Effects Of Infliximab Therapy Research Articles

The effectiveness of infliximab for Kawasaki disease in children: systematic review and meta-analysis.

BackgroundKawasaki disease (KD) is a self-limited illness that results in coronary artery aneurysms (CAAs) and threatens children’s health and lives. The therapeutic effects of single intravenous immunoglobulin gamma (IVIG) vs. infliximab (IFX) (with or without IVIG) in young children with KD remain unclear. Thus, we made a meta-analysis and systematic review, including all of the studies which have evaluated the effectiveness and safety of IFX and IVIG KD patients.MethodsThe databases of the Cochrane Library, PubMed and Embase websites were searched for articles appearing from inception until December 31, 2020. Clinical studies that compared IFX either as initial therapy plus IVIG or rescue therapy after IVIG (IFX group) failure compared with IVIG treatment alone (IVIG group) in treating KD patients were included.ResultsThe meta-analysis included nine studies characterizing 712 patients. The treatment response was significantly higher in the adjunctive IFX therapy group than in the IVIG therapy group [odds ratio (OR) 2.64; 95% CI: 1.52–4.59; P=0.0005]. Subgroup analysis, the effect of IFX therapy on treatment response is more effectiveness in the group of the high-risk KD patients than IVIG therapy (OR 6.07; 95% CI: 2.30–16.04; P=0.0003; random-effects model). Further analysis showed no difference in the improvement of CAAs in short-term follow-up between the two groups. However, adding IFX either as initial therapy or as additional therapy all showed an advantageous effect regarding the ∆Z score of the left anterior descending (LAD) (MD =0.29; 95% CI: 0.27–0.31; P<0.00001) and right coronary artery (RCA) (MD =0.24; 95% CI: 0.22–0.26; P<0.00001). Further, IFX exhibited significant effect on the treatment response compared with IVIG therapy in the Asian group (OR, 2.84; 95% CI: 1.51–5.36; P=0.001; random-effects model), and the beneficial effects of IFX were given without increasing the risk of AEs.ConclusionsThis meta-analysis emphasizes the importance of IFX on the treatment response in the high-risk KD patients. IFX may play a role in the Asian KD patients and prevention of progressive CAA, and does not increase the risk of AEs in KD patients.

Effect of Infliximab Therapy in Functional Improvement in Patients with Ankylosing Spondylitis

ABSTRACT Introduction Ankylosing spondylitis (AS), one of the spondyloarthropathies predominantly affecting younger people, is notorious for morbidity with pain, functional impairment, and disability. Infliximab, a chimeric tumor necrosis factor (TNF) alpha inhibitor, has been proven as a safe and effective biologic in respect to improvement in clinical and radiological parameters in AS. This study is a humble attempt to look for disability limitations by infliximab therapy in patients with AS. Aims and objectives To look for functional improvement in AS patients treated with Infliximab in comparison with control group who were treated conservatively. Materials and methods A randomized controlled trial was done in the Department of Physical Medicine and Rehabilitation, Institute of Postgraduate Medical Education &amp; Research and Seth Sukhlal Karnani Memorial Hospital, Kolkata, West Bengal, India, from December 2015 to May 2017, recruiting 20 AS patients who fulfilled the Assessment of SpondyloArthritis International Society (ASAS) criteria and had significant functional limitation. After Ethics Committee clearance, two groups were made randomly. Both groups I and II were included in the rehabilitation program. Group I, in addition, received injection infliximab on days 0, 14, and 42. Assessment by the Bath ankylosing spondylitis functional index (BASFI) and visual analog scale (VAS) for lower back pain was done before intervention and 2, 6, 12 weeks after initiation of treatment. Results Statistically significant positive outcome difference was seen in the first group in comparison with control group based on both outcome parameters. Conclusion Infliximab is a safe and highly efficacious biologic therapy in limiting disability in AS patients when treated early. How to cite this article Konar A, Pramanik R, Ghorai D, Banerjee A. Effect of Infliximab Therapy in Functional Improvement in Patients with Ankylosing Spondylitis. Indian J Phy Med Rehab 2017;28(2):59-63.

