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PubMed2006

The TNF/ADAM 17 system: implication of an ADAM 17 haplotype in the clinical response to infliximab in Crohn's disease.

Infliximab, a chimeric anti-tumour necrosis factor (TNF)-alpha antibody induces a clinical response in 70% of Crohn's disease patients and the response to infliximab therapy could be partially determined by genetic factors. The implication of both transmembrane and soluble forms of the TNF-alpha in the mechanism of action of infliximab has been demonstrated. The aim of our work was first to perform a complete study of TNF variants role in the response to infliximab in Crohn's disease. Secondly, considering the role of ADAM 17 in TNF-alpha shedding, the ADAM 17 locus was also studied. The response to infliximab was evaluated in 222 Caucasian Crohn's disease patients with a luminal (n=160) or fistulizing (n=62) form of the disease. Clinical and biological response evaluation was based on the Crohn's Disease Activity Index score and C-reactive protein level evolutions, respectively. The entire TNF gene was sequenced on the complete cohort. Twelve single nucleotide polymorphisms spanning the ADAM 17 locus were studied and haplotypes rebuilt. A clinical response was observed in 64% of the patients and biological response in 77.1% of patients. No association was found between the TNF gene and the response to infliximab. One haplotype in the ADAM 17 region was associated with a clinical response to infliximab in CD patients (adjusted P=0.045). In conclusion, our results exclude, with a reasonable power, an implication of the TNF gene in the response to infliximab in Crohn's disease, but reveal a potential role of the ADAM 17 gene in this response.

ADAM Proteins↗
PubMed2003

Infliximab for hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic disease characterized by significant morbidity. Current medical therapies are only minimally effective at treating the disease. Infliximab is a chimeric monoclonal antibody with high affinity for tumour necrosis factor (TNF)-alpha. TNF-alpha is known to induce proinflammatory cytokines and may play an important role in the therapy of a number of disparate inflammatory disorders. Infliximab has shown promise for the therapy of rheumatoid arthritis and psoriasis. OBJECTIVES: Retrospectively to evaluate the effectiveness of infliximab for the treatment of HS. METHODS: A retrospective chart review was performed for patients who received infliximab at the University of Miami Department of Dermatology. Patients were contacted and asked retrospectively to rate their disease activity immediately prior to and after therapy. RESULTS: Patients' self-reported disease activity scores were significantly decreased (P = 0.0001, paired t-test) following infliximab infusion. This correlated with physician-observed clinical improvement. CONCLUSIONS: Infliximab is a promising agent for the treatment of HS. These initial results suggest that infliximab is associated with objective and subjective improvement in HS. Further controlled studies of the efficacy of infliximab and its effect on the course of the disease are warranted.

Adult↗
PubMed2003

Magnetic resonance imaging of the effects of infliximab on perianal fistulizing Crohn's disease.

OBJECTIVES: Although the clinical efficacy of infliximab as measured by closure of fistulas in Crohn's disease has been demonstrated, its influence on the inflammatory changes in the fistula tracks is less clear. The aim of the present study was to assess the behavior of perianal fistulas before and after infliximab treatment. METHODS: Magnetic resonance imaging (MRI) and clinical evaluation were performed in a total of 18 patients before and after treatment with infliximab. An MRI-based score of perianal Crohn's disease severity was developed using both criteria of local extension of fistulas (complexity, supralavetoric extension, relation to the sphincters and of active inflammation (T2 hyperintensity, presence of cavities/abscesses, and rectal wall involvement). RESULTS: The MRI score was reliable in assessing the fistula tracks, with a good interobserver concordance (p < 0.001). Fistula tracks with signs of active inflammation were found in all 18 patients at baseline and collections in seven. After short-term infliximab treatment, active tracks persisted in eight of 11 patients who had clinically responded to infliximab. After long-term (46 wk) infliximab therapy, MRI signs of active track inflammation had resolved in three of six patients. CONCLUSIONS: We have developed an MRI-based score of perianal Crohn's disease severity to assess the anatomical evolution of Crohn's fistulas. Our study demonstrates that despite closure of draining external orifices after infliximab therapy, fistula tracks persist with varying degrees of residual inflammation, which may cause recurrent fistulas and pelvic abscesses. Whether complete fistula fibrosis occurs over time with repeated infliximab infusions needs further study.

