Anti-tumor Necrosis Factor Medications Research Articles

Long-term Safety Monitoring and Efficacy Status of Infliximab and its Biosimilars in Psoriasis Management

Abstract: Infliximab (INF), a murine human monoclonal antibody, is a substantially more successful biologic than topical drugs for treating mild to severe psoriasis because it clears the skin rapidly due to its fast onset of action. Loss of responsiveness over time and some adverse effects, especially the experience of infusion reactions, are the major causes of non-compliance with INF medication. Therefore, evaluation of the long-term reliability of anti-tumor necrosis factor (TNF) medications is necessary for the assessment of the risks associated with long-term anti-TNF therapy. For psoriasis, there are registered safety statistics; however, these individuals might not receive the same level of care as those in a randomized study. Few assessments of the safety of anti- TNF medications across indications, including their biosimilars, are present, but it’s still unknown how anti-infliximab antibodies arise and produce harmful effects. INF biosimilars, when subjected to human studies to reduce cost and improve access, provide therapeutic benefits with associated adverse events, showing variations in incidence depending upon varying patient populations and no new safety indications. During therapy, certain individuals develop antibodies against INF, which are believed to be linked to a loss of response (LOR). Additional research aimed at identifying individuals who are susceptible to treatment resistance is likely to assist doctors in accurately selecting the appropriate candidates for anti-TNF-α therapy and enhancing the long-term effectiveness of the treatment. From clinical studies, we expect to learn about how to utilize INF or its biosimilars more effectively in the management of psoriasis. Therefore, the paper focuses on the efficacy and safety monitoring of INF and developed biological therapies.

The Effect of Anti-Tumor Necrosis Factor Therapy on The Plasma Atherogenic Index in Rheumatic Diseases.

Background: The risk of atherosclerosis is increased in individuals with rheumatological disease. The objective of this study is to examine the heightened susceptibility to atherosclerosis in persons afflicted with rheumatological disorders. This study aimed to assess the impact of anti-tumor necrosis factor (anti-TNF) medication on the plasma atherogenic index (PAI) in persons diagnosed with rheumatological disease. Methods: This study used a retrospective cross-sectional design to investigate a cohort of 136 patients with rheumatological disease who were undergoing anti-TNF therapy (Group 1), as well as a comparison group of 117 patients getting conventional therapy (Group 2). Measurements of PAI were conducted at the initial baseline and again at the sixth month of treatment. Results: Initially, there was no statistically significant disparity observed in PAI values between the two cohorts. After a period of 6 months, a notable reduction in PAI was identified in the group receiving anti-TNF medication (P = 0.01), while no significant alteration was detected in the group receiving conventional treatment. Conclusion: It provides findings showing that anti-TNF therapy can reduce the PAI in individuals with rheumatological disease. This may indicate a potential cardiovascular protective effect of anti-TNF therapy.

Pulmonary sarcoidosis: A comprehensive review: Past to present

Sarcoidosis is a sterile non-necrotizing granulomatous disease without known causes that can involve multiple organs with a predilection for the lung and thoracic lymph nodes. Worldwide it is estimated to affect 2–160/100,000 people and has a mortality rate over 5 years of approximately 7%. For sarcoidosis patients, the cause of death is due to sarcoid in 60% of the cases, of which up to 80% are from advanced cardiopulmonary failure (pulmonary hypertension and respiratory microbial infections) in all races except in Japan were greater than 70% of the sarcoidosis deaths are due to cardiac sarcoidosis.Scadding stages for pulmonary sarcoidosis associates with clinical outcomes. Stages I and II have radiographic remission in approximately 30%–80% of cases. Stage III only has a 10%–40% chance of resolution, while stage IV has no change of resolution. Up to 40% of pulmonary sarcoidosis patients progress to stage IV disease with lung parenchyma fibroplasia, bronchiectasis with hilar retraction and fibrocystic disease. These patients are at highest risk for the development of precapillary pulmonary hypertension, which may occur in up to 70% of these patients. Sarcoid patients with pre-capillary pulmonary hypertension can respond to targeted pulmonary arterial hypertension medications. Stage IV fibrocytic sarcoidosis with significant pulmonary physiologic impairment, >20% fibrosis on HRCT or pre-capillary pulmonary hypertension have the highest risk of mortality, which can be >40% at 5-years.First line treatment for patients who are symptomatic (cough and dyspnea) with parenchymal infiltrates and abnormal pulmonary function testing (PFT) is oral glucocorticoids, such as prednisone with a typical starting dose of 20–40 mg daily for 2 weeks to 2 months. Prednisone can be tapered over 6–18 months if symptoms, spirometry, PFTs, and radiographs improve. Prolonged prednisone may be required to stabilize disease. Patients requiring prolonged prednisone ≥10 mg/day or those with adverse effects due to glucocorticoids may be prescribed second and third line treatements. Second and third line treatments include immunosuppressive agents (e.g., methotrexate and azathioprine) and anti-tumor necrosis factor (TNF) medication; respectively. Effective treatments for advanced fibrocystic pulmonary disease are being explored. Despite different treatments, relapse rates range from 13% to 75% depending on the stage of sarcoid, number of organs involved, socioeconomic status, and geography. ConclusionThe mortality rate for sarcoidosis over a 5 year follow up is approximately 7%. Unfortunately, 10%–40% of patients with sarcoidosis develop progressive pulmonary disease, and >60% of deaths resulting from sarcoidosis are due to advance cardiopulmonary disease. Oral glucocorticoids are the first line treatment, while methotrexate and azathioprine are considered second and anti-TNF agents are third line treatments that are used solely or as glucocorticoid sparing agents for symptomatic extrapulmonary or pulmonary sarcoidosis with infiltrates on chest radiographs and abnormal PFT. Relapse rates have ranged from 13% to 75% depending on the population studied.

