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Infliximab Treatment (infliximab + treatment)

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Selected Abstracts

Anti tumour necrosis-, therapy increases the number of FOXP3+ regulatory T cells in children affected by Crohn's disease

IMMUNOLOGY, Issue 2 2008
Ida Ricciardelli
Summary Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract. Its pathogenesis is not completely understood, though the prevailing model is that the intestinal flora drives a strong intestinal T helper 1 (Th1)/Th17 type immune response and inflammation in the genetically susceptible host. This leads to overly aggressive T-cell responses to normal bacteria causing tissue damage. Intestinal homeostasis and maintenance of tolerance to harmless antigens in the intestine has been shown to be maintained by CD4+ CD25+ T regulatory cells (Treg) in animal models of inflammatory bowel diseases. Here we investigated whether Infliximab, a chimeric monoclonal antibody directed against tumour necrosis factor (TNF)-, shown to be highly effective in the treatment of CD, has any effect on mucosal CD4+ CD25+ (FOXP3+) Tregs. Colonic mucosal biopsies from children with active Crohn's disease treated in vivo with Infliximab and controls were analysed to determine FOXP3 expression by immunofluorescence and reverse transcription,polymerase chain reaction. We observed that FOXP3+ T cells were significantly reduced in mucosa of CD patients with active disease compared with controls and restored to normal following Infliximab treatment. The frequency of FOXP3+ cells and mRNA expression was significantly increased in CD mucosa from patients treated in vivo with Infliximab compared with CD patients treated with conventional therapies. In conclusion, we show that Infliximab treatment does not solely neutralize soluble TNF-,, but also affects activation and possibly expansion of mucosal regulatory T cells. We suggest that anti TNF-, immunotherapy can also restore mucosal homeostasis in Crohn's disease. [source]

Infliximab treatment for Crohn's disease: One-year experience in a Dutch Academic Hospital

INFLAMMATORY BOWEL DISEASES, Issue 2 2002
Dr. Daan W. Hommes
Abstract The aim of this study was to report the 1-year clinical experience with infliximab treatment for Crohn's disease (CD) in the Netherlands. All 73 CD patients receiving infliximab infusions were prospectively followed during 1 year after the drugs' registration in the Netherlands. Clinical response and adverse events were assessed for both active luminal disease as well as fistulous disease. A total of 212 infusions were administered to 57 patients with active luminal CD and 16 patients with fistulous CD. The mean duration between infusions was 60 days. In 17% of patients, adverse events were recorded, of which one was serious. The response rate was 81% in active luminal CD and 87% in fistulous disease. Response rates were highest in patients receiving concomitant methotrexate as maintenance therapy. Steroids could successfully be tapered off in 73% of responding luminal CD patients and 100% of responding CD patients with fistulae. Eleven patients showed a loss of response to continuous infliximab readministration. Our clinical experience with infliximab for active luminal and fistulous CD showed that the administration is safe, effective, and has high steroid-sparing efficacy. Higher response rates were seen with methotrexate as concomitant medication. [source]

Infliximab treatment for symptomatic Crohn's disease strictures

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2009
A.-L. PELLETIER
Summary Background, Some reports have suggested that infliximab may induce obstructive symptoms and, although there is no firm evidence, it is usually contra-indicated in-patients with Crohn's disease (CD) and strictures. Aims, To evaluate the effect of infliximab on symptomatic strictures of the small intestine in CD and to identify predictive factors of clinical response. Methods, This retrospective study included symptomatic patients treated with infliximab after conventional treatment had failed. The short-term (week 8) and long-term results were classified according to predefined criteria as complete, partial response, or failure. Results, Before infliximab, 18 patients had complete obstruction or intermittent chronic abdominal pain. Fourteen patients were treated by corticosteroids and 13 received immunosuppressive drugs. At week 8, complete, partial response and failure were observed in 10, 7 and 1 patients, respectively. Fourteen patients continued maintenance infliximab treatment after week 8. During the most recent evaluation (median follow-up: 18 months), 8 patients were on maintenance infliximab treatment; only eight were still on prednisone; there were five complete responses, 10 partial responses and three failures. Initiating prednisone or increasing its dosage was the only factor associated with a short-term complete response. Conclusions, Infliximab may be effective in patients with symptomatic strictures from CD, and should be tested before considering surgery. [source]

