Infliximab Treatment Research Articles

Infliximab therapy in parenchymal neuro-Behçet's disease: A single-center experience.

Parenchymal neuro-Behçet's disease involvement is the most serious complication of Behçet's disease, and no sufficient data on its treatment exists. This study aims to investigate the efficacy and safety of infliximab treatment in neuro-Behçet's disease patients with parenchymal involvement. Patients who were diagnosed with Behçet's disease with parenchymal neurological involvement and underwent infliximab treatment for at least 12months were included in the study. Demographic, clinical, and radiological data of the patients were accessed through the electronic database of our hospital. This study comprises 19 patients who were diagnosed with neuro-Behçet's disease and used infliximab: 12 male and 7 female patients. The mean age of the patients was 36.5±11.7years, and the diagnostic age was 26.3±10.8years. The duration of treatment with infliximab was 32.3months (minimum 11, max 79). In the 19 patients receiving infliximab treatment, 11 (58%) patients achieved remission (complete disappearance of neurological symptoms) and 7 (37%) patients achieved disease stability (no new neurological findings); steroid treatments were discontinued for these 18 patients. In addition, only 5 patients were concomitantly taking immunosuppressive drugs with the infliximab. Infliximab was discontinued after the development of a new parenchymal attack in the 9th month of infliximab treatment. In conclusion, parenchymal neurological involvement in Behçet's disease is an important cause of disability, and no sufficient data exists in literature on its treatment. The results of our study suggest that infliximab treatment was effective and safe in neuro-Behçet's disease parenchymal involvement for preventing long-term neurological attacks and discontinuing corticosteroid treatment.

The Selective 5-HT1A Agonist SR57746A Protects Intestinal Epithelial Cells and Enteric Glia Cells and Promotes Mucosal Recovery in Experimental Colitis.

Neurotrophic growth factors can stabilize the intestinal barrier by preventing the apoptosis of enteric glial cells (EGCs) and enterocytes. We reasoned that a selective 5-HT1A receptor agonist may have neuroprotective properties in the gut and that topical application of SR57746A might be an effective treatment strategy in inflammatory bowel disease (IBD). The therapeutic potential of 5-HT1A receptor agonist SR57746A in IBD was evaluated in vitro (nontransformed NCM460 colonic epithelial cells, SW480 colorectal carcinoma cells) and in vivo (murine dextran sulfate sodium [DSS] colitis and CD4-T-cell transfer colitis). In vitro, we analyzed the effect of SR57746A on apoptosis in intestinal epithelial cells (IECs) and EGCs, and upon proliferation, migration, and intracellular signaling in IECs. In vivo, the effect of topical application of SR57746 on disease activity and on histological and endoscopic findings was compared with intraperitoneal infliximab and placebo, respectively. The SR57746A activates PI3-K/AKT- and ERK-signaling in IECs. Depending on ERK- and AKT activation, SR57746A potently prevents apoptosis of IECs without inducing proliferation or migration in these cells. Moreover, SR57746A prevented apoptosis in EGCs in vitro. Topical SR57746A treatment significantly reduced mucosal injury in 2 experimental murine colitis models and was as effective as intraperitoneal infliximab treatment. Treatment with SR57746A prevents inflammatory cell damage and apoptosis in IECs and EGCs, similar to the neurotrophic effects of EGCs on IECs. Topical treatment with SR57746A could be a candidate for clinical evaluation in the treatment of IBD.

Infliximab-related Optic Neuritis in a Patient with Crohn's Disease: a Case Report and Literature Review

Purpose: We report a case of optic neuritis related to infliximab treatment in a patient with Crohn’s disease, along with a review of the relevant literature.Case summary: A 22-year-male patient complained of blurred vision in the left eye for 2-3 weeks. His best-corrected visual acuity was 8/20 in the left eye. Relative afferent pupillary defect was detected in the left eye and the pupils were of equal size. There was no pain on ocular movement. The results of slit-lamp and fundus examinations were normal. A visual field test revealed a central to inferior visual field defect in the left eye. Orbit magnetic resonance imaging revealed perineural enhancement of the left optic nerve. He had a 5-year history of Crohn’s disease and had been treated with intravenous infliximab (600 mg every 2 weeks). A diagnosis of retrobulbar optic neuritis associated with infliximab was made. He was infused with high-dose methylprednisolone, which was changed to per oral administration. His visual acuity and visual field defect improved after 3 months.Conclusions: Tumor necrosis factor-α inhibitors, such as infliximab, may cause optic neuritis. Therefore, history-taking is important for differential diagnosis and appropriate treatment.

