scholarly journals Clinical outcomes, predictors of prognosis and health economics consequences in IBD patients after discontinuation of the first biological therapy

2020 ◽  
Vol 13 ◽  
pp. 175628482098121
Author(s):  
Uday N. Shivaji ◽  
Alina Bazarova ◽  
Tamsin Critchlow ◽  
Samuel C. L. Smith ◽  
Olga Maria Nardone ◽  
...  
Keyword(s):  
Direct Costs ◽  
Adverse Outcomes ◽  
Tertiary Centre ◽  
Kaplan Meier ◽  
Bowel Diseases ◽  
Recorded Data ◽  
Inflammatory Bowel ◽  
Logistic Regressions ◽  
Cost Implications

Background: In real-world clinical practice, biologics in inflammatory bowel diseases (IBD) may be discontinued for a variety of reasons, including discontinuation initiated by gastroenterologists. The aims of the study are to report outcomes after discontinuation and predictors of prognosis after a minimum follow-up of 24 months; outcomes of gastroenterologist-initiated discontinuation with resulting direct cost implications on the health system were also studied. Methods: IBD patients who discontinued their first-use biologics between January 2013 and December 2016 were identified at our tertiary centre. Reasons for discontinuation and pre-defined adverse outcomes (AO) were recorded. Data were analysed using univariable and multivariable logistic regressions within a machine learning technique to predict AO. Gastroenterologist-initiated discontinuations were analysed separately, and Kaplan–Meier survival analysis performed; direct costs of AO due to discontinuation were assessed. Results: A total of 147 patients discontinued biologics (M = 74; median age 39 years; Crohn’s Disease = 110) with median follow-up of 40 months (range 24–60 months). In the total cohort, there were fewer AO among gastroenterologist-initiated discontinuations compared with patient-initiated; 54% (of the total group) had AO within 6 months. Among 59 gastroenterologist-initiated discontinuations, 23 (40%) had IBD-related AO within 6 months and 53 (90%) patients had AO by end of follow-up. Some 44 (75%) patients needed to restart biologics during follow-up, and direct costs due to AO and restart of biologics were high. Conclusions: The proportion of patients who have AO following discontinuation of biologics is high; clinicians need to carefully consider predictors of poor prognosis and high relapse rates when discussing discontinuation. The direct costs of managing AO probably offset theoretical economic gains, especially in the era where cost of biologics is reducing. Biologics should probably be continued without interruptions in most patients who have achieved remission for the duration these remain effective and safe.

scholarly journals P220 Predictors of prognosis after discontinuation of first-use biologics in IBD patients with at least 24 months follow-up

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S252-S253
Author(s):  
U N Shivaji ◽  
A Bazarova ◽  
T Critchlow ◽  
S C Smith ◽  
O M Nardone ◽  
...  
Keyword(s):  
Adverse Outcomes ◽  
Patient Choice ◽  
Multivariable Logistic Regression Analysis ◽  
Tertiary Referral Centre ◽  
Kaplan Meier ◽  
Number Of Patients ◽  
Learning Technique ◽  
Logistic Regressions ◽  
Using Data