P591. The effect of Infliximab therapy on the Neutrophil-Lymphocyte and Platelet-Lymphocyte Ratios in Inflammatory Bowel Disease patients

P591. The effect of Infliximab therapy on the Neutrophil-Lymphocyte and Platelet-Lymphocyte Ratios in Inflammatory Bowel Disease patients

Mo1738 Efficacy of a Novel JAK1-Specific Inhibitor in a Mouse Model of Acute and Chronic Colitis

Introduction and aim: Indoleamine 2,3-dioxygenase (IDO) is expressed in innate immune cells and acts as the first rate-limiting step in the tryptophan (TRP) catabolism along the kynurenine pathway. Decreased serum TRP levels have been associated with active inflammation in Crohn's disease (CD) due to induction of IDO (Gupta, Inflamm Bowel Dis 2012). We studied the effect of infliximab-induced downregulation of inflammation on serum levels of TRP and kynurenine, as well as mucosal IDO expression in patients with inflammatory bowel disease (IBD). Methods: Serum samples and endoscopically-derived ileal or colonic mucosal biopsies were obtained from controls and patients with active IBD, and this before and after their first treatment with infliximab. Short-term clinical response and mucosal healing were assessed by experienced clinicians at 4 or 10 weeks after a single infusion or induction schedule, respectively (Ferrante, Inflamm Bowel Dis 2007; Schnitzler, GUT 2009). Serum TRP and kynurenine were measured by high performance liquid chromatography, and IDO mucosal gene expression was measured by Affymetrix Human Genome U133 Plus 2.0 Arrays. Data were analyzed with SPSS software using non-parametric tests and p-values of 9-fold increased in active IBD patients before infliximab therapy vs. controls (pileum=0.001 and pcolon<0.001). Although the IDOmucosal expression levels significantly decreased after infliximab therapy in IBD responders when compared to their baseline samples (pshort-term response and pmucosal healing<0.001), the colonic expression still remained significantly higher than controls (pshort-term response<0.001 and pmucosal healing=0.002). Serum TRP levels were significantly decreased (p<0.001) and the kynurenine/ tryptophan (K/T) ratio was significantly increased (p=0.001) in active IBD patients when compared to controls. However, we found no significant effect of infliximab therapy on both the TRP levels and K/T ratio. Conclusion: This study demonstrates that mucosal IDO expression levels are increased and serum TRP levels decreased in IBD patients with active disease. Of note, after controlling the inflammation with infliximab therapy, both levels remained impaired in IBD responders showing a complete mucosal healing. This persistent upregulation of IDO in patients with complete colonic healing may explain why mucosal ulcers recur very early if patients do not receive maintenance therapy with infliximab.

Mo1737 The Effect of Infliximab Therapy on the Tryptophan Metabolism and Indoleamine 2,3-Dioxygenase Expression (IDO) in Patients With Inflammatory Bowel Disease

Introduction and aim: Indoleamine 2,3-dioxygenase (IDO) is expressed in innate immune cells and acts as the first rate-limiting step in the tryptophan (TRP) catabolism along the kynurenine pathway. Decreased serum TRP levels have been associated with active inflammation in Crohn's disease (CD) due to induction of IDO (Gupta, Inflamm Bowel Dis 2012). We studied the effect of infliximab-induced downregulation of inflammation on serum levels of TRP and kynurenine, as well as mucosal IDO expression in patients with inflammatory bowel disease (IBD). Methods: Serum samples and endoscopically-derived ileal or colonic mucosal biopsies were obtained from controls and patients with active IBD, and this before and after their first treatment with infliximab. Short-term clinical response and mucosal healing were assessed by experienced clinicians at 4 or 10 weeks after a single infusion or induction schedule, respectively (Ferrante, Inflamm Bowel Dis 2007; Schnitzler, GUT 2009). Serum TRP and kynurenine were measured by high performance liquid chromatography, and IDO mucosal gene expression was measured by Affymetrix Human Genome U133 Plus 2.0 Arrays. Data were analyzed with SPSS software using non-parametric tests and p-values of 9-fold increased in active IBD patients before infliximab therapy vs. controls (pileum=0.001 and pcolon<0.001). Although the IDOmucosal expression levels significantly decreased after infliximab therapy in IBD responders when compared to their baseline samples (pshort-term response and pmucosal healing<0.001), the colonic expression still remained significantly higher than controls (pshort-term response<0.001 and pmucosal healing=0.002). Serum TRP levels were significantly decreased (p<0.001) and the kynurenine/ tryptophan (K/T) ratio was significantly increased (p=0.001) in active IBD patients when compared to controls. However, we found no significant effect of infliximab therapy on both the TRP levels and K/T ratio. Conclusion: This study demonstrates that mucosal IDO expression levels are increased and serum TRP levels decreased in IBD patients with active disease. Of note, after controlling the inflammation with infliximab therapy, both levels remained impaired in IBD responders showing a complete mucosal healing. This persistent upregulation of IDO in patients with complete colonic healing may explain why mucosal ulcers recur very early if patients do not receive maintenance therapy with infliximab.

