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INTRODUCTION: The approval of biosimilars in the management of inflammatory bowel diseases (IBDs) has offered an answer to a growing concern about healthcare costs, and availability of treatments. Several studies have been conducted to demonstrate proof of biosimilars effectiveness as treatment in Crohn's disease (CD). AREAS COVERED: Since 2013, the European Medicines Agency has approved five biosimilars for infliximab and eight for adalimumab. Initial data leading to approval were extrapolated from studies conducted in patients with rheumatological or dermatological diseases, but recent studies filled the gap of clinical data among patients with IBD. In this review, 75 studies were included, with data from a total of 20 707 patients with CD. Clinical data on biosimilars in the treatment of CD show equivalence in terms of efficacy, either as induction or maintenance of treatment and regardless of previous exposure to originator or other biosimilar. EXPERT OPINION: Since biosimilar market entry, utilization of infliximab increased by 89.9% and by 22.4% for adalimumab in European countries. With a 10-year insight since the first approval of biosimilar in Europe, biosimilars prescriptions should be implemented in routine clinical practice given the efficacy and safety profile.

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INTRODUCTION: In children, ulcerative colitis (UC) is often more severe and extensive than in adults and hospitalization for acute exacerbations occurs in around a quarter of subjects. There is a need for effective drugs, which could avoid or reduce the use of corticosteroids which, especially in children, are burdened by a number of severe side effects. The introduction in therapy of monoclonal antibodies has completely changed the therapeutic scenario and the prognosis of the disease. AREAS COVERED: In this review, the use of the monoclonal antibodies directed against tumor necrosis factor (TNF)α or other inflammatory targets for the treatment of pediatric UC will be discussed. A search of the literature was done using the keywords 'pediatric,' 'ulcerative colitis,' 'inflammatory bowel disease,' 'monoclonal antibodies;' 'infliximab,' 'adalimumab,' 'golimumab,' vedolizumab," 'ustekinumab' and 'risankizumab.' EXPERT OPINION: The use of monoclonal antibodies has greatly increased in recent years in pediatric UC, both in patients who did not respond to conventional therapies, and, more often, as initial therapy. Thanks to therapeutic drug monitoring and to the availability of biologics with different targets, therapy has become more targeted and personalized, with a significant improvement in response, in quality of life, and with a good safety profile.

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There is considerable uncertainty regarding the safety and efficacy of biological therapies during pregnancy. We report a case of a 46-year-old female, diagnosed with ulcerative colitis over 30 years ago, who was successfully managed with infliximab and ustekinumab. She experienced no exacerbation of her condition during two pregnancies, demonstrating the safety of biologic therapy in maintaining disease remission during pregnancy. This case report highlights successful outcomes despite the uncertainties associated with biologic therapy during pregnancy and includes a brief review of the relevant literature.

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BACKGROUND: Type 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 PRESENTATION: A 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. CONCLUSIONS: Our 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.

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Hidradenitis suppurativa patients have an increased risk of developing cancer. This includes not only hematologic malignancies and solid tumors, but also cutaneous squamous cell carcinoma originating within the hidradenitis suppurativa lesions. The development of squamous cell carcinoma is most commonly associated with Caucasian men who smoke and have severe gluteal or perianal lesions of more than 25 years duration. Other factors that have occasionally been associated with hidradenitis suppurativa-related squamous cell carcinoma include treatment with a tumor necrosis factor-alpha inhibitor (such as infliximab and adalimumab), genodermatoses (such as keratitis-ichthyosis-deafness syndrome and Dowling-Degos disease), and paraneoplastic syndromes (such as hypercalcemia, hypercalcemia-leukocytosis, and paraneoplastic neuropathy). The tumor may demonstrate the presence of human papillomavirus; even after treatment, patients have a poor prognosis since cancer metastasis, or recurrence, or both commonly occurs. The potential role of human papillomavirus vaccination for cancer prevention and early treatment of squamous cell carcinoma with targeted therapy (with an epidermal growth factor inhibitor such as cetuximab) and/or checkpoint inhibitor immunotherapy (such as cemiplimab and pembrolizumab) remains to be determined. Rarely, hidradenitis suppurativa lesions have mimicked cutaneous metastases in patients with visceral malignancy by demonstrating an increased uptake of fluorine-18 fluorodeoxyglucose on positron emission tomography and/or computerized tomography scans. Also, both primary cancers (such as cutaneous squamous cell carcinoma and mucinous adenocarcinoma) and breast cancer skin metastases can masquerade as hidradenitis suppurativa lesions. Therefore, when a lesion is located at a current or prior site of hidradenitis suppurativa that is new or rapidly growing and/or does not respond to hidradenitis suppurativa-directed therapy, prompt evaluation to establish or exclude the diagnosis of cancer should be considered.

