Safety, Efficacy and Persistence of Advanced Therapies in Inflammatory Bowel Disease: Results from ORIGINS. A Retrospective Observational Study.

BACKGROUND AND AIMS: Real-world assessments of efficacy and safety of advanced therapies used for inflammatory bowel disease (IBD) patients are limited. We aimed to report safety, efficacy and treatment persistence of new molecules (infliximab, adalimumab, vedolizumab, tofacitinib, ustekinumab) in a retrospective multicentric national Romanian analysis. METHODS: We conducted a nationwide, retrospective observational multicentric study. Data were collected retrospectively from electronic and paper files. Patients who started on one of the five investigated molecules during December 2019-December 2021 were included. The main outcome measures were clinical remission, endoscopic healing, persistence on treatment and safety data. RESULTS: A total of 678 adult patients from 24 Romanian IBD centers with a diagnosis of ulcerative colitis or Crohn's disease were included. Participants had previously failure to one (268, 39.5%), two (108, 15%) or more treatment lines and only 38% (259) were biologic naïve. In the 24 months study period, most patients were started on vedolizumab (192, 28%), followed by adalimumab, infliximab, ustekinumab and tofacitinib. In biologic-naïve patients, most physicians (72%) preferred anti-TNF treatment as first line biologic (93 patients started on infliximab, 92 on adalimumab), followed by vedolizumab, ustekinumab and tofacitinib. During follow-up, 71% (470, p=0.05) of patients achieved clinical remission and 36% (134, p=0.03) achieved mucosal healing. The 6 months milestone for persistence was reached in 78% (530) of cases. Almost half of patients (47%, 316 patients) persisted on their current treatment for over 12 months. Overall, an adverse reaction was reported for 67 (10.4%) patients, with no lethal events. CONCLUSIONS: Population of biologic-experienced IBD patients in Romania is increasing and is becoming more difficult to achieve long-term disease control. Discontinuation rates for advanced therapies are high.

Efficacy and Safety of Ledispavir/Sofosbuvir with or without Ribavirin in patients with Decompensated Liver Cirrhosis and Hepatitis C Infection: a Cohort Study.

BACKGROUND AND AIMS: Ledipasvir/Sofosbuvir (LDV/SOF) with or without Ribavirin (RBV) has shown good results in terms of efficacy and safety in clinical trials in advanced liver cirrhosis, but real-life data are still needed in order to confirm this profile. We investigated the efficacy and safety of LDV/SOF in a large Romanian population with liver cirrhosis and genotype 1b hepatitis C virus (HCV). METHODS: We analyzed a multicentric retrospective cohort enrolling 349 patients with decompensated liver cirrhosis due to HCV who received LDV/SOF±RBV 12/24 weeks (301/48). Patients were included between 2017-2018, all with genotype 1b. Main inclusion criteria were liver cirrhosis and detectable HCV RNA. The cases were followed-up monthly during therapy and 12 weeks after the end of therapy. RESULTS: The cohort included 60% females with a median age of 61, 16% interferon (IFN) pre-treated, 53% with comorbidities, 40/53/7 % with Child Pugh A/B/C, 4% with virus B co-infection and 8% with previously treated hepatocellular carcinoma. Mean initial MELD score was 11.92 (6.82÷ 24.5). Six patients were lost during follow-up. Sustained virologic response (SVR) in intention-to-treat was reported in 85.1%. Predictive factors of SVR in decompensated cirrhosis were female gender (p=0.01), advanced age (p<0.001), lower bilirubin levels (p=0.002) and lower CTP score (p=0.02). In patients with CTP score B or C low bilirubin levels (p=0.003), low INR (p<0.001), increased platelet count (p=0.04), low CTP score (p<0.001), lack of encephalopathy (p=0.02), serum albumin >3.5g/dl (p=0.002) predicted improvement of liver function. Serious adverse events were reported in 16/349 (4.6%), most of them due to severe liver decompensation (9/16). CONCLUSIONS: LDV/SOF±RBV proved to be highly efficient in our difficult to treat population with 85.1% SVR.

Environmental Factors in Romanian and Belgian Patients with Inflammatory Bowel Disease - a Retrospective Comparative Study.