Antinuclear antibodies following infliximab treatment in patients with rheumatoid arthritis or spondylarthropathy

ARTHRITIS & RHEUMATISM, Issue 4 2003
Leen De Rycke
Objective To investigate the effect of infliximab treatment on antinuclear antibodies (ANAs), anti,double-stranded DNA (anti-dsDNA), antinucleosome, antihistone, and anti,extractable nuclear antigen (anti-ENA) antibodies in rheumatoid arthritis (RA) and spondylarthropathy (SpA) patients. Methods Sera from 62 RA and 35 SpA patients treated with infliximab were tested at baseline and week 30 (RA group) or week 34 (SpA group). ANAs were tested by indirect immunofluorescence (IIF) on HEp-2 cells. Anti-dsDNA antibodies were detected by IIF on Crithidia luciliae and by enzyme-linked immunosorbent assay (ELISA) and were further isotyped with ,, ,, and , chain,specific conjugates at various time points. Antinucleosome antibodies were tested by ELISA. Antihistone and anti-ENA antibodies were detected by line immunoassay. Results Initially, 32 of 62 RA patients and 6 of 35 SpA patients tested positive for ANAs. After infliximab treatment, these numbers shifted to 51 of 62 (P < 0.001) and 31 of 35 (P < 0.001), respectively. At baseline, none of the RA or SpA patients had anti-dsDNA antibodies. After infliximab treatment, 7 RA patients (P = 0.016) and 6 SpA patients (P = 0.031) became positive for anti-dsDNA antibodies. All 7 anti-dsDNA,positive RA patients had IgM and IgA anti-dsDNA antibodies. Three of the 6 anti-dsDNA,positive SpA patients had IgM and IgA anti-dsDNA antibodies, and 2 had IgM anti-dsDNA antibodies alone. In both diseases, the IgM anti-dsDNA antibodies appeared before the IgA anti-dsDNA antibodies. During the observation period, no IgG anti-dsDNA antibodies or lupus symptoms were observed. The development of antinucleosome, antihistone, or anti-ENA antibodies following infliximab treatment was observed in some patients, but the numbers were not statistically significant. Conclusion Infliximab treatment may induce ANAs, and especially IgM and IgA anti-dsDNA antibodies, in RA and SpA patients. However, no anti-dsDNA IgG antibodies or lupus symptoms were observed during the period of observation in this study, and the development of antinucleosome, antihistone, or anti-ENA antibodies was not statistically significant. These observations do not exclude potential induction of clinically significant lupus in the long term, and further followup is therefore mandatory. [source]

Infliximab treatment results in significant improvement in the quality of life of patients with severe psoriasis: a double-blind placebo-controlled trial

BRITISH JOURNAL OF DERMATOLOGY, Issue 5 2005
S.R. Feldman
Summary Background, Psoriasis is a chronic disease that significantly diminishes the health-related quality of life (HRQOL). Infliximab is a chimeric, tumour necrosis factor , monoclonal antibody that has been shown to improve the signs and symptoms of plaque psoriasis. Objectives, The objective of this study was to evaluate the effect of infliximab induction therapy on the HRQOL of patients with severe plaque psoriasis. Methods, In this double-blind, placebo-controlled trial, 249 patients were randomly assigned to receive intravenous infusions of 3 or 5 mg kg,1 of infliximab or placebo and were treated at weeks 0, 2 and 6. Patients completed the Dermatology Life Quality Index (DLQI) at baseline and week 10. Results, Infliximab induction therapy resulted in a substantial improvement in HRQOL. At week 10, patients in the infliximab 3- and 5-mg kg,1 groups showed a median percentage improvement in DLQI scores of 84·0% and 91·0%, respectively, compared with 0% in the placebo group (P < 0·001). The median decrease from baseline in DLQI score at week 10 was 8·0 and 10·0 for the 3 and 5 mg kg,1 infliximab groups, respectively, compared with 0 in the placebo group (P < 0·001). Thirty-three per cent and 40% of patients in the 3 and 5 mg kg,1 infliximab groups, respectively, had a DLQI score of 0 at week 10, compared with 2% in the placebo group (P < 0·001). There was a strong correlation between the percentage change from baseline at week 10 in Psoriasis Area and Severity Index (PASI) scores and the percentage change in DLQI scores during the same period (Spearman's correlation, 0·61, P < 0·001). When the infliximab and placebo treatment groups were combined, patients with at least 75% improvement in PASI scores between baseline and week 10 had a greater mean improvement in DLQI scores (81%) than those with 50,75% improvement in PASI during the same period (60%). Conclusions, Infliximab induction therapy resulted in significant improvement in HRQOL in patients with severe psoriasis. [source]

