Sa1120 The Effect of Anti-Drug Antibodies on Adverse Events Profile in Patients With Crohn's Disease Treated With Certolizumab Pegol: Results of an Integrated Safety Analysis From Clinical Trials

ObjectiveTo review long-term certolizumab pegol (CZP) safety across all approved indications: rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), psoriasis (PSO) and Crohn’s disease (CD).MethodsData were pooled across 49 UCB-sponsored CZP clinical trials (27 RA, one axSpA, one PsA, five PSO, 15 CD) to August 2017. Serious adverse events (SAEs) of interest (infections, malignancies, autoimmunity/hypersensitivity events, major adverse cardiovascular events (MACE), gastrointestinal (GI) perforations, psoriasis events, laboratory abnormalities) and deaths were medically reviewed by an external expert committee, using predefined case rules. Incidence rates (IRs)/100 patient-years (PY) are presented by indication; standardised mortality and malignancy rates were calculated using WHO/GLOBOCAN/SEER databases. Pregnancies with maternal CZP exposure are also reported.ResultsOf 11 317 CZP-treated patients across indications (21 695 PY CZP exposure; maximum: 7.8 years), infections were the most common SAEs (overall IR: 3.62/100 PY; IRs ranged from 1.50/100 PY(PSO) to 5.97/100 PY(CD)). The IR for malignancies was 0.82/100 PY, including lymphoma (0.06/100 PY). MACE and GI perforation IRs in CZP-treated patients were 0.47/100 PY and 0.08/100 PY and were highest in RA and CD, respectively. Patients with PSO had the lowest SAE rates. The incidence of deaths and malignancies aligned with expected general population data.ConclusionThis extensive overview of the CZP safety profile in clinical trials, across all indications, provides large-scale confirmation of previous reports. No new safety signals or relevant non-disease-related laboratory abnormalities were identified. The study demonstrated some indication-specific differences in certain SAE rates that may be attributable to the underlying inflammatory disease.

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Efficacy and safety of certolizumab pegol therapy for 26 weeks in an unselected Crohn's disease population: Results of the FACTS II survey

Zeitschrift für Gastroenterologie ◽

10.1055/s-0030-1263685 ◽

2010 ◽

Vol 48 (08) ◽

Author(s):

SR Vavricka ◽

A Schöpfer ◽

G Bansky ◽

J Binek ◽

C Felley ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Certolizumab Pegol ◽

Efficacy And Safety

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Prebiotics and Probiotics in Inflammatory Bowel Disease: Where are we now and where are we going?

Current Clinical Pharmacology ◽

10.2174/1574884715666200312100237 ◽

2020 ◽

Vol 15 (3) ◽

pp. 216-233 ◽

Cited By ~ 1

Author(s):

Maliha Naseer ◽

Shiva Poola ◽

Syed Ali ◽

Sami Samiullah ◽

Veysel Tahan

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Clinical Trials ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Adverse Effects ◽

Bowel Disease ◽

Relapse Prevention ◽

Remission Induction ◽

Inflammatory Bowel

The incidence, prevalence, and cost of care associated with diagnosis and management of inflammatory bowel disease are on the rise. The role of gut microbiota in the causation of Crohn's disease and ulcerative colitis has not been established yet. Nevertheless, several animal models and human studies point towards the association. Targeting intestinal dysbiosis for remission induction, maintenance, and relapse prevention is an attractive treatment approach with minimal adverse effects. However, the data is still conflicting. The purpose of this article is to provide the most comprehensive and updated review on the utility of prebiotics and probiotics in the management of active Crohn’s disease and ulcerative colitis/pouchitis and their role in the remission induction, maintenance, and relapse prevention. A thorough literature review was performed on PubMed, Ovid Medline, and EMBASE using the terms “prebiotics AND ulcerative colitis”, “probiotics AND ulcerative colitis”, “prebiotics AND Crohn's disease”, “probiotics AND Crohn's disease”, “probiotics AND acute pouchitis”, “probiotics AND chronic pouchitis” and “prebiotics AND pouchitis”. Observational studies and clinical trials conducted on humans and published in the English language were included. A total of 71 clinical trials evaluating the utility of prebiotics and probiotics in the management of inflammatory bowel disease were reviewed and the findings were summarized. Most of these studies on probiotics evaluated lactobacillus, De Simone Formulation or Escherichia coli Nissle 1917 and there is some evidence supporting these agents for induction and maintenance of remission in ulcerative colitis and prevention of pouchitis relapse with minimal adverse effects. The efficacy of prebiotics such as fructooligosaccharides and Plantago ovata seeds in ulcerative colitis are inconclusive and the data regarding the utility of prebiotics in pouchitis is limited. The results of the clinical trials for remission induction and maintenance in active Crohn's disease or post-operative relapse with probiotics and prebiotics are inadequate and not very convincing. Prebiotics and probiotics are safe, effective and have great therapeutic potential. However, better designed clinical trials in the multicenter setting with a large sample and long duration of intervention are needed to identify the specific strain or combination of probiotics and prebiotics which will be more beneficial and effective in patients with inflammatory bowel disease.