Background:Several environmental factors have been associated with onset of inflammatory bowel diseases (IBD): smoking, hygiene, microorganisms, oral contraceptive pills (OCPs), non-steroid anti-inflammatory drugs, antibiotics, appendectomy, diet, breastfeeding, vitamin D, stress and ambient air pollution. The aim of this study was to investigate the prevalence of these factors in a Romanian and Belgian population with IBD. Material and methods:A total of 129 patients with an IBD diagnosis (76 from Romania and 53 from Belgium) participated in an interview and were asked to fill in a questionnaire regarding environmental factors before and after the onset of IBD; 35 Romanian and 21 Belgian healthy individuals constituted the control group. Results:A total of 40 patients with ulcerative colitis (UC) and 89 with Crohn's disease (CD) were included. Gender distribution was 43% males and 57% females. They had a median age of 42 years (range between 19-74 years), a median disease duration of eight years and 79% were in clinical remission. Both Romanian and Belgian IBD patients reported an increased antibiotic consumption before IBD onset compared to controls: 58% vs 10% (p<0.001) and 51% vs 5% (p<0.001), respectively. Belgian IBD patients declared significantly more frequent OCP use (53% vs 9%, p <0.001), they were breastfed in a lower proportion (49% vs 76%, p <0.001) and had experienced a higher level of psychosocial stress (p<0.001). Conclusion:Antibiotic consumption before IBD onset may play a pivotal role in IBD development in both Romanian and Belgian populations. In Belgian patients, OCP consumption, a higher level of psychosocial stress and lack of breastfeeding may also be involved.

The prevalence of malnutrition and the evolution of nutritional status in patients with moderate to severe forms of Crohn's disease treated with Infliximab.

BACKGROUND & AIMS: Malnutrition is variably encountered in adult patients with Crohn's disease. We evaluated the nutritional status at the beginning and during Infliximab treatment in patients with Crohn's disease. METHODS: Patients with moderate/severe flares of disease treated with Infliximab for induction and maintenance of remission were included in a prospective observational study. Body Mass Index and Nutritional Risk Index were calculated in each patient at 0, 6 weeks and than every 8 weeks for one year. RESULTS: From 30 patients treated with Infliximab 59.3% had low BMI, 35.7% being undernourished. The severity of Crohn's disease did not correlate with low BMI but did correlate with Nutritional Risk Index (p = 0.001). In all patients that responded to Infliximab treatment progressive weight gain was observed, all but one patient reaching normal BMI after one year. Mean weight gain was significantly more elevated (p = 0.001) and time needed to reach normal BMI was longer in the undernutrition group (p = 0.01). Clinical remission was the principal factor associated with weight gain (p = 0.001), while there was no influence of endoscopic remission on nutritional status. CONCLUSIONS: In patients with moderate/severe forms of Crohn's disease malnutrition is frequently encountered. Induction and maintenance treatment with Infliximab determines weight gain and corrects malnutrition in all patients with clinical remission.

Efficacy and safety of peginterferon alpha-2a (40KD) in HBeAg-positive chronic hepatitis B patients.

AIM: The study was designed to evaluate the efficacy and safety of peginterferon alpha-2a in HBeAg-positive chronic hepatitis B patients, nonresponders or relapsers after previous lamivudine or standard interferon therapy. METHODS: This prospective, national, multicentric, open label, not randomized trial enrolled 43 HBeAg-positive chronic hepatitis B patients with detectable HBsAg for at least 6 months prior to screening, positive HBeAg and negative anti-HBe, serum HBV DNA levels of at least 500,000 copies/mL by PCR assay, elevated ALT up to 10 x ULN, no response or relapse after previous lamivudine or standard interferon therapy. All eligible patients received pegIFN alpha-2a 180 micrograms weekly for 48 weeks with 24 weeks treatment free follow-up. There were two main efficacy assessments: HBeAg seroconversion and viral supression below 100,000 copies/mL. RESULTS: HBeAg seroconversion rate at the end-of-treatment was 4.65% (n=2; p less than 0.05) increasing to 11.62% 24 weeks after end of therapy (n=5; p less than 0.05). The rate of viral supression at levels below 100,000 copies/mL was 23.25% (n=10; p less than 0.05) at end-of-treatment, and 16.3% (n=7; p less than 0.05) at end of follow-up. ALT normalization was obtained in 20.9% (p less than 0.05) of patients at end-of-treatment, the percentage being significantly higher - 37.2% (p less than 0.05) at the end of follow-up. CONCLUSIONS: Even in a difficult-to-treat patient population with HBeAg-positive chronic hepatitis B, peginterferon alpha 2a proved to be efficient in a defined proportion of patients. The increase in HBeAg seroconversion rate from end-of-treatment (4.65%) to the end of follow-up period (11.62%) also proves the benefits of prolonged immunological effect of pegIFN alpha 2a.