Infliximab Therapy In Patients Research Articles

Correlation between Treatment Outcomes and Serum Vitamin D Levels As Well As Infliximab Trough Concentration among Chinese Patients with Crohn's Disease.

The relationship between vitamin D (vit-D) levels and the effectiveness of infliximab (IFX) in patients with Crohn's disease (CD) remains controversial. To evaluate the interaction between vit-D levels and the response to IFX therapy in patients with CD. This was a retrospective cohort study. Serum vit-D and IFX trough concentrations (TC) were measured in 84 patients, and statistical analyses were performed. The total vit-D deficiency rate at enrollment, at week 14 and week 38, was 64.3%, 41.67%, and 37.5%, respectively (P < 0.001). CD activity index (CDAI) (120, range, 93-142.75) and simplified endoscopic activity score for CD (SES-CD) (2, range, 0-4) at week 14 were lower than that of enrollment (CDAI, 136.5, range, 101.25-196; SES-CD 13, range, 5-23) (P < 0.001). The biochemical remission (BR), clinical remission (CR), endoscopic remission (ER), and response (ERe) rates of week 38 were 76.1%, 88.5%, 22.4%, and 67.2%, respectively. vit-D levels at enrollment were positively correlated with CDAI at week 38 (P = 0.024). IFX serum TC was related to BR (P = 0.036), CR (P = 0.032) at week 14, and ERe (P = 0.009) at week 38. Among Chinese patients with CD, vit-D levels prior to IFX therapy are related to CDAI scores, and IFX serum TC is associated with BR, CR, and ERe.

Predictors of the efficacy of infliximab in patients with ulcerative colitis

Introduction. The currently known prognostic criteria for biological therapy have limitations and have not been widely used in clinical practice. Aim. Find predictors of the effectiveness of biological therapy with infliximab in patients with ulcerative colitis. Materials and methods. The object of the study was patients (n = 52) diagnosed with Ulcerative Colitis in the active form of the disease, including 27 men and 25 women undergoing therapy with infliximab. Follow-up was carried out for three years from the start of therapy. The age of the examined persons ranged from 19 to 64 years (mean age 34.76 ± 2.13 years). The mean score on the Mayo scale was 6.1 ± 3.49. Results. In the course of our study, we obtained the following data on the effectiveness of infliximab therapy in patients with severe ulcerative colitis: a significant improvement in the dynamics of laboratory and instrumental parameters was recorded in 25 people (43.8%); the onset of stable clinical remission — in 15 people (26.3%); disease progression — in 5 cases (8.7%); lack of dynamics or a less pronounced effect — in 12 cases (21.2%). Conclusions. We have identified a system of clinical and laboratory factors that make it possible to predict the effectiveness of biological therapy with infliximab in patients with ulcerative colitis. The mathematical model in the form of a discriminant function makes it possible to divide patients into groups depending on the possible effect of the use of biological therapy with infliximab before its initiation (the sensitivity of the model is 83.3%, the specificity is 71.4%).

Discontinuation of Infliximab Therapy in Patients with Crohn’s Disease

BackgroundWhether infliximab therapy can be successfully discontinued after patients with Crohn’s disease have attained sustained, clinical, biochemical, and endoscopic remission is unknown.MethodsWe conducted a multicenter, randomized, double-blind, placebo-controlled withdrawal study of infliximab in patients with Crohn’s disease who were in clinical, biochemical, and endoscopic remission after standard infliximab maintenance therapy for at least 1 year. Patients were randomly assigned 1:1 to continue infliximab therapy or to receive matching placebo for 48 weeks. The primary end point was time to relapse.ResultsThis study randomly assigned 115 patients to either the infliximab-continuation group or to the infliximab-discontinuation group. No relapses were observed among the 59 patients continuing infliximab, whereas 23 of 56 patients discontinuing infliximab experienced relapse. Time to relapse was significantly shorter among patients who discontinued infliximab than among those who continued infliximab (hazard ratio, 0.080; 95% confidence interval [CI], 0.035 to 0.186; P<0.001). At the end of the trial at week 48, relapse-free survival was 100% in the infliximab-continuation group and 51% in the infliximab-discontinuation group. The key secondary end point, time to loss of remission, was significantly shorter among patients discontinuing infliximab therapy than those continuing infliximab (hazard ratio, 0.025; 95% CI, 0.003 to 0.187; P<0.001). No unexpected adverse events were reported.ConclusionsDiscontinuation of infliximab for patients with Crohn’s disease receiving long-term infliximab therapy and in clinical, biochemical, and endoscopic remission leads to a considerable risk of relapse. (Funded by the Nordic Trial Alliance [NordForsk], the Medical Fund of the Danish Regions [Regionernes Medicin og Behandlingspulje], the Danish Colitis-Crohn Association, and the A.P. Moller Foundation; ClinicalTrials.gov number, NCT01817426; EudraCT number, 2012-002702-51.)