Body mass index, HbA1c and serum C-reactive protein are predictors of secondary failure in infliximab continuance for Japanese psoriasis patients: A hospital-based retrospective case-control study.

Biologics has had a great impact on psoriasis treatment as well as the life of psoriasis patients. Infliximab (IFX), one of the biologics targeting tumor necrosis factor (TNF), is the first of the biologics introduced to Japanese psoriasis patients. Many patients had benefits of IFX from initial applications and sustained remission of skin lesions and arthritis. Some, however, fall into so-called secondary failure, in which patients become less responsive to IFX when the treatment is repeated. The mechanism of secondary failure and the background of patients with secondary failure have not been completely elucidated. To address this issue, we retrospectively evaluated psoriasis patients treated with IFX in our department. In this retrospective, single-center, case-control study based on the clinical record, a total of 34 patients were enrolled. We excluded 7 patients who discontinued IFX because of adverse events of IFX. We divided other 27 patients into two groups; 16 patients who kept using IFX (Continuance group); and 11 patients who switched to other treatments (Discontinuance group). Among various clinical features, body mass index (BMI), HbA1c, and serum CRP level were significantly higher in the Discontinuance group than the Continuance group. The results indicated that these three clinical features of BMI, HbA1c and serum CRP level before treatment are the predictors of successful IFX treatment and suggest that improvement of metabolic conditions contributes to avoiding secondary failure and discontinuance of IFX.

Infliximab Treatment Does Not Lead to Full TNF-α Inhibition: A Target-Mediated Drug Disposition Model.

Infliximab, an anti-tumour necrosis factor (TNF)-α monoclonal antibody, has been approved in chronic inflammatory disease, including rheumatoid arthritis, Crohn's disease and ankylosing spondylitis. This study aimed to investigate and characterise target-mediated drug disposition of infliximab and antigen mass turnover during infliximab treatment. In this retrospective cohort of 186 patients treated with infliximab for rheumatoid arthritis, Crohn's disease or ankylosing spondylitis, trough infliximab concentrations were determined from samples collected between weeks 0 and 22 after treatment initiation. Target-mediated pharmacokinetics of infliximab was described using target-mediated drug disposition modelling. Target-mediated elimination parameters were determined for rheumatoid arthritis and Crohn's disease, assuming ankylosing spondylitis with no target-mediated elimination. The quasi-equilibrium approximation of a target-mediated drug disposition model allowed a satisfactory description of infliximab concentration-time data. Estimated baseline TNF-α amounts were similar in Crohn's disease and rheumatoid arthritis (R0 = 0.39 vs 0.46 nM, respectively), but infliximab-TNF complex elimination was slower in Crohn's disease than in rheumatoid arthritis (kint = 0.024 vs 0.061 day-1, respectively). Terminal elimination half-lives were 13.5, 21.5 and 16.5 days for rheumatoid arthritis, Crohn's disease and ankylosing spondylitis, respectively. Estimated amounts of free target were close to baseline values before the next infusion suggesting that TNF-α inhibition may not be sustained over the entire dose interval. The present study is the first to quantify the influence of target antigen dynamics on infliximab pharmacokinetics. Target-mediated elimination of infliximab may be complex, involving a multi-scale turnover of TNF-α, especially in patients with Crohn's disease. Additional clinical studies are warranted to further evaluate and fine-tune dosing approaches to ensure sustained TNF-α inhibition.

Monitoring frequency of interferon gamma release assay for tuberculosis surveillance following infliximab therapy in patients with Crohn's disease.

