Predictors of Response to Vedolizumab in Patients with Ulcerative Colitis: Results from the Greek VEDO-IBD Cohort.

BACKGROUND: Optimization of treatment with biologics is currently an unmet need for patients with ulcerative colitis (UC). Real-world studies provide neutral estimates of drug efficacy and safety within unselected patient populations and allow for the recognition of specific characteristics that affect response to therapy. AIMS: We aimed to depict the efficacy of vedolizumab in patients with UC in a real-world setting and identify prognosticators of improved outcomes. METHODS: Patients with active UC who commenced treatment with vedolizumab were prospectively followed up. Patient-reported outcomes (PROs) and clinical/endoscopic-reported outcomes were recorded at baseline and at weeks 14 and 54. Predefined endpoints of early and persistent efficacy were analyzed against clinical characteristics to identify prognostic factors for response. RESULTS: We included 96 patients (anti-TNF-exposed = 38.5%). At week 14, 73 patients (76%) had clinical response and 54 (56.3%) clinical remission. At week 54, the primary endpoint of vedolizumab persistence was met by 72 patients (75%), whereas steroid-free clinical remission by 59.4%. Among patients who had endoscopy, rates for mucosal healing (Mayo endoscopic score of 0) were 29.8% at week 14 and 44.6% at week 54, respectively. Vedolizumab treatment led to significant improvements in quality of life. Corticosteroid-refractory or anti-TNF-refractory disease, articular manifestations, and high baseline UC-PRO2 were associated with decreased efficacy of vedolizumab in the primary and secondary outcomes. CONCLUSIONS: Vedolizumab is characterized by high efficacy and long-term treatment persistence in UC. More aggressive disease, as indicated by refractoriness to steroids or anti-TNFs and elevated baseline PROs, may predict suboptimal response and help pre-treatment prognostic stratification of patients.

The burden and management of anemia in Greek patients with inflammatory bowel disease: a retrospective, multicenter, observational study.

BACKGROUND: Anemia is a common extraintestinal manifestation of Inflammatory Bowel Disease (IBD) affecting negatively the patients' quality of life. The aim of this study was to determine the frequency and real-life management of anemia in IBD patients in Greece. METHODS: This study was conducted in 17 Greek IBD referral centers. Demographic, clinical, laboratory, IBD and anemia treatment data were collected and analyzed retrospectively. RESULTS: A total of 1394 IBD patients [560 ulcerative colitis (UC), 834 Crohn's disease (CD)] were enrolled. Anemia at any time was reported in 687 (49.3%) patients of whom 413 (29.6%) had episodic and 274 (19.7%) had recurrent/persistent anemia. Anemia was diagnosed before IBD in 45 (6.5%), along with IBD in 269 (39.2%) and after IBD in 373 (54.3%) patients. In the multivariate analysis the presence of extraintestinal manifestations (p = 0.0008), IBD duration (p = 0.026), IBD related surgeries and hospitalizations (p = 0.026 and p = 0.004 accordingly) were risk factors of recurrent/persistent anemia. Serum ferritin was measured in 839 (60.2%) IBD patients. Among anemic patients, 535 (77.9%) received treatment. Iron supplementation was administered in 485 (90.6%) patients, oral in 142 (29.3%) and intravenous in 393 (81%). CONCLUSIONS: The frequency of anemia in IBD patients, followed at Greek referral centers, is approximately 50%. Development of recurrent/persistent anemia may be observed in 20% of cases and is independently associated with the presence of extraintestinal manifestations, IBD duration, IBD related surgeries and hospitalizations. Anemia treatment is administered in up to [Formula: see text] of anemia IBD patients with the majority of them receiving iron intravenously.

Efficacy of Vaccination and Revaccination Against Hepatitis B Virus Using 2 Different Strategies in Patients With Inflammatory Bowel Disease.

