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.

scholarly journals Belgian IBD Research Group [BIRD] Position Statement 2019 on the Use of Adalimumab Biosimilars in Inflammatory Bowel Diseases

2019 ◽  
Vol 14 (5) ◽  
pp. 680-685 ◽  
Author(s):  
Michaël Somers ◽  
Peter Bossuyt ◽  
Marc Ferrante ◽  
Harald Peeters ◽  
Filip Baert
Keyword(s):  
Inflammatory Bowel Disease ◽  
Research Group ◽  
Bowel Disease ◽  
Inflammatory Diseases ◽  
Safety Data ◽  
Position Statement ◽  
European Medicines Agency ◽  
Immune Mediated ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Abstract The emergence of biosimilars is generally considered as an opportunity to guarantee accessibility to affordable treatments and to enhance financial sustainability of national health systems. Since 2017, five biosimilars of adalimumab were approved by the European Medicines Agency [EMA] for use in inflammatory bowel disease: ABP 510, SB5, GP2017, FKB327, and MSB11022. In this position statement, the available efficacy and safety data of the different adalimumab biosimilars in immune-mediated inflammatory diseases are summarised. Furthermore, the Belgian IBD research group [BIRD] formulates statements concerning the use of adalimumab biosimilars in inflammatory bowel disease.

scholarly journals The safety of drugs for inflammatory bowel disease during pregnancy and breastfeeding: the DUMBO registry study protocol of GETECCU

2021 ◽  
Vol 14 ◽  
pp. 175628482110180
Author(s):  
María Chaparro ◽  
María G. Donday ◽  
Francisco Abad-Santos ◽  
Francisco Javier Martín de Carpi ◽  
Miguel Ángel Maciá-Martínez ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Safety Data ◽  
Severe Infection ◽  
Controlled Study ◽  
Registry Study ◽  
Binary Logistic Regression Model ◽  
Serious Adverse Events ◽  
Severe Infections ◽  
Inflammatory Bowel

Background: Active disease during conception and pregnancy in women with inflammatory bowel disease (IBD) increases the risk of pregnancy complications and adverse neonatal outcomes. The use of IBD treatments during pregnancy should be weighed against their adverse effects on the neonate, but longer-term safety data and data on serious infection rates and malignancies postnatally are lacking, particularly for newer drugs, such as tofacitinib, vedolizumab and ustekinumab. Methods: This ongoing, prospective registry study being conducted at 70 centres in Spain is enrolling pregnant women who are ⩾18 years, are at any point in pregnancy up to the end of the second trimester and have a diagnosis of Crohn’s disease, ulcerative colitis or unclassified IBD. Patients will receive treatment decided independently by their IBD specialist. Each incident gestation will be followed up through pregnancy and the first 4 years postnatally. Three cohorts will be compared: biologicals exposed, immunomodulatory exposed and non-exposed. The primary endpoint is the risk of severe infection in newborns postnatally up to 4 years of age; other endpoints include serious adverse events (SAEs) such as pregnancy and delivery complications, neonatal SAEs, development [Ages and Stages Questionnaire-3 (ASQ3)], and malignancy incidence, up to 4 years of age. IBD specialists will collect maternal data (baseline/end of each trimester/1 month post-delivery), neonatal birth data, and the SAE and ASQ3 data in children exposed during pregnancy, reported every 3 months by the mother. Statistical analysis will include summary statistics for quantitative variables, comparisons of qualitative variables with significance set at p < 0.025 and a binary logistic regression model to determine the risk factors for severe infections. Results: Enrolment began in September 2019 and study completion is expected in September 2028. Conclusions: This prospective, controlled study will provide evidence on the long-term safety profile in children after intrauterine and lactation exposure to biological and immunomodulatory IBD treatments, including data on postnatal severe infections, development and malignancies. ClinicalTrials.gov identifier: NCT03894228

scholarly journals Long-term effectiveness, safety and immunogenicity of the biosimilar SB2 in inflammatory bowel disease patients after switching from originator infliximab

2021 ◽  
Vol 14 ◽  
pp. 175628482098280
Author(s):  
Sarah Fischer ◽  
Sarah Cohnen ◽  
Entcho Klenske ◽  
Heike Schmitt ◽  
Francesco Vitali ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Adverse Events ◽  
Disease Activity ◽  
Bowel Disease ◽  
Serious Adverse Events ◽  
Mayo Score ◽  
Normal Ranges ◽  
Inflammatory Bowel ◽  
The Individual