To characterize the pattern of positive conversion of interferon gamma release assay (IGRA) in patients with Crohn's disease (CD) during infliximab therapy in China, which has a high burden of tuberculosis. Eligible patients with CD who received serial IGRA screening during infliximab therapy from January 2015 to March 2020 were retrospectively included. The positive conversion rate of IGRA and the risk of subsequent tuberculosis of the patients were analyzed. A total of 128 patients with CD were included, and the median time from the initiation of IFX treatment to positive conversion or the last follow-up test of IGRA was 43.6 weeks. At baseline 3.9% of the patients were positive for IGRA and received prophylactic anti-tuberculosis treatment. In the other 123 patients with negative IGRA at baseline, 6.5% had IGRA positive conversion during infliximab treatment, and one (12.5%) who was exposed to Mycobacterium tuberculosis was diagnosed as having active tuberculosis. The conversion rate at 40 weeks, 2 years and 3 years after treatment were 10.0% (6/60), 2.2% (1/46) and 5.9% (1/17), respectively. Age, sex, history of smoking and alcohol consumption, disease severity (Crohn's disease activity index score) and immunosuppressive therapy were not significantly associated with latent tuberculosis test conversion. Positive conversion of IGRA occurs early during treatment with infliximab for CD and the monitoring frequency of IGRA should be appropriately increased at the early stage of treatment. Physicians should pay attention to patient's history of tuberculosis exposure and carry out surveillance in a timely fashion.

A random forest model predicts responses to infliximab in Crohn’s disease based on clinical and serological parameters

Background Infliximab (IFX) has revolutionised the treatment for Crohn’s disease (CD) recently, while a part of patients show no response to it at the end of the induction period. We developed a random forest-based prediction tool to predict the response to IFX in CD patients. Methods This observational study retrospectively enrolled the patients diagnosed with active CD and received IFX treatment at the Gastroenterology Department in Xiangya Hospital of Central South University between January 2017 and December 2019. The baseline data were recorded in the beginning and were used as predictor variables to construct models to forecast the outcome of the response to IFX. Results Our cohort identified a total of 174 patients finally with a response rate of 29.3% (51/174). The area under the receiver operating characteristic curve (AUC) for the model, based on the random forest was 0.90 (95%CI: 0.82–0.98), compared to the logistic regression model with AUC of 0.68 (95%CI: 0.52–0.85). The optimal cut-off value of the random forest model was 0.34 with the specificity of 0.94, the sensitivity of 0.81 and the accuracy of 0.85. We demonstrated a strong association of IFX response with the levels of complement C3 (C3), high density lipoprotein, serum albumin, Controlling Nutritional Status (CONUT) score and visceral fat area/subcutaneous fat area ratio (VSR). Conclusion A novel random forest model using the clinical and serological parameters of baseline data was established to identify CD patients with baseline inflammation to achieve IFX response. This model could be valuable for physicians, patients and insurers, which allows individualised therapy.

A Novel Model Based on Serum Biomarkers to Predict Primary Non-Response to Infliximab in Crohn's Disease.

BackgroundInfliximab is effective in inducing and maintaining remission in patients with Crohn’s disease (CD), but primary non-response (PNR) occurs in 10-30% of cases. We investigated whether serum biomarkers are effective in predicting PNR in patients with CD.MethodsFrom January 2016 to April 2020, a total of 260 patients were recruited to this prospective and retrospective cohort study. Serum samples were collected at baseline and week 2 of infliximab treatment. Serum levels of 35 cytokines were assessed in 18 patients from the discovery cohort and were further evaluated in the 60-patient cohort 1. Then, candidate cytokines and other serological biomarkers were used to construct a predictive model by logistic regression in a 182-patient cohort 2. PNR was defined based on the change of CD activity index or clinical symptoms.ResultsAmong the 35 cytokines, matrix metalloproteinase 3(MMP3) and C-C motif ligand 2 (CCL2) were two effective serum biomarkers associated with PNR in both the discovery cohort and cohort 1. In cohort 2, serum level of MMP3, CCL2 and C-reactive protein (CRP) at 2 weeks after infliximab injection were independent predictors of PNR, with odds ratios (95% confidence interval) of 1.108(1.059-1.159), 0.940(0.920-0.965) and 1.102(1.031-1.117), respectively. A PNR classifier combining these three indicators had a large area under the curve [0.896(95% CI:0.895-0.897)] and negative predictive value [0.918(95%CI:0.917-0.919)] to predict PNR to infliximab.ConclusionsMMP3, CCL2, and CRP are promising biomarkers in prediction of PNR to infliximab, and PNR classifier could accurately predict PNR and may be useful in clinical practice for therapy selection.

