Biologics In Inflammatory Bowel Disease Research Articles

S1135 Formulation Preferences, Satisfaction, and Quality of Life in Patients Receiving Intravenous Biologics for Inflammatory Bowel Disease: A Saudi Arabian Study

S1135 Formulation Preferences, Satisfaction, and Quality of Life in Patients Receiving Intravenous Biologics for Inflammatory Bowel Disease: A Saudi Arabian Study

Systematic review with meta-analysis of the effectiveness of subcutaneous biologics versus intravenous biologics in inflammatory bowel diseases

Background Biologic therapies are commonly used for inflammatory bowel disease (IBD) patients. Multiple biologic medicines can now be given both intravenously and subcutaneously. The different administration routes present provide different advantages regarding dose escalation, healthcare resource utilisation, pharmacokinetics, convenience and safety. Comparator effectiveness studies between intravenous and subcutaneous administration are lacking. Aim Our primary outcome was to compare the effectiveness between intravenous and subcutaneous biologics in rates of clinical remission. Methods We performed a systematic review and meta-analysis to include all relevant articles from MEDLINE (Ovid), EMBASE, PubMed and Cochrane Central Register of Controlled Trials from 1 January 2003 to 28 January 2024. Studies that compared intravenous and subcutaneous administration of the same biologic therapy in IBD patients and reported effectiveness outcomes were included. This study was registered on PROSPERO (CRD42023442675). Results Twenty studies met the inclusion criteria for the systematic review. Nine vedolizumab cohort studies were meta-analysed for clinical remission and no difference was found in clinical remission rates between intravenous and subcutaneous administration (relative risk = 0.99; 95% confidence interval: 0.88, 1.11). Six infliximab cohort studies were meta-analysed for clinical remission and no difference was found in clinical remission rates between intravenous and subcutaneous administration (relative risk = 0.91; 95% confidence interval: 0.77, 1.08). Conclusions Our findings in the first meta-analysis comparing the effectiveness of intravenous and subcutaneous biologic therapies in IBD suggest there is no difference in the effectiveness between these two administration routes. However, further high-quality studies, particularly head-to-head studies are needed to confirm this finding.

Targets for the Immune Balance of Biologics in Inflammatory Bowel Disease

Targets for the Immune Balance of Biologics in Inflammatory Bowel Disease

Integrin β6 deficiency protects mice from experimental colitis and colitis-associated carcinoma by altering macrophage polarization.

Given the key role of integrins in maintaining intestinal homeostasis, anti-integrin biologics in inflammatory bowel disease (IBD) are being investigated in full swing. However, the unsatisfactory efficacy and safety of current anti-integrin biologics in clinical trials limit their widespread use in clinic. Therefore, it is particularly important to find a target that is highly and specifically expressed in the intestinal epithelium of patients with IBD. The function of integrin αvβ6 in IBD and colitis-associated carcinoma (CAC) with the underlying mechanisms has been less studied. In the present study, we detected the level of integrin β6 within inflammation including colitis tissues in human and mouse. To investigate the role of integrin β6 in IBD and CAC, integrin β6 deficient mice were hence generated based on the construction of colitis and CAC model. We noted that integrin β6 was significantly upregulated in inflammatory epithelium of patients with IBD. Integrin β6 deletion not only reduced infiltration of pro-inflammatory cytokines, but also attenuated disruption of tight junctions between colonic epithelial cells. Meanwhile, lack of integrin β6 affected macrophage infiltration in mice with colitis. This study further revealed that lack of integrin β6 could inhibit tumorigenesis and tumor progression in CAC model by influencing macrophage polarization, which was also involved in attenuating the degree of intestinal symptoms and inflammatory responses in mice suffering from colitis. The present research provides a potentially new perspective and option for the treatment of IBD and CAC.

Review of the safety with biologics in inflammatory bowel disease

Review of the safety with biologics in inflammatory bowel disease

P510 Comparative effectiveness of Ustekinumab against other biologics in Inflammatory Bowel Disease: a propensity score analysis.