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Aims: A strategy based on therapeutic drug monitoring and population pharmacokinetic (popPK) models would likely increase the rate of clinical remission (CR) after infliximab (IFX) induction in patients with Crohn's disease (CD). This study aimed to evaluate the relationship between early IFX levels and antibodies to infliximab (ATI) and CR at week 14 and simulate the probability of attaining the identified exposure target. Methods: Patients with CD (n = 140) treated with IFX were enrolled to develop the popPK model. Of these, 43 moderate-to-severe patients with CD were followed up at week 14. Simulations were performed on patients with different dosage regimens and covariates. Results: IFX levels >20.08 µg/mL at week 2, >18.44 µg/mL at week 6, and >3.08 µg/mL at week 14 were linked to CR. A one-compartment model fit the data best. The covariates influencing clearance were fat free mass, albumin and ATI levels. To achieve IFX levels >20.08 µg/mL at week 2, ≥400 mg IFX was predicted to be required in over 50% patients with 45-70 kg and 35-45 g/L albumin, except for patients with 70 kg and 30 g/L albumin. Conclusion: IFX levels >20.08 µg/mL at week 2 and absence of ATI at week 14 are associated with CR. Optimising IFX induction dosing will be critical to achieve the target of early IFX levels associated with CR.

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The introduction of steroid therapy in 1955 markedly decreased the mortality rate of severe ulcerative colitis (UC) from 24% in the placebo group to 7%, and it is currently less than 1% in specialist centers. Despite this advancement, the response of severe UC to steroids has stagnated over the past 50 years, with a high rate of colectomy persisting for severe to moderately severe cases. Infliximab (IFX) (Remicade, Centocor Inc., Malvern, PA, United States), an intravenously administered chimeric monoclonal immunoglobulin G1 antibody targeting tumor necrosis factor-alpha (TNF-α), has shown efficacy in numerous randomized controlled trials for treating moderate to severe and fistulizing Crohn's disease, particularly in patients unresponsive to conventional therapies. This led to its approval by the US Food and Drug Administration in 1998 for treating active and fistulizing Crohn's disease. Most clinical research on IFX has focused on Crohn's disease, which is characterized as a Th1-type condition driven by pro-inflammatory cytokines like TNF-α. Conversely, UC has traditionally been viewed as a Th2-type condition where TNF-α plays a lesser role. However, recent studies indicate that TNF-α might also contribute to the pathogenesis of UC. These findings highlight the necessity for larger randomized controlled trials to further investigate the benefits of therapies like IFX, with the ultimate goal of improving treatment outcomes and quality of life for patients with inflammatory bowel disease.

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Neuropsychiatric disorders present a global challenge to public health. Mechanisms associated with neuropsychiatric disorders etiology include apoptosis, oxidative stress, and neuroinflammation. Tumor necrosis factor alpha, an inflammatory cytokine, mediates pathophysiology of neuropsychiatric disorders. Therefore, its inhibition by infliximab might afford a valuable target for intervention. Infliximab is commonly used to treat inflammatory diseases, including ulcerative colitis, Crohn's disease, and rheumatoid arthritis. Recently, it has been shown that infliximab improves cognitive dysfunction, depression, anxiety, and life quality. Here, we review contemporary knowledge supporting the need to further characterize infliximab as a potential treatment for neuropsychiatric disorders.

