Use Of Immunomodulators Research Articles

The Mayo Endoscopic Score Is a Novel Predictive Indicator for Malignant Transformation in Ulcerative Colitis: A Long-Term Follow-Up Multicenter Study

BackgroundData on the relative risk of malignant transformation in ulcerative colitis (UC) are insufficient. We investigated the potential value of the Mayo endoscopic score (MES) for predicting malignant transformation in patients with UC.MethodsData of patients with UC evaluated at our institute from June 1986 to December 2019 were retrospectively analyzed. The MES used in the study indicated the results of the first colonoscopy after hospitalization. We defined MES of 0–1 as low and MES of 2–3 as high. Univariable and multivariate logistic regression models were used for statistical analysis.ResultsAmong the 280 eligible patients with UC with a median follow-up time of 14 (interquartile range, 10.0–18.0) years, those with a high MES were more likely to develop malignant transformation. High MES positively correlated with the degree of malignancy and was an independent risk factor for UC-associated dysplasia and colorectal cancer (CRC, odds ratio [OR], 9.223; 95% confidence interval [CI], 1.160–73.323; p = 0.036). Disease duration >5 years (OR, 2.05; 95% CI, 1.177–3.572; p = 0.011), immunomodulator use (OR, 4.314; 95% CI, 1.725–10.785; p = 0.002), biologics nonuse (OR, 3.901; 95%CI, 2.213–6.876; p < 0.001), and Hb <90 g/L (OR, 2.691; 95% CI, 1.251–5.785; p = 0.011) were contributing factors for high MES.ConclusionHigh MES could be a novel predictor of malignant transformation in UC. Clinicians should optimize the use of biologics and immunomodulators early and should actively correct anemia to improve the MES and then reduce the incidence of UC-associated dysplasia and CRC.

The use of the probiotic «Subtilis-C» in the breeding of the Nile tilapia (Oreochromis niloticus)

With intensive cultivation technologies, fish are exposed to stress factors associated with intensive breeding. They reduce the immunity of cultivated objects. In addition, the aquatic environment is a good substrate for the development of microorganisms, including pathogenic ones, which aggravates the situation. Therefore, increasing the immunity of fish is an urgent task of their breeding. One of the ways to enhance the immune resistance of the body is the use of immunomodulators. The purpose of this work was to study the effect of the probiotic “Subtilis-S” on the productivity and hematological status of fish. At the beginning of the experiment, the tilapia females (7 heads per aquarium) were separated from the males. Males were kept individually. The fish of the experimental groups received the probiotic “Subtilis-S” as a feed additive for two months at the rate of 1 g/kg of feed. A month after the start of the experiment, the males were hooked up to the females (one male in each aquarium). After gestation, the larva was taken from the females and planted in separate containers. During the experiment, fertilization of eggs occurred in 80% of females in the experimental group and 50% in the control. The results of fish appraisal showed that the probiotic “Subtilis-S” had no effect on the growth and mass accumulation of tilapia: no significant differences in the main zootechnical parameters were found in the fish of the experimental and control groups. In the leukogram of tilapia treated with “Subtilis-S”, the proportion of lymphocytes increased due to a decrease in immature forms of the myeloid series; for rod-shaped neutrophils, the differences are significant. Which probably indicates the activation of a specific link of the immune defense. In the blood of experienced tilapia, in contrast to the control, there is a small percentage of eosinophils and basophils, that is, there is an increase in the nonspecific link of cellular immunity. The use of the probiotic “Subtilis-S” as a feed additive enhances the immunity of tilapia and increases the survival of fish in aquaculture, as well as increases their fertility.

The influence of immunomodulators on the formation of vaccine-induced cholera immunity

Introduction. Due to the remaining tense situation on cholera in the world, research continues on the creation of new preventive drugs, as well as ways to increase the immunogenicity of existing anti-cholera vaccines. The combined use of vaccines with immunomodulators and cytokines is successfully used for the specific prevention of various infections, including particularly dangerous ones.The aim of the work is an experimental study of the effect of immunomodulators on the immunogenic and protective activity of the cholera bivalent chemical vaccine in order to assess the possibility of their use to improve the specific prevention of cholera.Materials and methods. The parameters of cellular and humoral local and systemic immune response in experimental animals vaccinated and receiving immunotherapy, as well as the effect of immunomodulators on the protective activity of antigens that are part of the cholera bivalent chemical vaccine, were evaluated.Results. The studies revealed that the use of immunomodulators in combination with the vaccine leads to an increase in the immunogenic properties of antigens. Immunomodulators stimulate the differentiation of CD4⁺- lymphocytes, ensuring the development of an immune response mainly along the humoral pathway, increase the number of B-lymphocytes, antigen-specific antibody-forming cells, as well as secretory immunoglobulin A in the intestines of vaccinated experimental animals. It is shown that the immunomodulator glucosaminylmuramyl dipeptide increases the protective properties of the antigens that are part of the chemical cholera bivalent vaccine. It was the most effective additive, since it protected all the animals included in the experiment from generalized cholera.Conclusion. The use of immunomodulators in anti-cholera vaccination, especially with glucosaminylmuramyl dipeptide, may be one of the approaches to improving the specific prevention of cholera.