BACKGROUND: Patients with inflammatory bowel disease (IBD) exhibit an increased risk for acquiring hepatitis B virus (HBV), thus they should be vaccinated preferably, if not already infected or immunized. We assessed the efficacy of HBV vaccination in IBD patients and impact of different factors on the immune response. We also evaluated the success rate of 2 different revaccination strategies in the nonresponders. METHODS: This was a retrospective observational cohort study carried out in 5 tertiary centers. All patients were tested for hepatitis B surface antigen, antibodies against hepatitis B surface antigen (anti-HBs), and antibodies against hepatitis B core antigen. Patients tested negative and underwent the standard schedule with 20 µg at 0, 1, and 6 months. Nonresponders (anti-HBs <10 IU/L) were offered a revaccination scheme with either 3 doses of 40 µg at 0, 1, and 6 months or an accelerated scheme with 20 µg at 0, 1, and 2 months. RESULTS: A total of 409 patients were included, and 273 (66.7%) of those (females: 49.5%; Crohn's disease [CD]: 56.7%) responded to baseline vaccination. A total of 189 (69.2%) of 273 (females: 48.1%; CD: 60.3%) developed anti-HBs >100 IU/L. Body mass index <30 kg/m2 (P = .017) was positively associated, while diagnosis of CD (P = .013), extensive UC (P <.0001), extraintestinal manifestations (P = .001), and treatment with immunomodulators/anti-tumor necrosis factor (P < .00) negatively affected the response. Revaccination was offered to 103 patients, and 58.3% of them achieved anti-HBs >10 IU/L. Both revaccination strategies were equally effective. CONCLUSIONS: IBD patients demonstrate lower response to HBV vaccination compared with the general population. Age, body mass index, type, disease activity, and immunosuppression negatively affect the response. Half of nonresponders may benefit from an enhanced revaccination attempt.

In this retrospective study, we addressed the impact of several factors on the immune response postvaccination against hepatitis B virus in a large cohort of >400 inflammatory bowel disease patients and compared the effectiveness of 2 different revaccination strategies on nonresponders.

Pregnancy outcomes in Greek women with inflammatory bowel disease: a longitudinal national retrospective study.

BACKGROUND: Inflammatory bowel disease (IBD) commonly affects patients of reproductive age. The effect of disease activity on the outcome of pregnancy and its impact on neonatal health are areas of intense research. METHODS: Α national retrospective study of pregnancies in women with IBD between 2010 and 2020 was carried out in 22 IBD reference centers in Greece. RESULTS IN TOTAL: 223 pregnancies in 175 IBD patients [122 Crohn's disease (CD)] were included. Mean age at diagnosis was 26 years (12-44) with a mean duration of 7.4 (0-23). Pregnancy as a result of IVF occurred in 15 cases (6.7%). At the beginning of gestation, 165 patients (74%) were under treatment: 48 (29%) with anti-tumor necrosis factor alpha agents, 43 (26%) with azathioprine, 101 (61%) with 5-aminosalicylates, and 12 (7%) with steroids. Forty-nine cases (22%) of IBD flares were recorded: Two-thirds (n = 30) were in clinical remission at the onset of pregnancy, whereas treatment with corticosteroids was required in 22 (45%). Patients with ulcerative colitis were at greater risk for flare compared to those with CD (P < 0.001). All but two pregnancies (99.1%) resulted in an uncomplicated delivery. In 147 cases (67.1%), c-section was performed. Two late fetal deaths (0.9%) were reported, both in patients with persistently active disease. After delivery, 75 patients (34%) presented with a disease flare, associated with active disease at the beginning of pregnancy (P < 0.001). CONCLUSION: The majority of Greek patients with IBD have a favorable pregnancy outcome. Active inflammation during gestation and a diagnosis of ulcerative colitis are negatively associated with pregnancy outcomes.

Diminutive Colon Metastasis From Breast Cancer: An Unexpected Finding in a Patient Undergoing Ulcerative Colitis Surveillance.

Metastatic lesions to the colon are far less common than primary tumors. Breast cancer metastasis to the colon is rarely reported, and it is often atypical in presentation and difficult to diagnose. We present a case of a diminutive asymptomatic breast cancer metastasis to the colon found during surveillance colonoscopy in a patient with long-lasting ulcerative colitis, which was initially regarded as a colitis-associated dysplastic lesion. Because early detection of metastatic disease plays a key role in the treatment of patients with breast cancer, a high index of suspicion must be maintained for atypical metastatic presentations to the gastrointestinal tract.

