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PubMed2006

Predictors of joint damage in patients with early rheumatoid arthritis treated with high-dose methotrexate with or without concomitant infliximab: results from the ASPIRE trial.

OBJECTIVE: To identify disease characteristics leading to progression of joint damage in patients with early rheumatoid arthritis (RA) treated with methotrexate (MTX) versus those treated with infliximab plus MTX. METHODS: Patients who had not previously been treated with MTX with active RA were randomly assigned to receive escalating doses of MTX up to 20 mg/week plus placebo or infliximab at weeks 0, 2, and 6, and every 8 weeks thereafter through week 46. Radiographic joint damage was assessed using the modified Sharp/van der Heijde score (SHS). The relationship between disease activity measures at baseline and week 14, as well as those averaged over time, were examined in relation to the change in SHS from baseline through week 54. RESULTS: C-reactive protein (CRP) levels, erythrocyte sedimentation rate (ESR), and swollen joint count were associated with greater joint damage progression in the MTX-only group, while none of these parameters was associated with progression in the infliximab plus MTX group. Mean changes in SHS among patients in the highest CRP (> or = 3 mg/dl) and ESR (> or = 52 mm/hour) tertiles in the MTX-only group were 5.62 and 5.89, respectively, compared with 0.73 and 1.12 in the infliximab plus MTX group (P < 0.001). Patients with greater joint damage at baseline (SHS > or = 10.5) showed less progression with infliximab plus MTX compared with MTX alone (-0.39 versus 4.11; P < 0.001). Patients receiving MTX alone who had persistently active disease at week 14 showed greater radiographic progression of joint damage than those taking MTX plus infliximab. CONCLUSION: High CRP level, high ESR, or persistent disease activity was associated with greater radiographic progression in the group taking MTX alone, while little radiographic progression was seen in patients receiving both MTX and infliximab, regardless of the abnormal levels of these traditional predictors.

Adolescent↗
PubMed2002

Life-threatening histoplasmosis complicating immunotherapy with tumor necrosis factor alpha antagonists infliximab and etanercept.

OBJECTIVE: Two tumor necrosis factor alpha (TNFalpha) antagonists were recently licensed in the US. Infliximab was licensed in 1998 for the treatment of Crohn's disease (CD), and since 1999, it has been licensed in combination with methotrexate for treatment of rheumatoid arthritis (RA). Etanercept was licensed in 1998 for treatment of RA and, more recently, for juvenile RA and psoriatic arthritis. Because of potential immunosuppression related to use of anti-TNFalpha agents, we sought to identify postlicensure cases of opportunistic infection, including histoplasmosis, in patients treated with these products. METHODS: The US Food and Drug Administration's (FDA) passive surveillance database for monitoring postlicensure adverse events was reviewed to identify all reports received through July 2001 of histoplasmosis in patients treated with either infliximab or etanercept. RESULTS: Ten cases of Histoplasma capsulatum (HC) infection were reported: 9 associated with infliximab and 1 associated with etanercept. In patients treated with infliximab, manifestations of histoplasmosis occurred within 1 week to 6 months after the first dose and typically included fever, malaise, cough, dyspnea, and interstitial pneumonitis. Of the 10 patients with histoplasmosis, 9 required treatment in an intensive care unit, and 1 died. All patients had received concomitant immunosuppressive medications in addition to infliximab or etanercept, and all resided in HC-endemic regions. CONCLUSION: Postlicensure surveillance suggests that acute life-threatening histoplasmosis may complicate immunotherapy with TNFalpha antagonists, particularly infliximab. Histoplasmosis should be considered early in the evaluation of patients who reside in HC-endemic areas in whom infectious complications develop during treatment with infliximab or etanercept.

Adult↗
PubMed2006

Infliximab treatment maintains employability in patients with early rheumatoid arthritis.

