scholarly journals P314 TNF gene activation used as criterion to discontinue biologic therapy – A patient series introducing the NovaPrime TNF kit

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S340-S341
Author(s):  
R Goll ◽  
J Kay-Martin ◽  
A Viola ◽  
E Paulssen ◽  
Ø K Moe ◽  
...  
Keyword(s):  
Gene Expression ◽  
Inflammatory Bowel Disease ◽  
Biologic Therapy ◽  
Biologic Drugs ◽  
Endoscopic Remission ◽  
Inflammatory Bowel ◽  
Tnf Gene ◽  
Normal Controls ◽  
Active Disease

Abstract Background Severe inflammatory bowel disease can be successfully treated with biologic drugs such as anti-TNF. However, there is no consensus on if and how to stop treatment. Our group has earlier shown that normalization of TNF gene expression may be a beneficial prognostic factor when attempting to discontinue biologic therapy. We here present data from a series of patients in endoscopic remission and with normalized TNF gene expression. Methods Severe inflammatory bowel disease can be successfully treated with biologic drugs such as anti-TNF. However, there is no consensus on if and how to stop treatment. Our group has earlier shown that normalization of TNF gene expression may be a beneficial prognostic factor when attempting to discontinue biologic therapy. We here present data from a series of patients in endoscopic remission and with normalized TNF gene expression. A total of 91 patients were recruited at hospitals in Norway and Italy: 55 patients (32 UC, 23 CD) in remission (picked by normalization of TNF using our in-house TNF qPCR), and for comparison: 14 patients with active disease, and 22 normal controls. Mucosal samples taken prior to drug discontinuation from all patients were re-measured for TNF mRNA by the NovaPrime TNF kit. Results A clear difference could be seen between normal controls and patients with active disease, showing highly elevated TNF mRNA values in the active disease group. The patients in remission had values resembling the normal controls with values generally below a cut-off of 9060 copies/µg total RNA by the NovaPrime TNF kit. The patients in remission were followed for up to 5 years noting two endpoints: relapse triggering any adjustment of medication, and relapse triggering restart of biologics. Median survival time before adjusting medication was 12 months for ulcerative colitis and 17 months for Crohn’s disease. Median time to restart of biologics was 21 months (2 – 40) overall, and after 3 years 43% still were not in need of biologic therapy. Conclusion We conclude that the NovaPrime TNF kit yields consistent readings comparable to our in-house assay, and that this industrial standard kit enables any PCR lab to perform TNF gene expression in samples from intestinal mucosa. A considerable proportion of patients with normalized TNF gene expression can maintain long term remission without biologic therapy, relieving health care costs and potential side effects of long-term therapy.

scholarly journals P343 Efficacy of adalimumab in mild-to-moderate inflammatory bowel disease: Real-life data from single-centre experience in the long-term period

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S329-S330
Author(s):  
F Akyüz ◽  
A Ormeci ◽  
N Namazova ◽  
M Guzel ◽  
A Abbasgoulizadeh ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Response Rate ◽  
Real Life ◽  
Loss Of Response ◽  
Endoscopic Remission ◽  
Inflammatory Bowel

Abstract Background Adalimumab (ADA) is one of the most preferred anti-TNF agents because of its ease of use in real life. We aimed to evaluate the efficacy of ADA in the long-term period of inflammatory bowel disease (IBD) patients. Methods Patients treated with adalimumab (ADA) as the first- and second-line biological treatment for mild to moderate active IBD between January 2009 and March 2019 were included. The clinical and endoscopic response rate of ADA were evaluated, retrospectively. Remission was defined in ulcerative colitis patients (UC), if stool frequency ≤ 3/day with no bleeding and no mucosal lesions at the colonoscopy. Remission was defined in Crohn’s disease patients (CD) if CDAI < 150 and mucosal healing at the colonoscopy. Results Fifty-eight patients (81% Crohn’s disease, 58.6% biologic naive) were included in this study. Mean age was 41.4 ± 12.3 years old (19–67 years) and 46.6% of them were female. Median follow-up time was 57 months in UC and 65 months in Crohn’s disease (CD). Infliximab experience rate before ADA in UC and CD was 36.4%, 42.6%, respectively. CD’s related surgery rate was 43.5%; surgery rate 87.5% before ADA therapy and 12.5% after ADA treatment. Clinical and endoscopic remission rates were 81.8% / 63.6% and 89.4%/ 63.4 in UC and CD, respectively at the end of follow-up period. Loss of response rate was 20% in UC and 28.3% in CD (table). Mean months for loss of response were 42 ± 25.4 months and 29.7 ± 12 months in UC and CD, respectively. Clinical remission was obtained by dose escalation in 66% of CD patients who had response loss. Loss of response rate was not significantly different between IFX naive and IFX experienced patients (p > 0.05). There was no significant adverse event during the follow-up period. Conclusion In real life, the efficacy of ADA treatment is high in mild-to-moderate active IBD. Endoscopic remission was also acceptable for this group of patients.

scholarly journals Safety of Biologic Therapy in Liver Transplant Recipients: Case Closed?