Adult↗
PubMed2003

The effects of infliximab maintenance therapy on health-related quality of life.

OBJECTIVES: The ACCENT I study evaluated the long term effects of infliximab as maintenance therapy for patients with Crohn's disease. Health-related quality of life (HRQL) was also assessed in the trial. METHODS: In ACCENT I, a total of 573 patients received a single infusion of 5 mg/kg infliximab at baseline. After assessment of response at wk 2, patients were randomly assigned repeat infusions of placebo at wk 2 and 6 and then every 8 wk thereafter until wk 46 (single dose), repeat infusions of 5 mg/kg of infliximab at the same time points (5 mg/kg maintenance), or 5 mg/kg of infliximab at wk 2 and 6 followed by 10 mg/kg (10 mg/kg maintenance). HRQL analyses presented include the 335 patients classified as wk-2 responders. The treatment regimens were compared with regard to their change from baseline in the IBDQ and Short Form-36 (SF-36) scores. RESULTS: Baseline scores indicated substantial impairment in HRQL. Throughout the study, all IBDQ and SF-36 scores were improved at all time points compared to baseline. After wk 10 and through wk 54, these improvements were greater in the two infliximab maintenance groups than in the single-dose group. The mean change from baseline to wk 54 in total IBDQ was greater in the 5-mg/kg maintenance group (22.1, p < 0.05) and 10-mg/kg maintenance group (30.2, p < 0.001) than in the single-dose group (8.9). Similarly, the mean change from baseline to wk 54 in the PCS of the SF-36 was greater in the 5-mg/kg maintenance group (6.1, p < 0.05) and 10-mg/kg maintenance group (7.2, p < 0.01) than in the single-dose group (2.5). CONCLUSIONS: Infliximab therapy provides substantially improved HRQL as measured by both the disease-specific IBDQ and the generic SF-36. A maintenance regimen of either 5 mg/kg or 10 mg/kg of infliximab is more effective than a single 5-mg/kg infliximab infusion in sustaining this benefit.

Adult↗
PubMed2001

Successful treatment of a small cohort of patients with adult onset of Still's disease with infliximab: first experiences.

OBJECTIVE: To test the efficacy of infliximab in the treatment of patients with severe and active adult onset Still's syndrome (AOSD) despite conventional immunosuppressive therapy. PATIENTS AND METHODS: Six patients with the diagnosis of AOSD according to the Yamagushi criteria of 1992 were treated with infliximab. All patients had severe disease with high clinical and serological activity. Patients were treated initially with high dose steroids or more intensive immunosuppressive therapy. Two patients had a history of multiple disease modifying antirheumatic drug (DMARD) treatments. One patient had a history of three years of AOSD with fever, chills, pleural and pericardial effusions, and hepatosplenomegaly. Despite these treatments, he developed increasing serological signs of inflammation and arthritis of both hips and peripheral joints. Another patient had a history of five years of AOSD with oligoarthritis, myalgias, and recurrent fever despite multiple DMARD treatment, including cyclophosphamide pulse therapy. Our patients with AOSD presented with massive polyarthralgias, polyarthritis, splenomegaly or hepatomegaly, the typical rash, sore throat, weight loss, serositis, continuing fever, leucocytosis, and raised C reactive protein (CRP), erythrocyte sedimentation rate (ESR), and ferritin levels. Four patients with early onset of the disease, fulfilling the diagnostic criteria for AOSD and a clinical and serological high disease activity, were included in our pilot study without any further DMARD treatment apart from the initial steroid treatment. Reduction of established treatment, mainly with steroids, caused a relapse of the disease in all our patients. Patients then received 3-5 mg/kg infliximab on weeks 0, 2, and 6, continuing with intervals of 6-8 weeks depending on the patient's individual disease activity. RESULTS: In all patients, fever, arthralgias, myalgias, hepatosplenomegaly, and the rash resolved after the first courses of treatment with infliximab. All serological variables (CRP, ESR, hyperferritinaemia) returned to normal. After three courses of infliximab infusions, splenomegaly could not be detected in any of our patients. One caused by hip postarthritic osteoarthrosis, requiring hip replacement. After three courses of treatment with infliximab, splenomegaly could not be detected in any of our patients. Up to now, our patients have received infliximab infusion treatment for between five and 28 months. Throughout this period all patients have continued to benefit from this treatment, with improvement in their clinical symptoms, joint counts, and serological disease activity. One of our patients had a moderate infusion reaction during the second treatment. The infusion was discontinued for one hour and then was resumed with no further problems. CONCLUSION: The disease improved remarkably in all six patients with AOSD after treatment with infliximab, also in the early stage of AOSD. These preliminary data suggest the potential therapeutic benefit of anti-tumour necrosis factor alpha treatment in AOSD.