Abstract Background Background: Increasing evidence supports the use of Ustekinumab (USTK) in patients with moderate to severe Crohn’s disease (CD) and Ulcerative colitis (UC). Comparison of USTK against other biologics is still lacking. Methods AIMS: to perform a propensity score analysis (PSA) for comparison of USTK against conventional Infliximab (IFX), proactive IFX and vedolizumab in CD and UC Methods retrospective study including patients under Ustekinumab (n=71), Vedolizumab (n=98), conventional IFX (n=70) and proactive IFX (n=148). PSA correcting for age, gender, IBD subtype, previous biologic exposure was performed for each comparison. We compared the rates of fecal calprotectin (Fc) remission (<150 µg/g), treatment discontinuation, hospitalization, and surgery at 52 weeks of treatment. Primary non-responders were excluded. Results Results: after PSP, ustekinumab showed lower rates of treatment discontinuation compared to vedolizumab (7.4% vs 37%, P< 0.001) with a trend for higher rates of Fc remission (42.6% vs 25.9%, P=0.104). Ustekinumab showed higher rates of Fc remission compared to conventional IFX (53.8% vs 19.2%, P= 0.020) with a trend for lower rates of hospitalization (7.7% vs 30.8%, P= 0.075). There were no differences between ustekinumab and proactive IFX in any of the clinical outcomes. Conclusion Conclusion: taking into account the potential limitations of PSP, our results suggest that ustekinumab may be as effective as proactive IFX with some benefits compared to vedolizumab and conventional IFX.

P720 Drug survival of first-line biologics in inflammatory bowel disease: large single-centre experience from UR-CARE

Abstract Background The expanding therapeutic armamentarium for inflammatory bowel disease (IBD) has led to uncertainty about the optimal first-line biological therapy for a given patient. Given the paucity of dedicated head-to-head trials, treatment decisions can be supported by network meta-analyses or real-world data. Our aim was to assess the drug survival of first-line biologics by drug class (anti-tumour necrosis factor [TNF] agents, anti-integrin, anti-interleukin [IL]-12/23) and identify potential predictors for prolonged drug survival in our cohort of IBD patients, supported by the United Registries for Clinical Assessment and Research (UR-CARE). Methods We prospectively included all adult patients with IBD treated with biological drugs and at least one follow-up visit between October 2021 and August 2022 at our tertiary referral centre. Patient data were collected retrospectively from records and included demographics, disease characteristics and drug survival. Data were collected in UR-CARE with data lock on August 1, 2022. Cox regression was used to assess the association of patient and disease characteristics with drug survival of first-line biologic drugs by drug class. Results We included 1047 adult patients with IBD (644 Crohn’s disease [CD], 403 ulcerative colitis [UC]) (Table 1). Among TNF antagonists, adalimumab was most frequently used in CD (280/644, 43.5%; infliximab: 241/644, 37.4%), infliximab was most frequently used in UC (169/403, 41.9%; adalimumab: 55/403, 13.6%; golimumab: 52/403, 12.9%). Unadjusted median drug survival of the first-line biologic did not differ by medication class in CD, but was significantly longer for vedolizumab than for anti-TNF agents in UC (hazard ratio [HR] for discontinuation 0.585, 95% confidence interval [CI] 0.41–0.84; P = 0.003) (Table 2). Disease duration and extent were not associated with drug survival. In CD, isolated ileal disease was associated with longer drug survival (HR 0.83, 95% CI 0.70–0.99; P = 0.04). Findings for both CD and UC were consistent in a sensitivity analysis of patients (CD 228, UC 202) started on biologics after January 1, 2019 when all three drug classes could be prescribed first line without limitations. Conclusion In our cohort of 1047 patients with IBD, the drug survival of first-line biologics was comparable regardless of drug class in CD. In UC, first-line vedolizumab was associated with longer drug survival. Disease location and duration did not impact drug survival.

P517 Ustekinumab monitoring levels predict the need for intensification in patients with inflammatory bowel disease.