The Future of Advanced Therapies for Pediatric Crohn's Disease.

Pediatric Crohn's disease commonly presents with moderate-to-severe intestinal inflammation with a greater risk of complications if remission is not achieved. Anti-tumor necrosis factor therapies have offered the possibility of deep and durable remission; however, many children do not respond or no longer respond over time. Further, some children do not require broader systemic immunosuppression to achieve remission and are better served by an alternative treatment strategy. Proper utilization of advanced biologic and small-molecule therapies, which have become available for adult patients since anti-tumor necrosis factor medications, is paramount for tighter disease control for a large proportion of children. Newer advanced therapies such as anti-integrin and anti-interleukin biologics, and several small-molecule agents capitalize on various mechanisms through narrower immunologic targets and reduced immunogenicity. Given limited regulatory approvals of these agents for use in children with Crohn's disease, clinicians continue to rely on data extrapolated from clinical trials in adult patients, sparse pediatric studies, and a growing real-world experience for treatment selection and optimization. In this article, we discuss currently available treatment options, pipeline drugs, and relevant data as they pertain to some of the most pressing clinical challenges faced in treating pediatric Crohn's disease.

Menstrual cycle abnormalities in women with inflammatory bowel disease and effects of biological therapy on gynecological pathology.

Inflammatory bowel disease (IBD) is a chronic condition that affects young individuals in their reproductive years. It may have long-term implications on their reproductive, sexual, and mental health. IBD has been related to menstrual abnormalities. Furthermore, the administration of biological therapy can also result in gynecological issues in addition to the disease itself. The purpose of this review was to present potential menstrual cycle problems in patients with IBD, as well as the impact of adalimumab and other anti-tumor necrosis factor medications on gynecological pathology.

A Summary of the Rare Reports of Osteonecrosis of the Jaw Associated With Tumor Necrosis-α Inhibitors in the United States Food and Drug Administration's Adverse Event Reporting System Database

Recent case reports highlight an association between osteonecrosis of the jaw (ONJ) and antitumor necrosis factor (anti-TNF) medications. Our study reviewed and described reports of anti-TNF associated ONJ reported to the United States of America's Food and Drug Administration Adverse Event Reporting System to explore this potential adverse drug reaction further. Using the Food and Drug Administration Adverse Event Reporting System database, we identified reported cases of ONJ between 2010 and 2021. Cases were included in our study if they reported any prior or concomitant anti-TNF medication use. Additionally, only adults (age 18+) and reports from health-care professionals were included. Cases lacking subject age or gender were excluded. After duplicates were removed, a dataset was created and demographics were described including age, gender, and indication for use. Naranjo scoring was conducted to assess adverse drug reaction probability. Subject demographics were then separately described for cases without reported denosumab or bisphosphonate therapy history and compared to those with reported history or concomitant denosumab or bisphosphonate therapy. Over twenty thousand cases of ONJ were reported. Forty-four potential cases (0.22%) of anti-TNF medication-associated ONJ were identified and reviewed. Of these, female gender comprised 77.3% (35 cases) and there was an average age of 61.3years±13.7years. Twenty cases (45.5%) had no prior/concomitant bisphosphonate or denosumab therapy. Of these, 55% (11 cases) were female and the average age was 54.5±17.3years. Rheumatoid arthritis was the most frequent indication for use (5 cases, 25%) followed by inflammatory bowel disease (IBD) and psoriatic arthritis (4 cases each, 20%) in this cohort. Twenty potential cases of anti-TNF-associated ONJ without prior or concomitant medications known to be associated with ONJ were identified and described. Interestingly, male gender was more frequent and subjects were younger in these cases compared to those with prior/concomitant bisphosphonates or denosumab therapy. Naranjo scoring indicated a probable interaction for three cases. Further studies are needed to clarify the association of ONJ and anti-TNF therapy, including investigating potential mechanisms and reporting future cases with sufficient detail to assess possible confounding factors.

