Initiation Of Infliximab Research Articles

The Role of Macrophages in the Response to TNF Inhibition in Experimental Arthritis.

The reduction of synovial tissue macrophages is a reliable biomarker for clinical improvement in patients with rheumatoid arthritis (RA), and macrophages are reduced in synovial tissue shortly after initiation of TNF inhibitors. The mechanism for this initial response is unclear. These studies were performed to identify the mechanisms responsible for the initial reduction of macrophages following TNF inhibition, positing that efflux to draining lymph nodes was involved. RA synovial tissue and synovial fluid macrophages expressed CCR7, which was increased in control macrophages following incubation with TNF-α. Human TNF transgenic (hTNF-Tg) mice were treated with infliximab after development of arthritis. Ankles were harvested and examined by histology, immunohistochemistry, quantitative RT-PCR, ELISA, and flow cytometry. hTNF-Tg mice treated with infliximab demonstrated significant clinical and histologic improvement 3 d after the initiation of therapy, at which time Ly6C+ macrophages were significantly reduced in the ankles. However, no evidence was identified to support a role of macrophage efflux to draining lymph nodes following treatment with infliximab. In contrast, apoptosis of Ly6C+ macrophages in the ankles and popliteal lymph nodes, decreased migration of monocytes into the ankles, and a reduction of CCL2 were identified following the initiation of infliximab. These observations demonstrate that Ly6C+ macrophage apoptosis and decreased ingress of circulating monocytes into the joint are responsible for the initial reduction of macrophages following infliximab treatment in hTNF-Tg mice.

P192 SURGICAL OUTCOMES IN CHILDREN HOSPITALIZED WITH UC RECEIVING INTENSIFIED INFLIXIMAB INDUCTION

Hospitalized children with severe Ulcerative Colitis who are steroid unresponsive often receive Infliximab (IFX). Standard IFX induction dose is 5mg/kg weeks 0, 2 & 6. The rationale for intensified infliximab induction (III) in severe UC is: higher inflammatory burden, increase in IFX clearance & stool losses. There are no pediatric data on the outcomes of III. Report clinical outcomes of hospitalized children with severe colitis who received III. Retrospective review of patients <18 years hospitalized October 2011-June 2017 with severe UC who received their 1st induction IFX. Patients were divided into 2 groups: III (IFX ≥15mg/kg in ≤14 days) vs controls (<15mg/kg in <14 days or >15mg/kg in >14 days). Data included patients’ demographics, PUCAI, CRP, albumin, prior therapy & clinical outcomes. We used two-sample t-test and Wilcoxon rank-sum for parametric and non-parametric data respectively to assess association between clinical variables & colectomy outcome. We identified 40 patients. Mean age at IFX induction 13.5 (± 3.7) years. All patients had prior steroid exposure. 2/40 patients had prior biologic exposure (Adalimumab). 16/40 patients received III. Data suggested higher CRP in the III group, but not reaching statistical significance. The two groups were similar in age, albumin and PUCAI scores at the time of first infliximab. 43% children in III group underwent colectomy vs 37% controls. Surgery occurred during the same hospitalization as IFX initiation for 57% of patients with III vs none in controls. Median time from 1st IFX to colectomy in III group was 30 days (range 13-107) vs 150 days (26-910), (P=0.0502). Our study suggests comparable clinical features between patients who received intensified IFX induction and controls. Although the data suggested shorter time to colectomy with intensified IFX induction without statistical significance, colectomy rate was relatively similar to non-intensified infusions.

Infliximab for the Treatment of Refractory Kawasaki Disease: A Nationwide Survey in Japan

To assess the safety and efficacy of infliximab (IFX) for the treatment of patients with Kawasaki disease (KD). This was a nationwide survey of 274 Japanese institutions exploring how IFX was used to treat patients with KD. The patients' sex, age, treatment course, pre- and post-IFX therapy blood test results, coronary artery lesions (CALs), and adverse events (AEs) were evaluated. We analyzed 434 patients with KD who received IFX between March 2005 and November 2014. The median age at onset was 33 months (range 1-138), and 66 patients (15.2%) were under 1 year old. In all cases, IFX was administered as additional treatment. The median days of illness at the initiation of IFX was 9 days. In 275 patients (63.4%), IFX was administered as third-line treatment, and in 106 patients (24.4%), IFX was administered as fourth-line treatment. Single dose IFX 5 mg/kg was administered to 412 patients (94.9%). After IFX, 363 patients (83.6%) became afebrile within 2 days, and the white blood cell count, percentage of neutrophils, and serum C-reactive protein levels significantly decreased (P < .001), although 119 patients (27.4%) received additional treatment. Before IFX, 132 patients (30.4%) had already developed CALs. In patients without CALs before IFX, 31 patients (10.3%) newly developed CAL after IFX, whereas 32 patients (24.2%) with CAL before IFX showed increased CAL severity. Eighty AEs were observed in 69 patients (15.9%); however, serious AEs were few and reversible. IFX might be an effective and tolerable treatment for refractory KD.

