Initiation Of Infliximab Research Articles

Long-term TNF-alpha therapy for preserving beta cell function in new onset type 1 diabetes: a case report

BackgroundType 1 diabetes mellitus (T1D) is an autoimmune disease caused by destruction of pancreatic islet beta-cells. There is significant residual beta-cell function, measured through circulating C-peptide, present at the time of T1D diagnosis but this subsequently decreases with time. Higher residual beta-cell function at diagnosis associates with better glycaemic control and less glucose variability, and later in the disease course with less hypoglycaemia, lower glucose variability and fewer microvascular complications. There is therefore value in preserving residual beta cell function in new onset T1D Immunotherapeutic agents can protect residual beta-cell function in type 1 diabetes. However, clinical trials of such agents, whilst demonstrating C-peptide preservation in short term studies, have yet to be taken forward into routine clinical care due to concerns around safety and long-term efficacy. Here we report the case of a gentleman with newly diagnosed T1D whose glycaemic control and insulin requirement improved whilst on a five year infusion programme of infliximab, a monoclonal antibody against TNF-alpha, for colitis.Case presentationA 52-year-old White Caucasian man was diagnosed with T1D in August 2018. Glucose was 25.6 mmol/L, HbA1c was 98mmol/mol and GAD antibodies were strongly positive. HbA1c marginally improved to 91mmol/mol following initiation of insulin detemir 5 units at night and 1:10 g of insulin aspart (November 2018). In June 2019, he developed rectal bleeding and abdominal pain. Following colonoscopy, he was diagnosed with “indeterminate colitis” and commenced on 6-weekly infusions of 400-450 mg infliximab. Thus far, he has received 32 doses and achieved colitis remission. Following infliximab initiation there was increased frequency of mild-moderate hypoglycaemia and he was gradually weaned off and discontinued detemir in June 2020. Since then, HbA1c improved from 57mmol/mol in August 2019 to 52mmol/mol in April 2022, remaining stable at 51mmol/mol. His most recent HbA1c is 54mmol/mol in February 2024. His c-peptide was 550pmol/L in October 2022 and 442pmol/L in February 2024, suggesting well-preserved beta-cell function almost 6 years post-diagnosis.ConclusionsOur patient’s improvement in glycaemic control can be explained by immunomodulation and C peptide preservation from infliximab. With the growing focus on type 1 diabetes disease modulation and working towards an ‘insulin free T1D’, our findings strengthen the evidence base for the repurposing of and long-term treatment with anti-TNF-α agents to preserve beta-cell function in new onset T1D.

Different infliximab induction dosing regimens do not affect remission rates up to 1 year in children with Crohn's disease.

Multiple studies in patients with Crohn's disease (CD) treated with anti-tumor necrosis factoralphaagents have shown that proactive therapeutic drug monitoring (TDM) during the maintenance phase leads to improved outcomes. We aimed to assess whether accelerated (IFX) administration during induction resulted in improved outcomes. This retrospective study included CD patients aged 5-17.9 years that were treated with IFX. We compared outcomes of patients treated during induction with 5-8 mg/kg dosing at Weeks 0, 2, 6, and 14 (Group 1), versus accelerated dosing (≥8 mg/kg and/or >4 infusions until Week 14, Group 2) of IFX. Primary outcome was steroid-free clinical remission by Week 52. Sixty-eight patients were included, of whom seven discontinued IFX before Week 14, due to infusion reactions, immunogenic failure, or primary nonresponse. Comparison of Group 1 (n = 25) and Group 2 (n = 36) showed similar clinical characteristics, as well as inflammatory markers, at IFX initiation. Despite receiving significantly more IFX, and reaching a higher trough level by Week 14 (10.3 ± 1.2 vs. 3.3 ± 0.7, p < 0.001), the median Pediatric Crohn's disease Activity Index (PCDAI) was slightly higher in Group 2 versus Group 1 (14 [5-20] vs. 5 [0-15], p = 0.02). However, at Weeks 26 and 52 the PCDAI and inflammatory markers were comparable between the groups. Moreover, about 70% in both groups achieved the desirable trough IFX levels by Week 52. Accelerated IFX dosing during induction did not result in improved outcomes up to 12 months follow-up. Prospective studies are required to determine the exact timing in which proactive TDM should be applied.

Risk factors for infliximab-induced infusion reactions based on a retrospective study of medical information.

Infliximab is indicated for a wide range of diseases, and infusion reactions (IRs) have been reported after infliximab administration in 17.6% of patients in clinical practice. This study aimed to identify the risk factors for IRs before the administration of infliximab based on available patient information. We retrospectively analyzed patients treated with infliximab. Data were compared between patients with and without IRs immediately before initiation of infliximab. Elevated C-reactive protein (CRP) (odds ratio (OR), 2.150; 95% confidence interval (CI), 1.329-3.477; p=0.002) before infliximab administration was a significant risk factor for developing an IR. Patients with elevated CRP levels before therapy initiation may require more careful monitoring after infliximab administration.