OBJECTIVE: To evaluate the impact of infliximab therapy on the employment status of patients with early rheumatoid arthritis (RA). METHODS: Methotrexate (MTX)-naive patients with active early RA were randomly allocated to receive MTX plus placebo or MTX plus infliximab (3 mg/kg or 6 mg/kg) at weeks 0, 2, and 6 and then every 8 weeks through week 46. Data for patients younger than age 65 years were included in the analyses. A patient was categorized as employable if he or she was employed or felt well enough to work if a job were available. RESULTS: The change in actual employment was not significantly different between patients receiving MTX plus infliximab and those receiving MTX plus placebo (0.5% versus 1.3%; P > 0.5). However, the proportion of patients whose status changed from employable at baseline to unemployable at week 54 was smaller in the group receiving MTX plus infliximab compared with that in the group receiving MTX alone (8% versus 14%; P = 0.05). Patients who were treated with infliximab plus MTX had a significantly greater likelihood of improvement rather than deterioration in employability (odds ratio 2.4; P < 0.001); this likelihood was not significantly greater in patients receiving MTX alone. The proportion of employed patients who lost workdays during the trial was smaller in the MTX plus infliximab group than in the MTX-alone group (P = 0.010). CONCLUSION: The actual employment rates among patients in the 2 treatment groups were not different. However, patients with early RA who were treated with MTX plus infliximab had a higher probability of maintaining their employability compared with those who were treated with MTX alone.

Antibodies, Monoclonal↗
PubMed2006

IgG and IgM anticardiolipin antibodies following treatment with infliximab plus methotrexate in patients with early rheumatoid arthritis.

OBJECTIVE: To assess the occurrence of anticardiolipin antibodies (aCL) in patients with early rheumatoid arthritis (RA) receiving treatment with infliximab plus methotrexate (MTX) versus MTX alone. METHODS: The first 299 patients enrolled in the randomized, Active-Controlled Study of Patients Receiving Infliximab for the Treatment of Rheumatoid Arthritis of Early Onset (ASPIRE) trial who had baseline (week 0) samples available for aCL testing were included in this study. Sera were collected at weeks 0, 30, and 54 from 110 patients taking infliximab 3 mg/kg plus MTX, 98 patients taking infliximab 6 mg/kg plus MTX, and 91 patients taking placebo plus MTX. IgG and IgM aCL were measured using an anticardiolipin assay. RESULTS: IgG and IgM aCL positivity at baseline was similar in all treatment groups. Most patients were negative for IgG aCL at baseline and remained so at the last followup evaluation. One percent (2 of 208) of patients who received infliximab plus MTX and were negative for IgG aCL at baseline were positive for IgG aCL at weeks 30 and 54. A slightly higher proportion of patients who received infliximab plus MTX and were negative for IgM aCL at baseline were positive for IgM aCL at weeks 30 and 54 (4.8% [10 of 208]) as compared with patients who received placebo plus MTX (1.1% [1 of 91]), but the difference was not significant. CONCLUSION: There was a low incidence of the development of aCL in patients with early RA who received infliximab in combination with MTX, and the difference was not significant compared with patients who received placebo plus MTX.

Adult↗
PubMed2007

Effect of the anti-tumor necrosis factor-alpha antibody infliximab on the ex vivo mucosal matrix metalloproteinase-proteolytic phenotype in inflammatory bowel disease.

BACKGROUND: Previous studies have shown an upregulation of matrix metalloproteinases (MMPs) in intestinal tissue of patients with inflammatory bowel disease (IBD) and significant clinical improvement after administration of the anti-TNF-a antibody infliximab. The aims of our study were to determine expression and secretion of MMP-1, -2, -3, -9, and their inhibitors TIMP-1, -2 by IBD versus control intestinal mucosa ex vivo and to assess the regulatory capacity by infliximab of the proteolytic phenotype. METHODS: Intestinal mucosal explants from 20 IBD and 15 control patients were cultured with or without infliximab and/or the T-cell activator pokeweed mitogen (PWM). Explants and culture supernatants were analyzed for MMPs, TIMPs, and TNF-alpha protein, activity and/or mRNA levels. All patients were genotyped for functional TNF-alpha, MMP, and TIMP single nucleotide polymorphism (SNP) loci. RESULTS: Expression of MMP and TIMP protein/activity in basal medium was higher in IBD versus control explants. Dependent on genotype at SNP loci, infliximab downregulated MMP-1, -3, and -9 relative to TIMP-1 and -2 and also decreased MMP-1 and -3 activities, while PWM enhanced these levels, partly counteracted again by infliximab. The expression of MMP-2 relative to TIMP did not change by treatment with infliximab and/or PWM. CONCLUSIONS: The high expression of MMPs in patients with IBD suggests a role for these proteinases in the pathogenesis of this disease. Infliximab seems to induce a genotype-associated matrix protective phenotype, which may contribute to the observed therapeutic efficacy of this drug in IBD, particularly at the mucosal surface.

