Infliximab Infusion Research Articles

Efficacy and safety of infliximab in patients with autoimmune hepatitis.

A limited number of drugs are used as standard or alternative therapies in autoimmune hepatitis (AIH). No specific recommendations are available for patients failing to respond to these therapies. We analyzed the efficacy and safety of infliximab in patients with AIH. We performed a retrospective study of 42 patients with AIH who received infliximab at 21 liver centers in 12 countries. Patients were categorized according to the reason for infliximab therapy. Patients in group 1 (n=20) had failed standard, second-line (mycophenolate mofetil and 6-mercaptopurine) or third-line (tacrolimus or cyclosporine) therapy. In group 2 (n=22), infliximab was given for treatment of concomitant extrahepatic autoimmune diseases. Patients received a median of 17 (range: 3-104) infliximab infusions. Complete biochemical response (CR) was achieved or maintained in 33 (78%) patients during infliximab therapy. In group 1, infliximab induced CR in 11 of 20 (55%) patients. In group 2, 16 patients with CR prior to infliximab maintained remission, and the remaining 6 patients with active AIH (5 on standard and 1 on both second-line and third-line therapy) showed CR following infliximab therapy. Infliximab led to CR in 75% (6/8) of nonresponders to second-line and in 46% (6/13) of failing third-line therapy. Overall, 65% (17/26) of the patients with active AIH achieved CR on infliximab. Infliximab was discontinued in 3 patients of group 1. One patient had a severe allergic reaction and 2 developed anti-infliximab autoantibodies. Our study suggests that infliximab may be an effective and safe rescue therapy in AIH.

Central retinal vein occlusion after infliximab therapy in a young patient with ulcerative colitis

AbstractInflammatory bowel disease (IBD) is a chronic condition, characterized by recurrent inflammation of the gastrointestinal tract. While the primary focus of IBD management consists in controlling gastrointestinal symptoms, IBD also presents an increased risk of thromboembolic complications. Tumor necrosis factor alpha (TNF‐α) inhibitors, namely infliximab, have become increasingly common in the management of multiple chronic inflammatory diseases such as IBD. However, recent studies have shown an association between treatment with infliximab and an increased thrombotic risk. We report an unusual case of retinal vein thrombosis in a patient with ulcerative colitis (UC) that occurred during infliximab infusion. This case highlights the need to remain vigilant when administering infliximab to individuals with IBD, particularly those with additional risk factors for thrombosis.

Infliximab in steroid-refractory immune-related hepatitis does not demonstrate hepatotoxicity and may shorten time on steroids

BackgroundImmune-related hepatitis (irHepatitis) is a relatively common immune-related adverse event (irAE) of checkpoint inhibitors. Often, it responds well to steroids; however, in refractory cases, further therapy is needed. Anti-tumor necrosis...

Infliximab Limits Injury in Myocardial Infarction.

The purpose of this study was to investigate a therapeutic approach targeting the inflammatory response and consequent remodeling from ischemic myocardial injury. Coronary thrombus aspirates were collected from patients at the time of ST-segment-elevation myocardial infarction and subjected to array-based proteome analysis. Clinically indistinguishable at myocardial infarction (MI), patients were stratified into vulnerable and resilient on the basis of 1-year left ventricular ejection fraction and death. Network analysis from coronary aspirates revealed prioritization of tumor necrosis factor-α signaling in patients with worse clinical outcomes. Infliximab, a tumor necrosis factor-α inhibitor, was infused intravenously at reperfusion in a porcine MI model to assess whether infliximab-mediated immune modulation impacts post-MI injury. At 3 days after MI (n=7), infliximab infusion increased proregenerative M2 macrophages in the myocardial border zone as quantified by immunofluorescence (24.1%±23.3% in infliximab versus 9.29%±8.7% in sham; P<0.01). Concomitantly, immunoassays of coronary sinus samples quantified lower troponin I levels (41.72±7.34 pg/mL versus 58.11±10.75 pg/mL; P<0.05) and secreted protein analysis revealed upregulation of injury-modifying interleukin-2, -4, -10, -12, and -18 cytokines in the infliximab-treated cohort. At 4 weeks (n=12), infliximab treatment resulted in significant protective influence, improving left ventricular ejection fraction (53.9%±5.4% versus 36.2%±5.3%; P<0.001) and reducing scar size (8.31%±10.9% versus 17.41%±12.5%; P<0.05). Profiling of coronary thrombus aspirates in patients with ST-segment-elevation MI revealed highest association for tumor necrosis factor-α in injury risk. Infliximab-mediated immune modulation offers an actionable pathway to alter MI-induced inflammatory response, preserving contractility and limiting adverse structural remodeling.

