anti-TNF Inhibitors Research Articles

Real-World Experience of the Association of HLADQA1*05 Allele With Loss of Response to Anti-TNF Inhibitors.

Antitumor necrosis factor (anti-TNF) biologics have revolutionized the treatment of inflammatory bowel disease (IBD). Previously, studies have shown an association between the HLADQA1*05 allele and the development of antibodies and were predictive of loss of response. We sought to investigate the rate of the HLADQA1*05 allele in patients with IBD at a New England center and its association with antibody development and discontinuation of anti-TNF therapy. A single center retrospective cohort study with patients on anti-TNF inhibitor therapy being followed at our IBD clinic who had testing performed for the HLADQA1*05 allele were identified and separated into 2 different groups: HLADQA1*05 positive (HLA carriers) or HLADQA1*05 negative (HLA noncarriers). Persistence of remaining on anti-TNF therapy, measurement of drug/antibody levels, and need for dose escalation were collected and stratified amongst the 2 groups. The prevalence of the HLADQA1*05 allele among all IBD patients followed was 53%. We identified 67 IBD patients being treated with anti-TNF medications, 46 (69%) patients with Crohn's disease and 21 (31%) with ulcerative colitis. Most of the HLA carriers (85%) and HLA noncarriers (92%) remained on anti-TNF therapy at the end of the study period. Thirty-six (84%) patients had therapeutic drug monitoring performed during maintenance therapy. Three patients in the HLA carrier group had meaningful antidrug antibody levels necessitating cessation of therapy compared to one patient in the HLA noncarrier group (P = .61). Only 3 (13%) of HLA carriers and 4 (21%) of HLA noncarriers were on combination therapy with an immunomodulator. 65% of HLA carriers required dose escalation compared to 50% of HLA noncarriers (P = .70). The prevalence of the HLADQA1*05 allele was 53% in our New England IBD patient population, similar to what has previously been reported in European studies. The majority of patients remained on anti-TNF therapy at the end of the study period despite carrier status. While there was a trend toward increased need for dose escalation among HLA carriers, this was not statistically significant. Future studies are needed to determine if the presence of the HLADQA1*05 allele leads to antibody development against anti-TNF inhibitors and treatment failure in patients with IBD.

S1046 Major Adverse Cardiovascular Events in Patients With IBD Taking Anti-TNF vs JAK Inhibitors: A Propensity Matched Cohort Analysis

S1046 Major Adverse Cardiovascular Events in Patients With IBD Taking Anti-TNF vs JAK Inhibitors: A Propensity Matched Cohort Analysis

Serological responses to vaccination in children exposed in utero to ustekinumab or vedolizumab: cross-sectional analysis of a prospective multicentre cohort

Evidence on serological responses to vaccination in children exposed to ustekinumab (UST) or vedolizumab (VDZ) in utero is lacking. This multicentre prospective study aimed to assess the impact of prenatal exposure to UST or VDZ due to maternal inflammatory bowel disease (IBD) on serological responses to vaccination and other immunological parameters in exposed children. Children aged ≥ 1 year who were exposed in utero to UST or VDZ and completed at least 1-year of mandatory vaccination were included. We assessed the serological response to vaccination (non-live: tetanus, diphtheria, and Haemophilus influenzae B; live: mumps, rubella, and measles), whole blood count, and immunoglobulin levels. The control group comprised unexposed children born to mothers without IBD. A total of 23 children (median age, 25 months) exposed to UST (n = 13) or VDZ (n = 10) and 10 controls (median age, 37 months) were included. The serological response to vaccination was comparable between the UST and VDZ groups and controls, with an adequate serological response rate of ≥ 80%. Only children exposed to UST showed a slightly reduced serological response to mumps (67% vs. 86% in controls), whereas all children exposed to VDZ showed an adequate response. The majority of the exposed children had normal levels of individual immunoglobulin classes, similar to the controls. No severe pathology was observed in any of the children.Conclusion: Despite the limited sample size, our findings suggest that in utero exposure to VDZ or UST does not significantly impair the vaccine response or broader immunological parameters in exposed children.What is known:• Treatment with anti-TNF inhibitors during pregnancy does not appear to affect serologic response to vaccination in exposed children.• Evidence on the efficacy of vaccination in children exposed to ustekinumab or vedolizumab in utero is almost lacking.What is new:• Our findings suggest that in utero exposure to ustekinumab or vedolizumab does not significantly affect the serological responses to common childhood non-live (tetanus, Haemophilus influenzae B, diphtheria) and live vaccines (measles, mumps, rubella).• No major adverse effects on overall immunological health were observed in children exposed in utero to ustekinumab or vedolizumab.