Adolescent↗
PubMed2004

The effect of infliximab on extraintestinal manifestations of Crohn's disease.

OBJECTIVE: The purpose of this open pilot study was to assess prospectively the effect of infliximab on extraintestinal manifestations in patients with active Crohn's disease refractory to conventional treatment. PATIENTS AND METHODS: Twenty-two consecutive patients with Crohn's disease and one with ulcerative colitis presenting at least one of the known extraintestinal manifestations of Crohn's disease participated in the study. All the patients had Crohn's disease activity index (CAI) scores above 2. Each patient received an intravenous infusion of infliximab at a dosage of 5 mg/kg. A thorough questionnaire was used reviewing the extraintestinal manifestations of Crohn's disease such as erythema nodosum, pyoderma gangrenosum, eye lesions, arthritis or arthralgia, sacroiliitis or inflammatory back pain, hepatic disease, hematologic manifestations (megaloblastic, iron deficiency or hemolytic anemia, thrombocytosis), thrombosis, and nephrolithiasis. Musculoskeletal complaints were evaluated using the parameters intensity of pain, duration of morning stiffness (in minutes), presence of inflammatory back pain, Schober's test of the lumbar region, chest expansion, and distance from occiput to wall. The clinical assessment was performed on the day of the infusion and 2 weeks later. RESULTS: Eleven out of 23 patients had arthralgia of inflammatory nature, three others had evidence of active synovitis on physical examination, and 11 reported inflammatory back pain. Four patients suffered from protracted pyoderma gangrenosum; three had resistant aphthous stomatitis. Eleven patients had more than one extraintestinal manifestation. All four with pyoderma gangrenosum demonstrated significant improvement of their ulcers after one course of infliximab, with complete resolution of the skin lesions in three of them after repeated infusions of infliximab. Aphthous stomatitis completely responded in all patients after a single infusion. Seven out of 11 patients with arthralgia and seven out of 11 with inflammatory back pain/sacroiliitis experienced benefit after treatment with infliximab and reported at least partial clinical improvement in duration of morning stiffness, tender joint count, and visual analogue scale for pain. Only one of three patients with frank arthritis demonstrated clear improvement, and two others failed to respond to infliximab treatment. CONCLUSION: These preliminary results are encouraging and suggest a promising role of infliximab in the treatment of extraintestinal symptoms of Crohn's disease.

Adult↗
PubMed2004

A review of the use of infliximab to manage cutaneous dermatoses.

BACKGROUND: Infliximab is a chimeric monoclonal antibody that binds specifically to human tumor necrosis factor-alpha (TNF-alpha), decreasing the effect of the cytokine in inflammatory diseases. OBJECTIVE: The aim of this study was to review the efficacy and safety of infliximab in the treatment of dermatological diseases. METHODS: A MEDLINE search (1966-January 2003), using the keyword "infliximab" was performed to find relevant articles pertaining to the use of infliximab in dermatology. RESULTS: Infliximab has been used in the following dermatological diseases: psoriasis, Behcet's disease, graft versus host disease, hidradenitis suppurativa, panniculitis, pyoderma gangrenosum, SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome, sarcoidosis, subcorneal pustular dermatosis, Sweet's syndrome, toxic epidermal necrolysis, and Wegener's granulomatosis. There is a generally good safety profile for infliximab, which is similar to that when it is used to treat Crohn's disease and rheumatoid arthritis. CONCLUSION: Although not approved for use in dermatological diseases, there have been numerous reports of the efficacy of infliximab in cutaneous inflammatory diseases. The most promise lies in those diseases that have increased amounts of TNF-alpha in the cutaneous lesions, such as psoriasis.

Antibodies, Monoclonal↗
PubMed2006

Effect of tumor necrosis factor alpha and infliximab on apoptosis of B lymphocytes infected or not with Epstein-Barr virus.

