Effectiveness of vedolizumab and ustekinumab as second biologic agent in achieving target outcomes in tumor necrosis factor antagonists experienced patients with inflammatory bowel disease (enroll-ex study)

Background: About a third of patients with inflammatory bowel disease (IBD) do not respond to anti-tumor necrosis factor (anti-TNF) therapy. In our study, we evaluated the effectiveness of vedolizumab and ustekinumab in achieving clinical and endoscopic outcomes in anti-TNF-experienced patients with IBD.Methods: We conducted a retrospective cohort study. Electronic medical records of patients with moderate to severe IBD, who were previously received anti-TNF therapies, were reviewed and evaluated retrospectively in a gastroenterology center. Outcomes of patients treated with ustekinumab or vedolizumab after failing one anti-TNF agent were evaluated. The primary outcomes were the percentage of hospitalization, surgery, mucosal healing and steroid-free remission. Mucosal healing was defined as a Mayo endoscopic score of 0 or 1 in ulcerative colitis (UC) and an SES-CD score of less than 3 in Crohn’s disease (CD). Outcomes were quantified using descriptive analysis.Results: A total of 207 (130 CD: 77 UC) patients with IBD who had previously received one anti-TNF agent were included in the study. Of the total cohort, 62 (30.0%) patients were receiving vedolizumab, and 145 (70.0%) patients were on ustekinumab. 101 (77.6%) patients with CD who failed one anti-TNF therapy were on ustekinumab. Of these patients, 26 (19.7%) patients were hospitalized, and 12 (11.9%) patients had IBD-related surgery. 16 (16.1%) patients had at least one corticosteroid course. 60 (59.0%) patients with CD on ustekinumab achieved mucosal healing. 29 (22.3%) patients with CD who failed one anti-TNF therapy were receiving vedolizumab. Of those, 7 (25%) patients were hospitalized, and 11 (37.9%) patients had IBD-related surgery. 15 (51.0%) patients achieved mucosal healing. 44 (57.1%) patients with UC who failed one anti-TNF therapy were on ustekinumab. Of these 6 (14.1%) patients were hospitalized, 3 (7.0%) patients had IBD-related surgery and 13 (30%) patients had at least 1 corticosteroid course. 25 (57.0%) patients achieved mucosal healing. 33 (42.8%) patients with UC who failed one anti-TNF therapy were receiving vedolizumab. Of those, 6 (18.6%) patients were hospitalized, and 16 (49.6%) patients had at least 1 corticosteroid course. 17 (53.2%) patients achieved mucosal healing.Conclusion: Ustekinumab and vedolizumab were both effective in achieving clinical outcomes in patients with IBD after failing an anti-TNF agent. However, patients receiving ustekinumab had numerically higher percentages of reaching target outcomes than patients receiving vedolizumab. A prospective head-to-head trial is warranted to confirm these findings

200-LB: Ceramide Kinase CERK Regulates Inflammatory Responses in Monocytes/Macrophages Induced by TNF-a

Obesity is associated with elevated levels of TNF-α and proinflammatory CD11c monocytes/macrophages. TNF-α mediated dysregulation in the plasticity of monocytes/macrophages is concomitant with pathogenesis of several inflammatory diseases, including metabolic syndrome, but the underlying mechanisms are incompletely understood. Since Ceramide kinase (CERK; a critical mediator of eicosanoid synthesis, and its product, ceramide-1-phosphate (C1P)) is a key enzyme for ceramide production involved in inflammation, we investigated whether the CERK contributed to the inflammatory changes in the monocytes/macrophages induced by TNF-α. In this study, we demonstrate that the disruption of CERK activity in monocytes/macrophages either by chemical inhibitor NVP- 231 or small interfering RNA (siRNA)against CERK gene results in defects in the TNF-α mediated expression of CD11c and CD11b and HLA-Dr. Furthermore, blockage of CERK in monocytes/macrophages inhibited the secretion of IL-1b and MCP-1. Phosphorylation of JNK, p38 and NF-κB resulting from TNF-α stimulation was also attenuated by the inhibition of CERK. Moreover, NF-kB/AP-1 activity was blocked by the inhibition of CERK. Our human data show that CERK was elevated in PBMCs from obese individuals and positively corelated with TNF-α. These findings indicate that CERK acts, in a part, as a master switch in the TNF-α mediated inflammatory responses in monocytes/macrophages. Disclosure F. Alrashed: None. R. Ahmad: None. Funding Kuwait Foundation for the Advancement of Sciences (RA-AM 2016007) </jats:sec

