scholarly journals Tandem use of Anti-TNF Agents in Patients with IBD who Fail First Line Anti-TNF Therapy: Real Life Lessons from a National Database.

2021 ◽  
Author(s):  
Ernst Fredericks ◽  
Abigail Titus ◽  
Shiraaz Gabriel ◽  
Willem De Villiers
Keyword(s):  
South African ◽  
Dose Escalation ◽  
Clinical Remission ◽  
Biologic Therapy ◽  
Real Life ◽  
Cost Effective ◽  
National Database ◽  
Biologic Agent ◽  
Life Lessons ◽  
Inflammatory Bowel

Abstract Background: Inflammatory bowel disease (IBD) is a chronic relapsing and remitting inflammation of the bowel. Biologic therapy is safe and effective in IBD. Anti-TNF agents were the first biologics introduced for treatment of IBD. As more and more anti-TNF agents joined the market, treating physicians started using ant-TNF agents consecutively when the first agent failed. Data for this treatment choice is scanty and therefore we set out to evaluate tandem use of anti-TNF agents in IBD patients.Method: The South African Gastroenterology Society (SAGES) established a national database for all IBD patients commenced on biologic therapy. We used this registry to evaluate the data for all patients who received consecutive anti-TNF agents. Demographic and clinical details as well as treatment outcomes for all patients were documented. Results: Eight-seven (7.6%) of 1150 patients received consecutive anti-TNF agents. The Crohn’s disease (CD) group had 42 (48%) patients and ulcerative colitis (UC) group 45 (52%). Gender distribution was equal with 45 (52%) male and 42 (48%) female patients. All patients failed the first anti-TNF agent over time, but better remission rates were obtained with consecutive anti-TNF agents. Patients treated with adalimumab during any stage of the study, had a higher rate of dose escalation compared to infliximab prior to switching to next anti-TNF agent. Similarly, side effects were also more significant with adalimumab, although few. Few patients required a switch to a third and further biologic agent. All patients remained in clinical remission over 4 years of the study.Conclusion: It is reasonable to try a second anti-TNF agent when the first agent failed in IBD. Switching between different anti-TNF agents maintained clinical remission and avoided surgery and hospitalisation. This is a cost-effective strategy especially in resource constraint settings. Adalimumab is associated with higher rates of dose escalation and worse side-effect profile

scholarly journals P725 Trends in biologic use prior to resective surgery for inflammatory bowel disease: A Canadian population-based study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S583-S584
Author(s):  
D Chopra ◽  
E Kennedy ◽  
A V Weizman ◽  
A Tennakoon ◽  
L E Targownik
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Disease Duration ◽  
Biologic Therapy ◽  
Demographic Data ◽  
Biologic Agent ◽  
Primary Role ◽  
Resective Surgery ◽  
Inflammatory Bowel ◽  
Incident Cases

Abstract Background Despite advances in medical therapy for inflammatory bowel disease (IBD), surgery is required in 50–80% of patients with Crohn’s disease (CD) and 20–30% of patients with ulcerative colitis (UC). Given that fibrostenotic disease may be playing a primary role in patients undergoing resective surgery, practices around biologic administration in this setting need to be clarified. We aimed to describe the pre-operative trends in biologic utilisation for IBD patients undergoing resective surgery. Methods The University of Manitoba IBD Epidemiology Database was used to identify all persons with IBD who underwent resective surgery between April 2005 and 2018. Demographic data were extracted to explore the baseline characteristics of persons on biologic therapy prior to IBD resective surgery. Proportion calculations were used to assess how often a new biologic agent was initiated within 3, 6, and 12 months prior to resective surgery. Results were stratified by type of IBD (UC vs. CD) and disease duration (<3 or ≥3 years) for incident cases. Results A total of 1412 IBD-related resective surgeries were identified from April 2005 to 2018. 67.1% of resective surgeries were performed for CD and 32.9% for UC. Results of analysis are presented below: Conclusion Overall, in Manitoba, rates of biologic initiation or re-start in the pre-operative period for IBD resective surgery are relatively small. Biologic therapy was initiated or re-started more frequently for CD than UC, and when disease duration was less than 3 years. This is reassuring and suggests that physicians are rarely choosing to initiate biologic therapy in futile situations. Work should be performed to see if these findings can be replicated in other practice settings.