A Novel Neutrophil-Based Biomarker to Monitor Disease Activity and Predict Response to Infliximab Therapy in Patients With Ulcerative Colitis.

BackgroundUlcerative colitis (UC) is characterized by refractory and recurrent mucosal inflammation, leading to a substantial healthcare burden. Diagnostic biomarkers predicting disease activity and treatment response remain elusive. To evaluate the application value of a novel neutrophil-based index (the neutrophil-to-albumin ratio, NAR) as a novel diagnostic biomarker in patients with UC and a predictive marker for disease activity and response to infliximab (IFX) therapy.MethodsClinical characteristics and laboratory parameters of enrolled subjects (patients with UC and healthy controls) were retrieved from the electronic medical record database of our hospital. Serum cytokine and fecal calprotectin levels were measured by enzyme-linked immunosorbent assay (ELISA). Mucosal expression levels of inflammatory agents were measured by quantitative RT-PCR (qRT-PCR).ResultsWe found that NAR, which had not yet been explored in UC, was significantly increased in patients with UC (n = 146) compared to that in controls (n = 133) (1.95 ± 0.41 vs. 1.41 ± 0.23, p < 0.0001). NAR showed a positive association with the disease activity and inflammatory load in patients with UC. Pre-treatment NAR was significantly lower in IFX responders than that in non-responders (2.18 ± 0.29 vs. 2.44 ± 0.21, p = 0.0118), showing a significant ability to discriminate initial responders from primary non-responders to IFX induction therapy (AUC = 0.7866, p = 0.0076). Moreover, pre-treatment NAR predicted postinduction serum IFX trough level.ConclusionOur study provides evidences to utilize NAR in the diagnosis, activity monitoring, and IFX response prediction in patients with UC.

ITRAQ and PRM-Based Proteomic Analysis Provides New Insights into Mechanisms of Response to Triple Therapy in Patients with Rheumatoid Arthritis.

BackgroundApproximately 30% of patients with rheumatoid arthritis (RA) respond poorly to combination therapy of multiple drugs. The molecular mechanisms of different responses to methotrexate + leflunomide + infliximab therapy in patients with RA were explored in this study.MethodsInfliximab was administered to patients with RA whose disease activity score was higher than 5.1 after 1 month of combination therapy with methotrexate and leflunomide. After 14 weeks of undergoing triple therapy, patients with RA were classified as responders and non-responders. Protein profiles at baseline and 14th week were investigated via isobaric tags for relative and absolute quantification (iTRAQ), and proteins with significant differences ≥1.2 folds change or ≤0.8 folds change were defined as differentially expressed proteins (DEPs). Overlapping DEPs between responders and non-responders were confirmed by parallel reaction monitoring (PRM). Bioinformatic analyses were performed for DEPs.ResultsThe results revealed 5 non-responders (NRs) and 15 responders (Rs). iTRAQ analysis indicated 13 overlapping DEPs and included 6 opposite change DEPs such as testicular tissue protein Li 70, cofilin 1, fibrinogen beta chain, galectin-10, serotransferrin (TF) and albumin. The difference in serotransferrin between responders and non-responders confirmed by PRM was significant. Verification by PRM indicated that TF was elevated in the Rs group and was reduced in the NRs group. Bioinformatic analysis indicated that serotransferrin was involved in the hypoxia-inducible factor-1 pathway and ferroptosis.ConclusionSerotransferrin-related molecular mechanism may be a new direction to study refractory RA.

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.

Clinical outcomes of patients with corticosteroid refractory immune checkpoint inhibitor-induced enterocolitis treated with infliximab

IntroductionImmune checkpoint inhibitors (CPIs) have changed the treatment landscape for many cancers, but also cause severe inflammatory side effects including enterocolitis. CPI-induced enterocolitis is treated empirically with corticosteroids, and infliximab...

The influence of proton pump inhibitor therapy on the outcome of infliximab therapy in inflammatory bowel disease: a patient-level meta-analysis of randomised controlled studies

ObjectiveIn treating patients with inflammatory bowel disease (IBD), how concomitant medications influence the response to infliximab is largely unexplored. We aim to evaluate whether proton pump inhibitors (PPIs) affect the...