Systemic Juvenile idiopathic arthritis in child complicated by amyloidosis with secondary nephrotic syndrome

A 7 years old girl diagnosed as case of juvenile idiopathic arthritis since the age of 1.5 years, generalized onset with systemic presentation is complicated by secondary nephrotic syndrome. Renal biopsy showing amyloidosis. Patient has severe disease course being complicated by sever flare ups of disease symptoms and body swelling. Since onset of disease patient got NSAIDs, methotrexate, steroids, anti TNF inhibitors with no or partial response. After diagnosis with secondary nephrotic syndrome due to secondary amyloidosis patient is started on intravenous tocilizumab. There is improvement of patient symptoms.

Correlation between Trabecular Bone Score and Homocysteine Level in Rheumatoid Arthritis Patients on Anti-TNF Inhibitors.

Rheumatoid arthritis (RA) is an independent osteoporosis risk factor. Biologic and immunosuppressive treatment, and levels of homocysteine and 25-OH vitamin D may influence the trabecular bone score (TBS) in RA patients. We aimed to compare the effects of biological (b) and conventional synthetic (cs) disease-modifying anti-rheumatic drugs (DMARDs) on TBS in patients with RA and hyperhomocysteinemia (HHcy) or 25-OH vitamin D deficiency. Patients who had tests conducted for trabecular bone score, bone mineral density (BMD), homocysteine (Hcy) and 25-OH vitamin D at an interval of one year and met the inclusion criteria were enrolled in this retrospective study. Sixty-four patients with RA were enrolled and were divided into the following two groups: the first group (34 patients) had received treatment with bDMARDs and the second group (30 patients) had received csDMARDs. BDMARDs and csDMARDs had a positive influence on TBS and BMD. The best results were observed in the Adalimumab group (p = 0.033). Hyperhomocysteinemia and 25-OH vitamin D deficiency led to lower TBS values. Both bDMARDs and csDMARDs positively affected TBS and BMD in RA patients. High homocysteine serum levels or 25-OH vitamin D deficiency had a negative impact on TBS and BMD after 12 months. Our study aims to show the potential benefits of anti-TNF α drugs on TBS. This impact appears to be strongly associated with serum 25-OH vitamin D and homocysteine levels. Anti-TNF drugs may increase bone mineral density and microstructure. As a result, they may minimize the incidence of fractures in RA patients.

