Infliximab Group Research Articles

Effects of tumor necrosis factor alpha blocker adalimumab in experimental spinal cord injury.

ObjectiveTumor necrosis factor alpha (TNF-α) have proven effects in pathogenesis of neuroinflammation after spinal cord injury (SCI). Current study is designed to evaluate the effects of an anti-TNF-α agent, adalimumab, on spinal cord clip compression injury in rats.MethodsThirty two male adult Wistar rats were divided into four groups (sham, trauma, infliximab, and adalimumab groups) and SCI was introduced using an aneurysm clip. Animals in treatment groups received 5 mg/kg subcutaneous adalimumab and infliximab right after the trauma. Malondialdehyde (MDA) levels were studied in traumatized spinal cord tissues 72 hours after the injury as a marker of lipid peroxidation.ResultsAnimals that received anti-TNF-α agents are found to have significantly decreased MDA levels. MDA levels were significantly different between the trauma and infliximab groups (p<0.01) and trauma and adalimumab groups (p=0.022). There was no significant difference in neurological evaluation of the rats using Tarlov scale.ConclusionThese results suggest that, like infliximab, adalimumab has favorable effects on lipid peroxidation induced by spinal cord trauma in rats.

Infliximab partially alleviates the bite force reduction in a mouse model of temporomandibular joint pain.

Temporomandibular joint (TMJ) disorder is clinically important because of its prevalence, chronicity, and therapy-refractoriness of the pain. In this study, we investigated the effect of infliximab in a mouse model of TMJ pain using a specially-engineered transducer for evaluating the changes in bite force (BF). The mice were randomly divided into three groups (7 mice per group): the control group, the complete Freund's adjuvant (CFA) group, and the infliximab group. BF was measured at day 0 (baseline BF). After measuring the baseline BF, CFA or incomplete Freund's adjuvant was injected into both TMJs and then the changes in BF were measured at days 1, 3, 5, 7, 9, and 13 after the TMJ injection. For measuring the BF, we used a custom-built BF transducer. Control, CFA, and infliximab groups showed similar baseline BF at day 0. From day 1, a significant reduction in BF was observed in the CFA group, and this reduction in BF was statistically significant compared to that in the control group (P < 0.05). This reduction in BF was maintained until day 7, and BF started to recover gradually from day 9. In the infliximab group also, the reduction in BF was observed on day 1, and this reduction was maintained until day 7. However, the degree of reduction in BF was less remarkable compared to that in the CFA group. The reduction in BF caused by injection of CFA into the TMJ could be partially alleviated by the injection of anti-tumor necrosis factor alpha, infliximab.

Autoimmunogenicity during anti-TNF therapy in patients with psoriasis and psoriatic arthritis.

IntroductionThe tumor necrosis factor (TNF-α) was initially described as lymphotoxin or cachectin. The discovery of therapies blocking the action of TNF-α, in 1988, started a new era in the therapy. One of often reported adverse effects related to the use of TNF-α antagonists is induction of the formation of autologous antibodies and antibodies neutralizing anti-TNF drugs. The development of anti-TNF-induced lupus or classical drug-induced lupus is more rarely reported.AimTo evaluate the presence and the level of anti-nuclear antibodies in patients with psoriasis and psoriatic arthritis and the influence of anti-TNF therapy used on the concentration of antinuclear antibody (ANA).Material and methodsA total of 28 subjects were included in the study. 71.4% of subjects were diagnosed with psoriatic arthritis and 28.6% with plaque psoriasis.ResultsAmong the patients with plaque psoriasis, the antinuclear antibodies were found in 25% of subjects and in 80% of patients with psoriatic arthritis. After the treatment an increase in the titer or appearance of antibodies was found in 66.7% in the infliximab group, 18.2% in the etanercept group and 54.7% in the adalimumab group. No subjects developed symptoms of drug-induced systemic lupus.ConclusionsOur findings have shown that all anti-TNF therapies induced ANA in psoriatic arthritis and psoriatic patients. Considering a mild course of lupus induced by anti-TNF treatment and, usually intrinsic, resolution of symptoms, the biological therapy still appears as a safe treatment for patients.