Chronic inflammation and immunosuppressive therapies increase the risk of non-Hodgkin's lymphoma associated or not with Epstein-Barr virus (EBV) infection. A possible link between infliximab treatment and increased risk of lymphoma has been suggested. Indeed, infliximab induces apoptosis of monocytes and activated T lymphocytes, but its effect on B lymphocytes infected or not with EBV is unknown. Secreted tumor necrosis factor (TNF) alpha and the expression level of TNF receptor 1 (TNFR1) and TNFR2 were compared in EBV-positive and negative B-cell lines. The impact of TNFalpha and infliximab on apoptosis of EBV-positive cells was analyzed regarding the activity of NF-kappaB. Increased expression of TNFalpha in EBV-positive cells suggested that infliximab could affect their survival. However, TNFalpha or infliximab incubation had no effect on apoptosis of EBV-positive cells. Loss of NF-kappaB activity sensitized lymphoblastoid cell lines to TNFalpha-induced apoptosis, but no direct effect of infliximab on apoptosis was detected. On the basis of our in vitro data, neither TNFalpha nor infliximab has a direct effect on apoptosis of B lymphocytes and EBV-positive cell lines. Thus, if an increased incidence of lymphoma were induced by TNFalpha blockers, it would not involve a direct effect on B cells but rather an impaired immune surveillance by T cells.

Antibodies, Monoclonal↗
PubMed2005

Infliximab may reverse the toxic effects induced by tumor necrosis factor alpha in human spermatozoa: an in vitro model.

OBJECTIVE: To examine the toxic effects of tumor necrosis factor alpha (TNF-alpha) on ejaculated spermatozoa and evaluate the ability of infliximab to reverse these effects. DESIGN: Prospective controlled study. SETTING: Cleveland Clinic Foundation, Cleveland, Ohio. PATIENT(S): Thirty-one healthy sperm donors. INTERVENTION(S): Exposure of human spermatozoa to varying concentrations of TNF-alpha (100, 300, 400, 500 pg/mL, and 2.5 microg/mL) and infliximab (400 microg/mL). MAIN OUTCOME MEASURE(S): Sperm motility, functional integrity of plasma membrane, and DNA fragmentation. RESULT(S): Spermatozoa quality declined following incubation with TNF-alpha in a dose-dependent and time-dependent manner. Sperm motility and membrane integrity were higher in the samples incubated with TNF-alpha plus infliximab than in the samples treated with TNF-alpha only. These parameters improved significantly and were comparable with both controls and sperm incubated with infliximab alone. Similarly, the percentage of spermatozoa with DNA fragmentation improved significantly following incubation with TNF-alpha plus infliximab and again was comparable with both controls and sperm incubated with infliximab alone. CONCLUSION(S): Spermatozoa may be exposed to abnormal levels of TNF-alpha in the male reproductive tract or during their passage into the female reproductive tract (in cases of endometriosis). Exposing spermatozoa to pathological concentrations of TNF-alpha can result in significant loss of their functional and genomic integrity. Infliximab could potentially be used to help treat female infertility caused by endometriosis in those with elevated levels of TNF-alpha in their peritoneal fluid.

Analysis of Variance↗
PubMed2005

Infliximab for the treatment of psoriasis: clinical experience at the State University of New York at Buffalo.

BACKGROUND: Infliximab has shown promising results for the treatment of moderate to severe psoriasis and psoriatic arthritis. METHODS: We conducted a retrospective study of all 52 patients treated with intravenous infliximab for severe psoriasis at a single practice site. These patients had recalcitrant plaque psoriasis (>33% body surface area), which was unresponsive to multiple conventional systemic therapies. Intravenous infliximab was administered at a dose of 5 mg/kg at 0, 2, 6, and 14 weeks and every 8 weeks thereafter. Patients were monitored for infections, infusion reactions, side effects, and response to therapy. RESULTS: Fifty-two patients (men = 32, women = 20) with a mean age of 47 (range, 22-76 years old) were included in this study. They were followed for a minimum of 4 months and a maximum of 33 months (median, 22 months). Patients received a mean total number of 12 infusions (range, 3-22). Forty-six of 52 patients (88%) had a clear or almost clear improvement based on the Physician's Global Assessment done by a single physician. Twelve patients (23%) required infliximab dose escalation to maintain control of their disease. Nine patients experienced infusion reactions. Thirteen patients experienced nonopportunistic infections; however, only one infection required temporary cessation of infliximab. LIMITATIONS: This was a retrospective study at a single practice site. CONCLUSION: Infliximab was extremely effective and well tolerated in this group of patients with severe, recalcitrant psoriasis. Thirty-nine of 52 patients have continued receiving treatment for a median duration of 25 months with excellent disease control. Infliximab can provide control of extensive psoriasis with continued intermittent infusions.

