Real-Life Efficacy of Tofacitinib in Various Situations in Ulcerative Colitis: A Retrospective Worldwide Multicenter Collaborative Study.

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

Serologic Response and Safety after a Third Dose of the COVID-19 BNT162b2 Vaccine in Patients with Inflammatory Bowel Diseases.

Vaccines are pivotal for control of the coronavirus disease (COVID-19) pandemic. Patients with inflammatory bowel diseases (IBDs) treated with antitumor necrosis factor (TNF)-α have lower serologic response after two COVID-19 vaccine doses. Data regarding a third vaccine dose are scarce. An Israeli multicenter prospective observational study recruited 319 subjects: 220 with IBD (79 treated with anti-TNFα) and 99 healthy control (HC) participants. All patients received two mRNA-BNT162b2 vaccines (Pfizer/BioNTech), 80% of whom received a third vaccine dose. Evaluation included disease activity, anti-spike (S) and nucleocapsid (N) antibody levels, anti-TNFα drug levels, and adverse events (AEs). All participants showed significant serologic response one month after receiving a third dose. However, three months later, the anti-S levels decreased significantly in patients treated with anti-TNFα compared with the non-anti-TNFα and HC groups. A correlation between serologic response to the third vaccine dose and anti-TNF drug levels was not found. No significant AE or IBD exacerbation was observed. Importantly, lower serologic response after the third vaccine dose predicted infection. A third dose of BNT162b2 is effective and safe in patients with IBD. Lower serologic response predicted infection, even in seropositive subjects. Lower serologic responses and their rapid decline suggest a fourth vaccine dose in this patient population.

Autoimmune Pancreatitis in Patients with Inflammatory Bowel Disease: A Real-World Multicentre Collaborative ECCO CONFER Study.

BACKGROUND: Autoimmune pancreatitis [AIP] is rarely associated with inflammatory bowel disease [IBD]. The long-term outcomes of AIP and IBD in patients with coexisting AIP-IBD and predictors of complicated AIP course have rarely been reported. METHODS: An ECCO COllaborative Network For Exceptionally Rare case reports project [ECCO-CONFER] collected cases of AIP diagnosed in patients with IBD. Complicated AIP was defined as a composite of endocrine and/or exocrine pancreatic insufficiency, and/or pancreatic cancer. We explored factors associated with complicated AIP in IBD. RESULTS: We included 96 patients [53% males, 79% ulcerative colitis, 72% type 2 AIP, age at AIP diagnosis 35 ±â€…16 years]. The majority of Crohn's disease [CD] cases [78%] had colonic/ileocolonic involvement. In 59%, IBD preceded AIP diagnosis, whereas 18% were diagnosed simultaneously. Advanced therapy to control IBD was used in 61% and 17% underwent IBD-related surgery. In total, 82% of patients were treated with steroids for AIP, the majority of whom [91%] responded to a single course of treatment. During a mean follow-up of 7 years, AIP complications occurred in 25/96 [26%] individuals. In a multivariate model, older age at AIP diagnosis was associated with a complicated AIP course (odds ratio [OR] = 1.05, p = 0.008), whereas family history of IBD [OR = 0.1, p = 0.03], and CD diagnosis [OR = 0.2, p = 0.04] decreased the risk of AIP complications. No IBD- or AIP-related deaths occurred. CONCLUSIONS: In this large international cohort of patients with concomitant AIP-IBD, most patients have type 2 AIP and colonic IBD. AIP course is relatively benign and long-term outcomes are favourable, but one-quarter develop pancreatic complications. Age, familial history of IBD, and CD may predict uncomplicated AIP course.

Comparison of Short- and Long-Term Effectiveness between Anti-TNF and Ustekinumab after Vedolizumab Failure as First-Line Therapy in Crohn's Disease: A Multi-Center Retrospective Cohort Study.