Acute Disease↗
PubMed2004

Chronic hepatitis B reactivation following infliximab therapy in Crohn's disease patients: need for primary prophylaxis.

BACKGROUND: There is little information about the effect of infliximab on the clinical course of liver disease in Crohn's disease patients with concomitant hepatitis B virus (HBV) infection. Theoretically, immunosuppression induced by infliximab will facilitate viral replication which could be followed by a flare or exacerbation of disease when therapy is discontinued. There are no specific recommendations on surveillance and treatment of HBV before infliximab infusion. Two cases of severe hepatic failure related to infliximab infusions have been described in patients with rheumatic diseases. PATIENTS AND METHODS: Hepatitis markers (C and B) and liver function tests were prospectively determined to 80 Crohn's disease patients requiring infliximab infusion in three hospitals in Spain. RESULTS: Three Crohn's disease patients with chronic HBV infection were identified. Two of the three patients with chronic HBV infection suffered severe reactivation of chronic hepatitis B after withdrawal of infliximab therapy and one died. A third patient, who was treated with lamivudine at the time of infliximab therapy, had no clinical or biochemical worsening of liver disease during or after therapy. From the remaining 80 patients, six received the hepatitis B vaccine. Three patients had antibodies to both hepatitis B surface antigen (anti-HBs) and hepatitis B core protein (anti-HBc) with normal aminotransferase levels, and one patient had positive anti-hepatitis C virus (HCV) antibodies, negative HCV RNA, and normal aminotransferase levels. Except for the patients with chronic HBV infection, no significant changes in hepatic function were detected. CONCLUSIONS: Patients with Crohn's disease who are candidates for infliximab therapy should be tested for hepatitis B serological markers before treatment and considered for prophylaxis of reactivation using antiviral therapy if positive.

Adolescent↗
PubMed2003

Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure: results of the anti-TNF Therapy Against Congestive Heart Failure (ATTACH) trial.

