bluuebunny/crossref_metadata_2025_split huggingface dataset:
P466 Real-world effectiveness and safety of golimumab in patients with ulcerative colitis: 52-weeks of post-marketing surveillance data in Japan
Authors: Nakamura S , Asano T , Tanaka Y , Sugimoto K , Yoshigoe S , Suzuki Y 
Published: January 2022

Abstract

Background
Golimumab (GLM) is an anti-TNF-α drug approved for treating ulcerative colitis (UC). Although its efficacy and safety were well established in clinical trials, real-world evidence was still limited. In the present study, we evaluated 52-week effectiveness and safety of GLM treatment for UC based on post-marketing surveillance data.

Methods
The prospective, post-marketing study was conducted in 393 patients from 163 medical facilities. Patients who had been prescribed GLM were enrolled between May 2017 and September 2019 in Japan. In accordance with Japanese indication, patients received subcutaneous injections of GLM, 200 mg at week 0, 100 mg at weeks 2 and 6, followed by 100 mg every 4 weeks. Clinical remission (partial Mayo score ≤2), predictors of remission, adverse drug reactions (ADRs), and predictors of ADR development were determined at week 52.

Results
Of 393 enrolled patients, 391 and 386 were included in safety and efficacy analysis set, respectively (Table 1). Overall, clinical remission in the intention-to-treat population was 13.0%, 53.9%, 52.6%, 48.2%, and 43.3% at baseline (BL) and at week 6, 22, 36, and 52, respectively (Table 2). In biologic naïve group, clinical remission was 9.2%, 59.1%, 61.0%, 52.4%, and 47.0% at BL and week 6, 22, 36, and 52, respectively, while in biologic experienced group, it was 15.8%, 50.0%, 46.4%, 45.0%, and 40.5% at BL and week 6, 22, 36, and 52, respectively. At week 52, clinical remission rate in the patients who concomitantly used corticosteroid (CS) at BL was significantly lower than that in the patients who did not receive CS (p=0.017, 37.3% vs 49.2%) (Fig. 1). No significant difference in remission rate was observed between immunomodulator (IM) users and IM non-users at baseline. From multivariate analysis, concomitant use of CS (p=0.001, odds ratio [OR] =0.488, 95% CI [confidence interval] 0.314–0.759) and partial Mayo remission at BL (p&lt;0.001, OR=4.329, 95% CI 2.056–9.115) were identified as independent factors associated with clinical remission. ADRs occurred in 71 patients (18.2%). The most common ADR was rash, reported in 9 patients (2.3%). Serious ADRs occurred in 40 patients (10.2%). The most frequent serious ADR was UC, reported in 8 patients (2.0%). In multivariate analysis, the presence of comorbidities was associated with ADR incidence (OR=2.000, 95% CI 1.183–3.380).

Conclusion
From the Japanese post-marketing data, the real-world effectiveness of GLM treatment was confirmed in both biologic naïve and experienced populations. Safety profile was generally consistent with previous findings, and no additional safety signals were identified. Concomitant use of CS, but not IM, may be likely to affect outcome of GLM therapy.
P469 Infliximab for induction of medically-induced remission in Crohn’s disease: a Cochrane systematic review
Authors: Radford S , Sinopoulou V , Gordon M , Eldragini M E A A , Darie A M , Akobeng A , Moran G W 
Published: January 2022

Abstract

Background
Infliximab is a monoclonal antibody that binds and neutralizes tumour necrosis factor-alpha, which is present in high levels in the blood serum, mucosa and stool of patients with Crohn’s disease (CD). We sought to determine the effectiveness and safety of infliximab in inducing remission in patients with CD.

Methods
On 31 August 2021, we searched CENTRAL, CINAHL, ClinicalTrials.gov, Embase, MEDLINE, and WHO ICTRP with no language, date, publication status, or document type limitations. We included randomized controlled trials (RCTs) in which infliximab was compared to placebo or another active comparator in adult (18 and over) patients with active CD. The review authors independently conducted data extraction and ‘Risk of bias’ assessment of the included studies. We expressed dichotomous and continuous outcomes as risk ratios and mean differences with 95% confidence intervals. We assessed the certainty of the evidence using GRADE methodology. The primary outcome was the proportion of patients who achieved clinical remission.