Early versus late initiation of infliximab for refractory uveitis in a cohort of Egyptian BD patients

Introduction Behçet’s syndrome is a multisystem inflammatory disease characterized by recurrent oral aphthous ulcers, genital ulcers, skin lesions, and uveitis. Ocular involvement, occurring roughly in 50% of patients, is one of the most feared complications of Behçet’s syndrome. Recurrent severe uveitis leads to irreversible severe vision loss. Purpose The main goals in the management of patients with Behçet’s uveitis are rapid resolution of intraocular inflammation, prevention of recurrent attacks, and achievement of complete remission and preservation of vision. Corticosteroids are generally used for the treatment of acute episodes of inflammation. According to the updated EULAR recommendations for the management of BS ‘any patient with BS and inflammatory eye disease affecting the posterior segment should be on a treatment regime such as azathioprine, cyclosporine-A, interferon alpha or monoclonal tumor necrosis factor alpha antagonists. Methods Infliximab has been increasingly used in the treatment of Behçet’s syndrome patients with uveitis when they are refractory to conventional immunosuppressive therapy. However, there is no consensus on the best time to start anti- tumor necrosis factor alpha therapy. In our study we evaluated the outcome of early initiation of infliximab for refractory uveitis in cohort of Egyptian Behçet’s syndrome patients. Conclusion Early administration of Intravenous Infliximab therapy for severe sight-threatening uveitis and chorioretinitis in Egyptian Behçet’s syndrome patients has a favorable value regarding BCVA. Multidisciplinary approach in managing Behçet’s uveitis is mandatory to reach better functional visual outcome.

Effects of prednisolone tapering on effectiveness of infliximab in patients with ulcerative colitis: data from a retrospective cohort

Background and objectiveThe influence of concomitant prednisolone on clinical outcomes and safety in infliximab-treated ulcerative colitis (UC) patients is unknown.Design, setting, participants and outcome measuresA retrospective cohort study was performed,...

COMPARABLE CLINICAL OUTCOMES IN PEDIATRIC PATIENTS WITH CROHN’S DISEASE TREATED WITH ACCELERATED VS. STANDARD INFLIXIMAB DOSING DURING INDUCTION

Abstract BACKGROUND Accelerated infliximab administration during induction is used extensively in pediatric patients with Crohn’s disease (CD), though the overall effect of this approach on patients’ outcomes in several studies has been questionable. We aimed to assess in a real-life cohort whether accelerated infliximab administration during induction resulted in improved clinical outcomes in pediatric CD. METHODS This single-center retrospective study included patients aged&amp;lt;18 years diagnosed with CD between 2016-2021 that were treated with infliximab. We compared outcomes of patients treated with standard-dosing (0,2,6,14, up to 8mg/kg) vs. accelerated-dosing. Primary outcome with steroid-free clinical remission by week 52. RESULTS Sixty-eight patients were included, of whom 7 discontinued infliximab prior to week 14, due to infusion reactions or primary non-response resulting in surgery. 25 received standard-dosing, and 36 accelerated-dosing, including 19 patients that received &amp;gt;8mg/kg infliximab at 1st infusion. Comparison of both groups at time of infliximab initiation showed similar demographic features, Paris classification, prior rates of medication failure and rates of current immunomodulator use. Importantly, the baseline median pCDAI (23.0 [12.5-26.5] vs. 18.8 [13.1-26.9]), CRP (1.5 [0.3-5.5] vs. 1.4 [0.4-3.4] and calprotectin (782 [66-3840] vs. 1060 [576-2900]) values were comparable in the standard- and accelerated-dosing groups, respectively. Patients in the accelerated-dosing group achieved a higher trough infliximab level by end of induction (10.3±6.6 vs. 3.3±3.4, P&amp;lt;0.001), and more patients were above the target trough infliximab level (78.1% vs. 21.8%, P&amp;lt;0.001). However, the median PCDAI and inflammatory markers at week 14, 26 and 52 were comparable between groups. Moreover, the rates of patients above the desired trough levels were also comparable at week 52 (71.4% vs. 70.6% in the accelerated vs. standard-dosing group). Finally, rates of treatment discontinuation were also similar among groups. CONCLUSIONS In a retrospective cohort, accelerated infliximab dosing during induction didn’t result in improved clinical outcomes up to 52 weeks.