Intermittent Appearance of Antibodies to Infliximab Is Not Associated With Reduced Efficacy in Patients With Inflammatory Bowel Diseases.

To assess the clinical significance of antibodies to infliximab (ATI) formation in patients with inflammatory bowel disease (IBD). Infliximab therapy in patients with IBD is highly effective though up to 50% of patients lose response to infliximab. ATI formation occurs in 6% to 60% of patients on scheduled infliximab maintenance therapy. Infliximab trough levels and ATI at trough were prospectively determined in patients with IBD on maintenance infliximab therapy. Patients on infliximab maintenance therapy with at least 3 ATI measurements were included. Patients were divided into 2 groups: sustained negative (<1 µg/mL) ATI levels, and fluctuating ATI levels (at least 1 sample with ATI <1 and at least one >1 µg/mL). Forty-eight patients with IBD with available clinical data and serum samples were included. 25 patients had sustained low ATI levels and 23 patients had fluctuating ATI levels. Both groups were similar in IBD subtype distribution (Crohn's disease in 73.9% and 60%), mean serum albumin levels (4.2 vs. 3.9 g/dL), and mean trough serum infliximab levels (3.3 vs. 4.6 µg/mL) in fluctuating ATI and low ATI groups, respectively. There were no significant differences in the rate of clinical response (64% vs. 76%) and mean serum C-reactive protein levels (9.4 vs. 8.5 mg/dL, ULN=5) in the fluctuating ATI and low ATI groups. Similar rates of clinical response in the fluctuating ATI and low ATI groups were observed in ulcerative colitis (33% vs. 40%) and Crohn's disease (76% vs. 100%). The fluctuating pattern of appearance of ATI in patients with IBD was not associated with loss of clinical response or a rise in C-reactive protein. The authors suggest that in clinical decision making, only sustained appearance of ATI should be considered as an adverse therapeutic factor.

Efficacy and Safety of Infliximab in HLA-B27-associated Ocular Inflammation Refractory or Intolerant to Conventional Immunomodulatory Therapy.

PurposeTo determine the efficacy and safety of infliximab therapy in patients with HLA B-27-associated ocular inflammation resistant or intolerant to conventional immunomodulatory therapy.MethodsThis was a retrospective observational case series. All cases were uveitic patients with positive HLA-B27, confirmed through HLA testing, resistant or intolerant to conventional immunomodulatory therapy. The primary outcome of the study was to identify the efficacy of infliximab determined by the control of inflammation, duration of remission, and the ability to reduce conventional immunomodulatory therapy. The secondary outcome was an improvement of two or more lines of best-corrected visual acuity (BCVA) on the Snellen visual acuity chart.ResultsTwenty-four patients (38 eyes) were included in the study. All patients were followed for 24 months. Twenty-one (87.5%) patients completed 24 months of follow-up. Sixteen (66.7%) patients had active uveitis at the beginning of therapy. One patient out of these active patients had active inflammation at the end of follow-up period. Thirteen (87.5%) out of sixteen active patients were in steroid-free remission. The mean duration of treatment to induce remission was 16.5 months (range 6–24 months). Corticosteroid was stopped in 19 (90.5%) patients by the end of the study. At the end of the study, in patients who achieved remission, 14 (58.3%) patients were in remission on infliximab therapy and 6 (25%) patients were in remission off infliximab therapy. Of the 38 eyes, 8 (21.05%) showed improvement in BCVA (three eyes had successful cataract extraction with intraocular lens implantation during infliximab therapy with no subsequent inflammation), while 26 eyes (68.4%) had stable BCVA over the 24-month study period. The side effects included allergic reaction, fatigue, cellulitis, headache, restlessness, elevation of liver enzymes, and anemia. Two patients (n = 24, 8.3%) experienced severe adverse effects and the treatment was stopped prematurely in these two patients.ConclusionInfliximab might induce and maintain the steroid-free remission in HLA-B27-associated ocular inflammation in patients resistant or intolerant to conventional immunomodulatory therapy.

Long-term efficacy of early infliximab-induced remission for refractory uveoretinitis associated with Behçet’s disease

BackgroundTo evaluate long-term efficacy of infliximab (IFX) in refractory uveoretinitis associated with Behçet’s disease (BD) depending on uveoretinitis duration.MethodsRecords of 16 patients with BD (32 eyes) followed for >5 years...