Abstract Background Therapeutic drug monitoring (TDM) is a valuable tool to optimize anti-TNF biologics in inflammatory bowel disease (IBD). However, for the non-anti-TNF agents (such as Ustekinumab-UST- an anti-IL12/23) TDM value and evidence in real-world IBD patients is scarce although emerging data suggest that higher drug concentration (>4.5 µg/ml) of these biologics agents predicts better clinical outcomes. We evaluated associations between UST levels and clinical outcomes in real-world IBD patients. Methods A cross-sectional study was performed in IBD patients who received maintenance therapy (≥16 weeks) with UST and followed in our IBD unit between June 2020 and May 2021. UST trough concentration was assessed at the time of inclusion and clinical outcome were reviewed by starting UST use (PRE), at the time of blood extraction (inclusion-EXT), and after 6 months of follow-up (POST). Clinical response was determined by Harvey-Bradshaw Index (HBI) (clinical remission; HBI≤4 points or pMayo ≤2 points) and biochemical response by fecal calprotectin (FC) (biochemical response CF>50 % reduction from basal value and biochemical remission CF <150 g/kg). The need for surgery, intensification, or change of treatment at the end of the follow-up was registered. Results A total of 62 patients (53.2% male; mean age 46 (41-50) years; Crohn’s disease n=57/ ulcerative colitis n=3/indeterminate colitis n=2) were included. The time from diagnosis to initiation of UST treatment was 149 (122-176) months. 35.5% of patients received co-treatment with immunosuppressors and 95,6% had received previous biologic agents (15,6% more than 2 previous biologics). The mean time of UST use was 13 (10-16) months. The mean UST level was established at 7.1 µg/ml (SD 4.3) with higher levels in intensified patients (UST every 4 weeks; n=17) at the time of extraction (9.4 µg/ml (4.3) vs. 6.2 µg/ml (4.0); p= 0.03). However, no differences were found in UST levels between patients achieving clinical remission (n=52,83.9%)) compared to non-responders (7.2 µg/ml (4.4) vs. 6.7 µg/ml (4.4), respectively; p=0. 71); nor in those achieving biological remission at 6 months (n= 31, 56.4%)) compared to non-responders ((7.0 µg/ml (4) vs 6.6 µg/ml (4.5), respectively; p= 0.7). Only 2 patients discontinued UST treatment and 7 patients needed to intensify treatment every 4 weeks during follow-up. In logistic regression analysis, the UST level lower than 4.5 µg/ml showed an independent predictive value for the need for UST intensification in the subsequent 6 months (OR 5.7, 95% CI 1.01-32.9). Conclusion UST is an effective drug for achieving clinical and biological remission in patients with IBD. UST level (<4.5 µg/ml ) may guide the need for treatment intensification at 6 months.

Persistence of Second and Third-Line Biologics in Inflammatory Bowel Disease: A Multi-Centre Cohort Study

Background: Despite proven efficacy of biologics in inflammatory bowel disease (IBD), many exhibit primary non-response or secondary loss of response and switch to subsequent biologic(s). Here, we identified early predictors of second- and/or third-line biologic persistence in IBD, in a real-world cohort of patients. Methods: A retrospective multicentre cohort study was conducted on patients receiving second- and/or third-line biologics for IBD from 2005–2021. Cox regression was applied to identify factors predictive of longer cumulative biologic persistence prior to treatment failure. Results: Of 179 patients who received ≥2 biologics, 159 (88.8%) received an anti-tumour necrosis factor (anti-TNF) first-line. There was a significantly increased likelihood of longer treatment persistence in recipients who received an anti-TNF first, versus those that received a non-anti-TNF agent first (p < 0.01). A diagnosis of CD (OR 7.1, 95% CI [2.3–21.7], p < 0.01), and endoscopic remission achieved on the first biologic (OR 10.4 [1.3–79.9], p = 0.03) were positive predictors of longer biologic persistence, whilst advancing age at IBD diagnosis (OR 0.97 [0.94–0.99], p = 0.04) and primary non-response to initial biologic (OR 0.3 [0.1–0.7], p < 0.01) were inversely associated with biologic persistence. Conclusions: These real-world data demonstrate multiple, simple to identify factors that offer the potential for early objectively assessed response to first-line biologic to predict future biologic persistence.