P782 Comparison of accelerated and standard infliximab induction regimens in Acute Severe Ulcerative Colitis using propensity score: A retrospective multicenter study in a Chinese cohort

Abstract Background The optimal regimen of infliximab salvage in acute severe ulcerative colitis (ASUC) patients remains controversial. This retrospective multicenter study aimed to compare accelerated and standard infliximab induction in a Chinese cohort of ASUC patients, and to explore risk factors associated with poor prognosis. Methods Data were collected retrospectively from steroid-refractory ASUC patients who received infliximab induction as rescue therapy at seven tertiary centers across China. Accelerated infliximab induction was defined as receiving two doses of infliximab on or before day 13 and/or receiving intensified doses of ≥ 7.5 mg/kg. Outcomes including colectomy and clinical remission (Mayo score ≤ 2 and every subscore ≤ 1 at day 14) rates were compared using propensity score adjustment for potential confounders. The variables in propensity score model was determined by logistic regression analysis for accelerated induction. Results A total of 76 patients were included: 29 received standard induction and 47 received accelerated induction. The overall disease severity was significantly higher in patients of accelerated group (Table). The 30-day colectomy rates did not differ between two groups (4.3% vs. 0%, P=0.522). However, the accelerated group had a higher 90-day colectomy rate (17.8% vs. 0%, P=0.019) and lower clinical remission rate (27.7% vs. 65.5%, P=0.001). (Figure. A) After adjusting with propensity score and institution, there was no significant difference in colectomy (P=0.20) or no clinical remission (P=0.48) hazards. Dose-effect curves plotted by restricted cubic splines (adjusted for propensity score and institution) showed decreased colectomy hazard with higher cumulative infliximab dosage within 5 days, while no improvement was observed for increasing cumulative infliximab dosage within 28 days. (Figure. B) Multivariate logistic regression analyses revealed female gender (OR=7.69, 95%CI: 1.96-33.33) and C-reactive protein (CRP) &amp;gt;10 mg/L at infliximab initiation (OR=5.00, 95%CI: 1.27-24.34) as independent risk factors for no clinical remission. (Figure. C) Conclusion After adjusting for confounders, there were no significant differences in colectomy or clinical remission rates between accelerated and standard infliximab induction among steroid-refractory ASUC patients. Elevated CRP at infliximab initiation indicated more intensive treatment or earlier surgery to be considered. And it would be better to give early intensified dosage within 5 days if needed.

P192 Personalizing treatment for predicting response to infliximab in children with Crohn’s disease using proteomic biomarkers

Abstract Background Identifying minimally invasive diagnostic biomarkers that predict and monitor response to TNF inhibitors would enable treatment to be personalized and increase knowledge of the biological pathways associated with response or lack thereof. Methods Children and adolescents with Crohn’s disease who started treatment with infliximab (IFX) were enrolled in a prospective, multi-center (n=6) trial to identify biomarkers that predict response to IFX. Electronic case report forms were prepared by Studytrax (Macon, GA). Subjects &amp;lt;18 years of age were diagnosed with Crohn’s disease using standard clinical/pathologic criteria. Clinical evaluation and serum samples were obtained prior to initiation of IFX, after induction (dose 4), at six months, and after one year or at the time of treatment withdrawal. There were 119 subjects enrolled and 102 subjects completed induction. Non-responders (n=15) were defined prior to the 4th infusion as having a PCDAI &amp;gt; 10, an elevated Physician Global Assessment (PGA) or requiring dose escalation or medication change. Responders at the 4th infusions were either in remission (PUCAI ≤ 10) or were described as quiescent by PGA. Using the 7k SomaScan (SomaLogic; Boulder, CO) proteomics platform, quantitative protein profiles were generated from banked pre-treatment (V1) and after the three-dose induction (V2) to identify candidate protein biomarkers predictive of therapeutic response. Associations between the 7,310 proteins detected with SomaScan and response to IFX were assessed using t test. Response predictor models were developed using linear regression with backward selection. We report our preliminary findings from a discovery cohort of 56 subjects who completed induction. Results There were 15/56 (27%) non-responders and 41/56 (73%) responders at V2 after IFX induction. SomaScan analysis of the 56 individuals identified sets of differentially expressed proteins discriminating between non-responders and responders at both V1 and V2 and also defined protein signatures that changed from V1 to V2 for responders and non-responders, respectively. Strikingly, only responders demonstrated significant decreases in pro-inflammatory pathways at V2 compared to V1, thereby correlating well with anticipated reduced inflammation in responders. A 6-protein linear regression model performed with an AUC of 0.99 for predicting IFX response at pre-treatment V1. Conclusion In a discovery cohort from a multicenter, prospective trial of children and adolescents treated with infliximab, a comprehensive proteomics platform was able to identify serum proteins that are highly associated with response to infliximab and accurately predict response prior to treatment.

Tofacitinib in Acute Severe Ulcerative Colitis (TACOS): A Randomized Controlled Trial.