Age as a Predictor of Serum Tumor Necrosis Factor Antagonist Drug and Antidrug Antibody Concentrations in Inflammatory Bowel Disease&mdash;A Nationwide Cohort Study

Background/Objectives: Tumor necrosis factor antagonists (anti-TNFs) have been shown to be an effective treatment for inflammatory bowel disease (IBD). Several factors are associated with anti-TNF treatment failure. This study aims to explore the impact of age on serum concentrations of anti-TNF drugs and antidrug antibodies (ADAbs). Methods: We retrospectively reviewed patients&rsquo; charts from July 2018 until September 2024 across seven medical centers. Patients with an established diagnosis of IBD receiving infliximab or adalimumab were included. The primary outcome of this study was the effect of age on the anti-TNFs serum drug concentration and ADAb levels. Linear regression was performed to explore the relationship between age and serum anti-TNF drug and ADAb levels. Results: 1093 patients were included in our cohort. In patients receiving infliximab, there was a significant association between older age and increasing ADAbs levels (p = 0.036), whereas in patients treated with adalimumab, there was no significant relationship between older age and ADAb levels (p = 0.771). There was no significant relationship between age and adalimumab serum concentration (p = 0.54). When stratified by age, patients taking infliximab who were &gt;30 years of age developed more ADAbs compared to those aged &le;30 (p = 0.003). Conclusions: Patients older than 30 years of age receiving infliximab monotherapy have higher ADAbs and lower serum drug concentrations than younger patients. There was no statistically significant difference in ADAbs and serum drug concentrations among patients receiving infliximab combination therapy or adalimumab monotherapy

COVID-19 Vaccine Booster Dose Willingness Among Patients with Inflammatory Bowel Disease on Infliximab and Vedolizumab: A Cross-Sectional Study

AbstractBackgroundVaccination has been effective in preventing COVID-19 infections and related mortality. However, waning immunity after the two-dose vaccination prompted health authorities to recommend a third dose of COVID-19 vaccine to boost immunity. The aim of our study was to assess willingness to receive a third (booster) dose among patients with IBD.MethodsA cross-sectional study was performed at a tertiary care inflammatory bowel disease center. Patients were recruited at the infusion room from January 1st, 2022, until March 31st, 2022. The primary outcome was the prevalence of BNT162b2 third (booster) dose in infliximab- or vedolizumab-treated patients with IBD. The secondary outcome evaluated whether the prevalence of BNT162b2 third (booster) dose differed based on type of COVID-19 vaccine, gender, age, type of biologic therapy and citizenship.ResultsIn total, 499 patients with IBD were included in this study. The median age was 34.5 years, and 60% had ulcerative colitis (UC). Among the study participants, 302 (60.5%) patients were vaccinated with BNT162b2, and 197 (39.5%) were vaccinated with ChAdOx1 nCoV-19. Of the total number of participants, 400 (80.2%) were receiving infliximab, and 99 (19.8%) were receiving vedolizumab. Overall, 290 (58.1%) of the included patients were willing to receive the third (booster) dose. Patients vaccinated with BNT162b2 were more likely to receive booster dose compared to patients vaccinated with ChAdOx1 nCoV-19 [201 (66.5%) vs 101 (33.5%), p = 0.014]. Infliximab-treated patients were more likely to receive booster dose compared to patients receiving vedolizumab [310 (77.5%) vs 62 (62.6%), p = 0.002]. There was no statistical difference in willingness to receive booster dose in terms of age, nationality, or gender.ConclusionThe percentage of patients with IBD willing or have received a third (booster) dose of BNT162b2 vaccine was lower compared to general population. In addition, patients who received two doses of BNT162b2 vaccines were more likely to receive a third (booster) dose compared to patients who received ChAdOx1 nCoV-19. Patients treated with infliximab were more likely to receive a third (booster) dose of COVID-19 vaccine.</jats:sec