BACKGROUND: The effectiveness of anti-TNF or ustekinumab (UST) as a second-line biologic after vedolizumab (VDZ) failure has not yet been described. AIMS AND METHODS: In this retrospective multicenter cohort study, We aim to investigate the effectiveness of anti-TNF and UST as second-line therapy in patients with Crohn's disease (CD) who failed VDZ as a first-line treatment. The primary outcome was clinical response at week 16-22. Secondary outcomes included the rates of clinical remission, steroid-free clinical remission, CRP normalization, and adverse events. RESULTS: Fifty-nine patients who failed on VDZ as a first-line treatment for CD were included; 52.8% patients received anti-TNF and 47.2% UST as a second-line therapy. In initial period (Week 16-22), the clinical response and remission rate was similar between both groups: 61.2% vs. 68%, p = 0.8 and 48.3% vs. 56%, p = 0.8 on anti-TNF and UST therapy, respectively. Furthermore, in the maintenance period the rate was similar: 75% vs. 82.3%, p = 0.8 and 62.5% vs. 70.5%, p = 0.8, respectively. Of the patients, 12 out of the 59 stopped the therapy, without a significant difference between the two groups (p = 0.6). CONCLUSION: Second-line biological therapy after VDZ failure therapy was effective in >60% of the patients with CD. No differences in effectiveness were detected between the use of anti-TNF and UST as a second line.

Inflammatory bowel disease in families with four or more affected first-degree relatives.

BACKGROUND: Family history increases the risk for inflammatory bowel diseases (IBDs). However, data on differences in phenotypic characteristics among patients with a strong family history of IBD are scarce and controversial. The aim of the study was to compare the phenotypic features of IBD patients with four or more affected first-degree relatives with sporadic cases of IBD. METHODS: Patients with familial and sporadic IBD were identified from the institutional IBD database. IBD patients from families with at least four first-degree affected relatives were selected for analysis and were compared to non-matched sporadic cases with IBD chosen randomly. Comparison for type of IBD (Crohn's disease (CD) vs. ulcerative colitis (UC)), age at onset as well as for disease extent, behavior, extraintestinal manifestations and indicators of severe disease were analyzed. RESULTS: Thirty-five patients with familial IBD (28 CD, seven UC) were compared to 88 sporadic IBD patients (61 CD, 24 UC and three IBDU). Disease duration was 10.3 ± 8.2 in the familial and 8.0 ± 7.2 years in the sporadic cases, p=.13. The familial cases were younger at diagnosis (19.3 ± 8.6 vs. 25.7 ± 11.8, p=.004). Patients with familial compared to sporadic IBD were significantly more likely to require steroid treatment (80% vs. 54.5%, p=.009), biological treatment (94.3%, vs. 63.6%, p<.001) or surgery (25.7%, vs. 11.4%, p=.048). CONCLUSIONS: IBD with a very strong positive family history is associated with younger age at onset and a more adverse IBD phenotype compared to sporadic IBD.

SARS-CoV-2 IgG Antibody Levels in Women with IBD Vaccinated during Pregnancy.

INTRODUCTION: Regulatory agencies supported vaccination of pregnant women with SARS-CoV-2 mRNA vaccines, including patients with IBD. No data exist regarding these vaccines in IBD during pregnancy. AIM: To assess the serologic response to two doses of the mRNA SARS-CoV-2 BNT162b2 vaccine in pregnant women with IBD vaccinated during pregnancy, compared to that of pregnant women without IBD, and non-pregnant women with IBD. METHODS: Anti-spike antibody levels were assessed in all women and in cord blood of consenting women. RESULTS: From December 2020 to December 2021, 139 women were assessed: pregnant with IBD-36, pregnant without IBD-61, and not pregnant with IBD-42. Antibodies were assessed in cords of two and nine newborns of women with and without IBD, respectively. Mean gestational ages at administration of the second vaccine doses were 22.0 weeks in IBD and 23.2 weeks in non-IBD, respectively. Mean (SD) duration from the second vaccine dose to serology analysis in pregnant women with IBD, without IBD, and in non-pregnant women with IBD was 10.6 (4.9), 16.4 (6.3), and 4.3 (1.0) weeks, respectively. All women mounted a serologic response. In multivariable analysis, no correlation was found between the specific group and antibody levels. In both pregnancy groups, an inverse correlation between antibody levels and the interval from the second vaccine dose was demonstrated. Cord blood antibody levels exceeded maternal levels in women with and without IBD. CONCLUSION: All patients with IBD mounted a serologic response. The interval between vaccine administration to serology assessment was the most important factor determining antibody levels. A third vaccine dose should be considered in pregnant women with IBD vaccinated at early stages of pregnancy.

Immune function in newborns with in-utero exposure to anti-TNFα therapy.