Infliximab for the treatment of CNS sarcoidosis: A multi-institutional series.

To describe clinical and imaging responses in neurosarcoidosis to infliximab, a monoclonal antibody against tumor necrosis factor-α. Investigators at 6 US centers retrospectively identified patients with CNS sarcoidosis treated with infliximab, including only patients with definite or probable neurosarcoidosis following rigorous exclusion of other causes. Of 66 patients with CNS sarcoidosis (27 definite, 39 probable) treated with infliximab for a median of 1.5 years, the mean age was 47.5 years at infliximab initiation (SD 11.7, range 24-71 years); 56.1% were female; 62.1% were white, 37.0% African American, and 3% Hispanic. Sarcoidosis was isolated to the CNS in 19.7%. Using infliximab doses ranging from 3 to 7 mg/kg every 4-8 weeks, MRI evidence of a favorable treatment response was observed in 82.1% of patients with imaging follow-up (n = 56), with complete remission of active disease in 51.8% and partial MRI improvement in 30.1%; MRI worsened in 1 patient (1.8%). There was clinical improvement in 77.3% of patients, with complete neurologic recovery in 28.8%, partial improvement in 48.5%, clinical stability in 18.2%, worsening in 3%, and 1 lost to follow-up. In 16 patients in remission when infliximab was discontinued, the disease recurred in 9 (56%), typically in the same neuroanatomic location. Most patients with CNS sarcoidosis treated with infliximab exhibit favorable imaging and clinical treatment responses, including some previously refractory to other immunosuppressive treatments. This study provides Class IV evidence that for patients with CNS sarcoidosis infliximab is associated with favorable imaging and clinical responses.

Patients with Crohn's Disease with High Body Mass Index Present More Frequent and Rapid Loss of Response to Infliximab.

Infliximab (IFX) is effective in inducing and maintaining remission in patients with luminal and anoperineal Crohn's disease (CD). However, treatment failure within 12 months after initiating IFX is observed in a significant proportion of patients. The aim of the present study was to determine whether the body mass index (BMI) affects response to IFX during the first year of treatment in patients with CD. All patients with luminal CD who began IFX between January 2010 and May 2014 were prospectively included. BMI was calculated before IFX treatment was begun, and patients were divided into 3 groups: normal BMI (BMI < 25 kg/m), overweight patients (BMI of 25.0-30 kg/m), and obese patients (BMI > 30.0 kg/m). The primary outcome was to evaluate the rate and delay of IFX optimization during the first year of treatment among normal weight, overweight, and obese patients. One hundred forty patients were included. Demographic and clinical characteristics at IFX initiation were comparable among the 3 groups. Within 12 months after the initiation of IFX, the rate of IFX optimization was significantly higher in overweight and obese patients than in the normal BMI group: 52%, 56%, and 20%, respectively (P = 0.0002). The median time until optimization of IFX was significantly shorter in overweight and obese patients than in the normal BMI group: 7, 7, and 10 months, respectively (P = 0.03). A BMI >25 kg/m was significantly associated with IFX optimization within 12 months on multivariate analysis. This is the first study to show that optimization of IFX is more frequent and faster in obese and overweight patients with CD and occurs within 12 months after beginning IFX, suggesting that an induction regimen with higher doses of IFX and a tight control of IFX concentrations may be needed in these patients.

Concomitant Therapy with Immunomodulator Enhances Infliximab Durability in Pediatric Inflammatory Bowel Disease.

