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Infliximab Therapy (infliximab + therapy)

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Medical Sciences	100%

Selected Abstracts

Infliximab therapy in a patient with Crohn's disease and chronic hepatitis B virus infection

INFLAMMATORY BOWEL DISEASES, Issue 5 2004
María del Valle García-Sánchez MD
No abstract is available for this article. [source]

Infliximab for refractory ulcerative proctitis

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11 2010
G. BOUGUEN
Aliment Pharmacol Ther,31, 1178,1185 Summary Background, Efficacy of infliximab in treating ulcerative proctitis remains unknown. Aim, To evaluate the clinical, biological and endoscopic efficacy of infliximab therapy in refractory proctitis. Methods, The charts of 420 patients treated with infliximab for ulcerative colitis were reviewed. Thirteen patients were treated with infliximab for refractory ulcerative proctitis in six referral centres between 2005 and 2009. Results, Following infliximab therapy induction, 9/13 patients (69%) had a complete response (defined as absence of diarrhoea and blood), 2/13 (15%) had a partial response and 2/13 (15%) were primary nonresponders. The median follow-up was 17 months (range, 3,48). Among the 11 patients with clinical response after infliximab induction therapy, 9 (82%) patients maintained response at last follow-up. Disappearance of rectal disorders was observed in all nine patients who maintained clinical response at last follow-up. Following infliximab induction therapy, the mean CRP level fell from 12.8 mg/L to 4.7 mg/L. Endoscopic evaluation was performed before and after infliximab in seven patients, showing an improvement in mucosal lesions in four patients, persistent mild endoscopic activity in two patients and no improvement in one patient. One patient underwent proctocolectomy. Conclusion, Infliximab therapy seems to be effective in inducing and maintaining a clinical response in refractory ulcerative proctitis. [source]

Infliximab safety profile and long-term applicability in inflammatory bowel disease: 9-year experience in clinical practice

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2010
Y. ZABANA
Aliment Pharmacol Ther,31, 553,560 Summary Background, Most available data on infliximab therapy come from large, short-term, pivotal RCTs and concerns about long-term safety profile still remain. Aim, To evaluate the long-term safety profile of infliximab in inflammatory bowel disease (IBD) in a clinical practice setting. Methods, Since 1999, all IBD patients treated with infliximab were registered and clinical outcomes prospectively recorded up to March 2008, loss of follow-up or patient's death. Infliximab regimens and preventive measures were in accordance with the prevalent guidelines or with the manufacturer's recommendations. Results, One hundred fifty-two patients were included (121 Crohn's disease, 24 ulcerative colitis, 7 indeterminate colitis), with a median of 5 infliximab infusions (IQR 3,8) and 87% of patients received at least three infusions. Seventy-nine per cent of them received concomitant immunomodulators and 70% were pre-medicated with hydrocortisone from the first infusion. After a median follow-up of 142 weeks, 13% presented infusion reactions, 13% viral or bacterial infections and two patients developed neoplasia. The mortality rate was 2.6% (four patients). Conclusions, Infliximab therapy is safe when the recommended preventive measures are implemented, with a rate of serious adverse events less than 10%. No new safety signals were found. [source]

Long-term outcome of non-fistulizing (ulcers, stricture) perianal Crohn's disease in patients treated with infliximab

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2009
G. BOUGUEN
Summary Background, In Crohn's disease, anal ulcers and stricture can be disabling. Aim, To evaluate long-term outcome of non-fistulizing perianal Crohn's disease under infliximab. Methods, The medical records of 99 patients with non-fistulizing perianal Crohn's disease at first infliximab infusion were reviewed. Complete responses (ulcer healing or stricture regression) after induction infliximab therapy and at the maximal follow-up were assessed. Results, Ninety-four patients (94.9%) had ulcers, 22 (22.2%) had stricture and 31 (31.3%) had draining perianal fistulas at first infliximab infusion. After infliximab induction therapy, 40/94 (42.5%) patients with ulcers, 4/22 (18.2%) with stricture and 10/31 (32.2%) with fistulas had a complete response. Eight patients were lost to follow-up. After a median follow-up of 175 weeks (range, 13,459), complete response rates for ulcers, stricture and fistulas were 72.3% (68/94), 54.5% (12/22) and 54.8% (20/31) respectively. Long-term response for cavitating ulcer was positively associated with concomitant immunosuppressant use (P = 0.017) and older age (P = 0.049). Among the 12 patients with complete regression of stricture, 6 patients also had anal dilatation. Complete response was associated with perianal pain relief and disappearance of soiling. Three patients with ulcers developed an anal abscess. Conclusions, Infliximab therapy may be effective in inducing and maintaining response for ulcers. [source]

