Factors Predicting Loss of Remission in Crohn's Disease Patients in Endoscopic Remission in the Real World: Results From TARGET-IBD.

Background: There is limited evidence that histologic remission improves outcomes in Crohn's disease (CD). We aimed to characterize a cohort of patients with CD in endoscopic remission and explore factors associated with subsequent loss of remission (LOR).

Methods: In total, 4474 patients were enrolled in TARGET-IBD, a longitudinal, observational cohort study.

Ozanimod in Patients With Moderate to Severe Ulcerative Colitis Naive to Advanced Therapies.

Background & Aims: The pivotal phase 3 True North (TN) study demonstrated the efficacy and safety of ozanimod in patients with moderately to severely active ulcerative colitis. This analysis assessed ozanimod during TN and the ongoing open-label extension (OLE) in patients with active disease who were naive to advanced therapies (ATs).

Methods: TN was a randomized, double-blind, placebo-controlled trial consisting of 10-week induction period and 42-week maintenance period.

Cardiovascular Safety of Ozanimod in Patients With Ulcerative Colitis: True North and Open-Label Extension Analyses.

Background & Aims: Evaluating cardiovascular safety of sphingosine 1-phosphate (S1P) receptor modulators is warranted due to S1P receptor expression on cardiomyocytes and vascular endothelial cells. This analysis reports the cardiovascular safety of ozanimod, an S1P receptor modulator, in patients with moderately to severely active ulcerative colitis from the phase 3 True North (TN) and open-label extension (OLE).

Methods: All patients who received ozanimod in TN (n = 796) and all eligible TN patients who entered the OLE (n = 823) were included.

Considerations for Colorectal Neoplasia Detection in Inflammatory Bowel Disease Clinical Trials.

Background: High-quality colonoscopic surveillance can lead to earlier and increased detection of colorectal neoplasia in patients with inflammatory bowel disease (IBD). In IBD clinical trials, endoscopy is used to assess mucosal disease activity before and after treatment but also provides an opportunity to surveil for colorectal neoplasia during follow-up.

Summary: Best practices for colorectal cancer identification in IBD clinical trials require engagement and collaboration between the clinical trial sponsor, site endoscopist and/or principal investigator, and central read team.

Artificial intelligence in inflammatory bowel disease: implications for clinical practice and future directions.

Inflammatory bowel disease encompasses Crohn's disease and ulcerative colitis and is characterized by uncontrolled, relapsing, and remitting course of inflammation in the gastrointestinal tract. Artificial intelligence represents a new era within the field of gastroenterology, and the amount of research surrounding artificial intelligence in patients with inflammatory bowel disease is on the rise. As clinical trial outcomes and treatment targets evolve in inflammatory bowel disease, artificial intelligence may prove as a valuable tool for providing accurate, consistent, and reproducible evaluations of endoscopic appearance and histologic activity, thereby optimizing the diagnosis process and identifying disease severity.

Artificial Intelligence in Inflammatory Bowel Disease Endoscopy: Implications for Clinical Trials.

Artificial intelligence shows promise for clinical research in inflammatory bowel disease endoscopy. Accurate assessment of endoscopic activity is important in clinical practice and inflammatory bowel disease clinical trials. Emerging artificial intelligence technologies can increase efficiency and accuracy of assessing the baseline endoscopic appearance in patients with inflammatory bowel disease and the impact that therapeutic interventions may have on mucosal healing in both of these contexts.

Declining Enrolment and Other Challenges in IBD Clinical Trials: Causes and Potential Solutions.

Background: Rates of enrolment in clinical trials in inflammatory bowel disease [IBD] have decreased dramatically in recent years. This has led to delays, increased costs and failures to develop novel treatments.

Aims: The aim of this work is to describe the current bottlenecks of IBD clinical trial enrolment and propose solutions.

Poor Patient-Reported Outcomes and Impaired Work Productivity in Patients With Inflammatory Bowel Disease in Remission.

Background And Aims: This study aimed to evaluate associations between disease severity, patient-reported outcomes (PROs), and work productivity in patients with inflammatory bowel disease (IBD [Crohn's disease (CD) and ulcerative colitis (UC)]).

Methods: Patients diagnosed with CD or UC enrolled in CorEvitas' IBD Registry (May 2017 to September 2019) were included (N = 1543; CD, n = 812; UC, n = 731). Disease severity was assessed using the Harvey-Bradshaw Index (CD) and partial Mayo Score (UC); psychosocial PROs (Patient-Reported Outcomes Measurement Information System [PROMIS]) and work productivity (Work Productivity and Activity Impairment [WPAI]) were assessed.

