bluuebunny/crossref_metadata_2025_split huggingface dataset:
P358 An observational, prospective cohort study to evaluate the long term safety and effectiveness of intravenous CT-P13 (biosimilar of infliximab) in patients with Crohn’s Disease or Ulcerative Colitis
Authors: Cheon J H , Kang H W , Lee S J , Kim S H 
Published: May 2021

Abstract

Background
CT-P13 is the world’s first approved biosimilar infliximab for all indications of the reference infliximab. The purpose of this study was to assess long term safety and effectiveness of CT-P13 intravenous (IV) in patients with Crohn’s Disease (CD) and Ulcerative Colitis (UC). We now present the result of safety and effectiveness of CT-P13 in patient with CD, UC for up to 5 years from this longitudinal, observational, prospective cohort Phase IV study.

Methods
The study was conducted from 17 April 2014 to 28 February 2020 in 22 and 21 study centres, in Korea and European Union, respectively. Patients were administered 5 mg/kg of CT-P13 by IV at weeks 0, 2 and 6 and every 8 weeks thereafter. The primary objective was to evaluate adverse events of special interest (AESI) including HBV reactivation, congestive heart failure, opportunistic infections, serious infection including sepsis, tuberculosis, serum sickness (delayed hypersensitivity reactions), hematologic reactions, systemic lupus erythematosus/lupus like syndrome, demyelinating disorders, lymphoma, hepatobiliary events, hepatosplenic T cell lymphoma (HSTCL), intestinal or perianal abscess (in CD), serious infusion reactions during a re-induction regimen following disease flare, sarcoidosis/sarcoid-like reactions, paediatric malignancy, leukaemia, malignancy, colon carcinoma, dysplasia (in UC), skin cancer, pregnancy exposure and bowel stenosis, stricture and obstruction (in CD).

Results
A total of 470 patients with inflammatory bowel disease (IBD) were analysed. Overall 352 (74.9%) patients have been continuously treated for more than 1 year and the mean duration of drug exposure was 26.3 months. The safety profile of CT-P13 and switching from the reference infliximab to CT-P13 was well-tolerated. A total of 329 (70.0%) patients experienced at least one treatment-emergent adverse event (TEAE). Adverse events of special interest of CT-P13 were analysed by safety analysis set (Table 1). Immunogenicity testing was optional and 72 (15.3%) patients had at least one ADA positive after first infusion of study drug. The incidence of TEAEs in ADA positive subset (83.3%) were slightly higher compared to the incidence of TEAEs in ADA negative subset (76.6%). The effectiveness results of clinical remission for each indication was generally well maintained after the study drug administration (Table 2).

Conclusion
The results show that CT-P13 was well-tolerated and efficacious in IBD patients. There was no new safety and effectiveness findings in patients who have been exposed to CT-P13 or patients who have switched treatment from the reference infliximab to CT-P13.
P391 Antibiotics in pediatric Inflammatory Bowel Diseases: a systematic review
Authors: Verburgt C , Heutink W P , Kuilboer L I M , Dickmann J D , van Etten-Jamaludin F S , Benninga M A , de Jonge W J , Van Limbergen J E , Tabbers M M 
Published: May 2021

Abstract

Background
Dysbiosis is the central concept in the current thinking regarding IBD pathogenesis. Current available therapies in pediatric Inflammatory Bowel Disease (IBD) focus on targeting the immune system by suppressing the immune response and often fail to sustain long term remission. Antibiotics directly target bacteria but are underrepresented in current (pediatric and adult) IBD treatment guidelines. We aimed to describe available evidence concerning the use of antibiotics in the treatment of pediatric IBD.

Methods
We systematically assessed efficacy and safety of antibiotics in pediatric IBD. CENTRAL, EMBASE (Ovid) and Medline (Pubmed) were searched for Randomized Controlled Trials (RCTs). Quality assessment of included articles was conducted with the Cochrane risk-of-bias tool.

Results
Two RCT’s (n=101, 4.4-18 years, 43% male) were included. Both studies had overall low risk of bias. In mild-to-moderate Crohn’s disease, azithromycin+metronidazole (AZ+MET) (n=35) compared to metronidazole (MET) alone (n=38) did not induce a significantly different response (PCDAI drop ≥12.5 points or remission) (p=0.07). For induction of remission (PCDAI≤10), AZ+MET was more effective than MET (p=0.025). In Acute Severe Colitis, the mean 5-day PUCAI was significantly lower in the antibiotic (vancomycin, amoxicillin, metronidazole, doxycycline)+intravenous corticosteroids (IVCS) group (n=16) compared to IVCS (n=12) alone (p=0.037), whereas remission (PUCAI&lt;10) did not differ (p=0.61). No significant drug-related adverse events were reported.