Adult↗
PubMed2006

A randomized comparison of continuous vs. intermittent infliximab maintenance regimens over 1 year in the treatment of moderate-to-severe plaque psoriasis.

BACKGROUND: Previous studies of infliximab in psoriasis have demonstrated rapid improvement with induction therapy and sustained response with regularly administered maintenance therapy. OBJECTIVE: The efficacy and safety of continuous (every-8-week) and intermittent (as-needed) maintenance regimens were compared. METHODS: Patients with moderate-to-severe psoriasis (n = 835) were randomized to induction therapy (weeks 0, 2, and 6) with infliximab 3 mg/kg or 5 mg/kg or placebo. Infliximab-treated patients were randomized again at week 14 to continuous or intermittent maintenance regimens at their induction dose. RESULTS: At week 10, 75.5% and 70.3% of patients in the infliximab 5 mg/kg and 3 mg/kg groups, respectively, achieved PASI 75; 45.2% and 37.1% achieved PASI 90 (vs 1.9% [PASI 75] and 0.5% [PASI 90] for placebo; P < .001). Through week 50, PASI responses were better maintained with continuous compared with intermittent therapy within each dose, and with 5 mg/kg compared with 3 mg/kg continuous therapy. LIMITATIONS: Longer term (>1 year) maintenance therapy and further study of infliximab serum concentrations over this period, in both PASI 75 responders and non-responders, would be preferable. CONCLUSIONS: Through week 50, response was best maintained with continuous infliximab therapy. Infliximab was generally well-tolerated in most patients.

Adult↗
PubMed2004

Infliximab continuation rates in patients with rheumatoid arthritis in everyday practice.

UNLABELLED: Infliximab is a major breakthrough in the management of rheumatoid arthritis (RA). We evaluated infliximab continuation rates and reasons for discontinuation in patients with RA. PATIENTS AND METHODS: We studied patients with RA started on infliximab at any time between March 2000 and December 2002, under the conditions of everyday practice (as opposed to clinical trial settings), as recommended by the French marketing license (3 mg/kg as an intravenous infusion at weeks 0, 2, and 6 then at 8-week intervals). The number of infliximab infusions, side effects, and nonresponse rates was recorded. The Kaplan-Meier method was used to evaluate treatment continuation. Reasons for discontinuation were studied. RESULTS: We included 41 patients, with a mean age of 54 years, a mean RA duration of 9 years, and a mean of three previous disease-modifying antirheumatic drug treatments. The total number of infliximab infusions was 461 with a mean of 10.8 per patient and a mean follow-up under treatment of 15.3 months. The proportions of patients still on infliximab were 82%, 74%, and 67% after 6, 12, and 24 months, respectively. The main reasons for discontinuation were escape phenomenon (n = 6, 42.8% of discontinuations) and allergy (n = 3); in one case each, the reason was primary ineffectiveness, severe infection, plans to start a pregnancy, poor compliance, and unavailability for follow-up. There were 59 recorded episodes of side effects, with a profile similar to that in the literature and in postmarketing databases. CONCLUSION: The infliximab continuation rate in everyday practice in patients with RA (67% after 2 years) was consistent with published data and with the results of controlled trials.

Adult↗
PubMed2002

Estimating the cost-effectiveness of 54 weeks of infliximab for rheumatoid arthritis.