Randomised clinical trial: First-line infliximab biosimilar is cost-effective compared to conventional treatment in paediatric Crohn's disease.

Data on cost-effectiveness of first-line infliximab in paediatric patients with Crohn's disease are limited. Since biologics are increasingly prescribed and accompanied by high costs, this knowledge gap needs to be addressed. To investigate the cost-effectiveness of first-line infliximab compared to conventional treatment in children with moderate-to-severe Crohn's disease. We included patients from the Top-down Infliximab Study in Kids with Crohn's disease randomised controlled trial. Children with newly diagnosed moderate-to-severe Crohn's disease were treated with azathioprine maintenance and either five induction infliximab (biosimilar) infusions or conventional induction treatment (exclusive enteral nutrition or corticosteroids). Direct healthcare consumption and costs were obtained per patient until week 104. This included data on outpatient hospital visits, hospital admissions, drug costs, endoscopies and surgeries. The primary health outcome was the odds ratio of being in clinical remission (weighted paediatric Crohn's disease activity index<12.5) during 104 weeks. We included 89 patients (44 in the first-line infliximab group and 45 in the conventional treatment group). Mean direct healthcare costs per patient were €36,784 for first-line infliximab treatment and €36,874 for conventional treatment over 2 years (p = 0.981). The odds ratio of first-line infliximab versus conventional treatment to be in clinical remission over 104 weeks was 1.56 (95%CI 1.03-2.35, p = 0.036). First-line infliximab treatment resulted in higher odds of being in clinical remission without being more expensive, making it the dominant strategy over conventional treatment in the first 2 years after diagnosis in children with moderate-to-severe Crohn's disease. NCT02517684.

INFLIXIMAB MARKET SHARE AND ASSOCIATED COST SAVINGS FOLLOWING BIOSIMILAR MARKET ENTRY

Abstract BACKGROUND Biologic medications have transformed treatment for autoimmune conditions, including inflammatory bowel disease (IBD), but have also contributed to rising healthcare expenditures in the United States (US). Biosimilars, which are highly similar in safety and efficacy to the originator biologic, were introduced to create competition and reduce cost. Limited studies exist evaluating the impact biosimilars have had on biologic market share and cost savings. The objective of this study was to evaluate the impact infliximab biosimilars have had on the cost and market share of the infliximab originator product. METHODS Infliximab claims were reviewed and analyzed using the Merative MarketScan Commercial Claims and Encounters Database. Using only outpatient claims, both the infliximab originator and biosimilars were identified using Current Procedural Terminology codes from January 1, 2015, to December 31, 2021. Patients with commercial insurance, ages 0 to 64 years, and receiving infliximab for any indication were included. The Medical Care Consumer Price Index was used to adjust for inflation to December 2021 dollars. Outcomes of interest included market share of all infliximab products, cost per infliximab infusion, and cost per vial (one vial=100 mg) of the medication. RESULTS There were 471,748 claims for infliximab infusions that met our inclusion criteria, with 42,100 unique patients, 55% female, and a median age of 40 (inter-quartile range (IQR) 26 – 52) years old at the time of medication initiation. Indications for infliximab products included IBD (67%), rheumatoid arthrtiis (18%), psoriasis (9%), ankylosing spondylitis (5%), other (4%), with some patients receiving infliximab for multiple indications. Utilization of infliximab biosimilars increased over time, reaching the highest utilization in December 2021, accounting for 24% of the market share. The median cost of the infliximab originator peaked at $1,491 per vial in December 2017, 13 months after market entry of the first biosimilar (infliximab-dyyb). The cost of the infliximab originator then decreased by 45% over time, reaching a low of $821 per vial in December 2021. Had infliximab biosimilars not been introduced to the market, the projected cost of the infliximab originator in December 2021 would have increased by 20% to $1793 per vial. Thus, infliximab biosimilars contributed to a theoretical decrease of 55% in the cost of infliximab originator during the time period studied. CONCLUSIONS The market share of infliximab biosimilars in the US has steadily increased since their introduction in 2016. The competition of infliximab biosimilars has contributed to the decrease in cost of both the infliximab originator and biosimilar products. Future studies are needed to determine if patients are seeing an out-of-pocket savings because of biosimilar introduction.