Background and aim: Anti-TNFα is measurable in infants exposed in utero up to 12 months of age. Data about the exposure effect on the infant's adaptive immunity are limited. We aimed to prospectively evaluate the distribution and function of T and B cells, in infants of females with inflammatory bowel disease, in utero exposed to anti-TNFα or azathioprine. Methods: A prospective multi-center study conducted 2014-2017. Anti-TNFα levels were measured in cord blood, and at 3 and 12 months. T-cell repertoire and function were analyzed at 3 and 12 months by flow-cytometry, expression of diverse T cell receptors (TCR) and T-cell receptor excision circles (TREC) quantification assay. Serum immunoglobulins and antibodies for inactivated vaccines were measured at 12 months. Baseline clinical data were retrieved, and 2-monthly telephonic interviews were performed regarding child infections and growth. Results: 24 pregnant females, age 30.6 (IQR 26.5-34.5) years were recruited, 20 with anti-TNFα (infliximab 8, adalimumab 12), and 4 with azathioprine treatment. Cord blood anti-TNFα was higher than maternal blood levels [4.3 (IQR 2.3-9.2) vs. 2.5 (IQR 1.3-9.7) mcg/ml], declining at 3 and 12 months. All infants had normal number of B-cells (n = 17), adequate levels of immunoglobulins (n = 14), and protecting antibody levels to Tetanus, Diphtheria, Hemophilus influenza-B and hepatitis B (n = 17). All had normal CD4+, CD8+ T-cells, and TREC numbers. TCR repertoire was polyclonal in 18/20 and slightly skewed in 2/20 infants. No serious infections requiring hospitalization were recorded. Conclusion: We found that T-cell and B-cell immunity is fully mature and immune function is normal in infants exposed in utero to anti-TNFα, as in those exposed to azathioprine. Untreated controls and large-scale studies are needed to confirm these results.

Anti-TNFα Treatment Impairs Long-Term Immune Responses to COVID-19 mRNA Vaccine in Patients with Inflammatory Bowel Diseases.

Patients with inflammatory bowel disease (IBD) treated with anti-tumor-necrosis factor-alpha (TNFα) exhibited lower serologic responses one-month following the second dose of the COVID-19 BNT162b2 vaccine compared to those not treated with anti-TNFα (non-anti-TNFα) or to healthy controls (HCs). We comprehensively analyzed long-term humoral responses, including anti-spike (S) antibodies, serum inhibition, neutralization, cross-reactivity and circulating B cell six months post BNT162b2, in patients with IBD stratified by therapy compared to HCs. Subjects enrolled in a prospective, controlled, multi-center Israeli study received two BNT162b2 doses. Anti-S levels, functional activity, specific B cells, antigen cross-reactivity, anti-nucleocapsid levels, adverse events and IBD disease score were detected longitudinally. In total, 240 subjects, 151 with IBD (94 not treated with anti-TNFα and 57 treated with anti-TNFα) and 89 HCs participated. Six months after vaccination, patients with IBD treated with anti-TNFα had significantly impaired BNT162b2 responses, specifically, more seronegativity, decreased specific circulating B cells and cross-reactivity compared to patients untreated with anti-TNFα. Importantly, all seronegative subjects were patients with IBD; of those, >90% were treated with anti-TNFα. Finally, IBD activity was unaffected by BNT162b2. Altogether these data support the earlier booster dose administration in these patients.

Endoscopic Postoperative Recurrence in Crohn's Disease After Curative Ileocecal Resection with Early Prophylaxis by Anti-TNF, Vedolizumab or Ustekinumab: A Real-World Multicentre European Study.