Abstract Background In clinical practice, patients with IBD have their biologic therapies withdrawn due to variety of reasons. The aim of the study was to report on predictors of prognosis in IBD patients after biologics have been discontinued, with a minimum follow-up of 24 months. Methods All IBD patients who discontinued their first-use biologic were identified between January 2013 and Dec 2016 from EMR at a tertiary referral centre, to ensure at least 24 months follow-up. Reasons for discontinuation and pre-defined adverse outcomes (steroid and other rescue therapies, hospitalisations, surgery including perianal) were recorded. The data were analysed using multivariable and univariable logistic regressions within a machine learning technique in order to predict adverse outcomes, within the stated timeframe. We tested the significance of the identified predictors and performed Kaplan–Meier survival analysis to compare patients with elective vs. non-elective discontinuation of biologics. Results 147 patients who discontinued biologics (M = 74, median age 39y; CD = 110) were identified. Follow-up ranged from 24 to 60 months (median 40 months). The reasons for non-elective discontinuation included side effects (n = 21, 14%), primary or secondary non-response (n = 33, 22%) and patient choice (n = 10, 7%), among others. 59 (40%) patients had elective discontinuation. In this cohort, elective discontinuation resulted in fewer IBD-related adverse outcomes (AO) compared with non-elective. Figure 1 shows a Kaplan–Meier curve comparing the two (p = 0.003). Using data from all 147 patients, multivariable logistic regression analysis was done to identify significant predictors of prognosis. These are represented in Table 1. Overall, a significant number of patients (n = 80, 54%) had AO within 6 months of discontinuation, and 96 (65%) patients needed biologics to be restarted by the end of the study follow-up period. Conclusion Among IBD patients who discontinued biologics, there were fewer AO when they were electively discontinued. However, majority of patients required restart of biologics to manage their disease during the follow-up period. Clinicians need to be cautious when considering biologic discontinuation given the high proportion of AO and re-escalation to biologics therapy.

scholarly journals P435 Real-world clinical outcomes after elective discontinuation of first-use biologics in IBD patients

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S395-S396
Author(s):  
U N Shivaji ◽  
A Bazarova ◽  
T Critchlow ◽  
O M Nardone ◽  
S C Smith ◽  
...  
Keyword(s):  
Real World ◽  
Adverse Outcomes ◽  
Machine Learning Technique ◽  
Tertiary Referral Centre ◽  
Kaplan Meier ◽  
Learning Technique ◽  
Logistic Regressions ◽  
The Uk ◽  
Almost All

Abstract Background In real-world clinical practice, biologics may be discontinued due to variety of reasons, including discontinuation by gastroenterologists, in the UK. The aim of the study was to report on outcomes after discontinuation in IBD patients after a minimum follow-up of 24 months. Methods All IBD patients who discontinued their first-use biologics between January 2013 and Dec 2016 were identified from the EMR at a tertiary referral centre to ensure at least 24 months follow-up. Reasons for discontinuation and pre-defined adverse outcomes (steroid and other rescue therapies, hospitalisations, surgery including perianal) were recorded. The data were analysed using multivariable and univariable logistic regressions within a machine learning technique in order to predict adverse outcomes within the stated timeframe. We performed Kaplan-Meier survival analysis for those patients who had biologics electively discontinued. Results In total, 147 IBD patients who discontinued biologics (M = 74.median age 39 years; CD = 110) were identified. Follow-up ranged from 24 to 60 months (median 40 months). One hundred and forty-four patients (98%) discontinued anti-TNF (1% biosimilar anti-TNF and 1% vedolizumab) and 69 (47%) were on thiopurines at start of biologics. Fifty-nine patients (40%) had biologics electively discontinued by their gastroenterologists and they were analysed separately. Of the 59 elective discontinuations, 22(37%) continued thiopurines after biologic stoppage; 37/59 (63%) patients had at least one adverse outcome (AO) within 6 months of discontinuation and 42/59 (71%) patients restarted biologics. Conclusion The majority of patients who electively discontinued biologics had IBD-related AO rapidly after the stoppage and needed to restart biologics. Almost all patients had AO by the end of the study follow-up period. This should be discussed with patients when considering discontinuation of biologics.

scholarly journals P453 Comparison of therapeutic effects between groups of thiopurine alone and combination of thiopurine with 5-ASA after remission introduced by oral tacrolimus for patients with severe ulcerative colitis

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S405-S406
Author(s):  
T Sato ◽  
K Kojima ◽  
R Koshiba ◽  
K Fujimoto ◽  
M Kawai ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Rank Test ◽  
Therapeutic Effects ◽  
Aminosalicylic Acid ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Time To Relapse