Influence of combination therapy with immune modulators on anti-TNF trough levels and antibodies in patients with IBD.

It is important to identify factors that can reduce the incidence of immunogenicity against anti-tumor necrosis factor medication in patients with inflammatory bowel disease. The objective of our study was to evaluate the influence of cotreatment with immune modulators (IMs) on trough levels (TLs) and antidrug antibodies. The records of all patients with inflammatory bowel disease at the Leiden University Medical Center who received either adalimumab or infliximab (IFX) in the year 2011 and/or 2012 (n = 352) were retrospectively evaluated about the assessment of TL and antibodies and use of IM. Two hundred seventeen patients were included (108 patients IFX; 109 patients adalimumab). Mean TL in the IFX group was higher in the combination therapy group compared with the monotherapy group, 4.6 versus 7.5 µg/mL, P = 0.04. In the adalimumab group, the difference was not significant. In patients with IFX monotherapy, the incidence of antibody formation was higher compared with patients with combination therapy (29.8% versus 5.7%, P = 0.001). IFX patients with a suboptimal dose of IM had a higher TL compared with patients who had an optimal dose, P = 0.02. The incidence of antibody formation was lower in IFX patients who immediately started with IMs compared with patients who did not (33.3% versus 66.7%, P = 0.04). The influence of combination therapy with IM on TL and antibodies to anti-tumor necrosis factor medication was significant for IFX-treated patients. Patients who started combination therapy immediately developed antibodies less often than patients who started later with concomitant medication.

Different therapeutic approaches on quality of life in patients with inflammatory bowel disease.

BackgroundThe chronic nature of inflammatory bowel disease leads to considerable impairment on the health related quality of life (HRQOL). The aims of the present study are to validate the mainland Chinese translation of the Inflammatory Bowel Disease Questionnaire (MCIBDQ), and to evaluate the impact of infliximab treatment on HRQOL in patients with IBD for the first time in China, as compared with other therapies of different levels. Furthermore, the impact of different medical therapies on marriage, employment and economic burden in IBD patients were also evaluated.MethodsConsecutive patients who met inclusion/exclusion criteria were investigated with MCIBDQ, SF-36, disease activity index (DAI), marriage, employment and economic burden questionnaires before and after treatment.ResultsMCIBDQ showed significant reliability and validity both in CD and UC patients. The scores of total SF-36, total MCIBDQ and all domains were found significantly increased, while both DAI and health transition on general health scores were found significantly decreased after infliximab treatment (all P < 0.001). Scores of SF-36 and MCIBDQ increased significantly more in infliximab group than non-infliximab group (all P < 0.05). Infliximab treatment was suggested to significantly reduce the negative impact on love (P = 0.037), increase work time (P = 0.016) and ease economic burden (P = 0.048).ConclusionsMCIBDQ was demonstrated to be a reliable and valid scale applied in Chinese IBD patients. Infliximab treatment was found to significantly improve HRQOL in IBD patients in comparison with conventional treatments. Negative impact on marriage, employment, and economic status was found in patients with IBD.Electronic supplementary materialThe online version of this article (doi:10.1186/s12876-014-0199-5) contains supplementary material, which is available to authorized users.

Length of hospital stay and associated hospital costs with infliximab versus cyclosporine in severe ulcerative colitis.

