P103 CLINICAL SERIOUS ADVERSE EVENTS OF INFLIXIMAB IN PEDIATRIC INFLAMMATORY BOWEL DISEASE: A LONG TERM RETROSPECTIVE STUDY

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.

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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

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.676 ◽

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.

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High anti-TNFα Concentrations are Not Associated With More Adverse Events in Pediatric Inflammatory Bowel Disease

Journal of Pediatric Gastroenterology and Nutrition ◽

10.1097/mpg.0000000000003240 ◽

2021 ◽

Vol Publish Ahead of Print ◽

Author(s):

Maya Zvuloni ◽

Manar Matar ◽

Rachel Levi ◽

Dror S. Shouval ◽

Raanan Shamir ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Adverse Events ◽

Bowel Disease ◽

Pediatric Inflammatory Bowel Disease ◽

Inflammatory Bowel

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Adverse Events Associated with Azathioprine Treatment in Korean Pediatric Inflammatory Bowel Disease Patients

Pediatric Gastroenterology Hepatology & Nutrition ◽

10.5223/pghn.2013.16.3.171 ◽

2013 ◽

Vol 16 (3) ◽

pp. 171 ◽

Cited By ~ 7

Author(s):

Ji Young Chun ◽

Ben Kang ◽

Yoo Min Lee ◽

Soo Youn Lee ◽

Mi Jin Kim ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Adverse Events ◽

Bowel Disease ◽

Pediatric Inflammatory Bowel Disease ◽

Azathioprine Treatment ◽

Inflammatory Bowel

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Efficacy of Anti-TNF Therapy for the Treatment of Patients with Moderate-to-Severe Inflammatory Bowel Disease; a First Iranian Report

Middle East Journal of Digestive Diseases ◽

10.15171/mejdd.2020.158 ◽

2019 ◽

Vol 12 (1) ◽

pp. 12-18

Author(s):

Samaneh Mohagheghi Darehranj ◽

Sudabeh Alatab ◽

Homayoon Vahedi ◽

Anahita Sadeghi ◽

Alireza Sima ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Adverse Events ◽

Bowel Disease ◽

National Level ◽

Complete Response ◽

Drug Discontinuation ◽

Serious Adverse Events ◽

Inflammatory Bowel ◽

One Year ◽

First Time

BACKGROUND The anti-TNF drugs are shown to be highly effective in treatment of patients with moderate-tosevere inflammatory bowel disease (IBD). Here, we aimed to assess the efficacy and safety of antiTNF therapy at the national level. METHODS IBD patients aged 15 > years who received Infliximab and/or CinnoRA® between 2013 to July 2018 were identified. The data extracted from medical dossier and telephonic interview. The efficacy of therapy was defined as time to drug discontinuation or need for IBD-related surgery. The safety was assessed based on patient’s reported adverse events. RESULTS We included 315 patients. The mean age of patients was 37.2 years and 62.2% of them developed the disease before age 30 years. Involvement of masculoskeletal system was reported in 7.3% of patients. Partial and complete response to Anti-TNF therapy was seen in 67% of patients. About 16% of patients did not respond to induction therapy and 16.9% of patients lost their response to Anti-TNF during one year. No serious adverse events, serious opportunistic infection, tuberculosis and malignancies reported by patients. Two patients reported pneumonia. CONCLUSION This study for the first time in our country, provides the evidences for efficacy of anti-TNF therapy in moderate to severe IBD patients.

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

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab073.091 ◽

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.

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Genetic Predictors of Long-term Response to Anti-TNF Agents in Pediatric Inflammatory Bowel Disease

Journal of Pediatric Gastroenterology and Nutrition ◽

10.1097/mpg.0000000000002840 ◽

2020 ◽

Vol Publish Ahead of Print ◽

Author(s):

Sara Salvador-Martín ◽

Ferrán Bossacoma ◽

Gemma Pujol-Muncunill ◽

Víctor Manuel Navas-López ◽

Carmen Gallego-Fernández ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Pediatric Inflammatory Bowel Disease ◽

Genetic Predictors ◽

Inflammatory Bowel ◽

Term Response

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Safety and Optimal Timing of BCG Vaccination in Infants Born to Mothers Receiving Anti-TNF Therapy for Inflammatory Bowel Disease

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjaa099 ◽

2020 ◽

Vol 14 (12) ◽

pp. 1780-1784 ◽

Cited By ~ 1

Author(s):

Sang Hyoung Park ◽

Hyo Jong Kim ◽

Chang Kyun Lee ◽

Eun Mi Song ◽

Sang-Bum Kang ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Adverse Events ◽

Bowel Disease ◽

Optimal Timing ◽

Third Trimester ◽

Serious Adverse Events ◽

Bcg Vaccination ◽

The Third ◽

Gestational Week ◽

Inflammatory Bowel

Abstract Backgrounds and Aims We aimed to evaluate the safety of Bacille Calmette–Guérin [BCG] vaccination in infants born to mothers receiving anti-tumour necrosis factor [anti-TNF] therapy for inflammatory bowel disease. Methods Adverse events of BCG vaccination were evaluated in 90 infants who were last exposed to anti-TNF agents at a median of gestational week 30. Results After receiving BCG vaccination at a median age of 6 months [range, 0.25–11 months], three infants [3.3%] showed injection site swelling, two of whom also showed axillar lymphadenopathy. The rates of adverse events were similar between infants who were last exposed to anti-TNF agents before the third trimester [n = 35] and those who were last exposed in the third trimester [n = 55] [2.9% vs 3.6%; p = 1.00]. All adverse events were spontaneously resolved and there were no serious adverse events such as active tuberculosis infection or death. Conclusions BCG vaccination after 6 months of age is of low risk in infants exposed to anti-TNF agents in utero.

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