Longitudinal trends in direct costs and healthcare utilization ascribable to inflammatory bowel disease in the biologic era: a nationwide, population-based study.

Biologic-era data regarding the direct cost and healthcare utilization of inflammatory bowel disease at the population level are limited, especially in Asia. Thus, we aimed to investigate the nationwide prevalence, direct cost, and healthcare utilization of inflammatory bowel disease in Korea in a recent 10-year period. Using the Korean National Health Insurance claim data from 2008 to 2017, we investigated all prescription medications and their associated direct costs, hospitalizations, and outpatient visits. We also estimated the nationwide prevalence of inflammatory bowel disease using population census data. The estimated inflammatory bowel disease prevalence significantly increased from 108.8/100 000 in 2008 to 140.4/100 000 in 2017. The overall annual costs for inflammatory bowel disease and the healthcare cost per capita increased from $24.5 million (in US dollars) to $105.1 million and from $458.4 to $1456.6 million, respectively (both P<0.001). Whereas the ratio of outpatient costs increased from 35.3% to 69.4%, that of outpatient days remained steady. The total annual medication cost and proportion rose from $13.3 million to $76.8 million and from 54.2% to 73.3%, respectively, mainly due to the increasing antitumor necrosis factor cost, from $1.5 million to $49.3 million (from 11.1% to 64.1% of the total annual drug cost and from 6.3% to 46.9% of the total annual cost). We observed increasing trends in the prevalence, direct costs, and healthcare utilization of inflammatory bowel disease in Korea in recent years. The attributable cost was mainly driven by rising expenditures on antitumor necrosis factor medications.

Ileo-Anal Pouch Anastomosis and New Remedial Approaches for Ulcerative Colitis: A Review Article.

Ulcerative colitis (UC)causes diffusefriability and superficial wall degeneration that is accompanied by bleeding. UC, now recognized as a global illness, affects millions of people globally. The most effective treatment for UC is Ileal Pouch Anal Anastomosis (IPAA). Many medical experts and patients favor proctocolectomy with IPAA because it improves bowel function and allows feces to pass via the anus.Considering the most recent research, systematic reviews, statistical analysis, and recommendations, a selective literature search was carried out. The database used was PubMed. The current work provides a summary of surgical alternatives, results, and pre-and postoperative treatment for UC patients. In the course of their illness, about 30% of UC patients will need surgery. Due to its natural limitation to the colon and rectum, UC may mostly be treated surgically. The preferred surgical process is a restorative proctocolectomy with an IPAA. A 30% postoperative complication rate and a 0.1% death rate for this operation are both shown in large studies. One of the biggest things preventing UC from being successfully treated surgically is pouchitis. A long-run success rate of the pouch is>90% after 10follow-ups, despite a significant surgical complication rate. For patients with UC to have the best possible outcome, extensive collaboration among the various specialties in the pre and postoperative context is crucial. In skilled centers, more than 90%of the total patients can eventually achieve a decent quality of life despite a 30% likelihood of early postoperative problems. UC patients may be cured with proctocolectomy, but there is a risk of morbidity that must be considered, especially in pediatric patients. As a result of advancements in our comprehension of the pathogenic mechanisms causing UC, new therapies have been proposed, the most significant change being the emergence of anti-tumor necrosis factor (TNF) medications.