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Letter: assessment of histological disease activity in Crohn's disease clinical trials—a step in the right direction, but further optimisation needed

Alimentary Pharmacology & Therapeutics ◽

10.1111/apt.16450 ◽

2021 ◽

Vol 54 (4) ◽

pp. 541-542

Author(s):

Andrew H. Tsoi ◽

Anand Murugasu ◽

Mayur Garg

Keyword(s):

Clinical Trials ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Disease Activity ◽

The Right

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P089 REAL-WORLD EXPERIENCE: CLINICAL AND ENDOSCOPIC EFFECTIVENESS OF STANDARD VEDOLIZUMAB DOSING AND MODIFIED MAINTENANCE DOSING IN PATIENTS WITH MODERATE-SEVERE CROHN’S DISEASE

Inflammatory Bowel Diseases ◽

10.1093/ibd/zaa010.187 ◽

2020 ◽

Vol 26 (Supplement_1) ◽

pp. S75-S75

Author(s):

Scott D Lee ◽

Anand Singla ◽

Caitlin Kerwin ◽

Kindra Clark-Snustad

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Adverse Events ◽

Real World ◽

Clinical Remission ◽

Mucosal Healing ◽

Clinical Disease ◽

Endoscopic Remission ◽

Starting Dose

Abstract Background Vedolizumab (VDZ) is an effective treatment for Crohn’s disease (CD); however, inadequate and loss of response is common. Pivotal VDZ trials evaluated alternative dosing intervals, demonstrating numeric but not statistical superiority in efficacy as compared to FDA-approved dosing. The safety and effectiveness of FDA-approved and modified-dosing schedules in a real-world population are unknown. We aimed to evaluate clinical and endoscopic effectiveness & safety of standard and modified maintenance VDZ dosing in a real world cohort. Methods We retrospectively reviewed CD patients (pts) treated with >3 months VDZ, assessing Harvey Bradshaw Index (HBI), Simple Endoscopic Score for Crohn’s disease (SESCD), Short Inflammatory Bowel Disease Questionnaire (SIBDQ), C-reactive protein (CRP), albumin and hematocrit prior to and following standard VDZ dosing, and prior to and following modified VDZ maintenance dosing. We measured duration on therapy and adverse events. Results We identified 226 eligible pts, mean age 41.5 years, 55.3% female, median disease duration 10 years, 88.9% with prior biologic exposure. Mean duration on VDZ was 28.3 months. Standard VDZ dosing: 61.5% of pts with active clinical disease and adequate follow up data achieved clinical response after 3–12 months; 41.0% had clinical remission. 51.9% of pts with active endoscopic disease and adequate follow up data achieved mucosal improvement; 42.3% had endoscopic remission; 26.0% had mucosal healing after 3–24 months. 50.0% of pts with elevated CRP and adequate follow up data normalized CRP after 3–12 months. Modified maintenance dosing: 72 non-remitters to standard VDZ dosing received modified VDZ maintenance dosing. 51.5% of pts with active clinical disease prior to starting dose modification and adequate follow up data achieved clinical response after 3–12 months of modified maintenance dosing; 42.4% had clinical remission. 22.2% of pts with SESCD ≥3 prior to starting dose modification achieved mucosal improvement after 3–24 months; 22.2% had mucosal healing. 26.7% of pts with SESCD ≥4 prior to starting modified dosing had endoscopic remission after 3–24 months. 50.0% of pts with elevated CRP and adequate follow up data normalized their CRP after 3–12 months. Safety: 82.7% of pts reported ≥1 adverse events, most commonly infection and worsening CD symptoms. Discussion Standard VDZ dosing resulted in clinical and endoscopic improvement in pts with moderate-severe CD, with prior exposure to multiple advanced therapies. For non-remitters to standard dosing, modified VDZ maintenance dosing improved clinical disease activity in ∼50% of pts and improved endoscopic disease activity in ∼20% of pts, suggesting that for pts who did not achieve remission with standard VDZ dosing, modified VDZ dosing may result in clinical and endoscopic improvement.

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