Open-label use of an aliphatic polyamine immunomodulator in patients hospitalized with COVID-19.

BackgroundEvidence-based therapies used to treat coronavirus disease (COVID-19) remain limited. Azoximer bromide (AZB; Polyoxidonium®) is an immunomodulating molecule frequently used in the Russian Federation. It offers demonstrable therapeutic benefit in upper respiratory tract infections. This study evaluated the safety and efficacy of AZB when used in combination with standard of care treatment in patients hospitalized with COVID-19.MethodsHospitalized patients with COVID-19 (n=81; nine sites) received AZB 12 mg intravenously once daily for 3 days then intramuscularly every other day until day 17. The primary endpoint included clinical status at day 15 versus baseline. Historical control data of 100 patients from a randomized, controlled, open-label trial conducted in China were included to serve as a direct control group.ResultsNotable clinical improvement, assessed by seven-point ordinal scale (OS) score and National Early Warning Score, was observed. Mean duration of hospitalization was 19.3 days. Indicators of pneumonia and lung function showed gradual recovery to normalization. No patients died but, by day 28, one patient still required respiratory support; this patient died on day 34. A higher proportion of patients receiving AZB required invasive or non-invasive ventilation (OS 5 or 6) at baseline compared with the historical control group. Improvement in mean OS score by day 14/15 was not notable in the control group (OS 3.99–3.87) but was clear in the AZB group (OS 4.36–2.90). Mean duration of hospitalization was similar in the control group (16.0 days); however, day 28 mortality was higher, at 25.0% (n=25).ConclusionAZB combined with standard of care was safe and well tolerated. An apparent clinical improvement could not be fully evaluated due to the lack of a direct control group; further assessment of AZB for the treatment of COVID-19 in a randomized, placebo-controlled study is warranted.

Enhancing the Response Rate to Recombinant Uricases in Patients with Gout

Refractory, or uncontrolled, gout is a chronic, progressive, inflammatory arthropathy resulting from continued urate deposition after failed attempts to lower serum uric acid below the therapeutic threshold with oral urate-lowering therapies such as allopurinol and febuxostat. Recombinant uricase is increasingly being used to treat refractory gout; however, the immunogenicity of uricase-based therapies has limited the use of these biologic therapies. Antidrug antibodies against biologic therapies, including uricase and PEGylated uricase, can lead to loss of urate-lowering response, increased risk of infusion reactions, and subsequent treatment failure. However, co-therapy with an immunomodulator can attenuate antidrug antibody development, potentially increasing the likelihood of sustained urate lowering, therapy course completion, and successful treatment outcomes. This review summarizes evidence surrounding the use of immunomodulation as co-therapy with recombinant uricases.

The Relationship Between Opioid Use and Healthcare Utilization in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

Pain is commonly experienced by patients with inflammatory bowel disease (IBD). Unfortunately, pain management is a challenge in IBD care, as currently available analgesics are associated with adverse events. Our understanding of the impact of opioid use on healthcare utilization among IBD patients remains limited. A systematic search was completed using PubMed, Embase, the Cochrane Library, and Scopus through May of 2020. The exposure of interest was any opioid medication prescribed by a healthcare provider. Outcomes included readmissions rate, hospitalization, hospital length of stay, healthcare costs, emergency department visits, outpatient visits, IBD-related surgeries, and IBD-related medication utilization. Meta-analysis was conducted on study outcomes reported in at least 4 studies using random-effects models to estimate pooled relative risk (RR) and 95% confidence interval (CI). We identified 1969 articles, of which 30 met inclusion criteria. Meta-analysis showed an association between opioid use and longer length of stay (mean difference, 2.25 days; 95% CI, 1.29-3.22), higher likelihood of prior IBD-related surgery (RR, 1.72; 95% CI, 1.32-2.25), and higher rates of biologic use (RR, 1.38; 95% CI, 1.13-1.68) but no difference in 30-day readmissions (RR, 1.17; 95% CI, 0.86-1.61), immunomodulator use (RR, 1.13; 95% CI, 0.89-1.44), or corticosteroid use (RR, 1.36; 95% CI, 0.88-2.10) in patients with IBD. On systematic review, opioid use was associated with increased hospitalizations, healthcare costs, emergency department visits, outpatient visits, and polypharmacy. Opioids use among patients with IBD is associated with increased healthcare utilization. Nonopioid alternatives are needed to reduce burden on the healthcare system and improve patient outcomes.