Abstract Background Although thiopurine is recommended to be used for maintenance after remission, the reliable data of maintenance introduced by tacrolimus is limited for patients with ulcerative colitis (UC). 5-aminosalicylic acid (5-ASA) is reported to induce 6-thioguanine nucleotides (6-TGN) levels higher in patients with inflammatory bowel diseases. However, the data of 5-ASA are few reported among East Asians. Methods A retrospective cohort study was conducted evaluating the 70 patients with severe UC who were primary responders to oral tacrolimus from April 2015 to March 2018. Twenty-seven patients were administered maintenance treatment with thiopurine. We evaluated the efficacy of thiopurines with and without 5-ASA in these patients, using ΔMCV, lowest WBC, highest 6TGN between groups of thiopurine alone and thiopurine+ 5-ASA. Kaplan–Meier analysis was used to assess time to relapse between groups of thiopurine and thiopurine+5-ASA. Results The median follow-up period was 430 days (interquartile range 207–952 days). The statistical significances were not found in patients background between groups of thiopurine and thiopurine+5-ASA. ΔMCV were significantly greater (p < 0.01), lowest WBC were significantly lower (p = 0.02) in the thiopurines+5-ASA group than in thiopurines alone group. The highest 6-TGN levels tended to be higher in thiopurine+5-ASA group than in thiopurine alone group (p = 0.09). The rate of relapse was significantly higher in the thiopurine alone group than in thiopurines+5-ASA group (p = 0.03). Kaplan–Meier curves confirmed that thiopurine+5-ASA group appeared to protect against relapse (log-rank test, p < 0.01). Conclusion Thiopurine+5-ASA induced significantly lower relapse than thiopurine alone after remission introduced by tacrolimus in the patients with severe UC, along with significantly greater the ΔMCV and lower the lowest WBC.

scholarly journals Serum biomarkers confirming stable remission in inflammatory bowel disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Christoph Kessel ◽  
Miha Lavric ◽  
Toni Weinhage ◽  
Markus Brueckner ◽  
Sytze de Roock ◽  
...  
Keyword(s):  
Disease Control ◽  
Serum Biomarkers ◽  
Treat To Target ◽  
Optimal Management ◽  
Tight Control ◽  
Follow Up Study ◽  
Number Of Patients ◽  
Bowel Diseases ◽  
Inflammatory Bowel

AbstractCrohn's disease (CD) and ulcerative colitis (UC) have a chronic-remittent course. Optimal management of inflammatory bowel diseases (IBD) relies on early intervention, treat-to-target strategies and a tight disease control. However, it is challenging to assess the risk of relapses in individual patients. We investigated blood-based biomarkers for the confirmation of disease remission in patients with IBD. We retrospectively analyzed samples of 40 IBD patients (30 UC, 10 CD) enrolled in a tight-control follow-up study. Half of the patients had a flare during follow up. Serum was analyzed for S100A12 as well as S100A8/A9 and for 50 further biomarkers in a bead-based multiplex assay. The concentrations of 9 cytokines/chemokines and S100A8/A9 significantly differed in IBD patients with unstable remission (before flares) when compared to IBD patients with stable remission. Although the number of patients was small, ROC curve analyses revealed a number of biomarkers (IL-1β, IL-1RA, IL-8, IL13, IL-15, IL-21, IL-25, IFN-β, CXCL9, CXCL10, CXCL11, Galectin-1, G-CSF and S100A8/A9) that were elevated in patients with later occurring relapses. While earlier studies on peripheral biomarkers in IBD are limited to only few analytes, our study using a broad screening approach identified serum biomarkers with the potential to indicate unstable disease control in IBD, which may help to steer individual therapies to maintain remission.

The SPOSIB SB2 Sicilian Cohort: Safety and Effectiveness of Infliximab Biosimilar SB2 in Inflammatory Bowel Diseases, Including Multiple Switches

2020 ◽  
Author(s):  
Fabio Salvatore Macaluso ◽  
Walter Fries ◽  
Anna Viola ◽  
Andrea Centritto ◽  
Maria Cappello ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Tumor Necrosis ◽  
Prospective Observational Study ◽  
Cumulative Number ◽  
Serious Adverse Events ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Necrosis Factor