PULMONARY HISTOPLASMOSIS IN A PATIENT WITH CROHN’S DISEASE ON ANTI-TNF INHIBITOR THERAPY

Abstract INTRODUCTION Infliximab, an anti-tumor necrosis factor (TNF) alpha inhibitor, is a commonly used biologic therapy for patients with inflammatory bowel disease (IBD). However, the increased risk of serious infections, including both new and re-activated infections, is a major concern while patients are on this therapy. Often the presence or development of such serious infections necessitates stopping treatment with anti-TNF inhibitors. We describe a case of a patient who developed Histoplasmosis while on infliximab but was later restarted on the same therapy due to risk of severe Crohn’s disease while maintaining him on ongoing Histoplasmosis treatment. CASE DESCRIPTION We describe the case of a 34-year-old male with a past medical history of Crohn’s disease on infliximab, hypertension, depression, and nephrolithiasis who presented to the hospital with dyspnea on exertion, cough, malaise, and night sweats, and was found to have multifocal pulmonary infiltrates on imaging, concerning for atypical pneumonia. He underwent a bronchoscopy and BAL, with pathology reports showing small oval shaped yeast within necrotic granulomas suspicious for Histoplasmosis. He was taken off infliximab and started on liposomal amphotericin for Histoplasma treatment initially, subsequently transitioned to itraconazole for total of 12 months. He was discharged home but was subsequently re-admitted to the hospital with a Crohn’s flare after being taken off infliximab. He was treated with steroids and started on vedolizumab for more gut-selectivity after a multidisciplinary risk/benefit discussion. However, patient was subsequently re-admitted with diarrhea and hematochezia, due to a Crohn’s disease flare while still on steroid taper and having received 2 doses of vedolizumab. He was transitioned to IV steroids and had a colonoscopy which showed large ulcers and mucosal inflammatory changes with a Simple endoscopic score for Crohn’s disease of 18. After a multidisciplinary discussion, he was restarted on infliximab. He was slowly tapered off steroids as his symptoms improved. Repeat colonoscopy after restarting infliximab showed improved but ongoing mucosal inflammatory changes with a Simple endoscopic score for Crohn’s disease of 7. DISCUSSION While anti-TNF inhibitor biologics are commonly used for patients with IBD, opportunistic and fungal infections remain a significant concern while on immunosuppressing biologic therapies, which necessitates stopping the anti-TNF inhibitor. Previously, a study has shown that it is safe to restart anti-TNF therapy after treatment for Histoplasmosis is completed for a 12-month duration. Our case shows that in patients such as ours with severe Crohn’s disease flares while off infliximab, treatment with anti-TNF inhibitors can be resumed after having a multidisciplinary risk/benefit discussion. Figure 1 Colonoscopy findings showing large ulcers and significant mucosal inflammatory changes after patient started on vedolizumab and admitted for Crohn’s Disease flare. Figure 2 Colonoscopy findings showing ongoing mucosal inflammation but improved from prior after restarting treatment with infliximab.

P1068 Limited long-term efficacy of corticosteroids in microscopic colitis emphasizing the need for advanced therapies

Abstract Background Microscopic colitis (MC) is a chronic inflammatory bowel disease, characterized by chronic watery diarrhea, and consisting of 2 subtypes: collagenous (CC) and lymphocytic (LC) colitis. It mainly affects middle-aged adults, although it can occur at any age. The only approved therapy is budesonide, preferably administered in a tapering regimen given the high relapse rates. However, little is known about the long-term natural history of the disease. Methods All adult patients diagnosed with MC after clinical and histological assessment at our referral center between 2014 and 2022 were reviewed. Patients with follow-up less than 3 months or in whom no clear description of initiated therapy could be identified by retrospective chart review, were excluded for evaluation of long-term outcomes. Clinical remission was defined according to the Hjortswang criteria as < 3 stools/day or < 1 watery stool/day. Data on relapse rates, subsequent therapies and surgery were collected. Results Three-hundred twenty-four patients were included, of whom 198 (CC 38.3%, LC 61.7%) were eligible for long-term assessment (Table 1) with a median follow-up of 3.7 [1.1 – 6.3] years. Median age at diagnosis was 63.4 [51.6-74.7] years. Concomitant diseases occurring in 3% or more included thyroid dysfunction (11.6%), coeliac disease (3.5%) and Parkinson’s disease (5.1%), which numerically was more prevalent in the LC (7.4%) than CC (1.3%) population (p=0.09). A minority of patients had a family predisposition of IBD (5.6%). Spontaneous clinical remission occurred in 37 (18.6%) patients, while 4 (2.0%) patients were treated with 5ASA. Most patients (79.3%) were treated with corticosteroids, resulting in 81.1% clinical remission within 3 months. Eighty-six patients (54.8%) flared upon steroid tapering and/or withdrawal requiring corticotherapy reinitiation, prolongation or dose intensification. Due to steroid resistance or dependency, subsequent treatment options included 5ASA (n=14), cholestyramine (n=11), methotrexate (n=6) and azathioprine (n=8), all with limited effect. More advanced therapies are being used, including anti-TNF agents (n=25), vedolizumab (n=9) and JAK inhibitors (n=8). Eighteen patients (9.2%) are currently on maintenance advanced therapies for MC. Two treatment-refractory patients underwent colectomy. Conclusion In this large single-center retrospective analysis, steroids confirmed their first line position to induce clinical remission in MC. However, more than 50% of patients relapsed upon steroid tapering and/or withdrawal, resulting in a substantial need for advanced therapy in this patient population. The long-term efficacy and safety of these advanced IBD therapies in MC should therefore be further investigated.