Data on long-term durability of infliximab (IFX) and outcomes of concomitant therapy with immunomodulator in pediatric inflammatory bowel disease are limited. Children with inflammatory bowel disease who received IFX ± immunomodulator were retrospectively reviewed. Predictors of induction response were assessed using a binary logistic regression model and long-term outcomes evaluated by Cox proportional hazards model. Propensity score matching examined long-term efficacy of concomitant therapy in patients with Crohn's disease (CD). Among 148 patients (113 CD, 35 ulcerative colitis; median age at IFX initiation 14.09 years [interquartile range 12.16-15.65]), 91% experienced response to induction therapy; patients with CD were more likely to respond (95% versus 77%, odds ratio = 2.63, 95% confidence interval, 1.01-6.85, P = 0.048). Despite dose optimization, secondary loss of response occurred at a rate of 9.01% and 8.33% per year for patients with CD and ulcerative colitis, respectively. A Cox proportional hazards model showed that concomitant therapy >6 months significantly lowered the risk of secondary loss of response in CD (hazard ratio = 0.39, 95% confidence interval, 0.17-0.88, P = 0.025). The same trend was observed in ulcerative colitis but did not reach significance. A higher proportion of patients on IFX monotherapy stopped IFX because of loss of response or infusion reactions (55% versus 21%, P < 0.001). Propensity score analysis of patients with CD showed significantly higher steroid-free remission rates for concomitant versus monotherapy at 1 year (78% versus 54%, P = 0.020) and 2 years (68% versus 46%, P = 0.044), and durability of response (P = 0.022). These data demonstrate sustained efficacy of IFX in a cohort of pediatric patients with inflammatory bowel disease with durability of response enhanced by concomitant therapy.

Long-term outcomes of infliximab treatment and predictors of response in 195 patients with ulcerative colitis: a hospital-based cohort study from Korea

Background: Large-scale studies regarding the long-term efficacy of infliximab (IFX) treatment in non-Caucasian patients with ulcerative colitis (UC) are lacking.Study: We analyzed the long-term outcomes of IFX in 195 Korean UC patients who received scheduled IFX treatments at Asan Medical Center. IFX failure was defined as IFX discontinuation due to colectomy or non-response to IFX, and additionally UC-related hospitalization or a need for rescue corticosteroids during the course of IFX.Results: Between December 2006 and October 2016, a total of 3101 infusions of IFX were administered to 195 patients over a median period of 21 months. At the end of the follow-up, 86 patients (44.1%) were still receiving IFX without failure. IFX was stopped in 73 (37.4%) patients due to colectomy (23 patients, 11.8%), non-response to IFX (35 patients, 17.9%) or other reasons such as adverse events or patients’ preferences (15 patients, 7.7%). An additional 36 (18.5%) patients experienced IFX failure during follow-up due to a need for rescue corticosteroids (13 patients, 6.7%), UC-related hospitalization (8 patients, 4.1%), or both (15 patients, 7.7%). The survival free of IFX failure was 58.1% at 1 year, 50.7% at 3 years and 44.8% at 5 years. In a multivariate regression analysis, cytomegalovirus colitis within 3 months before IFX initiation was a predictor of IFX failure (hazard ratio 1.57; 95% confidence interval 1.04–2.37; p = .032).Conclusions: The long-term efficacy of IFX in a large, real-life cohort of Korean UC patients appears to be comparable to that in previously published Western studies.

Safety and Efficacy of Infliximab Therapy in the Setting of Steroid-Refractory Acute Graft-versus-Host Disease

Acute graft-versus-host disease (aGVHD) is the leading cause of morbidity and mortality after allogenic hematopoietic cell transplantation (HCT). Corticosteroids are the first-line treatment; however, less than one-half of patients achieve durable remission. Studies suggest that TNF-α, a cytokine released from the bone marrow during conditioning, is involved in the pathogenesis of aGVHD. We retrospectively evaluated the outcome of anti-TNF-α therapy with infliximab in 35 patients with steroid refractory (SR) aGVHD. Infliximab was administered intravenously at 10 mg/kg for a median of 4 doses (range, 1 to 6) on a weekly basis. The overall response rates were 40% (17% complete response [CR], 23% partial response [PR]) at 4 weeks, 23% (9% CR, 14% PR) at 8 weeks, and 17% (all CR) at 12 weeks. Twenty-nine (83%) patients had infectious complications within 12 weeks of initiation of infliximab. These infections included 40 bacterial infections, 6 invasive fungal infections, and 5 viral reactivations. Twelve patients (34%) died secondary to infections. Overall survival at 12 weeks and 6 months from the start of infliximab therapy was 37% (13 of 35) and 17% (6 of 35), respectively; with most deaths secondary to complications from GVHD and infections. In conclusion; the use of infliximab therapy in patients with SR-aGVHD is associated with a modest poorly sustained response along with a heightened risk of severe infections. Future studies with more effective and less toxic therapies are needed for these patients.