Results
We included 9 RCTs (1130 participants). Three studies compared multiple arms with different infliximab doses (between 5mg and 20mg/kg) to placebo. Two studies each with three arms compared azathioprine and placebo, infliximab and placebo, or infliximab and azathioprine combined. One study compared infliximab with biosimilar CT-P13. One study compared infliximab and azathioprine with steroids and azathioprine and only infliximab if no response. The final study compared a single dose (5mg/kg) of infliximab to placebo. In all trials that didn’t require a purine analogue to be given to both study groups, they allowed such concomitant use in both groups. There is evidence that infliximab combined with azathioprine is superior to azathioprine combined with placebo in inducing clinical remission for CD (RR 1.97, 95% CI 1.60–2.42, moderate certainty evidence downgraded due to risk of bias, NNT = 3). Sensitivity analysis considering a fixed effects model and then removing a study where most received azathioprine in both groups instead of all, had no impact on the result, which remained significant. There is evidence that there may be no difference in withdrawals from adverse events between infliximab combined with azathioprine and azathioprine combined with placebo when inducing clinical remission for CD (RR 0.74, 95% CI 0.29–1.86, low certainty evidence downgraded due to serious imprecision). The evidence is uncertain for all other comparisons and outcomes due to imprecision from small sample sizes.

Conclusion
There is evidence that infliximab with azathioprine is probably better than azathioprine, however the remaining data is based on limited total patient numbers and offers limited scope for meta-analysis.
P480 Comparison of executive functioning profiles among adults with Crohn’s disease and Ulcerative colitis
Authors: Zelnik Yovel D , Meyer S , Richter V , Shirin H , Broide E 
Published: January 2022

Abstract

Background
Psychological factors that influence inflammatory bowel disease (IBD) outcome can impact patients’ ability to cope and aid the management of the disease. Executive functions (EFs) are cognitive processes, which enable the achievement of selected goals and overcoming new challenges. The role of EFs in the management of IBD is still not fully understood.
We assess the EFs in IBD patients and compare EFs between patients with Crohn’s disease (CD) and ulcerative colitis (UC).

Methods
An anonymous online survey, including demographic, clinical data and the validated self-report BRIEF-A questionnaire, was sent to adult IBD patients. BRIEF-A score above 65 is considered an impaired EF. Logistic regression was used to study the association between disease type (UC vs CD) and suspected EF deficits, while controlling for potential cofounders by use of a propensity score.

Results
148 IBD patients (34% UC) with mean age of 31.5 years old (50% females) were included. BRIEF-A scale and index scores were within the normal range (&lt;65). Most of the scores were significantly better in CD than UC patients: shift (57.9 vs 52.7, p=0.015), monitor (50.54 vs 46.24, p=0.029), working memory (57.83 vs 52.18, p=0.03), plan (54.97 vs 49.2, p=0.005), organization of materials (52.95 vs 48.98, p=0.019). CD patients had a better Global Executive Composite (59.27 vs 53.7, p=0.008).

Conclusion
IBD patients in the study had normal EF profiles assessed by the BRIEF-A questionnaire. However, UC and CD patients presented different executive profiles. Understanding these differences can enable interventions that may improve patient’s quality of life.
P482 Pre-screening IBD patients starting biologic therapies, a positive single centre quality improvement project
Authors: Colclough J , Ali M , Shami N , Aitchison L , Hurst A , Shams-Khan H 
Published: January 2022

Abstract

Background
Biologic therapies have revolutionised the management of IBD however their use can be associated with opportunistic infections and malignancy. BSG guidance1 outlines the necessary pre-screening investigations required before starting these treatments. We assessed our compliance with these guidelines before and after implementing a proforma led SOP to evaluate whether there was any improvement in clinical practice.