Intravenous corticosteroids are the mainstay of treatment of patients hospitalized with acute severe ulcerative colitis (ASUC). However, 30%-40% of the patients are refractory to corticosteroids. We investigated whether addition of tofacitinib to corticosteroids improved the treatment responsiveness in patients with ASUC. This single-center, double-blind, placebo-controlled trial randomized adult patients with ASUC (defined by the Truelove Witts severity criteria) to receive either tofacitinib (10 mg thrice daily) or a matching placebo for 7 days while continuing intravenous corticosteroids (hydrocortisone 100 mg every 6 hours). The primary end point was response to treatment (decline in the Lichtiger index by >3 points and an absolute score <10 for 2 consecutive days without the need for rescue therapy) by day 7. The key secondary outcome was the cumulative probability of requiring initiation of infliximab or undergoing colectomy within 90 days following randomization. All analyses were performed in the intention-to-treat population. A total of 104 patients were randomly assigned to a treatment group (53 to tofacitinib and 51 to placebo). At day 7, response to treatment was achieved in 44/53 (83.01%) patients receiving tofacitinib vs 30/51 (58.82%) patients receiving placebo (odds ratio 3.42, 95% confidence interval 1.37-8.48, P = 0.007). The need for rescue therapy by day 7 was lower in the tofacitinib arm (odds ratio 0.27, 95% confidence interval 0.09-0.78, P = 0.01). The cumulative probability of need for rescue therapy at day 90 was 0.13 in patients who received tofacitinib vs 0.38 in patients receiving placebo (log-rank P = 0.003). Most of the treatment-related adverse effects were mild. One patient, receiving tofacitinib, developed dural venous sinus thrombosis. In patients with ASUC, combination of tofacitinib and corticosteroids improved treatment responsiveness and decreased the need for rescue therapy.

Fecal Calprotectin at Postinduction Is Capable of Predicting Persistent Remission and Endoscopic Healing after 1 Year of Treatment with Infliximab in Pediatric Patients with Crohn's Disease.

: The recent update on Selecting Therapeutic Targets in Inflammatory Bowel Disease initiative has added a decrease in fecal calprotectin (FC) to an acceptable range as an intermediate target for Crohn's disease (CD). We aimed to investigate whether postinduction FC could predict future persistent remission (PR) and endoscopic healing (EH) after 1 year of treatment with infliximab (IFX) in pediatric patients with CD. : This multicenter retrospective observational study included pediatric patients with CD who were followed up for at least 1 year after starting IFX. The association of postinduction FC with PR and EH was investigated. : A total of 132 patients were included in this study. PR and EH were observed in 71.2% (94/132) and 73.9% (82/111) of the patients, respectively. In multivariate logistic regression analysis, only the postinduction FC level was associated with PR (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.08 to 0.66; p=0.009). The FC levels at initiation of IFX and postinduction were significantly associated with EH (OR, 0.73; 95% CI, 0.53 to 0.99; p=0.044 and OR, 0.20; 95% CI, 0.06 to 0.49; p=0.002, respectively). According to the receiver operating characteristic curve analysis, the optimal cutoff level for postinduction FC associated with PR was 122 mg/kg, and that associated with EH was 377 mg/kg. : Postinduction FC was associated with PR and EH after 1 year of treatment with IFX in pediatric patients with CD. Our findings emphasize the importance of FC as an intermediate target in the treat-to-target era.

CT enterography-based radiomics combined with body composition to predict infliximab treatment failure in Crohn's disease.

Accurately predicting the treatment response in patients with Crohn's disease (CD) receiving infliximab therapy is crucial for clinical decision-making. We aimed to construct a prediction model incorporating radiomics and body composition features derived from computed tomography (CT) enterography for identifying individuals at high risk for infliximab treatment failure. This retrospective study included 137 patients with CD between 2015 and 2021, who were divided into a training cohort and a validation cohort with a ratio of 7:3. Patients underwent CT enterography examinations within 1month before infliximab initiation. Radiomic features of the intestinal segments involved were extracted, and body composition features were measured at the level of the L3 lumbar vertebra. A model that combined radiomics with body composition was constructed. The primary outcome was the occurrence of infliximab treatment failure within 1year. The model performance was evaluated using discrimination, calibration, and decision curves. Fifty-two patients (38.0%) showed infliximab treatment failure. Eight significant radiomic features were used to develop the radiomics model. The model incorporating radiomics model score, skeletal muscle index (SMI), and creeping fat showed good discrimination for predicting infliximab treatment failure, with an area under the curve (AUC) of 0.88 (95% CI 0.81, 0.95) in the training cohort and 0.83 (95% CI 0.66, 1.00) in the validation cohort. The favorable clinical application was observed using decision curve analysis. We constructed a comprehensive model incorporating radiomics and muscle volume, which could potentially be used to facilitate the individualized prediction of infliximab treatment response in patients with CD.