S974 Comparison of Surgical Rates in Biologic Naive Crohn's Disease Patients on Ustekinumab and Vedolizumab

Introduction: Between 25% to 45% of patients with Crohn’s Disease (CD) require surgical treatment of their disease between 5 and 10 years of diagnosis. Anti-tumor necrosis factor (anti-TNF) therapy has been associated with lower surgical rates in IBD. However, the rate of surgical intervention in ustekinumab- and vedolizumab-treated biologic naïve CD to date patients is unknown. We aimed to investigate the effect of ustekinumab and vedolizumab on intestinal resection rates in bio-naïve CD patients. Methods: A commercial database (Explorys Inc, Cleveland, OH) was utilized, which included electronic health record data from 26 major integrated US healthcare systems. We identified bio-naïve CD patients. The primary outcome was to examine the association between anti-tumor necrosis factor (anti-TNF) medications, ustekinumab, and vedolizumab therapy and the rate of bowel resection in bio-naïve CD patients after at least 12 weeks of treatment. Secondary endpoints were factors associated with increased risk of surgical intervention in these bio-naïve CD patients. Results: The database included over 70 million individuals in which we identified 249,300 (0.35%) adult ( >18 years) patients with CD. Among all CD patients, 1.7% received ustekinumab, 2.4% received vedolizumab, and 16% received anti-TNF as first-line biologic therapy. The rate of intestinal resection was lower among ustekinumab-treated compared to vedolizumab-treated bio-naïve CD patients (11.8% vs. 13.9%, p = 0.001). The rate of intestinal resection was higher among vedolizumab-treated compared to anti-TNF-treated bio-naïve CD patients (13.9% vs. 12.5%, p < 0.0001). However, intestinal resection rates did not significantly differ between ustekinumab-treated compared to anti-TNF-treated bio-naïve CD patients (11.8% vs. 12.5%, p = 0.15). Compared to anti-TNF, tobacco smoking, fistulas, and abscesses were more commonly associated with intestinal resection in ustekinumab- and vedolizumab-treated bio-naïve CD patients. Age < 65 years and intestinal fistulas were commonly associated with ustekinumab-treated bio-naïve CD patients compared to vedolizumab. (Figure) Conclusion: In this large cohort of bio-naïve CD patients, the rate of intestinal resection was lower in ustekinumab-treated and anti-TNF treated patients compared to Vedolizumab after at least 12 weeks of therapy. Further prospective studies are needed to compare the effectiveness and safety of first-line Ustekinumab and Vedolizumab therapy in IBD patients (Table). Figure 1.: Comparison of intestinal resection rates in bio-naive CD patients after at least 12 weeks of ustekinumab, vedolizumab, and anti-TNF. Table 1. - Characteristics of biologic naive CD patients requiring intestinal resection after at least 12 weeks of ustekinumab and vedolizumab Factors UstekinumabN = 510 (%) VedolizumabN = 850 (%) Odds ratio (95% confidence interval), P value Age Adults (18-65y) 460 (90%) 710 (84%) 1.81 (1.28-2.55), 0.0007 Seniors ( >65y) 50 (10%) 140 (16%) 0.55 (0.39-0.77), 0.0007 Race White 460 (90%) 760 (89%) 1.08 (0.75-1.56), 0.64 Non-white 50(10%) 90 (11%) 0.91 (0.63-1.32), 0.64 Gender Female 300 (59%) 460 (54%) 1.21 (0.97-1.51), 0.90 Male 210 (41%) 390 (46%) 0.82 (0.66-1.03), 0.90 Clinical characteristics Tobacco user (current and former) 490 (96%) 820 (96%) 0.89 (0.50-1.59), 0.71 Clostridium difficile infection 70 (14%) 150 (18%) 0.74 (0.54-1.01), 0.05 Small bowel obstruction 10 (2%) 30 (4%) 054 (0.26-1.12), 0.10 Fistula of intestine 230 (45%) 330 (38%) 1.29 (1.03-1.61), 0.02 Anorectal fistula 150 (20%) 230 (27%) 1.12 (0.88-1.43), 0.34 Perianal abscess 100 (20%) 140 (16%) 1.23 (0.93-1.64), 0.14 Anorectal abscess 80 (16%) 130 (15%) 1.03 (0.76-1.39), 0.84 Neoplasm of colon 70 (14%) 160 (19%) 0.68 (0.54-0.93), 0.01 Malignant neoplasm of colon 10 (2%) 30 (4%) 0.54 (0.26-1.12), 0.10

Inflammatory Bowel Disease and Pregnancy

Inflammatory Bowel Disease and Pregnancy

DOP26 COVID-19 vaccine effectiveness in Inflammatory Bowel Disease patients on tumor-necrosis factor inhibitors: Real world data from a mass-vaccination campaign