Methods
A pre-screening checklist proforma was created for all IBD patients starting biologic therapies at Southport and Ormskirk hospital and compliance with BSG guidelines was measured before and after its implementation. Data was collected retrospectively using electronic patient records over two 12-month cycles; pre-implementation (Nov 2018 – Oct 2019) and post-implementation (Feb 2020 – Jan 2021).

Results
31 patients (42% female, median age 48, range 19–84) were started on biologics before the checklist was implemented and 25 after (40% female, median age 40, range 17–73). Compliance with screening tests for baseline bloods and infections improved from 58.1% to 100%, with the largest improvements in Hep B and TB. See figure 1. Checking patient’s vaccination history improved from 0% to 88% and adequate cervical screening improved from 3.2% to 66.7%. Overall, 80% of patients met full BSG pre-screening guidelines following implementation of the proforma, compared to 0% prior to this.

Conclusion
The use of a pre-screening checklist has drastically improved the pre-screening process from 0% compliance to 88%, therefore improving patient safety prior to starting biologic therapies. This data compares favourably with national audit data where only 60% of patients had adequate pre-screening2. It has allowed us to standardise care to screen for contraindications to treatment, especially opportunistic infections. There is still room for improvement when assessing patients’ vaccination and cervical screening histories, however these rely on documentation of the discussion in notes and may underestimate the number of patients receiving this advice.
Overall we have shown a dramatic improvement in the quality of our care and therefore patient safety. We will continue to use the checklist as well as educating staff within the hospital about the importance of pre-screening before starting patients on biologic therapies.

References
1. Lamb CA, et al. British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut 2019;68:s1-s106.
2. Arnott I, et al. 2016. National clinical audit of biological therapies. Royal College of Physicians. https://www.rcplondon.ac.uk/projects/outputs/national-clinical-audit-biological-therapies-annual-report-2016.
P483 Patient-reported quality of life, anxiety, and depression associated with switching originator infliximab to biosimilar
Authors: Ritter T E , Mehta S A , Van Anglen L J 
Published: January 2022

Abstract

Background
Non-medical switching from biologics to biosimilars is becoming increasingly common. Previous studies have demonstrated efficacy and safety of switching originator to biosimilar infliximab in inflammatory bowel disease (IBD) patients. Limited data exist on patient-reported quality of life (QOL) and possible emotional duress associated with these switches. The purpose of this study was to describe the impact of non-medical switches to infliximab biosimilars on QOL, anxiety, and depression.

Methods
This was a retrospective review of all IBD patients switched from originator to infliximab biosimilar at a large multicenter gastroenterology private practise in Texas. Patients were asked to complete standardised questionnaires on a quarterly basis beginning 3/2021, concurrent with large US payor policy changes mandating non-medical biosimilar switches. The Short Inflammatory Bowel Disease Questionnaire (SIBDQ) was used to assess disease-specific QOL. The Hospital Anxiety and Depression Scale (HADS) was used to determine anxiety and depression. All questionnaires through 10/2021 were collected and designated as “pre” or “post” based on the date of the patient’s non-medical switch to infliximab biosimilar. Wilcoxon rank sum test was used to compare scores. We also performed subset analyses on patients with both “pre” and “post” questionnaires with paired t-test.

Results
From 3/2021 to 10/2021, a total of 81 questionnaires were submitted by 54 patients who underwent non-medical switches to an infliximab biosimilar. 30 questionnaires were submitted prior to (“pre”) and 51 questionnaires were submitted after (“post”) the non-medical switch. Median “pre” SIBDQ score was 58 (IQR 53–63). Median “pre” HADS-Anxiety and HADS-Depression score were 3.5 (IQR 1–6) and 1 (IQR 0–5), respectively. As shown in Figure 1, “post” scores were unchanged [SIBDQ 59 (IQR 54–63); HADS-Anxiety 3 (IQR 1–7); HADS-Depression 2 (IQR 1–4)]. Subset analyses included 14 patients who submitted both “pre” and “post” questionnaires. Similarly, no significant changes were observed [Figure 2].