scholarly journals P378 Mucosal healing is achieved in most of the inflammatory bowel disease patients in clinical remission with vedolizumab: a real-life single-centre experience

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S355-S355
Author(s):  
M I Calvo Moya ◽  
I Omella Usieto ◽  
M I Vera Mendoza ◽  
V Matallana Royo ◽  
I Gonzalez Partida ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Clinical Practice ◽  
Bowel Disease ◽  
Clinical Remission ◽  
Real Life ◽  
Mucosal Healing ◽  
Surveillance Colonoscopy ◽  
Previously Treated ◽  
Inflammatory Bowel

Abstract Background Current therapeutic goals in inflammatory bowel disease (IBD) include not only the mere absence of symptoms but also the resolution of endoscopic lesions, so-called mucosal healing (MH), which has been related to better outcomes. Data regarding the achievement of MH with vedolizumab (VDZ) in real-life clinical practice is still scarce. Methods Retrospective cohort study was carried out in a tertiary hospital between January 2015 and April 2019 including patients with a basal colonoscopy showing activity and who achieved clinical remission under treatment with VDZ, defined by partial Mayo score <2 for ulcerative colitis (UC) and Harvey–Bradshaw Index score (HBI) <4 for Crohn’s disease (CD). Surveillance colonoscopy was performed along with the follow-up according to clinical practice. In UC patients, MH was defined as Mayo Endoscopic Subscore (MES) = 0; the endoscopic response was defined by a decrease in MES ≥1 point. In CD, MH was defined by achievement SES-CD = 0–3 or Rutgeerts index i0; the endoscopic response was defined by a decrease of SES-CD of 50% or Rutgeerts index <i2 with at least 1 point of decease compared with baseline. Results In total, 118 patients treated with VDZ were analysed, but only 45 met inclusion criteria with a median follow-up of 21 (IQR: 14–19) months. Surveillance colonoscopy was performed after a median time of 12 months (IQR:9–17) of treatment. MH achieved in 33/45 patients (73%): 17/23 CD patients (74%) and 16/22 UC patients (73%). The endoscopic response was achieved in 9 of the remaining 12 patients: 3/6 CD patients and 6/6 UC patients. Only 3 (7%) of patients included showed no endoscopic benefit at the time of surveillance endoscopy. In multivariate analysis, probability of not achieving MH was 75% in patients previously treated with immunosuppressants (ISS) (HR 0.25, 0.11–0.55 IC95; p = 0.001) and 60% in patients previously treated with anti-TNFα (HR 0.40, 0.18–0.90 95% CI; p = 0.026). Type of IBD, concomitant ISS, corticosteroid use at induction, baseline endoscopy score or duration of disease before VDZ treatment were not associated with the achievement of MH. Conclusion In our experience, most of the patients who achieve clinical remission with VDZ also achieve MH. Refractory patients were less likely to achieve MH despite having achieved clinical remission.

P131 NATIONAL TRENDS IN HOSPITALIZATION, SURGICAL RESECTION, AND COMORBIDITIES IN PEDIATRIC INFLAMMATORY BOWEL DISEASES

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S26-S27
Author(s):  
Faith Ihekweazu ◽  
Deepa Dongarwar ◽  
Hamisu Salihu ◽  
Richard Kellermayer
Keyword(s):  
Postoperative Complications ◽  
Biologic Therapy ◽  
Intestinal Resection ◽  
Annual Incidence ◽  
Therapeutic Options ◽  
National Database ◽  
Annual Percent Change ◽  
Inflammatory Bowel ◽  
Incidence Of Hospitalization ◽  
Over Time