COVID-19 in elderly: Management issues

Introduction: COVID 19 has once again brought to the forefront the issue of vulnerability of the geriatric population to diseases. Advanced age itself and comorbidities (obesity, DM, HTN/IHD, COPD, CLD, CKD, immunocompromised states, transplant, malignancy and CHD), which increase with age, are the main risk factors for contracting severe COVID 19. Immunosenescence, unpredictable disease course, atypical symptoms, pathophysiological changes in respiratory system and a state of hypercoagulability associated with aging are responsible for increased severity and mortality of SARS CoV 2 in the elderly. Management: Diagnosis: RT PCR is the gold standard investigation for diagnosis though it has approximately 33% false negative rate. Classification: On the basis of dyspnea, respiratory rate and SpO2 in room air, patients are classified as mild, moderate and severe cases. On the basis of severity of case, investigation and monitoring is planned. Treatment: Mild cases are advised home isolation whereas moderate and severe cases require hospitalization. Mild cases usually subside with use of anti pyretics, immunomodulators (Zinc, Vit C, D), hydration, anti tussives and anti virals (Doxycycline, Ivermectin, Favipiravir). Oxygen therapy and steroids form the mainstay of treatment in moderate and severe cases. Anti coagulants, anti viral (Remdesivir) and monoclonal antibody (Tocilizumab) are used as and when required. Newer drugs like antibody cocktail and 2-DG have also been developed. Chest physiotherapy (proning and spirometric exercise) enhances recovery. Prevention: COVID appropriate behavior (use of mask, hand hygiene and physical distancing) and priority vaccination of elderly are the most important tools to safeguard geriatric population.

Predictors of each quality of life dimension in Crohn’s disease patients initiating an anti-TNF treatment: differentiated effects of patient-, disease-, and treatment-related characteristics

Background and aims In Crohn’s disease (CD), a composite therapeutic target was recently recommended, including both objective measurement (endoscopic remission) and Patient-Reported Outcomes (resolution of abdominal pain and normalization of bowel function). All dimensions of health-related quality of life (HRQoL) are impacted: not only bowel symptoms but also systemic symptoms, emotional wellbeing and social function. Thus, understanding the predictors of each HRQoL dimension would improve patient management. However, analysis of these factors has only been found in a few publications, with some limitations. Therefore, this study aimed to explore the evolution of the HRQoL of CD patients during six months after initiation of anti-TNF and to identify its predictors. Methods We analyzed data of 56 patients included in a multicenter prospective cohort study (COQC-PIT). HRQoL measures (using IBDQ-32) and data related to patient, disease and treatment characteristics were collected every two months. Generalized estimating equations were used. Results Overall HRQoL was significantly improved 2 months after anti-TNF initiation, and then stagnated. Patient, disease, and treatment characteristics have differentiated impacts on the overall score and on each dimension of quality of life. Subcutaneous anti-TNF had no significant effect on overall HRQoL, improving only emotional function and bowel symptoms. Concomitant use of corticosteroids and/or immunomodulators impaired almost all dimensions. Having children or working altered bowel symptoms. Disease duration and active smoking negatively impact emotional function and systemic symptoms. Conclusions Each HRQoL dimension, not only bowel symptoms, and their influencing factors should therefore be considered in medical decision-making, especially in months following the initiation of a new treatment such as anti-TNF.

An International, Retrospective Study of Off-Label Biologic Use in the Treatment of Hypereosinophilic Syndromes

Treatment of hypereosinophilic syndrome (HES) often requires the use of immunomodulators with substantial side effect profiles. The emergence of biologics offers an alternative treatment modality. To examine real-world practice data to describe the safety and consequences of various biologics suspected to directly or indirectly affect eosinophilic inflammation for the treatment of HES. Retrospective data from 13 centers were collected via an online Research Electronic Data Capture repository. Inclusion criteria included (1) peripheral eosinophil count of 1,500/mm3 or greater without a secondary cause; (2) clinical manifestations attributable to the eosinophilia; and (3) having received mepolizumab (anti-IL-5), benralizumab (afucosylated anti-IL-5 receptor α), omalizumab (anti-IgE), alemtuzumab (anti-CD52), dupilumab (anti-IL-4 receptor α), or reslizumab (anti-IL-5) outside a placebo-controlled clinical trial. Of the 151 courses of biologics prescribed for 121 patients with HES, 59% resulted in improved HES symptoms and 77% enabled tapering of other HES medications. Overall, 105 patients were receiving daily systemic glucocorticoids at the time of a biologic initiation and were able to reduce the glucocorticoid dose by a median reduction of 10 mg of daily prednisone equivalents. Biologics were generally safe and well-tolerated other than infusion reactions with alemtuzumab. Thirteen of 24 patients had clinical improvement after switching biologics and nine patients responded to increasing the dose of mepolizumab after a lack of response to a lower dose. Biologics may offer a safer treatment alternative to existing therapies for HES, although the optimal dosing and choice for each subtype of HES remain to be determined. Limitations of this study include its retrospective nature and intersite differences in data collection and availability of each biologic.