The role of infliximab in treating refractory cardiac sarcoidosis

Abstract Introduction Cardiac sarcoidosis (CS) is associated with therapeutic challenges, and a high morbidity and mortality. Tumour necrosis factor alpha inhibitors like infliximab may be a treatment option for patients with persistent myocardial inflammatory activity despite conventional immunosuppressive treatment with steroids and steroid-sparing agents. Purpose To identify the safety and efficacy of infliximab in the treatment of refractory cardiac sarcoidosis. Methods We conducted a review of refractory CS patients who had been or were actively on treatment with Infliximab at our specialist tertiary care hospital from January 2017 to January 2023. Serial echocardiographic and FDG-PET scan changes as well as long term clinical data on morbidity and mortality was recorded. Results Six CS patients on infliximab were retrospectively identified. The mean age at CS diagnosis was 47.0±5.9 years and mean duration between CS diagnosis and starting infliximab was 21.4±14.2 months (Table 1). Infliximab was commenced due to persistent inflammation on FDG-PET scan and/or CMR despite being on at least two agents (prednisolone and methotrexate ± hydroxychloroquine) in 5 cases and prednisolone alone (intolerance to methotrexate) in one case. At baseline, 3 patients presented with ventricular arrhythmias, 2 with atrioventricular block and 2 with heart failure. After a mean follow up of 21.2±15.5 months of being on infliximab, 5/6 CS patients had decreased myocardial uptake on PET (1 was awaiting a scan) which included complete resolution of FDG-PET signal in one patient (Table 2). A trend in improvement of mean LVEF [52.7±6.6% to 60.2±5.9%, p = 0.10] and reduction of mean prednisolone dose [19.2±6.6mg to 11.3±7.0mg, p = 0.08] was observed during Infliximab treatment. None of the patients had worsening of LVEF or admission with acute heart failure whilst being on infliximab. A total of 4/6 patients had an Implantable Cardioverter Defibrillator device in situ at the time of Infliximab initiation. No major arrhythmias were observed during follow up. One patient died following complications of patent foramen ovale repair. There were three new cases of infection (1 pneumonia and 2 COVID-19 pneumonitis) and one case of renal cell carcinoma diagnosis three years after Infliximab treatment initiation. The drug safety was overall satisfactory since none of the patients required hospitalisation (Table 2). Case 2 patient stopped infliximab after 13 months of treatment and was found to have disease relapse seven months later. During a 20 month follow up of being on infliximab again, he demonstrated complete resolution of FDG uptake on subsequent FDG-PET scan. Conclusion This study supports the use of infliximab in refractory CS by demonstrating improvement in clinical, functional and tissue characterization parameters. However, infliximab is associated with an increased risk of infections.

Infliximab for Treatment of Immune Adverse Events and Its Impact on Tumor Response.

Background: Immune-related adverse events (irAEs) challenge the use of immune checkpoint inhibitors (ICIs). We performed a retrospective study to evaluate response to infliximab for immune-related adverse event management, and infliximab's effect on progression-free survival (PFS) and overall survival (OS) with a focus on melanoma and genitourinary cancers. Methods: We retrospectively reviewed records of all cancer patients exposed to infliximab after immune checkpoint inhibitor (ICI) treatment from 2004 to 2021 at the MD Anderson Cancer Center. Survival was assessed utilizing the Kaplan-Meier method. Univariate and multivariate logistic regression was utilized to evaluate predictors of infliximab response, OS, and PFS. Results: We identified 185 cancer patients (93 melanoma and 37 genitourinary cancers) treated with ICI and who received infliximab to treat irAEs. Within 3 months of treatment initiation, 71% of the patients responded to infliximab, 27% had no response, and 2% had unknown response. Among different irAEs, colitis was associated with increased response to infliximab at 3 months, irrespective of the type of malignancy. We evaluated best tumor response before and after infliximab in the entire cohort and again in the melanoma and genitourinary (GU); the findings were similar in the melanoma cohort and the entire cohort, where best tumor response before and after infliximab was not significantly different. In the melanoma cohort, acute kidney injury (AKI) was associated with increased risk of death, p = 0.0109, and having response to infliximab was associated with decreased risk of death, p = 0.0383. Interestingly in GU cancer patients, myositis was associated with increased risk of death, p = 0.0041, and having a response to infliximab was marginally associated with decreased risk of death, p = 0.0992. As regards PFS, in a multivariate Cox regression model, having a history of cardiovascular disease remained significantly associated with shorter PFS in the melanoma cohort. For patients with GU cancers, response to infliximab was associated with longer PFS. Conclusions: Our study is among the largest retrospective analyses of infliximab use for irAE management. Patients with colitis were the best responders to infliximab. AKI before initiation of infliximab in the melanoma subcohort and myositis in GU subcohort are associated with higher risk of death. Our results indicate no association between infliximab and cancer progression with the exception of genitourinary cancers.

Similar Growth Outcomes in Children with Inflammatory Bowel Disease Initiated on Infliximab Originator or Biosimilar.

