scholarly journals P527 A review of adverse events associated with immunosuppressive treatments in inflammatory bowel disease patients

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S453-S454
Author(s):  
D Tassone ◽  
N Ding
Keyword(s):  
Inflammatory Bowel Disease ◽  
Combination Therapy ◽  
Adverse Events ◽  
Bowel Disease ◽  
Immunosuppressive Agents ◽  
Current Evidence ◽  
Malignancy Risk ◽  
Serious Infection ◽  
Increased Risk ◽  
Inflammatory Bowel

Abstract Background Medical therapies that suppress various pathways involved in inflammation comprise the mainstay of inflammatory bowel disease (IBD) treatment. Adverse events, including the development of serious infection and malignancy, have been associated with these therapies. This study evaluates the current evidence regarding serious adverse events associated with immunosuppressive agents in the IBD patient population. Methods A systematic search was conducted in September 2019 by combining three key research themes: inflammatory bowel disease, immunosuppression, and adverse events. For this systematic review, adverse events are defined as either the development or recurrence of malignancy or the development of serious infection necessitating hospital admission. Results There is a demonstrated association between thiopurine use and increased risk of both nonmelanoma skin cancer (NMSC) or lymphoma. The length of thiopurine exposure required to increase NMSC risk is, however, unclear. Of the papers reporting on exposure length and NMSC risk, the thiopurine exposure duration required to result in a statistically significant increase in NMSC risk varied from 6 months to 5 years. Among the studies retrieved, there is a lack of consensus on malignancy risk associated with the use of anti-TNF agents. From 5 studies on malignancy risk associated with the use of anti-TNF agents, one concluded that malignancy risk is increased while three concluded that risk is unchanged from baseline. The fifth study is inconclusive on any possible association. Confounding by past or concurrent thiopurine exposure remains an issue. There is a clear association between combination therapy with both thiopurines and anti-TNF agents and increased malignancy risk when compared with exposure to either thiopurine or anti-TNF therapy alone. Anti-integrin agents were not found to be associated with an increase in adverse effects when compared with placebo, while nil studies on ustekinumab were retrieved. Individual studies on infection risk do not consistently stratify infections according to severity, limiting any analysis. Conclusion An established association between thiopurine use and increased risk of both lymphoma or NMSC exists. However, the duration of thiopurine exposure necessary to increase NMSC risk is uncertain. There is a lack of consensus on whether anti-TNF agents increase malignancy risk due to confounding from past or concurrent thiopurine exposure. Combination therapy increases malignancy risk when compared with exposure to either thiopurine or anti-TNF therapy alone. Limited studies on the newer biologic therapies were retrieved. Finally, evidence which stratifies infections according to severity is lacking.

scholarly journals Immunogenicity of the Currently Recommended Pneumococcal Vaccination Schedule in Patients With Inflammatory Bowel Disease

2019 ◽  
Author(s):  
Mariëlle van Aalst ◽  
Hannah M Garcia Garrido ◽  
Josephine van der Leun ◽  
Bob Meek ◽  
Ester M M van Leeuwen ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Immune Response ◽  
Combination Therapy ◽  
Bowel Disease ◽  
Immunosuppressive Agents ◽  
Pneumococcal Vaccination ◽  
Vaccination Schedule ◽  
Control Group ◽  
Increased Risk ◽  
Inflammatory Bowel

Abstract Background Patients with inflammatory bowel disease (IBD) are at increased risk of invasive pneumococcal infections. Therefore, vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) 2 months later is recommended. However, the level of immunogenicity induced by this vaccination schedule in IBD patients with and without immunosuppressive medication remains unclear. Methods We prospectively assessed the immunogenicity of PCV13 followed by PPSV23 in IBD patients by measuring serotype-specific pneumococcal immunoglobulin G antibody concentrations at baseline and 4–8 weeks postvaccination. Response to vaccination was defined as a postvaccination antibody concentration ≥1.3 μg/mL for 70% of the measured serotypes. We analyzed the immunogenic effect of 4 different medication regimens: (1) conventional immunomodulators (ie, oral prednisolone >10 mg/day, thiopurines, methotrexate); (2) anti–tumor necrosis factor agents; (3) combination therapy; and (4) no treatment with immunosuppressive agents (control group). Results One hundred forty-one IBD patients were included, of whom 37 were controls. Adequate response to vaccination was 59% (61/104) in patients using immunosuppressive agents (groups 1–3) vs 81% (30/37) in controls (odds ratio, 0.33 [95% confidence interval, .13–.82]). A combination of different immunosuppressive drugs most severely impaired the immune response to pneumococcal vaccination (response, 52% [15/29]). Conclusions Although the sequential vaccination schedule of PCV13 followed by PPSV23 is safe, immunogenic, and thus beneficial in the majority of IBD patients, those receiving immunosuppressive agents, and especially those receiving combination therapy, have an impaired immune response compared to controls. Therefore, preferably, vaccinations should be administered before the initiation of immunosuppressive therapy.

