Background/Objectives: Psoriasis is a chronic, inflammatory, immuno-mediated cutaneous disease characterized by a prominent TNFα-IL23/IL17 immune axis. In recent years, targeted therapies have become standard practice for managing moderate-to-severe psoriasis and have demonstrated efficacy. At the same time, identifying factors associated with the success or failure of TNFα inhibitor therapy remains one of the most difficult aspects in psoriasis treatment. Methods: A clinical, non-randomized study was conducted to evaluate the impact of TNFα inhibitors on the plasma cytokine profiles in patients with moderate-to-severe psoriasis vulgaris (ICD-10 code L40.0). The patients were treated with either etanercept, adalimumab, or infliximab for 16 weeks. Plasma cytokine profiles were assessed using a BioPlex200 System. Results: By the 16th week of therapy, a positive treatment response (PASI ≥ 75) was observed in 51 patients (63%), while 30 patients (37%) showed no response (PASI ≤ 50). When using etanercept, a positive effect was observed in 11 patients (41%), in 14 patients (52%) using adalimumab, and in 26 patients (96%) using infliximab. Analysis of the baseline cytokine levels revealed no differences between the \"positive effect\" and \"no effect\" groups, except for IL20, which was 2.61 times higher in the \"positive effect\" group compared to the \"no effect\" group, suggesting its potential predictive role in the effectiveness of therapy with TNFα inhibitors. Treatment led to a decrease in IL17F, IL31, sCD40L, and VEGF for all patients, and in IL20 for the \"positive effect\" group. The increase in ICAM1 in the \"no effect\" group suggests the possible retention of active migration and the fixation of T cells in the affected skin in these patients. No significant difference in cytokine levels was observed when categorizing patients into subgroups based on the effectiveness of therapy with etanercept, infliximab, and adalimumab; only a pre- and post-treatment difference in the whole cohort was noted. A random forest model showed the importance of VEGF, sCD40L, and ICAM1. Conclusions: The baseline levels of VEGF, sCD40L, and ICAM1, as well as IL20, could serve as potential predictors of treatment effectiveness using TNFa inhibitors. However, this hypothesis requires confirmation with a larger patient population.

UNASSIGNED: Acne inversa (AI) is a refractory inflammatory skin disease, and TNF-α plays an important role in the pathogenesis of AI. By blocking TNF-α, infliximab (IFX) has been proven to be a promising method.
UNASSIGNED: To explore the underlying mechanisms of IFX treatment in AI patients.
UNASSIGNED: In this research, we integrated transcriptome sequencing data from the samples of our patients with AI and the GEO database. Ex vivo skin culture of AI patients was conducted to evaluate the efficacy of IFX treatment. Animal studies and cell experiments were used to explore the therapeutic effect and mechanism of IFX treatment.
UNASSIGNED: Both TNF-α and NLRP3 inflammasome-related pathways were enriched in skin lesions of AI patients and murine AI models. After IFX treatment, the NLRP3 inflammasome-related pathway was effectively blocked, and the IL-1β level was normalized in ex vivo AI skin explants and murine AI models. Mechanistically, IFX suppressed the NF-κB signaling pathway to lower the expression of NLRP3 and IL-1β in keratinocytes.
UNASSIGNED: IFX treatment alleviated skin lesions in murine AI models and downregulated NLRP3 and IL-1β expression levels by inhibiting the NF-κB signaling pathway, which was helpful for understanding the mechanism of IFX therapy.

BACKGROUND: Inflammatory bowel disease (IBD), consists of two primary types: Ulcerative Colitis (UC) and Crohn\'s Disease (CD). Infliximab (IFX) and Adalimumab (ADA) are frequently utilized in the management of moderate to severe cases of IBD.
OBJECTIVE: This study aimed to assess the efficacy and safety of IFX and ADA in individuals diagnosed with moderate to severe IBD.
METHODS: This study is a prospective open-labeled randomized parallel study that included moderate to severe IBD patients treated with either IFX or ADA. A total of 56 patients participated, with 34 patients received IFX and 22 patients received ADA. Various measures, including Crohn\'s Disease Activity Index (CDAI), Mayo Score/ Disease Activity Index (DAI), and C-reactive protein (CRP) levels, were taken at baseline and week 14 to assess the efficacy of the treatments. In addition, the levels of drugs and sTREM-1 were measured at 14 weeks. Patient safety was monitored throughout the study period.
RESULTS: In the group received IFX, there was a notable decrease in CDAI (P = 0.045), DAI (P = 0.026), and CRP (P = 0.023 for CD, and P = 0.021 for UC) levels. In addition, the group received ADA experienced a significant reduction in CDAI (P = 0.001), DAI (P = 0.032), and CRP (P < 0.018 for CD and P = 0.003 for UC) levels. Responders had higher drug concentrations than non-responders, notably IFX concentration was higher in responders with CD (P = 0.001) and UC (P < 0.001). ADA concentration was higher in UC (P <= 0.001) and all CD patients responded to the treatment. The same trend was observed for sTREM-1 levels in CD and UC patients (P = 0.042, and P = 0.015, respectively) in the IFX group. In UC patients treated with ADA, the level of sTREM-1 was significantly low (P = 0.002).
CONCLUSIONS: Both IFX and ADA have a good safety profile and deliver a beneficial clinical and laboratory response in moderate-severe IBD patients.
BACKGROUND: This study is registered on ClinicalTrials.gov under the identifier NCT05291039. (You can access the study at https://clinicaltrials.gov/study/NCT05291039 (First Posted: March 22, 2022).