2019 ◽  
Vol 26 (6) ◽  
pp. 960-960
Author(s):  
Brian C Davis
Keyword(s):  
Inflammatory Bowel Disease ◽  
Liver Transplantation ◽  
Biologic Therapy ◽  
Transplant Recipients ◽  
Long Term Outcomes ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection ◽  
Inflammatory Bowel ◽  
Liver Transplant Recipients

Patients with inflammatory bowel disease who undergo liver transplantation may be considered for biologic therapy, but providers should closely monitor for infections such as cholangitis and Clostridioides difficile infection. Further research in prospective registries with long-term outcomes is needed.

scholarly journals De-escalation of IBD Therapy: When, Who, and How?

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Akbar K Waljee ◽  
Natapat Chaisidhivej ◽  
Sameer D Saini ◽  
Peter D R Higgins
Keyword(s):  
Inflammatory Bowel Disease ◽  
Side Effects ◽  
Biologic Therapy ◽  
Successful Therapy ◽  
Disease Exacerbation ◽  
Inflammatory Bowel ◽  
Practical Guidance ◽  
Biologic Medication ◽  
Risk Of Relapse

Abstract When patients with inflammatory bowel disease reach clinical remission with biologic therapy, a question that often comes up is, “when can I stop my biologic medication?” This is a question fraught with challenges for both physicians and patients. For physicians, there are valid concerns that stepping down from a successful therapy will lead to relapse and disease exacerbation, and that stepping down could lead to anti-biologic antibodies. For patients, the question is often driven by concerns about long-term side effects and costs of biologics. This review provides an overview of the rationale for, and risks of, withdrawal of IBD therapy. Selected studies have shown how to identify subsets of patients in whom de-escalation can be performed with low risk of relapse. Practical guidance on when and how to de-escalate IBD therapy is provided.

scholarly journals P389 Post induction infliximab trough levels predict long-term endoscopic remission in paediatric patients with inflammatory bowel disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S362-S363
Author(s):  
K van Hoeve ◽  
E Dreesen ◽  
I Hoffman ◽  
M Ferrante ◽  
S Vermeire
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Clinical Remission ◽  
Drug Exposure ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Endoscopic Remission ◽  
Inflammatory Bowel ◽  
Trough Levels

Abstract Background Although higher infliximab (IFX) trough levels (TL) have been associated with better outcomes, the ideal predictive sampling time and cut-points to achieve endoscopic remission remain unclear in children with inflammatory bowel disease (IBD). Therefore, we evaluated the pharmacokinetics of IFX during induction to predict long-term outcome of IFX. Methods All children with Crohn’s disease (CD) or ulcerative colitis (UC) starting IFX therapy (5 mg/kg at weeks 0–2–6–12) for active luminal disease from May 2017 till May 2019 were followed prospectively. IFX levels were measured by Ridascreen IFX Monitoring ELISA (TL at weeks 2–6–12, peak at weeks 0–2–6 and intermediate at weeks 1–4). IFX levels and cumulative drug exposure (area under the curve (AUC) till week 12) were correlated with the outcome at month 6. Clinical remission was defined as PUCAI/PCDAI <10, biochemical remission as CRP ≤5 mg/l + ESR ≤20 mm/h, endoscopic remission as SES-CD <3 or Mayo endoscopic sub-score = 0 and deep remission if both clinical + endoscopic remission. Results were analysed using Mann–Whitney U-test (presented as median [IQR]). Results A total of 252 serum induction levels were included from 32 patients (20 CD and 12 UC; 38% male; median age at start of IFX 13.8 years [11.3–14.9]; 84% on concomitant thiopurines). Clinical remission was achieved in 24 (75%) patients and 18 (56%) were in endoscopic remission (all in deep remission) at month 6. Endoscopic remission at month 6 was associated with significantly higher median IFX TL at week 4 (38.8 µg/ml [24.3–46.0] vs. 23.5 µg/ml [10.5–36.6], p = 0.017), at week 6 (19.9 µg/ml [10.1–26.3] vs. 11.1 µg/ml [3.7–19.9], p = 0.031), at week 12 (9.6 µg/ml [5.5–11.9] vs. 3.5 µg/ml [2.7–7.2], p = 0.004; fig1.) and higher AUC week 0–12 (4574.7 µg*day/ml [3783.0–5160.8] vs. 3722.9 µg*day/ml [3102.2–3991.9], p = 0.008). Median IFX TL at week 12 were significantly higher in children with clinical remission (8.6 µg/ml [5.1–12.0] vs. 4.3 µg/ml [3.1–5.9], p = 0.033), but not for biological remission (6.7 µg/ml [4.0–12.0] vs. 4.3 µg/ml [1.2–7.2], p = 0.250; Figure 2) at month 6. ROC analysis identified an IFX TL at week 12 ≥ 5.0 µg/ml and an AUC weeks 0–12 ≥ 4056.0 µg*day/ml as minimal target to achieve endoscopic remission at mo. 6 (AUROC: 0.796 [95% CI: 0.62–0.97] and AUROC: 0.778 [95% CI: 0.61–0.94], respectively; Figure 3.). Height, haemoglobin and PCDAI score at start of IFX therapy, significantly correlated with week 12 IFX TL. Conclusion Adequate IFX exposure during induction in paediatric IBD patients is associated with significantly better clinical, endoscopic and deep remission rates at month 6. Model-informed precision dosing can assist physicians to achieve optimal exposure during induction more precisely (and rapidly) what is essential for an optimal outcome.