AB0082 The efficacy of anti-tnf treatment on urinary type-ii collagen c-telopeptyde levels in patients with rheumatoid arthritis

BackgroundThe aim of the present study was to evaluate the efficacy of anti-TNF treatment on urinary type-II collagen C-telopeptyde (CTX-II) levels which is a cartilage destruction marker in patients with...

Changes in disease activity, lung function and quality of life in patients with refractory sarcoidosis after anti-TNF treatment

Objectives: The effect of infliximab therapy in rheumatoid arthritis and Crohn's disease has been well documented. However, literature on infliximab therapy in the rare disease sarcoidosis is scarce. The aim of our study is to evaluate change in disease activity and quality of life upon infliximab treatment in patients with refractory sarcoidosis.Research design and methods: Retrospective cohort study of 48 patients who received infliximab treatment at a national referral center for sarcoidosis. The clinical effect of infliximab treatment was analyzed in terms of change in disease activity (18F-FDG PET, serum angiotensin-converting-enzyme [ACE], serum-soluble interleukin-2 receptor [sIL-2R]), lung function (predicted VC, FEV1 and DLCOc), fatigue severity (CIS) and physical functioning (SF-36). Study parameters were assessed before the first dose (week 0) and after the last dose (week 18).Results: We found significant decreases in the serum markers ACE and sIL-2R and in SUVmax on 18F-FDG PET. Furthermore, a significant improvement in fatigue severity and physical functioning scores was observed. In patients with a pulmonary treatment indication, we found significant improvements in percentages of predicted VC (7.6%), FEV1 (7.9%) and DLCOc (3.5%).Conclusions: Infliximab improves PET-scan, serum markers, lung function and quality of life in patients with refractory sarcoidosis.

Effects of infliximab therapy on transmural lesions as assessed by magnetic resonance enteroclysis in patients with ileal Crohn's disease

Background and aimsAnti TNF therapy induces mucosal healing in patients with Crohn's disease, but the effects on transmural inflammation in the ileum are not well understood. Magnetic resonance-enteroclysis (MRE) offers excellent imaging of transmural and peri-enteric lesions in Crohn's ileitis and we aimed to study its responsiveness to anti TNF therapy. MethodsIn this multi-center prospective trial, anti TNF naïve patients with ileal Crohn's disease and with increased CRP and contrast enhanced wall thickening received infliximab 5mg/kg at weeks 0, 2 and 6, and q8 weeks maintenance MRE was performed at baseline, 2 weeks and 6 months and assessed based on a predefined MRE score of severity in ileal Crohn's Disease. ResultsTwenty patients were included; of those, 18 patients underwent MRE at week 2 and 15 patients at weeks 2 and 26 as scheduled. Inflammatory components of the MRE index decreased by ≥2 points and by ≥50% at week 26 (primary endpoint) in 40% and 32% of patients (per protocol and intention to treat analysis, respectively). The MRE index improved in 44% at week 2 and in 80% at week 26. Complete absence of inflammatory lesions was observed in 0/18 at week 2 and 13% (2/15) at week 26. The obstructive elements did not change. Clinical and CRP improvement occurred as early as wk 2, but only CDAI correlated with the MRE index. ConclusionImprovement of MRE occurs from 2 weeks after infliximab therapy onwards and correlates with clinical response but normalization of MRE is rare.