Effects of disease-modifying anti-rheumatic drugs on sacroiliac MRI score in axial spondyloarthritis: a systematic review and meta-analysis.

Sacroiliac bone marrow edema is an important factor in the diagnosis and management of axial spondyloarthritis (axSpA). The aim of this meta-analysis is to assess the effect of the different bDMARDs and tsDMARDs on the SPARCC score at 12-16 and 48-52 weeks. A systematic review, performed on PubMed (including Medline), Cochrane (CENTRAL) and DOAJ databases, included randomized controlled studies evaluating the sacroiliac joint (SIJ) SPARCC score at 12-16 or 48-52 weeks in patients with axSpA meeting the ASAS 2009 criteria or the modified New York criteria. We included studies evaluating the effects of the different treatments on the SPARCC score of SIJ in axial spondyloarthritis in comparison to a control group. Eighteen studies were included in the meta-analysis. Nine studies evaluated the effect of TNFα inhibitors (TNFi), three for IL-17 inhibitors, and four for JAK inhibitors. At 12 and 16 weeks, SIJ SPARCC score was significantly improved by TNFi (WMD: - 3.29 [95% CI - 4.25; - 2, 34]), by IL-17 inhibitors (WMD: - 4.66 [95% CI - 6.22; - 3.09]), and by JAK inhibitors (JAKi) (WMD: - 3.06 [95% CI - 3.24; - 2.89]). There was no difference between the molecule subgroups. At 48-52 weeks, TNFα inhibitors reduced more SIJ SPARCC, but not significantly (WMD: - 2.26 [95% CI - 4.94; 0.42]), than placebo groups who began a TNFi treatment with delay. Our meta-analysis shows a comparable improvement of the SIJ SPARCC score regarding TNFi, JAKi, and IL-17 inhibitors at three months and suggests the presence of an opportunity window. Key Points • Anti-TNF Ab, anti-IL17 Ab, and JAK inhibitor treatments reduce the sacroiliac joint SPARCC scores. • There is no difference between the different treatments in the reduction of the sacroiliac joint SPARCC score after 3 months in axial spondyloarthritis.

Impact of anti-tumor necrosis factor treatment on lipid profiles in Korean patients with ankylosing spondylitis.