Defining the ultrasound longitudinal natural history of newly diagnosed pediatric small bowel Crohn disease treated with infliximab and infliximab-azathioprine combination therapy.

Little is known about changes in the imaging appearances of the bowel and mesentery over time in either pediatric or adult patients with newly diagnosed small bowel Crohn disease treated with anti-tumor necrosis factor-alpha (anti-TNF-α) therapy. To define how bowel ultrasound findings change over time and correlate with laboratory inflammatory markers in children who have been newly diagnosed with pediatric small bowel Crohn disease and treated with infliximab. We included 28 pediatric patients treated with infliximab for newly diagnosed ileal Crohn disease who underwent bowel sonography prior to medical therapy and at approximately 2weeks, 1month, 3months and 6months after treatment initiation; these patients also had laboratory testing at baseline, 1month and 6months. We used linear mixed models to compare mean results between visits and evaluate whether ultrasound measurements changed over time. We used Spearman rank correlation to assess bivariate relationships. Mean subject age was 15.3±2.2years; 11 subjects were girls (39%). We observed decreases in mean length of disease involvement (12.0±5.4 vs. 9.1±5.3cm, P=0.02), maximum bowel wall thickness (5.6±1.8 vs. 4.7±1.7mm, P=0.02), bowel wall color Doppler signal (1.7±0.9 vs. 1.2±0.8, P=0.002) and mesenteric color Doppler signal (1.1±0.9 vs. 0.6±0.6, P=0.005) at approximately 2weeks following the initiation of infliximab compared to baseline. All laboratory inflammatory markers decreased at 1month (P-values<0.0001). There was strong correlation between bowel wall color Doppler signal and fecal calprotectin (ρ=0.710; P<0.0001). Linear mixed models confirmed that maximum bowel wall thickness (P=0.04), length of disease involvement (P=0.0002) and bowel wall color Doppler signal (P<0.0001) change over time in response to infliximab, when adjusted for age, sex, azathioprine therapy, scanning radiologist and baseline short pediatric Crohn's disease activity index score. The ultrasound appearance of the bowel changes as early as 2weeks after the initiation of infliximab therapy. There is strong correlation between bowel wall color Doppler signal and fecal calprotectin.

Su1914 - Comparative Effectiveness Analysis of Flares, Hospitalisations, and Corticosteroid Use Among Biologic Naïve Patients with Inflammatory Bowel Disease Within 12 Months of Initiation of Vedolizumab or Infliximab

Su1914 - Comparative Effectiveness Analysis of Flares, Hospitalisations, and Corticosteroid Use Among Biologic Naïve Patients with Inflammatory Bowel Disease Within 12 Months of Initiation of Vedolizumab or Infliximab

Long-term outcomes of refractory neurosarcoidosis treated with infliximab.

Central nervous system localizations of sarcoidosis may be refractory to conventional treatment such as steroids and immunosuppressive drugs. Infliximab, a TNF-α antagonist chimeric antibody, has been shown to be effective for treatment of these localizations. The aim of this study was to evaluate the efficacy and safety, in particular the long-term outcomes, of the use of infliximab for the treatment of neurosarcoidosis. We retrospectively reviewed medical records of patients with neurosarcoidosis who had been treated with infliximab between 2009 and 2015. All patients had histologically proven non-caseating granulomas. Eighteen patients with histologically proven sarcoidosis were included in this study. All had neurological involvement consisting of meningeal (n=16), cerebral (n=10), spinal cord (n=6), and/or optic nerve (n=5) involvement. Sixteen patients had previously received at least one immunosuppressive drug in addition to corticosteroids, including cyclophosphamide in 11 patients. All patients received treatment with infliximab (3-7.5mg/kg) associated with corticosteroids (n=18), low-dose methotrexate (n=15), azathioprine (n=2), or mycophenolate (n=1). Sixteen out of 18 patients improved clinically (initial median modified Rankin scale score of 3, final median score of 1; p<0.0001). At 6months after initiation of infliximab, six patients obtained complete remission (33%), ten attained partial remission (56%), and two had stable disease (11%). The median follow-up time was 20months (range 6-93). Nine patients relapsed during follow-up (50%). Eight patients developed toxic side effects and seven of these side effects were infectious events. Infliximab is an efficacious treatment of refractory neurosarcoidosis. However, relapses frequently occurred during follow-up.