scholarly journals DOP52 Safety of Inflammatory Bowel Disease drugs during pregnancy and breastfeeding: Mothers and babies’ outcomes (DUMBO registry)

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S086-S088
Author(s):  
M Chaparro ◽  
M García Donday ◽  
C Calviño Suarez ◽  
S Rubio ◽  
M Figueira ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Immunosuppressive Treatment ◽  
Safety Data ◽  
European Medicines Agency ◽  
Serious Adverse Events ◽  
Clinical Safety ◽  
Inflammatory Bowel ◽  
Active Disease

Abstract Background Prospective registries are necessary to evaluate the safety of inflammatory bowel disease (IBD) treatment during pregnancy and in children in the long term. Aims The overall aim of DUMBO registry is to know the risk of serious adverse events (SAEs) during pregnancy and in children up to 4 years of age exposed during pregnancy to drugs for IBD (mainly focused on biologics), compared to unexposed children. In this analysis we aim to evaluate the risk of SAEs during pregnancy and the predictive factors of it (mainly focused on IBD drugs). Methods Prospective, observational and multicentre registry, which enrols pregnant women with IBD (Crohn’s disease, ulcerative colitis, IBD-unclassified) over 5 years in 70 centres in Spain. The registry was kicked off in September 2019. SAE was defined based on “Clinical Safety Data Management: Definitions and Standards for Expedited Reporting by European Medicines Agency”. Study protocol is summarized in figure 1. Results 433 women have been included so far; 241 got pregnant at least 9 months before this interim analysis (table 1). Mean age was 34 years, and 17% of women had active disease at any time during pregnancy. 23% of pregnancies were exposed to immumodulators (thiopurines), 25% to biologics and 10% to combo therapy (biologics and immunomodulators). 85 pregnancies (35%) were exposed to biologics (60 anti-TNF, 17 ustekinumab, and 8 vedolizumab) either in combo or in monotherapy. There were 237 newborns (227 singleton and 5 pair of twins), 9 miscarriages and 1 abortion. 72% of patients had vaginal delivery and 28% C-sections (18% due to perianal CD or active disease). A total of 59 pregnancies (24.5%) reported at least one SAE: 32% in exposed to biologics and 20.5% in non-exposed group (p>0.05) (figure 2). Four out of 17 pregnancies exposed to ustekinumab and 3 out of 8 exposed to vedolizumab had SAEs (non-related with the drug). In the multivariate analysis, adjusted by disease activity, in comparison with no immunosuppressive treatment, neither immunosuppressants [Odds ratio (OR)=1.1, 95% confidence interval (CI)=0.3–4.3] nor biologics in monotherapy or in combo (OR=0.8; 95%CI=0.2–3) were associated with higher risk of SAEs. 40 patients (17%) were hospitalised due to complications during pregnancy or delivery (figure 3). Two patients underwent surgery during pregnancy due to IBD complications Conclusion IBD treatment (either immunomodulators or biologics) does not increase the risk of SAEs during pregnancy. Nevertheless, one-quarter of IBD women suffer SAEs during pregnancy and about 20% need hospitalisation, which should be taken into account when managing IBD during pregnancy.

Mo1857 - Vedolizumab Levels During Induction are Associated with Long-Term Clinical and Endoscopic Remission in Patients with Inflammatory Bowel Disease

2018 ◽  
Vol 154 (6) ◽  
pp. S-827-S-828
Author(s):  
Andres J. Yarur ◽  
Alexandra Bruss ◽  
Brandon Berens ◽  
Caroline Fox ◽  
Poonam M. Beniwal-Patel ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Endoscopic Remission ◽  
Inflammatory Bowel
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