Abstract Background Therapeutic options for pediatric inflammatory bowel disease (PIBD) have dramatically changed over the last decades with the widespread use of biologic medications. However, the overall impact of biologic therapy on PIBD outcomes (specifically hospitalizations, comorbidities, surgical rates, and postoperative complications) remains unclear. We aimed to fill this gap in the literature by using a large, validated, national database, to study the change in outcomes over the last decade. We hypothesized that morbidity in pediatric IBD has decreased over time with the increased use of biologic therapy. Methods The National Inpatient Sample (NIS) Database and ICD-9-CM codes were utilized to identify inpatient admissions with a primary or secondary diagnosis of pediatric Crohn’s disease (CD) or ulcerative colitis (UC) from 2002–2015. Trends in hospitalizations, comorbidities (including malnutrition and weight loss), surgical procedures, and post-operative complications were examined using joinpoint regression analysis. Results There were 119,282 admissions for PIBD during the study period. The annual incidence of hospitalization increased significantly over time for both CD (average annual percent change [AAPC] 6.0%, 95%confidence interval [CI] 4.7, 7.2) and UC (AAPC 7.2%, 95% CI 6.2, 8.1). The rate of intestinal resection decreased in CD patients (AAPC -6.4%, 95%CI, -8.7, -4.1) while postoperative complications remained unchanged. However, comorbidities increased significantly in CD patients (AAPC 6.8%, 95%CI, 4.6, 9.0). For pediatric UC patients, postoperative complications (AAPC 6.7%, 95%CI, 1.2, 12.4), and comorbidities (AAPC 10.2%, 95%CI, 8.8–11.6) increased significantly over time while intestinal resection rates remained stable. Conclusions Intestinal resection rate in pediatric CD has decreased over time, but not in pediatric UC. Annual incidence of hospitalization and comorbidities continue to increase in PIBD despite the increased availability and use of biologic medications. Our findings emphasize the critical need for prevention and novel therapeutic options for this vulnerable patient population.

scholarly journals P481 Effectiveness and safety profile of biological therapy in inflammatory bowel disease: real life data from an active pharmacovigilance project

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S470-S471
Author(s):  
A Viola ◽  
M A Barbieri ◽  
V Pisana ◽  
P M Cutroneo ◽  
W Fries ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Safety Profile ◽  
Index Date ◽  
Descriptive Analysis ◽  
Real Life ◽  
Biologic Agent ◽  
Skin Reactions ◽  
Inflammatory Bowel

Abstract Background Biological therapies are now the mainstay for the treatment of Inflammatory bowel disease (IBD). Post-marketing activities become crucial for monitoring the long-term safety. Aim of this project was to evaluate the effectiveness and the safety profile of biologics for the treatment of IBD patients during a prospective pharmacovigilance study. Methods From January 2017 to December 2020, all patients with Crohn’s Disease (CD) and Ulcerative Colitis (UC) treated with at least one biologic agent at the start of the study or commenced a biologic during the study period were enrolled. Demographic, clinical, and disease-related data were collected. A descriptive analysis of patients’ characteristics at the index date was performed. Moreover, an analysis of all adverse events (AEs) and all primary/secondary failures expressed as number of AEs or failures/10 treatment years was carried out taking into account the total years of treatment for each biologic including all patients treated with a biologic at least once during the follow-up period. Results A total of 654 patients were enrolled, 58.4% with CD and 41.6% with UC. Mean age (±SD) was 44 ± 17 years and 59.0% were males. At the index date, the following treatments were used: 40.8% adalimumab (ADA), 33.3% infliximab (IFX), 21.3% vedolizumab (VED), 2.4% ustekinumab (UST), and 2.1% golimumab (GOL). Patients naïve for biologic therapy were 79.1%. The total years of treatment were 887 yrs for ADA, 663 yrs for IFX, 309 yrs for VED, 89 yrs for UST, and 51 yrs for GOL. Data for AEs and failures were the following: IFX – 1.1 AEs and 0.8 failures, ADA – 0.8 and 0.9, VED – 1.1 and 1.8, GOL – 1.2 and 3.4, and UST - 1.4 and 0.9, respectively (Tab.1). During follow-up, 196 AEs were reported. Infections mainly occurred in patients treated with GOL and ADA (8.7% and 7.6%, respectively), skin reactions in patients treated with ADA (7.6%), while infusion related reactions with IFX (12.6%). A higher frequency of malignancies was observed in patients on treatment with VED (3.4%). Conclusion There were no major differences for AEs between the different treatments, but a higher frequency of failures with GOL and VED, both rarely used as first line therapies. Nevertheless, the acquisition of data from clinical practice should be endorsed to better define the safety and efficacy profile of new biologic agents in IBD.