P470 Comparative effectiveness analysis of flares, hospitalisations, and corticosteroid use among biologic naïve patients with inflammatory bowel disease within 12 months of initiation of vedolizumab or infliximab

Background: This study aimed to compare IBD-related flare, hospitalisations, and corticosteroid use within one year of initiation of vedolizumab (VDZ) versus infliximab (IFX) among biologic-naïve IBD patients in a real-world setting. Methods: We undertook retrospective analysis of data from 01/05/2014 to 27/07/2016 in the US Explorys Universe electronic medical records database. Inclusion criteria included: diagnosis with UC (ICD-9 556.xx) or CD (ICD-9 555.xx); initiation of VDZ or IFX as 1st-line biologic therapy; age ≥18 years; ≥12 months of medical history, and; ≥12 months of follow-up. Patients commencing concomitant biologic therapies were excluded. Propensity scores were used to match VDZ initiators to IFX initiators (1:2). IBD-related flare was defined as ≥1 of: prescription for IV corticosteroids; IBD-related hospitalization; or IBD-related surgery. The percentage of patients experiencing ≥1 flare in the first 12 months of follow-up was reported, with focus on the proportion of patients admitted for an IBD-related hospitalization (and annual rate). The proportion of patients who received ≥1 oral/IV/rectal corticosteroid prescription, during induction (0–98 days follow-up), and post-induction (99–365 days follow-up) were also reported. Results: 81 VDZ initiators were matched to 162 IFX initiators. Among VDZ patients, median age was 44 years (interquartile range, IQR: 30, 56), 63.0% (n=51) had CD, 51.9% (n=42) were female, and median time since diagnosis was 3.6 years (IQR: 1.2, 6.2). No significant differences were observed in baseline characteristics between VDZ and IFX patients. Within 12 months of treatment initiation, 30.9% (95% CI: 21.9, 41.6) VDZ and 31.5% (95% CI: 24.8, 39.0) IFX patients experienced flare. In particular, 12.3% (95% CI: 6.8, 21.3) of the VDZ patients experienced IBD-related hospitalisation, and the associated annual rate was 0.2 (95% CI: 0.1, 0.4); among IFX patients the percentage was 17.9% (95% CI: 12.8, 24.5), and annual rate 0.4 (95% CI: 0.3. 0.5). During induction 28.4% (95% CI: 19.7, 39.0) VDZ patients and 33.3% (95% CI: 26.5, 40.9) IFX patients were treated with corticosteroids; during maintenance these proportions were 35.8% (95% CI: 26.2, 46.7) and 39.5% (95% CI: 32.3, 47.2), respectively. Conclusions: In a real-world setting, within one year of biologic treatment initiation, IBD patients receiving VDZ as 1st-line biologic therapy experienced numerically lower rates of flares compared with IFX. Similarly, a smaller proportion of VDZ patients experienced hospitalisation or received steroid treatment. Further studies in larger cohorts are required to confirm these trends.

P382 A panel of serum markers for early detection of endoscopic healing with infliximab in patients with ulcerative colitis