Disrupted Circadian Rest-Activity Cycles in Inflammatory Bowel Disease Are Associated With Aggressive Disease Phenotype, Subclinical Inflammation, and Dysbiosis.

Patients with inflammatory bowel disease (IBD)—Crohn's disease (CD), and ulcerative colitis (UC), have poor sleep quality. Sleep and multiple immunologic and gastrointestinal processes in the body are orchestrated by the circadian clock, and we recently reported that a later category or chronotype of the circadian clock was associated with worse IBD specific outcomes. The goal of this study was to determine if circadian misalignment by rest-activity cycles is associated with markers of aggressive disease, subclinical inflammation, and dysbiosis in IBD. A total of 42 patients with inactive but biopsy-proven CD or UC and 10 healthy controls participated in this prospective cohort study. Subjects were defined as having an aggressive IBD disease history (steroid dependence, use of biologic or immunomodulator, and/or surgery) or non-aggressive history. All participants did two weeks of wrist actigraphy, followed by measurement of intestinal permeability and stool microbiota. Wrist actigraphy was used to calculate circadian markers of rest-activity– interdaily stability (IS), intradaily variability (IV), and relative amplitude (RA). Aggressive IBD history was associated with decrease rest-activity stability (IS) and increased fragmentation compared to non-aggressive IBD and health controls at 0.39 ±.15 vs. 0.51 ± 0.10 vs. 0.55 ± 0.09 (P < 0.05) and 0.83 ± 0.20 vs. 0.72 ± 0.14 (P < 0.05) but not HC at 0.72 ± 0.14 (P = 0.08); respectively. There was not a significant difference in RA by IBD disease history. Increased intestinal permeability and increased TNF-α levels correlated with an increased rest activity fragmentation (IV) at R = 0.35, P < 0.05 and R = 0.37, P < 0.05, respectively; and decreased rest-activity amplitude (RA) was associated with increased stool calprotectin at R = 0.40, P < 0.05. Analysis of intestinal microbiota showed a significant decrease in commensal butyrate producing taxa and increased pro-inflammatory bacteria with disrupted rest-activity cycles. In this study, different components of circadian misalignment by rest-activity cycles were associated with a more aggressive IBD disease history, increased intestinal permeability, stool calprotectin, increased pro-inflammatory cytokines, and dysbiosis. Wrist activity allows for an easy non-invasive assessment of circadian activity which may be an important biomarker of inflammation in IB.

Effect of transdermal immunomodulation on liver regeneration

Introduction. The use of immunomodulators to regulate reparative processes in affected organs and tissues remains a pressing issue. Of greatest interest is liver regeneration after extended hepatic resection (EHR) in donors in right lobe living related donor liver transplantation. We propose a transdermal therapeutic system (TTS) with an immunomodulator to enhance the natural process of liver tissue regeneration. Objective: to study the effect of transdermal administration of immunomodulator sodium aminodihydrophthalazinedione on early recovery processes in the liver after EHR in in vivo experiments.Materials and methods. Sodium aminodihydrophthalazinedione was used as an active substance in TTS in the form of powder for preparation of intramuscular injection solution (Galavit®, SELVIM LLC). An experimental EHR model was performed on 22 male Wistar rats weighing 350–380 g. After HER, all animals were divided into two groups. Group 1 (n = 10) consisted of untreated animals. In group 2 (n = 12), TTS was applied immediately after liver resection. The experiment lasted for 48 hours; the TTS was changed once after 24 hours from the beginning of application.Results. In either group, there was no significant difference in the weight of liver remnant gain and in biochemical blood parameters at 48 hours after EHR. Assessment of the mitotic index (MI) of hepatocytes 48 hours after EHR revealed a significant increase in MI in both groups in comparison with the baseline (before liver resection) equal to 0.14 ± 0.07‰. The MI in group 1 and group 2 animals was 12.70 ± 4.9‰ and 17.43 ± 4.90‰, respectively (p ≤ 0.05).Conclusion. Studies on the regenerative activity of sodium aminodihydrophthalazinedione TTS on an experimental EHR model in rats showed that this drug form had a pronounced stimulating effect on the mitotic activity of liver cells.

Immunomodulators: still having a role?

Immunomodulators, particularly the thiopurines and to a lesser extent methotrexate, were standard of care for inflammatory bowel diseases, including Crohn's disease and ulcerative colitis, for >40 years. While there has been a renaissance in available therapies with the advent of biologics and small molecules, an impetus remains for the ongoing use of thiopurines and methotrexate. This is particularly true for the maintenance of remission and when used in combination therapy with infliximab to suppress anti-biologic antibodies. This article summarizes the data behind immunomodulator use in Crohn's disease, focusing on the beneficial role these drugs still have while acknowledging their clinical limitations.

Sarcodia suiae Water Extract Promotes the Expression of Proinflammatory and Th1-Type Cytokines and Delay the Onset of Mortality in Cobia (Rachycentron canadum) During Photobacterium damselae subsp. damselae Infection.