BACKGROUND: The application of infliximab (IFX) to immune-mediated disease is limited by the significant individual variability and associated clinical nonresponse, emphasizing the importance of therapeutic drug monitoring (TDM). Because of the cross-reactivity, limited linear range, and high costs, the clinical application of the previous reported methods was limited. Here, an improved high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method was developed to address the issues.
METHODS: This study developed an improved bioanalytical HPLC-MS/MS method coupling nanosurface and molecular-orientation limited proteolysis technology. The commercially available compound P14R was selected as the internal standard. This method was developed with fewer volume of reagents and was thoroughly validated. The validated method was applied to TDM in pediatric inflammatory bowel disease (IBD).
RESULTS: Chromatography was performed using a Shim-pack GISS-HP C18 metal-free column (3 μm, 2.1 × 100 mm) with a gradient elution of 0.1% formic acid in water and acetonitrile at 0.4 mL/min. Detection and quantitation were performed using electrospray ionization (ESI) and multiple reaction monitoring in the positive ion mode. The method was validated to demonstrate its selectivity, linearity, accuracy, precision, recovery, matrix effect, and stability. The method exhibited a linear dynamic range of 0.3-100 μg/mL, with intra- and inter-day precision and relative errors below 15%. The recovery and matrix effect were measured as 87.28%-89.72% and 41.98%-67.17%, respectively, which were effectively compensated by the internal standard. A total of 32 samples collected from 24 pediatric patients with IBD were analyzed using the validated method, and only 46.9% achieved the reported targeted trough level.
CONCLUSIONS: This study developed an improved HPLC-MS/MS method for the quantitative determination of IFX concentration in human plasma. The accurate, reliable, and cost-effective method was validated and utilized in the analysis of clinical samples. The results confirmed the importance of TDM on IFX and the clinical application prospects of the improved method.

UNASSIGNED: Infliximab (IFX) biosimilars are available to treat inflammatory bowel disease (IBD), offering cost reductions versus originator IFX in some jurisdictions. However, concerns remain regarding the efficacy and safety of originator-to-biosimilar switching. This systematic literature review evaluated safety and effectiveness of switching between IFX products in patients with IBD, including multiple switchers.
UNASSIGNED: Embase, PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials were searched to capture studies (2012-2022) including patients with IBD who switched between approved IFX products. Effectiveness outcomes: disease activity; disease severity; response to treatment; patient-reported outcomes (PROs). Safety outcomes: incidence and rate of adverse events (AEs); discontinuations due to AEs, failure rate; hospitalizations; surgeries. Immunogenicity outcomes (n, %): anti-drug antibodies; patients receiving concomitant immunomodulatory medication.
UNASSIGNED: Data from 85 publications (81 observational, two randomized controlled trials) was included. Clinical effectiveness outcomes were consistent with the known profile of originator IFX with no difference after switching. There were no unexpected/serious AEs after switching, and rates of AEs were generally consistent with the known profile of IFX.
UNASSIGNED: Most studies reported that clinical, PROs, and safety outcomes for originator-to-biosimilar switching were clinically equivalent to originator responses. Limited data are available regarding multiple switches.
UNASSIGNED: www.crd.york.ac.uk/prospero identifier is CRD42021289144.

OBJECTIVE: Multiple studies in patients with Crohn\'s disease (CD) treated with anti-tumor necrosis factor alpha agents have shown that proactive therapeutic drug monitoring (TDM) during the maintenance phase leads to improved outcomes. We aimed to assess whether accelerated infliximab administration during induction resulted in improved outcomes.
METHODS: This retrospective study included CD patients aged 5-17.9 years that were treated with infliximab. 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 infliximab. Primary outcome was steroid-free clinical remission by Week 52.
RESULTS: Sixty-eight patients were included, of whom seven discontinued infliximab 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 infliximab initiation. Despite receiving significantly more infliximab, 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 infliximab levels by Week 52.
CONCLUSIONS: Accelerated infliximab 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.

