cardiovascular comorbidities. Procedure characteristics associated with SAEs included polypectomy—especially of polyps larger than 1 cm with an increased risk of perforation (odds ratio, 4.1; 95% CI, 3.4–5.0) and bleeding (odds ratio, 13.3; 95% CI, 11.7–15.1). Less-experienced endoscopists and endoscopists who performed a smaller number of colonoscopies were independently associated with a risk of SAEs.
In an analysis of national claims databases in France, we found SAEs related to screening and diagnostic colonoscopies to be more frequent in older patients, in patients with comorbidities, and with less-experienced endoscopists. Patients at risk of SAE should be identified and colonoscopies should be performed or supervised by experienced endoscopists.
Vedolizumab is used to treat patients with ulcerative colitis (UC), although there is a delay before it is effective. Induction therapy with a calcineurin inhibitor (cyclosporine or tacrolimus) in ...combination with vedolizumab as maintenance therapy could be an option for patients with an active steroid-refractory UC. We assessed the efficacy and safety of this combination.
We performed a retrospective observational study, collecting data from 12 referral centers in France that were included in the Groupe d'Etude Thérapeutique des Affections Inflammatoires du tube Digestif. We collected information on 39 patients with an active steroid-refractory UC (31 with active severe UC and 36 failed by treatment with a tumor necrosis factor antagonist) who received a calcineurin inhibitor as induction therapy along with vedolizumab as maintenance therapy. Inclusion date was the first vedolizumab infusion. The outcomes were survival without colectomy, survival without vedolizumab discontinuation, and safety.
After a median follow-up period of 11 months, 11 patients (28%) underwent colectomy. At 12 months, 68% of the patients survived without colectomy (95% CI, 53%-84%) and 44% survived without vedolizumab discontinuation (95% CI, 27%-61%). No deaths occurred and 4 severe adverse events were observed.
In a retrospective analysis of 39 patients with an active steroid-refractory UC (most refractory to a tumor necrosis factor antagonist), we found that initial treatment with a calcineurin inhibitor in combination with vedolizumab allowed more than two thirds of patients to avoid colectomy. Further studies are needed to assess the safety of this strategy.
Introduction
Small bowel functions are more complex than colon functions, and short bowel conditions are associated with increased mortality. Gastrointestinal dysfunction in critically ill patients ...is common, probably underestimated, and associated with a poor prognosis. However, a validated definition of acute intestinal failure is lacking, in absence of a marker to measure it. Consequently, small bowel dysfunction is not clearly integrated into the overall approach used to treat ICU patients.
Materials and Methods
Review of the literature on gastrointestinal dysfunction in critically ill patients, and proposition of a definition of acute intestinal failure.
Conclusion
On the one hand, small bowel ischemia is related to acute reduction of enterocyte mass and loss of gut barrier function by epithelial lifting of villi. On the other hand, systemic inflammatory response syndrome (SIRS) and sepsis could be linked to an acute dysfunction of enterocytes without enterocyte reduction. Citrulline is an amino acid mainly synthesized by small bowel enterocytes. Various contexts of chronic and acute reduction of enterocyte mass have been correlated with low plasma citrulline concentration. Critically ill patients with shock have an acute reduction of enterocyte mass and reduced gut citrulline synthesis, leading to a low plasma citrulline concentration. Acute intestinal failure could be defined as an acute reduction of enterocyte mass and/or acute dysfunction of enterocytes, associated or not with loss of gut barrier function. The influence of SIRS and acute renal failure on plasma citrulline concentration and the value of this concentration as an indicator of acute intestinal failure in critically ill patients must be further evaluated.
Vedolizumab (VDZ) has been incriminated in the occurrence of articular manifestations in patients with inflammatory bowel diseases (IBDs). The aim of this study was to describe musculoskeletal ...manifestations occurring in IBD patients treated by VDZ and to identify risk factors.
In this retrospective monocentric study, we included all consecutive patients treated by VDZ for IBD in our hospital. Incident musculoskeletal manifestations occurring during VDZ treatment were analysed and characteristics of patients with and without articular inflammatory manifestations were compared.
Between 2013 and 2017, 112 patients were treated with VDZ for IBD: ulcerative colitis (n = 59), Crohn's disease (n = 49) and undetermined colitis (n = 4). Four patients (3.6%) had a history of SpA, whereas 13 (11.6%) had a history of peripheral arthralgia. Some 102 (91.1%) patients had previously received anti-TNF. After a mean (S.d.) follow-up of 11.4 (8.6) months, 32 (28.6%) patients presented 35 musculoskeletal manifestations, of which 18 were mechanical and 17 inflammatory. Among the latter, 11 had axial or peripheral SpA, 5 had early reversible arthralgia and 1 had chondrocalcinosis (n = 1). Among the 11 SpA patients, only 3 (2.6%) had inactive IBD and may be considered as paradoxical SpA. The only factor associated with occurrence of inflammatory manifestations was history of inflammatory articular manifestation 7/16 (43.8%) vs 10/80 (12.5%), P = 0.007.
Musculoskeletal manifestations occurred in almost 30% of IBD patients treated with VDZ, but only half of them were inflammatory. Since most of the patients previously received anti-TNF, occurrence of inflammatory articular manifestations might rather be linked to anti-TNF discontinuation than to VDZ itself.
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