BACKGROUND: Endoscopic-post-operative-recurrence [ePOR] in Crohn's disease [CD] after ileocecal resection [ICR] is a major concern. We aimed to evaluate the effectiveness of early prophylaxis with biologics and to compare anti-tumour necrosis factor [anti-TNF] therapy to vedolizumab [VDZ] and ustekinumab [UST] in a real-world setting. METHODS: A retrospective multicentre study of CD-adults after curative ICR on early prophylaxis was undertaken. ePOR was defined as a Rutgeerts score [RS] ≥ i2 or colonic-segmental-SES-CD ≥ 6. Multivariable logistic regression was used to evaluate risk factors, and inverse probability treatment weighting [IPTW] was applied to compare the effectiveness between agents. RESULTS: The study included 297 patients (53.9% males, age at diagnosis 24 years [19-32], age at ICR 34 years [26-43], 18.5% smokers, 27.6% biologic-naïve, 65.7% anti-TNF experienced, 28.6% two or more biologics and 17.2% previous surgery). Overall, 224, 39 and 34 patients received anti-TNF, VDZ or UST, respectively. Patients treated with VDZ and UST were more biologic experienced with higher rates of previous surgery. ePOR rates within 1 year were 41.8%. ePOR rates by treatment groups were: anti-TNF 40.2%, VDZ 33% and UST 61.8%. Risk factors for ePOR at 1 year were: past-infliximab (adjusted odds ratio [adj.OR] = 1.73 [95% confidence interval, CI: 1.01-2.97]), past-adalimumab [adj.OR = 2.32 [95% CI: 1.35-4.01] and surgical aspects. After IPTW, the risk of ePOR within 1 year of VDZ vs anti-TNF or UST vs anti-TNF was comparable (OR = 0.55 [95% CI: 0.25-1.19], OR = 1.86 [95% CI: 0.79-4.38]), respectively. CONCLUSION: Prevention of ePOR within 1 year after surgery was successful in ~60% of patients. Patients treated with VDZ or UST consisted of a more refractory group. After controlling for confounders, no differences in ePOR risk were seen between anti-TNF prophylaxis and other groups.

Surgery due to Inflammatory Bowel Disease During Pregnancy: Mothers and Offspring Outcomes From an ECCO Confer Multicentre Case Series [Scar Study].

AIMS: i] To evaluate the evolution of pregnancies and offspring after inflammatory bowel disease [IBD] surgery during pregnancy; and ii] to describe the indications, the surgical techniques, and the frequency of caesarean section concomitant with surgery. METHODS: Patients operated on due to IBD during pregnancy after 1998 were included. Participating clinicians were asked to review their databases to identify cases. Data on patients' demographics, IBD characteristics, medical treatments, IBD activity, pregnancy outcomes, surgery, delivery, and foetal and maternal outcomes, were recorded. RESULTS: In all, 44 IBD patients were included, of whom 75% had Crohn's disease; 18% of the surgeries were performed in the first trimester, 55% in the second, and 27% in the third trimester. One patient had complications during surgery, and 27% had postsurgical complications. No patient died. Of deliveries, 70% were carried out by caesarean section. There were 40 newborns alive. There were four miscarriages/stillbirths [one in the first, two in the second, and one in the third trimester]; two occurred during surgery, and another two occurred 2 weeks after surgery; 14% of the surgeries during the second trimester and 64% of those in the third trimester ended up with a simultaneous caesarean section or vaginal delivery. Of the 40 newborns, 61% were premature and 47% had low birth weight; 42% of newborns needed hospitalisation [25% in the intensive care unit]. CONCLUSIONS: IBD surgery during pregnancy remains an extremely serious situation. Therefore, surgical management should be performed in a multidisciplinary team, involving gastroenterologists, colorectal surgeons, obstetricians, and neonatal specialists.

COVID-19 in Patients with Inflammatory Bowel Disease: The Israeli Experience.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are chronic, immune-mediated inflammatory bowel diseases (IBD) affecting millions of people worldwide. IBD therapies, designed for continuous immune suppression, often render patients more susceptible to infections. The effect of the immune suppression on the risk of coronavirus disease-19 (COVID-19) is not fully determined yet. OBJECTIVE: To describe COVID-19 characteristics and outcomes and to evaluate the association between IBD phenotypes, infection outcomes and immunomodulatory therapies. METHODS: In this multi-center study, we prospectively followed IBD patients with proven COVID-19. De-identified data from medical charts were collected including age, gender, IBD type, IBD clinical activity, IBD treatments, comorbidities, symptoms and outcomes of COVID-19. A multivariable regression model was used to examine the effect of immunosuppressant drugs on the risk of infection by COVID-19 and the outcomes. RESULTS: Of 144 IBD patients, 104 (72%) were CD and 40 (28%) were UC. Mean age was 32.2 ± 12.6 years. No mortalities were reported. In total, 94 patients (65.3%) received biologic therapy. Of them, 51 (54%) at escalated doses, 10 (11%) in combination with immunomodulators and 9 (10%) with concomitant corticosteroids. Disease location, behavior and activity did not correlate with the severity of COVID-19. Biologics as monotherapy or with immunomodulators or corticosteroids were not associated with more severe infection. On the contrary, patients receiving biologics had significantly milder infection course (p = 0.001) and were less likely to be hospitalized (p = 0.001). Treatment was postponed in 34.7% of patients until recovery from COVID-19, without consequent exacerbation. CONCLUSION: We did not witness aggravated COVID-19 outcomes in patients with IBD. Patients treated with biologics had a favorable outcome.