Cyclosporine and infliximab (IFX) seem equally effective as rescue therapy in hospitalized patients with severe ulcerative colitis (UC), although associated hospital stay and costs may differ. The aim of this study was to compare the duration of hospital stay and associated costs from initiation of rescue therapy to time of discharge in hospitalized patients with corticosteroid-refractory UC receiving cyclosporine or IFX. Colectomy rates after 6 months were used as the outcome parameter for treatment success. Hospital records of patients admitted between November 2003 and August 2012 at a tertiary referral center were analyzed. Forty-two patients were included (cyclosporine group: 26 patients; IFX group: 16 patients). Patient characteristics were comparable, with the exception that cyclosporine-treated patients more often had a pancolitis (89 vs. 63%, P=0.046). The median length of hospital stay was 11.0 (interquartile range 7.75-13.25) versus 4.0 days (interquartile range 4.0-5.75) in the cyclosporine and IFX group (P<0.01), respectively. The mean in-hospital costs were significantly higher in the cyclosporine-treated versus IFX-treated patients (6121 vs. 4853 euros, P<0.05), whereas the total costs up to 3 months after initiation of rescue therapy were significantly higher in the IFX group (6787 vs. 9983 euros, P<0.01). There were no significant differences in colectomy rates at 6 months (23 and 31% for cyclosporine and IFX, P=0.50). More side-effects were observed during treatment with cyclosporine. Length of hospital stay and in-hospital costs have been reduced significantly since the introduction of IFX as rescue therapy for severe UC instead of cyclosporine. However, the total treatment costs are higher in IFX-treated patients.

Early anti-TNF treatment in pediatric Crohn’s disease. Predictors of clinical outcome in a population-based cohort of newly diagnosed patients

Objective. Pediatric Crohn’s disease (CD) is often debilitating, with upper gastrointestinal (GI) involvement and complications over time. Treatment with tumor necrosis factor (TNF) blockers can induce and maintain remission. We wanted to evaluate the outcome of patients medically treated for CD to investigate whether clinical, endoscopic and biochemical factors at diagnosis are associated with the early initiation of treatment with the TNF blocker infliximab. Materials and methods. Patients aged <18 years, diagnosed with CD were characterized according to the Porto criteria, with endoscopy, magnetic resonance imaging and biochemical tests before individual treatment. They were followed prospectively until a prescheduled examination within 2 years. Results. Thirty-six pediatric patients were included, 18 (50%) received infliximab. Infliximab-treated patients had shorter disease duration, more upper GI involvement (p = 0.03) and higher median C-reactive protein (CRP) (28 vs. 7.5 mg/l, p = 0.02), erythrocyte sedimentation rate (ESR) (32 vs. 18 mm/h, p = 0.01) and fecal calprotectin (1506 vs. 501 mg/kg, p = 0.01) levels. Infliximab treatment was well tolerated, and 15/18 of patients achieved clinical remission. At follow-up, 11/17 in the infliximab group and 8/13 in the non-infliximab group achieved ileocolonic mucosal healing. A majority in the infliximab group had a marked reduction of CD-specific upper GI lesions but persistence of unspecific upper GI inflammation at follow-up. Conclusion. High levels of inflammatory markers and upper GI lesions were associated with initiation of infliximab treatment. A substantial proportion of patients still had unspecific lesions in the upper GI tract regardless of treatment. Future studies must clarify the prognostic role of persistent upper GI-involvement despite mucosal healing in the ileocolon.

Response Rates to Anti-TNF Biologic Therapy After Failure of a Prior Biologic: A Retrospective Analysis of a Single Center’s Experience