P350 The effect of infliximab therapy on nutritional status in patients with Crohn's disease

P350 The effect of infliximab therapy on nutritional status in patients with Crohn's disease

Effects of Infliximab Therapy on Transmural Lesions Assessed by MRI Enteroclysis in Patients With Ileal Crohn's Disease: The ACTIF Study

to a change in their management. Findings unrelated to IBD were reported in 14% that warranted further investigations or consultations (including 3 new cancers). Conclusions: Crohn's disease of the TI can be missed at ileoscopy either due to skipping of the distal TI or due to disease confined to the intramural portion of the bowel wall. CTE complements ileocolonoscopy in assessing disease activity in patients with Crohn's disease.

Calprotectin as a Biomarker for Remission in UC Patients Under IFX Therapy

Background: Faecal calprotectin correlates with endoscopic and histological disease activity in patients with ulcerative colitis (UC). Recently, it has been shown that infliximab therapy is effective for the induction and the maintenance of UC disease remission. Aims: To evaluate the evolution of calprotectin levels under infliximab therapy. Patients and Methods: 53 patients with active UC from 17 centers were treated with infliximab therapy (5 mg/kg) at baseline, week 2, and week 6. Patients were evaluated at each infusion and week 10 by clinical Mayo score and lab testing. Faecal calprotectin was measured every week. Sigmoidoscopies were performed at baseline, week 6 and week 10 and graded from 0-3. Endoscopic remission was further defined by a score of 1 or less. Remission per protocol was defined as endoscopic remission and a decrease of calprotectin with 80 % or < 50 mg/kg. Results: After 10 weeks, 2 patients stopped therapy due to inefficacy. Three patients stopped due to safety reasons: 2 allergic reactions, 1 patient had a vertebral fracture. Additionally, 12 patients had missing data, mostly attributable to refusal of the week 10 colonoscopy. Those patients were excluded from complete case analysis, further depicted with an asterisk (*). Remission per protocol was obtained in 58%* of patients (or 54% by ITT analysis with multiple imputation). Endoscopic remission in 63%* of patients (or 59% by ITT analysis). Median calprotectin levels decreased from 1767 (IQR 3140)* at baseline to 72.5 (IQR 444)* at week 10 (p<0.001). Moreover, patients who went in endoscopic remission at week 10 showed a significant steep decrease of calpro scores between baseline and week 2 (p< 0.001) compared to patients who did not show a remission. From week 3 on, this course was more flattened (Figure). Clinical Mayo score and faecal calprotectin measurements showed an excellent correlation with endoscopic remission, reflected by an AUC of ROC analyses of 0.94 (0.87-1) for Mayo score and 0.91 (0.81-1) for calpro measurements at week 10*: all patients (63%*) with a Calpro score of <50, and all patients (63%*) with a normal clinical Mayo score (=0) were in colonoscopic remission. Similar results were obtained with ITT repeated measures analysis: AUC of 0.97 (0.94-1) for the Clinical Mayo score and 0.85 (0.77-0.92) for the calpro measurements. A calprotecin level of 50 mg/kg or a decrease of at least 80% at week predicted an endoscopic remission at week 10 with a specificity of 67%* and sensitivity of 54%*. Conclusions: Infliximab induces a remission in 58% of UC patients with active disease associated with a fast and significant decrease of faecal calprotectin levels. Calprotectin levels are as reliable as the Clinical Mayo score to evaluate the effect of infliximab therapy and correlate with endoscopic scores.

Mononeuritis multiplex unter dem TNF-alpha-Hemmer Infliximab

A 21-year-old patient with ankylosing spondylitis under treatment with the TNF-alpha inhibitor infliximab developed a multifocal, demyelinating axonal neuropathy affecting several peripheral nerves simultaneously (mononeuritis multiplex). This represents an additional rare peripheral nervous system side effect of infliximab therapy. The underlying cause is unknown. Intravenous immunoglobulin therapy (0.4 g/kg per day for five days) led to a complete regression of muscle paresis and sensory defects in this case.