scholarly journals Effectiveness and Safety of the Sequential Use of a Second and Third Anti-TNF Agent in Patients With Inflammatory Bowel Disease: Results From the Eneida Registry

2019 ◽  
Author(s):  
María José Casanova ◽  
María Chaparro ◽  
Miguel Mínguez ◽  
Elena Ricart ◽  
Carlos Taxonera ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Combination Therapy ◽  
Adverse Events ◽  
Bowel Disease ◽  
Tumor Necrosis ◽  
Significant Proportion ◽  
Short Term ◽  
Loss Of Response ◽  
Inflammatory Bowel ◽  
Necrosis Factor

Abstract Background The effectiveness of the switch to another anti–tumor necrosis factor (anti-TNF) agent is not known. The aim of this study was to analyze the effectiveness and safety of treatment with a second and third anti-TNF drug after intolerance to or failure of a previous anti-TNF agent in inflammatory bowel disease (IBD) patients. Methods We included patients diagnosed with IBD from the ENEIDA registry who received another anti-TNF after intolerance to or failure of a prior anti-TNF agent. Results A total of 1122 patients were included. In the short term, remission was achieved in 55% of the patients with the second anti-TNF. The incidence of loss of response was 19% per patient-year with the second anti-TNF. Combination therapy (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.8–3; P < 0.0001) and ulcerative colitis vs Crohn’s disease (HR, 1.6; 95% CI, 1.1–2.1; P = 0.005) were associated with a higher probability of loss of response. Fifteen percent of the patients had adverse events, and 10% had to discontinue the second anti-TNF. Of the 71 patients who received a third anti-TNF, 55% achieved remission. The incidence of loss of response was 22% per patient-year with a third anti-TNF. Adverse events occurred in 7 patients (11%), but only 1 stopped the drug. Conclusions Approximately half of the patients who received a second anti-TNF achieved remission; nevertheless, a significant proportion of them subsequently lost response. Combination therapy and type of IBD were associated with loss of response. Remission was achieved in almost 50% of patients who received a third anti-TNF; nevertheless, a significant proportion of them subsequently lost response.

scholarly journals Immunisation status of children and adolescents with a new diagnosis of inflammatory bowel disease

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Timothy Ford ◽  
Margie Danchin ◽  
Alissa McMinn ◽  
Kirsten Perrett ◽  
George Alex ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Risk Groups ◽  
Current Evidence ◽  
Varicella Zoster ◽  
National Immunisation ◽  
Paediatric Patients ◽  
Increased Risk ◽  
Inflammatory Bowel ◽  
Special Risk

Abstract Background Patients with Inflammatory Bowel Disease (IBD) are at increased risk of serious infections, including vaccine preventable diseases. Current evidence suggests uptake of additional recommended special risk vaccinations is low. Identification of IBD patients prior to commencing immunosuppressive therapy allows for optimisation of vaccination, including timely administration of live-attenuated and additional recommended vaccines, such as influenza and pneumococcal vaccines. Methods Paediatric patients (0–18 years) seen at the tertiary Royal Children’s Hospital, Melbourne, Australia, with a recent diagnosis of IBD were referred by the Gastroenterology Unit to our Specialist Immunisation Clinic (SIC) for assessment and provision of routine and special risk vaccines. Data was collected via a standardised REDCap questionnaire completed in or post attendance at the SIC and included serology results where available. Results Sixty-nine paediatric patients were recruited to the study between 2014 and 2017. Median age at IBD diagnosis was 11.25 years (IQR 4.64 years), with median time between diagnosis and SIC review of 0.88 years (IQR 2.84 years). At initial review 84.1% (58/69) of patients were up to date with vaccines on the Australian National Immunisation Program (NIP) schedule. Of those who were tested, serological evidence of immunity was demonstrated in 38.3% (23/60) of patients for Hepatitis B, 66.7% (36/54) for measles, 51.9% (28/54) for rubella and 41.9% (26/62) for Varicella Zoster Virus. Prior to SIC review 47.8% (33/69) had additional vaccinations and 92.8% (64/69) had vaccinations administered in the 12 months following SIC assessment. The Pneumococcal conjugate vaccine (76.8%, 53/69) was the most commonly administered vaccine after SIC review, followed by influenza vaccine (69.6%, 48/69). Within 12 months of SIC review 43.5% (30/69) of patients had completed the schedule and were up-to-date as recommended by the SIC. Conclusions Children with IBD and other special risk groups can benefit from early referral to a SIC team to ensure optimal administration of routine and additionally recommended vaccines, especially live and additional special risk vaccines. The value of optimising immunisations could also be applied to other special risk groups, including adult IBD cohorts, particularly those commencing newer biologic immunosuppressive medications.