Background: The need for surrogate markers to detect endoscopic healing in inflammatory bowel disease (IBD) is imminent. Previously, neutrophil gelatinase B-associated lipocalin and matrix metalloproteinase-9 (NGAL-MMP-9) complex was found to be superior to CRP for detection of endoscopic healing with infliximab (IFX) in patients with ulcerative colitis (UC)[1]. Both cathelicidin LL-37 and chitinase 3-like 1 (CHI3L1) are secreted by neutrophils and were previously associated with IBD [2,3]. The aim of this study was to investigate whether LL-37 and/or CHI3L1 could improve detection of endoscopic healing with IFX in UC patients. Methods: Serum samples were obtained from 145 UC patients (41% female, median [IQR] age 41.3 [30.8–51.9] years) who underwent endoscopy following IFX initiation and from 75 controls (56% female, median [IQR] age 33.6 [29.2–51.8] years). Endoscopic healing with IFX was defined as a Mayo endoscopic subscore of 0 or 1. CRP, NGAL-MMP-9 and neutrophils were previously determined [1], and LL-37 and CHI3L1 were measured with ELISA (Hycult Biotech and R&D systems, respectively). For all markers, optimal cut-offs were determined with ROC analysis and binary variables were entered in a logistic regression model to generate the Ulcerative Colitis Response Index (UCRI). Non-parametric tests were performed and p-values <0.05 were considered significant. Results: Median (IQR) time to serum sampling after IFX was 8.2 (6.0–14.0) weeks. 83 patients (57%) had endoscopic healing, whereas 62 patients (43%) did not. Median [IQR] LL-37 levels (ng/ml) were significantly lower in healers (24.3 [16.1–41.4]) compared to non-healers (37.3 [24.0–53.8], p=0.002), but remained elevated compared to controls (16.7 [10.2–27.1]; p<0.001). Median [IQR] CHI3L1 levels (ng/ml) were significantly lower in healers (20.9 [14.3–34.4]) compared to both non-healers (30.0 [22.7–53.9], p<0.001) and controls (31.9 [19.6–48.6], p=0.003). UCRI consisted of CRP (Odds ratio [95% CI] 3.3 [1.4–7.5]), CHI3L1 (3.1 [1.3–7.7]), neutrophils (4.9 [2.1–11.2]) and LL-37 (2.5 [1.0–6.4]). The AUC of UCRI was 0.83 and Q1 (0.0–2.6) was able to discriminate healing with 54% sensitivity, 92% specificity, 60% NPV and 90% PPV, whereas Q4 (7.2–9.8) was able to discriminate non-healing with 37% sensitivity, 95% specificity, 67% NPV and 85% PPV. Finally, UCRI could detect endoscopic healing as early as 3 weeks after IFX initiation (Hazard ratio [95% CI] 4.1 [2.6–6.5]). Conclusions: In the search for surrogate markers of endoscopic healing, UCRI was shown to accurately identify UC patients who fail to achieve healing with IFX and may help in early decision making to therapy switch.

Short-Term Outcome of Infliximab Therapy in Pediatric Crohn's Disease: A Single-Center Experience.

PurposeStudies on the efficacy of infliximab (IFX) in a large population of pediatric patients with Crohn's disease (CD) are limited, and prognostic factors are not well-known. The aim of this study was to evaluate outcomes of IFX in pediatric patients with CD and to identify factors associated with poor prognosis.MethodsWe retrospectively analyzed medical data of 594 pediatric patients with CD between 1987 and 2013 in a tertiary center. Of these, 156 children treated with IFX were enrolled and were followed up for at least a year with intact data. Outcomes of induction and maintenance, classified as failure or clinical response, were evaluated on the tenth and 54th week of IFX therapy.ResultsWe treated 156 pediatric patients with CD with IFX, and the median duration of IFX therapy was 47 months. For IFX induction therapy, 134 (85.9%) patients experienced clinical response on the 10th week. Among the 134 patients who showed response to induction, 111 (82.8%) patients maintained the clinical response on the 54th week. In multivariate analysis, low hematocrit (p=0.046) at the time of IFX initiation was associated with the failure of IFX induction. For IFX maintenance therapy, longer duration from the initial diagnosis to IFX therapy (p=0.017) was associated with maintenance failure on the 54th week.ConclusionWe have shown the acceptable outcomes of IFX in a large cohort of pediatric CD patients in Korea. Hematocrit and early introduction of IFX may be prognostic factors for the outcomes of IFX.

Prognostic factors for long-term infliximab treatment in Crohn's disease patients: a 20-year single centre experience.