Background: Long-term data on inflammatory bowel disease (IBD) patients switched from originator to biosimilar infliximab SB2 are lacking. The aim of the conducted study was to investigate the effectiveness, immunogenicity and safety of a large prospectively followed-up IBD patient cohort that was entirely switched from originator infliximab to biosimilar SB2 treatment. Methods: This was a prospective, single-center, longitudinal, observational study describing clinical outcomes in IBD patients, over an 80-week period following switch from originator infliximab to SB2. Primary outcome measures were change of disease activity [Harvey-Bradshaw Index for Crohn’s disease (CD), partial Mayo Score for ulcerative colitis (UC)], C-reactive protein (CRP), infliximab trough levels (TLs), anti-drug antibodies (ADAs) and adverse events. Results: One hundred and forty-four IBD patients (94 CD, 50 UC), with median duration of 30.5 months’ (range 2–110) treatment with originator infliximab were evaluated. Mean change of disease activity compared with baseline was −0.9 (SD 2.6), –0.4 (2.2) and –0.4 (2.0) in CD; 0.1 (1.1), 0.1 (1.1) and 0.1 (1.3) in UC patients at weeks 24, 48 and 72. Median infliximab TLs were 6.2 µg/ml (interquartile range 2.3–12.2), 5.0 µg/ml (2.7–10.0), 6.6 µg/ml (3.5–12.4) and 5.1 µg/ml (2.7–10.9) at baseline and weeks 24, 48 and 72. Median CRP levels were within normal ranges throughout the study. After the switch, 9.8% of the patients developed new ADAs. Persistence on SB2 was 90% (95% confidence interval 0.85–0.95), 79% (0.72–0.86), 72% (0.64–0.80) at weeks 26, 52 and 78. Serious adverse events occurred in 11 patients. Conclusion: Over the individual patient follow-up of 80 weeks, switch to biosimilar SB2 from originator infliximab does not result in increased disease activity or changed immunogenicity patterns. The switch to SB2 was well tolerated.

scholarly journals P548 Efficacy, safety, and pharmacokinetics after switching from infliximab originator to biosimilar SB2 in inflammatory bowel disease patients: A long-term observational, prospective cohort study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S466-S467
Author(s):  
S Fischer ◽  
S Mesfin ◽  
E Klenske ◽  
H Schmitt ◽  
F Vitali ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Cohort Study ◽  
Adverse Events ◽  
Disease Activity ◽  
Bowel Disease ◽  
Patient Visit ◽  
Serious Adverse Events ◽  
Inflammatory Bowel

Abstract Background SB2 is a biosimilar infliximab approved for the treatment of inflammatory bowel disease (IBD) patients. These are the first prospective data investigating long-term efficacy, safety, and pharmacokinetics after switching from infliximab originator to biosimilar SB2 in IBD patients. Methods This is a prospective, observational cohort study of patients that underwent a switch from infliximab originator to biosimilar SB2 in 2017 as part of routine care at the outpatient Clinic for IBD at the University Hospital of Erlangen, Germany. Long-term safety and clinical effectiveness were recorded over a follow-up period of 18-months. Clinical disease activity was assessed by the Harvey–Bradshaw Index (HBI) in Crohn’s disease (CD) and the partial Mayo Score (pMS) in ulcerative colitis (UC) patients. C-reactive protein (CRP) was analyzed at every patient visit, and IFX trough-level (TL) and anti-IFX antibodies (ADA) were measured prior to every SB2 administration, using the Promonitor® tests. The occurrence of adverse events was registered at every patient visit. Results A total of 148 IBD patients (96 CD, 52 UC) was enrolled. The median duration of previous infliximab treatment before the switch was 29 months (range 1.0–110.0). Median disease activity in CD was an HBI of 3 (0–16) at switch (baseline), 2 (0–13) at month 6, 3 (0–15) at month 12 and 2.5 (0–11) at month 18. Median disease activity in UC was a pMS of 0 (0–6) at baseline, 1 (0–4) at month 6, 1 (0–4) at month 12 and 1 (0–5) at month 18. The median TL for all IBD patients was 6.3 mg/ml (0.1–33.7) at baseline, 5.0 mg/ml (0.1–34.3) at month 6, 6.3 mg/ml (0.1–35.8) at month 12 and 5.1 mg/ml (0.1–35.4) at month 18. CRP for all IBD patients was 2.2 mg/l (0.1–45.6) at baseline, 2.2 mg/l (0.1–90.4) at month 6, 2.3 mg/l (0.1–169.5) at month 12 and 2.7 mg/l (0.1–19.8) at month 18. In the 18-month follow-up period, 12/103 (11.7%) of patients who were ADA-negative at baseline developed ADA post-switch. Altogether, 40 (27%) IBD patients discontinued SB2 treatment during the 18-month follow-up period (4 anaphylaxis, 20 loss of response, 7 non-serious and 9 serious adverse events), 2 paused during pregnancy, 1 discontinued in clinical remission, 10 were lost to follow-up (7 change of physician, 3 unknown). Serious adverse events comprised 3 malignancies (breast and prostate carcinoma, neuroendocrine malignancy), 1 liver abscess and 5 intestinal surgical procedures (1 perforation, 1 ileus, and 3 stenoses). Conclusion Switching from IFX originator to biosimilar SB2 was not associated with an increase in disease activity. No clinically meaningful changes in IFX trough levels or immunogenicity were identified. Altogether, SB2 was well tolerated in a real-life setting.