Abstract Background No data on the recently introduced infliximab (IFX) biosimilar SB2 in inflammatory bowel disease (IBD) are available. Methods The Sicilian Prospective Observational Study of Patients With IBD Treated With Infliximab Biosimilar SB2 is a multicenter, observational, prospective study performed among the cohort of the Sicilian Network for Inflammatory Bowel Disease. All consecutive IBD patients starting the IFX biosimilar SB2 from its introduction in Sicily (March 2018) to September 2019 (18 months) were enrolled. Results Two hundred seventy-six patients (Crohn disease: 49.3%, ulcerative colitis: 50.7%) were included: 127 (46.0%) were naïve to IFX and naïve to anti-tumor necrosis factor medications (anti-TNFs), 65 (23.5%) were naïve to IFX and previously exposed to anti-TNFs, 17 (6.2%) were switched from an IFX originator to SB2, 43 (15.6%) were switched from the biosimilar CT-P13 to SB2, and 24 (8.7%) were multiply switched (from IFX originator to CT-P13 to SB2). The cumulative number of infusions of SB2 was 1798, and the total follow-up time was 182.7 patient-years. Sixty-seven serious adverse events occurred in 57 patients (20.7%; incidence rate: 36.7 per 100 patient-year), and 31 of these events caused the withdrawal of the drug. The effectiveness after 8 weeks of treatment was evaluated in patients naïve to IFX (n = 192): 110 patients (57.3%) had steroid-free remission, while 56 patients had no response (29.2%). At the end of follow-up, 72 patients (26.1%) interrupted the treatment, without significant differences in treatment persistency estimations between the five groups (log-rank P = 0.15). Conclusions The safety and effectiveness of SB2 seem to be overall similar to those reported for the IFX originator and CT-P13.

scholarly journals Risk, Course, and Effect of SARS-CoV-2 Infection in Children and Adults with Chronic Inflammatory Bowel Diseases

Children ◽  
2021 ◽  
Vol 8 (9) ◽  
pp. 753
Author(s):  
Angelica Corrias ◽  
Gian Mario Cortes ◽  
Flaminia Bardanzellu ◽  
Alice Melis ◽  
Vassilios Fanos ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Bacterial Infections ◽  
Immunosuppressive Treatment ◽  
Epidemiological Data ◽  
Adverse Outcomes ◽  
Biologic Drugs ◽  
Angiotensin Converting Enzyme 2 ◽  
Increased Risk ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Susceptibility and disease course of COVID-19 among patients with inflammatory bowel diseases (IBD) are unclear and epidemiological data on the topic are still limited. There is some concern that patients with immuno-mediated diseases such as IBD, which are frequently treated with immunosuppressive therapies, may have an increased risk of SARS-CoV-2 infection with its related serious adverse outcomes, including intensive care unit (ICU) admission and death. Corticosteroids, immunomodulators, and biologic drugs, which are commonly prescribed to these patients, have been associated with higher rates of severe viral and bacterial infections including influenza and pneumonia. It is not known whether these drugs can be so harmful as to justify their interruption during COVID-19 infection or if, on the contrary, patients with IBD can benefit from them. As shown by recent reports, it cannot be excluded that drugs that suppress the immune system can block the characteristic cytokine storm of severe forms of COVID-19 and consequently reduce mortality. Another cause for concern is the up-regulation of angiotensin converting enzyme-2 (ACE2) receptors that has been noticed in these patients, which could facilitate the entry and replication of SARS-CoV-2. The aim of this narrative review is to clarify the susceptibility of SARS-CoV-2 infection in patients with IBD, the clinical characteristics of patients who contract the infection, and the relationship between the severity of COVID-19 and immunosuppressive treatment.

scholarly journals P295 VALIDation of the IBD-Disk instrument for assessing disability in inflammatory bowel diseases in a population-based cohort: The VALIDate study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S299-S301
Author(s):  
C Le Berre ◽  
A Bourreille ◽  
M Flamant ◽  
G Bouguen ◽  
L Siproudhis ◽  
...  
Keyword(s):  
Internal Consistency ◽  
Inflammatory Bowel Diseases ◽  
Population Based ◽  
Large Cohort ◽  
Inactive Disease ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Physician Patient ◽  
Over Time