The Inflammatory Bowel Disease-Disk Tool for Assessing Disability in Inflammatory Bowel Disease Patients: Validation of the Greek Version.

BACKGROUND: The Inflammatory Bowel Disease-Disk (IBD-Disk) is a physician-administered tool that evaluates the functional status of patients with Inflammatory Bowel Disease (IBD). The aim of our study was to validate the content of the IBD-Disk in a Greek cohort of IBD patients. METHODS: Two questionnaires [the IBD Disk and the IBD-Disability Index (IBD-DI)] were translated into Greek and administered to IBD patients at baseline visit, after 4 weeks and 6 months. Validation of the IBD Disk included measuring of concurrent validity, reproducibility, and internal consistency. RESULTS: A total of 300 patients were included at baseline and 269 at follow-up. There was a good correlation between the total scores of the IBD-Disk and IBD-DI at baseline (Pearson correlation 0.87, p < 0.001). Reproducibility of the total IBD-Disk score was very good [intra-class correlation coefficient (ICC), 95% confidence interval (CI) 0.89 (0.86-0.91)]. Cronbach's coefficient alpha for all items achieved 0.90 (95%CI 0.88-0.92), demonstrating a very good homogeneity of the IBD-Disk items. Female gender and extraintestinal manifestations were significantly associated with a higher IBD-Disk total score. CONCLUSIONS: The Greek version of the IBD-Disk proved to be a reliable and valid tool in detecting and assessing IBD-related disability in a Greek cohort of IBD 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.

The natural history of COVID-19 in patients with inflammatory bowel disease: a nationwide study by the Hellenic Society for the study of IBD.

OBJECTIVES: COVID-19 has evolved into a global health crisis, variably affecting the management of patients with chronic illnesses. Patients with inflammatory bowel disease (IBD) may represent a vulnerable population due to frequent administration of immune-modifying treatments. We aimed to depict the natural history of COVID-19 infection in Greek patients with IBD at a nationwide level via unbiased reporting of all cases that were registered during the sequential waves of the pandemic. METHODS: Following a national call from the Hellenic Society for the study of IBD, we enrolled all IBD patients with established diagnoses of COVID-19. Clinical and epidemiological data, including COVID-19 modifying factors and IBD-associated therapies, were analyzed against adverse outcomes (hospitalization, ICU admission and death). RESULTS: We identified 154 IBD patients who were diagnosed with COVID-19 (men: 58.4%; mean age=41.7 years [SD = 14.9]; CD: 64.3%). Adverse outcomes were reported in 34 patients (22.1%), including 3 ICU admissions (1.9%) and two deaths (1.3%). Multivariate logistic regression analysis showed that age (OR = 1.04, 95% CI, 1-1.08) and dyspnea at presentation (OR = 7.36, 95% CI, 1.84-29.46) were associated with worse outcomes of COVID-19 infection. In contrast, treatment with biologics, in particular anti-TNF agents, exerted a protective effect against an unfavorable COVID-19 disease course (OR = 0.4, 95% CI, 0.16-0.99). Patients on subcutaneous biologics were more likely to halt treatment due to the infection as compared to those on intravenous biologics. CONCLUSIONS: IBD patients who developed COVID-19 had a benign course with adverse outcomes being infrequent. Treatment with anti-TNF biologics had a protective effect, thus, supporting continuation of therapy during the pandemic.

Efficacy of prophylactic antiviral therapy and outcomes in HBsAg-negative, anti-HBc-positive patients receiving chemotherapy: a real-life experience.