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BACKGROUND: Thiopurine co-therapy with anti-tumour necrosis factor-alpha (anti-TNFα) agents is associated with higher anti-TNFα drug levels and reduced immunogenicity in inflammatory bowel disease (IBD). AIMS: We aimed to evaluate the association between 6-thioguanine nucleotide (6-TGN) and anti-TNFα levels and the optimal 6-TGN threshold level associated with higher anti-TNFα levels in combination therapy. METHODS: We performed a retrospective cross-sectional multicentre study of patients with IBD on combination anti-TNFα and thiopurine maintenance therapy between January 2015 and August 2021. Primary outcomes were infliximab and adalimumab levels. Secondary outcomes were antibodies to infliximab (ATI) or adalimumab (ATA). Univariable and multivariable linear regression were performed to identify variables associated with anti-TNFα levels. Receiver operator characteristic curves were used to define the optimal 6-TGN cut-off levels associated with therapeutic anti-TNFα levels. RESULTS: The study included 743 paired 6-TGN and anti-TNFα levels (640 infliximab and 103 adalimumab). 6-TGN levels were associated with infliximab levels, but not adalimumab levels, on univariable and multivariable regression. The optimal 6-TGN cut-off associated with therapeutic infliximab levels (≥5 mcg/mL) was 261 pmol/8 × 108 red blood cell (RBC) (area under the curve (AUC) = 0.57) for standard infliximab dosing and 227.5 pmol/8 × 108 RBC (AUC = 0.58) for escalated dosing. For therapeutic adalimumab levels (≥7.5 mcg/mL), the 6-TGN cut-off was 218.5 pmol/8 × 108 RBC (AUC = 0.59) for standard adalimumab dosing and 237.5 pmol/8 × 108 RBC (AUC = 0.63) for escalated dosing. CONCLUSION: 6-TGN levels were weakly associated with infliximab but not adalimumab levels in combination therapy. 6-TGN levels in the lower end of the therapeutic range (230-260 pmol/8 × 108 RBC) may be adequate to maintain higher infliximab levels, particularly with escalated infliximab dosing.

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OBJECTIVE: Infliximab is a first-line biologic agent for the treatment of Crohn's disease (CD), in which loss of response (LOR) remains a challenge in the treatment of patients with CD. The study aimed to explore the association between body composition parameters and LOR to infliximab in CD patients. METHODS: 118 patients with CD admitted to the First Affiliated Hospital of Wenzhou Medical University and treated with infliximab from June 2015 to December 2021 were retrospectively enrolled. The body composition of patients was analyzed by computed tomography (CT). The primary outcome measure was the one-year LOR. Patients were divided into the Remission group and the LOR group to analyze the association between body composition parameters and the LOR to infliximab. RESULTS: The rate of sarcopenia in the LOR group was higher than in the Remission group (83.7% vs. 60.0%, P=0.008). Multivariate analysis showed that females had a lower risk of sarcopenia than males (OR=0.30, 95%CI 0.11-0.81, P =0.017); BMI was significantly associated with sarcopenia (OR=0.68, 95%CI 0.56-0.83, P <0.001); L1 CD and L2 CD had a lower risk of sarcopenia than L3 CD (OR=0.29, 95%CI 0.10-0.83, P =0.021; OR=0.25, 95%CI 0.07-0.87, P=0.028). CONCLUSIONS: Sarcopenia was identified as a risk factor for developing LOR in infliximab-treated patients.

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BACKGROUND: Low muscle mass (LMM) can be a frequent complication in Crohn's disease (CD). We attempted to explore the effect of LMM on the efficacy of biologics in patients with CD. METHODS: The retrospective cohort study included moderate-to-severe CD patients treated with infliximab or ustekinumab, and appendicitis patients as control. The skeletal muscle area (SMA) of L3 was assessed to evaluate the patients' muscle mass. After propensity score matching, the impact of LMM on drug efficacy was assessed in CD patients. RESULTS: A total of 269 patients with CD and 172 appendicitis patients were included. The CD group had lower skeletal muscle density and BMI, and a higher risk of developing LMM than the control group. BMI (OR = 0.48, p < 0.001) and previous use of biologics (OR = 2.94, p = 0.019) were found to be independently associated with LMM. LMM was found to be associated with a decrease in clinical response (at weeks 8-14), clinical remission (at weeks 8-14, 24-30 and 52) and biochemical remission (at week 52). At weeks 24-30 and 52, LMM was independently associated with loss of response (LOR). We found LMM could be a predictor of lower clinical remission at week 30, lower clinical remission at week 52 and a higher LOR rate at week 30 in infliximab. While in ustekinumab, LMM was associated with lower endoscopic remission at week 24, biochemical remission at week 52 and a higher LOR rate at weeks 24 and 52. CONCLUSIONS: The prevalence of LMM was higher in the CD group compared to the control group. For CD patients with LMM, the efficacy of infliximab and ustekinumab was relatively poor in both the short-term and long-term.