Impact of biologics and small molecules for Inflammatory Bowel Disease on COVID-19 Related Hospitalization: A Systematic Review and Meta-analysis

AbstractBackgroundThe use of biological therapies and small molecules have been a concern for patients with inflammatory bowel disease (IBD) during COVID-19 pandemic. We aim to assess the association between risk of COVID-19 related hospitalization and these agents.MethodA systematic review and meta-analysis of all published studies from December 2019 to September 2021 was performed to identify studies that reported COVID-19 related hospitalization in IBD patients receiving biological therapies or tofacitinib. The risk ratio (RR) was calculated to compare the relative risk of COVID-19 related hospitalization in patients receiving these medications to those who were not, at the time of the study.Results18 studies were included. The relative risk of hospitalization was significantly lower in patients with IBD and COVID-19 who were receiving biologic therapy with RR of 0.47 (95% CI: 0.42-0.52, p &lt; 0.00001). The RR was lower in patients receiving anti-TNFs compared to those who did not [RR= 0.48 (95% CI: 0.41-0.55, p &lt; 0.00001)]. Similar finding was observed in patients taking ustekinumab [RR= 0.55 (95% CI: 0.43-0.72, p &lt; 0.00001)]. Combination therapy of anti-TNF and an immunomodulator did not lower the risk of COVID-19 related hospitalization [RR= 0.98 (95% CI: 0.82-1.18, p =0.84]. The use of vedolizumab [RR= 1.13 (95% CI: 0.75-1.73, p =0.56] and tofacitinib [RR= 0.81 (95% CI: 0.49-1.33, p =0.40] was not associated with lower risk of COVID-19 related hospitalization.ConclusionRegarding COVID-19 related hospitalization in IBD, anti-TNFs and ustekinumab were associated with favorable outcomes. In addition, vedolizumab and tofacitinib were not associated with COVID-19 related hospitalization.</jats:sec

The Role of Clinical Pharmacists in Improving Quality of Care in Patients with Inflammatory Bowel Disease: An Evaluation of Patients’ and Physicians’ Satisfaction

Background: Inflammatory bowel disease (IBD) is a chronic and complex disease that requires a multidisciplinary team, including clinical pharmacists, to improve the quality of care and patient outcome. This present study aimed to assess the satisfaction of patients with IBD and physicians regarding clinical pharmacist interventions in outpatient and inpatient settings. Methods: A survey-based study was performed between 1 March and 1 August 2022 in a tertiary care IBD center. Two different questionnaires were distributed among patients and physicians focusing on satisfaction with the clinical pharmacist services. Patient demographics were obtained. Descriptive statistics were used to summarize the results of the survey. Results: A total of 108 patients with IBD and 23 physicians participated in this study. Among study participants, Crohn’s disease (CD) accounted for 64.8% of the total participants, while 35.2% of patients had ulcerative colitis (UC). Regarding the patient survey, most patients were extremely satisfied with clinical pharmacists’ services, during which the majority strongly agreed or agreed that they were satisfied with the counseling session. However, five patients were unsure about the amount of time spent with the clinical pharmacist. There were no patients dissatisfied with any of the services. Finally, two physicians were not sure regarding clinical pharmacists monitoring patients’ responses in of terms of toxicity and adverse effects. Conclusions: the current study illustrates patients’ and physicians’ high satisfaction with clinical pharmacists’ services in outpatient and inpatient settings. The findings of this study as well as previous studies necessitate expanding the clinical pharmacist services in the gastroenterology field

COVID-19 Vaccine Booster Dose Willingness among Patients with Inflammatory Bowel Disease on Infliximab and Vedolizumab: A Cross-Sectional Study