Severe adverse reactions to Infliximab therapy are common in young children with inflammatory bowel disease

ACTA PAEDIATRICA, Issue 1 2007
K-L Kolho
Abstract Since 2000 we have introduced 141 Infliximab infusions to 23 children with severe inflammatory bowel disease. A total of seven severe adverse reactions occurred in 26% (6 of 23) of the children. Four reactions were acute (anaphylaxis n = 2; allergic reaction n = 2) and 3/4 of these children were younger than 10 years of age. Two children developed an abscess and one child had septicaemia and brain lesions related to progressive multifocal leucoencephalopathy. Conclusion: adverse reactions to Infliximab infusions are common. Young children seem to be prone to severe allergic reactions although they are on azathioprine and conventional glucocorticoid therapy. [source]

Peripheral neuropathy with infliximab therapy in inflammatory bowel disease

INFLAMMATORY BOWEL DISEASES, Issue 12 2009
D.C. Burger MD, MBBS (Hons)
No abstract is available for this article. [source]

Severe Legionella pneumophila pneumonia following infliximab therapy in a patient with Crohn's disease

INFLAMMATORY BOWEL DISEASES, Issue 8 2009
Florian Beigel MD
Abstract Background: Immunosuppressive therapy with anti-TNF-, antibodies is effective in patients with inflammatory bowel disease (IBD). However, there is an increased risk for infections associated with this therapy. Methods: Here, we report the case of a 58-year-old patient with Crohn's disease (CD) treated with steroids and azathioprine who developed severe Legionella pneumophila pneumonia after 3 infusions of infliximab. The patient presented at our IBD department with severe active CD complicated by inflammatory small bowel stenoses and entero-enteral fistulas despite long-term high-dose steroid therapy. To achieve steroid tapering and control of disease activity, immunosuppressive therapy with azathioprine was initiated. Due to persistent symptoms, infusion therapy with the anti-TNF-, antibody infliximab was started, subsequently leading to significant clinical improvement. However, after the third infliximab infusion the patient was hospitalized with fever, severe fatigue, and syncope. Results: Laboratory findings and chest X-ray revealed left-sided pneumonia; cultural analysis showed L. pneumophila serogroup 1 leading to respiratory insufficiency, which required mechanical ventilation for 2 weeks in the intensive care unit. After discontinuation of all immunosuppressive agents and immediate antibiotic therapy the patient recovered completely. Conclusions: To our knowledge, this is the third case of L. pneumophila pneumonia in an IBD patient treated with infliximab. Similar to other published cases, concomitant treatment of immunosuppressives and anti-TNF agents is a major risk factor for the development of L. pneumophila infection, which should be ruled out in all cases of pneumonia in patients with such a therapeutic regimen. Appropriate prevention strategies should be provided in these patients. (Inflamm Bowel Dis 2009) [source]

Predictive model for the outcome of infliximab therapy in Crohn's disease based on apoptotic pharmacogenetic index and clinical predictors