Lower Serologic Response to COVID-19 mRNA Vaccine in Patients With Inflammatory Bowel Diseases Treated With Anti-TNFα.

BACKGROUND & AIM: Patients with inflammatory bowel diseases (IBD), specifically those treated with anti-tumor necrosis factor (TNF)α biologics, are at high risk for vaccine-preventable infections. Their ability to mount adequate vaccine responses is unclear. The aim of the study was to assess serologic responses to messenger RNA-Coronavirus Disease 2019 vaccine, and safety profile, in patients with IBD stratified according to therapy, compared with healthy controls (HCs). METHODS: Prospective, controlled, multicenter Israeli study. Subjects enrolled received 2 BNT162b2 (Pfizer/BioNTech) doses. Anti-spike antibody levels and functional activity, anti-TNFα levels and adverse events (AEs) were detected longitudinally. RESULTS: Overall, 258 subjects: 185 IBD (67 treated with anti-TNFα, 118 non-anti-TNFα), and 73 HCs. After the first vaccine dose, all HCs were seropositive, whereas ∼7% of patients with IBD, regardless of treatment, remained seronegative. After the second dose, all subjects were seropositive, however anti-spike levels were significantly lower in anti-TNFα treated compared with non-anti-TNFα treated patients, and HCs (both P < .001). Neutralizing and inhibitory functions were both lower in anti-TNFα treated compared with non-anti-TNFα treated patients, and HCs (P < .03; P < .0001, respectively). Anti-TNFα drug levels and vaccine responses did not affect anti-spike levels. Infection rate (∼2%) and AEs were comparable in all groups. IBD activity was unaffected by BNT162b2. CONCLUSIONS: In this prospective study in patients with IBD stratified according to treatment, all patients mounted serologic response to 2 doses of BNT162b2; however, its magnitude was significantly lower in patients treated with anti-TNFα, regardless of administration timing and drug levels. Vaccine was safe. As vaccine serologic response longevity in this group may be limited, vaccine booster dose should be considered.

Short-term effectiveness and safety of tofacitinib in ulcerative colitis - real world data from tertiary medical centers in Israel.

BACKGROUND: We sought to define the effectiveness and safety of tofacitinib in a real-world (RW) cohort of Israeli patients with moderate to severe ulcerative colitis (UC). METHODS: This was a multi-center retrospective observational cohort study (2019-2020) to assess the effectiveness and safety of tofacitinib induction and maintenance therapy up to 26 weeks. Clinical response and remission were defined as a reduction in Simple Clinical Colitis Activity Index (SCCAI) or partial Mayo score (PMS) of ≥3 points, and SCCAI ≤2 or a PMS ≤1, respectively. RESULTS: We included 73 patients, 47% male; median age 26 years [IQR: 19.5-39.5], disease duration 7 years [IQR: 2.5-14.5], follow-up 7.1 months [IQR: 3-12], 91% biologics-experienced, and 74% ≥ 2-biologics. Half of patients used concomitant corticosteroids (CS). Overall, 56.1% discontinued therapy due to either lack of response and/or adverse events (AEs), median time to discontinuation - 9.7 months [IQR 3.4-16]. Overall, response, remission, and CS-free-remission were achieved in 47.6%, 20.6%, and 17.5% of patients, respectively. At early maintenance (week 26), response, remission, and CS-free-remission were achieved in 65%, 22.5%, and 20% of patients, respectively. At week 26, tofacitinib 10 mg BID was still used in 43%. Seventeen patients (23.2%) had an adverse event including herpes zoster- 2.7%, hospitalization- 12.3%, and colectomy- 2.7%. CONCLUSIONS: Tofacitinib was effective in achieving CS-free-remission in about 1/5 of highly biologics -experienced patients with UC. Despite a considerable proportion of patients maintained on tofacitinib 10 mg bid, it was well tolerated and safe. Earlier positioning of tofacitinib in the therapeutic algorithm may result in improved outcomes.

Important relation between self-efficacy, sense of coherence, illness perceptions, depression and anxiety in patients with inflammatory bowel disease.