When to Start Immunomodulators in Inflammatory Bowel Disease?

2016 ◽  
Vol 34 (1-2) ◽  
pp. 125-131 ◽  
Author(s):  
Ala I. Sharara
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Opportunistic Infections ◽  
Current Evidence ◽  
Treat To Target ◽  
Steroid Dependent ◽  
Increased Risk ◽  
Inflammatory Bowel ◽  
Maintenance Of Remission ◽  
Steroid Sparing

Background: Immunomodulators (IMMs), including thiopurines (TPs) and methotrexate (MTX), are commonly used in the treatment of inflammatory bowel disease (IBD). Key Messages: In ulcerative colitis (UC), TPs have modest steroid-sparing effects and established efficacy in maintenance of remission. The role of MTX in UC is unclear but current evidence suggests no benefit over placebo. In Crohn's disease (CD), MTX is not effective for induction but has a modest steroid-sparing effect and is superior to placebo in maintenance of remission in responders. The addition of MTX to infliximab reduces immunogenicity and boosts infliximab levels but does not improve outcomes in active CD. TPs are not effective for induction of remission in CD but have proven steroid-sparing effects and modest efficacy in maintenance of remission and prevention of postoperative recurrence. Although effective in pediatric CD, recent evidence has questioned the benefit of early TPs in newly diagnosed adult CD. The addition of TPs to infliximab reduces immunogenicity and inflammatory markers, leads to higher infliximab levels and improves outcomes in patients with early disease. However, the benefit of continued TP therapy in this setting is unclear and should be weighed against possible side effects including an increased risk of opportunistic infections, lymphoma and non-melanoma skin cancer. Conclusions: IMMs are an important therapeutic option in IBD particularly in non-severe steroid-dependent disease and for maintenance of remission. Combination with anti-TNF agents is an important emerging option as part of a treat-to-target strategy but further research regarding patient selection, long-term use and de-escalation options is needed.

scholarly journals Immunisation Status of Children and Adolescents with a New Diagnosis of Inflammatory Bowel Disease

2020 ◽  
Author(s):  
Timothy Ford ◽  
Margie Danchin ◽  
Alissa McMinn ◽  
Kirsten Perrett ◽  
George Alex ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Risk Groups ◽  
Current Evidence ◽  
Varicella Zoster ◽  
National Immunisation ◽  
Paediatric Patients ◽  
Increased Risk ◽  
Inflammatory Bowel ◽  
Special Risk