Conclusion
Our results highlight the lack of evidence in pediatric IBD. More evidence is needed to assess if implementation in daily practice is necessary.
P422 COVID 19 infection in IBD patients treated with biologic therapy-experience from tertiary center in Serbia
Authors: Sokic Milutinovic A , Jevtovic M , Jovicic I 
Published: May 2021

Abstract

Background
COVID 19 pandemic is caused by newly discovered coronavirus that started end of December 2019 and is ongoing. Patients with severe forms of Crohn’s disease (CD) and ulcerative colitis (UC) treated with biologic therapy are considered to be at increased risk of infectious diseases due to the immunosuppressive effect of biologic drugs. Available guidelines recommend that biologic therapy is continued during the pandemic. Since data on COVID 19 infection in this subgroup of IBD patients is limited we aimed to assess presence of risk factors related to virus transmission, incidence and severity of COVID 19 infection in patients on biologic therapy in tertiary center in Serbia.

Methods
Study was conducted in Clinic for Gastroenterology and Hepatology, Clinical center of Serbia. We included 263 IBD patients on biologic therapy in the study (mean age 41±13, 142 males). There were 162 CD and 101 UC patients. Standardized questionnaire was used to assess presence of different risk factors relevant for virus transmission and also symptoms and severity of disease if patient was infected with COVID 19.

Results
Out of 263 patients 41 (22 CD, 19 UC) was COVID 19 positive. Mean age of COVID 19 positive patients was 43±14, 19 were males and 22 females. In COVID 19 positive group 26 patients were on anti-TNF therapy (15 on infliximab and 6 on adalimumab), while 15 were treated with vedolizumab. Risk factors for COVID 19 infection were use of public transportation (p&lt;0.05), active disease (p&lt;0.05), residency in capital city (p&lt;0.05) and presence of COVID 19 infection in a household member (p&lt;0.05). Other factors such as age, sex, blood type, use of conventional immunosuppressive therapy and class of biologic drug did not differ between infected and uninfected group. Pneumonia was diagnosed in 7 patients (17%) and hospital admission was necessary in 4 cases (9.75%). All hospitalized patients were using corticosteroids due to relapse of IBD. Most common symptoms of infection were fever in 26 (63.4%), tiredness in 19 (46.3%) and loss of taste and smell in 17 (41.4%) patients. All patients recovered successfully and none needed mechanical ventilation.

Conclusion
Use of biologic therapy during COVID 19 pandemic is safe in IBD patients. Since we did not observe any fatal outcomes and all patients had mild to moderate COVID 19 presentation it is possible that biologic therapy, especially anti-TNF, has a protective role in preventing cytokine storm during COVID 19 infection.
P427 Efficacy and safety of vedolizumab and adalimumab in Asian adults with moderately to severely active ulcerative colitis: Post-hoc analysis of the VARSITY trial
Authors: Kim J S , Leung W K , Wu D C , Lindner D , Fadeeva O , Demuth D 
Published: May 2021

Abstract

Background
The VARSITY trial, the first head-to-head study comparing the efficacy and safety of biologics in patients with moderately to severely active ulcerative colitis (UC), demonstrated superior clinical remission with vedolizumab (VDZ) versus adalimumab (ADA) at week 52. This post-hoc analysis describes outcomes in patients from Asia included in the VARSITY trial.

Methods
Adult patients with moderately to severely active UC (Mayo score 6–12; endoscopic sub-score ≥2), refractory to conventional therapies and anti–tumour necrosis factor-naïve or -experienced (exposure capped at 25%) were included. This analysis focussed on patients from Hong Kong, Taiwan and South Korea. Patients were randomised (1:1) to receive intravenous (IV) VDZ (300mg) and subcutaneous (SC) placebo on day 1 of weeks 2, 6, 14, 22, 30, 38 and 46 or SC ADA, at weeks 1 (total dose:160mg) and 2 (80mg) and every 2 weeks (40mg) plus IV placebo thereafter until week 50. The primary endpoint was clinical remission at week 52. Secondary endpoints included rates of endoscopic improvement, corticosteroid (CS)-free remission and histological remission at week 52. Patients with missing endpoint assessment at week 52 were considered non-responders. Data were analysed descriptively.