INTRODUCTION: Anxiety and depression are common disturbances in patients with inflammatory bowel diseases (IBD), and were found to impact the disease course. Illness perceptions (IPs), self-efficacy (SE) and sense of coherence (SOC) are important psychological functions, used by the individual to cope with his chronic disease. AIMS: to investigate the association of IP, SE and SOC on anxiety and depression among patients with IBD. PATIENTS AND METHODS: Patients filled questionnaires including: demographic, socioeconomic and clinical features. Depression and anxiety were assessed using the Hospital Anxiety and Depression Scale. IP, SE and SOC were assessed using the Brief Illness perception Questionnaire, IBD-SE and SOC scales. RESULTS: The study sample consisted of 299 patients with IBD, median age 34.15, 63% females, 70.9% had Crohn's disease, filled the questionnaires. In the multivariate analysis, lower results in IP, SE and SOC were found to be associated with significantly increase anxiety (OR 8.35, p<0.001; OR 4.18, p=0.001; OR 4.67, p<0.001, respectively) and depression (OR 15.8, p=0.001; OR 10.99, p=0.029; OR 6.12, p=0.014. CONCLUSIONS: Anxiety and depression are associated with IP, SE and SOC in patients with IBD. Clinicians should be aware of this impact, recognise their patients' psychological abilities to cope with the disease and improve those abilities, when needed, in order to achieve a better coping with the disease and to prevent the development of anxiety and depression.

Gastroenterologists' Attitude Regarding Medical Cannabis for Inflammatory Bowel Diseases in Israel.

BACKGROUND: The use of medical cannabis (MC) for inflammatory bowel diseases (IBDs) is expanding. Current evidence does not support the efficacy of MC for reducing inflammation in IBD patients. Even so, many gastroenterologists encounter the issue of recommending use of MC to IBD patients. METHODS: A Web-based survey was completed by 84 (34%) gastroenterologists in Israel. RESULTS: Out of 84 physicians whom completed the questionnaire, 59 (70%) were male, 34 (40%) were under age 50 years, 71 (85%) were adult gastroenterologists, and 53 (63%) work mainly in a hospital. Of them, 15, 41, and 44% of physicians think that MC is very effective, mildly effective, and not effective at all, respectively. Physicians will commonly, rarely, and never recommend MC in 31, 47, and 22%, respectively. Older physicians (above age 50 years) were significantly more likely to have a positive attitude towards MC in both questions. When presented with a clinical scenario of a patient in deep remission, requesting to increase the dose, 32% would increase, 49% would maintain, and only 18% would stop prescribing MC altogether; 48% of physicians did not know the recommended initial dose for MC. Only 2 (2.5%) physicians initiated the use of MC to all patients. Female gastroenterologists were significantly more likely to initiate MC, p = 0.048. CONCLUSION: The use of MC for IBD patients is commonly encountered. Completely different attitudes regarding this treatment were seen. Age above 50 years and female physicians generally had a more positive attitude towards the use of MC. Guidelines and clear recommendations are needed.

Peripartum anesthetic management of patients with inflammatory bowel disease, a retrospective case-control study.

OBJECTIVE: Inflammatory bowel diseases (IBD) are a group of pathologies associated with an increased rate of abortions, premature deliveries, cesarean sections and other morbidity during the peripartum period. The objective of this retrospective study was to investigate the anesthetic management for delivery of women with IBD. MATERIAL AND METHODS: The records of patients with IBD, who delivered at our Center, were obtained for data which included anesthetic and obstetric management as well as neonatal outcome. Five subgroups were defined based on mode of delivery, presence or absence of epidural in normal vaginal delivery (NVD) and urgency of cesarean section, each of which was compared with control groups of healthy parturients in the same period. Additionally, the rate of cesarean sections and the use of epidural analgesia for NVD were compared with the general obstetric population of our center in the same period. RESULTS: 107 patients with IBD who delivered at our center were studied. The rates of cesarean sections and emergency cesarean sections were significantly higher compared to the general population. However, the rate of instrumental delivery and of epidural analgesia use for NVD were similar. Among those who underwent cesarean sections, no significant differences were found in anesthesia type, surgery duration, number of complications, type of monitoring or postoperative management compared to the control group. CONCLUSION: Peripartum anesthetic management of patients with IBD does not differ significantly from that of parturients without it. Anesthesiologists can plan their anesthesia in a similar way as they do in healthy parturients.