To investigate the effects of anti-tumor necrosis factor (TNF) treatment on lipid profiles and identify risk factors for an increase in total cholesterol (TC) after the anti-TNF treatment in ankylosing spondylitis (AS) patients. This retrospective cohort study analyzed AS patients who received the first-line anti-TNF treatment. Patients with at least nine months of follow-up were included; those who were under 18 years or on any lipid-lowering agent were excluded. A linear mixed model was used to assess the impact of anti-TNF inhibitors on disease activity and lipid profile (TC, low-density lipoprotein [LDL], high-density lipoprotein [HDL], and triglycerides [TG]). Univariable and multivariable linear regression were used to identify risk factors for an increase in TC after 3 months of anti-TNF treatment. A total of 315 AS patients were enrolled (78.1% male, median age 32.0 [26.0~41.0]). TC, HDL, and TG levels significantly increased particularly within the first 3 months of anti-TNF treatment, while LDL level did not show significant changes. Changes in inflammatory markers and lipid particles (TC, LDL, TG) were correlated over time, but HDL showed no significant correlation. Older age, higher baseline erythrocyte sedimentation rate, and lower baseline LDL level were related to an increase in TC after 3 months of the anti-TNF treatment. In AS patients, anti-TNF treatment has been found to increase lipid particles, potentially due to its anti-inflammatory effects. Future research should explore the underlying mechanism and the clinical implications of dyslipidemia, particularly the occurrence of cardiovascular events, following anti-TNF treatment in AS patients.

Practical applications of precision medicine in Psoriasis

The high prevalence of psoriasis creates a significant barrier for the global healthcare system, affecting nearly 7.4 million US adults with direct treatment costs accumulating to over $12 billion annually [1]. Biologic drugs have become a major component of psoriasis management, with anti-TNF inhibitors, IL-17 inhibitors, IL-12, TYK 2 inhibitors, and other medications becoming integral to a patient’s psoriasis treatment regimen [1,2]. However, given the ubiquitous use of biologics in psoriasis management, the response to these medications is not homogenous, with differences in patient genomics contributing to nearly 70% of the inter-individual drug response differences [2]. Pharmacogenetics provides dermatologists with more targeted treatment modalities to illicit the best response in psoriasis patients with minimal adverse effects. Given the costly nature of biologic medications, identifying the optimal drug for each patient may reduce annual healthcare expenditures.

Risk of infection in patients with hidradenitis suppurativa on biologics or other immunomodulators: a systematic review and meta-analysis.

Hidradenitis suppurativa (HS) is a painful skin condition that significantly affects patients' quality of life. Biologic agents, including anti-TNF agents and IL-17 inhibitors, have shown promise as treatment options for HS. However, there is concern about the increased risk of infections associated with these therapies. We conducted a systematic review and meta-analysis following PRISMA and MOOSE guidelines. We searched PubMed and Embase until February 1, 2023. The primary outcome of interest was the incidence of any infectious complications. Secondary outcomes included serious and opportunistic infections in HS patients treated with biologics or other immunomodulators. Twenty-four studies met our inclusion criteria, comprising 1,696 patients. The pooled incidence rate for any infection was 24.2%, primarily consisting of mild respiratory and skin infections. Subgroup analysis based on the mechanism of action (MOA)showed a pooled incidence of 7.77% for anti-IL1, 14.24% for anti-PDE4, and 21.96% for anti-TNF. Notably, patients receiving anti-IL17 had the highest incidence rate of infection at 33.6%, but the relative risk compared to placebo was not significantly elevated (0.99, 95% CI: 0.86-1.14). Serious infections were rare, with pooled incidences of 0.39% for anti-IL17 and 0.03% for anti-TNF. Opportunistic infections were infrequent, with 10 reported cases, including eight oral candidiasis, one cryptosporidiosis, and one Blastocystis hominis infection. The use of biologic therapies in HS patients does not significantly increase the risk of infectious complications. Additionally, the occurrence of serious or opportunistic infections in HS patients treated with biologics appears to be minimal.

S1197 Real-World Experience of the Correlation of HLADQ-A0105 Allele with Development of Immunogenicity Against Anti-TNF Inhibitors at a Single Center in the United States

S1197 Real-World Experience of the Correlation of HLADQ-A0105 Allele with Development of Immunogenicity Against Anti-TNF Inhibitors at a Single Center in the United States

P27 A case of unilateral scleritis and biopsy proven retinal vasculitis in an elderly woman with rheumatoid arthritis and previous retinal detachment surgery with silicone oil band

P27 A case of unilateral scleritis and biopsy proven retinal vasculitis in an elderly woman with rheumatoid arthritis and previous retinal detachment surgery with silicone oil band

Real-world Evidence Comparing Tofacitinib and Vedolizumab in Anti-TNF-experienced Patients With Ulcerative Colitis.