Less prevalent use of biologics for inflammatory bowel disease in patients from Non-Academic hospitals – a Danish register-based study of a region with 580,000 citizens

Introduction Biologic therapy is widely used for inflammatory bowel disease (IBD) and may decrease surgery rates. However, it remains uncertain if there is unwarranted geographic variation in access to biologic therapy. The aim of the study was to explore if all patients had equal access to biologic therapy in the North Denmark Region. Methods A cross-sectional register-based study of use of biologics, hospital contacts and surgery among all IBD patients having a hospital contact in the geographically well-defined North Denmark Region during 2016–2018. ICD-10 diagnosis codes, hospital contacts and procedure codes were retrieved from the region’s hospital registry. The population is served by an Academic Hospital and two Non-Academic Hospitals constituting three referral areas (according to postal codes). Results In total, 2371 patients with ulcerative colitis (UC) and 1383 patients with Crohn’s disease (CD) had a hospital contact in the region during 2016–2018. Compared to patients from the Academic Hospital, patients from the Non-Academic Hospitals experienced a lower incidence of biologic therapy for UC IRR 0.786 (0.621: 0.994), as well as for CD IRR 0.912 (0.781: 1.065). The incidence of bowel related hospital contacts were higher in patients from Non-Academic hospitals for both UC IRR 1.318 (1.207: 1.438) and CD IRR 1.165 (0.915: 1.483). Conclusions Patients with IBD living in a referral area to a Non-Academic Hospital in the North Denmark Region are less likely to receive biologics. This was associated with an increased prevalence of IBD related surgical procedures.

Computer-Aided Imaging Analysis of Probe-Based Confocal Laser Endomicroscopy With Molecular Labeling and Gene Expression Identifies Markers of Response to Biological Therapy in IBD Patients: The Endo-Omics Study.

We aimed to predict response to biologics in inflammatory bowel disease (IBD) using computerized image analysis of probe confocal laser endomicroscopy (pCLE) in vivo and assess the binding of fluorescent-labeled biologics ex vivo. Additionally, we investigated genes predictive of anti-tumor necrosis factor (TNF) response. Twenty-nine patients (15 with Crohn's disease [CD], 14 with ulcerative colitis [UC]) underwent colonoscopy with pCLE before and 12 to 14 weeks after starting anti-TNF or anti-integrin α4β7 therapy. Biopsies were taken for fluorescein isothiocyanate-labeled infliximab and vedolizumab staining and gene expression analysis. Computer-aided quantitative image analysis of pCLE was performed. Differentially expressed genes predictive of response were determined and validated in a public cohort. In vivo, vessel tortuosity, crypt morphology, and fluorescein leakage predicted response in UC (area under the receiver-operating characteristic curve [AUROC], 0.93; accuracy 85%, positive predictive value [PPV] 89%; negative predictive value [NPV] 75%) and CD (AUROC, 0.79; accuracy 80%; PPV 75%; NPV 83%) patients. Ex vivo, increased binding of labeled biologic at baseline predicted response in UC (UC) (AUROC, 83%; accuracy 77%; PPV 89%; NPV 50%) but not in Crohn's disease (AUROC 58%). A total of 325 differentially expressed genes distinguished responders from nonresponders, 86 of which fell within the most enriched pathways. A panel including ACTN1, CXCL6, LAMA4, EMILIN1, CRIP2, CXCL13, and MAPKAPK2 showed good prediction of anti-TNF response (AUROC >0.7). Higher mucosal binding of the drug target is associated with response to therapy in UC. In vivo, mucosal and microvascular changes detected by pCLE are associated with response to biologics in inflammatory bowel disease. Anti-TNF-responsive UC patients have a less inflamed and fibrotic state pretreatment. Chemotactic pathways involving CXCL6 or CXCL13 may be novel targets for therapy in nonresponders.