scholarly journals P415 The anti-IL-23/IL-12 agent Ustekinumab is an effective and safe induction therapy in patients with Crohn’s disease refractory or intolerant to anti-TNF: a multicentre Italian study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S379-S379
Author(s):  
A Gubbiotti ◽  
B Barberio ◽  
F Zingone ◽  
R D’Incà ◽  
L Bertani ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Remission ◽  
Real Life ◽  
Previous Treatment ◽  
Categorical Variables ◽  
Biologic Agent ◽  
Chi Square ◽  
Faecal Calprotectin ◽  
Chi Square Test

Abstract Background There are limited real-life studies in medical literature evaluating the efficacy and safety of Ustekinumab, an Anti-IL-23/Anti IL-12 agent, in patients with Crohn’s disease (CD) who required treatment because of refractoriness or intolerance to previous biological treatments. Thus, the aim of this study was to assess the effectiveness and tolerability of Ustekinumab in anti-TNF refractory or intolerant CD patients. Methods All CD patients who completed induction with Ustekinumab in three Italian IBD Units (Padua, Santorso, and Pisa) were enrolled. Patients were evaluated after induction (first intravenous dose followed by a subcutaneous dose at 8 weeks) and clinical (Harvey- Bradshaw-Index) and biochemical data, including faecal calprotectin (FC) and C-reactive protein (CRP) were collected. Information on the need of optimisation (every 12 or 8 weeks) and adverse events were also collected. Continuous and categorical variables were expressed as mean with standard deviation (sd) and frequency with percentages, respectively. Comparisons between variables were conducted using paired t-test and chi-square test. Data were analysed using STATA11.1 software. Results Sixty-three patients were included (41 males, mean age 43 ± sd 13.2 years). All of them had previously been treated with at least one biologic agent and 95.2% with oral steroids. The main indications for starting therapy were: previous treatment failure (77.2%) and pharmacological intolerance (17.5%). At the time of the induction, 28.6% patients were under steroid treatment. Post induction, clinical remission was obtained in 63.5% patients, while steroid-free clinical remission in 52.4%. Moreover, a statistically significant reduction of FC (from 916 μg/l to 444 μ/l, p < 0.001) and normalisation of CRP (n = 14, 33.3%; p < 0.001) were observed. After induction, 3 adverse effects were reported, and in two treatment discontinuations was necessary (i.e. 1 case of pyelonephritis and 1 case of a re-activation of entero-cutaneous fistula). Finally, among 63 patients enrolled, 51 (80.9%) were optimised with a maintenance regimen of 8 weeks sub-cutaneous doses. Conclusion Our study shows that Ustekinumab seemed is effective in achieving clinical remission and steroid-free clinical remission after induction in the majority of CD patient despite the refractoriness to anti-TNF treatment. Moreover, the drug appeared safe and well tolerated. On the other hand, treatment optimisation to 8 weeks was adopted in most of the patients, in order to guarantee a better outcome.