Antitumor necrosis factor (anti-TNF) inhibitors are first-line treatment among patients with ulcerative colitis (UC). With time, patients tend to lose response or become intolerant, necessitating switching to small cell biologics such as tofacitinib or vedolizumab. In this real-world study of a large, geographically diverse US population of TNF-experienced patients with UC, we evaluated the effectiveness and safety of newly initiating treatment with tofacitinib vs vedolizumab. We conducted a cohort study using secondary data from a large US insurer (Anthem, Inc.). Our cohort included patients with UC newly initiating treatment with tofacitinib or vedolizumab. Patients were required to have evidence of treatment with anti-TNF inhibitors in the 6 months prior to cohort entry. The primary outcome was treatment persistence >52 weeks. Additionally, we evaluated the following secondary outcomes as additional measures of effectiveness and safety: (1) all-cause hospitalization; (2) total abdominal colectomy; (3) hospitalization for infection; (4) hospitalization for malignancy; (5) hospitalization for cardiac events; and (6) hospitalization for thromboembolic events. We used fine stratification by propensity scores to control for confounding by demographics, clinical factors, and treatment history at baseline. Our primary cohort included 168 new users of tofacitinib and 568 new users of vedolizumab. Tofacitinib was associated with lower treatment persistence (adjusted risked ratio, 0.77; 95% CI, 0.60 -0.99). Differences in secondary measures of effectiveness or safety between tofacitinib initiators vs vedolizumab initiators were not statistically significant (all-cause hospitalization, adjusted hazard ratio, 1.23; 95% CI, 0.83-1.84; total abdominal colectomy, adjusted HR, 1.79; 95% CI, 0.93-3.44;and hospitalization for any infection, adjusted HR, 1.94; 95% CI, 0.83-4.52). Ulcerative colitis patients with prior anti-TNF experience initiating tofacitinib demonstrated lower treatment persistence compared with those initiating vedolizumab. This finding is in contrast to other recent studies suggesting superior effectiveness of tofacitinib. Ultimately, head-to-head randomized, controlled trials that focus on directly measured end points may be needed to best inform clinical practice.

Comparison of the Persistence of Anti-TNF Agents and Ustekinumab in Patients with Crohn’s Disease: A Study Based on the Korean National Database

Biologics play an important role in the treatment of moderate to severe Crohn's disease (CD). Ustekinumab was approved for such patients in the Republic of Korea on 1 December 2018. Therefore, we need to compare the efficacy of ustekinumab and anti-TNF inhibitors. We compared one-year persistence rates between anti-TNF inhibitors and ustekinumab in moderate-to-severe CD patients using Korean National Health Insurance Service data from 1 December 2016 to 30 November 2021. We also analysed the risk factors for the non-persistence of biologics. The one-year persistence rates with index therapy in bio-naïve and bio-experienced patients were 87.7% and 69.7% for infliximab (p < 0.001), 85.1% and 72.8% for adalimumab (p < 0.001), and 92.1% and 89.8% for ustekinumab (p = 0.333), respectively. The risk factors for non-persistence were older age, non-use of an immune modulator, and previous biologic exposure in both the infliximab and adalimumab groups. The one-year persistence rate of ustekinumab was higher than that of anti-TNF inhibitors in bio-naïve patients (hazard ratio [HR] 0.53; 95% confidence interval [CI] 0.35-0.81; p = 0.003) and bio-experienced patients (HR 0.32; 95% CI 0.22-0.45; p < 0.001). Ustekinumab was superior in bio-naïve CD patients compared to anti-TNF inhibitors. However, the follow-up time was relatively short; further studies should continuously collect and analyse data.