scholarly journals Down-Regulation of Colonic ACE2 Expression in Patients With Inflammatory Bowel Disease Responding to Anti-TNF Therapy: Implications for COVID-19

2021 ◽  
Vol 7 ◽  
Author(s):  
Xiao-Zhi Li ◽  
Yun Qiu ◽  
Louisa Jeffery ◽  
Fen Liu ◽  
Rui Feng ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Protein Expression ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Immunosuppressive Treatment ◽  
Before And After ◽  
Healthy Control ◽  
Inflammatory Bowel ◽  
Factor Α ◽  
Active Disease

Background and Aims: Angiotensin-converting enzyme II (ACE2) is the key molecule for understanding the pathophysiology of COVID-19. The risk of COVID-19 and impact of immunosuppressive treatment on disease course in patients with inflammatory bowel disease (IBD) remain controversial. We aimed to determine the change of intestinal ACE2 expression before and after biologics treatment including anti-tumor necrosis factor α (anti-TNFα), anti-integrin, and anti-interleukin (IL)12/23 in IBD patients.Methods: We analyzed the ACE2 expression through the public database of paired intestinal biopsies from IBD patients before and after biologic therapy. Change of ACE2 RNA and protein expression were validated in two independent cohorts (Birmingham cohort and Guangzhou cohort). The correlation between ACE2 expression and disease activity was also analyzed.Results: Mining information from the GEO database showed that compared with healthy control, intestinal ACE2 expression was downregulated in ileum of CD patients, while upregulated in colon of both CD and UC patients. Colonic ACE2 RNA expression was decreased significantly in patients responding to anti-TNFα but not anti-integrin and anti-IL12/23, which was validated in the Birmingham cohort. Using the Guangzhou cohort including 53 patients matched by pre- and post-anti-TNFα therapy, colonic ACE2 protein expression was significantly downregulated after anti-TNFα treatment in responders (P &lt; 0.001) rather than non-responders. Colonic ACE2 expression was significantly higher in patients with severe histologically active disease compared with those with moderate (P &lt; 0.0001) and mild (P = 0.0002) histologically active disease.Conclusion: Intestinal inflammation influences the expression of intestinal ACE2 in IBD patients, with different alterations in the ileum and colon. Colonic ACE2 expression was downregulated after anti-TNFα therapy in IBD patients responding to treatment. This might provide new clues regarding the risk of SARS-CoV-2 infection and the potential benefit of sustaining anti-TNFα treatment in patients with IBD.

Biosimilars of Adalimumab in Inflammatory Bowel Disease: Are we Ready for that?

2019 ◽  
Vol 25 (1) ◽  
pp. 7-12 ◽  
Author(s):  
Marjorie Argollo ◽  
Gionata Fiorino ◽  
Daniela Gilardi ◽  
Federica Furfaro ◽  
Giulia Roda ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Health Care Providers ◽  
Bowel Disease ◽  
Biological Treatment ◽  
Reference Product ◽  
European Medicines Agency ◽  
Care Providers ◽  
Inflammatory Bowel ◽  
To Receive ◽  
The Ideal