BackgroundSome studies have shown decreased serological response to vaccination in patients on anti-tumor necrosis factor (TNF) medications. While the large majority of these patients do seroconvert after vaccination, titers have generally been lower and one study showed reduced neutralizing and inhibitory functions. One real-world population-based study compared found no increased infection rate in anti-TNF treated patients, but infection rates were low. The low event rate mandates exploration in longer-term population-based data. We used the epi-Israeli IBD Research Nucleus (IIRN) database to explore the effectiveness of COVID-19 vaccination in IBD patients in Israel.MethodsWe included all IBD patients insured in two of the four Israeli HMOs, covering 35% of the population, by validated algorithms, and selected those who received two doses of Pfizer BNT162b2 vaccine. These were matched by date of vaccination ±3 days and demographic variables to non-IBD controls. The primary outcome was incidence of positive COVID-19 PCR following vaccination between December, 2020 to June, 2021.Results12,640 IBD patients received two vaccine doses; the matched cohort included 4,946 matched pairs (total 9,892 subjects). Mean age was 50.5±16.1 years and median follow-up was 22 weeks (range 4.1–24.4). Fifteen (0.3%) vaccinated IBD patients tested positive compared with 15 (0.3%) vaccinated non-IBD controls (OR=1 [95%CI 0.49–2.05], p=1.0). Patients on anti-TNF and/or corticosteroids did not have a higher incidence of positivity – neither compared to the entire group nor to IBD patients treated with vedolizumab/ustekinumab, even after precise matching for demographics, underlying diseases and IBD severity.ConclusionIn a large population-based cohort of IBD patients in Israel, vaccine effectiveness was equivalent to non-IBD controls and was not influenced by treatment with anti-TNF or corticosteroids. Notwithstanding previous findings of impaired serological response in anti-TNF treated IBD patients, this real-world large-scale study shows that vaccine protection is robust in IBD patients, including those on immunosuppressive medications.

The Effect of Early vs Delayed Initiation of Adalimumab on Remission Rates in Patients With Crohn's Disease With Poor Prognostic Factors: The MODIFY Study.

Data on the effectiveness of anti-tumor necrosis factor medications in patients with Crohn's disease (CD) with poor prognostic factors (PPFs) are scarce. This study aimed to generate real-world evidence on the effect of early (≤24 months after diagnosis) vs delayed (>24 months) initiation of adalimumab (ADL) on the 26-week remission rate (Harvey-Bradshaw Index ≤4) in these patients. This multicentre, retrospective, chart review study performed in 10 Greek hospitals enrolled adult patients with moderate to severe CD (Harvey-Bradshaw Index ≥8) with ≥3 PPFs who were initiated on ADL ≥12 months before enrollment. A sample size of 164 patients (early:delayed cohort allocation ratio, 30:70) was required to address the primary endpoint. Eligible patients (n = 171) were consecutively enrolled. In the early vs delayed cohorts, the 26-week remission rates (off-steroids) using the last-observation-carried-forward imputation method were 60.7% (37/61) vs 47.2% (50/106), respectively (Δ = 13.5%, P = .044). The respective remission rates were 61.2% vs 42.4% among anti-tumor necrosis factor-naive patients (P = .023) and 58.3% vs 53.2% among anti-tumor necrosis factor-experienced patients (P = .374). The 52-week remission rates using as-observed data were 78.8% and 60.3%, and the intestinal resection rates were 6.5% and 11.9% in the early vs delayed ADL cohorts, respectively. Patients with CD with PPFs who received early vs delayed treatment with ADL achieved higher clinical response and remission rates. This effect was more pronounced in those patients who were bio-naive and steroid-dependent/refractory with concurrent extraintestinal manifestations than those who were not.

P617 Trends in Pediatric Inflammatory Bowel Disease-attributable direct costs: A Canadian population-based analysis

Abstract Background Background: In addition to its symptomatic burden, inflammatory bowel disease (IBD) has a major financial burden on patients and healthcare systems. However, there is a paucity of evidence on IBD-attributable costs in children. In a population-based analysis, we determined the trends of IBD-attributable direct costs over 22 years. Methods Data were extracted from Manitoba Health Provider Claims, and other population registry datasets from 1995 to 2017. Children with IBD were matched by age, sex, and location with children without IBD. IBD-attributable direct costs were calculated using utilization counts from the administrative data and cost estimates from different sources. Inpatient hospitalization and outpatient procedure costs were estimated using the resource intensity weight (RIW) that is attached to each record in the data. Costs were expressed in 2018 Canadian dollars. Results We included 733 (428 with Crohn’s disease) prevalent cases who were diagnosed with IBD before the age of 18 years and were followed for 2450 person-years. An age, sex and geography matched control group of 6763 persons without IBD who were followed for 21558 person-years was included. The median annual physician’s billing fees increased from $381 (IQR 215–1064) in 1995 to $936 (IQR 579–1932) in 2017 (p&amp;lt;.001). The annual ambulatory care days for persons with IBD also significantly increased from a median of 8 days per year (IQR 5–13) in 1995 to 12 days per year (IQR 8–17) in 2017 (p &amp;lt; 0.0001) while they remained stable (median 2 days per year) in the control group (p=0.12). The annual medication costs per patient increased from a median of $270.9 in 1995 to $7944 in 2017 (p&amp;lt;.0001). Between 2012 and 2017, the median annual medication costs for all persons on anti-tumor necrosis factor (TNF) medications were $28,582 (IQR 21854–36736)compared to $861for persons with IBD not on an anti-TNF agent (IQR 355–1,714) (p&amp;lt;0.0001) with a relatively stable costs over the 5-year period. The median annual direct costs per patient with IBD was $1810.716 in 2004 as compared to $14791.55 (p&amp;lt;.0001) in 2017. Conclusion Over 2 decades, there was a significant increase in the pediatric IBD-attributable direct costs mainly driven by medication costs mainly anti-TNF biologics.

