Home About us Contact
|
Home About us Contact | ||
|
|
||
Infusion Reactions (infusion + reaction)
Selected AbstractsEfficacy and tolerance of infliximab in children and adolescents with Crohn's diseaseINFLAMMATORY BOWEL DISEASES, Issue 6 2004Dr. Thierry Lamireau Abstract Infliximab, a monoclonal antibody against tumor necrosis factor-alpha, has been shown to be effective for the treatment of refractory Crohn's disease in adult patients, but experience in pediatrics is limited. This retrospective study included 88 children and adolescents, 39 girls and 49 boys, with a median age of 14 years (range 3.3,17.9). Infliximab was indicated for active disease (66%) and/or fistulas (42%) that were refractory to corticosteroids (70%), and/or other immunosuppressive (82%) agents, and/or parenteral nutrition (20%). Patients received 1 to 17 infusions (median 4) of 5 mg/kg (range 3.8,7.3) of infliximab during a median time period of 4 months (1,17 months). Infusion reaction was noted in 13 patients (15%), with a total of 16 reactions in 450 infusions (4%). At Day 90 after the first infusion of infliximab, symptoms improved in 49% of patients, whereas 29% of patients were in remission and 13% of patients relapsed. From Day 0 to Day 90, Harvey,Bradshaw score decreased from 7.5 to 2.8 (P < 0.001), C-reactive protein from 36 to 16 mg/L (P < 0.01), and 1-hour erythrocyte sedimentation rate from 35 to 17 mm (P < 0.01). Dosage of corticosteroids decreased from to 0.59 to 0.17 mg/kg/d (P < 0.001); 53% of patients could be weaned of corticosteroids and 92% of parenteral nutrition. Treatment with infliximab is well tolerated and effective in most children and adolescents with Crohn's disease that is refractory to conventional immunosuppressive therapy. Nevertheless, long-term efficacy remains to be shown, and further studies are urgently needed to precisely determine the best modality of continuing treatment. [source] Clinical trial: benefits and risks of immunomodulators and maintenance infliximab for IBD-subgroup analyses across four randomized trialsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2009G. R. LICHTENSTEIN Summary Background, Benefits and risks of concomitant immunomodulators and maintenance infliximab in inflammatory bowel disease (IBD) patients have not been adequately evaluated. Aim, To assess the effect of concomitant immunomodulator and infliximab maintenance therapy using data from four prospective, randomized Phase 3 trials in IBD patients. Methods, Overall, 1383 patients from ACCENT I and ACCENT II [luminal and fistulizing Crohn's disease trials] and ACT 1 and ACT 2 [ulcerative colitis trials] were analysed. Patients were treated with placebo or infliximab 5 or 10 mg/kg at weeks 0, 2 and 6 followed by every-8-week maintenance therapy. Clinical response, clinical remission, fistula response, complete fistula response, infection and infusion reaction rates; serum infliximab concentrations and immunogenicity were summarized by baseline concomitant immunomodulator subgroup (use or non-use). Results, Overall, almost 40% of evaluated IBD patients received concomitant immunomodulators. Efficacy, infection, and serious infection rates were generally similar in patients who received maintenance therapy with or without concomitant immunomodulators. There were no consistent differences in serum infliximab concentrations with or without immunomodulators in patients who received scheduled maintenance therapy. Concomitant immunomodulators reduced infusion reactions and immunogenicity. Conclusion, Concomitant immunomodulators did not improve efficacy or pharmacokinetics in IBD patients who received maintenance infliximab. [source] The safety profile of anti-tumour necrosis factor therapy in inflammatory bowel disease in clinical practice: analysis of 620 patient-years follow-upALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2009C. W. LEES Summary Background, Anti-TNF agents are now widely used in Crohn's disease (CD), and in ulcerative colitis (UC). Aim, To review the safety profile of anti-TNF agents in all patients treated with infliximab in Edinburgh from 1999 to 2007. Methods, Complete data were available on 202/207 patients comprising 157 CD, 42 UC and three coeliac disease. Median follow-up was 2.4 years (1.0,4.9) with a total of 620 patient-years follow-up. About 19.1% of CD patients were subsequently treated with adalimumab. Results, Seven