Identification of poor prognostic joint locations in an early rheumatoid arthritis cohort at risk of rapidly progressing disease: a post-hoc analysis of the Phase III AGREE study.

Background: Rheumatoid arthritis (RA) is a heterogeneous disease with established poor prognostic factors such as seropositivity, joint damage, and high disease activity at an early, treatment-naïve stage of disease. However, few studies have examined if specific joint locations are correlated with these factors in such a population. This analysis explored the potential correlation of individual swollen and erosive joints with other disease characteristics at baseline and with remission rates in a post-hoc analysis of the Phase III randomized AGREE study.

Prediction of flare following remission and treatment withdrawal in early rheumatoid arthritis: post hoc analysis of a phase IIIb trial with abatacept.

Background: Drug-free remission is a desirable goal in rheumatoid arthritis (RA) for both patients and clinicians. The aim of this post hoc analysis was to investigate whether clinical and magnetic resonance imaging (MRI) variables in patients with early RA who achieved remission with methotrexate and/or abatacept at 12 months could predict disease flare following treatment withdrawal.

Methods: In the AVERT study of abatacept in early RA, patients with low disease activity at month 12 entered a 12-month period with all treatment discontinued (withdrawal, WD).

Implementation of the OMERACT Psoriatic Arthritis Magnetic Resonance Imaging Scoring System in a randomized phase IIb study of abatacept in psoriatic arthritis.

Objectives: To investigate if the OMERACT PsA MRI Scoring System (PsAMRIS), including a novel total inflammation score, shows sensitivity to change with an agent (abatacept) known to impact clinical outcomes in PsA.

Methods: We performed a post hoc analysis of a randomized phase IIb study of abatacept in patients with PsA and inadequate DMARD response. Participants received one of three abatacept dosing regimens [ABA3, ABA10 or ABA30/10 mg/kg (30 mg/kg switched to 10 mg/kg after two doses)] or placebo until day 169, then ABA10 through day 365.

P038 Ozanimod First-Dose Cardiac Effects in Patients with Moderately to Severely Active Ulcerative Colitis and Relapsing Multiple Sclerosis.

Background: Ozanimod, an oral sphingosine 1-phosphate (S1P) receptor modulator that selectively targets S1P1 and S1P5, is approved in the US for treating moderately to severely active ulcerative colitis (UC) and in multiple countries for treating relapsing forms of multiple sclerosis (MS). In a Phase 1 study of ozanimod in healthy participants, first-dose cardiac effects were mitigated with gradual dose escalation. Based on these results, an initial 7-day ozanimod dose escalation regimen was implemented in all Phase 2 and 3 UC and MS trials.

Endoscopy and central reading in inflammatory bowel disease clinical trials: achievements, challenges and future developments.

Central reading, that is, independent, off-site, blinded review or reading of imaging endpoints, has been identified as a crucial component in the conduct and analysis of inflammatory bowel disease clinical trials. Central reading is the final step in a workflow that has many parts, all of which can be improved. Furthermore, the best reading algorithm and the most intensive central reader training cannot make up for deficiencies in the acquisition stage (clinical trial endoscopy) or improve on the limitations of the underlying score (outcome instrument).

Background Glucocorticoid Therapy Has No Impact on Efficacy and Safety of Abatacept or Adalimumab in Patients with Rheumatoid Arthritis.

To date, the impact of background glucocorticoids (GC) on the efficacy and safety of abatacept or adalimumab in patients with active rheumatoid arthritis (RA) is not clearly established. This post hoc analysis of (AMPLE) trial (NCT00929864) compared efficacy and safety outcomes over 2 years in patients treated with abatacept or adalimumab plus background methotrexate (MTX), who continued GC (≤10 mg/day) versus those who were not receiving GC (no-GC). Of 646 randomized patients, 317 received abatacept + MTX (161 GC, 156 no-GC) and 326 received adalimumab + MTX (162 GC, 164 no-GC).

Poor prognostic factors in predicting abatacept response in a phase III randomized controlled trial in psoriatic arthritis.

In ASTRAEA (NCT01860976), abatacept significantly increased American College of Rheumatology criteria 20% (ACR20) responses at Week 24 versus placebo in patients with psoriatic arthritis (PsA). This post hoc analysis explored relationships between prospectively identified baseline characteristics [poor prognostic factors (PPFs) ] and response to abatacept. Patients were randomized (1:1) to receive subcutaneous abatacept 125 mg weekly or placebo for 24 weeks; those without ≥ 20% improvement in joint counts at Week 16 switched to open-label abatacept.

Disease activity measures at baseline predict structural damage progression: data from the randomized, controlled AMPLE and AVERT trials.