Cobia (Rachycentron canadum) is a marine fish of high economic value that grows at a fast rate. However, intensive fish farming has led to disease outbreaks in cobia cultures, which is highly costly to the industry. The impact of infectious diseases on cobia production has led to the inappropriate and increased use of chemicals and antibiotics, which negatively affects the environment and human health and promotes the spread of drug-resistant pathogens. Hence, prophylactic measurements, such as the use of immunomodulators, are required to improve the health of cultured animals against pathogens. In this study, we examined the effects of Sarcodia suiae water extract (SSWE) in cobia in vitro and in vivo. We found that treatment with SSWE could significantly increase the expression of cytokines (e.g., IL-1β, IL-6, IL-10, IL-12, and TNF-α) and chemokines (e.g., IL-8) in primary cultured head kidney leukocytes. Intraperitoneal injection of SSWE (20 μg/g body weight) promoted higher expression of IL-6, IL-8, IL-10, IL-12, chemokines (e.g., CC1), and antibodies (e.g., IgT) in head kidney and spleen tissues of the fish compared with other dose levels. Additionally, we describe for the second time (only after India) of the isolation of Photobacterium damselae subsp. damselae (Phdd) from a deadly epizootic in cage-farmed cobia. An intraperitoneal inoculation of SSWE before Phdd challenge showed that SSWE treatment could delay the onset of mortality of cobia. Finally, fish that received SSWE intraperitoneally before infection with Phdd exhibited elevated expression of Th1-type cytokines, namely, IL-8, IL-12, TNF-α, and IFN-γ. At the same time, the expression of Th2-related factors (such as IL-10 in the head kidney, and IgM and IgT in the spleen) were lower for the fish that received SSWE instead of PBS before the Phdd challenge. The results indicate that SSWE treatment facilitates the induction of Th1-type cytokines in cobia to fight against Phdd infection and has the potential to be used as an immunostimulant and vaccine adjuvant for fish.

COVID-19 INFECTIONS IN VACCINATED PATIENTS WITH INFLAMMATORY BOWEL DISEASE: OUTCOMES AND RISK FACTORS FOR SEVERE DISEASE

BACKGROUNDThere are limited data on coronavirus disease 2019 (COVID-19) in vaccinated patients with inflammatory bowel disease (IBD). We aimed to describe outcomes and identify risk factors for hospitalization, severe COVID-19, and death in this population.METHODSData from the Surveillance Epidemiology of Coronavirus Under Research Exclusion in Inflammatory Bowel Disease (SECURE-IBD) database were analyzed. Patients with IBD who received at least one vaccine dose prior to diagnosis of COVID-19 were included. Patients received mRNA (Pfizer and Moderna), adenovirus vector (CanSino, AstraZeneca, Sputnik, and Janssen), or inactivated SARS-CoV-2 (Sinovac) vaccines. Partial vaccination was defined as having not received the full complement of doses for the vaccine received. Outcomes were hospitalization, death, and severe COVID-19, a composite of intensive care unit admission, mechanical ventilation, and/or death.RESULTSAmong 141 cases, 12 (8.5%) were hospitalized, 4 (2.8%) had severe COVID-19, and 1 (0.7%) died. During the same period, proportions in the unvaccinated were 9.3%, 1.9%, and 1.2%, respectively. Nearly three-quarters of patients with COVID-19 after vaccination were on biologics and one-third were taking immunomodulators. Fewer hospitalizations occurred in those with completed vaccine series than partially complete series (5.7% vs 13.2%, p = 0.13), and in those receiving mRNA vaccines than adenovirus vector (4.7% vs 22.7%, p = 0.01) or inactivated SARS-CoV-2 (4.7% vs 16.7%, p=0.15) vaccines. Only 2.9% of those with completed mRNA series were hospitalized. Patients on biologic monotherapy were less frequently hospitalized than patients on immunomodulator monotherapy (4.2% vs 27.3%, p=0.03) or combination therapy (4.2% vs 10.0%, p = 0.36). Overall, hospitalized patients were older (mean age 50 years vs 40 years, p = 0.03). Severe COVID-19 was less common in those receiving mRNA vaccines than adenovirus vector (0.9% vs 4.6%; p = 0.31) or inactivated SARS-CoV-2 (0.9% vs 16.7%; p = 0.02) vaccines. Of the four patients with severe COVID-19, two were taking tumor necrosis factor antagonists, three were taking azathioprine, and one had chronic lung disease. The only death was in a patient on triple immunosuppression with adalimumab, azathioprine, and systemic steroids.CONCLUSIONIn patients with IBD, incomplete vaccination, non-mRNA vaccines, and immunomodulator use are associated with increased risk of adverse events during COVID-19 infections.