The long-term efficacy of infliximab in patients with Crohn's disease is suboptimal. To study prognostic factors for real-life long-term effcacy of infliximab in Crohn's disease. All consecutive Crohn's disease patients treated with infliximab at a tertiary centre were retrospectively analysed. Only patients who received scheduled infliximab maintenance treatment were considered. Patient- and disease-related factors were used to identify independent predictors of infliximab failure-free survival using Cox proportional hazards regression. Of 1031 patients with Crohn's disease, 261 were eligible for inclusion. Median time on infliximab was 2.4 [IQR 1.4-4.7] years, and 65 (24.9%) patients experienced infliximab failure. Estimated 5-year infliximab failure-free survival was 65.9% (95% CI 58.3-73.5). Multivariate Cox regression identified disease duration ≥1 year (HR 2.5 (95% CI 1.2-5.2), P = 0.02), L1 disease location [HR 2.0 (1.1-3.5), P = 0.02], prior anti-TNF use [HR 2.3 (1.1-4.8), P = 0.03], haemoglobin <13.5 g/dL [HR 2.3 (1.2-4.4), P = 0.02], not using therapeutic drug monitoring [HR 8.0 (4.1-15.6), P = 1 × 10(-9) ], and first dose optimisation within first year [HR 3.7 (2.1-6.6), P = 5 × 10(-6) ] as independent predictors of infliximab failure-free survival. Stratifying patients into risk groups resulted in estimated 3-year infliximab failure-free survival rates ranging from 95.3% (94.2-96.4) to 26.3% (8.6-44.0) depending on the number of risk factors (P = 8 × 10(-13) ). This study identified several easy to obtain predictors of infliximab failure in patients with Crohn's disease, and these are in line with previous reports. Those with a high-risk profile for infliximab failure in whom infliximab initiation is considered, should be treated as early as possible making use of therapeutic drug monitoring.

Anti-TNF Therapy Within 2 Years of Crohn's Disease Diagnosis Improves Patient Outcomes: A Retrospective Cohort Study.

Although biological agents targeting tumor necrosis factor (TNF) alpha are effective in the management of Crohn's disease (CD), use of anti-TNF agents is often delayed until after failure of other treatment modalities, resulting in potentially long delays between diagnosis and initiation of infliximab or adalimumab. We aim to determine if early treatment with anti-TNF agents reduces the rate of surgical resection and clinical secondary loss of response in CD patients. A retrospective cohort study was conducted evaluating CD outpatients who were primary responders to anti-TNF therapy, on a maintenance regimen with infliximab or adalimumab from 2003 to 2014. Patients were stratified by time to first dose of anti-TNF therapy; early initiation was defined as starting anti-TNF therapy within 2 years of diagnosis. The primary outcome was occurrence of surgical resection or clinical secondary loss of response requiring dose escalation. Kaplan-Meier analysis was used to assess time to the primary outcomes. One hundred ninety CD patients met inclusion criteria (100 infliximab, 90 adalimumab). Median follow-up duration was 154.4 weeks (inter quartile range, 106.4-227.8). Fifty-three patients (27.9%) had early initiation of anti-TNF therapy. Fewer patients in the early initiation group required surgery (5.7% versus 30.7%, P < 0.001) or experienced clinical secondary loss of response (45.3% versus 67.2%, P = 0.006). In Kaplan-Meier analysis, early initiation of anti-TNF therapy prolonged time to surgery (P = 0.001) and secondary loss of response (P = 0.006). In CD patients, early initiation of infliximab or adalimumab within the first 2 years of diagnosis reduces the rate of surgery and secondary loss of response requiring dose escalation.

Biologic Treatment Registry Across Canada (BioTRAC): a multicentre, prospective, observational study of patients treated with infliximab for ankylosing spondylitis

ObjectivesTo describe the profile of patients with ankylosing spondylitis (AS) treated with infliximab in Canadian routine care and to assess the effectiveness and safety of infliximab in real world.Setting46 primary...

Comparison of real-world outcomes of adalimumab and infliximab for patients with ulcerative colitis in the United States