BACKGROUND: Preclinical and preliminary clinical data have suggested that tumor necrosis factor-alpha (TNFalpha) may play a role in the evolution and progression of heart failure and that inhibition of TNFalpha may favorably modify the course of the disease. We evaluated the efficacy and safety of infliximab, a chimeric monoclonal antibody to TNFalpha, in patients with moderate-to-severe heart failure. METHODS AND RESULTS: One hundred fifty patients with stable New York Heart Association class III or IV heart failure and left ventricular ejection fraction <or=35% were randomly assigned to receive placebo (n=49), infliximab 5 mg/kg (n=50), or infliximab 10 mg/kg (n=51) at 0, 2, and 6 weeks after randomization and were followed-up prospectively for 28 weeks. Neither dose of infliximab improved clinical status at 14 weeks, the primary endpoint of the study, despite suppression of inflammatory markers (C-reactive protein and interleukin-6) and a modest increase in ejection fraction in the patients receiving 5 mg/kg (P=0.013). Furthermore, after 28 weeks, 13, 10, and 20 patients were hospitalized for any reason in the placebo, 5 mg/kg infliximab, and 10 mg/kg infliximab groups, respectively. The combined risk of death from any cause or hospitalization for heart failure through 28 weeks was increased in the patients randomized to 10 mg/kg infliximab (hazard ratio 2.84, 95% confidence interval 1.01 to 7.97; nominal P=0.043). CONCLUSIONS: Short-term TNFalpha antagonism with infliximab did not improve and high doses (10 mg/kg) adversely affected the clinical condition of patients with moderate-to-severe chronic heart failure.

Antibodies, Monoclonal↗
PubMed2003

Infliximab use in patients with severe graft-versus-host disease and other emerging risk factors of non-Candida invasive fungal infections in allogeneic hematopoietic stem cell transplant recipients: a cohort study.

Acute graft-versus-host disease (GVHD) is a common complication of allogeneic hematopoietic stem cell transplantation (HSCT). It has been proposed that tumor necrosis factor alpha (TNF-alpha) blockade with infliximab may be an effective treatment for severe (grades III-IV) GVHD. We determined if infliximab use in this high-risk population was associated with an additional increased risk of non-Candida invasive fungal infections (IFIs). Records of the 2000-2001 HSCT cohort at our institution were reviewed. Fifty-three (20%) of 264 evaluable patients developed severe GVHD and 11 of these 53 (21%) received infliximab for treatment. Proven or probable IFI was documented in 10 (19%) of 53 patients with severe GVHD (incidence rate of 0.99 cases/1000 GVHD patient-days). When stratified by infliximab use, 5 of 11 infliximab recipients developed an IFI (6.78 cases/1000 GVHD patient-days), compared with 5 of 42 IFI cases among nonrecipients (0.53 cases/1000 GVHD patient-days). In a time-dependent Cox regression model among patients with severe GVHD, the adjusted IFI hazard ratio of infliximab exposure was 13.6 (P =.004; 95% CI, 2.29-80.2). We conclude that infliximab administration is associated with a significantly increased risk of non-Candida IFI in HSCT recipients with severe GVHD disease. Pre-emptive systemic antifungal therapy against molds should be considered in patients who develop severe GVHD after HSCT if infliximab is used.

Adolescent↗
PubMed2005

Endoscopic and histologic evidence of persistent mucosal healing and correlation with clinical improvement following sustained infliximab treatment for Crohn's disease.

OBJECTIVES: The long-term effect of infliximab on endoscopic and histologic disease activity and expression of inflammatory markers was assessed in Crohn's disease patients who received infliximab as episodic or scheduled maintenance therapy therapy over 54 weeks (ACCENT 1). METHODS: All patients received Infliximab 5 mg/kg at week 0 and at week 2 were then randomized as responders or nonresponders to placebo or infliximab (5 or 10mg/kg). Patients received placebo or infliximab 5 mg/kg at weeks 2 and 6 followed by placebo or infliximab (5 or 10mg/kg) every 8 weeks or episodically on loss of response. Crohn's Disease Activity Index (CDAI), Crohn's Disease Endoscopic Index of Severity (CDEIS), Inflammatory Bowel Disease Questionnaire (IBDQ), and colonic and ileal Global Histologic Disease Activity (CGHAS and IGHAS) scores were determined at weeks 0, 10, and 54. Tumor necrosis factor-alpha (TNF-alpha), gelatinase B, Infliximab, tenascin, clusters of differentiation marker 68 (CD68), and intercellular adhesion molecule-1 (ICAM-1) were detected in mucosal biopsies by immunohistochemistry. RESULTS: At baseline, CDEIS significantly correlated with CGHAS only. Further at baseline, both CDEIS and the worst CGHAS or IGHAS, were significantly correlated with CD68, ICAM-1, and gelatinase B expression. At week 10, improvement in CGHAS only, correlated significantly with better CDAI, CDEIS, and IBDQ scores. Improvements in CDEIS and GHAS at week 10 correlated with reductions in gelatinase B and CD68, whereas only GHAS improvement correlated with decreased TNF-alpha expression. At week 54, decreased gelatinase B expression continued to correlate with improved CDEIS and GHAS while decreased CD68 and TNF-alpha expression correlated with GHAS and CDEIS improvement, respectively. CONCLUSIONS: Endoscopic and histologic evidence of mucosal healing was associated with a sustained reduction in the expression of inflammatory markers. Infliximab-induced improvement in the clinical signs and symptoms of Crohn's disease was associated with endoscopic and histologic evidence of sustained mucosal healing.