Neutrophil-lymphocyte ratio at 14th week predicts loss of response to 52-week infliximab therapy in patients with Crohn's disease

Loss of response (LOR) has become an important clinical problem in patients with Crohn's disease receiving infliximab (IFX) treatment. Neutrophil-lymphocyte ratio (NLR) has been shown to correlate with the activity of inflammatory bowel disease (IBD), and NLR at the 14th week of IFX therapy potentially allows the prediction of sustained response to IFX in Crohn's patients. The aim of this study was to explore whether NLR at the 14th week of IFX therapy could predict the occurrence of LOR to IFX in Crohn's patients. Between January, 2012 and December, 2016, 54 patients with Crohn's disease underwent a 52-week treatment with IFX and successfully achieved response to the induction treatment in Zhongnan Hospital. We retrospectively examined their medical records and assessed the association between NLR at 14 weeks and LOR during IFX therapy. Of the 54 patients, 15 (27.8%) showed LOR to IFX during the follow-up. We noted a significant increase in NLR at 14 weeks in the patients with LOR as compared with the patients with sustained response to IFX[3.51 (2.9-6.25) vs 1.77 (1.23-2.56), P=0.00]. Receiver-operating characteristic analysis showed that at the cut-off value of 2.75, NLR at 14 weeks was predictive of LOR within 52 weeks of IFX therapy with a sensitivity of 93.33% and a specificity of 84.62%, and the area under curve (AUC) of NLR was 0.903 (0.731-0.959). Univariate analysis revealed a significant correlation between relapse-free survival and the NLR at 14 weeks (P=0.00). Multivariate analysis identified NLR at 14 weeks as an independent prognostic factor for LOR with a hazard ratio of 1.851 (95% CI:1.096-3.026, P=0.021). NLR at the 14th week during IFX therapy is a useful predictor for LOR in patients with Crohn's disease.

Long-Term Efficacy of Anti-Tumor Necrosis Factor Agents in Pediatric Luminal Crohn's Disease: A Systematic Review of Real-World Evidence Studies.

PurposeTo determine the long-term efficacy of the anti-tumor necrosis factor (TNF) agents, infliximab (IFX) and adalimumab (ADA), in pediatric luminal Crohn's disease (CD) by performing a systematic literature review.MethodsAn electronic search was performed in Medline, Embase, and the Cochrane Library from inception to September 26, 2019. Eligible studies were cohort studies with observation periods that exceeded 1 year. Studies that reported time-to-event analyses were included. Events were defined as discontinuation of anti-TNF therapy for secondary loss of response. We extracted the probabilities of continuing anti-TNF therapy 1, 2, and 3 years after initiation.ResultsIn total, 2,464 papers were screened, 94 were selected for full text review, and 13 studies (11 on IFX, 2 on ADA) met our eligibility criteria for inclusion. After 1 year, 83–97% of patients were still receiving IFX therapy. After 2 and 3 years the probability of continuing IFX therapy decreased to 67–91% and 61–85%, respectively. In total, 5 of the 11 studies subgrouped by concomitant medication consistently showed that the probabilities of continuing IFX therapy in patients with prolonged immunomodulator use were higher than those in patients on IFX monotherapy.ConclusionThis review of real-world evidence studies confirms the long-term therapeutic benefit of IFX therapy in diverse cohorts of children with luminal CD. Moreover, it supports the view that combination therapy with an immunomodulator prolongs the durability of IFX therapy in patients who previously failed to recover following first-line therapy. The limited number of time-to-event studies in patients on ADA prevented us from drawing definite conclusions about its long-term efficacy.

Safety of infliximab in real clinical practice

A wide range of highly effective genetically engineered biological preparations introduced into clinical rheumatology in recent years causes a special interest in their safety.Purpose of the study. Evaluation of the safety of infliximab therapy in patients with rheumatoid arthritis.Materials and methods. The authors' own data, which analyzed the undesirable effects of infliximab in 135 patients with rheumatoid arthritis in actual clinical practice, are presented. A case report of the adverse reaction of combination therapy with leflunomide and infliximab is presented.Results and its discussion. The overall tolerability of infliximab was satisfactory. Adverse events were observed in 28.1 % of cases, including 19.1 % of patients (14.1 %) had serious side effects that required discontinuation of the drug.Findings. In most cases, infliximab is safe for use in actual clinical practice. Patients should be informed about the risks of undesirable effects and the need for a rheumatologist's examination before each infliximab administration before prescribing therapy.

Tenascin-C Is Increased in Inflammatory Bowel Disease and Is Associated with response to Infliximab Therapy.