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Ulcerative colitis has been associated with psychological distress and an aberrant immune response. The immunomodulatory role of systemic cytokines produced during experimental intestinal inflammation in tonic immobility (TI) defensive behavior remains unknown. The present study characterized the TI defensive behavior of guinea pigs subjected to colitis induction at the acute stage and after recovery from intestinal mucosa injury. Moreover, we investigated whether inflammatory mediators (tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-8, IL-10, and prostaglandins) act on the mesencephalic nucleus, periaqueductal gray matter (PAG). Colitis was induced in guinea pigs by intrarectal administration of acetic acid. The TI defensive behavior, histology, cytokine production, and expression of c-FOS, IBA-1, and cyclooxygenase (COX)-2 in PAG were evaluated. Colitis reduced the duration of TI episodes from the first day, persisting throughout the 7-day experimental period. Neuronal c-FOS immunoreactivity was augmented in both columns of the PAG (ventrolateral (vlPAG) and dorsal), but there were no changes in IBA-1 expression. Dexamethasone, infliximab, and parecoxib treatments increased the duration of TI episodes, suggesting a modulatory role of peripheral inflammatory mediators in this behavior. Immunoneutralization of TNF-α, IL-1ß, and IL-8 in the vlPAG reversed all effects produced by colitis. In contrast, IL-10 neutralization further reduced the duration of TI episodes. Our results reveal that peripherally produced inflammatory mediators during colitis may modulate neuronal functioning in mesencephalic structures such as vlPAG.

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Immune checkpoint inhibitors (ICIs), including anti-programmed cell death protein 1 and its ligand (PD-1/PD-L1) as well as anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4), have been widely used for treating solid tumors. Myocarditis is a potentially lethal immune-related adverse events (irAEs) caused by ICIs therapy. The treatment of steroid-refractory myocarditis is challenging. We reported two non-small-cell lung cancer patients with steroid-refractory myocarditis induced by ICI. The symptoms were not resolved after pulse corticosteroid therapy and subsequent treatment including intravenous immunoglobulin and mycophenolate mofetil. Considering the level of serum interleukin (IL)-6 decreased by > 50% and level of serum tumor necrosis factor-α (TNF-α) increased during the course of the disease, infliximab was used. Myocarditis gradually alleviated after infliximab treatment. The cases revealed that specific cytokine inhibitors have promising roles in the treatment of steroid-refractory myocarditis. Infliximab could be considered for patients with low level of IL-6 and elevated level of TNF-α.

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Metastatic Crohn's disease is the rarest cutaneous manifestation of Crohn's disease, it presents as cutaneous lesions in areas that are anatomically non-contiguous with the gastrointestinal tract. It requires a high index of suspicion for diagnosis which is confirmed on histopathology. Infliximab can be an effective treatment.

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BACKGROUND AND AIMS: Switching from the intravenous to the subcutaneous biosimilar infliximab (SC-IFX) has been shown to safely maintain clinical remission and increase drug levels in patients with Crohn's disease (CD) and ulcerative colitis (UC). The aim of this study was to evaluate long-term outcomes after switching from intravenous IFX (IV-IFX) to SC-IFX, the drug concentration thresholds for maintaining remission and other predictors for loss of response after the switch. METHODS: Multicenter observational study involving CD and UC patients who were in clinical remission for at least 24 weeks and scheduled to switch from IV-IFX to SC-IFX. RESULTS: Two hundred and twenty patients were included [74 UC (34%) and 146 (66%) CD]. IV-IFX was administered for 52.5 months [range 25-89]. Pre-switch, 106 (49%) patients were receiving intensified IV-IFX. While SC-IFX levels significantly increased following the switch from IV to SC-IFX, clinical parameters, C-reactive protein and faecal calprotectin remained unchanged during follow-up. SC-IFX levels were significantly higher between patients receiving the standard IV-IFX dose than those with the intensified dose. Immunomodulator therapy at baseline and perianal disease had no effect on IFX trough levels, whereas higher body mass index was associated with increased levels. The suggested optimal SC-IFX cut-off concentration for clinical and biochemical remission based on ROC analysis was 12.2 µg/mL (AUC: 0.62) at week 12 and 13.2 µg/mL (AUC: 0.57) at week 52. Drug persistence was 92% at week 52, with a good safety profile. CONCLUSION: Switching from IV-IFX to SC-IFX safely maintains long-term remission in patients with CD and UC. In maintenance, the optimal cut-off point associated with remission was 12-13 µg/mL.