INFLAMMATORY BOWEL DISEASES, Issue 4 2007
Tibor Hlavaty
Abstract Background: Infliximab (IFX) is an effective therapy for refractory luminal and fistulizing Crohn's disease (CD). Predictors of response could improve selection of patients with a higher probability of favorable outcomes and could improve the safety profile. We aimed to develop a predictive model for the response to infliximab in CD. Methods: Genetic and clinical data collected in a previous pharmacogenetic study of apoptosis genes were analyzed using SAS Enterprise miner modeling software and SPSS 12.0. We proposed a novel apoptotic pharmacogenetic index (API) with a score ranging from 0 (low apoptotic response) to 3 (high apoptotic response) and subsequently developed a decision tree model. Results: Response and remission rates significantly increased with API score (P = 0.005 in the group of patients with luminal CD, P = 0.02 in the group of patients with fistulizing CD). Patients with an API , 1 (n = 59) had the lowest response and remission rates in both the luminal CD (50% and 39.5%, respectively) and fistulizing CD (61.9% and 28.6%, respectively) groups, compared to those with an API of 2 (n = 158), whose response and remission rates were 73.8% and 56.1%, respectively, in the luminal CD group and 85.7% and 44.9%, respectively, in the fistulizing CD group; and those with an API of 3 (n = 10), whose response and remission rates were 100% and 85.7%, respectively, in the luminal CD group and 100% and 0% in the fistulizing CD group. Response in patients with an API , 1 was significantly influenced by concurrent azathioprine therapy in the luminal CD (21.4% versus 78.9%, P < 0.001) and in the fistulizing CD (46.6% versus 100%, P = 0.04) groups. In patients with an API of 2, we saw an interaction with age older than 40 years and location of disease (response 52.2% versus 83.9%, P = 0.008) in the luminal CD group and with baseline CRP greater than 5 mg/L (73.9% versus 93.9%, P = 0.04) in the fistulizing CD group. Conclusions: From our newly proposed apoptotic pharmacogenetic index and clinical predictors, we developed a model for prediction of low, medium, and high responses to the first infusion of IFX in patients with CD. Further studies are needed to confirm the hypothesis generated by our study. (Inflamm Bowel Dis 2007) [source]

Clinical experience with infliximab among Filipino patients with rheumatic diseases

INTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 2 2006
Sandra V. NAVARRA
Abstract Aim:, To describe the clinical experience with infliximab among Filipino patients with rheumatic diseases, specifically disease indications, dose regimens, clinical response, and adverse events. Methods:, We reviewed the data on Filipino patients who were given infliximab by rheumatologists for a rheumatic disease indication. The case report form included demographic profile, underlying rheumatic disease, comorbidities, concurrent medications, dose and frequency of infliximab, physicians' assessment of clinical response, and adverse events. The frequency of doses, intervals between doses, and discontinuation status were recorded. Results:, Included were 64 patients (35 females), with a mean age of 44 years. Most (41%) had rheumatoid arthritis, followed by psoriasis/psoriatic arthritis (31.2%) and ankylosing spondylitis (17.2%). Average disease duration from diagnosis to initiation of infliximab therapy was 7.6 years ± 6.7 SD. Among 35 patients, the interval between maintenance infusions ranged from 6 to 13.6 weeks, with a mean of 8.27 weeks. Clinical response was good to excellent in more than 80% of patients. Discontinuation rate was 10.9% and 28.1% at 3 and 12 months, respectively. Infusion-related adverse events were mild and transient, and 14 (21.8%) cases of infection resolved with appropriate therapy. Infliximab was temporarily withheld in five (7.8%) patients with active tuberculosis. Summary:, These findings substantiate the superior clinical efficacy of infliximab and manageable adverse events among Filipinos with rheumatic diseases. It also demonstrates dose regimens in clinical practice in a third world setting with limited resources. [source]

Systematic review: steroid withdrawal in anti-TNF-treated patients with inflammatory bowel disease

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2010
E. Bultman
Aliment Pharmacol Ther 2010; 32: 313,323 Summary Background, The increasing awareness of increased risk for opportunistic infections when combining several immunosuppressant drugs led to new treatment goals for inflammatory bowel disease including limited use of steroids. Aim, To conduct a systematic review to establish figures for steroid withdrawal in anti-TNF treated inflammatory bowel disease-patients. Methods, Medline was searched using the search-terms Ulcerative Colitis (UC) [Mesh], Crohn Disease (CD) [Mesh], IBD [Mesh], crohn, colitis, IBD and steroid sparing, all combined with infliximab and adalimumab. We selected English-language publications that addressed the effect of anti-TNF on steroid withdrawal. Studies had to assess patients with luminal CD or UC. Numbers of patients who were able to withdraw steroids were calculated. Results, Six studies could be included; five reporting on infliximab and one on adalimumab. Studies were heterogeneously designed. Overall, in the adult population, up to 38% of the patients were able to withdraw corticosteroids during infliximab therapy. In the paediatric population, up to 75% of the patients were able to withdraw corticosteroids during infliximab therapy. Conclusions, Although a consensus on the definition of steroid-sparing is lacking, approximately two-thirds of the inflammatory bowel disease-patients are unable to withdraw corticosteroid treatment during anti-TNF therapy. [source]