Conclusion
Non-medical switches to infliximab biosimilar did not affect QOL or mental health. To our knowledge, this is the first biosimilar switch study to incorporate anxiety and depression measures. These relationships should continue to be assessed.
P490 Patients with inflammatory bowel disease should be vaccinated against pneumococcus and influenza despite immunosuppressive therapy
Authors: Dohos D , Müller K E , Sipos Z , Kiss S , Dembrovszky F , Kovács N , Solymár M , Erőss B , Hegyi P , Sarlós P 
Published: January 2022

Abstract

Background
Patients with inflammatory bowel disease (IBD) have a high risk for infection. Pneumonia related to influenza and pneumococcal infection is one of the most common infection-related complication in IBD. Our aim was to evaluate the immunogenicity of pneumococcal and influenza vaccination in patients with IBD receiving different treatment.

Methods
We searched four databases for studies evaluating seroprotection and seroconversion rates after influenza or pneumococcal vaccination in IBD. In meta-analysis, odds ratios (OR) were calculated with 95% confidence intervals (CI).

Results
Twelve studies (1429 patients) were included in this meta-analysis. The seroconversion rate after pneumococcal vaccination was significantly lower in the immunosuppressed group and in the subgroup of patients with anti-TNF mono- or combination therapy compared to the non-immunosuppressed patients (OR = 0.38, 95% CI: 0.23–0.62, OR = 0.28, 95% CI: 0.15–0.53, and OR = 0.27, 95% CI: 0.15–0.49, p &lt; 0.001, respectively). Following influenza vaccination there was no significant difference in the seroprotection rate between immunosuppressed and non-immunosuppressed patients (OR = 0.59, 95% CI: 0.34–1.03, p = 0.065). Seroprotection rate was not significantly reduced in patients with immunomodulator compared to anti-TNF monotherapy or combination therapy (OR = 1.45, 95% CI: 0.62–3.38, p = 0.84 and OR = 0.91 95% CI: 0.37–2.22, p = 0.391, respectively). Following both vaccinations, the seroresponse was not significantly reduced in patients treated with immunomodulator monotherapy compared to non-immunosuppressed patients.

Conclusion
Our results suggest that response rate is reduced in patients treated with anti-TNF therapy but not in patients treated with immunomodulator monotherapy. Patients treated with immunosuppressive treatment should be vaccinated against pneumococcus and influenza despite immunosuppressive therapy.
P492 A comparison of treatment effects for clinical, endoscopic and histological remission in ulcerative colitis clinical trials
Authors: Sedano R , Hogan M , Zou G , Narula N , Singh S , Ma C , Jairath V 
Published: January 2022

Abstract

Background
Clinical remission, defined by the Mayo Clinic Score (MCS) or modified MCS, is the accepted regulatory endpoint in drug development for ulcerative colitis (UC). Whilst histologic remission is a more stringent outcome, recent trials have reported numerically higher rates compared to endoscopic or clinical remission rates at the same timepoint, suggesting that histologic remission may be a more sensitive endpoint for detecting treatment response

Methods
A systematic review was performed from inception to December 2020, including all placebo-controlled drug trials for adults with UC. Clinical, endoscopic, and histologic induction remission rates for active treatment and placebo arms were pooled on the logit scale using a random-effects model to account for both between- and within-study variability. Risk ratios (RR) and risk differences comparing the rate of remission in active treatment arms to the rate of remission in placebo arms were also pooled using a random-effects model.