P897 The association of HLA-DQA1*05 carriage with immunogenicity to anti-tumour necrosis factor therapy and drug persistence in Asian patients with inflammatory bowel disease

Abstract Background HLA-DQA1*05 carriage increases anti-tumour necrosis factor (TNF) immunogenicity and lowers drug persistence in European inflammatory bowel disease (IBD) patients. There is a paucity of data for Asian patients. We hypothesize that the HLA-DQA1*05 allele is present in our local IBD population and may be associated with similar clinical and pharmacokinetic outcomes as European cohorts. Methods A single-centre retrospective study of consecutive IBD patients on Infliximab (IFX) or Adalimumab (ADM) was performed. HLA-DQA1*05 carriage was tested with Sanger sequencing. Serum anti-drug antibody (ADA) levels were analysed at each IFX infusion and per physician discretion for ADM. Concomitant immunomodulator (IM) therapy with Azathioprine or Methotrexate was recorded. Primary outcome was immunogenicity to IFX or ADM, defined as ADA concentration ≥10 AU/ml at any time point. Secondary outcomes were loss of response (LOR), defined as IBD symptom-related treatment intensification, and persistence, defined as anti-TNF continuation at end of follow-up. The effects of HLA-DQA1*05 carriage on outcomes and predictors of persistence were analysed. Results 39 patients (28 Crohn’s disease, 11 ulcerative colitis) were included (mean age 39 years, median disease duration 10 years). 24 patients had IFX as first anti-TNF agent (21 with IM, 3 as monotherapy), 7 of whom had second-line ADM with IM. 15 patients had ADM as first anti-TNF agent (13 with IM, 2 as monotherapy), 2 of whom had second-line IFX (1 with IM). 15/39 (38.5%) patients were positive for HLA-DQA1*05. 42/48 (87.5%) of anti-TNF exposures were on IM. In HLA-DQA1*05 carriers compared to non-carriers, development of ADA (61.1% vs 47.8%, p=0.397) and LOR (42.1% vs 31.0%, p=0.433) was numerically higher but not statistically different. Persistence of first anti-TNF agent was similar between carriers and non-carriers at the end of follow-up (median 28.0 months vs 21.5 months, p=0.364) (Figure 1). ADA development was not associated with LOR (p=0.07) or persistence (p=0.29). 19/48 (39.6%) of anti-TNF exposures discontinued treatment at the end of follow-up, 13 of whom experienced LOR. 10/13 (76.9%) of patients with LOR were female. Female sex was significantly associated with anti-TNF non-persistence on univariable (OR 4.82, 95% CI 1.38-16.75, p=0.01) and multivariable logistic regression (OR 7.24, 95% CI 1.35-38.90, p=0.02), after adjusting for HLADQA1*05 carriage, presence of ADA and anti-TNF order (first versus second-line) (Table 1). Conclusion In Asian IBD patients, HLA-DQA1*05 carriage may not affect immunogenicity nor treatment persistence, especially with proactive therapeutic drug monitoring and concurrent IM. Female sex negatively affects persistence. Larger prospective studies are needed.

Immune checkpoint inhibitor-induced colitis with endoscopic evaluation in Chinese cancer patients: a single-centre retrospective study

BackgroundWe investigated the clinical and endoscopic features, management strategies, and outcomes of Chinese cancer patients with immune checkpoint inhibitor (ICI)-induced colitis.MethodThis single-centre retrospective study included patients who developed ICI-induced colitis and underwent endoscopic evaluation from June 1, 2019 to October 1, 2023. We analysed clinical features, ICI-induced colitis-related information, management strategies, and outcomes.ResultsA total of 25 patients were included; most were male (88%) with a median age of 59 years. Eleven (44%) patients had grade 2 colitis, and 14 (56%) had grade 3 colitis. The median time from ICI initiation to colitis onset was 105 days. The median duration from symptom onset to endoscopic evaluation was 11 days. Regarding endoscopic evaluation, colitis involved the entire colon in 13 (52%) patients, and 15 (60%) had ulcers. Twenty-three (92%) patients received steroids, and 3 (12%) added infliximab (IFX). Most patients (n=19, 76%) achieved remission with complete tapering of the steroid taken for the first colitis episode. Among the 6 (24%) patients who did not taper initial, 5 patients increased their steroid dosage with 2 added IFX, leading to symptom remission and successful steroid tapering, while one patient experienced continuous non-remission despite increasing the steroid and receiving two infusions of IFX. Of the 8 (32%) ICI rechallenge patients, 4 achieved long-lasting benefit without colitis recurrence. The other 4 experienced recurrent colitis after ICI rechallenge and permanently discontinued ICIs. The median duration from ICI rechallenge to colitis recurrence was shorter than the time to colitis onset. One patient developed steroid-refractory colitis and recovered with one infusion of IFX.ConclusionEndoscopy has value in the evaluation and optimal management of ICI-induced colitis in Chinese cancer patients. IFX is necessary for treating colitis, especially in steroid-refractory/resistant patients. ICI rechallenge can achieve benefit, but permanently discontinuing ICIs is needed if colitis recurs. Future large-scale prospective studies are required for more accurate assessments and validation.