COMPARISON OF THE INFLAMMATORY BOWEL DISEASES PHENOTYPE AND COURSE IN THE ELDERLY- AND EARLY-ONSET PATIENTS

Abstract BACKGROUND AND AIMS It is unknown if clinical phenotype and course of the disease are comparable between early- and elderly-onset inflammatory bowel diseases (IBD). There is also an ongoing dispute on whether elderly-onset IBD is a separate entity. We aimed to seek differences in disease phenotype, course, complications, and treatment between early- and elderly-onset IBD patients. METHODS This retrospective cohort study on registered IBD patients in the Iranian Registry of Crohn’s and Colitis (IRCC) compared demographics, extent of ulcerative colitis (UC), Crohn’s disease (CD) location and behavior, extraintestinal manifestations, disease activity during the previous six months, and two weeks, IBD-related surgery and medications between early- and elderly-onset IBD. We defined early-onset and elderly-onset IBD as 30 years or less and 60 years and above, respectively. We used univariable analysis to investigate the association between age of diagnosis and outcomes. Variables with P-value &amp;lt;0.1 were entered into the generalized linear model to study the relative risk of age of diagnosis adjusted for gender and disease duration for the outcomes. RESULTS From 8911 IBD patients that were recruited in the IRCC from December 2017 till June 2021, 4503 were enrolled, including 4134 (46.4%) early-onset and 369 (4.1%) elderly-onset cases. Among them, 3596 (79.8%) had UC, and 907 (20.2%) had CD. Figure 1 shows relative risk of outcomes in patients with UC based on patients’ age of diagnosis adjusted for disease duration and gender. The risk of left colitis was 1.7 times higher among elderly-onset UC patients (95%CI:1.4-2.1, P&amp;lt;0.001). Early-onset IBD cases had a higher prevalence of extraintestinal manifestations (p&amp;lt;0.001). Early-onset UC cases more often used prednisolone (p=0.031), immunomodulators (p&amp;lt;0.001) and anti-tumor necrosis factors (TNF) (p=0.002). Elderly-onset UC patients had 0.7 times lower risk of active disease in the past six months in comparison with elderly-onset cases (95%CI:0.5-0.9, p=0.003). Elderly-onset CD patients had 1.7 times the risk of ilium involvement (95%CI: 1.1-2.5, p=0.010), and elderly-onset CD cases had 0.2 times the risk of stricture formation compared to early cases (95%CI:0.1-0.8, p=0.028). Early-onset CD was associated with higher use of prednisolone (p=0.024), immunomodulators (p&amp;lt;0.001) and anti-TNF (p=0.024). Disease activity during the previous six months , two weeks and IBD-related surgery were similar between the two groups. Figure 2 demonstrates relative risk of outcomes in patients with CD based on patients’ age of diagnosis adjusted for disease duration and gender. CONCLUSION Early-onset IBD was associated with a more aggressive phenotype and higher prednisolone, immunomodulators, and anti-TNF use. There is a need for a more detailed investigation of treatment complications and surgery types in future studies.

P290 Therapeutic requirements in patients with Ulcerative Proctitis. Is it necessary immunosuppressive therapy in these patients?

Abstract Background Ulcerative proctitis may have a mild and less aggressive course, although evidence is scarce because these patients are excluded from participation in randomized controlled clinical trials. The aim is to identify clinical characteristics and complications associated with ulcerative proctitis refractory to conventional therapy. Methods Patients included in the prospectively maintained ENEIDA registry from GETECCU with ulcerative proctitis were included. Socio-demographic data were evaluated. We defined ulcerative proctitis based on ECCO guidelines and immunosuppression as the use of immunomodulators and/or biologics. Logistic regression was used to identify the independent factors associated with immunosuppressive therapy among the different socio-demographic data. Results From a total of 34.716 patients with ulcerative colitis, 6281 (18%) patients with ulcerative proctitis were identified. Mean age was 53 ±15 years and mean duration of illness was 12 ± 9 years. Surgery was necessary only in 2% of patients, 31 (0.5%) panprotocolectomy or subtotal colectomy. The clinical characteristics of the patients with and without immunosupressive therapy are summarized at table 1. A total of 3691 patients received oral 5-ASA (58.8%) and 4652 (74.1%) topic 5ASA. 636 (10.1%) were refractory to 5-ASA and corticosteroids, necessitating immunosuppression: 459 patients with azathioprine (7%), 28 with 6-mercaptopurine (0.4%), 49 with methothrexate (0.8%), 191 with infliximab (9%), 125 with adalimumab (2%), 50 with golimumab (0.8%), 57 with vedolizumab (0.9%), 6 with ustekinumab (0.1%) and 3 with tofacitinib (0.0). 316 (5%) patients needed one biologic therapy, 95 (1.5%) needed 2 biologics and 40 (0.6%) at least three different biologics. Longer duration of illness and use of corticosteroids were associated with higher risk of immunosuppression. Conclusion Good clinical outcomes were recorded in ulcerative proctitis, with only 10% of patients treated with immunosuppression therapy. The risk factors of immunosuppression were longer duration of illness and use of corticosteroids.