No Change in Surgical and Hospitalization Trends Despite Higher Exposure to Anti-Tumor Necrosis Factor in Inflammatory Bowel Disease in the Québec Provincial Database From 1996 to 2015.

Crohn disease (CD) and ulcerative colitis (UC) have high health care expenditures because of medications, hospitalizations, and surgeries. We evaluated disease outcomes and treatment algorithms of patients with inflammatory bowel disease (IBD) in Québec, comparing periods before and after 2010. The province of Québec's public health administrative database was used to identify newly diagnosed patients with IBD between 1996 and 2015. The primary and secondary outcomes included time to and probability of first and second IBD-related hospitalizations, first and second major surgery, and medication exposures. Medication prescriptions were collected from the public prescription database. We identified 34,644 newly diagnosed patients with IBD (CD = 59.5%). The probability of the first major surgery increased after 2010 in patients with CD (5 years postdiagnosis before and after 2010: 8% [SD = 0.2%] vs 15% [SD = 0.6%]; P < 0.0001) and patients with UC (6% [SD = 0.2%] vs 10% [SD = 0.6%] ;P < 0.0001). The probability of the second major surgery was unchanged in patients with CD. Hospitalization rates remained unchanged. Patients on anti-tumor necrosis factor (anti-TNF) medications had the lowest probability of hospitalizations (overall 5-year probability in patients with IBD stratified by maximal therapeutic step: 5-aminosalicylic acids 37% [SD = 0.6%]; anti-TNFs 31% [SD = 1.8%]; P < 0.0001). Anti-TNFs were more commonly prescribed for patients with CD after 2010 (4% [SD = 0.2%] vs 16% [SD = 0.6%]; P < 0.0001) in the public health insurance plan, especially younger patients. Corticosteroid exposure was unchanged before and after 2010. Immunosuppressant use was low but increased after 2010. The use of 5-ASAs was stable in patients with UC but decreased in patients with CD. The probability of first and second hospitalizations remained unchanged in Québec and the probability of major surgery was low overall but did increase despite the higher and earlier use of anti-TNFs.

Adherence of Infusible Biologics During the Time of COVID-19 Among Patients With Inflammatory Bowel Disease: A Nationwide Veterans Affairs Cohort Study

Adherence of Infusible Biologics During the Time of COVID-19 Among Patients With Inflammatory Bowel Disease: A Nationwide Veterans Affairs Cohort Study

Baseline Disease Activity and Steroid Therapy Stratify Risk of COVID-19 in Patients With Inflammatory Bowel Disease

Baseline Disease Activity and Steroid Therapy Stratify Risk of COVID-19 in Patients With Inflammatory Bowel Disease

Concordance between tuberculin skin test and interferon-gamma release assay for latent tuberculosis screening in inflammatory bowel disease.