Objective: Data from two double-blind, randomized, Phase III studies were analysed to investigate the ability of Routine Assessment of Patient Index Data 3, DAS28 (CRP), modified (M)-DAS28 (CRP) and Simplified or Clinical Disease Activity Indices to predict structural damage progression in RA.

Methods: This post hoc analysis included data from the 2-year Abatacept vs adaliMumab comParison in bioLogic-naïvE RA subjects with background MTX (AMPLE) trial in biologic-naïve patients with active RA (<5 years) and an inadequate response to MTX, and the 12-month treatment period of the Assessing Very Early Rheumatoid arthritis Treatment (AVERT) trial in MTX-naïve patients with early RA (⩽2 years) and poor prognostic indicators. Adjusted logistic regression analysis assessed the relationship between baseline disease activity and structural damage progression (defined as change from baseline greater than the smallest detectable change) at 12 and 24 months in AMPLE and 6 and 12 months in AVERT.

Efficacy of Abatacept and Adalimumab in Patients with Early Rheumatoid Arthritis With Multiple Poor Prognostic Factors: Post Hoc Analysis of a Randomized Controlled Clinical Trial (AMPLE).

Introduction: Patients with rheumatoid arthritis (RA) with poor prognostic factors, such as seropositivity for anti-citrullinated protein antibodies and early erosions, may benefit from early intensive treatment. However, information to guide physicians on the best choice of therapy in these patients is limited. The objective of this study was to describe the efficacy of subcutaneous abatacept versus adalimumab over 2 years in patients with seropositive, erosive early RA in the AMPLE study.

Baseline Objective Inflammation by Magnetic Resonance Imaging as a Predictor of Therapeutic Benefit in Early Rheumatoid Arthritis With Poor Prognosis.

Objective: High magnetic resonance imaging (MRI)-detected inflammation is associated with greater progression and poorer outcomes in rheumatoid arthritis (RA). This analysis aimed to determine if baseline MRI inflammation was related to clinical response and remission in the Assessing Very Early Rheumatoid arthritis Treatment (AVERT) study.

Methods: AVERT was a phase IIIb, randomized, controlled trial with a 12-month, double-blind treatment period enrolling patients with early (≤2 years' duration), anti-citrullinated peptide-positive methotrexate (MTX)-naive RA.

Determining MRI Inflammation Targets When Considering a Rheumatoid Arthritis Treat-to-Target Strategy: Results of a Randomized, Placebo-Controlled Trial.

Introduction: Magnetic resonance imaging (MRI) is increasingly used in patients with rheumatoid arthritis (RA) to determine residual inflammation after treatment and as a predictor of structural damage progression. Establishing an optimal threshold of inflammatory activity that predicts lower risk of structural damage progression may inform treatment decisions. This post hoc analysis investigated whether patients with RA at low risk of structural damage progression can be identified based on MRI inflammation thresholds.

Body mass index and treatment response to subcutaneous abatacept in patients with psoriatic arthritis: a analysis of a phase III trial.

Objective: This analysis of the phase III Active PSoriaTic Arthritis RAndomizEd TriAl (ASTRAEA) evaluated the effect of baseline body mass index (BMI) on subsequent response to subcutaneous (SC) abatacept in patients with psoriatic arthritis (PsA).

Methods: In ASTRAEA, patients with active PsA were randomised (1:1) to receive blinded weekly SC abatacept 125 mg or placebo for 24 weeks. Treatment response at week 24 was assessed by the proportions of patients achieving American College of Rheumatology 20% improvement response, Disease Activity Score in 28 joints (DAS28 (C reactive protein (CRP))) ≤3.

Correction to: On-drug and drug-free remission by baseline symptom duration: abatacept with methotrexate in patients with early rheumatoid arthritis.

The article "On-drug and drug-free remission by baseline symptom duration: abatacept with methotrexate in patients with early rheumatoid arthritis", written by Vivian P.Bykerk, was originally published Online First without open access.

Improved patient-reported outcomes in patients with psoriatic arthritis treated with abatacept: results from a phase 3 trial.

Background: To explore the effect of abatacept treatment on patient-reported outcomes (PROs) in psoriatic arthritis (PsA).

Methods: Patients with PsA were randomised (1:1) to subcutaneous abatacept 125 mg weekly/placebo for 24 weeks with early escape (EE) to open-label abatacept (week 16). Adjusted mean changes from baseline to weeks 16 (all patients) and 24 (non-EE responders) in Health Assessment Questionnaire-Disability Index (HAQ-DI), Short Form-36 (SF-36; physical and mental component summary and domains), Dermatology Life Quality Index and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) were evaluated.