Premedication Does Not Influence the Incidence of Infliximab Infusion Reactions in Pediatric Patients with Inflammatory Bowel Disease-A Single Center Case-Control Study.

Background: Infusion reactions (IRs) are the most common adverse events (AEs) of infliximab (IFX) treatment in patients with inflammatory bowel disease (IBD). Prophylactic premedication (PM) with corticosteroids or antihistamines prior to IFX infusions has been used in clinical practice, but its efficacy is not known. The aim of this study was to assess the influence of steroid PM on IR incidence in pediatric patients with IBD receiving IFX. Methods: We performed a case–control study that included pediatric patients with IBD receiving IFX. Patients were divided into four subgroups according to the agent and PM they received: Remicade (original drug) + PM, and two biosimilars—Reshma +/− PM, and Flixabi—PM. At our site, until 2018, PM with steroids was used as a part of standard IFX infusion (PM+); however, since then, this method has no longer been administered (PM−). IRs were divided into mild/severe reactions. Differences between subgroups were assessed with the appropriate chi-square test. Multivariate logistic regression was used to assess associations between PM and IR incidence, correcting for co-medication usage. Results: There were 105 children (55 PM+, 44 male, mean age 15 years) included in the study who received 1276 infusions. There was no difference between the PM+ and PM− subgroups, either in incidence of IR (18.2% vs. 16.0% of patients, p > 0.05) or in percentage of infusions followed by IR (2.02% vs. 1.02% of infusions, p > 0.5). The OR of developing IR when using PM was 0.34, and the difference in IRs ratio in PM+ and PM− patients was not statistically significant (95% CI, 0.034–1.9). There were 11/18 (61.1%) severe IRs (anaphylactic shock) reported in all patients (both PM+ and PM−). Conclusion: At our site, the incidence of IR was low, and PM did not decrease the incidence of IR in pediatric patients with IBD receiving IFX. These results indicate that PM with steroids should not be a standard part of IFX infusion to prevent IR.

Infliximab Biosimilar CT-P13 Observational Studies for Rheumatoid Arthritis, Inflammatory Bowel Diseases, and Ankylosing Spondylitis: Pooled Analysis of Long-Term Safety and Effectiveness.

Long-term, real-world safety and effectiveness data are required to support biosimilar use. This analysis pooled 5-year findings from observational studies of infliximab biosimilar CT-P13 treatment in patients with rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and ankylosing spondylitis (AS). Patients enrolled in the CT-P13 4.2, 4.3, or 4.4 Korea/European Union registries were analysed if they had initiated infliximab treatment with CT-P13 (CT-P13 group) or had switched from reference infliximab to CT-P13 (switched to CT-P13 group). The primary objective was to investigate long-term safety by evaluating adverse events of special interest (AESIs) per the CT-P13 risk-management plan. Incidence rates per 100 patient-years (PYs) were calculated. Additional long-term safety endpoints, immunogenicity (assessments optional), and effectiveness were evaluated. Overall, 736 patients (642 CT-P13; 94 switched to CT-P13) were analysed. Median (range) exposure to CT-P13 was 19.433 (0.03-63.11) months overall. The incidence of treatment-emergent adverse events was 69.0% (CT-P13 group) and 60.6% (switched to CT-P13 group). Infusion-related reaction/hypersensitivity/anaphylactic reaction was the most frequent AESI overall, with an incidence of 4.3828 per 100 PY (95% confidence interval: 3.3603-5.6185). For most AESIs, incidence rates per 100 PY were broadly comparable between treatment groups, considering overlapping 95% confidence intervals. At baseline, 42/445 (9.4%) and 21/59 (35.6%) evaluable patients in the CT-P13 and switched to CT-P13 groups, respectively, were antidrug antibody (ADA)-positive. After CT-P13 treatment during the study, 188/425 (44.2%) evaluable patients had≥1 ADA-positive result, including 147/425 (34.6%) patients with negative or no ADA results reported at baseline. Effectiveness tended to increase over time for all indications. The analysis did not identify any new safety findings for patients with RA, IBD, and AS treated with CT-P13 for up to 5years in those who were infliximab-naïve at CT-P13 initiation, or those who had switched from reference infliximab to CT-P13. ClinicalTrials.gov identifiers: NCT02557295 (CT-P13 4.2; retrospectively registered on 23 September 2015); NCT02326155 (CT-P13 4.3; retrospectively registered on 25 December 2014); NCT02557308 (CT-P13 4.4; retrospectively registered on 23 September 2015).