scholarly journals P438 Real-life effectiveness and safety of ABP501, an adalimumab biosimilar, in inflammatory bowel disease: a multicentre Italian study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S397-S397
Author(s):  
B Barberio ◽  
F Zingone ◽  
A Ferronato ◽  
A Buda ◽  
P Melatti ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Adverse Events ◽  
Bowel Disease ◽  
Clinical Remission ◽  
Real Life ◽  
Infusion Reaction ◽  
Categorical Variables ◽  
Azathioprine Therapy ◽  
Inflammatory Bowel ◽  
T1 And T2

Abstract Background Recently, various adalimumab (ADA) biosimilars have been approved by the EMA with the same indications of the reference product (Humira), despite the lack of data in terms of efficacy and safety in patients with inflammatory bowel disease (IBD). The aim of our study was to verify the effectiveness and tolerability of ABP501, an ADA Biosimilar, in IBD in the short-term. Methods All consecutive moderate-to-severe IBD patients who completed induction with ABP501 at three Italian IBD Units (Padua, Santorso, Feltre) were included. We collected data on partial Mayo (p-Mayo) Score, Harvey–Bradshaw Index (HBI), C reactive protein (CRP), faecal calprotectin (FC), concomitant steroid and azathioprine therapy at baseline (T0), after induction (T1) and at six months (T2). Information on the need for optimisation and adverse events (AEs) were also collected. Continuous and categorical variables were expressed as mean with standard deviation and frequency with percentages, respectively. Comparisons between variables were conducted using a t-test and chi-square test. Data were analysed using STATA11.1 software. Results Thirty-three IBD patients [17 with ulcerative colitis (CU), 18 with Crohn’s disease (CD)] that completed induction (T1) were considered, with 18 of them who completed at least six months of therapy (T2). Clinical remission was achieved by 14/33 (45.5%) and 8/18 (44.4) patients at T1 and T2, respectively. Steroid-free clinical remission was obtained by 14/33 (42.4%) and 8/18 (44.4) patients at T1 and T2, respectively. After induction FC tended to decrease from baseline to T2, without reaching statistical significance (p = 0.1). However, a significant decrease in CRP levels (p < 0.02) was observed. After induction, AEs occurred in 11 (33.3%) patients: 2 had an infection, 8 reported headache or myalgia or arthralgia, and one experienced a local infusion reaction. Moreover, AEs were observed in 6/18 (33.3%) at T2: 5 had arthralgia and 1 had a local infusion reaction. After induction 4/33 (12.12%) stopped therapy for lack of response, whereas the dropout occurred in 6/12 (33.3%) at six months (4 for loss of response and 2 for adverse events). Finally, 7/33 (21.2%) and 5/18 (27.7%) patients needed therapeutic optimisation at T1 and T2, respectively. Conclusion ABP501 seemed to be successful in achieving clinical remission and steroid-free clinical remission, but further data are required. Overall the therapy was well tolerated.

scholarly journals Real-life burden of adverse reactions to biological therapy in inflammatory bowel disease: a single-centre prospective case series

2021 ◽  
Author(s):  
Tiziana Larussa ◽  
Antonio Basile ◽  
Caterina Palleria ◽  
Chiara Iannelli ◽  
Ada Vero ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Biological Therapy ◽  
Biologic Therapy ◽  
Subcutaneous Tissue ◽  
Real Life ◽  
Case Series ◽  
Single Centre ◽  
Post Marketing Surveillance ◽  
Inflammatory Bowel