Effects of infliximab therapy on abdominal fat and metabolic profile in patients with Crohnʼs disease

Tumor necrosis factor is an adipocytokine possessing a well-established lipolytic effect. In Crohn's disease (CD) patients, infliximab therapy may thus result in visceral fat accumulation, which is associated with an increased risk of metabolic syndrome. A total of 132 CD patients were investigated. In a first prospective study, magnetic resonance imaging (MRI) quantification of subcutaneous and visceral abdominal fat was performed before and 8 weeks after initiation of infliximab induction therapy (5 mg/kg at weeks 0, 2, and 6) in 21 responding patients treated for perianal disease. In a second prospective study, fasting glycemia, glycated hemoglobin (HbA1c), HDL, LDL, and total cholesterol and triglyceride levels were assessed in 111 responding patients receiving infliximab infusions every 8 weeks, with a mean follow-up of 41 weeks. A significant homogeneous 18% increase in total abdominal fat was observed in the 21 CD patients after infliximab induction therapy (P = 0.027), independently of body mass index evolution. Infliximab maintenance therapy was associated with a decrease in glycemia (P < 0.0001) and HbA1c (P = 0.0005) concentrations, together with an increase in both total cholesterol (P = 0.02) and HDL cholesterol (P = 0.008) concentrations. All glycemic and lipid parameters remained within the normal range throughout the study. Infliximab induction therapy is associated with a significant increase in abdominal fat tissue in CD patients. Infliximab maintenance therapy has no deleterious effects on lipid profile and is accompanied by a decrease in glycemia and HbA1c concentrations, probably by reversing the impairment of tumor necrosis factor-induced insulin-mediated glucose uptake.

Effects of infliximab therapy on biological markers of synovium activity and cartilage breakdown in patients with rheumatoid arthritis

Background:Defining the remission criteria of rheumatoid arthritis (RA) remains a critical issue. Markers of synovium activity, urinary glucosyl-galactosyl-pyridinoline (Glc-Gal-PYD) and of cartilage destruction, urinary C-terminal crosslinking telopeptide of type II...

Linear growth during infliximab therapy: Results of the REACH multicenter study

Linear growth, a marker of therapeutic success in pediatric Crohn's disease (CD), was evaluated during maintenance infliximab (IFX) therapy in the context of the REACH multicenter, randomized open-label study comparing two dosing regimens. 112 children and adolescents (59% males; mean age 13.3 yrs, range 6-17 yrs) with moderately-to-severely active CD (Pediatric Crohn's Disease Activity Index [PCDAI >30]; mean 41.2, standard deviation 8.3) received a 3-dose induction of IFX 5mg/kg at weeks 0, 2 and 6. At week 10, responders (n = 103 [88%]) were randomized to receive IFX 5mg/kg at regularly scheduled infusions q8 or q12 weeks from week6 through week46 or42, respectively. 54 responders with a baseline bone age <13 yrs (female, n=20) or <14 yrs (male, n=34) were classified as having presumed growth potential (PGP). Their growth parameters (height and height velocity) before and after infliximab therapy (randomized: n=33 q8 week dosing; n=21 q12 week dosing) were analyzed after standardizing for age and gender. At IFX therapy initiation, mean z-scores for height (-1.0; 95% confidence interval [CI], -1.3 to -0.7) increased by a mean of 0.4 (95% CI 0.3 to 0.5). At week 54, 29/54 (54%) were in clinical response (delta PCDAI≥15 and PCDAI≤30), and 24/54 (44%) were in clinical remission (PCDAI≤10). The effects of IFX therapy on height velocity z-scores for various subgroups are presented below. Maintenance IFX therapy is associated with improved linear growth velocity and height centile in pediatric Crohn's patients treated before or in early puberty. Ultimate height in children with moderate-to-severe CD may be less compromised with IFX therapy than with conventional therapies.