Performance of a New Rapid Point-of-Care Test for Infliximab Levels in Patients with Inflammatory Bowel Disease: A Comparison to ELISA

BackgroundTherapeutic drug monitoring of infliximab levels in patients with inflammatory bowel disease (IBD) optimizes patients’ treatment. The reference technique is based on enzyme-linked immunosorbent assay (ELISA) although point of care (POC) assays are being developed.AimsTo assess the performance of a new rapid immunochromatographic POC assay (Promonitor Quick IFX) compared with ELISA technique to measure infliximab levels in patients with IBD.MethodsA prospective, observational, unicentric study was performed on capillary blood samples from patients with IBD before infliximab infusion (trough levels). Infliximab levels and anti-infliximab antibodies were measured using the ELISA technique (Promonitor IFX) and the POC assay. Correlation between both techniques was assessed by Pearson’s coefficient. Quantitative differences were evaluated by Bland–Altman analysis. Samples were stratified according to infliximab therapeutic ranges (< 3 μg/mL, 3–8 μg/mL, and > 8 μg/mL).ResultsA total of 135 experimental samples were assessed. Infliximab levels showed a high correlation between POC and ELISA tests (r = 0.84, P < 0.001). The mean difference between tests was 1.46 μg/mL (P < 0.001), being minimal for concentrations < 8 μg/mL. POC and ELISA assays showed an overall concordance of 87.4%. Most samples were in the same therapeutic range, which lead to equivalent therapeutic decisions. POC and ELISA assays detected the presence of anti-infliximab antibodies in 2.2% and 3.7% of the samples, respectively.ConclusionsPOC assay results in blood samples from patients with IBD were comparable to those obtained with the reference ELISA technique. The POC assay could be considered for routine testing based on its ease of use and rapidity.

Reacción paradójica psoriaforme por infliximab

Reacción paradójica psoriaforme por infliximab

Current knowledge of TNF-α monoclonal antibody infliximab in treating Kawasaki disease: a comprehensive review.

Kawasaki disease (KD), an autoinflammatory disease primarily affecting young children, characterized by consisting of acute systemic vasculitis and coronary artery involvement in severe cases. Intravenous immunoglobulin gamma (IVIG) combined with aspirin therapy is the first-line regimen for the prevention of coronary aneurysms in the acute phase of KD. The etiology and pathogenesis of KD are unclear, but its incidence is increasing gradually, especially in the cases of IVIG-naïve KD and refractory KD. Conventional therapies for refractory KD have unsatisfactory results. At present, infliximab (IFX), a human-murine chimeric monoclonal antibody that specifically blocks tumor necrosis factor-α (TNF-α), has made great progress in the treatment of KD. This review revealed that IFX infusion (5 mg/kg) could effectively modulate fever, reduce inflammation, improve arthritis, diminish the number of plasma exchange, decrease hospitalizations, and prevent the progression of coronary artery lesions. The adverse effects of IFX administration included skin rash, arthritis, respiratory disease, infusion reaction, hepatomegaly, and vaccination-associated complications. But the incidence of these adverse effects is low. The clear optimal application protocol of the application of IFX for either initial combination therapy or salvage therapy in KD is still under investigation. In addition, there are no effective biomarkers to predict IFX resistance. Further multicenter trials with large sample size and long-term follow-up are still needed to validate the clinical efficacy and safety of IFX for IVIG-resistant KD or refractory KD.

Aggregate Formation and Antibody Stability in Infusion Bags: The Impact of Manual and Robotic Compounding of Monoclonal Antibodies

Monoclonal antibodies (mAbs) can be damaged during the aseptic compounding process, with aggregation being the most prevalent form of degradation. Protein aggregates represent one of several risk factors for undesired immunogenicity of mAbs, which can potentially lead to severe adverse drug reactions and less effective treatments. Since data on aggregate and particle formation by robotic compounding is missing, we aimed to compare the antibody stability between robotic- and manual compounding of mAbs with regard to formation of (sub)visible aggregates. Infliximab and trastuzumab were compounded into infusion bags with the APOTECAchemo robot or manually by nurses or pharmacy technicians. The products were analyzed by quantifying (sub)visible particles with nanoparticle tracking analysis, dynamic light scattering (DLS), light obscuration, micro-flow imaging, high pressure size exclusion chromatography (HP-SEC), and visual inspection. HP-SEC showed high percentages monomers in trastuzumab (99.4 % and 99.4 %) and infliximab (99.5 % and 99.6 %) infusion bags for both manual and robotic compounding, respectively. DLS indicated more consistent and reproducible results with robotic compounding, and confirmed monodisperse samples with a higher polydispersity index for manual compounding (0.16, interquartile range; IQR 0.14–0.18) compared to robotic compounding (0.12, IQR 0.11–0.15). This study shows that the studied compounding methods had a minor impact on the number of aggregates and particles, and that robotic compounding of mAbs provided at least similar quality as manual compounding.