Background: Vaccination has been effective in preventing COVID-19 infections and related mortality. However, waning immunity after two-dose vaccination prompted health authorities to recommend a third dose of COVID-19 vaccine to boost immunity. The aim of our study was to assess willingness to receive a third (booster) dose among patients with inflammatory bowel disease (IBD). Methods: A cross-sectional study was performed at an IBD tertiary care center. Patients were recruited at the infusion room from 1 January 2022 to 31 March 2022. The primary outcome was the prevalence of a third (booster) dose of the BNT162b2 vaccine in infliximab- or vedolizumab-treated patients with IBD. The secondary outcome evaluated whether the prevalence of a third (booster) dose of the BNT162b2 vaccine differed based on type of COVID-19 vaccine, gender, age, type of biologic therapy, and citizenship. Results: In total, 499 patients with IBD were included in this study. The median age was 34.5 years, and 60% had ulcerative colitis (UC). Among the study participants, 302 (60.5%) patients were vaccinated with BNT162b2, and 197 (39.5%) were vaccinated with ChAdOx1 nCoV-19. Of the total number of participants, 400 (80.2%) were receiving infliximab, and 99 (19.8%) were receiving vedolizumab. Overall, 290 (58.1%) of the included patients were willing to receive the third (booster) dose. Patients vaccinated with BNT162b2 were more likely to be willing to receive a booster dose compared to patients vaccinated with ChAdOx1 nCoV-19 (201 (66.5%) vs. 103 (52.0%), p = 0.014). Infliximab-treated patients were more likely to be willing to receive a booster dose compared to patients receiving vedolizumab (310 (77.5%) vs. 62 (62.6%), p = 0.002). There was no statistical difference in willingness to receive a booster dose in terms of age, nationality, or gender. Conclusions: The percentage of patients with IBD willing to receive or having already received a third (booster) dose of BNT162b2 vaccine was lower compared to the general population. In addition, patients who received two doses of BNT162b2 vaccines were more likely to be willing to receive a third (booster) dose compared to patients who received ChAdOx1 nCoV-19. Patients treated with infliximab were more likely to be willing to receive a third (booster) dose of COVID-19 vaccine

Biologic Therapies for the Treatment of Post Ileal Pouch Anal Anastomosis Surgery Chronic Inflammatory Disorders: Systematic Review and Meta-analysis

AbstractBackgroundChronic inflammatory disorders after ileal pouch-anal anastomosis (IPAA) surgery are common. These include chronic pouchitis, Crohn’s disease of the pouch, prepouch ileitis, and rectal cuff inflammation. The aim of this study was to evaluate the efficacy of biologic therapies in treating these disorders.MethodSystematic review of all published studies from inception to April 1st, 2021 was performed to investigate the efficacy of biologic therapies for post IPAA chronic inflammatory disorders. The primary outcome was the efficacy of biologic therapies in achieving complete response or remission. A subgroup analysis was performed for each disorder separately.ResultsA total of 24 studies were identified including 682 patients. Using a random effect model, the overall pooled efficacy of biologic therapies in achieving complete response or remission in patients with post IPAA surgery chronic inflammatory disorders was 60% (95% Confidence Interval (CI), 56 - 64). Specifically, the pooled efficacy of ustekinumab was 75% (95% CI, 64 - 85, p = 0.007), whereas the efficacy of vedolizumab was 60% (95% CI, 52 - 68, p = 0.172). In addition, the efficacy infliximab and adalimumab were 59% (95% CI, 53 - 64, p &lt;0.01) and 51% (95% CI, 42 - 60, p = 0.452) respectively.ConclusionUstekinumab, infliximab, vedolizumab and adalimumab are effective in achieving complete response or remission in post IPAA surgery chronic inflammatory disorders. There is also a clear trend toward higher efficacy in patients with Crohn’s disease of the pouch compared to chronic pouchitis. More studies are needed to determine the efficacy of biologics in cuffitis.SummaryChronic inflammatory disorders after ileal pouch-anal anastomosis surgery are common. These include chronic pouchitis, Crohn’s disease of the pouch, prepouch ileitis, and rectal cuff inflammation. This study aimed to evaluate the efficacy of biologic therapies in achieving complete response or remission in these disorders.</jats:sec