Objective: We compared the real-world effectiveness of initiating adalimumab and infliximab among patients in the US who were naïve to tumor necrosis factor (TNF) inhibitors. Methods: A retrospective chart review was conducted to evaluate the real-world effectiveness among adults with ulcerative colitis (UC) initiating adalimumab or infliximab. Charts of patients with UC were abstracted by treating physicians (randomly selected from a nationally representative panel) in April 2014. Patient eligibility criteria included: adalimumab or infliximab initiation on/after 1 October 2012; no prior anti-TNF therapy, history of Crohn’s disease, or colectomy; and ≥6 months of follow-up. Information on clinical outcomes (partial Mayo score, remission rate, physician global assessment (PGA), stool frequency, and rectal bleeding) and treatment patterns (dose escalations, discontinuations, switches, and treatment augmentations) were retrospectively reported by treating physicians. Kaplan–Meier curves and multivariate Cox proportional hazards regression models were used to assess the time to clinical outcomes and treatment changes for each therapy. Results: Overall, 170 physicians participated, contributing data on 380 and 424 patients who initiated adalimumab and infliximab, respectively. Baseline clinical characteristics were similar between groups. Both adalimumab- and infliximab-treated patients showed substantial improvements from baseline to follow-up in effectiveness measures; results of these measures were similar between the adalimumab and infliximab cohorts. Time to remission (p = 0.5241), no rectal bleeding (p = 0.7648), normal stool count (p = 0.9941), and normal PGA (p = 0.7697) showed no significant differences between therapies in unadjusted and adjusted comparisons. Unadjusted and adjusted time to event analysis of discontinuation (p = 0.7151), dose escalation (p = 0.6310), treatment augmentation (p = 0.1209), and switching (p = 0.7975) showed no significant differences between the two cohorts. Limitations: Retrospective, observational design. Conclusions: Adalimumab and infliximab were similarly effective in the treatment of moderate-to-severe UC in the real-world clinical setting.

Long-Term Outcomes of Infliximab Treatment in 582 Korean Patients with Crohn's Disease: A Hospital-Based Cohort Study.

To date, no large-scale studies have evaluated long-term outcomes of infliximab (IFX) treatment in Korean patients with Crohn's disease (CD). We analyzed long-term clinical responses to IFX in 582 Korean CD patients who received scheduled IFX treatments at Asan Medical Center. Clinical responses were defined as maintaining IFX without major abdominal surgery (MAS) or dose intensification. Between February 2002 and July 2015, a total of 11,990 IFX infusions were administered to 582 Korean patients with CD over a median period of 36months. At the end of follow-up, 316 (54.3%) were still receiving IFX without MAS (71 patients, 12.2%) or dose intensification (86 patients, 14.8%). IFX was stopped in 109 (18.7%) patients because of a loss of response (48 patients, 8.2%), adverse events (30 patients, 5.2%), or patient preferences or problems with reimbursement (31 patients, 5.3%). The cumulative survival for maintenance of IFX without MAS or dose intensification was 89.0, 75.9, 68.3, and 50.8% at 1, 2, 3, and 5years, respectively. Multivariate regression analysis identified older age at the initiation of IFX (≥40years, P=0.006) and a longer disease duration (≥3years, P=0.020) as independent positive predictors of a poorer response to IFX. The long-term efficacy of IFX in a large, real-life cohort of Korean patients with CD appears to be similar to that in previously published Western studies. Our findings support the early use of IFX to obtain better clinical outcomes.

Extent of Early Clinical Response to Infliximab Predicts Long-term Treatment Success in Active Ulcerative Colitis.

The long-term effectiveness of infliximab (IFX) in ulcerative colitis (UC) and predictors of treatment response remain poorly characterized. A retrospective cohort study was conducted in 213 consecutive patients with active steroid-refractory or steroid-dependent UC treated with induction and scheduled maintenance IFX at an inflammatory bowel disease referral center. Outcomes included annual steroid-free remission (SFR), IFX failure with discontinuation, colectomy, and serious adverse events. The 1- and 5-year cumulative probabilities for SFR were 39% and 14%, for IFX failure were 31.7% and 55.6%, and for colectomy were 19.2% and 37.4%, respectively. A sensitivity analysis considering the last clinical observation in patients with incomplete follow-up demonstrated a long-term SFR rate of 36%. Among responders to IFX induction therapy, achieving clinical remission before maintenance IFX therapy predicted SFR at 1 year (adjusted odds ratio = 4.50; 95% CI, 1.75-11.53), whereas the need for IFX dose intensification during the first year of therapy predicted a lower odds of SFR at 1 year (adjusted odds ratio = 0.28; 95% CI, 0.11-0.67) and a greater hazard of IFX failure beyond 1 year (adjusted hazard ratio = 2.57; 95% CI, 1.14-5.81). Older age and shorter UC duration at IFX initiation predicted poorer long-term outcomes. In patients with moderate-to-severe UC treated with scheduled IFX at an inflammatory bowel disease center, close to half of the patients are still on IFX at 5 years, although a smaller proportion of patients achieve long-term SFR. The magnitude and stability of early response to IFX is associated with long-term therapeutic benefit to this agent.