Adult↗
PubMedDate not supplied

Use of infliximab in pediatric patients with inflammatory bowel disease.

BACKGROUND: The concentration of tumor necrosis factor, a proinflammatory cytokine, is increased in the gastrointestinal mucosa of patents with active Crohn's disease (CD) and ulcerative colitis (UC). Neutralization of tumor necrosis factor decreases the mucosal inflammatory response of adults with CD. Little information is available on the use of monoclonal antibody to tumor necrosis factor (infliximab) in children and adolescents with CD or UC. OBJECTIVE: To evaluate the clinical response and side effects of patients to infliximab. METHODS: A retrospective review of data regarding 18 pediatric and adolescent patients with active CD (n = 15) and UC (n = 3) poorly controlled with conventional therapy. All patients received one to six intravenous infusions of infliximab 5 mg/kg, while receiving their usual medications. RESULTS: All patients experienced clinical improvement, including decrease in the frequency of stooling and resolution of extraintestinal symptoms such as arthropathy, malaise, and skin manifestations after treatment with infliximab. All but one patient had a documented decrease in the erythrocyte sedimentation rate. Prednisone dosage was tapered in all but two patients, and discontinued in seven patients. Intravenous infusion of infliximab was well tolerated. One patient developed a rash several days after the infusion. A patient who received six infliximab infusions developed recurrent Staphylococcus aureus infections, as well as septic arthritis and chronic osteomyelitis during the follow-up period, raising the issue of the long-term safety of infliximab. CONCLUSIONS: Treatment of our patients with refractory CD and UC with infliximab was associated with remarkable clinical improvement. Although the drug may have an important role in their management, further assessment of long-term safety and efficacy is needed.

Adolescent↗
PubMed2005

Infliximab: a review of its use in Crohn's disease and rheumatoid arthritis.

Infliximab (Remicade) is a chimeric monoclonal antibody against tumour necrosis factor (TNF)-alpha that has shown efficacy in Crohn's disease and rheumatoid arthritis with a disease-modifying activity and rapid onset of action. It is administered intravenously, generally in a schedule with initial infusions at 0, 2 and 6 weeks, followed by administration once every 8 weeks. Infliximab is effective in the treatment of patients with moderately to severely active Crohn's disease with an inadequate response to other treatment options or those with fistulising disease. In combination with methotrexate, infliximab reduced signs and symptoms and delayed disease progression in patients with active, methotrexate-refractory rheumatoid arthritis and in those with early disease. The drug was generally well tolerated. Recrudescence of tuberculosis infection and worsening of heart failure and demyelinating disease are among some of the concerns with anti-TNFalpha therapy, requiring cautious use of these agents in high-risk patients. Current data suggest that infliximab may be cost effective, especially when long-term clinical outcomes and burden of the diseases are taken into account. More robust, prospective pharmaco-economic studies are required to better ascertain the cost effectiveness of infliximab. Direct head-to-head comparative trials of infliximab with other biological agents are not yet available and would be helpful in determining with greater certainty the place of infliximab in the management of these diseases. Nonetheless, infliximab, like other biological agents, is a valuable treatment option in patients with moderately to severely active Crohn's disease (including fistulising disease) or rheumatoid arthritis (including early disease).