Introduction: Our goal was to identify and compare the overall efficacy of biologics in our population when given either as an initial agent or after prior biologic failure. Methods: This is a retrospective cohort study in which we established a database of all patients at the Crohn’s and colitis center at Robert Wood Johnson University Hospital since the development of our electronic medical record in 2007. We then performed a chart review to identify all patients treated with biologics and reviewed and compared clinical assessments of response between the agents. Results: Eight hundred ninety-six charts were reviewed of which 227 (25.3%) had received a biologic. One hundred sixty-five (72.7%) had Crohn’s disease and 61 (26.9%) had ulcerative colitis. In patients with Crohn’s disease, there was no statistically significant difference in response rates between initial treatment with infliximab (64.5%), adalimumab (60.0%), and certolizumab (66.7%). When used as a second or third biologic, there was a trend towards increased response with infliximab (83.3%) vs. adalimumab (52.6%) and certolizumab (58.8%). This did not reach statistical significance and was limited by the small number of patients in the infliximab group. We then evaluated the combined response rate of all biologics after failure or loss of response of 2 previous biologics. Only 25 (15.2%) of our patients were treated with a third biologic. In this group 56.0% responded. In patients with ulcerative colitis, the majority were initially treated with infliximab. The response rate for infliximab as an initial agent was 60.4%. There were too few patients in the other groups to evaluate for a statistical difference. As a second line agent adalimumab had a 36.4% response rate, however, this group was limited to 11 patients. Conclusion: Infliximab, adalimumab, and certolizumab have similar response rates when given as an initial biologic in Crohn’s disease. When given as a second or third biologic, infliximab had a trend towards an increased response, however this did not meet statistical significance and was limited by group size. Interestingly, when any third biologic was given after 2 prior treatment failures, 56.0% of patients still responded supporting this approach to treatment. For ulcerative colitis, the majority of our patients were initially treated with infliximab which had a response rate of 60.4%. When used as a second biologic, adalimumab had a response rate of 36.4%, however, this was limited by group size.

Efficacy of infliximab in treatment of pediatric Crohn's disease in China

To investigate the efficacy of infliximab versus corticosteroids in achieving clinical remission in pediatric patients with Crohn's disease in China. Data of all newly diagnosed active Crohn's disease pediatric cases seen from June 2009 to December 2013 in Children's Hospital, Zhejiang University School of Medicine were retrospectively recorded and reviewed. the age of the children was less than 18 years; pediatric Crohn's disease activity index (PCDAI) was more than 10; infliximab or corticosteroids were used for inducing remission; infliximab, immunosuppressive medications or mesalamine was prescribed for maintaining remission. Patients in steroids group were followed up for more than 1 year. The enrolled patients were divided into two groups: infliximab group and steroids group. Clinical data, laboratory findings and side effects of the medications were collected at week 2, 4, 12, 24 and 48. PCDAI and Crohn's disease endoscopic index score (CDEIS) were calculated. Clinical response rate, clinical remission rate, relapse rate, mucosal healing and growth were evaluated. Eleven children received infliximab therapy and 11 subjects received corticosteroids. In Infliximab group, 6, 5 and 7 patients were in clinical remission at week 2, 4, and 8, while so were 6, 9, and 9 patients in steroids group. The difference was not statistically significant (χ² = 0.00, 3.14, 0.92, P > 0.05). In infliximab group, 8, 8, and 11 patients were in clinical remission at week 2, 4, and 8, so were 8, 9, and 9 patients in steroids group. The difference was not statistically significant (χ² = 0.00,0.26, 2.20, P > 0.05). When compared with data at baseline, significant decreases were observed in the median PCDAI between the two groups at week 2, 4, and 8 (all P < 0.05). But there were no significant differences between two groups at week 2, 4, and 8 (all P > 0.05). At week 12, 24 and 48, 8/11, 7/8, 3/5 cases on infliximab versus 7/11, 9/11, 8/11 cases on steroids maintained remission. There was no significant differences between the two groups (all P > 0.05). In 7 patients and 9 patients remission was successfully induced at week 8. The relapse rate was similar at week 12, 24, and 48 (χ² = 0.83, 0.09, 1.00, all P > 0.05). Height for age Z score in infliximab group was significantly higher than that in steroids group at week 24 (P < 0.05). Body mass index Z score between the two groups at week 8, 24, and 48 were not statistically significant (all P > 0.05). Of the children treated with infliximab, 3 developed side effects. All the children treated with steroids got Cushing's syndrome. In children with Crohn's disease, infliximab therapy is as effective as corticosteroids to induce remission.Less side effects were observed with infliximab therapy compared with immunosuppressive medication and mesalamine.

