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Background The SARS-CoV-2 pandemic has raised issues in the management of inflammatory bowel diseases (IBD). This study aimed to assess the efficacy of different anti-SARS-CoV-2 vaccines under different treatments in IBD patients and identify predictive factors associated with lower serological response, including anti-TNF drug levels. Methods A prospective, multicentre study of IBD patients was conducted following mRNA and non-mRNA anti-SARS-CoV-2 vaccination. Healthy control (HC) patients were enrolled to reduce bias. Baseline and week 14 samples were obtained following the second dose to assess the impact of conventional and biological treatments. Clinical and biochemical activity, serological response level, and anti-TNF drug levels were measured. Results This study included 199 IBD (Table 1.; mean age, 40.9 ± 12.72 years) and 77 HC participants. Most patients (76.9%) and all HCs received mRNA vaccines. Half of the IBD patients were on biological treatment (Table 2.; anti-TNF 68.7%). Combined immunomodulation and biological treatment were associated with lower serological response (Figure 1.; p0.05). Vaccination had no impact on disease activity. Conclusion Anti-SARS-CoV-2 vaccination is considerably efficacious in IBD patients, with mRNA vaccines promoting better antibody levels. The negative impact of combined biological treatment, especially with high adalimumab drug levels, on serological response to vaccination should be considered. Although mid-term durability of vaccination is encouraging, more data are needed to expand existing understanding on this issue.

Background Several studies have proven similarity in terms of efficacy and safety between infliximab (IFX) or adalimumab (ADA) biosimilars and their corresponding originators. However, there is still a paucity of data on the impact of switching from an originator to a biosimilar on patients’ subjective disease control in clinical practice. In Hungary, a mandatory non-medical switch program regarding anti-TNFs was launched in 2021. We aimed to assess symptom control and perception of adverse events following non-medical switch in patients with inflammatory bowel disease (IBD). Methods In this cross-sectional, questionnaire-based study, Hungarian patients with IBD who switched from infliximab originator to biosimilar GP1111 or from adalimumab originator to biosimilar GP2017 after receiving at least one dose of biosimilar were interviewed. The subjective efficacy was measured using a 10-point interval rating scale, and adverse events were assessed. The difference in efficacy before and after the switch was calculated and compared within and between the two drugs. All statistical analysis was performed using R Statistical Software. Results A total of 179 patients were interviewed (median age 41 years, interquartile range 32 to 47; 135 and 44 patients with Crohn’s disease and ulcerative colitis, respectively). There were 73 ADA and 106 IFX switches in our cohort. The subjective efficacy of IFX biosimilar was rated lower compared to IFX reference product (8.72±1.68 vs. 7.77±2.34; p=0.001). The ADA biosimilar was rated higher than their reference product (9.02±1.61 vs. 8.42±1.93; p=0.017). Comparing the satisfaction of non-medical switch between biosimilar groups, patients receiving ADA were more satisfied with the new treatment as patients in the IFX group (p=0.032). The incidence of new perceived adverse events was 85 % in the ADA and 55 % in the IFX group (p Conclusion Our study confirmed the efficacy of the switch to a biosimilar in the case of ADA, while reduced efficacy was experienced with IFX biosimilar. Based on the different adverse event profiles of biosimilars, the importance of switching the product for medical reasons should be emphasized.

Background Data about the effect of different immunosuppressive treatments of IBD patients on seroconversion and on different SARS-CoV-2 vaccinations are scarce. To avoid impaired vaccine responses and worse outcome of COVID-19, factors attenuating protective immunity shoud be shought. Methods Anti SARS-CoV-2S antibody levels of IBD patients in remission were measured by immunoassay (Roche) before vaccination and on the second week. Antibody responses were compared among different treatment groups (biologics, combination, azathioprin, without immunomodulation) and between mRNA and other type of vaccines. Anti TNF alpha levels were also assesed, 24 hours before vaccination considering correlation with seroconversion. Results Thirty-eight (31.7%) ulcerative colitis and eighty-two (68,2%) Crohn’s disease patients were included (median age, 39.1 years, 53.3% female). No serious comorbidities were present. Eighty-two patients (68.3%) were on biological therapy, fifty-two (43%) were treated with azathioprine alone or in combination. Two doses of mRNA vaccines were administered to ninty-eight patients ((81,7%) Moderna:, 20, Pfizer:, 78). The other type of vaccines were AstraZeneca (16) Sputnik V (3) and Sinopharm (3). The median anti-SARS-CoV-2S antibody level was, 2733 U/mL (IQR:, 535–7764) on the, 14th day after vaccination (IQR:, 14–17). Significant differences were revealed between the groups of patients treated with biological agents or non-biological therapy (median:, 1649 U/ml vs., 5711.5 U/ml; p=0.013) and between patients recieving mRNA and non-mRNA vaccine (median:, 3367.5 U/ml vs., 392.6 U/ml;p Conclusion Altough all vaccines cause seroconversion in IBD patients who are in remission, the rate of seroconversion is lower in patients treated with immunosupressant, biological agent or combo therapy or recieving non-mRNA vaccines. As the level of anti-TNF-alpha agents do not affect the rate of seroconversion there is probably no need for matching the time of vaccination and anti-TNF therapy.