SAT624 Neurosarcoidosis Presenting With Panhypopituitarism

Abstract Disclosure: E.M. Niedzialkowska: None. T. Blazin: None. K. Strubchevska: None. M. Kozyk: None. N. Saini: None. Introduction: Neurosarcoidosis is estimated to occur in approximately 5-15% patients with sarcoidosis. Pituitary involvement may be present in up to 5% of those cases and can manifest as hypothalamus, adenohypophysis dysfunction or arginine vasopressin deficiency (AVP-D) in isolated fashion or variedly combined. Clinical case: 32 year old male presented with chief complaint of worsening bilateral lower extremity weakness, urinary incontinence, polyuria and polydipsia. 9 months prior to admission the patient was diagnosed with neurosarcoidosis. At that time brain MRI showed diffuse leptomeningeal enhancement, chest CT showed hilar lymphadenopathy, lumbar puncture with CSF analysis showed protein 227 mg/dl (N&amp;lt;38), ACE 6 U/l (N &amp;lt;2.5), WBC 10 (N&amp;lt;5) with 88% lymphocytes. Hilar lymph node biopsy was consistent with non-caseating granuloma. The patient was diagnosed with neurosarcoidosis and started on prednisone and methotrexate. The patient was referred to our institution for further evaluation. On examination gait ataxia and gynecomastia were noted. Laboratory results showed urine specific gravity of 1.001, LH 0.4 mIU/ml (N 0.6-1.2), FSH 1.1 mIU/ml (N 1-12), ACTH &amp;lt;5 pg/ml (N 6-46), cortisol 2.1 ug/dl (N 2.9-19.4), prolactin 10.5 ng/ml (N 2-18), total testosterone 4 ng/dl (N 240-1080), free testosterone 0.1 ng/dl (N 4.8-19), TSH 0.58 uIU/ml (N 0.4-4.5), free ft3 1.5 pg/ml (N 1.7-3.7), free ft4 0.6 ng/dl (N 0.7-1.5), IGF-1 52 ng/ml (N 71-234), Copeptin proAVP of &amp;lt;2.8 pmol/l( N&amp;gt;13.2), urine osmolality of 72 mOsmol/kg, blood osmolality of 297 mOsmol/kg (N &amp;lt;295), vit D 25-OH 9 ng/ml (N 30-100), vit D 1,25-OH 57.3 pg/ml (N 19.9-79.3). MRI of the spine showed extensive nodular enhancement of the leptomeninges of the cervical, thoracic spine and lumbar cauda equina nerve roots. Brain MRI was positive for numerous small nodular enhancement involving leptomeninges and pituitary stalk. The patient was started on desmopressin with significant improvement of symptoms and increase in urine osmolality to 709 mOsmol/kg. Due to risk of hypercalcemia and normal vit D 1,25-OH vitamin D supplementation was not initiated. For neurosarcoidosis the patient was started on pulse dose methylprednisolone and infliximab infusion. Upon discharge he was transitioned to oral hydrocortisone and started on levothyroxine and testosterone replacement therapy. Conclusion: We present a case of pituitary neurosarcoidosis presenting with AVP-D, secondary hypothyroidism, secondary adrenal insufficiency, hypogonadism and growth hormone deficiency. Panhypopituitarism with complete anterior and posterior pituitary dysfunction is extremely rare and might be found in up to 13% cases of pituitary sarcoidosis. The diagnosis should be considered in patients with sarcoidosis and endocrine dysfunctions. Presentation: Saturday, June 17, 2023

Treatment of immunoglobulin-resistant kawasaki disease: a Bayesian network meta-analysis of different regimens.

This study aimed to gather evidence from clinical trials on the efficacy and safety of the available treatments for intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) in children. This work adopted the Newcastle-Ottawa scale to analyse the quality of the enrolled articles. A network meta-analysis was performed using clinical trials that compared drugs used to treat IVIG-resistant KD. Aggregate Data Drug Information System software v.1.16.5 was employed to analyse whether infliximab, second IVIG infusions, and intravenous pulse methylprednisolone (IVMP) were safe and effective. Ten studies, involving 704 patients with IVIG-resistant KD, were identified and analysed. Overall, infliximab exhibited remarkable antipyretic activity compared with the second IVIG infusions (2.46, 1.00-6.94). According to the drug rank, infliximab was the best option against IVIG-resistant KD. Regarding adverse effects, the infliximab group was more prone to hepatomegaly. A second IVIG infusion was more likely to result in haemolytic anaemia. IVMP treatment was more susceptible to bradycardia, hyperglycaemia, hypertension, and hypothermia. In addition, infliximab, IVMP, and the second IVIG infusions showed no significant differences in the risk of developing a coronary artery aneurysm (CAA). Infliximab was the best option against IVIG-resistant KD, and IVMP, infliximab, and second IVIG infusions have not significant differences of prevent CAA in patients with IVIG-resistant KD. Identifier: https://osf.io/3894y.

Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized With COVID-19 Pneumonia

Immune dysregulation contributes to poorer outcomes in COVID-19. To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia. Randomized, double-masked, placebo-controlled clinical trial using a master protocol to investigate immunomodulators added to standard care for treatment of participants hospitalized with COVID-19 pneumonia. The results of 3 substudies are reported from 95 hospitals at 85 clinical research sites in the US and Latin America. Hospitalized patients 18 years or older with confirmed SARS-CoV-2 infection within 14 days and evidence of pulmonary involvement underwent randomization between October 2020 and December 2021. Single infusion of abatacept (10 mg/kg; maximum dose, 1000 mg) or infliximab (5 mg/kg) or a 28-day oral course of cenicriviroc (300-mg loading dose followed by 150 mg twice per day). The primary outcome was time to recovery by day 28 evaluated using an 8-point ordinal scale (higher scores indicate better health). Recovery was defined as the first day the participant scored at least 6 on the ordinal scale. Of the 1971 participants randomized across the 3 substudies, the mean (SD) age was 54.8 (14.6) years and 1218 (61.8%) were men. The primary end point of time to recovery from COVID-19 pneumonia was not significantly different for abatacept (recovery rate ratio [RRR], 1.12 [95% CI, 0.98-1.28]; P = .09), cenicriviroc (RRR, 1.01 [95% CI, 0.86-1.18]; P = .94), or infliximab (RRR, 1.12 [95% CI, 0.99-1.28]; P = .08) compared with placebo. All-cause 28-day mortality was 11.0% for abatacept vs 15.1% for placebo (odds ratio [OR], 0.62 [95% CI, 0.41-0.94]), 13.8% for cenicriviroc vs 11.9% for placebo (OR, 1.18 [95% CI 0.72-1.94]), and 10.1% for infliximab vs 14.5% for placebo (OR, 0.59 [95% CI, 0.39-0.90]). Safety outcomes were comparable between active treatment and placebo, including secondary infections, in all 3 substudies. Time to recovery from COVID-19 pneumonia among hospitalized participants was not significantly different for abatacept, cenicriviroc, or infliximab vs placebo. ClinicalTrials.gov Identifier: NCT04593940.

BG10 A case of pachydermoperiostosis (primary hypertrophic osteoarthropathy)

Abstract We report a case of a 21-year-old man who was referred from the community with concern about persistent swollen and inflamed eyelids together with possible facial acne. He was known to have hypertrophic osteoarthropathy under the care of rheumatology for which he was on regular infliximab infusions. He had previously been treated with methotrexate (intolerant) azathioprine and adalimumab (lack of efficacy). He also had a long-standing history of inflammatory bowel disease and associated complications: iron-deficiency anaemia, previous choledochal cyst and biliary stricture, as well as previous deficiencies in vitamins B12, A and E. The patient was known to the genetics team, with prior genetic testing demonstrating that he is homozygous for a pathogenic SLC02A1 variant (c.1264_1265delAC). This gene encodes a prostaglandin transporter involved in mediating the uptake and clearance of prostaglandins in numerous tissues. On examination, he was found to have pronounced thickening of the facial skin, especially the forehead, alongside deep furrowing of the scalp. The eyelids were severely swollen and inflamed, with prominent straight eyelashes. There were milia present on the face predominantly on the brow and cheeks. There was clubbing of all digits on his hands and feet. The cutaneous findings were deemed all in keeping with pachydermoperiostosis. Pachydermoperiostosis, also known as primary/idiopathic hypertrophic osteoarthropathy, Touraine–Solente–Gole syndrome and Rosenfeld–Kloepfer syndrome, was first described by Friedrich in 1868. This is a rare condition, and both autosomal dominant and autosomal recessive modes of inheritance have been noted. The condition usually presents during puberty and the hallmark features are thickening and coarsening of the facial skin, periostosis and digital clubbing. Other cutaneous features can include seborrhoea with sebaceous hyperplasia, acne, hyperhidrosis and cutis verticis gyrata. Ocular manifestations include blepharoptosis, floppy eyelid syndrome, and hypertrophy of both the eyelids and palpebral conjunctiva. Crohn disease and multiple bone and joint issues are known features of the condition (Doshi D. Touraine–Solente–Gole syndrome. Orbit 2018; 37:97–101; Tabatabaei SA, Masoomi A, Soleimani M et al. Pachydermoperiostosis: a clinicopathological description. J Curr Ophthalmol 2019; 31:450–3). This reported case demonstrates both classic cutaneous and other organ system features of this rare genetic condition. It highlights the importance of being able to recognize all the associated findings when a patient presents with thickening of their facial skin and eyelids.