Antibodies, Monoclonal↗
PubMed2006

Spotlight on infliximab in Crohn disease and rheumatoid arthritis.

Infliximab (Remicade) is a chimeric monoclonal antibody against tumor necrosis factor (TNF)-alpha that has shown efficacy in Crohn disease and rheumatoid arthritis with a disease-modifying activity and rapid onset of action. It is administered intravenously, generally in a schedule with initial infusions at 0, 2, and 6 weeks, followed by administration once every 8 weeks. Infliximab is effective in the treatment of patients with moderately to severely active Crohn disease with an inadequate response to other treatment options or those with fistulizing disease. In combination with methotrexate, infliximab reduced signs and symptoms and delayed disease progression in patients with active, methotrexate-refractory rheumatoid arthritis and in those with early disease. The drug was generally well tolerated. Recrudescence of tuberculosis infection and worsening of heart failure and demyelinating disease are among some of the concerns with anti-TNFalpha therapy, requiring cautious use of these agents in high-risk patients. Current data suggest that infliximab may be cost effective, especially when long-term clinical outcomes and burden of the diseases are taken into account. More robust, prospective pharmacoeconomic studies are required to better ascertain the cost effectiveness of infliximab. Direct head-to-head comparative trials of infliximab with other biological agents are not yet available and would be helpful in determining with greater certainty the place of infliximab in the management of these diseases. Nonetheless, infliximab, like other biological agents, is a valuable treatment option in patients with moderately to severely active Crohn disease (including fistulizing disease) or rheumatoid arthritis (including early disease).

Antibodies, Monoclonal↗
PubMedDate not supplied

[Incidence and management of infusion reactions to infliximab in 186 italian patients with rheumatoid arthritis: the Padua experience].

OBJECTIVE: We report the incidence and treatment of infusion reactions to infliximab, a chimeric monoclonal IgG1 antibody against tumor necrosis factor alpha, in a large cohort of patients with rheumatoid arthritis. PATIENTS AND METHODS: One hundred eighty six patients with rheumatoid arthritis treated with infliximab for a total of 216.6 patient years were retrospectively evaluated. Patients received 2160 infliximab infusions at the Division of Rheumatology at the University Hospital of Padua from May, 2000 to April, 2004. Specific treatment protocols for initial and subsequent acute infusion reactions were followed and the outcomes documented. RESULTS: The overall incidence of infusion reactions to infliximab was 0.8% (19 out of 2160 of infusions), affecting 10.2% of patients (19 out of 186). Mild, moderate, or severe acute reactions occurred in 0.1% (3 of 2160), 0.6% (13 of 2160), and 0.04% (1 of 2160) of infliximab infusions, respectively. Delayed infusion reactions occurred in 0.09% (2 of 2160) of infusions. Use of specific treatment protocols resulted in rapid resolution of all acute reactions to infliximab. With a prophylaxis protocol, all patients who experienced an initial mild acute reaction were able to receive additional infusions. CONCLUSIONS: Using appropriate treatment protocols, infliximab infusion reactions were effectively treated and prevented in patients with mild acute reactions upon retreatment. In the case of moderate to severe infusion reactions, the risks and the benefits of the continuation of infliximab therapy need to be carefully considered.

Adolescent↗
PubMed2004

The efficacy of switching from etanercept to infliximab in patients with rheumatoid arthritis.