CHARACTERIZING THE JOHNS HOPKINS INFLAMMATORY BOWEL DISEASE COHORT USING OMOP CDM

Abstract BACKGROUND Inflammatory Bowel Disease (IBD) is an increasingly prevalent condition that results in weight loss, bloody diarrhea, and poor quality of life. Traditional population-based research on patients with IBD has involved use of relatively shallow claims data that is deficient in precise demographics. IBD research using richly detailed electronic health record (EHR) data has been difficult due to the need for laborious manual chart review to extract information, but new methods and technology allow for rapid EHR data extraction. We present here the results of the extraction of IBD patient data from our EHR into the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). METHODS This study is an observational cohort study using patient health care data from our EHR extracted into the OMOP CDM. Transforming data into the standard CDM format allows for information from different databases and coding schema to be compared and aggregated. We used a de-identified dataset of all patients seen at Johns Hopkins Medicine since 2016. Our cohort of IBD, Crohn’s disease (CD), and Ulcerative Colitis (UC) patients were stratified by age, sex, race, weight, and pregnancy status. Within the cohorts, we obtained demographics, comorbidities, symptoms, labs, medications, and other data. We validated the extraction by comparison with EHR queries using Slicer/Dicer (SD). RESULTS There were 11,357 IBD patients including 6,512 CD patients and 4,224 UC patients. There were more female patients for both CD and UC (56.4% v 57.5%) and more white patients for both CD and UC (55.4% v 56.7%) compared to black (23.5% v 22.6%) and Asian patients (5.6% v 4.9%). CD and UC patients were treated with systemic steroids (49.1% v 51.5%), 5-ASA (24.9% v 47.2%) anti-TNF inhibitors (24.0% v 12%), IL12/23 inhibitors (8.4% v 2.7%), and JAK inhibitors (0.3% v 1.8%). Using SD queries, the percent differences were determined between the OMOP and EHR data, revealing a 0.54% difference in the number of CD patients and 10.36% difference in the number of UC patients (Table 1). CONCLUSION Using OMOP CDM to analyze clinical characteristics and outcomes for patients with IBD is a valuable method for obtaining de-identified patient data, reducing patient risk, and facilitating rapid creation of on-demand cohorts for multi-institutional research studies. This advantage is balanced by the lack of access to row-level data to validate cohorts. Local validation of data extraction through SD queries can allow for rapid creation of cohorts for big data research. The most significant differences between SD queries and OMOP CDM was in the calculation of prevalence of medications and race, suggesting that differing data extraction coding methods could result in queries that underestimate rates of treatment due to proprietary local coding schema.

Successful long-term treatment of paediatric ulcerative colitis with vedolizumab: a case report

Biologics are recommended to treat paediatric ulcerative colitis (UC) that is chronically active or steroid-dependent despite aminosalicylic acids (5-ASA) and thiopurine treatments. Anti-tumour necrosis factor inhibitors (Anti-TNF inhibitors) are the...