Abstract Background Inflammatory bowel diseases (IBD) are disabling disorders. The IBD-Disability Index (IBD-DI) was developed for quantifying disability in IBD patients but is difficult to use. The IBD-Disk is a shortened and visual adaptation of the IBD-DI. It has not been validated yet. The main objectives were to validate the IBD-Disk in a large cohort of IBD patients and to assess its variability over time. Methods From March 2018 to July 2019, IBD patients from three university-affiliated hospitals responded twice to both IBD-Disk and IBD-DI at 3–12 months intervals (NCT03590639). Validation included concurrent validity, reproducibility, internal consistency, and evaluation of IBD-Disk correlation with IBD activity. Variability was assessed by comparing scores between baseline and follow-up visits. Results A total of 559 patients (73% Crohn’s disease, 27% ulcerative colitis) were included and 389 were followed up (Table 1). There was a good correlation between IBD-Disk and IBD-DI scores (r = 0.75, p < 0.001) (Figure 1). The IBD-Disk was significantly higher in patients with active disease according to Physician/Patient Global Assessment (Figure 2), clinical scores (Figure 3), and biomarkers levels, compared with patients with inactive disease. Reproducibility was excellent (intra-class correlation coefficient = 0.90), as well as internal consistency (Cronbach’s α = 0.89). The IBD-Disk score significantly decreased in patients becoming inactive over time. Conclusion This is the first study to validate the IBD-Disk in a large cohort of IBD patients, demonstrating that it is a valid and reliable tool for quantifying disability in clinical practice. Further studies are warranted to assess its correlation with endoscopic activity, to explore its responsiveness to change, and to evaluate the factors associated with disability.

scholarly journals Articular manifestations in patients with inflammatory bowel disease treated with vedolizumab

Rheumatology ◽  
2020 ◽  
Vol 59 (11) ◽  
pp. 3275-3283 ◽  
Author(s):  
Anastasia Dupré ◽  
Michael Collins ◽  
Gaétane Nocturne ◽  
Franck Carbonnel ◽  
Xavier Mariette ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Inflammatory Bowel Diseases ◽  
Bowel Disease ◽  
Bowel Diseases ◽  
History Of ◽  
Musculoskeletal Manifestations ◽  
Inflammatory Bowel

Abstract Objective Vedolizumab (VDZ) has been incriminated in the occurrence of articular manifestations in patients with inflammatory bowel diseases (IBDs). The aim of this study was to describe musculoskeletal manifestations occurring in IBD patients treated by VDZ and to identify risk factors. Methods In this retrospective monocentric study, we included all consecutive patients treated by VDZ for IBD in our hospital. Incident musculoskeletal manifestations occurring during VDZ treatment were analysed and characteristics of patients with and without articular inflammatory manifestations were compared. Results Between 2013 and 2017, 112 patients were treated with VDZ for IBD: ulcerative colitis (n = 59), Crohn’s disease (n = 49) and undetermined colitis (n = 4). Four patients (3.6%) had a history of SpA, whereas 13 (11.6%) had a history of peripheral arthralgia. Some 102 (91.1%) patients had previously received anti-TNF. After a mean (S.d.) follow-up of 11.4 (8.6) months, 32 (28.6%) patients presented 35 musculoskeletal manifestations, of which 18 were mechanical and 17 inflammatory. Among the latter, 11 had axial or peripheral SpA, 5 had early reversible arthralgia and 1 had chondrocalcinosis (n = 1). Among the 11 SpA patients, only 3 (2.6%) had inactive IBD and may be considered as paradoxical SpA. The only factor associated with occurrence of inflammatory manifestations was history of inflammatory articular manifestation [7/16 (43.8%) vs 10/80 (12.5%), P = 0.007]. Conclusion Musculoskeletal manifestations occurred in almost 30% of IBD patients treated with VDZ, but only half of them were inflammatory. Since most of the patients previously received anti-TNF, occurrence of inflammatory articular manifestations might rather be linked to anti-TNF discontinuation than to VDZ itself.

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