Biologics for Inflammatory Bowel Disease in Clinical Practice: A Calabria (Southern Italy) Prospective Pharmacovigilance Study.

The use of immune-modifying biological agents has markedly changed the clinical course and the management of Inflammatory bowel diseases (IBDs). Active post-marketing surveillance programs are fundamental to early recognize expected and unexpected adverse events (AEs), representing a powerful tool to better determine the safety profiles of biologics in a real-world setting. This study aimed to identify the occurrence of AEs and therapeutic failures linked to biological drugs used in gastroenterology units during a prospective pharmacovigilance program in Southern Italy. Patients affected by IBDs and treated with a biologic agent, from 1 January 2019, to 31 December 2021 (study period) in three gastroenterology units were enrolled. Overall, 358 patients with a diagnosis of active Crohn's disease or ulcerative colitis satisfying inclusion criteria have been enrolled. Infliximab (IFX) was the most administered drug at the index date (214; 59.8%), followed by Adalimumab (ADA; 89; 24.9%), Golimumab (GOL; 37; 10.3%), Vedolizumab (VDZ; 17; 4.7%) and Ustekimumab (UST; 1; 0.3%). Seventy-three patients (20.4%) experienced at least one AE, while 62 patients (17.3%) had therapeutic ineffectiveness. No serious AEs were reported in the follow-up period in the enrolled patients. AEs have been described with IFX (50/214; p = 0.47), GOL (7/37; p = 0.78), ADA (13/89; p = 0.18), and VDZ (3/17; p = 0.52), no AEs have been noticed with UST (0/1). Based on the low rate of AEs observed and withdrawal from treatment, our data seem to corroborate the favorable beneficial/risk profile of biologics for IBDs.

Increased monocyte abundance as a marker for relapse after discontinuation of biologics in inflammatory bowel disease with deep remission.

Monocytes are involved in the upstream inflammatory process in the immune reaction in inflammatory bowel disease (IBD). Patients with IBD who discontinued biologics have been found to relapse, even after checking for deep remission. This study investigated whether monocytes could act as a predictor of relapse in patients who experienced relapse after the discontinuation of biologics. To this end, pediatric patients (<19 years old, n = 727) diagnosed with IBD from January 2003 to December 2021 were retrospectively reviewed. Clinical features, monocytes, and disease activity at the time of discontinuing biologics were evaluated by dividing patients into a relapsed group and a non-relapsed group after discontinuing biologics. The percentage of monocytes (8.65% vs. 6.42%, P < 0.001), the absolute monocyte count (614.79 cells/μL vs. 381.70 cells/μL, P < 0.001), and the monocyte/polymorphonuclear leukocyte (PMN) ratio (0.18 vs. 0.11, P < 0.001) at the time of discontinuation were significantly higher in patients who experienced relapse. As a result of multivariate analysis, the monocyte percentage (odds ratio: 2.012, P < 0.001) and monocyte/PMN ratio (odds ratio: 4.320E+14, P = 0.002) were evaluated as risk factors for relapse. Diagnostic capability was confirmed using area under operating characteristic curve (0.782) of the monocyte percentage for assessing the relapse within 6 months with cutoff value of 8.15% (P < 0.001). The findings presented in this study indicate that the patients with high monocyte counts experienced relapse after the discontinuation of biologics. A monocyte percentage of over 8.15% in theblood at the time of discontinuation was found to be associated with a high probability of relapse within 6 months, even in deep remission.