Safety of Accelerated Infliximab Infusions in Children With Inflammatory Bowel Disease: A Retrospective Cohort Study.

Accelerated infliximab (IFX) infusions have shown to be safe in adults with inflammatory bowel disease (IBD), but data on its safety in pediatric IBD is limited. This study aimed to assess the incidence and timing of infusion reactions (IR) in children with IBD who received accelerated (1-h) versus standard (2-h) IFX infusions. This retrospective cohort study included IBD patients 4-18 years of age and initiated IFX between January 2006 and November 2021 at Amsterdam University Medical Centre, location Academic Medical Centre (AMC) and VU Medical Centre (VUmc). The AMC protocol was adjusted in July 2019 from standard to accelerated infusions with 1-h intrahospital post-infusion observation period, whereas in VUmc only standard infusions were administered without an observation period. After merging the departments in 2022, all VUmc patients were allocated to the accelerated infusions (AMC) protocol. Primary outcome was the incidence of acute IR among maintenance accelerated versus standard infusions. Totally, 297 (150 VUmc, 147 AMC) patients (221 Crohn disease; 65 ulcerative colitis; 11 IBD-unclassified) with cumulative n = 8381 IFX infusions were included. No statistically significant difference in the per-infusion incidence of IR was observed between maintenance standard infusions (26/4383, 0.6% of infusions) and accelerated infusions (9/3117, 0.3%) ( P = 0.33). Twenty-six of 35 IR (74%) occurred during the infusion, while 9 occurred post-infusion (26%). Only 3 of 9 IR developed in the intrahospital observation period following the switch to accelerated infusions. All post-infusion IR were mild, requiring no intervention or only oral medication. Accelerated IFX infusion without a post-infusion observation period for children with IBD seems a safe approach.

Accelerated Infliximab Infusion Safety and Tolerability Is Non-inferior to Standard Infusion Protocol in Inflammatory Bowel Disease Patients: A Randomized Controlled Study.

Infliximab is typically given over an infusion time of 2 hours, leading to a significant burden in inflammatory bowel disease (IBD) patients. We aimed to determine the safety and cost-effectiveness of an accelerated infliximab infusion of 1 hour, compared with the standard 2-hour infusion. Open-label randomized trial where IBD patients receiving maintenance infliximab infusions were randomly assigned to 1- and 2-hour infusion groups, corresponding to study and control groups, respectively. The primary outcome was the rate of infusion reactions. Secondary outcomes were assessment of the effect of premedications and immunomodulators on the rate of infusion reactions, and cost-effectiveness analysis. The cost-effectiveness analysis was based on direct nursing costs for the infusion time, indirect infusion center costs, and cost of productivity loss for patients. This trial is registered with ClinicalTrials.gov, NCT05340764. From November 2020 to November 2021, 96 patients were randomly assigned: 51 (53%) to the 1-hour infusion group and 45 (47%) to the 2-hour infusion group. Over a median time of 1 year, 309 infusions were administered in the control group, and 376 in the study group. Fifty-seven (18%) infusions in the control group and 45 (12%) infusions in the study group experienced an infusion reaction. The only infusion reaction was asymptomatic hypotension not requiring infusion discontinuation. No other infusion reactions (mild or moderate/severe) were seen. Diphenhydramine was associated with an increased rate of infusion reactions (OR 2.04 [95% CI 1.18-3.52], P = .01). The average costs were estimated to reduce by 37% in the accelerated infusion group. Accelerated 1-hour infusions are non-inferior in safety and superior in cost-effectiveness compared with standard 2-hour infusions in IBD patients receiving maintenance infliximab infusions. Registered with ClinicalTrials.gov, NCT05340764.