Infliximab for refractory ulcerative proctitis

Infliximab safety profile and long-term applicability in inflammatory bowel disease: 9-year experience in clinical practice

Long-term outcome of non-fistulizing (ulcers, stricture) perianal Crohn's disease in patients treated with infliximab

Infliximab and other immunomodulating drugs in patients with inflammatory bowel disease and the risk of serious bacterial infections

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2009
S. SCHNEEWEISS
Summary Background, There remain concerns about the safety of infliximab therapy in patients with inflammatory bowel disease (IBD). Aim, To assess the association between the initiation of infliximab and other immunomodulating drugs and the risk of serious bacterial infection in the treatment of IBD. Methods, We assembled a cohort study of patients with IBD, including Crohn's disease (CD) and ulcerative colitis (UC). All patients initiating an immunomodulating drug between January 2001 and April 2006 were identified in British Columbia from linked health care utilization databases. Exposure of interest was initiation of infliximab or corticosteroids compared with initiation of other immunosuppressive agents, including azathioprine, mercaptopurine (MP) and methotrexate (MTX). Outcome of interest was serious bacterial infections requiring hospitalization, including Clostridium difficile. Results, Among 10 662 IBD patients, the incidence rate of bacteriaemia ranged from 3.8 per 1000 person-years (95% confidence interval 2.1,6.2) for other immunosuppressive agents to 7.4 (3.3,19.3) for infliximab with slightly higher rate for serious bacterial infections resulting in an adjusted relative risk 1.4 (0.47,4.24). Clostridium difficile infections occurred in 0/1000 (0,5.4) among 521 infliximab initiations and 14/1000 (10.6,18.2) for corticosteroids. Corticosteroid initiation tripled the risk of C. difficile infections (RR = 3.4; 1.9,6.1) compared with other immunosuppressant agents. This corticosteroid effect was neither dose-dependent nor duration-dependent. Bacteriaemia and other serious bacterial infections were not increased by corticosteroids or infliximab (5 events). Conclusions, In a population-based cohort of patients with IBD, we found no meaningful association between infliximab and serious bacterial infections, although some subgroups had few events. Corticosteroid initiation increased the risk for C. difficile infections in these patients. [source]

Experience of maintenance infliximab therapy for refractory ulcerative colitis from six centres in England

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2009
E. A. RUSSO
Summary Background, Infliximab is used for treatment of Crohn's disease and, following the Active Ulcerative Colitis Trials (ACT) 1 and 2, it has been used as rescue and maintenance therapy in moderate and severe ulcerative colitis (UC). Aim, To report on English experience with maintenance infliximab in terms of response and colectomy rates and side-effect profile in UC. Methods, A retrospective audit conducted by using a web-based questionnaire filled in by 12 gastroenterologists from six English centres. Results, Of the 38 patients receiving induction with infliximab, 28 (73.6%) maintained an ongoing response (8-weekly infusions 5 mg/kg) for a mean duration of 16.8 months (range 4,59), with 21 (55.3%) being in remission. Three of 38 patients (7.9%) who also responded had a secondary loss of response after an average of 10 months (range 8,13); seven of 38 patients (18.4%) showed no response. The colectomy rate was seven of 38 (18.4%, five non-responders and two with secondary loss of response). Adverse effects occurred in five patients (13.2%). Two discontinued infliximab (alopecia, invasive breast cancer). The three less-severe adverse effects were acute and delayed-type hypersensitivity reactions and one persistent otitis media. Conclusion, Our experience suggests acceptable response rates, colectomy rates and side-effect profile of maintenance therapy with infliximab in moderate and severe UC. [source]

Review article: interactions between genotype and response to therapy in inflammatory bowel diseases