Factors Associated with Inflammatory Bowel Disease Flare During Pregnancy Among Women with Preconception Remission.

BACKGROUND: The factors associated with inflammatory bowel diseases (IBD) relapse throughout gestation in those with preconception remission remain unknown. AIMS: We aimed to investigate disease and pregnancy course among IBD women with quiescent disease at conception. METHODS: Women with IBD attending a multidisciplinary clinic for preconception, antenatal and postnatal treatment were prospectively recruited during 2011-2018. RESULTS: Overall, 298 women with IBD with quiescent disease at the time of conception constituted the study cohort. Of these, 112 (37.6%) women experienced disease flare during pregnancy. The risk of disease relapse was higher in those with ulcerative colitis (UC) as compared to those with Crohn's disease (CD) (48.1% vs. 31.8%, P = 0.005). The proportion of women with prior IBD-related gastrointestinal surgery was lower in those who experienced disease flare up (13.4% vs. 26.3%, P = 0.009). The use of biologic therapy at the time of conception was associated with lower rates of disease relapse (25.0% vs. 43.9%, P = 0.001). In multivariate analysis, use of conventional medications or no treatment (aOR [95% CI]: 2.0 (1.12, 3.57), P = 0.02) and lack of prior history of IBD-related surgery (aOR [95% CI]: 3.13 (1.37, 7.14), P = 0.007) were independently positively associated with disease relapse. Rates of hospitalization during pregnancy (21.4% vs. 2.2%, P < 0.001) and preterm delivery (22.3% vs. 9.1%, P = 0.002) were higher, and birthweight was lower (median 2987 vs. 3153 grams, P = 0.05) in those with disease flare as compared to those who maintained remission. CONCLUSION: Prior IBD-related surgery and biologic therapy were found as independent protective factors against relapse during pregnancy among women with quiescent disease at conception.

Disease flare at prior pregnancy and disease activity at conception are important determinants of disease relapse at subsequent pregnancy in women with inflammatory bowel diseases.

PURPOSE: Disease flare throughout gestation are not uncommon among women with inflammatory bowel diseases (IBD), and can substantially affect pregnancy outcomes. We aimed to evaluate the effect of prior pregnancy outcome on the risk of disease flare at subsequent pregnancy in women with IBD. METHODS: Women with IBD attending a multidisciplinary clinic for the preconception, antenatal and postnatal treatment were prospectively recruited during 2011-2018. RESULTS: Overall, 476 IBD women were followed during the study period. Of them, 69 (14.5%) had two pregnancies throughout follow-up period and constituted the study cohort. Among these 69 women, 48 (69.6%) had Crohn's disease and 21 (30.4%) ulcerative colitis. The median interpregnancy interval was 20 [11-32] months. Overall, 34 (49.3%) women experienced disease flare at the subsequent pregnancy. In multivariate analysis, active disease at conception (odds ratio [95% CI]: 25.65 (3.05, 25.52), P < 0.001) and history of disease flare at the previous pregnancy (odds ratio [95% CI]: 4.21 (1.10, 16.58), P < 0.001) were the only independent predictors of disease relapse in current gestation. Rates of hospitalization during pregnancy (14.7% vs. 0, P = 0.02) and preterm delivery (32.4% vs. 5.7%, P = 0.006) were higher, and neonatal birth weight was lower (median 3039 vs. 3300 g, P = 0.03), in those with disease flare as compared to those with maintained remission. CONCLUSION: History of disease relapse at previous gestation and periconception disease activity were found as important predictors of disease flare among IBD women. These data would facilitate adequate counseling and informed management decisions among reproductive-aged IBD women and their treating physicians.

Preconception counseling of females with inflammatory bowel disease.

Inflammatory bowel diseases (IBD) are commonly diagnosed in women of childbearing age. As such, pregnancy is often encountered in this subset of patients. Management of pregnancy in IBD patients poses numerous challenges as ensuring the safety of the mother and the fetus is required. Disease remission prior to pregnancy is a key determinant of both the course of IBD throughout gestation and pregnancy outcome. Thus, adequate preconception care is of paramount importance in order to achieve optimal maternal and perinatal outcomes and maintain disease quiescence throughout gestation. In addition, preconception care has a major role in improving patient's knowledge, concerns and misbeliefs related to reproductive-health issues among IBD patients. In this review, we discuss the various aspects involved in the preconception care of IBD patients.