UNASSIGNED: Infliximab is a chimeric monoclonal antibody against tumor necrosis factor alpha, and GP1111 (Zessly®, Sandoz) is the most recently approved infliximab biosimilar in Europe. We reviewed the approval process and key evidence for GP1111, focusing primarily on the indications of rheumatoid arthritis (RA) and inflammatory bowel disease (IBD).
UNASSIGNED: This narrative review discusses pre-clinical, clinical, and real-world data for GP1111.
UNASSIGNED: Results from the Phase III REFLECTIONS trial in patients with moderate-to-severe active RA despite methotrexate therapy confirmed the similarity in efficacy and safety between GP1111 and reference infliximab. Switching from reference infliximab to GP1111 in REFLECTIONS had no impact on efficacy or safety. Since the European approval of GP1111 in March 2018, real-world data have also confirmed the efficacy and safety of switching from another infliximab biosimilar to GP1111 in patients with RA and IBD. In addition, budget impact analysis of various sequential targeted treatments in patients with RA found that GP1111 was cost-effective when used early after failure of conventional synthetic disease-modifying antirheumatic drugs. Therefore, 5 years\' post-approval experience with GP1111 in RA and IBD, and key clinical and real-world evidence, support the safety and efficacy of continued use of GP1111 in all infliximab-approved indications.

The intestine constantly encounters and adapts to the external environment shaped by diverse dietary nutrients. However, whether and how gut adaptability to dietary challenges is compromised in ulcerative colitis is incompletely understood. Here, we show that a transient high-fat diet exacerbates colitis owing to inflammation-compromised bile acid tolerance. Mechanistically, excessive tumor necrosis factor (TNF) produced at the onset of colitis interferes with bile-acid detoxification through the receptor-interacting serine/threonine-protein kinase 1/extracellular signal-regulated kinase pathway in intestinal epithelial cells, leading to bile acid overload in the endoplasmic reticulum and consequent apoptosis. In line with the synergy of bile acids and TNF in promoting gut epithelial damage, high intestinal bile acids correlate with poor infliximab response, and bile acid clearance improves infliximab efficacy in experimental colitis. This study identifies bile acids as an \"opportunistic pathogenic factor\" in the gut that would represent a promising target and stratification criterion for ulcerative colitis prevention/therapy.

BACKGROUND: Data regarding the clinical outcome of patients with immune checkpoint inhibitor (ICI)-induced colitis are scant. We aimed to describe the 12-month clinical outcome of patients with ICI-induced colitis.
METHODS: This was a retrospective, European, multicentre study. Endoscopy/histology-proven ICI-induced colitis patients were enrolled. The 12-month clinical remission rate, defined as a Common Terminology Criteria for Adverse Events diarrhoea grade of 0-1, and the correlates of 12-month remission were assessed.
RESULTS: Ninety-six patients [male:female ratio 1.5:1; median age 65 years, interquartile range (IQR) 55.5-71.5 years] were included. Lung cancer (41, 42.7%) and melanoma (30, 31.2%) were the most common cancers. ICI-related gastrointestinal symptoms occurred at a median time of 4 months (IQR 2-7 months). An inflammatory bowel disease (IBD)-like pattern was present in 74 patients (77.1%) [35 (47.3%) ulcerative colitis (UC)-like, 11 (14.9%) Crohn\'s disease (CD)-like, 28 (37.8%) IBD-like unclassified], while microscopic colitis was present in 19 patients (19.8%). As a first line, systemic steroids were the most prescribed drugs (65, 67.7%). The 12-month clinical remission rate was 47.7 per 100 person-years [95% confidence interval (CI) 33.5-67.8). ICI was discontinued due to colitis in 66 patients (79.5%). A CD-like pattern was associated with remission failure (hazard ratio 3.84, 95% CI 1.16-12.69). Having histopathological signs of microscopic colitis (P = 0.049) and microscopic versus UC-/CD-like colitis (P = 0.014) were associated with a better outcome. Discontinuing the ICI was not related to the 12-month remission (P = 0.483). Four patients (3.1%) died from ICI-induced colitis.
CONCLUSIONS: Patients with IBD-like colitis may need an early and more aggressive treatment. Future studies should focus on how to improve long-term clinical outcomes.

BACKGROUND: Immune-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 factor (TNF) antibodies are used for management of multiple irAEs, but there are little data in irHepatitis. Here, we report on safety and efficacy of infliximab in 10 cases of steroid-refractory irHepatitis.
METHODS: We retrospectively reviewed patients treated with infliximab for steroid-refractory grade ≥3 irHepatitis at the Department of Dermatology, University Hospital Zurich. The positive response to infliximab was defined as no further increase in alanine aminotransferase (ALT)/aspartate aminotransferase (AST) above 50% than at the time of first infliximab infusion and control of irHepatitis without therapies other than steroids and infliximab.
RESULTS: 10 patients with steroid-resistant irHepatitis grade ≥3 were treated with infliximab 5 mg/kg, of whom 7 (70%) responded positively. In two cases, the liver values increased over 50% before the irHepatitis could be controlled. In another case, therapies other than infliximab and steroids were given. At the median follow-up of 487 days, 90% of the patients demonstrated resolved irHepatitis without AST/ALT elevation following infliximab infusions.
CONCLUSIONS: Treatment of irHepatitis with infliximab did not result in hepatotoxicity and led to long-lasting positive response in 9 of 10 of the cases. Further research is needed to evaluate the role of anti-TNF antibodies in management of irHepatitis.