S1015 Adverse Events and Compliance Among Inflammatory Bowel Disease Patients Treated With Home versus Office-Based Biologic Infusions

Introduction: Home infusion of infliximab (IFX) and vedolizumab (VDZ) for inflammatory bowel disease (IBD) has recently expanded owing to insurance company requirements and patient (pt) preference for convenience. These biologics are associated with a number of adverse events (AEs). Previous data suggest increased rates of AEs and reduced efficacy of biologics when given at home rather than in a medical office. We sought to assess the rates of AEs, biologic discontinuation, and adherence to follow-up in IBD pts receiving home versus office-based infusions. Methods: This was a single center retrospective cohort study of adult pts with IBD receiving IFX or VDZ either at home or an office-based infusion center. AEs were defined as immediate (< 24 hour) and delayed (day 1-7) transfusion reaction, steroid initiation, drug discontinuation, or IBD-related emergency room visits, admission, and surgery. Patients were followed for a maximum duration of 150 weeks. Adherence to follow-up was determined by biannual clinic visits and labwork. Chi squared and Fisher’s exact tests were used, where appropriate, to determine statistical significance. Kaplan-Meier plot created using SPSS software. Results: 287 pts (46.0% female, mean age 40.8 years, 61.3% CD, 38.7% UC) were included. The majority were non-Hispanic white with an elevated BMI. The office-based infusion group had more former smokers (35.9% vs 19.0%, p< 0.05), longer disease duration (11.2 vs 8.1 years, p< 0.05), and greater disease severity (Harvey-Bradshaw Index (HBI) 4.9 vs 3.8, p< 0.05) compared to the home infusion group (Table). AEs were higher among office-based infusions (80 vs 56, p< 0.05) driven by delayed transfusion reactions (4 vs 0, p < 0.05), surgery (6 vs 0, p < 0.05), and medication discontinuation (44 vs 35, p < 0.05) (Figure). Pts receiving home infusions were less likely to follow-up in clinic (53.2% vs 71.4%, p< 0.05) and obtain routine labwork (37.9% vs 58.1%, p< 0.05). Conclusion: Among IBD pts on IFX or VDZ therapy, office-based infusions were associated with higher rates of AEs especially delayed transfusion reactions, need for surgery, and medication discontinuation. Treatment bias may exist towards starting more stable patients on home infusion given the less severe disease that we observed in that group. Adherence to clinic followup and routine labwork was much lower with home infusion. Home biologic infusion appears to be a viable treatment option for IBD if adequate adherence to followup care is maintained.Figure 1.: Adverse event free survival among those on home and office based infusion of biologics for inflammatory bowel disease. Table 1. - Demographics, disease characteristics, adverse events, and compliance among inflammatory bowel disease patients receiving biologic infusion at home or at the office HomeInfusion OfficeInfusion n = 154 n = 133 Age 37.3 (12.2) 45.0 (16.4) p < 0.05 Female 81 (52.6%) 52 (39.1%) p < 0.05 Race Non-Hispanic White 131 (85.1%) 102 (77.3%) Black 12 (7.8%) 21 (15.9%) Asian 6 (3.9%) 5 (3.8%) Hispanic 4 (2.6%) 2 (1.5%) Other 1 (0.6%) 2 (1.5%) BMI 27.7 (6.5) 27.0 (6.5) Current Smoker 10 (6.5%) 10 (7.6%) Former Smoker 29 (19.0%) 47 (35.9%) p < 0.05 Disease Duration (Years) 8.1 (8.1) 11.2 (12.6) P < 0.05 Previous IBD SurgeryHarvey Bradshaw Index 39 (26.2%)3.9 (2.9) 37 (28.9%)4.8 (3.8) p < 0.05 Ulcerative Colitis 61 50 Proctitis 12 (19.7%) 13 (26%) Left-Sided 16 (26.2%) 13 (26%) Pancolitis 33 (54.1%) 24 (48%) Crohn's Disease 93 83 Ileal 25 (26.9%) 24 (28.9%) Colonic 22 (23.7%) 19 (22.9%) Ileocolonic 42 (45.2%) 40 (48.2%) Upper GI 4 (4.3%) 1 (1.2%) Inflammatory 52 (55.9%) 42 (50.1%) Stricturing 18 (19.4%) 26 (31.3%) Fistulizing 23 (24.7%) 15 (18.1%) Perianal 26 (27.1%) 21 (22.8%) Concurrent Medication Mesalamine 30 (19.6%) 44 (33.3%) P < 0.05 Thiopurines 14 (9.2%) 15 (11.4%) Methotrexate 3 (2.0%) 9 (6.8%) Biologic Use Naive 86 (56.2%) 74 (55.6%) Previous Use 67 (43.8%) 59 (44.4%) # Previous Biologics 1.4 (0.7) 1.5 (0.7) Major Adverse Event 56 80 p < 0.05 Transfusion Reaction, Immediate 8 9 Transfusion Reaction, Delayed 0 4 p < 0.05 ED Visit 0 1 Admission 7 6 Surgery 0 6 p < 0.05 Steroid Initiation 6 10 Discontinuation 35 44 p < 0.05 Office Visit Every 6 Months 53.2% 71.4% p < 0.05 Labs Obtained Every 6 Months 37.9% 58.1% p < 0.05

