scholarly journals Incidence comparison of adverse events in patients with inflammatory bowel disease receiving different biologic agents: retrospective long-term evaluation

2021 ◽  
Author(s):  
Brigida Barberio ◽  
Edoardo Vincenzo Savarino ◽  
Timothy Card ◽  
Cristina Canova ◽  
Francesco Baldisser ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Adverse Events ◽  
Bowel Disease ◽  
Biologic Agents ◽  
Term Evaluation ◽  
Inflammatory Bowel

scholarly journals THE SAFETY, TOLERABILITY, AND EFFECTIVENESS OF BIOLOGICS/SMALL MOLECULE THERAPY IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE AND CIRRHOSIS

2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S45-S46
Author(s):  
Muyi Li ◽  
Sameer Khan ◽  
Deborah Proctor ◽  
Jill Gaidos ◽  
Badr Al-Bawardy
Keyword(s):  
Inflammatory Bowel Disease ◽  
Adverse Events ◽  
Small Molecules ◽  
Small Molecule ◽  
Bowel Disease ◽  
Clinical Remission ◽  
Infusion Reaction ◽  
Mucosal Healing ◽  
Biologic Agents ◽  
Inflammatory Bowel

Abstract Introduction Biologic agents and small molecules have been shown to be effective and relatively safe in the treatment of inflammatory bowel disease (IBD). However, data is lacking regarding the use of these agents in patients with IBD and concomitant cirrhosis. The aim of this study is to examine the safety, tolerability and effectiveness of biologics and small molecules in patients with IBD and concomitant cirrhosis. Methods This is a retrospective study of adult patients diagnosed with both IBD and cirrhosis (by liver biopsy or Fibroscan) treated with biologic agents or small molecule agents between 2012 and 2020 within the Yale-New Haven Hospital system. We included patients on tofacitinib or any of the following biologic agents: infliximab, adalimumab, certolizumab pegol, golimumab, vedolizumab, ustekinumab. Primary outcomes were rates of adverse events (infection, infusion reaction, IBD-related hospitalization) and mortality. Secondary outcomes were clinical remission (defined by the physician global assessment) and mucosal healing (Mayo endoscopic score of 0 or 1 for ulcerative colitis (UC) and absence of erosion/ulcerations in Crohn’s disease (CD)). Results A total of 18 patients (72% CD, 28% UC) with median age of 50 (26–73) years were included (Table 1). Decompensated cirrhosis was present in 33.3% of the population prior to initiation of biologic/small molecule therapy. The most common etiology of cirrhosis was primary sclerosing cholangitis at 38.9%. IBD therapy included: infliximab/adalimumab (44.5%), vedolizumab (27.7%), and ustekinumab (22.2%) and tofacitinib (5.6%). A total of 4 patients (22.2%) were on concomitant corticosteroid therapy and 3 on combination therapy with thiopurines (Table 2). Adverse events occurred in 27.7% (n=5; 1 infusion reaction and 4 infections). The 4 patients with infections included: 2 on infliximab/adalimumab, 1 on ustekinumab, 1 on vedolizumab. Two of these patients were on concomitant thiopurines and 1 on corticosteroid. Biologic therapy was stopped in 3 patients, 2 for non-response and 1 for an infusion reaction. Mortality rate was 11% and all were liver-related. Clinical remission was achieved in 66.7% and mucosal healing was noted in 72.7% (8/11). Conclusions In this cohort of patients with IBD and cirrhosis, biologic/small molecule therapies were effective for IBD. Approximately a quarter of patients experienced adverse events that were mainly due to infections. Larger studies are needed to elucidate the relative safety of different biologic agents and small molecules in IBD patients with cirrhosis.

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 P477 Italian real-life study evaluating the long-term effectiveness of vedolizumab for the treatment of inflammatory bowel disease: the elderly cohort

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S419-S422
Author(s):  
D Pugliese ◽  
G Privitera ◽  
A Armuzzi
Keyword(s):  
Inflammatory Bowel Disease ◽  
Adverse Events ◽  
Bowel Disease ◽  
Real Life ◽  
Treatment Persistence ◽  
Diagnosis Of Cancer ◽  
Inflammatory Bowel ◽  
New Diagnosis