Lewis and Sumner syndrome following infliximab treatment in Crohn's disease: A report of 2 cases

INFLAMMATORY BOWEL DISEASES, Issue 9 2010
Stephane Nancey MD
First page of article [source]

Splenic function and IgM-memory B cells in Crohn's disease patients treated with infliximab

INFLAMMATORY BOWEL DISEASES, Issue 5 2008
Antonio Di Sabatino MD
Abstract Background: Under experimental chronic inflammation, tumor necrosis factor (TNF)-, plays a role in damaging spleen marginal zone. This latter has a crucial function in mounting B cell-dependent immune responses against infections by encapsulated bacteria. In Crohn's disease (CD), a chronic inflammatory disorder where TNF-, is centrally involved, impaired splenic function may increase the susceptibility to bacterial infections. On this basis, we aimed to investigate the influence of anti-TNF therapy on splenic function in CD patients. Methods: Peripheral blood samples were obtained from 15 CD patients before and after treatment with infliximab administered at weeks 0, 2, and 6 at a dose of 5 mg/kg. Counting of erythrocytes with membrane abnormalities (pitted red cells) was used as an indicator of splenic function. Multicolor flow cytometry was performed to analyze circulating B cells. Results: A substantial clinical improvement in 10 of the 15 CD patients was associated with a significant reduction of pitted red cells (from median 6.0% to 3.6%; P < 0.01) after 10 weeks of treatment. In responder patients the improvement of splenic function was accompanied by a parallel increase of circulating IgM-memory B cells (from median 6.9% to 13.3%; P < 0.005). Splenic function was not ameliorated in nonresponder patients. Conclusions: Splenic function improved in CD patients who responded to infliximab and was accompanied by a concomitant restoration of the IgM-memory B cell pool responsible for the protection against encapsulated bacteria. Restoration of splenic function after infliximab treatment is intriguing and requires further investigation. (Inflamm Bowel Dis 2008) [source]

Infliximab and the risk of latent viruses reactivation in active Crohn's disease

INFLAMMATORY BOWEL DISEASES, Issue 7 2007
Alessandro Lavagna MD
Abstract Background: Infliximab is used for refractory Crohn's disease but there are concerns regarding long-term safety. Recently, JC-polyomavirus (JCV) was studied after 3 cases of progressive multifocal leukoencephalopathy (PML) were found after treatment with natalizumab. The aim of this study was to investigate the short-term effect of infliximab on reactivation of several harmful latent viruses. Methods: Sixty consecutive patients scheduled for infliximab induction course were prospectively enrolled. Blood samples were taken before each infliximab infusion at 0, 2, 6, and 14 weeks. Specific polymerase chain reaction (PCR) analyses were performed to detect JCV, Epstein,Barr virus (EBV), human herpes virus-6, (HHV-6), -7, -8, and cytomegalovirus (CMV). Results: Indications to infliximab were luminal and fistulizing disease in 49 and 15 cases, respectively. Clinical improvement and remission were achieved in 54 (90%) and 39 (65%) of patients, respectively, at 6 weeks. No patient was JCV-positive at any timepoint. EBV serology was positive for 59/60 patients (98%); EBV-PCR tests were transiently positive (>40 copies/105 Peripheral blood mononuclear cells, PBMC) in 4 (7%) patients after infliximab, but in each case were negative at subsequent timepoints. All patients were negative for HHV-6, -7, and -8 at all timepoints. CMV serology was positive in 42 patients (70%), but no CMV-PCR-positive patient was observed. There was no association between concomitant treatments or clinical characteristics and viral status. Conclusions: Our results support the safety of short-term infliximab treatment with respect to latent virus reactivation. The long-term effects of infliximab, particularly for the issue of lymphoproliferative disorders, warrants further studies with larger populations, but so far data are reassuring. (Inflamm Bowel Dis 2007) [source]