Therapeutic potential of targeted-gold nanospheres on collagen-induced arthritis in rats.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes functional disability due to bone destruction and severe joint pain. Current anti-rheumatic treatments develop severe complications and do not provide complete remission. Gold nanoparticles (AuNPs) have garnered attention because of their unique physical and chemical properties. In this study, we have evaluated the therapeutic effects of gold nanospheres (AuNSs) with two different ligands (targeted-nanoparticles) against collagen-induced arthritis (CIA) and compared the outcomes with conventional methotrexate (MTX) and biological (infliximab) treatments. Clinical evaluation was performed by radiographic and histological examinations. The bioaccumulation of AuNSs in vital organs was assessed. The mechanistic studies targeting pro-inflammatory/anti-inflammatory and angiogenic mediators' expressions were performed. Radiographic examination showed that the targeted AuNSs reduced joint space narrowing and bone erosion. Moreover, histopathological examination of rat ankle joints demonstrated that targeted AuNSs reduce bone and cartilage degeneration/inflammation. Gold nanospheres-conjugated with nucleus localized peptide (nuclear membrane-targeted) (AuNSs@NLS) has resolved bone destruction and inflammation compared to gold nanospheres-conjugated at polyethylene glycol (AuNSs@PEG). Although the AuNSs accumulated in different organs in both cases, they did not induce any toxicity or tissue damage. The two different targeted AuNSs significantly suppress inflammatory and angiogenic mediators' expression and induced anti-inflammatory cytokine production, but the AuNSs@NLS had superior therapeutic efficacy. In conclusion, these results suggested that nuclear membrane-targeted AuNSs effectively attenuated arthritis progression without systemic side effects.

Infliximab treatment of glycogenosis Ib with Crohn's-like enterocolitis: A case report

BACKGROUNDGlycogen storage disease type Ib (GSD-Ib) is a glycogen metabolism disorder that leads to the manifestations of inflammatory bowel disease (IBD), especially Crohn’s disease (CD)-like colitis. Although biological agents are effective for treating CD, their application in the treatment of GSD-Ib with CD-like colitis has been rarely reported.CASE SUMMARYA 13-year-old Han male was diagnosed with GSD-Ib with CD. The patient was treated with granulocyte colony-stimulating factor. When he had symptoms of CD-like colitis, he was continuously pumped with enteral nutrition and administered oral mesalazine for 2 wk; however, the symptoms did not improve significantly. Hence, infliximab (IFX) was administered. Hitherto, the patient has been followed up for 1 year, and no clinical manifestations have been observed. After 6 mo of treatment (fifth IFX treatment), the disease activity index and all inflammatory indexes decreased, and a review of the colonoscopy data showed that the ulcers appeared smooth.CONCLUSIONIn this study, the patient was successfully treated with IFX. In cases of GSD-Ib, IBD should be highly considered.