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The management of refractory ulcerative colitis (UC) and acute severe UC (ASUC) is challenging due to the lack of standardized approaches in cases resistant to multiple treatments. In this editorial, I investigate the efficacy and safety of Janus kinase inhibitors, particularly upadacitinib and tofacitinib, in controlling severe and refractory disease. I highlight a notable case report by Xu et al, which explores the case of a patient with primary nonresponse to two classes of biologics and two fecal microbiota transplants who exhibited a remarkable response to upadacitinib. Furthermore, I discuss the use of tofacitinib in refractory UC and ASUC, either as monotherapy or in combination with biologics, which has shown promising response rates. Additionally, emerging evidence of upadacitinib efficacy in ASUC is presented. Overall, these cases emphasize the complex nature of managing refractory ASUC and the potential of small-molecule therapies to achieve remission. Further research is needed to refine treatment strategies for patients with treatment-resistant UC.

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INTRODUCTION: Behcet's syndrome is a rare inflammatory disorder characterized by oral and genital ulcers, skin lesions, and uveitis. It exhibits a higher prevalence along the historic Silk Road. Neuro-Behcet syndrome (NBS) affects the central nervous system and poses significant morbidity and mortality risks. Infliximab, a TNF-alpha antagonist, has shown potential in NBS management, although the current evidence is mainly derived from case series due to the lack of randomized controlled trials. OBJECTIVE: This retrospective study aimed to evaluate the disease outcomes during the first and second years following infliximab treatment in NBS patients experiencing attacks despite prior conventional immunosuppressive therapy. The study also sought to investigate the safety profile and adverse effects associated with infliximab. METHODS: Fifty-three NBS patients were examined, with 22 receiving infliximab as either monotherapy or in combination with other therapies. Retrospective analysis was conducted on demographic data, clinical characteristics, and treatment responses. Treatment efficacy was measured using the Expanded Disability Status Scale (EDSS) modified for NBS. The study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist guidelines. RESULTS: Among the study cohort, 60.4% had parenchymal NBS, and 39.6% had nonparenchymal NBS. Treatment with infliximab resulted in remission or disease stabilization in 95% of patients after one year and 68.7% after 2 years. Relapse rates were 4.5% at 1 year and 18.7% at 2 years, with disease progression observed in two cases. Adverse effects were primarily mild to moderate, with no reports of serious adverse events. CONCLUSION: Infliximab exhibited efficacy in achieving remission or stabilization in NBS patients, maintaining a favorable safety profile. The timing of infliximab treatment may prevent the accumulation of disability and hinder disease progression. Nonetheless, future prospective studies are necessary to confirm these findings and refine treatment strategies for this complex condition.