Long-term oral tacrolimus therapy in refractory to infliximab fistulizing Crohn's disease.

INFLAMMATORY BOWEL DISEASES, Issue 1 2005
A Pilot Study
Abstract Aims: To evaluate efficacy and safety of oral tacrolimus in cases of fistulizing Crohn's disease (FCD), which is refractory to conventional therapy including infliximab. Methods: Patients with fistulas, previously and unsuccessfully treated with all conventional therapy (i.e., antibiotics, azathioprine, or 6-mercaptopurine and infliximab), were enrolled in a prospective, uncontrolled, open-label study of long-term treatment with oral tacrolimus (0.05 mg/kg every12 h). The evaluation of the clinical response was complemented by use of the perianal Crohn's disease activity index (PCDAI) and magnetic resonance imaging-based score (MRS) with determined periodicity. Results: Ten patients were included in the study (enterocutaneous fistula, 3 patients; perianal fistula, 4 patients; rectovaginal fistula, 3 patients) with 6 to 24 months of follow-up. Five patients were steroid-dependent, and 4 patients needed maintenance treatment with immunosuppressant agents. Four patients (40%) achieved complete clinical responses, which were verified by PCDAI and MRS. Five patients (50%) achieved partial responses (i.e., important decreases in fistula drainage, size, discomfort, and PCDAI/MRS values). Decreases in both the PCDAI and MRS were statistically significant (P < 0.05). All steroid-dependent patients stopped therapy with prednisone, and concomitant immunosuppressive therapy was tapered. The response was maintained, and no new flare-up of the disease was observed. Only mild adverse events were detected (1 patient withdrew from treatment due to headache), and no case of nephrotoxicity or diabetes was detected. One patient had received no benefit from therapy after 6 months. Conclusions: Oral tacrolimus could be an effective and safe treatment for patients with FCD, even if there has been no response to infliximab treatment. Randomized studies are needed to compare oral tacrolimus with infliximab in terms of efficacy, safety, and costs. [source]

Colonic sarcoidosis, infliximab, and tuberculosis: A cautionary tale

INFLAMMATORY BOWEL DISEASES, Issue 4 2004
Prof. Dario Sorrentino MD
Abstract The antitumor necrosis factor, infliximab, has been recently shown to be effective in refractory sarcoidosis including the intestinal form of this disease. We have tried this therapy in a 55-year-old woman under immunosuppressive therapy for longstanding sarcoidosis presenting with abdominal pain apparently caused by a colonic localization of the disease. The latter diagnosis was based, as recommended, on the presence of nonnecrotizing granulomas in mucosal biopsies, the presence of systemic disease, and the careful exclusion of other granulomatous diseases, including tuberculosis. After the first IV infusion (10 mg/kg BW), she quickly improved, but the wellbeing lasted approximately 4 weeks. She then received another dose of infliximab, but she soon developed low-grade fever and weakness and shortly succumbed of miliary tuberculosis. Likely, infliximab precipitated a pre-existing mycobacterial infection of the intestine. Given the likelihood of underdiagnosing intestinal tuberculosis,and the risks associated with infliximab treatment,this case suggests that this drug should be used with extreme caution, if at all, when a diagnosis of colonic sarcoidosis is suspected. [source]

Infliximab treatment for Crohn's disease: One-year experience in a Dutch Academic Hospital