Background The use of biosimilar adalimumab (ADA) is effective and safe in inflammatory bowel disease (IBD), although clinical data on switching between ADA biosimilars is still rare. At the end of 2020, a non-medical switch to biosimilar ADA became mandatory in Hungary due to reimbursement policy changes of the National Health Insurance Fund of Hungary (NEAK). The aim of the present study was to evaluate short- and medium term clinical efficacy, drug sustainability and safety comparing non-medical switches from the originator to biosimilar ADA, and between ADA biosimilars. Methods 246 consecutive patients on maintenance ADA therapy (n=181 Crohn’s disease [CD] and n=65 ulcerative colitis [UC], male/female: 44%/56%, median disease duration: 10years(y) (IQR: 10–16)) were included from 4 IBD centers between September 2019 and December 2020. Data on clinical efficacy, using Crohn’s Disease Activity Index (CDAI) and partial Mayo Score (pMayo), laboratory parameters (C-reactive protein – CRP) and adverse events were collected at 8–12 weeks prior switch, at baseline, and 8–12 weeks, 20–24 weeks after switch. Drug sustainability following the switch was evaluated after a median of 41 weeks (IQR: 35–42) follow-up time. Results A total of 246 IBD patients (n=153 patients [115CD/38UC, median age: 38y(IQR: 27–45)] and n=93 patients [66CD/27UC, 32y(IQR: 26–40.5)] underwent a non-medical switch from the originator to a biosimilar, and biosimilar to biosimilar. Clinical disease activity based on CDAI and pMayo scores are presented in Figures 1 and 2. No significant difference was found in the proportion of patients in clinical remission at week 8–12 prior switch / switch / week 8–12 and week 20–24 in either patients switched from originator to biosimilar (86.8% / 88.2% / 86.0% / 85.0%; p=0.87 among groups) or biosimilar to biosimilar (72.0% / 77.4% / 84.9% / 77.6%; p=0.21). 89.2% and 83.1% of patients who were in clinical remission at switch/baseline sustained clinical remission up to week 20–24 in the first and second cohorts. Mean CRP levels were also unchanged during follow-up in both cohorts (p=0.71 and p=0.94). Drug survival was similar between originator to biosimilar and biosimilar to biosimilar switch cohorts, with a probability of 90.6% (SE: 2.4) and 85.8% (SE:3.7) to stay on drug after 40 weeks (log-rank: p=0.271). Figure 3. Two cases of skin reactions were registered as adverse events, one leading to treatment discontinuation. Conclusion Clinical remission was sustained following non-medical switch from originator or biosimilar adalimumab to a biosimilar in IBD patients. Medium-term drug sustainability following the switch was high, and comparable between patients with an originator to biosimilar and a biosimilar to biosimilar switch.

Background Anti-tumor necrosis factor alpha treatments are effective and safe as first line therapy, however, their long-term efficacy is limited by primary (PNR) and secondary non-response (LOR) resulting in treatment discontinuation in approximately, 40–50% of cases. Vedolizumab (VDZ) and ustekinumab (UST) therapy could be good alternative in patient with anti-TNF failure, however, no direct comparison has been made. This study aimed to assess treatment persistence and long-term efficacy of VDZ and UST as second- and third line biological therapies in Crohn’s disease (CD) patients refractory to anti-TNF therapy. Methods In this multicentre study, CD patients on VDZ or UST maintenance therapy were enrolled. We analysed data of medical history retrospectively in case of both agents. Demographic and clinical data at baseline and one-year were obtained. Clinical (CDAI Results 200 UST and, 96 VDZ-treated patients were included in the study. After exclusion of confounders, 162 UST and, 77 VDZ-treated patients were completed the follow-up. Mean age was, 41,1 (±16,5) and, 37,9 (±11,3) years at both agents at baseline. Steroid-free clinical and biochemical remission rates did not differ between VDZ and UST groups at one year (73% vs, 73% and, 67% vs., 51%). Kaplan-Meyer analysis revealed superiority of UST during follow up (86,5% vs., 62,9%, p Conclusion We confirmed that VDZ and UST are effective and safe alternatives to CD patients who have failed to anti-TNF therapy. UST has a superiority in drug persistence compared to VDZ. Second compared to third line of sequential therapy results in better outcome in drug persistence in case of both agents, however, head-to-head comparison of both agents are needed to verify our data.