Introduction: Biosimilars present a considerable potential to reduce costs related to clinical management allowing health-care providers to reinvest this money, leading to a wider access to an effective biological treatment with monoclonal antibodies (mAb). Infliximab biosimilars have already been incorporated in daily clinical practice and are currently used in all indications for which the reference product (RP) was approved. Areas covered: In the next few years, also adalimumab biosimilars will become available for the treatment of inflammatory bowel disease (IBD). In fact, several of them (ABP501, BI 695501, GP2017, and SB5) have been approved by the European Medicines Agency (EMA) with the same indications of the reference product (Humira ®). Initial preclinical data proved a strong similarity between all biosimilars and the RP. Moreover, phase 3 studies in rheumatoid arthritis and psoriasis showed no differences in terms of efficacy, safety, and immunogenicity. Data on IBD patients are urgently needed. Expert opinion: Biosimilars of adalimumab showed equivalent clinical efficacy to the RP in other immunemediated diseases. However, defining the ideal patient’s profile to receive or to be switched to a biosimilar, choosing one biosimilar vs. another, or cross-switching among biosimilars, will become the next challenge in IBD.

Novel Targets For Therapeutic Intervention in Inflammatory Bowel Disease. What is the Best Way to Assess the Safety Profile of a Drug?

2019 ◽  
Vol 25 (1) ◽  
pp. 57-63 ◽  
Author(s):  
Clara Yzet ◽  
Stacy S. Tse ◽  
Maia Kayal ◽  
Robert Hirten ◽  
Jean-Frédéric Colombel
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Evaluation Process ◽  
Population Based ◽  
Stage Of Development ◽  
Remission Rates ◽  
Safety Parameters ◽  
Post Marketing ◽  
Inflammatory Bowel

The emergence of biologic therapies has revolutionized the management of inflammatory bowel disease (IBD) by halting disease progression, increasing remission rates and improving long-term clinical outcomes. Despite these well-described benefits, many patients are reluctant to commence therapy due to drug safety concerns. Adverse events can be detected at each stage of drug development and during the post-marketing period. In this article, we review how to best assess the safety parameters of new IBD medications, from the earliest stage of development to population-based registries, with a focus on the special populations often excluded from the evaluation process.

scholarly journals Long-Term Effectiveness of Oral Ferric Maltol vs Intravenous Ferric Carboxymaltose for the Treatment of Iron-Deficiency Anemia in Patients With Inflammatory Bowel Disease: A Randomized Controlled Noninferiority Trial

2021 ◽  
Author(s):  
Stefanie Howaldt ◽  
Eugeni Domènech ◽  
Nicholas Martinez ◽  
Carsten Schmidt ◽  
Bernd Bokemeyer
Keyword(s):  
Inflammatory Bowel Disease ◽  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Primary Endpoint ◽  
Bowel Disease ◽  
Deficiency Anemia ◽  
Ferric Carboxymaltose ◽  
Inflammatory Bowel ◽  
Intent To Treat

Abstract Background Iron-deficiency anemia is common in inflammatory bowel disease, requiring oral or intravenous iron replacement therapy. Treatment with standard oral irons is limited by poor absorption and gastrointestinal toxicity. Ferric maltol is an oral iron designed for improved absorption and tolerability. Methods In this open-label, phase 3b trial (EudraCT 2015-002496-26 and NCT02680756), adults with nonseverely active inflammatory bowel disease and iron-deficiency anemia (hemoglobin, 8.0-11.0/12.0 g/dL [women/men]; ferritin, &lt;30 ng/mL/&lt;100 ng/mL with transferrin saturation &lt;20%) were randomized to oral ferric maltol 30 mg twice daily or intravenous ferric carboxymaltose given according to each center’s standard practice. The primary endpoint was a hemoglobin responder rate (≥2 g/dL increase or normalization) at week 12, with a 20% noninferiority limit in the intent-to-treat and per-protocol populations. Results For the intent-to-treat (ferric maltol, n = 125/ferric carboxymaltose, n = 125) and per-protocol (n = 78/88) analyses, week 12 responder rates were 67% and 68%, respectively, for ferric maltol vs 84% and 85%, respectively, for ferric carboxymaltose. As the confidence intervals crossed the noninferiority margin, the primary endpoint was not met. Mean hemoglobin increases at weeks 12, 24, and 52 were 2.5 vs 3.0 g/dL, 2.9 vs 2.8 g/dL, and 2.7 vs 2.8 g/dL with ferric maltol vs ferric carboxymaltose. Treatment-emergent adverse events occurred in 59% and 36% of patients, respectively, and resulted in treatment discontinuation in 10% and 3% of patients, respectively. Conclusions Ferric maltol achieved clinically relevant increases in hemoglobin but did not show noninferiority vs ferric carboxymaltose at week 12. Both treatments had comparable long-term effectiveness for hemoglobin and ferritin over 52 weeks and were well tolerated.

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