Effect of concurrent elemental diet on infliximab treatment for Crohn's disease

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 7 2006
Torao Tanaka
Abstract Background:, Infliximab and elemental diet (ED) have been shown to be effective in the management of Crohn's disease. However, few experiences have been reported regarding their combination therapy. The aim of the present study was to investigate the efficacy and safety of infliximab in Japanese patients, the first such study in Asia, as well as the effect of concomitant ED. Methods:, One hundred and ten consecutive patients receiving infliximab were followed up to week 16 after the last infusion, and clinical response and primary outcome were collected. A response was defined as a reduction in Harvey,Bradshaw Index for inflammatory disease and closure of fistula in fistulizing disease. Results:, Out of 75 inflammatory and 35 fistulizing disease patients, 68 (90.7%) and 25 (71.4%) responded at week 4, and 38 (50.7%) and 14 (40.0%) continued to respond until week 16, respectively. Interestingly, inflammatory disease patients with concurrent ED had a significantly higher response rate at week 16 (68.4%) than those without ED (32.4%, P = 0.0026). The effects of ED were independent of the usage of azathioprine and smoking habit. Conclusions:, Infliximab was clinically useful in the treatment of Crohn's disease in Japanese patients as well as in those in Western countries. The efficacy of concurrent ED was suggestive and should be confirmed in a randomized controlled study. [source]

Clinical trial: colectomy after rescue therapy in ulcerative colitis , 3-year follow-up of the Swedish-Danish controlled infliximab study

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2010
A. Gustavsson
Aliment Pharmacol Ther 2010; 32: 984,989 Summary Background, The long-term efficacy of infliximab as rescue therapy in steroid-refractory ulcerative colitis is not well described. Aim, To examine the long-term efficacy of infliximab as a rescue therapy through a 3-year follow-up of a previous placebo-controlled trial of infliximab in acute steroid-refractory ulcerative colitis. Method, In the original study, 45 patients were randomized to a single infusion of infliximab 5 mg/kg or placebo, and at 3 months, 7/24 patients given infliximab were operated vs. 14/21 patients given placebo. Three years or later, patients were asked to participate in a clinical follow-up. Results, Another seven patients underwent colectomy during follow-up: five in the infliximab group and two in the placebo group. After 3 years, a total of 12/24 (50%) patients given infliximab and 16/21 (76%) given placebo (P = 0.012) had a colectomy. None of eight patients in endoscopic remission at 3 months later had a colectomy compared with 7/14 (50%) patients who were not in remission (P = 0.02). There was no mortality. Conclusion, The benefit of rescue therapy with infliximab in steroid-refractory acute ulcerative colitis remained after 3 years. The main advantage of infliximab treatment occurred during the first 3 months, whereas subsequent colectomy rates were similar in the two groups. Mucosal healing at 3 months influenced later risk of colectomy. [source]

Meta-analysis: pre-operative infliximab treatment and short-term post-operative complications in patients with ulcerative colitis

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2010
Z. YANG
Aliment Pharmacol Ther,31, 486,492 Summary Background, Infliximab was approved for use in ulcerative colitis in recent years. It has been debated if infliximab increases the risk of post-operative complications in patients with ulcerative colitis. Aim, To perform a meta-analysis that examines the relationship between preoperative infliximab treatment and short-term post-operative complications in patients with ulcerative colitis. Methods, We searched the PubMed and MEDLINE databases to identify observational studies on the impact of pre-operative infliximab use on short-term post-operative complications in ulcerative colitis. Infectious complications mainly included wound infection, sepsis and abscess, whereas non-infectious complications included intestinal obstruction, thromboembolism and gastrointestinal haemorrhage. Pooled odds ratios (ORs) were calculated for each relationship. Results, A total of 5 studies and 706 patients were included in our meta-analysis. Overall, we did not find a strong association between pre-operative treatment of infliximab and short-term infectious [OR 2.24, 95% confidence interval (CI) 0.63,7.95] or non-infectious (OR 0.85, 95% CI 0.50,1.45) post-operative complications in ulcerative colitis patients. On the contrary, we discovered that pre-operative infliximab use increased short-term total post-operative complications (OR 1.80, 95% CI 1.12,2.87). Conclusions, Pre-operative infliximab use increased the risk of short-term post-operative complications. Subgroup analysis is underpowered to assess the nature of these complications but shows a trend towards increased post-operative infection. [source]