OBJECTIVE: To describe the degree of clinical benefit in patients with rheumatoid arthritis (RA) who receive infliximab therapy after lack of efficacy with etanercept. METHODS: In a retrospective study among 6 centers primarily designed to assess the safety of infliximab in combination with leflunomide, a standardized chart review form was used to collect data on 93 patients with RA. During that study, it was noted that some of these patients had switched from etanercept to infliximab. In this study, we compared the response of subjects switching from etanercept to infliximab (n = 20) to that of subjects receiving infliximab with no prior tumor necrosis factor (TNF) therapy (n = 73). RESULTS: The swollen and tender joint count, patient and physician global assessments, morning stiffness, and C-reactive protein all improved substantially in both groups, with no statistical difference in the degree of benefit between the groups. At the time of chart review, switchers had received a statistically higher dose of infliximab than controls (4.4 vs 3.19 mg/kg; p = 0.006) with a total of 5.7 and 5 infusions, respectively. CONCLUSION: In this retrospective study, previous lack of efficacy with etanercept did not predict lack of efficacy with infliximab. Indeed, the degree of clinical improvement was similar in both groups, although switchers were receiving a higher dose of infliximab at the time of chart review. Our findings suggest that clinical response may differ between anti-TNF agents, and lack of response to one agent may not predict a lack of response to another.

Antibodies, Monoclonal↗
PubMed2004

Infliximab dose and clinical status: results of 2 studies in 1642 patients with rheumatoid arthritis.

OBJECTIVE: Infliximab is an effective anti-tumor necrosis factor (TNF) agent widely used in the treatment of rheumatoid arthritis (RA). Initially recommended at a dose of 3 mg/kg, subsequent label revisions allowed doses up to 10 mg/kg or at 4-week intervals rather than the originally suggested 8-week intervals, if clinically indicated. The doses used have implications for efficacy and costs, but no data exist for actual dose used in the US. This study evaluates the dosage and rates of increase in infliximab-treated patients with RA. METHODS: Study 1: Review of patient charts and infusion records for 394 RA patients from 2 large rheumatology practices comprising 15 rheumatologists in Dallas, Texas. Study 2: Survey of 1324 RA patients using infliximab participating in a longitudinal study of RA outcomes. Patients completed a detailed questionnaire about clinical status and infliximab use. RESULTS: The results of the 2 studies were similar: the average infliximab dose was 5 mg/kg, increasing most rapidly until the end of the first years, after which the increase was slowed. Increases > 3 mg/kg occurred in 61% of patients in Study 1 and 56% in Study 2. The 8-week treatment interval was almost universally used, and more than 95% of infusions occurred in this interval. The most common reason for increase in dose was insufficient response. Among patients who completed 4 infusions, 75% remained on therapy at 2 years after infliximab start. The average improvement in Health Assessment Questionnaire disability score was 0.28. CONCLUSION: Infliximab dose increases are common, particularly during the first year of treatment. The average dose is 5 mg/kg. Seventy-five percent of patients continue using infliximab 2 years after treatment onset.

Antibodies, Monoclonal↗
PubMed2004

[Effect of infliximab in the treatment of refractory inflammatory bowel disease with complication].

BACKGROUND/AIMS: Many studies on infliximab have confirmed its efficacy in the remission induction and even maintenance in refractory and fistulizing Crohn's disease. We report the treatment efficacy of infliximab in Crohn's disease and ulcerative colitis refractory to steroid treatment and the complications of infliximab treatment. METHODS: We performed infliximab administration in 5 cases (3 Crohn's disease, 2 ulcerative colitis) refractory to systemic steroid treatment and 5 cases of Crohn's disease with fistula. Patients received an intravenous infusion of infliximab at 3-5 mg/kg body weight. RESULTS: In 3 cases of refractory Crohn's patients, clinical response and remission induction were obtained in 2 (67%) and 1 cases (33%). After infusion of infliximab, the occlusion of internal fistula could be found in all 2 cases. Two out of 3 cases of anal fistula were completely healed. In two cases of refractory ulcerative colitis, one case who showed clinical manifestation of toxic megacolon had improved and avoided the colectomy, but the other case did not respond to the infusion of infliximab and underwent colon resection. CONCLUSIONS: We found that administration of infliximab is an effective alternative for refractory and fistulizing Crohn's disease but further studies are necessary for refractory ulcerative colitis.