Results
For induction trials, 15/84 reported clinical, endoscopic, and histologic remission rates at the same timepoint. Clinical remission was mostly defined as a MCS≤2 with no individual subscore&gt;1 (10/15;66.6%), and endoscopic remission as MES=0 (6/15; 40%) or MES≤1 (9/15; 60%). Histologic remission was defined using Geboes score in 10/15(66.7%) trials, with a score≤1.0 in 4/10(40%), score=0 in 3/10(30%), and score&lt;3.0 in 3/10(30%) trials. For placebo/active treatment arms, the pooled clinical, endoscopic, and histologic remission rates were 11.3%(95% CI 7.4–16.9%) /17.8%(95% CI 13.7–22.8%), 13.4%(95% CI 8.5–20.5%) /18.7% (95% CI 12.2–27.5%), and 18.2%(95% CI 13.8–23.6%) /27%(95% CI 20.6–34.7%), respectively(Figure 1). The differences in pooled clinical, endoscopic, and histologic remission rates between active treatment and placebo were 7.2%(95% CI 4.3%–10.1%), 6.6% (95% CI 2.5%–10.7%), and 8.4% (95% CI 4.3%–12.4%), respectively(Figure 2A), and the pooled RR comparing clinical, endoscopic, and histologic remission rates in the active treatment and placebo arms were 1.59 (95%CI 1.19–2.13), 1.49 (95%CI 1.16–1.90), and 1.47 (95%CI 1.20–1.81), respectively(Figure 2B)

Conclusion
Histologic remission has been proposed as a treatment target for patients with UC, given an association between this outcome and lower rates of clinical relapse.1 Although we found numerically higher pooled histologic remission rates for active treatment and placebo arms, compared to pooled clinical and endoscopic remission rates, we found no difference in the pooled RR for clinical, endoscopic, and histologic remission rates in the active treatment and placebo arms. Whilst histology has the potential to serve as a more efficient endpoint for drug development, more studies are needed.
P506 Rates of clinical remission among patients with Ulcerative Colitis from real-world clinical practice settings from Germany
Authors: Bokemeyer B , Picker N , Kromer D , Rosin L , Patel H 
Published: January 2022

Abstract

Background
Patients with Ulcerative Colitis (UC) may not equally respond to advanced therapies. Therapy modifications such as dose adjustments, augmentation, and use of corticosteroids (CS) are required to achieve remission. This study aimed to examine the rates of clinical remission requiring adjustments with advanced therapies among UC patients from real-world clinical practices in Germany.

Methods
Using a retrospective chart review, patients with UC treated with an advanced therapy (adalimumab, infliximab, golimumab, vedolizumab, and tofacitinib) between 01/2017 through 09/2019 were selected from 18 outpatient gastroenterology practices across Germany. Patients with at least 12 months of data before (baseline) and after initiating an advanced therapy (Index Date) were included. Data was collected up to 24 months after index date. Clinical remission was assessed based on a partial Mayo score ≤1. Among patients with remission, therapy adjustments were assessed based on the following: Dose escalation, augmentation with conventional therapies, CS use for ≥12 weeks, or any use of CS during the maintenance phase. Time to remission was analysed using Kaplan-Meier analysis and associated factors were assessed within a multivariate Cox regression model. Patients were censored at end of the study period or if they discontinued or switched the index therapy.

Results
Among 149 patients included (females: 50.3%; median age: 40 years; median follow-up: 25.9 months), 75 (50.3%) received an anti-TNF agent, 48 (32.2%) vedolizumab, and 26 (17.4%) tofacitinib. Of these, 96 (64.4%) patients were biologic-naïve, and 42 patients (28.2%) were receiving concurrent CS at the index date. Within one year, remission was achieved in 49 out of 134 patients (46.1%; median time: 19.3 months [95%-CI: 7–24 months]; Figure 1). Among patients with remission at 24 months, therapy adjustments were required in 35.8% of patients. Most common adjustments included dose escalation (9.0%) and use of CS during the maintenance phase (11.9%). In an adjusted model, chances of remission were halved in biologic-experienced patients vs. naïve patients (hazard ratio [HR]: 0.49; p&lt;0.05), while patients with concurrent use of conventional therapy at baseline were associated with a higher chance of achieving remission (HR: 1.82; p&lt;0.05).

Conclusion
Less than half of UC patients treated with advanced therapies in Germany achieved clinical remission after one year. More than half of the patients required 1.5 years to achieve clinical remission. Among those who achieved remission within two years, one third required additional therapy modifications. More effective therapies are needed to achieve earlier and better outcomes among patients with UC in Germany.