Results
A total of 45 patients (VDZ: n=21; ADA: n=24) were included. At baseline (VDZ and ADA, respectively), the mostly male population (71.4% and 58.3%) had a mean (SD) age of 46.4 (14.7) and 40.4 (15.1) years; severe disease: 33.3% and 54.2%; mean (SD) disease duration: 6.8 (5.5) and 5.4 (3.5) years; and were biologic-naïve: 85.7% and 79.2%. At week 52, a higher rate of clinical remission was achieved in VDZ- vs. ADA-treated patients (28.6% vs. 16.7%; Table). Adverse events (AEs) occurred in 71.4% (VDZ) and 87.5% (ADA) of patients; serious AEs occurred in 4.8% (VDZ) and 16.7% (ADA) of patients. AEs led to study drug discontinuation in 4.8% (VDZ) and 8.3% (ADA) of patients; no deaths occurred.

Conclusion
Patients from Asian countries with moderately to severely active UC achieved higher rates of clinical, CS-free, and histological remission as well as endoscopic improvement with VDZ vs. ADA. VDZ and ADA were both generally safe and well tolerated. Descriptive trends were consistent with findings in the larger VARSITY cohort.
P431 Teduglutide use and nutritional outcomes in short bowel syndrome with intestinal failure: a real-world claims database analysis
Authors: Micic D , Jiang J , Chen L , Fan T , Mu F , Satija A , Downes N , Shrestha S , Wu E , Swallow E , Wojtowicz A , Raphael B P 
Published: May 2021

Abstract

Background
Teduglutide (TED) is a glucagon-like peptide 2 analogue approved for the treatment of patients with short bowel syndrome (SBS) requiring parenteral support (PS). SBS is a rare condition resulting from a reduced absorptive surface area of the small intestine, most commonly due to inflammatory bowel disease (IBD). Patients with SBS with intestinal failure (SBS-IF) remain dependent on PS to maintain adequate calorie, fluid, electrolyte and micronutrient stability. In phase 3 clinical trials, TED reduced PS requirements in patients with SBS-IF. This study aimed to assess PS use and discontinuation rates among patients with SBS on TED using real-world data.

Methods
This retrospective cohort study of adults with SBS-IF (≥18 years) with ≥1 TED pharmacy claim(s) used the US-based administrative healthcare claims IBM MarketScan database (2009–2019). The first TED claim was defined as the index date. Patients required ≥6 months of continuous enrolment prior to index date (baseline period) and no history of malignancy. Primary analysis was conducted during the follow-up period (index date to earliest of continuous enrolment end or 2 years post-index). A sensitivity analysis was also conducted among the cohort during the TED utilization period (index date to the earliest of continuous enrolment end or TED discontinuation). Patients required PS use during both baseline and follow-up/TED utilization periods (primary and sensitivity analyses). PS discontinuation was defined as a PS utilization gap of ≥30 days. A generalized estimating equation linear regression model evaluated if PS use (days/week) changed significantly from baseline to selected time points post-index.

Results
Of 110 identified patients with SBS-IF, mean age was 53.4 (SD 13.2) years and 77 (70%) were women. Included were 51 (46%) patients with Crohn’s disease and 20 (18%) with ulcerative colitis. The main comorbidities were renal disease (23%) and liver disease (15%). PS frequency was 4.6 (2.5), 3.3 (2.9), 2.9 (3.0) and 3.6 (3.0) days/week at baseline and months 6 (p&lt;0.0001), 12 (p&lt;0.0001), and 24 (p=0.0267), respectively. PS discontinuation increased over time to 34.4%, 46.7% and 65.2% at 3, 6, and 12 months, respectively. The sensitivity analysis demonstrated similar rates of PS use and discontinuation.

Conclusion
In this real-world study of adults with SBS-IF, including &gt;50% with IBD, TED was associated with PS reductions comparable to those achieved in clinical trials and higher PS discontinuation rates even when using a conservative analysis approach. Future research will be required to determine individual predictive factors of PS discontinuation.
P433 Sex-based differences in response to tumor necrosis factor inhibitor induction therapy for ulcerative colitis: a pooled analysis of individual patient-level clinical trials data
Authors: Agrawal M , Petralia F , Tepler A , Durbin L , Reinisch W , Colombel J F , Shah S 
Published: May 2021

Abstract

Background
There are increasing data on sex-based differences in IBD epidemiology, phenotype and outcomes. The purpose of this study was to characterize sex-based differences in response to tumor necrosis factor inhibitor (TNFi) therapies in patients with ulcerative colitis (UC).