Tartrate-resistant acid phosphatase 5b is a potential biomarker for rheumatoid arthritis: a pilot study in Han Chinese

Background Bone damage around the joints is one of the major pathophysiological mechanisms that leads to rheumatoid arthritis (RA) chronic disability. Serum tartrate-resistant acid phosphatase 5b (TRACP-5b) is secreted by osteoclasts, its activity can be used as a clinically relevant bone resorption marker. The aim of this study was to test whether the measurement of serum levels of TRACP-5b in patients with RA would correlate with measures of disease activity and with responses to therapy. Methods Fifty-six patients were randomly assigned to receive recombinant human cytotoxic tlymphocyte-associated antigen-4 immunoglobulin (RhCTLA4-Ig), infliximab or methotrexate (MTX). The clinical and serologic indicators of RA activity were evaluated at baseline and at 24 weeks. Serum TRACP-5b was measured by Enzyme-linked Immunosorbent Assay (ELISA) at 0, 12 and 24 weeks. Hand X-rays were obtained at baseline. Results At baseline, the levels of TRACP-5b correlated with the severity of X-ray damage, disease duration (r=0.332, P=0.012), and tender joint count (r=0.408, P=0.002). The 24 weeks values of TRACP-5b for RhCTLA4-Ig group and infliximab group differed significantly from the baseline values in each group (P &lt;0.05; P &lt;0.05), whereas only the value for RhCTLA4-Ig group differed significantly from the 24 weeks value for the MTX group (P &lt;0.01). Considering the two biologics-treated groups together, the TRACP-5b levels at 24 weeks differed significantly from the baseline values only in those patients who reached an ACR70 level (P &lt;0.05). Conclusions Measurement of serum TRACP-5b in RA patients reflects clinical and radiological measures of disease activity, treatment with certain biologics, and degree of response to therapy. TRACP-5b should be investigated further as a potential biomarker to predict response to therapy, including slowing of radiographic progression.

FRI0023 Is Positivity of Rheumatoid Factor and Anti-Cyclic Citrullinated Peptide Associated with the Response Rate of Infliximab, Tocilizumab, and Abatacept in Treatment of Rheumatoid Arthritis?

BackgroundRecent reports have shown that positivity for rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) can influence the efficacy of rheumatoid arthritis (RA) treatment. Additionally, RF+ and ACPA+ statuses were...

FRI0008 Baseline Osteopontin Levels PREDICT the Clinical Efficacy of TOCILIZUMAB not Infliximab in Bio-Naive Rheumatoid Arthritis Patients: the Keio First BIO Cohort at 1 Year

ObjectivesTo explore baseline predictive factors for clinical remissions at 1 year after tocilizumab (TCZ) or infliximab (IFX) treatment in bio-naïve RA patients.MethodsConsecutive bio-naïve RA patients at our hospital initiating TCZ...

Treatment of Pediatric Takayasu arteritis with infliximab and cyclophosphamide: experience from an American-Brazilian cohort study.

Pediatric Takayasu arteritis (pTA) is difficult to treat and can lead to significant morbidity and mortality. The objective of this study was to describe clinical characteristics for pTA and determine the safety and efficacy of cyclophosphamide (CYC) and infliximab (IFX) in pTA. This was a retrospective analysis of 23 pTA patients seen at Children's Hospital Los Angeles and Universidade Federal de São Paulo-Brazil from 1990 to 2011. All patients fulfilled the 1990 American College of Rheumatology criteria for Takayasu arteritis. Disease activity was assessed using a modified National Institutes of Health score. Twenty-three patients (14 female and 9 male patients), mean age of 15.7 ± 6.0 years, were included. Cyclophosphamide was used before IFX treatment in 17 of 23 and IFX before CYC in 2 of 23 patients. The average time from disease onset to treatment initiation was 2.6 ± 2.4 years for CYC and 4.1 ± 2.4 years for IFX. Nine (60%) of 15 patients failed CYC, and of these 6 were changed to IFX with subsequent clinical stabilization in 5 (83%) of 6. Two patients initially treated with IFX were switched to CYC because of lack of appropriate response: 1 patient later worsened, and the other was lost to follow-up. Five opportunistic infections requiring hospitalization occurred in the CYC group, whereas none were observed in the IFX group. Patients in the IFX group were more likely to decrease or stop their corticosteroids when compared with the CYC patients. Cyclophosphamide is often used as initial treatment but has many adverse effects. In this retrospective case series, IFX was equivalent to CYC with fewer adverse effects, making IFX an alternative therapeutic option for pTA.