Tumour necrosis factor antagonists and inflammatory bowel diseases: a national practice survey

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2009
A. OUSSALAH
Aliment Pharmacol Ther,30, 854,863 Summary Background, Although the use of tumour necrosis factor (TNF) antagonists is increasingly codified, several unresolved issues remain. Aim, To conduct a French national survey on TNF antagonists use in inflammatory bowel disease (IBD). Methods, A postal questionnaire was sent to all French gastroenterologists among whom 450 prescribe TNF antagonists for IBD. Only anti-TNF prescribers were invited to respond. Results, A total of 333 questionnaires could be analysed, which represented a rate of survey completeness of 74%. Scheduled maintenance infliximab treatment was prescribed by 92% of gastroenterologists. In Crohn's disease in remission after 1 year of TNF antagonists, 77.4% of physicians continued treatment. In luminal Crohn's disease, 97% of hospital practitioners introduced infliximab as first-line anti-TNF therapy vs. 78% of physicians with nonhospital activity (P = 0.002); only 22.5% of gastroenterologists opted for adalimumab as first-line therapy. In Crohn's disease in remission after 6 months of azathioprine in combination with infliximab, 63.8% of practitioners discontinued azathioprine. In case of pregnancy during anti-TNF treatment, 35.1% of physicians discontinued therapy at the time of conception and did not administer anti-TNF therapy during pregnancy. Conclusions, The attitudes of French gastroenterologists generally reflect the recommendations regarding the use of anti-TNF and concomitant immunosuppressive therapy in IBD. [source]

Infliximab treatment for symptomatic Crohn's disease strictures

Early changes in rectal nitric oxide and mucosal inflammatory mediators in Crohn's colitis in response to infliximab treatment

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2007
T. LJUNG
SUMMARY Background Treatment with tumor necrosis factor-, monoclonal antibody (infliximab) reduces clinical activity and intestinal inflammation in Crohn's disease. Aim To study the time-course of the effects of infliximab with reference to mucosal cytokine and inducible nitric oxide synthase expression. Methods Thirty-two patients with Crohn's disease were treated with single dose infliximab (5 mg/kg). Disease activity was assessed days 1, 3, 7 and 28 using Harvey,Bradshaw index. Rectal nitric oxide levels were determined and rectal biopsies collected before treatment, 1 h after infusion and on days 3, 7 and 28. Immunohistochemical staining against inducible nitric oxide synthase, tumor necrosis factor-,, interleukin-1, and interferon-, were performed. Results Clinical response was seen in 14 patients with down-regulation of global immunohistochemistry expression, reaching nadir day 3. Rectal nitric oxide was increased at baseline (3578 ± 1199 parts per billion, ppb) compared with controls (89 ± 13 ppb) (P < 0.001). In patients with clinical response, rectal nitric oxide decreased from 3926 ± 1687 ppb to 1050 ± 428 ppb day 28 (P < 0.05). Conclusions Down-regulation of mucosal inflammatory mediators occurs after infliximab. Rectal nitric oxide levels parallel down-regulation of inducible nitric oxide synthase, tumor necrosis factor-,, interleukin-1, and interferon-, and may serve as a quantitative biomarker of intestinal inflammation. [source]

Infliximab regulates lamina propria T lymphocytes in patients with Crohn's disease