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 10 2006
K. R. HERRLINGER
Summary Background More than half of the patients with inflammatory bowel diseases are candidates for immunosuppressive therapy. However, even the most effective drugs used in inflammatory bowel disease are only successful in about two-thirds of patients. Adverse events limit their use in a further substantial proportion of patients. Recent research has focussed on the possibility of predicting a drugs' efficacy and/or toxicity by identifying polymorphic variants in the genes encoding enzymes involved in metabolic pathways. Aim To highlight recent advances and limitations in the field of pharmacogenetics in inflammatory bowel disease. Results Recent pharmacogenetic studies have mainly focussed on immunosuppressive agents including corticosteroids, azathioprine, methotrexate and infliximab. Several polymorphic genes encoding enzymes involved in the metabolism of these drugs have been identified including the inosine triphosphate pyrophosphatase in thiopurine therapy, the methylene tetrahydrofolate reductase in methotrexate therapy and polymorphisms in apoptosis genes in infliximab therapy. However, at the present time, genotyping for the variants of the thiopurine methyltransferase gene, an enzyme important for the metabolism of the thiopurine drugs, is the only useful test in clinical practice. Conclusions Although the field of pharmacogenetics in inflammatory bowel disease is promising most new targets have so far failed to translate into clinical practice. Future pharmaceutical trials should include pharmacogenetic research to test appropriate candidate genes in a prospective manner. [source]

Review article: infliximab therapy for inflammatory bowel disease , seven years on

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2006
P. RUTGEERTS
Summary Infliximab, the chimeric monoclonal IgG1 antibody to tumour necrosis factor, is indicated for refractory luminal and fistulizing Crohn's disease and extra-intestinal manifestations of inflammatory bowel disease. Recently, the active ulcerative colitis trials (ACT) studies have shown that infliximab is also efficacious to treat ulcerative colitis resistant to standard therapy. Induction with 5 mg/kg infliximab at weeks 0, 2 and 6 is advocated. The response to infliximab is improved when concomitant immunosuppressive therapy is given. As the majority of patients will relapse if not retreated, a long-term strategy is necessary. Although episodic therapy can be used, the optimal strategy is systematic maintenance treatment with 5 mg/kg intravenous (i.v.) every 8 weeks. Long-term maintenance therapy with infliximab results in a reduction of the rate of complications, hospitalizations and surgeries associated with Crohn's disease. Safety problems with the monoclonal antibody infliximab treatment mainly concern the formation of antibodies to infliximab, which may lead to infusion reactions, loss of response and serum sickness-like delayed infusion reactions. Latent tuberculosis needs to be screened for. The rate of other opportunistic infections is slightly increased mainly in patients treated concomitantly with immunosuppression. There is no evidence that malignancy rates in patients treated with antitumour necrosis factor strategies are increased. [source]

Golimumab in patients with active rheumatoid arthritis despite treatment with methotrexate: A randomized, double-blind, placebo-controlled, dose-ranging study,

ARTHRITIS & RHEUMATISM, Issue 4 2008
Jonathan Kay
Objective To assess the efficacy, safety, and pharmacology of subcutaneous administration of golimumab in patients with active rheumatoid arthritis (RA) despite treatment with methotrexate (MTX). Methods Patients were randomly assigned in a double-blinded manner to receive injections of placebo plus MTX or 50 mg or 100 mg golimumab every 2 or 4 weeks plus MTX through week 48. Patients originally assigned to receive injections every 2 weeks had the interval increased to every 4 weeks starting at week 20. The primary end point was the proportion of patients meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) at week 16. The study was powered to detect a difference in the primary end point when the combined golimumab groups and at least 1 of the individual dose groups were compared with placebo. Results The primary end point was attained. Sixty-one percent of patients in the combined golimumab plus MTX dose groups achieved an ACR20 response at week 16 compared with 37% of patients in the placebo plus MTX group (P = 0.010). In addition, 79% of patients in the group receiving 100 mg golimumab every 2 weeks achieved an ACR20 response (P < 0.001 versus placebo). Through week 20 (after which patients receiving placebo were switched to active infliximab therapy), serious adverse events were reported in 9% of patients in the combined golimumab groups and in 6% of patients in the placebo group. Conclusion Golimumab plus MTX effectively reduces the signs and symptoms of RA and is generally well tolerated in patients with an inadequate response to MTX. [source]