Growth is an important clinical outcome, especially in childhood-onset inflammatory bowel disease (IBD). Prior research has demonstrated growth improvements with infliximab therapy. There are limited studies evaluating whether clinical and growth outcomes in children initiated on the infliximab originator and infliximab biosimilar are similar. This was a single-center retrospective review of patients with IBD, younger than 17 years old, and initiated on the infliximab originator or biosimilar for at least 12 months between April 2016 and February 2021. Propensity score matching was utilized. Laboratory values, disease activity scores, and growth values were collected at baseline (prior to infliximab initiation), 6 months, and 12 months post initiation. Linear mixed models with random intercepts were used to test differences in measures over time and between study groups. There were 113 patients on the originator and 39 patients on a biosimilar who met eligibility criteria. Propensity score methodology identified 37 dyads (1:1 match). Weight, height, and body mass index z scores increased over time (from baseline to 12 months) for both groups ( P < 0.05) and there was a similar rate of change between study groups. Clinical outcomes of lab values (albumin, C-reactive protein, and hemoglobin) and disease activity scoring were similar from baseline to 12 months between study groups. There were similar improvements in growth and clinical outcomes in patients initiated on the infliximab originator compared to an infliximab biosimilar agent. This study adds to the limited research evaluating whether infliximab biosimilars have similar growth outcomes in children with IBD.

Implementation of risk minimization measures to reduce the risk of tuberculosis among tumor necrosis factor medication users.

To examine the adherence to risk minimization measures (RMMs) in newly treated patients with anti-tumor necrosis factor-alpha (anti-TNF-α) medications at one of the largest tertiary care hospitals in Saudi Arabia. We included patients who had at least one prescription of infliximab or adalimumab. The index date was the first recorded date of infliximab or adalimumab prescription. New users of anti-TNF-α were divided into pre- and post-RMM implementation groups. The outcome of interest was the proportion of patients that received tuberculosis (TB) screening, including a chest X-ray (CXR) or a QuantiFERON test within 1 month prior to the index date. A pre-post RMM implementation comparison of TB screening among infliximab users showed a significant increase in the rates of CXR tests (from 7.5% before RMM implementation to 13.8% after RMM implementation, p < 0.001) and the rates of QuantiFERON tests (4.5% before RMM implementation to 24.1% after RMM implementation, p < 0.001). RMMs were introduced to the study site at the same time as adalimumab was approved and the proportion of patients receiving TB screening was 25.2%. TB screening prior to initiation of infliximab or adalimumab was not optimal. However, we noted an improvement in TB screening after the implementation of RMMs for infliximab. Future research may address reasons for low adherence to testing requirements for TB prior to initiation of anti-TNF-α medications.

Infliximab for vascular involvement in Behçet's syndrome

ObjectiveVascular involvement is an important cause of morbidity and mortality in patients with Behçet's syndrome (BS). We aimed to survey the efficacy and safety of infliximab (IFX) in BS patients with vascular involvement followed in a dedicated tertiary center. MethodsCharts of all BS patients who used IFX for vascular involvement between 2004 and 2022 were reviewed. Primary endpoint was remission at Month 6, defined as lack of new clinical symptoms and findings associated with vascular lesion, lack of worsening of the primary vascular lesion and a new vascular lesion on imaging, and CRP < 10 mg/L. Relapse was defined as development of a new vascular lesion or recurrence of the preexisting vascular lesion. ResultsAmong the 127 patients (102 men, mean age at IFX initiation: 35.8 ± 9.0 years) treated with IFX, 110 (87%) had received IFX for remission induction and 87 of these (79%) were already on immunosuppressives when the vascular lesion requiring IFX developed. The remission rate was 73% (93/127) at Month 6 and 63% (80/127) at Month 12. Seventeen patients experienced relapses. Remission rates were better among patients with pulmonary artery involvement and venous thrombosis compared to patients with non-pulmonary artery involvement and venous ulcers. Fourteen patients had adverse events leading to IFX discontinuation and 4 had died due to lung adenocarcinoma, sepsis, and pulmonary hypertension-related right heart failure due to pulmonary artery thrombosis (n = 2). ConclusionInfliximab seems to be effective in majority of BS patients with vascular involvement, even in those who are refractory to immunosuppressives and glucocorticoids.

Infliximab trough levels are associated with endoscopic healing but not with transmural healing at one year treatment with infliximab in pediatric patients with Crohn's disease.