Abstract Background Vedolizumab (VDZ) is the first biological therapy for Inflammatory Bowel Disease (IBD) tested, in pivotal trials, on patients up to 80 years old and has usually been presented as a safer choice in frail patients. However, real-world data on the effectiveness and safety of VDZ in elderly (≥ 65 years) are scarce. The aim of this study is to explore the effectiveness and safety of VDZ in a large real-life cohort of elderly IBD patients, with a 2 years follow-up. Methods The Long-term Italian Vedolizumab Effectiveness (LIVE) study included CD and UC patients started on VDZ from April 2016 to June 2017 at 40 centres of the Italian Group for the study of inflammatory bowel disease (IG-IBD). Patients were prospectively followed-up to June 2019. Co-primary endpoints were to evaluate cumulative VDZ treatment persistence and safety. Results Of 966 patients, 174 (18%; 81 CD, 93 UC) were ≥ 65 years old at enrolment. Mean disease duration at baseline was 10.9 years ± SD10 (CD 12.5 ± 11, UC 9.6 ± 9). VDZ was used as a first biologic therapy in 78 patients (44.8%). 25 patients (14.4%) had a history of previous cancer. The majority of CD patients had a stricturing behaviour (45, 55.6%) and had already undergone surgery (41, 49.4%). 48 UC patients (51.6%) had extensive colitis. Moderate-to-severe endoscopic activity was present in 80% of CD and in 92% of UC, according to SES-CD and endoscopic Mayo score, respectively. Cumulative VDZ treatment persistence at 12 and 24 months was 71.8% (71.6% CD and 72.0% UC) and 54% (54.2% CD and 53.8%% UC), respectively. 52.9% (40 CD; 52 UC), 4.0%, 3.5%% and 2.9% of patients were on concomitant steroids at baseline, 6, 12, and 24 months, respectively. Clinical remission at 12 and 24 months was achieved in 28.7% (31 CD and 29 UC) and in 31.6% (25 CD and 30 UC) of patients. Mean C-reactive protein was 15.6 mg/l ± SD 20 (CD 15.9 ± 21; UC 15.2 ± 19) at baseline and dropped to 8.4 mg/l ± 10 (CD 8.0 ± 8, UC 8.9 ± 11) at 12 months and to 5.9 mg/l ± 6 (CD 5.8 ± 5, UC 6 ± 7) at 24 months. Dose escalation was necessary for 20.3% and 24.7% of patients within the first 12 and 24 months. 44 adverse events were reported: 16 infections.,6 new diagnosis of cancer/dysplasia (2 colon, 1 kidney, 1 prostate, 1 lung, 1 melanoma), 4 arthritis, 3 skin rash, 2 drug-induced cholestasis,11 miscellaneous. 11 patients (6.3%) underwent VDZ withdrawal because of adverse events (6 new diagnosis of cancer/dysplasia; 4 infections; 1 cholestasis). One patient died for pneumonia complications. Conclusion In this preliminary analysis of the largest reported real-world cohorts of elderly IBD patients treated with VDZ, up to 55% of patients persisted on therapy after two years; an acceptable safety profile was observed throughout the entire follow-up period.

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 Efficacy, safety and drug survival of thioguanine as maintenance treatment for inflammatory bowel disease: a retrospective multi-centre study in the United Kingdom

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Ahmed B. Bayoumy ◽  
Elsa L. S. A. van Liere ◽  
Melek Simsek ◽  
Ben Warner ◽  
Aathavan Loganayagam ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
United Kingdom ◽  
Adverse Events ◽  
Clinical Response ◽  
Bowel Disease ◽  
Multi Centre Study ◽  
The United Kingdom ◽  
Inflammatory Bowel

Abstract Background Thioguanine (TG) is a thiopurine which has been used for patients with inflammatory bowel disease (IBD), who have failed azathioprine (AZA) or mercaptopurine (MP) due to adverse events or suboptimal response. Its widespread use has been hampered due to concerns about nodular regenerative hyperplasia (NRH) of the liver. The aim of this study was to investigate the long-term efficacy and safety of low-dose TG therapy in IBD patients failing AZA and MP. Methods A retrospective multicentre study was performed in IBD patients who failed prior treatment with conventional thiopurines with or without following immunomodulation (thiopurine-allopurinol, biologicals, methotrexate, tacrolimus) and were subsequently treated with TG as rescue monotherapy between 2003 and 2019 at three hospitals in the United Kingdom. Clinical response, adverse events, laboratory results, imaging and liver biopsies were retrospectively collected. Results A total of 193 patients (57% female and 64% Crohn’s disease) were included, with a median daily TG dose of 20 mg (range: 20–40 mg), a median treatment duration of 23 months (IQR 10–47) and a median follow-up of 36 months (IQR 22–53). The clinical response rate at 12 months was 65 and 54% remained on TG until the end of follow-up. Adverse events consisted primarily of elevated liver tests (6%), myelotoxicity (7%) and rash (5%). NRH was histologically diagnosed in two patients and two other patients (1%) developed non-cirrhotic portal hypertension. The median 6-TGN and TPMT levels were 953 pmol/8 × 105 RBC (IQR 145–1761) and 47 mu/L (IQR 34.5–96). Conclusions Long-term follow-up suggests that TG can be an effective and well-tolerated therapy in more than half of difficult-to-treat and multi-therapy failing IBD patients. Findings of this study indicate that TG can be used safely and the occurrence of hepatotoxicity was low. The incidence rate of NRH was within the background incidence.

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, <30 ng/mL/<100 ng/mL with transferrin saturation <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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