S49 Insurance Delays Biologic Treatment of Pediatric IBD in Tertiary Care Center

Background: Use of biologic medications, such as anti-TNF inhibitors, anti-integrins, and anti-IL-12/23s, for treating pediatric inflammatory bowel disease (IBD) has shown great success in controlling disease and inducing remission. They are often now the therapy of choice in pediatric IBD with evidence of enhanced utility when used early in the disease course. However, the process to get a biologic medication approved for IBD, particularly in pediatrics where FDA approvals lag, is often lengthy and delayed due in large part to the insurance pre-authorization process. While others have reported on insurance delays, it has not been well described how delays are associated with drug choice, payor, past drug failures, and year of initiation. Methods: Patients under 22 years of age at biologic order date were included from a Prospective BioBank Program, which includes longitudinal, clinical patient data, at the IBD Center and Infusion Center of a large, US tertiary care center from 2014-2022. Biologic medications with at least one infusion treatment were considered (infliximab and biosimilars, ustekinumab, vedolizumab). Biologic order date, first infusion date, and insurance at infusion time were recorded. Available prior biologic failures at time of order were also recorded. Results: Data from 211 infusion biologic orders (with known order and initiation date) was recorded, representing 158 individual patients (105 CD, 45 UC, 5 IBD-U; median age at biologic order = 15.12 years). There was a mean delay of 20 days (median = 15, IQR = 16) between medication order and first treatment infusion. Patients ordered ustekinumab (n = 86) experienced significantly more delays of greater than 2 weeks to first infusion than patients ordered infliximab (n = 81, P = 0.0044) or vedolizumab (n = 44, P = 0.035). Though limited sample size, patients with public insurance (n = 8) experienced a similar proportion of delays greater than 2 weeks as patients with private insurance (n = 151) (62.5% and 60%, respectively). There was no significant difference in delay when comparing patient health insurance company at time of infusion (Aetna, n = 23; Cigna, n = 23; Empire Bluecross Blueshield, n = 35; Oxford, n = 20; and United Healthcare n = 33). Over half (57%) of patients with a previously-failed biologic of known order-to-infusion delay time (n = 45) had a greater delay to get their second biologic than their previous biologic. Delays of greater than 2 weeks to first infusion were significantly more likely for biologics ordered 2018-2022 (n = 135) than biologics ordered 2014-2018 (n = 76, P = 0.0049). Conclusion(s): Long delays to receive crucial medication are commonplace in IBD in the US. Documentation of prior failures is often required to achieve approval, but history of prior failures lengthened the approval process. Though biologic treatments have advanced and shown success over the time period considered, patients were more likely to experience lengthy delays to treatment in more recent years. While insurance type and company do not seem to play an important role in treatment delay, biologic choice does. Further research is required to explore how delays may influence physician biologic selection and hinder attempts at precision therapy.

Infliximab and Tofacitinib Attenuate Neutralizing Antibody Responses Against SARS-CoV-2 Ancestral and Omicron Variants in Inflammatory Bowel Disease Patients After 3 Doses of COVID-19 Vaccine

Infliximab and Tofacitinib Attenuate Neutralizing Antibody Responses Against SARS-CoV-2 Ancestral and Omicron Variants in Inflammatory Bowel Disease Patients After 3 Doses of COVID-19 Vaccine

S1033 Upending Ustekinumab: IV Dosing as Maintenance Dosing

Introduction: Ustekinumab is indicated for moderate to severe Crohn’s disease (CD) patients who failed previous treatment. Standard dosing is combining a single intravenous (IV) weight-based induction with subcutaneous (subQ) maintenance every 8 weeks. Although effective, secondary loss of response occurs despite dose optimization. Our aim was to evaluate the safety and effectiveness of Ustekinumab re-induction and IV maintenance in patients with refractory CD. Methods: We identified four individuals with CD at a single tertiary Veterans Affairs medical center. Each patient received IV induction with Ustekinumab after failed previous treatment with corticosteroids and anti-TNF inhibitors. Following transition to subQ maintenance dosing, these individuals had loss or inadequate response as seen with objective measures (C-reactive protein, fecal calprotectin, endoscopy, radiography). Despite dose optimization to every four weeks, drug trough levels remained subtherapeutic (< 4.5 µg/dL) with ongoing active disease. As salvage therapy, these patients then received weight-based IV maintenance dosing every four weeks. Disease activity was reassessed after three months. Results: All achieved endoscopic and/or radiographic remission with therapeutic drug troughs. No adverse effects were reported. Conclusion: In our early observation, ustekinumab re-induction with continued IV maintenance was a safe and effective treatment. This novel approach may be an option for patients with a loss or inadequate response to standard ustekinumab therapy. Our sample size is small, so our study may be underpowered; however, data collection is ongoing.