Tenascin-C (TNC) is an extracellular matrix glycoprotein expressed in response to inflammation and tissue damage. The role of TNC in patients with inflammatory bowel disease (IBD) is not well understood. In this study, we analyzed the expression of TNC in the inflamed mucosa of patients with ulcerative colitis (UC) and Crohn's disease (CD). Serum TNC levels were determined by the enzyme-linked immunosorbent assay (ELISA), and the levels of TNC in patients with different disease activities were compared. The expression of TNC was derived from a GEO dataset. THP-1 cells were stimulated with TNC to evaluate the proinflammatory role of TNC. We found higher TNC expression in the inflamed mucosa of patients with UC and CD compared with normal controls (NCs). TNC was mainly expressed in the stromal area of the intestinal mucosa. The median serum levels of TNC were significantly higher in UC (median 74.1 ng/ml, range 42.6–102.1 ng/ml) and CD (median 59.2 ng/ml, range 44.0–80.9 ng/ml). We also found that serum TNC levels were correlated with Mayo scores in UC and Crohn's disease activity index (CDAI) in CD. Through GSE14580, we demonstrated that patients who were nonresponsive to infliximab treatment had higher mucosal TNC mRNA expression. High TNC mRNA expression in the inflamed intestinal mucosa was associated with poor response to infliximab therapy in patients with UC. Furthermore, THP-1 cells stimulated with TNC showed increased expression of IL-6, but not TNF-α, IL-8, MCP-1, or IL-1β. Thus, increased TNC levels may participate in the pathogenesis of IBD and may serve as a biomarker for disease activity and response to treatment with infliximab.

Optimising infliximab induction dosing for patients with ulcerative colitis.

The therapeutic failure of infliximab therapy in patients with ulcerative colitis remains a challenge even 2 decades after its approval. Therapeutic drug monitoring (TDM) has shown value during maintenance therapy, but induction therapy has still not been explored. Patients may be primary nonresponders or underexposed with the standard dosing regimen. We aimed to: (i) develop a population pharmacokinetic-pharmacodynamic model; (ii) identify the best exposure metric that predicts mucosal healing; and (iii) build an exposure-response (ER) model to demonstrate model-based dose finding during induction therapy with infliximab. Data were retrospectively collected from a clinical database. A total of 583 samples, from 204 patients, was used to develop a population pharmacokinetic model to generate exposure metrics for subsequent ER modelling. A subset of 159 patients was used to develop a logistic regression ER model, describing the relationship between infliximab exposure and ordered transitions between Mayo endoscopic subscore (MES) 3, 2 and ≤1 (baseline to post-induction). A 1-compartment population pharmacokinetic model with interindividual and interoccasion variability was found to fit the data best. Covariates influencing exposure were C-reactive protein, albumin, baseline MES, fat-free mass, concomitant corticosteroid use and pancolitis. The cumulative area under the infliximab concentration-time curve until endoscopy (CAUCendoscopy ) was found to be the best exposure metric for predicting mucosal healing (baseline MES >1 and post-induction MES ≤1). The model predicted that 70% of patients will attain mucosal healing with infliximab administered at days 0, 14 and 42 and a target CAUCendoscopy of 3752mg/L*day at day 84. TDM-based dose individualisation targeting CAUCendoscopy has the potential to improve the effectiveness of infliximab during induction therapy.

OP25 Targeting endoscopic outcomes through combined pharmacokinetic and pharmacodynamic monitoring of infliximab therapy in patients with Crohn’s disease

OP25 Targeting endoscopic outcomes through combined pharmacokinetic and pharmacodynamic monitoring of infliximab therapy in patients with Crohn’s disease

Effects of Epithelial IL-13Rα2 Expression in Inflammatory Bowel Disease.