P252 Low adherence is associated with worse disease course in Ulcerative Colitis: a retrospective study from a single referral center

Abstract Background New therapeutic approaches for ulcerative colitis (UC) are becoming available but still there is no robust evidence for predictors of poor outcome. We aimed to evaluate factors associated with a more aggressive UC course. Methods Data of all UC outpatients followed for at least 3 years after diagnosis were retrospectively collected. Demographic, anamnestic data, disease characteristics and treatment were collected. Disease patterns were defined according to the IBSEN study (Henriksen M. et al1). Disease worsening at 3 years was defined as the presence of disease extension at endoscopy, proctocolectomy and or early use of biologics. Risk factors for chronically active disease were assessed. Moreover, the following outcomes were explored according to disease extent at diagnosis (E1-E2 vs E3): corticosteroid free remission, hospitalization, early use of immunomodulators and biologics, colorectal cancer, adherence, mucosal healing at 3 years. Survival analysis was carried out to estimate the probability of receive a biological treatment within 3 and 5 years from diagnosis according to disease extent (E1 vs E2 vs E3) and disease patterns. Results A total of 345 UC patients were included and followed for a mean period of 94 months. Patients with extensive colitis had a higher rate of colectomy (p &amp;lt; 0.001), hospitalizations (p=0.004) and of chronically active disease 3 years after diagnosis (p &amp;lt; 0.001) and were more likely to receive early biologics and IMM (p= 0.04 and p=0.01 respectively) (Figure 1). The only factor associated with chronic active disease was non-adherence (p &amp;lt; 0.03; OR 0.49, 95% CI: 0.26–0.95) (Table 1). No differences were found for the probability to receive biologics within 3 and 5 years from diagnosis according to Montreal extension at diagnosis and disease pattern. Conclusion Patients diagnosed with pancolitis were more likely to underwent colectomy or to have a chronically active disease with a higher rate of hospitalization, early use of IMM or biologics. The only predictor for chronically active UC was the lack of adherence to therapy within the first 3 years after diagnosis. Reference 1. Henriksen M, et al; IBSEN Study Group. Ulcerative colitis and clinical course: results of a 5-year population-based follow-up study (the IBSEN study). Inflamm Bowel Dis. 2006;12:543–50. The study was supported by a grant from Ferring S.p.A.

Clinical factors to predict flare-up in patients with inflammatory bowel disease during international air travel: A prospective study.

Backgrounds and aimsInflammatory bowel disease (IBD) patients often experience disease flare-ups during international air travel. We aimed to identify risk factors associated with IBD flare-up during international air travel.MethodsPatients with scheduled international air travel were enrolled in the study from the Seoul National University Bundang Hospital IBD clinic. Flight information and clinical data were collected via questionnaires and personal interviews, and risk factors associated with IBD flares were determined.ResultsBetween May 2018 and February 2020, 94 patients were prospectively enrolled in the study (mean age, 33.0 years; males, 53.2%; mean disease duration, 56.7 months), including 56 (59.6%) with ulcerative colitis and 38 (40.4%) with Crohn’s disease. Of the 94 patients enrolled, 15 (16.0%) experienced an IBD flare-up and 79 (84.0%) remained in remission throughout travel. Logistic regression analysis revealed that high fecal calprotectin levels before travel (odds ratio [OR]: 1.001, 95% confidence interval [CI]: 1.000–1.001, p = 0.016), the presence of a comorbidity (OR: 6.334, 95% CI: 1.129–35.526, p = 0.036), and history of emergency room visit (OR: 5.283, 95% CI: 1.085–25.724, p = 0.039) were positively associated with disease flare-up. The previous and current use of immunomodulators and biologics, time of flight, altitude, number countries visited, travel duration, objective of visit, and previous medical consultations were not associated with disease flare-up.ConclusionsElevated fecal calprotectin levels, history of emergency room visits, and the presence of a comorbidity predicted IBD flare-up during international air travel.

P405 Primary non-response and loss-of-response to first-line biological therapies are more common in patients with Ulcerative Colitis than Crohn’s Disease – preliminary results from the Danish IBD Biobank Project