It is well known that infliximab (IFX) trough levels (TLs) are associated with endoscopic healing (EH) in Crohn's disease (CD). We investigated whether IFX TLs are associated with transmural healing (TH) in pediatric patients with CD following 1-year treatment. Pediatric patients with CD treated with IFX were included in this single-center prospective study. IFX TL tests, magnetic resonance enterography (MRE), and colonoscopies were simultaneously conducted after 1-year IFX treatment. TH was defined as a wall thickness of ≤3 mm without inflammatory signs evaluated using MRE. EH was defined as a Simple Endoscopic Score for Crohn's disease of <3 points on colonoscopy. Fifty-six patients were included. EH and TH were observed in 60.7% (34/56) and 23.2% (13/56) of patients, respectively. IFX TLs were higher in patients with EH (median, 5.6 vs. 3.4 µg/mL, P = 0.002), whereas IFX TLs showed no significant difference in patients with and without TH (median, 5.4 vs. 4.7 µg/mL, P = 0.574). No significant difference was observed in EH and TH between patients whose intervals were shortened or not. Multivariate logistic regression analysis showed that IFX TLs and disease duration to IFX initiation were associated with EH (odds ratio [OR] = 1.82, P = 0.001, and OR = 0.43, P = 0.02, respectively). In pediatric patients with CD, IFX TLs were associated with EH but not with TH. Further studies investigating long-term TH and proactive dosing based on therapeutic drug monitoring may clarify whether an association between IFX TLs and TH exists.

A203 EARLY PROACTIVE DRUG MONITORING STRATEGY OF INFLIXIMAB AS MONOTHERAPY FOR INFLAMMATORY BOWEL DISEASE IN PAEDIATRIC PATIENTS IS ASSOCIATED WITH GOOD SUSTAINED CLINICAL REMISSION

Abstract Background Monotherapy with Infliximab (IFX) can be as efficient as combotherapy with immunomodulators in the treatment and maintenance of remission for children with inflammatory bowel disease (IBD) if an early proactive therapeutic drug monitoring strategy is adequately performed. This strategy may allow optimization of blood levels of IFX in order to obtain a sustained clinical response. Purpose This study demonstrated that with appropriate early trough levels of IFX before dose #3 and dose #4 , monotherapy was very efficient in inducing remssion at week 52 . Method A retrospective study was conducted at CHU Sainte-Justine, Montréal,Canada .Children with IBD 2 to 18 years old diagnosed between 01/2018 and 06/2020 and treated with IFX less than 30 days after diagnosis were included .IFX blood levels were collected before the 3rd and/or 4th dose of IFX and regularly thereafter. Adjustments were done in IFX dose per infusion according to blood levels and clinical response. The primary outcome was clinical remission at one year after diagnosis.The secondary outcomes included: (1) At 52 weeks, the median (IQR) dose of IFX (mg/kg) and the intervals between IFX infusions ; (2) the median (IQR) number of IFX dose changes and the median (IQR) number of blood trough levels of IFX done. Result(s) 101 patients were included : 56.4% males; 81CD; 18 UC; 2 IBDU. Mean age at diagnosis was 13.2 years (IQR = 11.20 to 15. 20). Median time to IFX initiation after diagnosis was 5 days (IQR :3-14).Median IFX dose #1: was 8.4 mg/kg (IQR = 5. 8 to 10). 90% of patient had an IFX optimisation (increasing dose and/or shortening intervals) after dose 3 or dose 4. At week 52, 36,5% of patients were receiving IFX infusion every 4 weeks and 30,6% every 6 weeks. The median IFX dose per infusion was 8,9mg/kg (IQR = 7.4- 9,8 ). The IFX doses at week 52 varied greatly according to age at diagnosis The median number of IFX blood level dosage was 4 per patient over a year (IQR=3-5).At week 52, 83 patients (84.6%) achieved clinical remission with a median IFX level of 10.96 (7.05-15.59). 74 /83 (89%) were on monotherapy and 9/83(10.8%) on combotherapy Image Conclusion(s) Early treatment for IBD with IFX as monotherapy and an early proactive optimization strategy is associated with a good sustained steroid free clinical remissionAt week 52, 83 patients (84.6%) achieved clinical remission with a median IFX level of 10.96 (7.05-15.59). 74 /83 (89%) were on monotherapy and 9/83(10.8%) on combotherapy.The majority of the patients required IFX optimization during their first year of treatment. We therefore recommend to proactively monitor blood levels of IFX before the third and fourth dose of IFX and thereafter, in order to lower the risk of treatment failure and anti-infliximab antibodies occurrence. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest C. Girard: None Declared, S. Ackhar: None Declared, S. Sassine: None Declared, L. Chapuy: None Declared, P. Jantchou: None Declared, C. Deslandres Speakers bureau of: moderator and speaker Abbvie and Janssen

Ten-year follow-up of infliximab treatment for uveitis in Behçet disease patients: A multicenter retrospective study.