Efficacy and safety of infliximab in the treatment of pediatirc Crohn's disease

Objective: To analyze the efficacy and safety of the biological agent infliximab (IFX) in the treatment of pediatric Crohn's disease. Methods: A total of 86 children with Crohn's disease who had received IFX in three hospitals (Ruijin Hospital, Ruijin Hospital North and Shanghai Children's Hospital) in Shanghai from January 2007 to December 2017 were included in this retrospective study. The efficacy of IFX was assessed by comparing clinical and laboratory data before and after IFX treatment. Student t test, Mann-Whitney U test or chi-square test were used to analyze the data of the two groups. Logistic reggression analysis were used to analyze the effects of variables such as age, clinical characteristics, disease behavior and combined medications on the efficacy and safety of IFX. Results: Among the 86 children with Crohn's disease in the study, 50 were males and 36 females. The IFX treatment was initiated at 12.0 (7.1, 13.6) years of age, and the follow-up period was 94.1 (47.8, 185.5) weeks. Efficacy analysis showed that in the induction remission phase, the clinical response rate was 97% (79/81) and the remission rate was 74% (60/81). In the maintenance remission phase, the clinical response rate was 75% (51/68) and the remission rate was 68% (46/68). After 34 weeks of treatment with IFX, pediatric Crohn's disease activity index (PCDAI) (5 (0, 10) vs. 36 (26, 45)), C-reactive protein (3 (1, 8) vs. 8 (3, 31) mg/L), erythrocyte sedimentation rate (10 (6, 10) vs. 35 (20, 50) mm/1 h), platelet ( (327±107)×109 vs. (438±159) ×109/L), albumin ((37±6) vs. (30±6) g/L), hemoglobin ((116±16) vs. (103±18) g/L), change of body weight (-0.5±1.2 vs. -1.0±0.9), anemia (29% (20/68) vs. 75% (51/68)), and perianal disease (13/21 vs. 0) were significantly improved (all P<0.05). By the end of 34 weeks of IFX treatment, 25% (17/68) of children experienced secondary loss of response to IFX. Logistic reggression analysis showed that PCDAI>30 was positively correlated with secondary loss of response (OR=3.823, 95%CI 1.015-15.328, P=0.048), and combined with azathioprine was conducive to maintaining efficacy of IFX (OR=0.440, 95%CI 0.106-1.033, P=0.044). The IFX-related adverse events included infusion reactions in 17% (15/86) and infections in 42% (36/86) of children. Analysis showed that age<6 years was a risk factor for infusion reactions (χ2=6.556, P=0.010), and combined use of steroids (χ2=5.230, P=0.022) may increase the incidence of infection. Conclusions: IFX is effective in the treatment of pediatric Crohn's disease with favorable safety. Reducing secondary loss of response to IFX is an urgent issue that need to be addressed. At the same time, it is necessary to pay close attention to the adverse events during IFX treatment.

Effects of infliximab on lung and circulating natural killer cells, CD56+ T cells and B cells in sarcoidosis

BackgroundTumour necrosis factor α (TNF-α) is pivotal in sarcoid granuloma formation, and inhibitors of TNF-α offer an attractive third-line treatment option in sarcoidosis. The sarcoid inflammation is characterised by an...

Early monitoring of infliximab serum trough levels predicts long-term therapy failure in patients with axial spondyloarthritis

Objective To evaluate whether serum infliximab trough levels (ITL) during the early stages of treatment are predictive of long-term clinical failure in patients with axial spondyloarthritis (axSpA). Methods Longitudinal observational study involving 81 patients with axSpA monitored during infliximab therapy. Serum ITL were measured before starting infliximab treatment and at weeks 2 (W2), W6 and W12 of treatment. Disease activity was assessed by Ankylosing Spondylitis Disease Activity Score (ASDAS) at baseline, W24 and W52, and every 6 months thereafter until treatment discontinuation, regardless of the reason. Non-clinically important improvement was defined by ΔASDAS<1.1. The association between serum levels during the early stages and clinical outcomes (non-clinically important improvement at W52, drug survival and drop-out due to secondary inefficacy) was investigated through logistic regression models and Kaplan Meier curves. Receiver operating characteristic (ROC) curves were employed to determine the best cut-off for serum ITL. Results Out of the 81 patients, 45 (56%) did not achieve clinical improvement at W52. These patients had lower serum ITL at W12 compared to those who improved: ITL [median (IQR)]: 4.1(0.9-8.3) µg/mL vs 7.1 (4.3–11.3) µg/mL, respectively;p = 0.007). ITL<6.7 µg/mL at W12 was significantly associated with: i) not achieving clinical improvement at W52 (OR: 2.3; 95%CI: 1.3–3.9); ii) shorter drug survival (5.0 years (95% CI 3.8–6.2) vs 7.0 years (95% CI 4.8–6.9; p = 0.04), and iii) higher drop-out rates due to secondary inefficacy (OR: 3.5; 95% CI: 1.2–10.2). Conclusion Low serum ITL at W12 were associated with long-term clinical failure in patients with axSpA, due to secondary inefficacy.

Changes in the gut microbiome associated with infliximab in patients with bipolar disorder.