Background: Mucosal IL-13 Receptor alpha 2 (IL13RA2) mRNA expression is one of the best predictive markers for primary non-responsiveness to infliximab therapy in patients with inflammatory bowel disease (IBD). The objective of this study was to understand how IL-13Rα2, a negative regulator of IL-13 signaling, can contribute to IBD pathology.Methods: IL13RA2 knockout (KO) and wild type (WT) mice were exposed to dextran sodium sulfate (DSS) in drinking water to induce colitis. Furthermore, mucosal biopsies and resection specimen of healthy individuals and IBD patients before the start of anti-tumor necrosis factor (anti-TNF) therapy were obtained for immunohistochemistry and gene expression analysis.Results: After induction of DSS colitis, IL13RA2 KO mice had similar disease severity, but recovered more rapidly than WT animals. Goblet cell numbers and mucosal architecture were also more rapidly restored in IL13RA2 KO mice. In mucosal biopsies of active IBD patients, immunohistochemistry revealed that IL-13Rα2 protein was highly expressed in epithelial cells, while expression was restricted to goblet cells in healthy controls. Mucosal IL13RA2 mRNA negatively correlated with mRNA of several goblet cell-specific and barrier genes, and with goblet cell numbers.Conclusions: The data suggest that IL-13Rα2 on epithelial cells contributes to IBD pathology by negatively influencing goblet cell recovery, goblet cell function and epithelial restoration after injury. Therefore, blocking IL-13Rα2 could be a promising target for restoration of the epithelial barrier in IBD.

Fecal Calprotectin Pretreatment and Induction Infliximab Levels for Prediction of Primary Nonresponse to Infliximab Therapy in Crohn’s Disease

Introduction: The association between infliximab (IFX) and fecal calprotectin (FC) levels on one hand, and the clinical and endoscopic response of patients with inflammatory bowel disease on the other, is well established. Objective and Methods: To investigate the association between inflammatory biochemical parameters and serum concentrations of IFX during induction treatment with a primary nonresponse in a prospective cohort of Crohn’s disease (CD) patients. Results: Of the 35 patients included, 8 (22.8%) had primary nonresponse at the end of induction. Induction IFX levels were lower among primary nonresponders at weeks 6 and 14 (week 6: median IFX level 7.3 vs. 11.2 μg/mL, respectively, p = 0.090; week 14: median IFX level 1.5 vs. 4.7 μg/mL, respectively, p = 0.020). FC levels were higher in patients with primary nonresponse versus primary response at weeks 0, 6, and 14 (week 0: median FC level 1,830 vs. 410 μg/g, ­respectively, p = 0.030; week 6: median FC level 1,150 vs. 230 μg/g, respectively, p = 0.074; week 14: median FC level 1,210 vs. 208 μg/g, respectively, p = 0.060). For the multivariate analysis, the median IFX level at week 14 and median FC level at week 0 were independently associated with primary nonresponse. A significant inverse correlation was determined between FC level at week 0 and IFX level at week 14 (Spearman’s rho correlation, 0.440; p < 0.05). Conclusions: IFX levels (at week 14) and baseline FC levels could predict primary nonresponse after induction IFX therapy in patients with CD. A high baseline inflammatory load might modify the pharmacokinetic processes of anti-tumor necrosis factor drugs. Drug level monitoring and measurement of baseline inflammatory parameters could improve the efficacy of IFX in the induction therapy of patients with active CD.

Asymptomatic hyperCKemia During Infliximab Therapy in Patients With Inflammatory Bowel Disease.

Both muscle-related complaints and elevated serum creatine kinase (CK) levels have been reported in patients with inflammatory bowel disease (IBD) treated with infliximab (IFX), mainly as case reports. The aim of this study was to investigate the effect of IFX therapy on serum CK levels in a cohort of Greek IBD patients. Demographic, clinical (including muscle complaints), and laboratory data of consecutive IBD patients undergoing IFX treatment and a matched control group of IBD patients without any use of biological treatment were retrospectively analyzed. In both groups, patients having at least 3 CK measurements, with at least 10 days' interval among them, were included. The IFX-treated IBD patient group included 82 individuals (75.6% Crohn's Disease [CD]; mean age, 44.7 ± 13.3 years; 60.9% men; median [interquartile range {IQR}] duration of IFX treatment, 27 [12-84] months). Eighty-two patients without treatment with any biological agent formed the control group (62.2% CD; mean age, 50.4 ± 16.4 years; 59.8% men). Twenty-five IFX-treated patients (30.5%) had elevated mean serum CK levels (>180 U/L), compared with 9 (11%) in the control group (P = 0.0003). The median CK value in the IFX group (123.5 U/L; IQR, 91-190.75) was significantly higher than that of the control group (81 U/L; IQR, 57-112.75; P < 0.0001). In the logistic regression analysis, the presence of hyperCKemia was independently correlated with the use of IFX (odds ratio, 4.03; IQR, 1.64-9.90; P = 0.002). No patient with hyperCKemia in both groups reported any persistent symptom of myopathy. More than 30% of IBD patients on IFX present asymptomatic persistent and treatment-related hyperCKemia. Further relevant prospective investigation is needed. 10.1093/ibd/izy088_video1izy088.video15778459427001.