OBJECTIVE: The aim of this study is to evaluate the outcomes of hepatitis B surface antigen (HBsAg)-negative, anti-HBc-positive patients who received immunosuppressive therapies. PATIENTS AND METHODS: We retrospectively evaluated the medical records of HBsAg-negative, anti-HBc-positive patients with hematological diseases or solid tumors who underwent immunosuppressive therapies and were referred because of positive baseline hepatitis B virus (HBV) serology or HBV reactivation. The referral date was according to the judgment of the treating physician at the time of identification of any signs of HBV infection. RESULTS: We included 55 HBsAg-negative, anti-HBc-positive patients. Of these, 31 received antiviral prophylaxis (group 1), whereas 24 patients did not receive any anti-HBV agent (group 2). The majority of patients [49/55 (89%)] had hematological malignancies and most of them 39/55 (71%) received rituximab-containing regimens. Lamivudine was used as antiviral prophylaxis in 13/31 (42%) patients of group 1. One patient in this group experienced HBV reactivation and was treated successfully with tenofovir add-on therapy. All patients in the second group experienced HBV reactivation and most of them [19/24 (79%)] were treated with tenofovir or entecavir as rescue therapy. Two of these patients (one of the tenofovir/entecavir subgroup and one of the lamivudine subgroup) eventually died because of hepatic failure despite rescue treatment. CONCLUSION: Patients with serological markers of previous HBV infection are still at risk for HBV reactivation. Screening of both anti-HBs and anti-HBc is mandatory before chemotherapy. Pre-emptive antiviral prophylaxis, including lamivudine, is highly effective in all subgroups of such patients, whereas deferring treatment upon HBV reactivation is not enough to rescue all cases.

Debilitating chronic diarrhea caused by generalized gastrointestinal cytomegalovirus infection in an immunocompetent adult.

Gastrointestinal cytomegalovirus (CMV) infection is a common opportunistic infection in immunocompromised patients, especially patients with acquired immunodeficiency syndrome and transplant recipients. In contrast, CMV infection of the gastrointestinal tract is rare in immunocompetent individuals. We report a case of severe, protracted, and debilitating diarrhea caused by generalized CMV infection of the gastrointestinal tract in an elderly woman with no apparent immunosuppression. An extensive diagnostic investigation demonstrated CMV-associated disease affecting both the upper and lower gastrointestinal tracts (esophagus, small intestine, and colon). Such extensive simultaneous involvement of the alimentary tract in an immunocompetent patient is rare and presents a diagnostic and therapeutic challenge. The diagnosis was based on a combination of endoscopic, histopathological, serological, and polymerase chain reaction analysis findings and our patient was successfully treated with intravenous ganciclovir. Our case demonstrates that gastrointestinal CMV infection should be considered in the differential diagnosis of severe chronic diarrhea in immunocompetent patients and that antiviral treatment may be justified in this setting.

Incidence of inflammatory bowel disease is rising and abdominal tuberculosis is falling in Bangladeshis in East London, United Kingdom.

OBJECTIVES: Ulcerative colitis (UC) and Crohn's disease (CD) were previously thought to be uncommon and abdominal tuberculosis (TB) common in patients from Bangladesh. We have reevaluated their incidence in Bangladeshis resident in East London. METHODS: Bangladeshis resident in Tower Hamlets presenting between 1997 and 2001 were identified from pathology, endoscopy, and medical records. Demographic, clinical, and management details were recorded. Incidences were calculated and compared with those from 1981 to 1989. RESULTS: Sixteen Bangladeshi patients with UC, 19 with CD, and 5 with abdominal TB were identified. Between 1997 and 2001, the age-standardized incidence of UC was 8.2/10(5)/yr (95% CI 2.5-13.9) compared with 2.4 (95% CI 0.8-3.8) in 1981-1989, and that of CD was 7.3/10(5)/yr (95% CI 2.0-12.6) (2.3, 95% CI 0.7-3.7 in 1981-1989). The standardized ratios for the incidences of UC and CD in recent periods compared with previous periods were 2.1 (95% CI 0.9-3.9) and 2.5 (1.2-4.6), respectively. There was a significant increase in the number of Bangladeshis developing CD by age <20 yr between the earlier and more recent periods (p < 0.02). The standardized incidence of abdominal TB was 2.5/10(5)/yr (95% CI 0.2-4.8) in 1997-2001, and 7.4 (95% CI 2.1-12.7) in 1985-1989 (p < 0.05). The standardized ratio for the incidence of TB in the two periods was 0.22 (95% CI 0.07-0.53). CONCLUSIONS: In Bangladeshis in East London, the incidence of IBD has increased and of abdominal TB has fallen over the last decade; CD has become a more likely diagnosis than abdominal TB. Clinicians in the Western world need to be aware of the changing incidences of IBD and abdominal TB in South Asians.