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

ARTHRITIS & RHEUMATISM, Issue 7 2007
Makoto Sugihara
Objective 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 , (TNF,) by binding to TNF messenger RNA (mRNA). TTP promotes deadenylation, TIA-1 inhibits translation, and HuR stabilizes TNF, mRNA. The aims of this study were to understand the posttranscriptional control of TNF, production in patients with rheumatoid arthritis (RA), and to identify parameters that may predict the efficacy of anti-TNF, therapy. Methods 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. TNF,, TTP, TIA-1, and HuR gene expression levels were analyzed by real-time polymerase chain reaction. Results At baseline, TTP and HuR gene expression levels, as well as the TTP:TNF,, TTP:HuR, and TIA-1:TNF, gene expression ratios were lower in patients with RA than in control subjects, while expression of TNF,, 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 TNF, and TTP, TNF, and TIA-1, TIA-1 and HuR, and TNF, 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. Conclusion Differences in ABP gene expression may affect TNF, gene expression. A higher TIA-1:HuR expression ratio might correlate with the response to infliximab therapy. [source]

Overexpression of synoviolin in peripheral blood and synoviocytes from rheumatoid arthritis patients and continued elevation in nonresponders to infliximab treatment

ARTHRITIS & RHEUMATISM, Issue 7 2006
Myew-Ling Toh
Objective Synoviolin is a novel E3 ubiquitin ligase that has been implicated in the pathogenesis of rheumatoid arthritis (RA). The purpose of this study was to examine the expression and regulation of synoviolin by tumor necrosis factor , (TNF,), both in vivo and in vitro. Methods A total of 54 RA patients and 23 healthy control subjects were analyzed before, 4 hours after the first infusion, and at week 22 of infliximab treatment. Clinical response was assessed by the American College of Rheumatology criteria for 20% improvement and the Disease Activity Score in 28 joints (DAS28) at 6 months. Synoviolin messenger RNA expression was measured by real-time reverse transcription,polymerase chain reaction in peripheral blood (PB) and fibroblast-like synoviocytes (FLS) and with and without TNF, or interleukin-1, (IL-1,) stimulation. Results Synoviolin expression was increased in whole PB obtained from RA patients as compared with that from healthy controls and was significantly reduced early and late after infliximab treatment in responders, but in not nonresponders. Reduction in synoviolin expression was associated with reduced levels of markers of disease activity, including C-reactive protein levels. Nonresponders to infliximab therapy had significantly higher synoviolin expression at baseline as compared with responders, and this elevation persisted despite infliximab therapy. PB CD14+ monocytes expressed increased synoviolin levels compared with CD3+ lymphocytes, and TNF, or IL-1, induced a further increase in expression in CD3+ cells. TNF, or IL-1, induced sustained synoviolin expression in RA FLS. Conclusion Elevated PB levels of synoviolin were identified in circulating PB mononuclear cells and were associated with nonresponse to infliximab treatment. Sustained up-regulation of synoviolin by IL-1, and TNF, may contribute to prolonged survival of immune cells and dysregulated FLS proliferation, leading to RA chronicity. [source]

Major reduction in spinal inflammation in patients with ankylosing spondylitis after treatment with infliximab: Results of a multicenter, randomized, double-blind, placebo-controlled magnetic resonance imaging study

ARTHRITIS & RHEUMATISM, Issue 5 2006
Jürgen Braun
Objective To determine whether the effects of anti,tumor necrosis factor , (TNF,) in reducing the signs and symptoms of ankylosing spondylitis (AS) coincide with a reduction in spinal inflammation as detected by magnetic resonance imaging (MRI). Methods Pre- and postgadolinium T1 and STIR MR images of the spine were acquired at baseline and at week 24 in patients with AS who participated in a multicenter, randomized, double-blind, placebo-controlled study. Patients were randomly assigned at an 8:3 ratio to receive infusions of infliximab (5 mg/kg) or placebo at weeks 0, 2, and 6 and then every 6 weeks thereafter. MR images were obtained and evaluated independently by 2 readers who were blinded to the treatment allocation and time sequence of the images. Results A total of 194 patients in the infliximab group and 72 patients in the placebo group had evaluable images at baseline and week 24. About 80% of the patients had at least 1 active spinal lesion at baseline, as assessed by MRI. The improvement in the MRI Activity Score after 6 months was significantly greater in the patients who received infliximab (mean 5.02, median 2.72) than in those who received placebo (mean 0.60, median 0.0) (P < 0.001). Almost complete resolution of spinal inflammation was seen in most patients who received infliximab, irrespective of baseline activity. Conclusion Patients with AS who received infliximab therapy showed a decrease in spinal inflammation as detected by MRI, whereas those who received placebo showed persistent inflammatory spondylitis. [source]