AB0381 Long-Term Clinical Effectiveness of Adalimumab, Etanercept, and Infliximab in Rheumatoid Arthritis (RA): an Observational Study from Italian Register, Gisea

BackgroundIn routine care, patients with active RA usually undergo treatment with TNF inhibitors. The choice of the durg is empirical and there are not established predictors of long-term clinical outcomesObjectivesTo...

AB0437 Clinical Utility of Measuring Drug and Anti-Drug Antibody Concentration of Biologic Agents in Rheumatoid Arthritis Patients with Moderate and High Disease Activity

BackgroundBiologicals possess a large variation in pharmacokinetics (1). Subtherapeutic drug levels and formation of anti-drug antibodies (ADAb) decrease their efficacy in rheumatoid arthritis (RA) patients (2). Measuring these can become...

THU0186 Infliximab VS Etanercept: the Importance of Immunogenicity and Serum Drug Monitoring in Clinical Practice

BackgroundTreatment with tumor necrosis factor (TNF) inhibitors in rheumatoid arthritis (RA) patients is based on the principle 'one size fits all', but different immunogenicity of these drugs has a profound...

FRI0254 Predictive Value of Pretreatment Resistin Levels for Erosive Disease in Early RA Treated with DMARDS and Infliximab

BackgroundResistin is an adipocytokine related to insulin resistance, inflammation and arthritis (1).ObjectivesWe investigated if resistin is associated with the disease activity and inflammation in DMARD-naïve rheumatoid arthritis (RA) patients, if...

AB0654 Survey of the Tolerance to the First Anti-TNF Therapy: Reasons for Discontinuation Including Loss of Efficacy and Adverse Effect of Different Anti-TNF Therapies (Data From Moscow Register)

BackgroundAnti-TNF therapy has been proven highly effective in patients with spondyloarthritis, but about 30% of the patients developed secondary inefficacy or adverse effects (AE).ObjectivesEstablishing the reasons and the frequency of...

What is the utility of routine ANA testing in predicting development of biological DMARD-induced lupus and vasculitis in patients with rheumatoid arthritis? Data from a single-centre cohort

ObjectiveTo determine whether serial ANA testing predicts biological disease modifying antirheumatic drugs (bDMARD)-associated ANA/dsDNA production in patients with rheumatoid arthritis (RA).MethodsSerial autoantibody profiles, bDMARD treatment sequences and clinical data were...

Influence of infliximab pretreatment on ischemia/reperfusion injury in rat intestine

The Pringle maneuver is used in hepatic surgery to prevent blood loss but is associated with ischemia- reperfusion injury. To investigate the effect of infliximab on inflammation and apoptosis in rat intestinal mucosa during ischemia-reperfusion (IR) injury. A total of 30 male Wistar albino rats were equally divided into three groups to be subjected to (i) sham operation (sham), (ii) IR injury via Pringle maneuver (pringle) or (iii) infliximab (IFX) group (IFX was given at a dose 3 mg/kg for 3 days before IR injury). Following reperfusion period of 60 min., intestinal tissue and blood samples were taken and processed by standard histological methods. The Pringle maneuver and following reperfusion caused significant histopathological changes, increased serum transaminases' activity and the levels of oxidative stress markers and decreased glutathione peroxidase activity. IFX pretreatment partially prevented these changes. Infliximab pretreatment may protect intestinal mucosa against ischemia-reperfusion injury. Further studies are needed to investigate mechanism and evaluate safety and optimal dosing of IFX in humans exposed to the possible tissue damage by ischemia-reperfusion.