PURPOSE: To estimate the cost-effectiveness of infliximab plus methotrexate for active, refractory rheumatoid arthritis. METHODS: We projected the 54-week results from a randomized controlled trial of infliximab into lifetime economic and clinical outcomes using a Markov computer simulation model. Direct and indirect costs, quality of life, and disability estimates were based on trial results; Arthritis, Rheumatism, and Aging Medical Information System (ARAMIS) database outcomes; and published data. Results were discounted using the standard 3% rate. Because most well-accepted medical therapies have cost-effectiveness ratios below $50,000 to $100,000 per quality-adjusted life-year (QALY) gained, results below this range were considered to be "cost-effective." RESULTS: At 3 mg/kg, each infliximab infusion would cost $1393. When compared with methotrexate alone, 54 weeks of infliximab plus methotrexate decreased the likelihood of having advanced disability from 23% to 11% at the end of 54 weeks, which projected to a lifetime marginal cost-effectiveness ratio of $30,500 per discounted QALY gained, considering only direct medical costs. When applying a societal perspective and including indirect or productivity costs, the marginal cost-effectiveness ratio for infliximab was $9100 per discounted QALY gained. The results remained relatively unchanged with variation of model estimates over a broad range of values. CONCLUSIONS: Infliximab plus methotrexate for 54 weeks for rheumatoid arthritis should be cost-effective with its clinical benefit providing good value for the drug cost, especially when including productivity losses. Although infliximab beyond 54 weeks will likely be cost-effective, the economic and clinical benefit remains uncertain and will depend on long-term results of clinical trials.

Adult↗
PubMed2002

Treatment of active ankylosing spondylitis with infliximab: a randomised controlled multicentre trial.

UNLABELLED: BACKGROUND Treatment options for patients with ankylosing spondylitis are few. We aimed to assess the effectiveness of infliximab, an antibody to tumour necrosis factor (TNF)-alpha, in treatment of such patients. METHODS: In this 12-week placebo-controlled multicentre study, we randomly assigned 35 patients with active ankylosing spondylitis to intravenous infliximab (5 mg/kg) and 35 to placebo at weeks 0, 2, and 6. One patient in the infliximab group was withdrawn from the study. Our primary outcome was regression of disease activity of at least 50%. To assess response, we used validated clinical criteria from the ankylosing spondylitis assessment working group, including disease activity (BASDAI), functional indices (BASFI), metrology (BASMI), and quality of life (short form 36). Analyses were done by intention to treat. FINDINGS: 18 (53%) of 34 patients on infliximab had a regression of disease activity at week 12 of at least 50% compared with three (9%) of 35 on placebo (difference 44% [95% CI 23-61], p<0.0001). Function and quality of life also improved significantly on infliximab but not on placebo (p<0.0001 and p<0.0001, respectively). Treatment with infliximab was generally well tolerated, but three patients had to stop treatment because of systemic tuberculosis, allergic granulomatosis of the lung, or mild leucopenia. INTERPRETATION: Our results show that treatment with infliximab is effective in patients with active ankylosing spondylitis. Since there are some potentially serious adverse effects, we recommend that this treatment mainly be used in co-operation with rheumatological centres.

Adult↗
PubMed2003

Infliximab in the treatment of refractory posterior uveitis.

PURPOSE: To determine the efficacy and safety of infliximab in the treatment of refractory posterior uveitis. DESIGN: Noncomparative interventional case series. PARTICIPANTS: Five patients with posterior uveitis were treated: 3 had Behçet's syndrome, and 2 had idiopathic posterior uveitis. INTERVENTIONS: Patients with sight-threatening uveitis refractory to other immunosuppressive agents were treated with infliximab. MAIN OUTCOME MEASURES: Intraocular inflammation, by using binocular indirect ophthalmoscopy score, retinal vasculitis, and visual acuity. Adverse effects of infliximab were documented. RESULTS: Within 2 weeks of the first infusion of infliximab, 4 of 5 patients showed marked improvement in vitreous haze and visual acuity. By the 6-month follow-up, the same four patients had achieved remission of posterior uveitis and had successfully withdrawn all other immunosuppressive therapy. Further infusions of infliximab were required in 3 patients. One patient developed ocular and systemic tuberculosis, which responded to antituberculous treatment. CONCLUSIONS: Infliximab is effective in the treatment of sight-threatening refractory posterior uveitis. However, patients should be thoroughly screened for tuberculosis before treatment and followed up closely during and after therapy with infliximab.

Adult↗
PubMed2005

[Desensitisation to infliximab in patients with Crohn's disease].