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2006
O. WATANABE
Summary Background and Aims The immune system is a major determinant of the pathophysiological inflammation, which may lead to gastrointestinal mucosal injury in patients with Crohn's disease. Cytokines such as tumour necrosis factor-alpha are well-known mediators of the immune system, and treatment with a chimeric anti-tumour necrosis factor-alpha antibody (infliximab) has been shown to be highly effective in patients with Crohn's disease. Recent evidence indicates that infliximab induces apoptosis in lamina propria T lymphocytes in these patients. To better understand the mechanisms of infliximab's effect on gastrointestinal inflammation, we investigated changes in the serum level of cytokines after treatment in these patients, and the effect of infliximab in inducing the apoptosis of T lymphocytes. Methods Thirteen patients with Crohn's disease were treated with infliximab at a dosage of 5-mg/kg body weight. Clinical response was evaluated using the Crohn's Disease Activity Index, and serum soluble interleukin-2 receptor, interleukin-6, tumour necrosis factor-alpha levels were analysed by enzyme-linked immunosorbent assay at 0 and 2 weeks after treatment. Apoptosis of peripheral and lamina propria T lymphocytes after culture with infliximab was detected by flow cytometry. Results Crohn's Disease Activity Index decreased in 12 of 13 patients, and serum soluble interleukin-2 receptor, interleukin-6 and tumour necrosis factor-alpha levels decreased in most patients after treatment with infliximab. Tumour necrosis factor-alpha level before treatment in the six patients in whom Crohn's Disease Activity Index decreased by more than 70 was <5 ng/mL. Infliximab induced the apoptosis of lamina propria but not of peripheral T lymphocytes. Conclusion These findings suggest that a low level of serum tumour necrosis factor-alpha is an indicator for infliximab treatment. The induction of apoptosis of lamina propria T lymphocytes by infliximab may be an important mechanism of its anti-inflammatory effect in patients with Crohn's disease. [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]

Documented tuberculin skin testing among infliximab users following a multi-modal risk communication interventions,

PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 1 2006
Deborah Shatin PhD
Abstract Purpose Following its licensure, tuberculosis (TB) was reported as a potential adverse effect of infliximab. Subsequently, the product circular was changed to recommend tuberculin skin testing before patients received infliximab, which was reinforced by several risk communication efforts. The aim of this study was to evaluate patterns and predictors of documented tuberculin skin testing in patients before and after manufacturer, federal, and academic risk communications. Methods Patients administered infliximab were identified from 11 health plans located throughout the United States, and claims data were examined to determine whether the patients had received a tuberculin skin test. Patients were divided into three cohorts depending on the timing of their first infliximab treatment in relation to the risk communication efforts. Results The overall tuberculin skin testing rate doubled from 15.4% in the first cohort to 30.9% in the last cohort, while the rate of pre-infliximab treatment testing increased from 0 to 27.7% (Chi-squared test for trend, p,<,0.0001 for both). Tuberculin skin testing rates were significantly higher in women, those with a diagnosis of rheumatoid or psoriatic arthritis, and those with a rheumatologist as prescriber. After multivariable analysis, only rheumatologist remained significantly associated with tuberculin skin testing. Conclusions Although the tuberculin skin testing rate was relatively low overall, tuberculin skin testing doubled over 30 months of ongoing risk communication efforts and under ascertainment likely occurred. We also found variation in the tuberculin skin testing rate associated with physician specialty. This study demonstrates a significant change in patient care following risk communication efforts. Copyright © 2005 John Wiley & Sons, Ltd. [source]

The relationship between synovial lymphocyte aggregates and the clinical response to infliximab in rheumatoid arthritis: A prospective study,,

ARTHRITIS & RHEUMATISM, Issue 11 2009
Ruth Klaasen
Objective Some patients with rheumatoid arthritis (RA) exhibit lymphocyte aggregates in the synovium. This study was undertaken to address whether the presence of lymphocyte aggregates before treatment could serve as a biomarker for the clinical response to tumor necrosis factor (TNF) blockade, and to confirm whether the aggregation of synovial lymphocytes is reversible after anti-TNF treatment. Methods Synovial tissue biopsy samples were obtained from 97 patients with active RA before the initiation of infliximab treatment. Lymphocyte aggregates in the synovial tissue were counted and also graded for size. Logistic regression analysis was performed to identify whether the presence of lymphocyte aggregates could be a predictor of the clinical response at week 16. Furthermore, the effects of TNF blockade on lymphocyte aggregates were compared between patients with RA and patients with psoriatic arthritis (PsA). Results Fifty-seven percent of RA synovial tissue samples contained lymphocyte aggregates, and 32% of the patients had large aggregates. Aggregates were found in 67% of clinical responders compared with 38% of nonresponders. The presence of aggregates at baseline was a highly significant predictor of the clinical response to anti-TNF treatment (R2 = 0.10, P = 0.008). Positivity for lymphocyte aggregates increased the power to predict the clinical response (R2 = 0.29), when analyzed in a prediction model that included baseline disease activity evaluated by the Disease Activity Score in 28 joints, anti,cyclic citrullinated peptide antibody positivity, and synovial TNF, expression. There was a reduction in lymphocyte aggregates after anti-TNF antibody therapy in both RA and PsA. Conclusion RA patients with synovial lymphocyte aggregates have, on average, a better response to infliximab treatment than those with only diffuse leukocyte infiltration. Moreover, the aggregation of synovial lymphocytes is reversible after anti-TNF antibody treatment. [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]