Abstract Background The use and cost of biological treatment in patients with inflammatory bowel diseases (IBD) continue to rise. Meanwhile, rates of primary non-response (PNR) and loss of response (LOR) are high. We aimed to investigate predictors of PNR and LOR in a real-world cohort of bio-naïve IBD patients. Methods This study included, 488 adult patients with IBD (52% UC, 47% CD, 1% IBDU) who initiated and completed induction therapy with a biological drug from May, 2019 – Oct, 2021 at five university hospitals covering, 2.1 M inhabitants. Clinical response to induction therapy was defined as a decrease at week, 14 in the Simple Clinical Colitis Activity Index (SCCAI)&amp;gt;1 in UC and a decrease in Harvey Bradshaw Index (HBI)&amp;gt;3 in CD patients. Clinical remission was defined as SCCAI&amp;lt;3 in UC and HBI&amp;lt;5 in CD. PNR was defined as lack of response or IBD surgery during the induction period. LOR was defined as need for systemic steroids, drug switch or IBD surgery during maintenance therapy. Multivariable logistic regression and COX-regression analyses were performed to assess predictors of outcomes. Results Biological treatment was initiated after a median of two years (IQR, 0–9.Table, 1). Most patients were treated with infliximab(97%) followed by adalimumab(2%) and vedolizumab (1%). Luminal activity was the most common indication(67%) followed by acute severe UC(17%) and need for post-operative prophylaxis(7%). Treatment was discontinued in, 27(6%) patients due to other reasons than PNR during induction therapy. PNR occurred in, 95(30%) of, 314 patients with available scores and was higher in UC patients (OR, 2.19,95%CI, 1.19–4.05,p=0.01.Table, 2), but lower in those who were former smokers (OR, 0.51,95%CI, 0.27–0.95,p=0.03). Clinical remission was achieved in, 234(52%) patients and lower in those with UC (OR, 0.48,95%CI, 0.32–0.74,p&amp;lt;0.01) or previous major surgery (OR, 0.48,95%CI, 0.25–0.92,p=0.03). LOR occurred in, 82(21%) of, 395 patients who received maintenance therapy. LOR rate was higher in patients with UC (HR, 2.00,95%CI, 1.20–3.33,p&amp;lt;0.01) and previous major surgery (HR, 2.85,95%CI, 1.47–5.52,p&amp;lt;0.01.Table, 3). UC was associated with a higher risk of drug discontinuation (HR, 1.85,95%CI, 1.20–2.85,p&amp;lt;0.01) and switch (HR, 2.01,95%CI, 1.17–3.46,p=0.01) whereas concomitant use of immunomodulator (IM) lowered the risk of both (HR, 0.47,95%CI, 0.27–0.81,p&amp;lt;0.01 and HR, 0.46,95%CI, 0.24–0.89,p=0.02.Table 4). Conclusion PNR occurred in one of four patients and LOR in one-fifth. Both PNR and LOR rates were higher in patients with UC. During maintenance therapy, UC patients had a higher risk of drug discontinuation and switch whereas concomitant use of IM decreased the risk of both. Funding: unrestricted grant from Takeda A/S, Louis-Hansen Fonden and public fund hosted by Hvidovre Hospital.

P257 The clinical decision support tool has low performance in predicting outcome to ustekinumab in Crohn’s disease

Abstract Background Several biologicals and small molecules have been added to the therapeutic arsenal of inflammatory bowel disease, which generated a wide interest in precision medicine. In this context, both clinical features and laboratory tests have shown some correlation with therapy outcome. Recently, an online clinical decision support tool1 (CDST) was built, using clinical and biochemical variables (e.g. disease location, prior anti-TNF exposure), to help physicians predict the outcome of various biological treatments in Crohn’s disease (CD). We sought to evaluate the predictive performance of this tool in patients with CD initiating ustekinumab (UST). Methods Baseline data were collected from consecutive CD patients who started UST IV induction followed by eight weekly UST 90 mg SC maintenance from December 2015 through March 2021 at our referral center. The probability of achieving clinical remission (low, intermediate, or high) was determined using the online CDST using patients’ data. Also, differences in rates of primary non-response and ustekinumab persistence were compared between CDST classifications. Primary non-response was defined as failing to attain endoscopic response (≥50% decrease in SES-CD) nor clinical response (a drop in the physician global assessment score or patients reported outcome), both assessed at month 6 after UST initiation. Finally, we studied the relation between the individual components used to construct the CDST and the three classifications in a univariate analysis. Results A total of 291 CD patients started UST, of whom 237 had objectively-assessed (CRP, fCal, symptoms or endoscopy) baseline disease activity. Using the CDST, the proportion of patients with “low”, “intermediate” or “high” probability to attain clinical remission were 11.8 % (n=28), 55.7 % (n=132) and 32.5 % (n=77), respectively. The CDST could not discriminate patients with primary non-response (p value = 0.18; Figure 1), nor identify trends in drug persistence (p value = 0.44; Figure 2). In the univariate analysis, 3 out of 9 components (active fistulizing disease, disease location and concomitant immunomodulatory use) were not significantly contributing to the CDST classification (Table 1). Conclusion The recently developed clinical decision support tool showed low performance in predicting short-term (primary clinical and endoscopic response) and long-term (drug persistence) real-life outcomes in CD patients starting UST. These findings underscore the necessity of incorporating molecular variables, in addition to clinical ones, to construct reliable and reproducible tools to predict therapeutic outcomes. 1. https://via.juxlyapps.com/pathway/archemedx/ibd-cdst/index.html#/disease-selection