The effects of Infliximab therapy on health-related quality of life in pediatric crohnʼs disease

The effects of Infliximab therapy on health-related quality of life in pediatric crohnʼs disease

The effects of Infliximab therapy on health-related quality of life in pediatric crohnʼs disease

The effects of Infliximab therapy on health-related quality of life in pediatric crohnʼs disease

The Effects of Infliximab Therapy on Health-Related Quality of Life in Ulcerative Colitis Patients

The impact of infliximab induction and maintenance therapy on health-related quality of life (HRQL) was evaluated in patients with ulcerative colitis (UC). In two placebo-controlled, double-blind studies (the Active Ulcerative Colitis Trials 1 and 2 [ACT 1 and 2]), 728 patients were randomized to placebo or infliximab 5 mg/kg or 10 mg/kg. Infusions were administered at weeks 0, 2, 6, and every 8 wk thereafter, up to week 22 (ACT 2) or 46 (ACT 1). Changes in Inflammatory Bowel Disease Questionnaire (IBDQ) and Medical Outcomes Study 36-Item Short Form Health Survey physical and mental component summary (PCS and MCS, respectively) scores were analyzed. Baseline scores for the pooled patient population indicated substantial impairment in HRQL. Improvement at week 8 in the total IBDQ score was significantly greater in the infliximab 5-mg/kg (40, P < 0.001) and 10-mg/kg (36, P < 0.001) groups compared with the placebo group (28). Improvement at week 8 was also significantly greater in the infliximab 5- and 10-mg/kg groups for the PCS (6.8 and 5.9, respectively) and MCS (5.9 and 6.4, respectively) compared with placebo (PCS = 3.7, MCS = 3.0, P < 0.01 for all comparisons). Continued benefit was seen at weeks 30 and 54 with infliximab maintenance therapy (P < 0.001 for all comparisons). Improvement in total IBDQ score correlated significantly (P < 0.001) with improvement in both PCS and MCS scores, and Mayo score. Infliximab therapy substantially improved HRQL in patients with UC. This benefit was sustained through 1 yr with maintenance infliximab therapy.

Effects of infliximab therapy on gene expression levels of tumor necrosis factor α, tristetraprolin, T cell intracellular antigen 1, and Hu antigen R in patients with rheumatoid arthritis

Tristetraprolin (TTP), T cell intracellular antigen 1 (TIA-1), and Hu antigen R (HuR) are adenine/uridine-rich element binding proteins (ABPs) that affect the production of tumor necrosis factor alpha (TNFalpha) by binding to TNF messenger RNA (mRNA). TTP promotes deadenylation, TIA-1 inhibits translation, and HuR stabilizes TNFalpha mRNA. The aims of this study were to understand the posttranscriptional control of TNFalpha production in patients with rheumatoid arthritis (RA), and to identify parameters that may predict the efficacy of anti-TNFalpha therapy. Peripheral blood mononuclear cells from 38 patients with RA were obtained before therapy and 2 weeks and 54 weeks after administration of the first dose of infliximab, and from 20 healthy control subjects. TNFalpha, TTP, TIA-1, and HuR gene expression levels were analyzed by real-time polymerase chain reaction. At baseline, TTP and HuR gene expression levels, as well as the TTP:TNFalpha, TTP:HuR, and TIA-1:TNFalpha gene expression ratios were lower in patients with RA than in control subjects, while expression of TNFalpha, TIA-1, and TIA-1:HuR was higher in patients with RA. The TTP:HuR expression ratio decreased significantly after administration of infliximab. Positive correlations were observed between TNFalpha and TTP, TNFalpha and TIA-1, TIA-1 and HuR, and TNFalpha and HuR gene expression in both healthy control subjects and patients with RA. At baseline, the TIA-1:HuR ratio tended to be higher in patients who achieved 50% improvement according to the American College of Rheumatology criteria (ACR50) at week 54 than in those who did not achieve at least an ACR20 response. Differences in ABP gene expression may affect TNFalpha gene expression. A higher TIA-1:HuR expression ratio might correlate with the response to infliximab therapy.

The Effects of Infliximab Therapy on Health‐Related Quality of Life in Pediatric Crohn's Disease

The Effects of Infliximab Therapy on Health‐Related Quality of Life in Pediatric Crohn's Disease