Rare Case of Neurosarcoidosis presenting as Isolated Longitudinal Extensive Transverse Myelitis (LETM). (P9-5.006)

<h3>Objective:</h3> NA <h3>Background:</h3> Neurosarcoidosis is seen in only 5–16% of the patients with sarcoidosis. Incidence of longitudinal extensive transverse myelitis (LETM) in neurosarcoidosis is even rarer. <h3>Design/Methods:</h3> 37-year-old male with history of recurrent LETM and seizure disorder was admitted for worsening lower extremity weakness and unresponsiveness. History was significant for transverse myelitis diagnosed 8 months ago after presenting with lower extremity weakness and urinary incontinence. MRI of the spine at that time revealed focus of abnormal T2 signal in upper thoracic spinal cord extending from the mid T3 level inferiorly through the T5–6 level, with associated cord expansion. <h3>Results:</h3> Repeat MRI of the spine and brain showed progression of disease in the spine with nodular leptomeningeal enhancement most prominent within the posterior fossa. Extensive workup including neuromyeltitis optica, paraneoplastic panel, anti-aquaporin Ab and Anti-MOG Ab testing was negative. Patient was treated with steroids and plasmapheresis treatment (PLEX). PLEX treatments were held due to concern for infection. He was switched to steroid taper and biweekly Rituximab infusion. Rituximab infusions were stopped due to side effects and patient was trialed on mycophenolate mofetil. However, patient was transitioned back to steroid taper and rituximab infusion after worsening of symptoms. Patient eventually underwent meningeal biopsy which showed granulomatous leptomeningitis and parenchymal microglial activation. With strong suspicion for Neurosarcoidosis now based on accumulated evidence the patient was restarted on IV methylprednisolone and subsequent steroid taper. Improvement of his symptoms with partial recovery of strength was noted. Patient was subsequently transitioned to Leflunomide, infliximab infusions and steroid taper. Follow up MRI of the brain and spinal cord showing improvement in areas of enhancement. <h3>Conclusions:</h3> Our patient presented with neurosarcoidosis manifesting as LETM with no prior diagnosis of sarcoidosis or evidence of system involvement on further thorough workup. The diagnosis was challenging confirmed after a neural biopsy given absence of non-neurological manifestations. <b>Disclosure:</b> Dr. Khosa has nothing to disclose. Dr. Anandaram has nothing to disclose. Dr. Khosa has nothing to disclose. Dr. Buttar has nothing to disclose.

Neurosarcoidosis Induced by TNF-alpha Inhibitor in a Patient with Ankylosing Spondylitis (P9-5.002)

<h3>Objective:</h3> To report a case of neurosarcoidosis associated with infliximab administration. <h3>Background:</h3> Sarcoidosis is a systemic immune mediated disease that can affect any organ. Neurological involvement accounts for 5–10% of cases and can be life-threatening. Infliximab, a TNF-alpha inhibitor agent, is used in the treatment of sarcoidosis. However, rarely, it can paradoxically induce sarcoidosis. <h3>Design/Methods:</h3> Case report. <h3>Results:</h3> A 35-year-old male with ankylosing spondylitis complained of refractory and recurrent headaches, confusion, and word-finding difficulties for 2 weeks duration. Symptoms began after the infliximab infusion, which he has been receiving for 2 years, was changed to a biosimilar product. Initial routine testing and MRI brain with/without contrast were unremarkable. He was treated for migraines including a 4-day course of steroids. However, the symptoms worsened. On presentation, the physical examination revealed inattentiveness, difficulty recognizing familiar faces, impaired calculations, and decreased fluency. EEG demonstrated moderate generalized background slowing with frequent runs of generalized rhythmic delta activity. Laboratory testing showed slightly elevated ESR (24 mm/h) and CRP (2.8 mg/dL). CSF was significant for WBC 174 cells/mcL, protein 133.4 mg/dL, ACE 4.6 U/L, CD4:CD8 ratio 3:1. CT chest, abdomen and pelvis demonstrated diffuse lymphadenopathy. Repeat MRI brain demonstrated leptomeningeal enhancement most pronounced in the bilateral posterior temporal and occipital lobes. CT facial bones with contrast described increased density with central enhancement of the right maxillary sinus. Biopsy of a left inguinal lymph node revealed noncaseating granulomas consistent with sarcoid. Treatment with prednisone resulted in significant clinical improvement and resolution of leptomeningeal enhancement at 1 month. These findings are suggestive of neurosarcoidosis with possible involvement of the leptomeninges, sinuses and lymph nodes. <h3>Conclusions:</h3> Most case reports in the literature of TNF-alpha inhibitors inducing sarcoidosis describe involvement of lungs, skin, and lymph nodes. This case highlights a rare complication of TNF-alpha inhibitor resulting in neurosarcoidosis. <b>Disclosure:</b> Dr. Pak has nothing to disclose. Dr. Askari has received personal compensation for serving as an employee of Stony Brook Hospital University. Dr. Treidler has nothing to disclose.