Methods
We conducted a pooled analysis of individual-level data from randomized clinical trials (RCTs) on induction therapy with infliximab and golimumab, accessed through the Yale University Open Data Access platform. We analyzed patients in the treatment and placebo arms separately. Using multivariable logistic regression modeling, we compared the primary outcome of clinical remission, and secondary outcomes of clinical response and mucosal healing, according to clinical trial definitions, between male and female patients with UC at week 6 (golimumab) or week 8 (infliximab) of induction therapy. Effect estimates were expressed as adjusted odds ratios (aOR) and 95% confidence intervals (CI).

Results
We included 1639 patients (696, 42.5% were women, Table) from two trials using infliximab (ACT-1 and 2) and one trial using golimumab (PURSUIT). Male patients were older than female patients in the treatment arm of the overall cohort [mean age (standard deviation) 31.31 (16.53) years and 29.34 (15.19) years, respectively). All other baseline characteristics, such as sex, race, Mayo score at screening, and concomitant systemic corticosteroid and immunomodulator use were comparable. Compared to female patients, male patients were significantly less likely to achieve clinical remission in both treatment and placebo arms (aOR 0.55, 95% CI 0.31, 0.97 and 0.34, 95% CI 0.15, 0.82, respectively, Figure). Compared to female patients, male patients were significantly less likely to achieve mucosal healing and clinical response in the treatment arm (aOR 0.47, 95% CI 0.27, 0.83 and 0.51, 95% CI 0.29, 0.90, respectively), but there was no significant difference in these secondary outcomes by sex in the placebo arm.

Conclusion
Based on this analysis of pooled data from RCTs, we demonstrate that clinical remission, response and mucosal healing with TNFi induction therapies are less likely in male patients compared to female patients with UC. Clinical remission is also less likely in male patients on placebo. These finding may lead to further research on sex-based differences in treatment outcomes, including mechanistic studies.
P529 Adalimumab persistence and its biosimilar in inflammatory bowel disease: experience in a tertiary centre
Authors: Fernandez Cano M C , Sánchez-Capilla A D , Martín-Rodríguez M M , Cabello-Tapia M J , Redondo-Cerezo E 
Published: May 2021

Abstract

Background
Adalimumab biosimilars experience in real practice is still limited. Some changes in efficacy, safety, adherence or tolerance in comparison with the original could lead to a cessation of this drug. We propose the use of persistence as a reliable parameter to report the absence of drug withdrawal. To date, there are no studies specifically about the persistence of these biosimilars compared to the original and this project aimed to analyze it, in addition to advance concerning safety.

Methods
We performed a retrospective study with 104 patients from our hospital, consecutively selected between 2018–20. Data were obtained from the digital medical record. The primary outcome measure was persistence during 1 year, represented in Kaplan-Meier analysis. We gathered secondary endpoints such as the treatment-emergent adverse events (TEAE), clinical efficacy, serum biomarkers such as protein-C-reactive (CRP) and faecal calprotectin (FC). Were considered mild TEAE which did not require its withdrawal and we were considered severe those which led to discontinuing the drug, needed hospital admission or specialized care.
Clinical response was considered according to Harvey–Bradshaw Index (HBI) (decrease ≥3 below the baseline) or Partial Mayo Index (PMS)( ≤ 2 points below baseline). We considered p &lt; 0.05 as statistical significance.

Results
Our sample included 104 patients divided into 3 groups: 50 received biosimilar (A), 29 original (B), and 25 started with biosimilar but previously had received original (were “denominated mixed group”)(C). The persistence of group A was higher (p =0.04) while concerning adverse reactions, no differences were obtained about mild and there were differences in severe ones (p = 0.009). Group C obtained higher severe TEAE. The inflammatory biomarkers were reduced in a similar proportion in the 3 groups, and 43% had a clinical response to Adalimumab at week 20 without differences between them.

Conclusion
According to our study, patients who received exclusive biosimilar presented a higher persistence. Regarding safety, biosimilars are safe with a similar profile in comparison to the reference drug in most clinical settings. However, based on our data, the switch within the same active principle (from original to biosimilar) could generate interferences in the clinical results and could cause the appearance of TEAEs that would suppose drug withdrawal. These aspects are related to the nocebo effect, and our advice is to avoid this strategy to minimize these negative effects of therapy switch. Further research is needed to improve the knowledge about adalimumab biosimilars with longer follow-up and with larger cohorts including multicentric researches.
P563 Comparison of long-term outcomes of infliximab with adalimumab in biologic naïve patients with Crohn’s disease: a tertiary referral center 13-year experience
Authors: Yuksel I , Durak M B , Kilic V , Kivrakoglu F , Kosar K , Erdogan C , Alkan A 
Published: May 2021

Abstract

Background
The comparative efficacy and safety of infliximab (IFX) and adalimumab (ADA) have shown variable results in biologic-naïve patients with Crohn’s disease (CD). Thus, long-term comparisons between IFX and ADA with or without immunomodulator therapies are still needed.
The purpose of this study was to evaluate the long-term clinical effectiveness and safety profile of IFX compared to ADA in biologic-naïve patients with CD.