I-CARE, a European Prospective Cohort Study Assessing Safety and Effectiveness of Biologics in Inflammatory Bowel Disease

There is a need to evaluate the benefit-risk ratio of current therapies in inflammatory bowel disease (IBD) patients to provide the best quality of care. The primary objective of I-CARE (IBD Cancer and serious infections in Europe) was to assess prospectively safety concerns in IBD, with specific focus on the risk of cancer/lymphoma and serious infections in patients treated with anti-tumor necrosis factor and other biologic monotherapy as well as in combination with immunomodulators. I-CARE was designed as a European prospective longitudinal observational multicenter cohort study to include patients with a diagnosis of Crohn's disease, ulcerative colitis, or IBD unclassified established at least 3 months prior to enrollment. A total of 10,206 patients were enrolled between March 2016 and April 2019, including 6169 (60.4%) patients with Crohn's disease, 3853 (37.8%) with ulcerative colitis, and 184 (1.8%) with a diagnosis of IBD unclassified. Thirty-two percent of patients were receiving azathioprine/thiopurines, 4.6% 6-mercaptopurine, and 3.2% methotrexate at study entry. At inclusion, 47.3% of patients were treated with an anti-tumor necrosis factor agent, 8.8% with vedolizumab, and 3.4% with ustekinumab. Roughly one-quarter of patients (26.8%) underwent prior IBD-related surgery. Sixty-six percent of patients had been previously treated with systemic steroids. Three percent of patients had a medical history of cancer prior to inclusion and 1.1% had a history of colonic, esophageal, or uterine cervix high-grade dysplasia. I-CARE is an ongoing investigator-initiated observational European prospective cohort study that will provide unique information on the long-term benefits and risks of biological therapies in IBD patients. (EudraCT, Number: 2014-004728-23; ClinicalTrials.gov, Number: NCT02377258).

Use of Biologics in Inflammatory Bowel Disease: Combination and Sequential Therapy

Inflammatory bowel disease (IBD) in the form of ulcerative colitis (UC) and Crohn's disease (CD) has multifactorial etiology and multiple inflammatory pathways. Newer treatments with biologic agents are used as an adjunct to conventional therapy. Biological agents such as anti-TNF, anti-integrin, and anti-interleukin are believed to be able to overcome the inflammation that underlies the occurrence of IBD. The “step up” approach in IBD therapy uses conventional drugs with low potency but fewer side effects as the first line, followed by biologic agents as second line therapy. However, the result is often a delay in the management of severe complications of IBD. A “top down” approach is currently being used to successfully prevent severe complications of IBD by using biologic agents early. Biological agent therapy can be initiated in moderate to severe IBD either in combination or sequentially. But in the end, various parameters must be considered before starting the use of biologic agents such as drug effectiveness, safety profile, drug availability, price, and patient preferences.

Children included in randomised controlled trials of biologics in inflammatory bowel diseases do not represent the real-world patient mix.