Background Inflammatory bowel disease potentially elevates the risk of infections, furthermore, disease activity and medical treatment(s) can increase the risk as well. However, both international data and recent studies do not confirm these preliminary conceptions regarding the SARS-CoV-2 infection. In addition, a number of studies have reported that less antibodies are produced against the virus in IBD patients. In January, 2021, the vaccination campaign has begun in Hungary as well, however, questions have been raised about the effectiveness and safety of the vaccine. Methods In this multicentre study, we assessed the prevalence and risk factors of COVID-19 infection, the willingness to receive COVID-19 vaccine and the efficacy of vaccination among IBD patients receiving biological therapy, based on a cross-sectional questionnaire-based study. To assess safety and antibody response to COVID-19 vaccines, we conducted a prospective study in the same Hungarian IBD centers. IgG antibody was quantified to SARS-CoV-2 spike protein and nucleocapsid, 1 week before and after the first vaccine and, 4 and, 8 weeks after the second vaccinane, respectively. Results 472 patients were enrolled in the first part of our study. SARS-CoV-2 infection was confirmed in, 16.9% of patients. Wearing gloves and masks were found to be effective in preventing infection (p=0.02; p=0.005), avoidance of communal areas had no effect on infection rates. Male sex increased the risk (p=0.008) of viral infection. Based on subjective complaints, UC patients had a worse disease course (p=0.002). Biological therapies did not increase the risk of infections. Patients vaccinated with mRNA vaccine had a significantly higher spike protein antibody titer one month after the second vaccination (p=0.004) compared to other vaccine types (Sinopharm©, Sputnik V©, Astra Zeneca©). Seropositivity was detected in, 98% of patients. Sinopharm© vaccination triggered the lowest number of side effect (p Conclusion Face mask was the most effective preventive tool. The risk of infection was not increased by biological therapy, therefore therapy discontinuation is not justified. Almost every vaccinated patient developed seropositivity two month after vaccination independently from the type of the vaccine, however, spike protein antibody was significantly higher following mRNA vaccinations.

Background Although efficacy and safety of ustekinumab (UST) in the treatment of inflammatory bowel disease have been demonstrated through randomized trials, data from real-life prospective cohorts are still of great interest. Our aim was to evaluate the clinical efficacy, drug sustainability, frequency of dose intensification, and results from therapeutic drug monitoring in UST treated Crohn’s disease (CD) patients using a prospective, nationwide, multicenter cohort from Hungary. Methods Patients were consecutively enrolled in this cohort between 2019 January and 2020 May from 5 academic centers and 5 county hospitals. Data from patient demographics, disease phenotype, treatment history (surgical history, prior and present medical therapies), clinical disease activity (using the Crohn’s Disease Activity Index (CDAI), Harvey Bradshaw Index (HBI)), biomarkers (C-reactive protein – CRP), and therapeutic drug monitoring were captured. Evaluations were performed at week8 (post-induction), w16-20, w32-36, and w52-56 follow-up visits. Results N=142 CD patients were included with a median follow-up time of 60 weeks (IQR:47.5–79.5w) [57.4% female; age 38.4±13.0 years]. Based on the Montreal classification, complicated disease behavior (B2orB3) was 48.2%, whereas ileocolonic disease location(L3) 55.7%. Perianal manifestation was present in 46.8% of the patients. Previous anti-TNF exposition was 97.2%, while previous vedolizumab failure was 25.5%. 66.2%/ 66.9% of the patients had moderate-to-sever clinical disease activity at baseline (CDAI>220/HBI>7). Clinical response and remission rates were 78.1% and 57.7% using CDAI, and 82.5% and 51.8% based on HBI scores after induction treatment (w8). One year clinical remission rates were 58% / 57.3% (CDAI/HBI) Composite clinical and biomarker remission (CDAI Conclusion Ustekinumab showed good drug sustainability and clinical efficacy in a population with severe disease phenotype and high rates of previous anti-TNF failure, however frequent and early dose intensification was required.

Primary sclerosing cholangitis (PSC) is a common cause for liver transplantation (OLT) in Europe. It is frequently associated with inflammatory bowel disease (IBD). PSC associated IBD often runs a quiescent course but becomes more aggressive after OLT in some patients. Our aim was to evaluate the activity of IBD in PSC patients before and after OLT in Hungary. We retrospectively analyzed data from 411 whole-liver transplantations from 1995 to 2010 that included 41 patients transplanted due to PSC (10%). Thirty-one PSC patients had IBD pre-OLT. We used the Mayo score (Disease Activity Index) to assess the severity of ulcerative colitis (UC) before and after OLT. Among 55% of patients who had pancolits, the majority (95%) were inactive or showed only mild activity before transplantation. After transplantation, disease activity was inactive in 10%; mild to moderate in 25% to 25%; and severe in 40% of cases. The Mayo score was higher after transplantation compared with the pretransplant level (2.91 ± 0.9 versus 6.64 ± 3.7, P = .009). Retransplantations (n = 5) were performed only among PSC patients with colonic involvement. In conclusion, the activity of IBD worsens in the majority of patients after OLT. Early colectomy should be considered to prevent severe complications and liver graft impairment.