BACKGROUND: Infliximab is a chimeric monoclonal antibody directed against tumour necrosis factor-alpha that has been shown to improve chronic refractory and fistulating Crohn's disease. Infliximab infusions have been associated both with immediate and delayed reactions. MATERIAL AND METHODS: Desensitisation was performed in four patients who had experienced immediate reactions to infliximab infusions and in one who had developed a delayed reaction. No therapeutic alternatives were available for these patients. Before desensitisation, skin tests were performed. RESULTS: Skin-tests were negative for all patients. Desensitisation was performed with serial dilutions of infliximab with monitoring of vital signs before each increment. After parenteral desensitisation, all five patients were able to tolerate infliximab infusion without complications or any requirement for antihistamines or steroids. However, two patients who had initially presented with an immediate reaction to infliximab experienced arthralgia and myalgia similar to a "serum sickness-type" of reaction 6 to 10 days after desensitisation. CONCLUSION: Even if there is no evidence of an allergic mechanism in infusion reactions to infliximab, successful desensitization can be achieved for patients experiencing acute reactions. The mechanism of desensitisation remains presently unknown. It is not yet possible to say if desensitization will be effective in preventing delayed reactions.

Adult↗
PubMed2004

Long-term treatment of rectovaginal fistulas in Crohn's disease: response to infliximab in the ACCENT II Study.

BACKGROUND & AIMS: The ACCENT II study (A Crohn's Disease Clinical Trial Evaluating Infiximab in a New Long-term Treatment Regimen in Patients With Fistulizing Crohn's Disease) evaluated the efficacy and safety of infliximab maintenance treatment in patients with fistulizing Crohn's disease. This post hoc analysis was conducted to determine the efficacy and safety of infliximab therapy in women with rectovaginal fistulas. METHODS: All patients received 5 mg/kg infliximab intravenously at weeks 0, 2, and 6. Patients who achieved response at weeks 10 and 14 then were randomized as responders if they had at least 50% of baseline fistulas closed, or as nonresponders, to receive placebo or infliximab 5 mg/kg every 8 weeks through week 54. RESULTS: Of 282 patients in the ACCENT II study, 25 of 138 (18.1%) women had a total of 27 draining rectovaginal fistulas at baseline. After infusions of infliximab at weeks 0, 2, and 6, 60.7% (17 of 28) and 44.8% (13 of 29) of rectovaginal fistulas were closed at weeks 10 and 14, respectively. Among responders, 72.2% (13 of 18) of rectovaginal fistulas were no longer draining at week 14. The duration of rectovaginal fistula closure was longer in the infliximab 5-mg/kg maintenance group (median, 46 wk) than in the placebo group (33 wk). CONCLUSIONS: Infliximab is effective in short-term closure of rectovaginal fistulas and maintenance treatment was more effective than placebo in prolonging rectovaginal fistula closure.

Abdominal Abscess↗
PubMed2004

Treatment of pyoderma gangrenosum with infliximab in Crohn's disease.

Pyoderma gangrenosum (PG) is an ulcerating noninfectious disease of the skin seen in 1 to 5% of patients with inflammatory bowel disease. The pathogenesis of PG has yet to be determined but may be related to abnormal T cell responses and the production of TNF-alpha, a powerful proinflammatory cytokine. Infliximab, a chimeric monoclonal antibody to TNF-alpha, has been approved for the treatment of Crohn's disease. We present four patients with PG treated with Infliximab for fistulizing Crohn's in whom complete healing of PG was achieved. Four patients with active fistulizing Crohn's disease and PG were treated. All patients were females ranging in age from 48 to 60 years, with a mean age of 54 years. Three of four patients had PG lesions located on the lower extremities; one patient had peristomal disease. All patients had at least colonic involvement of their Crohn's. The patients received either a single infusion or a series of three 5 mg/kg Infliximab infusions. All four patients demonstrated rapid healing of PG within 4 weeks of the first infusion of Infliximab. PG healing followed improvement in bowel disease. Complete resolution without recurrence was noted in all patients. Rapid resolution of PG was noted in four female patients with fistulizing Crohn's disease treated with Infliximab. Healing was complete, without recurrence. The anti-TNF-alpha properties of Infliximab suggest that healing may be mediated by the drug's effect on cytokine pathways, perhaps by blunted T cell activation early in the inflammatory cascade. We suggest an independent effect of Infliximab on PG.

Adult↗