ObjectivesAvailable information exists supporting the gut–brain axis, but additional information is needed to explore how the gut microbiome changes when exposed to mood disorder treatments. We sought to explore the effects of a novel treatment for bipolar disorder (BD), infliximab, on the gut microbiome.MethodsParticipants with a primary diagnosis of BD (n = 15) who participated in a 12‐week, randomized placebo‐controlled trial evaluating the efficacy of adjunctive infliximab in the treatment of BD were recruited and followed. Stool samples were collected prior to randomization and at 12 weeks. 16S rRNA sequencing was employed in order to analyze the gut microbial community profile.ResultsA total of 17 participants were randomized to infliximab (n = 9; mean [SD] age, 47.6 [10.3] years; 8 female) or to placebo (n = 8; mean [SD] age, 45.9 [10.7] years; 7 female) but two participants from the infliximab group were lost to follow‐up post randomization. Across all time points, there were no differences in the diversity on either Shannon or Simpson's Diversity indices. Comparison of Aitchison distances revealed a lack of clustering of the microbiota by time point, but did reveal a small overall effect of treatment that was not significantly different at individual time points. There were also no effects of either time or treatment on differential abundance at either the amplicon sequence variant or genus level.ConclusionsThese observations indicate that no community‐wide changes in the microbiota diversity and profile were detected after the use of infliximab treatment.

Limited long-term treatment persistence of first anti-TNF therapy in 538 patients with inflammatory bowel diseases: a 20-year real-world study.

SummaryBackgroundAnti‐TNF antibodies were the first biologic treatment option for patients with inflammatory bowel diseases.AimsTo assess length of treatment persistence of first anti‐TNF therapy and influencing factors used in the standard care of patients with inflammatory bowel diseases.MethodsSingle‐centre, retrospective study from a register including patients who received anti‐TNF therapy in the last 20 years at the study centre. Kaplan‐Meier analysis with log‐rank test was used to describe treatment persistence. With multivariable Cox regression analysis, risk factors for treatment failure were investigated.ResultsFive hundred thirty‐eight patients (CD, Crohn's disease: 367, UC, ulcerative colitis: 147, inflammatory bowel disease unclassified: 24) with a median follow‐up of 8.1 years were included. Median (95% confidence interval) treatment persistence in the total cohort was 2.3 years (28 [22, 38] months), and nearly half of patients withdrew from treatment within 2 years. Male patients were treated longer than females (male: 37 [25, 48] months, female: 23 [14, 33] months, P = 0.002). Treatment persistence was longer in CD compared to UC (CD: 39 [30, 50] months, UC: 13 [9, 19] months, P < 0.001), and patients with CD remained longer on adalimumab than on infliximab treatment (adalimumab: 67 [55, 95] months, infliximab: 19 [14, 31] months, P < 0.001). Treatment failure (52%) and side effects (25%) were the most common reasons for withdrawal from therapy; 14% withdrew due to remission. Female sex was identified as independent predictor for treatment failure in UC (hazard ratio [CI]: 1.73 [1.02‐2.92], P = 0.04).ConclusionLong‐term treatment persistence of first anti‐TNF therapy was limited in patients with inflammatory bowel diseases, primarily due to treatment failure and side effects.

Real World Outcomes and Hepatotoxicity of Infliximab in the Treatment of Steroid-Refractory Immune-Related Adverse Events.

Background and aims: Current guidelines state that infliximab is contraindicated for the treatment of immune checkpoint inhibitor-related hepatitis (ir-hepatitis) due to the risk of inducing further liver damage. As this recommendation is largely based on the use of infliximab for rheumatologic diseases, we evaluated the efficacy and hepatotoxicity of infliximab in patients with steroid-refractory immune-related adverse events (irAEs). Methods: We retrospectively reviewed consecutive patients treated with infliximab for irAEs at Princess Margaret Cancer Centre. To assess hepatotoxicity, we compared the mean value of ALT, AST, and total bilirubin (BT) before and after infliximab treatment. We used logistic regression to assess factors associated with infliximab efficacy. Results: Between January 2010 and February 2019, 56 patients were identified. The median age of the patients was 63 (27–84) years. Colitis was the most frequent toxicity (66%), followed by pneumonitis (11%). Infliximab was used to treat ir-hepatitis in one patient. The median number of infliximab doses was 1 (1–3) and led to toxicity resolution in 43 (76%) patients. The mean ALT, AST, and BT levels before and after infliximab treatment were not statistically different. The patient treated for ir-hepatitis had a complete recovery, with no incremental liver toxicity. Conclusions: In this dose-limited setting, infliximab was effective in resolving irAEs and did not induce hepatotoxicity.