Adolescent↗
PubMedDate not supplied

Regulation of serum chemokines following infliximab therapy in patients with rheumatoid arthritis.

OBJECTIVE: We studied the effects of the multiple infusions of infliximab, a chimeric anti-tumor necrosis factor alpha (anti-TNF-alpha) antibody, on the serum chemokines levels in patients with active rheumatoid arthritis (RA). METHODS: RA patients were supposed to receive 9 infusions of infliximab (3mg/kg) at weeks 0, 2, 6, and every 8 weeks thereafter with the same dose. All patients continued treatment with methotrexate (MTX) (7.5-20mg/week). Serum concentrations of interleukin-8 (IL-8), RANTES (regulated upon activation, normal T cell expressed and secreted) and monocyte chemoattractant protein-1 (MCP-1) were assessed by ELISA at weeks 0, 2, 6, 14, 38, prior to infusion, and additionally at week 62. RESULTS: Initial infusion of infliximab caused reduction in serum IL-8, RANTES and MCP-1 (in all cases p < 0.001) levels. Subsequent infliximab administrations also significantly decreased serum chemokines levels, but was less effective. Prior to the first infliximab infusion serum concentrations of studied chemokines correlated with markers of RA activity such as the erythrocyte sedimentation rate (ESR) or CRP levels, number of swollen joints and disease activity score (DAS). Following next drug infusions such associations were far less significant. Infliximab treatment induced a significant reduction in the number of monocytes observed through the whole study (in all cases p < 0.05). CONCLUSION: Anti-TNF-alpha antibody therapy accompanied by MTX, beside a rapid clinical improvement, reduced serum chemokines concentrations in RA patients. Subsequent administrations of infliximab sustained chemokines decrease, although to a lesser extent than the first two dose of infliximab.

Adult↗
PubMed2005

What next after infliximab?

The use of infliximab (Remicade) has revolutionized the care of Crohn's disease (CD) patients who have proved refractory to standard treatment. The use of infliximab is very well tolerated in the majority of patients but in a small subset of patients may lead to the production of antibodies (termed "antibodies to infliximab"-ATI). The production of these antibodies has been associated with the development of both acute and delayed infusion reactions, although even in patients who develop ATIs, these reactions are relatively uncommon. Nonetheless, these reactions may occasionally be severe enough to lead to intolerance to infliximab. Another group of patients, after initially having excellent responses to infliximab, experience an attenuated response or loss of response over time. What is the cause of this loss of efficacy? ATIs may play a role in some patients but other potential reasons for this phenomenon have provoked much debate. The importance of other cytokines after TNF-alpha has been neutralized may be relevant as (this has been shown to be the case in rheumatoid arthritis (RA) is the idea of beneficial autoimmunity production to TNF-alpha. (Wildbaum G, Nahir MA, Karin N. Beneficial autoimmunity to proinflammatory mediators restrains the consequences of self-destructive immunity. Immunity 2003;19:679-88.) It has been shown that during the course of an autoimmune condition, the immune system mounts a beneficial autoantibody response to proinflammatory mediators. This response counteracts, to a certain degree, the autoimmune pathology. This natural counteraction has been illustrated in animal models of autoimmunity, and there has been evidence demonstrated that this occurs in human RA. Whether this occurs in Crohn's is unknown; infliximab is a chimeric monoclonal antibody containing an approximately 25% murine region. It had been hoped that the development of humanized or fully human monoclonal antibodies would provide therapeutic antibodies that did not induce an immune response. While this has unfortunately not proven to be the case-these products still have significant immunogenicity-these products do present an alternative therapy when infliximab cannot be used. In light of this, adalimumab (Humira) a human monoclonal antibody used for treating rheumatologic conditions has been investigated as an alternate treatment for patients with CD who after initially responding to infliximab experience intolerance or loss of efficacy. Is this a viable alternative?

Adalimumab↗