The safety of infliximab, combined with background treatments, among patients with rheumatoid arthritis and various comorbidities: A large, randomized, placebo-controlled trial

ARTHRITIS & RHEUMATISM, Issue 4 2006
Rene Westhovens
Objective To assess the risk of serious infections following 22 weeks of infliximab therapy, and to further characterize the safety profile of infliximab in combination with background treatments during 1 year in patients with rheumatoid arthritis (RA) with various comorbidities. Methods Patients with active RA despite receiving methotrexate (MTX) were randomly assigned to receive infusions of placebo (group 1, n = 363), 3 mg/kg infliximab (group 2, n = 360), or 10 mg/kg infliximab (group 3, n = 361) at weeks 0, 2, 6, and 14. At week 22, patients in placebo group 1 began receiving 3 mg/kg infliximab, and patients in group 3 continued to receive an infliximab dose of 10 mg/kg. Patients in group 2 who failed to meet predefined response criteria received increasing doses of infliximab in increments of 1.5 mg/kg. Results At week 22, the relative risk of developing serious infections in groups 2 and 3, compared with group 1, was 1.0 (95% confidence interval [95% CI] 0.3,3.1, P = 0.995) and 3.1 (95% CI 1.2,7.9, P = 0.013), respectively. The incidence of serious adverse events was 7.8% in groups 2 and 3 compared with 7.5% in group 1. From week 22 to week 54, 11.8%, 9.9%, and 10.3% of patients in groups 1, 2, and 3, respectively, reported occurrences of serious adverse events. Through week 54, 1 patient in group 1, 2 patients in group 2, and 4 patients in group 3 developed active tuberculosis. Conclusion The risk of serious infections in patients receiving the approved infliximab dose of 3 mg/kg plus MTX was similar to that in patients receiving MTX alone. Patients receiving the unapproved induction regimen of 10 mg/kg infliximab plus MTX followed by a 10 mg/kg maintenance regimen had an increased risk of serious infections through week 22. [source]

Infliximab (Remicade?) in uveitis: a review

ACTA OPHTHALMOLOGICA, Issue 2009
A ABU EL ASRAR
Tumor necrosis factor (TNF)-, has been implicated as an important mediator in autoimmune ocular inflammatory disease pathogenesis as shown by animal studies and its detection in the ocular fluids of patients with uveitis. Blockade of TNF-, has emerged as one of the most promising therapies in autoimmune diseases including uveitis. Currently, there are three TNF-, antagonists: two monoclonal antibodies (infliximab and adalimumab) and a soluble receptor that binds soluble TNF-, (etanercept). Infliximab is a chimeric monoclonal antibody directed against TNF-,. It binds with high affinity to both the soluble and the membrane-bound TNF-, and inhibits a broad range of biologic activities of TNF-,. Binding to membrane TNF-, can mediate programmed cell death. Several studies reported that infliximab therapy was rapidly effective and safe treatment for refractory noninfectious uveitis including childhood uveitis and is indicated as rescue therapy for relapses of ocular inflammation or as maintenance therapy when conventional immunosuppression fails. It also allowed a reduction of corticosteroids and immunosuppressive drugs required to control the disease. However, repeated infusions are required to maintain long-term remission. Moreover, infliximab administration is costly and requires hospital admission. Adalimumab, fully humanized monoclonal anti- TNF-, antibody, was also found to be effective and safe therapy for the management of refractory noninfectious uveitis. Several studies reported that infliximab was more effective than etanercept in the treatment of refractory uveitis. Perhaps infliximab's ability to target membrane-bound TNF-, in addition to the soluble form may contribute to its increased efficacy in comparison with etanercept for uveitis. [source]