Abstract Background:Patients with Inflammatory Bowel Disease (IBD) are at increased risk of serious infections, including vaccine preventable diseases. Current evidence suggests uptake of additional recommended special risk vaccinations is low. Identification of IBD patients prior to commencing immunosuppressive therapy allows for optimisation of vaccination, including timely administration of live-attenuated and additional recommended vaccines, such as influenza and pneumococcal vaccines. Methods:Paediatric patients (0-18 years) seen at the tertiary Royal Children’s Hospital, Melbourne, Australia, with a recent diagnosis of IBD were referred by the Gastroenterology Unit to our Specialist Immunisation Clinic (SIC) for assessment and provision of routine and special risk vaccines. Data was collected via a standardised REDCap questionnaire completed in or post attendance at the SIC and included serology results where available. Results:Sixty-nine paediatric patients were recruited to the study between 2014 and 2017. Median age at IBD diagnosis was 11.25 years (IQR 4.64 years), with median time between diagnosis and SIC review of 0.88 years (IQR 2.84 years). At initial review 84.1% (58/69) of patients were up to date with vaccines on the Australian National Immunisation Program (NIP) schedule. Of those who were tested, serological evidence of immunity was demonstrated in 38.3% (23/60) of patients for Hepatitis B, 66.7% (36/54) for measles, 51.9% (28/54) for rubella and 41.9% (26/62) for Varicella Zoster Virus. Prior to SIC review 47.8% (33/69) had additional vaccinations and 92.8% (64/69) had vaccinations administered in the 12 months following SIC assessment. The Pneumococcal conjugate vaccine (76.8%, 53/69) was the most commonly administered vaccine after SIC review, followed by influenza vaccine (69.6%, 48/69). Within 12 months of SIC review 43.5% (30/69) of patients had completed the schedule and were up-to-date as recommended by the SIC.Conclusions:Children with IBD and other special risk groups can benefit from early referral to a SIC team to ensure optimal administration of routine and additionally recommended vaccines, especially live and additional special risk vaccines. The value of optimising immunisations could also be applied to other special risk groups, including adult IBD cohorts, particularly those commencing newer biologic immunosuppressive medications.

37 Monitoring the evolution of inflammatory bowel disease (IBD) in pediatric and adult cohorts of patients to identify biomarkers to predict cancer risk

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A38-A38
Author(s):  
Shilpa Ravindran ◽  
Heba Sidahmed ◽  
Harshitha Manjunath ◽  
Rebecca Mathew ◽  
Tanwir Habib ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Colorectal Cancer ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Mesenchymal Transition ◽  
Increased Risk ◽  
Hamad Medical Corporation ◽  
Inflammatory Bowel ◽  
Left And Right

BackgroundPatients with inflammatory bowel disease (IBD) have increased risk of developing colorectal cancer (CRC), depending on the duration and severity of the disease. The evolutionary process in IBD is driven by chronic inflammation leading to epithelial-to-mesenchymal transition (EMT) events in colonic fibrotic areas. EMT plays a determinant role in tumor formation and progression, through the acquisition of ‘stemness’ properties and the generation of neoplastic cells. The aim of this study is to monitor EMT/cancer initiating tracts in IBD in association with the deep characterization of inflammation in order to assess the mechanisms of IBD severity and progression towards malignancy.Methods10 pediatric and 20 adult IBD patients, admitted at Sidra Medicine (SM) and Hamad Medical Corporation (HMC) respectively, have been enrolled in this study, from whom gut tissue biopsies (from both left and right side) were collected. Retrospectively collected tissues (N=10) from patients with malignancy and history of IBD were included in the study. DNA and RNA were extracted from fresh small size (2–4 mm in diameter) gut tissues using the BioMasher II (Kimble) and All Prep DNA/RNA kits (Qiagen). MicroRNA (miRNA; N=700) and gene expression (N=800) profiling have been performed (cCounter platform; Nanostring) as well as the methylation profiling microarray (Infinium Methylation Epic Bead Chip kit, Illumina) to interrogate up to 850,000 methylation sites across the genome.ResultsDifferential miRNA profile (N=27 miRNA; p<0.05) was found by the comparison of tissues from pediatric and adult patients. These miRNAs regulate: i. oxidative stress damage (e.g., miR 99b), ii. hypoxia induced autophagy; iii. genes associated with the susceptibility to IBD (ATG16L1, NOD2, IRGM), iv. immune responses, such as TH17 T cell subset (miR 29). N=6 miRNAs (miR135b, 10a196b, 125b, let7c, 375) linked with the regulation of Wnt/b-catenin, EM-transaction, autophagy, oxidative stress and play role also in cell proliferation and mobilization and colorectal cancer development were differentially expressed (p<0.05) in tissues from left and right sides of gut. Gene expression signature, including genes associated with inflammation, stemness and fibrosis, has also been performed for the IBD tissues mentioned above. Methylation sites at single nucleotide resolution have been analyzed.ConclusionsAlthough the results warrant further investigation, differential genomic profiling suggestive of altered pathways involved in oxidative stress, EMT, and of the possible stemness signature was found. The integration of data from multiple platforms will provide insights of the overall molecular determinants in IBD patients along with the evolution of the disease.Ethics ApprovalThis study was approved by Sidra Medicine and Hamad Medical Corporation Ethics Boards; approval number 180402817 and MRC-02-18-096, respectively.

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