Subclinical Cardiac Organ Damage in Patients with Moderate to Severe Psoriasis.

We explored the association between subclinical cardiac organ damage (OD) with comorbidities and psoriasis severity in 53 psoriasis patients on infliximab treatment (age 47 ± 15 years, 30% women) and 99 controls without psoriasis (age 47 ± 11 years, 28% women). Cardiac OD was assessed by echocardiography as the presence of increased left ventricular (LV) relative wall thickness (RWT), LV hypertrophy or dilated left atrium. Psoriasis severity was graded using the psoriasis area and severity index (PASI). The prevalence of hypertension was 66% in psoriasis vs. 61% in controls (p = 0.54) and cardiac OD seen in 51 and 73%, respectively (p = 0.007). Psoriasis was associated with a lower prevalence of cardiac OD (odds ratio (OR) 0.32, 95% confidence interval (CI) 0.13–0.77, p = 0.01) independent of age, sex, smoking, body mass index, and hypertension. Among psoriasis patients, hypertension was associated with increased risk of subclinical cardiac OD (OR 6.88, 95% CI 1.32–35.98, p = 0.02) independent of age, sex, and body mass index. PASI at treatment initiation was associated with a higher RWT at follow-up, independent of sex, age, and hypertension (β 0.36, p = 0.006) while no association with current PASI was found. In conclusion, cardiac OD was less prevalent in psoriasis patients on infliximab treatment than controls. Hypertension was the major covariable for subclinical cardiac OD in psoriasis.

P460 Biomarkers reflecting extracellular matrix turnover and inflammation can be used to monitor disease activity and treatment response in patients with Crohn’s disease undergoing infliximab induction therapy

Abstract Background Crohn’s disease (CD) is a relapsing-remitting inflammatory disease of the gastrointestinal (GI) tract characterized by high protease activity and increased extracellular matrix (ECM) turnover. Although immunotherapeutic drugs such as anti-TNFα have shown great promise in the treatment of CD, still up to 20–40% of patients do not respond to therapy. Failure to establish effective treatment may lead to further disease progression and potential disease complications. The aim of this study was to investigate whether biomarkers of ECM turnover and intestinal inflammation could serve as non-invasive tools for monitoring treatment response to anti-TNFα in patients with CD. Methods Serum biomarkers of matrix metalloproteinase (MMP)-related type I collagen degradation (reC1M), intestinal inflammation (VICM [macrophage activity], CPa9-HNE [serum calprotectin, neutrophil activity]) and type III collagen formation (PRO-C3) were measured using competitive ELISA in patients with CD (n=54) undergoing infliximab (IFX) induction therapy. Disease activity was defined by composite assessment of the Harvey-Bradshaw Index (HBI) together with physician’s global assessments (PGA). Clinical remission (HBI &amp;lt;5) was assessed at week 14. Wilcoxon signed-rank tests were applied for pairwise comparisons of biomarker levels between baseline and week 14. Table 1. Differences in biomarker levels between baseline and week 14 in CD patients receiving IFX treatment stratified by response. Biomarker concentrations presented as median [IQR]. Results In patients responding to IFX treatment (n=50), serum levels of reC1M, VICM, and CPa9-HNE (all P&amp;lt;0.05) were significantly lower at week 14 compared to baseline. However, serum levels of PRO-C3 (P&amp;lt;0.01) were significantly elevated in responders at week 14 compared to baseline. No significant changes were observed in the biomarkers between baseline and week 14 in those not responding to IFX treatment (n=4). Conclusion Serum biomarkers for type I collagen degradation (reC1M), intestinal inflammation (VICM, CPa9-HNE) and type III collagen formation (PRO-C3) are linked to the pathology of CD, reflecting treatment response. Together, these biomarkers could be used as surrogate markers for disease monitoring during IFX treatment in CD to further improve disease management.