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BACKGROUND: Achieving long-term clinical remission in Crohn's disease (CD) with antitumor necrosis factor α (anti-TNF-α) agents remains challenging. AIMS: This study aims to establish a prediction model based on patients' clinical characteristics using a machine-learning approach to predict the long-term efficacy of infliximab (IFX). METHODS: Three cohorts comprising 746 patients with CD were included from 3 inflammatory bowel disease (IBD) centers between June 2013 and January 2022. Clinical records were collected from baseline, 14-, 30-, and 52-week post-IFX treatment. Three machine-learning approaches were employed to develop predictive models based on 23 baseline predictors. The SHapley Additive exPlanations (SHAP) algorithm was used to dissect underlying predictors, and latent class mixed model (LCMM) was applied for trajectory analysis of the longitudinal change of blood routine tests along with long-term IFX therapy. RESULTS: The XGBoost model exhibited the best discrimination between long-term responders and nonresponders. In the internal training and testing set, the model achieved an AUC of 0.91 (95% CI, 0.86-0.95) and 0.71 (95% CI, 0.66-0.87), respectively. Moreover, it achieved a moderate predictive performance in the independent external cohort, with an AUC of 0.68 (95% CI, 0.59-0.77). The SHAP algorithm revealed disease-relevant laboratory measurements, notably hemoglobin (HB), white blood cells (WBC), erythrocyte sedimentation rate (ESR), albumin (ALB), and platelets (PLT), alongside age at diagnosis and the Montreal classification, as the most influential predictors. Furthermore, 2 distinct patient clusters based on dynamic laboratory tests were identified for monitoring the long-term remission. CONCLUSIONS: The established prediction model demonstrated remarkable discriminatory power in distinguishing long-term responders from nonresponders to IFX therapy. The identification of distinct patient clusters further emphasizes the need for tailored therapeutic approaches in CD management.

The study developed a machine-learning model using clinical data to predict long-term efficacy of IFX in Crohn's disease. The XGBoost model demonstrated strong discriminatory power, revealing influential predictors and distinct patient clusters, emphasizing the importance of tailored therapeutic approaches in CD management.

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Background: Despite infliximab biosimilars becoming widely used in inflammatory bowel disease (IBD) patients, real-world non-medical switching is sparse. A biosimilar non-medical switch was launched in British Columbia in 2019, the first Canadian province to do so, from Remicade to an approved biosimilar (CT-P13 or SB2). Aims: This study aims to obtain real-world evidence evaluating the clinical outcomes of non-medical switching from Remicade to the infliximab biosimilars. Methods: This is a retrospective observational study of stable IBD patients from the IBD Centre of BC who underwent the non-medical infliximab switch. The primary outcome is treatment continuation at 12 ± 2 months post-switch. Secondary outcomes include frequency of loss of response, adverse events, and immunogenicity within the first 12 months post-switch. A control group of patients maintained on the originator served as a comparison. Results: Patients in the biosimilar switch group (n = 264) and originator group (n = 99), show similar demographics and disease characteristics. There was no difference in infliximab continuation between the biosimilar group (94.9%) and the originator group (90.1%) (P = 0.18). Reasons for discontinuation of infliximab included loss of response (4.04% vs 4.91%), immunogenicity (1.01% vs 0.75%), or adverse effect (1.01% vs 2.3%) in the infliximab originator vs biosimilar switch group, respectively. Similarly, no differences in safety or efficacy were observed between patients switched to CT-P13 or SB2. Conclusions: Non-medical biosimilar switch of infliximab demonstrates similar clinical outcomes compared to originator molecule continuation for therapy of IBD. These data support the safety and efficacy of non-medical infliximab switching in IBD patients.

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Psoriasis is a chronic, inflammatory skin disease characterized by a dysregulated immune response and systemic inflammation. Up to one-third of patients with psoriasis have psoriatic arthritis (PsA). Targeted treatment with antibodies neutralizing tumor necrosis factor (TNF) can ameliorate both diseases. We here explored the impact of long-term infliximab treatment on the composition and activity status of circulating immune cells involved in chronic skin and joint inflammation. Immune cells were analyzed by multicolor flow cytometry. We measured markers of immune activation in peripheral blood mononuclear cell (PBMC) populations in 24 infliximab-treated patients with psoriasis/psoriatic arthritis compared to 32 healthy controls. We observed a significant decrease in the frequency of both peripheral natural killer (NK) cells and their subset CD56dimCD16+ NK cells in PsA compared to healthy controls and patients with psoriasis. The latter had a strong positive correlation with PASI in these patients, while CD56brightCD16- NK cells were negatively correlated with PASI. In addition, we observed an upregulation of CD69+ intermediate CD14+CD16+ and CD69+ classical CD14+CD16- monocytes in PsA and increased activity of CD38+ intermediate CD14+CD16+ monocytes in patients with psoriasis. Compared to healthy controls, psoriasis patients demonstrated shifts of the three B cell subsets with a decrease in transitional CD27-CD38high B cells. Our exploratory study indicates a preserved pathophysiological process including continuous systemic inflammation despite clinical stability of the patients treated with infliximab.