Background/AimsLatent tuberculosis screening is mandatory prior to initiating anti-tumor necrosis factor (anti-TNF) medications. Guidelines recommend interferon-gamma release assays (IGRA) as first line screening method for the general population. Studies provided conflicting evidence on IGRA and tuberculin skin test (TST) performance in inflammatory bowel disease (IBD) patients. We assessed test concordance and the effects of immunosuppression on their performance in IBD patients.MethodsWe searched MEDLINE, Embase and Cochrane databases (2011–2018) for studies testing TST and IGRA in IBD. Primary outcome was TST and IGRA concordance. Secondary outcomes were effects of immunosuppressive therapy on performance. Immunosuppression defined as either steroids, thiopurine, methotrexate or cyclosporine use. We used the pooled random effects model to adjust for heterogeneity analyzed using (I2–Q statistics). We compared the fixed model to exclude smaller study effects.ResultsSixteen studies (2,488 patients) were included. Pooled TST and IGRA concordance was 85% (95% confidence interval [CI], 81%–88%; P=0.01). Effects of immunosuppression were reported in 8 studies (814 patients). The odds ratio of testing positive by IGRA decreased to 0.57 if immunosuppressed (95% CI, 0.31–1.03; P=0.06). The odds ratio of testing positive by TST if immunosuppressed was 1.14 (95% CI, 0.61–2.12; P=0.69). The fixed model yielded similar results, however the negative effect of immunosuppression on IGRA reached statistical significance (P=0.01).ConclusionsWhile concordance was 85% between TST and IGRA, the performance of IGRA seems to be negatively affected by immunosuppression. Given the importance of detecting latent tuberculosis prior to anti-TNF initiation, further randomized controlled trials comparing the performance of TST and IGRA in IBD patients are needed.

The SPOSIB SB2 Sicilian Cohort: Safety and Effectiveness of Infliximab Biosimilar SB2 in Inflammatory Bowel Diseases, Including Multiple Switches.

No data on the recently introduced infliximab (IFX) biosimilar SB2 in inflammatory bowel disease (IBD) are available. The Sicilian Prospective Observational Study of Patients With IBD Treated With Infliximab Biosimilar SB2 is a multicenter, observational, prospective study performed among the cohort of the Sicilian Network for Inflammatory Bowel Disease. All consecutive IBD patients starting the IFX biosimilar SB2 from its introduction in Sicily (March 2018) to September 2019 (18 months) were enrolled. Two hundred seventy-six patients (Crohn disease: 49.3%, ulcerative colitis: 50.7%) were included: 127 (46.0%) were naïve to IFX and naïve to anti-tumor necrosis factor medications (anti-TNFs), 65 (23.5%) were naïve to IFX and previously exposed to anti-TNFs, 17 (6.2%) were switched from an IFX originator to SB2, 43 (15.6%) were switched from the biosimilar CT-P13 to SB2, and 24 (8.7%) were multiply switched (from IFX originator to CT-P13 to SB2). The cumulative number of infusions of SB2 was 1798, and the total follow-up time was 182.7 patient-years. Sixty-seven serious adverse events occurred in 57 patients (20.7%; incidence rate: 36.7 per 100 patient-year), and 31 of these events caused the withdrawal of the drug. The effectiveness after 8 weeks of treatment was evaluated in patients naïve to IFX (n = 192): 110 patients (57.3%) had steroid-free remission, while 56 patients had no response (29.2%). At the end of follow-up, 72 patients (26.1%) interrupted the treatment, without significant differences in treatment persistency estimations between the five groups (log-rank P = 0.15). The safety and effectiveness of SB2 seem to be overall similar to those reported for the IFX originator and CT-P13.

Exposure to Anti-tumor Necrosis Factor Medications Increases the Incidence of Pouchitis After Restorative Proctocolectomy in Patients With Ulcerative Colitis.