SummaryBackgroundPatients enrolled in randomised controlled trials (RCTs) may differ from the target population due to restricted eligibility criteria.AimTo compare treatment response to biologics in routine practice for children with inflammatory bowel diseases (IBD) who would and would not have been eligible for enrolment in the regulatory RCT of the same drug.MethodsWe enrolled children with IBD who initiated adalimumab, infliximab, vedolizumab or ustekinumab. The eligibility criteria as defined in the RCT of the corresponding biologic were applied to each patient. The primary outcome was 12‐month steroid‐free remission (SFR) without switching biologics or undergoing surgery.ResultsWe screened 289 children (198 [68%] with Crohn's disease [CD], 91 [32%] with ulcerative colitis [UC]) with 326 initiations of biologics. Only 62 of 164 (38%) children with moderate–to‐severe disease would have been eligible for inclusion in the original RCTs. The SFR rate was higher in the eligible children (51%) than in the ineligible children (31%; OR 2.3 [95%CI 1.2–4.5]; p = 0.01). The main exclusion criterion was prohibited previous therapies (47%). Ineligible CD patients were older, more often had a family history of IBD and had higher levels of CRP than eligible children; in UC there were no differences between the groups.ConclusionMost children with IBD who initiate biologics would not have been eligible to be included in the corresponding regulatory RCTs. The outcomes of ineligible patients were worse than for eligible patients. Results from RCTs should be interpreted with caution when applied to clinical practice.

Financial Conflicts of Interest in Propensity Score-Matched Studies Evaluating Biologics and Biosimilars for Inflammatory Bowel Disease.

BackgroundPropensity score matching (PSM), a statistical technique that estimates a treatment effect by accounting for predictor covariates, has been used to evaluate biologics for inflammatory bowel disease (IBD). Financial conflicts of interest are prevalent in the marketing of biologic medications. It is unclear whether this burden of conflicts is present among authors of PSM studies comparing IBD biologics and biosimilars.ObjectiveThis study was aimed to determine the prevalence of financial conflicts of interest among authors of PSM studies evaluating IBD biologics and biosimilars.MethodsWe conducted a systematic search for PSM studies comparing biologics and biosimilars in IBD treatment. We identified 21 eligible studies. Two independent authors extracted self-declared conflicts from the disclosures section. Each participating author was searched on the Centers for Medicare & Medicaid Services Open Payments to identify payment amounts and undisclosed conflicts. Primary outcome was the prevalence of author conflicts. Secondary analyses assessed for an association between conflict prevalence and reporting of positive outcomes.ResultsAmong 283 authors, conflicts were present among 41.0% (116 of 283). Twenty-three per cent (27 of 116) of author conflicts involved undisclosed payments. Studies with positive outcomes were significantly more likely to include conflicted authors than neutral studies (relative risk = 2.34, 95% confidence interval: 1.71 to 3.21, P < 0.001).ConclusionsOverall, we found a high burden of undisclosed conflicts among authors of PSM studies comparing IBD biologics and biosimilars. Given the importance of PSM studies as a means for biologic comparison and the potential for undue industry influence from these payments, authors should ensure greater transparency with reporting of industry relationships.

Therapeutic Drug Monitoring of Biologics in Crohn's Disease.

Reactive therapeutic drug monitoring (TDM) is considered the standard of care for optimizing biologics in inflammatory bowel disease (IBD) including Crohn's disease (CD). Preliminary data show that proactive TDM is associated with positive outcomes in IBD and can be also used to efficiently guide therapeutic decisions in specific clinical scenarios. Higher biological drug concentrations are associated with favorable therapeutic outcomes in specific IBD populations or phenotypes including pediatric CD, perianal fistulizing CD, small bowel CD, and following an ileocolonic resection for CD. Future perspectives of TDM include the use of rapid testing, pharmacogenomics, and pharmacokinetic dashboards toward individualized therapy.

Influence of comorbidities on treatment considerations for first-line biologic prescribing in patients with inflammatory bowel disease in the UK

BackgroundAnti-tumour necrosis factor (anti-TNF) therapies are the most commonly used biologics for inflammatory bowel disease (IBD), but for patients with a comorbidity, newer agents may be a more appropriate treatment...