To evaluate 10-year outcome of infliximab (IFX) treatment for uveitis in Behçet disease (BD) patients using a standardized follow-up protocol. Retrospective longitudinal cohort study. 140 BD uveitis patients treated with IFX enrolled in our previous study. Medical records were reviewed for demographic information, duration of IFX treatment, number of ocular attacks before IFX initiation, best corrected visual acuity (VA) at baseline and 1, 2, 3, 4, 5, and 10 years after IFX initiation, uveitis recurrence after IFX initiation and main anatomical site, concomitant therapies, and adverse events (AEs). 10-year IFX continuation rate and change in LogMAR VA. Of 140 BD patients, 106 (75.7%) continued IFX treatment for 10 years. LogMAR VA improved gradually after initiation of IFX, and the improvement reached statistical significance from 2 years of treatment. Thereafter, significant improvement compared with baseline was maintained until 10 years, despite a slight deterioration of logMAR VA from 5 years. However, eyes with worse baseline decimal VA < 0.1 showed no significant improvement from baseline to 10 years. Uveitis recurred after IFX initiation in 50 patients (recurrence group) and did not recur in 56 (non-recurrence group). Ocular attacks/year before IFX initiation was significantly higher in the recurrence group (2.82 ± 3.81) than in the non-recurrence group (1.84 ± 1.78). In the recurrence group, uveitis recurred within 1 year in 58% and within 2 years in 74%. Seventeen patients (34%) had recurrent anterior uveitis, 17 (34%) had posterior uveitis, and 16 (32%) had panuveitis, with no significant difference in VA outcome. In addition, logMAR VA at 10 years did not differ between the recurrence and non-recurrence groups. AEs occurred among 43 patients (30.7%), and 24 (17.1%) resulted in IFX discontinuation before 10 years. Among BD patients with uveitis who initiated IFX, approximately 75% continued treatment for 10 years, and their VA improved significantly and was maintained for 10 years. Uveitis recurred in one-half of the patients, but visual acuity did not differ significantly from the patients without recurrence.

110. Improving Pneumococcal Vaccination in Patients Treated with Tumor Necrosis Factor-alpha Inhibitors: A Multidisciplinary Education-Based Quality Improvement Project

Abstract Background In 2012, pneumococcal conjugate vaccine (PCV13) and pneumococcal polysaccharide vaccine (PPSV23) were recommended for immunocompromised adults ≥19 years, but pneumococcal vaccination (PV) in these patients (pts) remains suboptimal. With a new PV (PCV20) allowing for simplified PV, we study rates of PV in pts on infliximab (INX) 1 year post-initiation of a pt and provider education-based quality improvement project aiming to increase PV in pts on Tumor Necrosis Factor-alpha inhibitors (TNF-αI). Methods Starting in 11/2020, pamphlets detailing PV indications were distributed to the Walter Reed National Military Medical Center infusion center and pharmacies to be given to pts prescribed/administered TNF-αI. Provider educational materials and pt pamphlets were given to services prescribing TNF-αI. Provider education was also offered to these services. Up to date (UTD) on PV was defined as receipt of PCV13 and PPSV23 (including additional PPSV23 dose ≥5 years post-initial PPSV23 if applicable). Ongoing INX (o-INX) was defined as INX initiation before 10/1/2020. Newly initiated INX (new-INX) was 10/1/2020-10/1/2021. One-year post implementation, we reviewed the PCV13 and PPSV23 immunization records of pts ≥19 years of age on INX from 1/1/21-12/31/21. This project was approved by the IRB under a non-research determination. Results 111 pts prescribed INX between 1/1/21-12/31/21 met inclusion criteria (87 o-INX and 24 new-INX). Prior to the intervention, of 87 o-INX pts, 45 (52%), 45 (52%), and 18 (21%) pts had received PCV13, ≥1 PPSV23 dose, and were UTD on PV respectfully. Between 1/1/21-12/31/21, 14 o-INX pts had PV (1 PCV13 and PPSV23, 7 PCV13, and 6 PPSV23), with 7 newly UTD (10% of the 69 previously not UTD), totaling 25 (29%) o-INX pts UTD on PV (figure 1). Of 24 new-INX pts, only 12 (48%), 9 (36%), and 6 (24%) had had PCV13, PPSV23, and were UTD on PV as of 12/31/21. No services prescribing TNF-αI requested the offered PV educational talks. Conclusion Despite frequent healthcare in a system where vaccination has no out of pocket expense, guideline-concordant PV was low in this cohort. With new, simplified PV, next steps include updated pt and targeted provider education. However, with prior small gains using multidisciplinary education, additional efforts to remove PV barriers may be needed. Disclosures Benjamin L. Custer, MD, Beam Therapeutics: Stocks/Bonds|CRISPR Therapeutics: Stocks/Bonds|glaxo-smith-kline: Stocks/Bonds|Hologic: Stocks/Bonds|Moderna: Stocks/Bonds|Pfizer: Stocks/Bonds|Regeneron: Stocks/Bonds|sanofi: Stocks/Bonds|Vertex Pharmaceuticals: Stocks/Bonds.