Methods
Data of all adult CD patients treated with IFX or ADA as their first biologic agent was collected retrospectively between December 2007 and February 2021. We compared CD-related hospitalization, CD-related major abdominal surgery, steroid use and serious infections leading to treatment cessation.

Results
Out of 224 biologic-naïve patients with CD, 101 started IFX first (median age at onset: 38.12 years, 61.4% male) and 123 started ADA first (median age at onset: 30.2 years, 64.2% male).
Median disease duration was 6.94 years (IQR: 3.82–12.17) and 6.91 years (IQR: 3.94–10.95) for IFX and ADA, respectively, of whom 33% and 37.4% had active smokers, 10.9% and 13.4% had family history of inflammatory bowel disease (IBD) 22.8% and 19.5% had perianal disease, 43.6% and 43.9 had prior major abdominal surgery and 52.6% and 49.6% had extraintestinal manifestations.
There were no significant differences between the two groups with respect to the age at onset of tumor necrosis factor antagonist, gender, smoking status, family history of IBD, perianal disease, prior major abdominal surgery, extraintestinal manifestations, prior immunomodulator (Thiopurine or Methotrexate) or steroid usage, all laboratory test results and Crohn’s Disease Activity Index (CDAI) score at baseline (p&gt;0.05).
Overall, the median follow-up time was 2.81 and 3.55 years after starting the first IFX and ADA group, respectively. There were no significant differences in the rate of steroid use (4% IFX vs. 10.6% ADA p=0.109), CD-related hospitalization (13.9% IFX vs. 22.8% ADA p=0.127), CD-related major abdominal surgery (9.9% IFX vs. 13% ADA p=0.608) and serious infections leading to treatment cessation (1% IFX vs 0.8% ADA p&gt;0.999) between IFX and ADA. These outcomes were similar in patients treated with IFX or ADA monotherapy or in combination with an immunomodulator.

Conclusion
In this retrospective observational tertiary referral center study, we observed that there was no significant difference in long-term effectiveness and safety of infliximab and adalimumab in biologic-naïve patients with CD.
P573 Comparative effectiveness of second-line biological therapies for Ulcerative colitis and Crohn’s disease in patients with prior failure of anti-tumour necrosis factor treatment
Authors: Hyun H K , Yu J , Kang E A , Park J , Park S J , Park J J , Kim T I , Kim W H , Cheon J H 
Published: May 2021

Abstract

Background
Therapeutic options for inflammatory bowel disease (IBD) have increased since the introduction of tumour necrosis factor (TNF) inhibitors a few decades ago. However, direct comparisons of the effectiveness of second-line biological agents in patients with ulcerative colitis (UC) and Crohn’s disease (CD) are lacking.

Methods
Patients with UC or CD who experienced anti-TNF treatment failure and subsequently used vedolizumab, ustekinumab, or tofacitinib as a second-line drug were retrospectively recruited. The primary outcomes were the clinical remission rate at week 16 and the cumulative relapse rate 48 weeks after receiving induction therapy.

Results
A total of 94 patients with UC or CD experienced anti-TNF treatment failure and received vedolizumab (UC : 37; CD : 28), ustekinumab (CD : 16), or tofacitinib (UC : 13). The clinical remission rates were not significantly different between the vedolizumab and tofacitinib groups in UC patients (56.8% vs. 46.2%, p = 0.509). In CD patients, the clinical remission rates were not significantly different between the vedolizumab and ustekinumab groups (53.6% vs. 50.0%, p = 0.820). Moreover, the cumulative rates of clinical relapse were not significantly different between the vedolizumab and tofacitinib groups in UC patients and between the vedolizumab and ustekinumab groups in CD patients (p = 0.396 and p = 0.692, respectively). Safety profiles were also similar among the treatment groups in both UC and CD patients.

Conclusion
After prior anti-TNF therapy failure, vedolizumab and tofacitinib in UC patients and vedolizumab and ustekinumab in CD patients showed similarities in terms of the efficacy in inducing and maintaining a clinical response.