Background/aim. Biologics represent a key therapeutic option in inflammatory bowel disease (IBD), but are associated with several side effects. Post-marketing surveillance, through a spontaneous adverse drug reactions (ADRs) monitoring system, is essential to assess the safety profile of biologics. The aim of the study was to prospectively evaluate the occurrence of ADRs in IBD patients treated with biologics from a single centre in Southern Italy. Methods. Data from patients with Crohn’s Disease (CD) and Ulcerative Colitis (UC) who underwent biological therapy were prospectively collected. ADRs were classified according to the Medical Dictionary for Regulatory Activities (MedDRA®). Results. Overall, 68 (54% male, 68% with UC and 32% with CD) biologic-naïve IBD patients underwent biological therapy. Mean follow-up was 11.7 ± 6.2 months. As a results of switches, for 68 patients we obtained 96 biologic prescriptions. Overall, 45 ADRs occurred in 36 (53%) patients, distributed as follows (ADRs/prescriptions): 19/37 with IFX-Remicade, 5/12 with IFX-Remsima, 8/9 with GOL, 11/26 with ADA, and 2/12 with VDZ. Mild ADRs were 29 (64%), moderate 15 (34%) and 1 (2%) severe. General disorders and administration related reactions were the most frequent ADRs (35%), followed by skin and subcutaneous tissue disorders (20%), infections (15%), musculoskeletal (11%), respiratory (6%) blood (4%), gastrointestinal (4%), and vascular disorders (2%). In 9 cases (20%) the ADRs resulted in definitive discontinuation of biologic therapy. Conclusion. In a prospective cohort of IBD patients, more than half experienced ADRs during biologic therapy. General disorders and administration related reactions were the most common ADRs, while infections were less common and rarely led to discontinuation of therapy. Findings underline the importance of surveillance in management of IBD patients during biologic therapy and implementing safety protocols with data from real-life settings.

scholarly journals P588 vedolizumab trough levels at week 6 and 14 correlate with clinical remission in inflammatory bowel disease patients

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S492-S492 ◽  
Author(s):  
M Marino ◽  
R Domenis ◽  
L Biribin ◽  
A Cifù ◽  
L Navarria ◽  
...  
Keyword(s):  
Disease Activity ◽  
Clinical Remission ◽  
Real Life ◽  
Inverse Correlation ◽  
Clinical Score ◽  
Induction Phase ◽  
Spearman's Rho ◽  
Spearman’S Rho ◽  
Inflammatory Bowel ◽  
Trough Levels

Abstract Background Vedolizumab (VDZ) is a therapeutic monoclonal antibody against α 4β 7 integrin approved for the treatment of inflammatory bowel diseases (IBDs). A relationship between VDZ exposure and clinical efficacy has been highlighted by several studies, but data are still controversial. In this perspective, our study aims to investigate the clinical usefulness of VDZ drug monitoring during the induction phase to support therapeutic management of IBD patients in the real life. Methods This retrospective study focus on a single cohort of 25 IBD patients (7 with Crohn’s disease and 18 with ulcerative colitis) treated with VDZ between 2016 and 2019. VDZ trough levels (TLs) and anti-VDZ antibodies (AVA) were measured before infusion at weeks 6, 14 and 22, using Promonitor® ELISA assays (Grifols). Disease activity was evaluated using international criteria, defining clinical remission when Mayo Partial Score <2 and Harvey–Bradshaw Index <5. Results VDZ TLs showed a significant inverse correlation with disease activity at each time point (week 6: Spearman’s rho = −0.659, p = 0.0003), (week 14: Spearman’s rho = −0.634, p = 0.0009), (week 22: Spearman’s rho = −0.476, p = 0.029). The median VDZ TLs was significantly higher in patients in clinical remission when compared with those with active disease, either at week 6 (42.3 vs. 19.8 µg/ml, p = 0.0005), and at week 14 (23 vs. 8.6 µg/ml, p = 0.003). Of note, at week 6, patients with VDZ TLs >24 µg/ml were significantly associated with a state of clinical remission compared with those showing VDZ TLs <24 µg/ml (9/12, 75% vs. 1/13, 7.7%; OR=36, [95% CI=3.19–401], p = 0.001). Anti-VDZ antibodies were detected in 1 patient out of 25 (4%). Conclusion VDZ TLs in the induction phase correlate with the clinical score in IBD patients, helping the management of the therapeutic efficacy of VDZ, from the very beginning of the biological treatment. In particular, at week 6, VDZ trough levels > 24 µg/ml may represent a potential drug concentration target to achieve long-term remission.

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