Pouchitis is the most frequent complication after IPAA in patients with ulcerative colitis. Antibiotics represent the mainstay of treatment, suggesting a crucial role of dysbiosis in the pathogenesis of this condition. Anti-tumor necrosis factor agents have been shown to adversely impact the gut microbiome and local host immunity. The aim of this study is to assess the effect of prior exposure to biologics on the development of pouchitis in patients who have ulcerative colitis. This is a retrospective case-control study. This study was conducted at a tertiary-care IBD center. Consecutive patients with ulcerative colitis who underwent restorative proctocolectomy between 2000 and 2010 were included. The primary outcome measured was the incidence of pouchitis. Four hundred seventeen patients with ulcerative colitis who underwent IPAA were included. The incidence of pouchitis was 40.4%. There were no differences in patient demographics, disease-specific factors, surgical approach, and short-term postoperative complications between patients who developed pouchitis compared to those that did not. Patients exposed to anti-tumor necrosis factor agents or preoperative steroids were significantly more likely to develop pouchitis (anti-tumor necrosis factor: 47.9% vs 36.5%, p = 0.027; steroids: 41.7% vs 23.3%, p = 0.048). However, on multivariable analysis, only anti-tumor necrosis factor therapy was an independent predictor for pouchitis (p = 0.05). Pouchitis was not associated with adverse long-term outcomes. The retrospective design was a limitation of this study. In a large cohort of patients undergoing IPAA for ulcerative colitis with at least a 5-year follow-up, anti-tumor necrosis factor exposure was the only independent risk factor for the development of pouchitis. These agents may "precondition" the pouch to develop pouchitis through alterations in the microbiome and/or local host immunity of the terminal ileum. See Video Abstract at http://links.lww.com/DCR/B19. LA EXPOSICIÓN A MEDICAMENTOS ANTI-TNF AUMENTA LA INCIDENCIA DE POUCHITIS DESPUÉS DE LA PROCTOCOLECTOMÍA RESTAURADORA EN PACIENTES CON COLITIS ULCEROSA:: La pouchitis es la complicación más frecuente después de la anastomosis anal de bolsa ileal en pacientes con colitis ulcerosa. Los antibióticos representan el pilar del tratamiento, lo que sugiere un papel crucial de la disbiosis en la patogénesis de esta afección. Se ha demostrado que los agentes anti-TNF tienen un impacto adverso en la microbiota intestinal y en la inmunidad local del huésped.El objetivo de este estudio es evaluar el efecto de la exposición previa a terapía biológica sobre el desarrollo de la pouchitis en pacientes con colitis ulcerosa.Estudio retrospectivo de casos y controles.Centro de tercer nivel de atención en enfermedades inflamatorias intestinales.Pacientes consecutivos con colitis ulcerosa que se sometieron a proctocolectomía restaurativa entre 2000-2010.Incidencia de pouchitis.Cuatrocientos diecisiete pacientes con colitis ulcerativa se sometieron a anastomosis anal de bolsa ileal. La incidencia de pouchitis fue del 40.4%. No hubo diferencias en la demografía del paciente, los factores específicos de la enfermedad, el abordaje quirúrgico y las complicaciones postoperatorias a corto plazo entre los pacientes que desarrollaron pouchitis en comparación con los que no lo hicieron. Los pacientes expuestos a agentes anti-TNF o esteroides preoperatorios fueron significativamente más propensos a desarrollar pouchitis (anti-TNF: 47.9% vs 36.5%, p = 0.027; esteroides: 41.7% vs 23.3%, p = 0.048). Sin embargo, en el análisis multivariable, solo la terapia anti-TNF fue un predictor independiente para la pouchitis (p = 0.05). La pouchitis no se asoció con resultados adversos a largo plazo.Diseño retrospectivo.En una gran cohorte de pacientes sometidos a anastomosis anal de bolsa ileal para la colitis ulcerosa con al menos 5 años de seguimiento, la exposición a terapía anti-TNF fue el único factor de riesgo independiente para el desarrollo de pouchitis. Estos agentes pueden "precondicionar" la bolsa para desarrollar una pouchitis a través de alteraciones en el microbioma y / o inmunidad local del huésped del íleon terminal. Vea el Resumen del video en http://links.lww.com/DCR/B19.

2921 Correlation Between the Cumulative Risk of Surgery and Timing of Anti-TNF Initiation in Crohn's Disease

INTRODUCTION: Despite their effectiveness in the management of Crohn's disease (CD), anti-tumor necrosis factor medications' use is often delayed until patients fail conventional therapy. There is more evidence in the literature that the early use of anti-TNF in the disease course may improve the long-term outcomes and decrease the risk of complications. However, the optimal time to start these agents is not well defined. In our study, using patient data at the University of Kansas Medical Center, we aimed to determine the cumulative risk of surgery based on the use of anti-TNF agents during the disease course. METHODS: A retrospective cohort study was conducted evaluating CD patients on anti-TNF agents (infliximab, adalimumab, and certolizumab pegol) seen at the University of Kansas Medical Center until May 2018. The primary outcome was the cumulative risk of surgery based on anti-TNF initiating time. RESULTS: A total of 229 patients with CD were enrolled, 143 in the early anti-TNF alpha group and 86 in the late group. Total of 128/229 required surgery. Our analysis demonstrated a positive correlation between the cumulative incidence of surgery and the duration between diagnosis and initiating anti-TNF alpha therapy. In fact, initiating anti TNF at the time of diagnosis prevented the need for surgery for 80-100% of patients. Whereas initiating anti TNF within 10 years of diagnosis prevented the need for surgery in 50% of the patients and more than 80% of patients who started anti-TNF alpha therapy after 20 years of diagnosis had a need for surgery. CONCLUSION: Our study suggests an increased risk of surgery in Crohn's disease patients with the late use of anti-TNF. Early initiation of anti-TNF alpha therapy at the time of diagnosis was associated with the least risk of the need for surgery.