Antinuclear antibodies following infliximab treatment in patients with rheumatoid arthritis or spondylarthropathy

Down-regulation of the nonspecific and antigen-specific T cell cytokine response in ankylosing spondylitis during treatment with infliximab

ARTHRITIS & RHEUMATISM, Issue 3 2003
Jianxiang Zou
Objective Treatment of active ankylosing spondylitis (AS) with the monoclonal tumor necrosis factor , (TNF,) antibody infliximab is highly clinically effective. This study was undertaken to investigate the precise mechanism of action of anti-TNF, treatment in AS. Methods Cytokine expression of CD4+ and CD8+ T cells was investigated before and 6 and 12 weeks after the start of treatment in 10 patients treated with infliximab, and before and after 6 weeks of treatment and 6 weeks after placebo was switched to infliximab in 10 patients treated initially with placebo. Peripheral blood mononuclear cells (PBMCs) were stimulated for 6 hours either nonspecifically with phorbol myristate acetate (PMA)/ionomycin or antigen specifically with a pool of 46 overlapping 18-mer peptides derived from the G1 domain of aggrecan. Cells were stained for T cell surface markers CD4 and CD8 and for the intracellular cytokines interferon-, (IFN,), TNF,, interleukin-4 (IL-4), and IL-10. Positive cells were quantified by flow cytometry. For monocyte-derived cytokines, PBMCs were stimulated with lipopolysaccharide (LPS) for 18 hours and TNF, and IL-10 in the supernatant were measured by enzyme-linked immunosorbent assay. Results Compared with baseline, infliximab treatment induced a significant decrease at 12 weeks in the number of CD4+ and CD8+ T cells that were positive for IFN, and TNF, upon PMA/ionomycin stimulation (P = 0.005). A significant reduction had already begun to occur at 6 weeks. No change in the percent IFN, or TNF, positivity among CD4+ and CD8+ subpopulations was observed after 6 weeks in patients treated with placebo. However, when these patients began infliximab treatment after 6 weeks of receiving placebo, there was a similar significant decrease in IFN, and TNF, production by CD4+ and CD8+ T cells (P < 0.05). Furthermore, infliximab treatment induced a significant reduction in the number of IFN,+ and TNF,+ CD8+ T cells (P = 0.005 at week 6 and week 12) after antigen-specific in vitro stimulation with G1-derived peptides. Between-group analysis showed that the change in the expression of IFN, and TNF, in both CD4+ and CD8+ T cells was significantly different between the infliximab and placebo groups (P = 0.001 for all variables). There was no change in the number of IL-10+ or IL-4+ T cells during treatment. No significant change in the production of TNF, and IL-10 upon in vitro stimulation of PBMCs with LPS was detectable during infliximab treatment. Conclusion Infliximab down-regulates both IFN, and TNF, secreted by T cells but does not induce a change in cytokines produced by monocytes during 3 months of treatment. This is likely to be a relevant mechanism for the clinical efficacy of this therapy. [source]

Regression of necrotizing scleritis in Wegener's granulomatosis after infliximab treatment

ACTA OPHTHALMOLOGICA, Issue 3 2010
Matti Kontkanen
No abstract is available for this article. [source]