deaths (3.3%) occurred in follow-up; only one death was <1 year post-infliximab (at day 72, from lung cancer). A total of six malignancies (three haematological, three bronchogenic) and six cases of suspected demyelination (three with confirmed neurological disease) were reported. In the 90 days following infliximab, 95 adverse events (36 serious) occurred in 58/202 (28.7%) patients. In all, 42/202 (20.8%) had an infectious event (22 serious) and 27/202 (13.4%) of patients had an infusion reaction: 19 acute (four serious) and eight delayed (three serious). Conclusions, Serious infections, malignancies and neurological disease complicate anti-TNF use in clinical practice. Although evidence for causality is unclear, potential mechanisms and predisposing factors need to be explored. In individual patients, the risk/benefit analysis needs to be carefully assessed and discussed prior to commencement of therapy. [source] Anti-infliximab IgE and non-IgE antibodies and induction of infusion-related severe anaphylactic reactionsALLERGY, Issue 5 2010A. Vultaggio To cite this article: Vultaggio A, Matucci A, Nencini F, Pratesi S, Parronchi P, Rossi O, Romagnani S, Maggi E. Anti-infliximab IgE and non-IgE antibodies and induction of infusion-related severe anaphylactic reactions. Allergy 2010; 65: 657,661. Abstract Background:, Infliximab is a chimeric monoclonal antibody against TNF-, useful in the treatment of many chronic inflammatory diseases. Severe anaphylaxis has been reported during therapy, although the exact mechanism has not been fully defined. The reactions have been related to the infliximab immunogenicity and development of specific antibodies. Aims of the study:, Evaluation of the development of IgE and non-IgE antibodies to infliximab and their relationship with infusion reaction. Methods:, Seventy-one patients (11 reactives, 11 therapeutically nonresponders, and 49 unreactive therapeutically responders) and 20 non,infliximab-exposed control subjects (ten rheumatoid arthritis, five spondyloarthropathies, five vasculitis) were evaluated for the presence of IgE (ImmunoCAP assay), IgM, and non,isotype-specific (ELISA assays) anti-infliximab antibodies. Sera were obtained at baseline and during the course of treatment, before each infliximab infusion. Results:, Eleven out of 71 patients had a hypersensitivity reaction to infliximab. Non,isotype-specific anti-infliximab antibodies were detected in eight reactive and two nonresponder patients. Three patients with severe reactions displayed anti-infliximab IgE antibodies and positive skin testing. Detectable levels of anti-infliximab IgM antibodies were shown in three additional IgE- and skin testing-negative patients. IgE and IgM antibodies to infliximab were not detectable in the two nonresponder patients. Antibodies developed before the 2nd and the 3rd infusion, and their appearance was strictly related to the timing of the reaction. Conclusions:, This report indicates that in some patients with infliximab-related severe reactions, IgE or IgM antibodies against infliximab were detectable. The majority of reactions could be predicted by the appearance of anti-infliximab antibodies. [source] P43 Acute urticaria to infliximabCONTACT DERMATITIS, Issue 3 2004Ana Giménez-Arnau Infliximab is a chimeric antitumor necrosis factor-alpha monoclonal antibody used to treat Crohn's disease and rheumatoid arthritis. Acute infusion reactions, headache, fever, chills, urticaria and chest pain were seen in 17% of patients with infliximab compared with 7% of those receiving placebo. Other adverse cutaneous reactions are fungal dermatitis, eczema, seborrhoea, hordeolum, bullous eruption, furunculosis, periorbital oedema, hyperkeratosis, rosacea, verruca, skin pigmentation, alopecia, leukocytoclastic vasculitis, lichenoid drug eruption, erythema multiforme, perniosis-like eruption, granuloma annulare and acute folliculitis. Any pathogenic mechanism has been suggested. Patch test with infliximab can induce flare-up of lesions, nausea and malaise and suggest a percutaneous absortion. A sixty years-old man with atopy background and rheumatoid arthritis treated with Remicare®, infliximab who developed a severe acute urticaria with angioedema is presented. The lesions appearance after previous endovenous administrations and the worsening spreading wheals days after the injection clinically suggested an hypersensitivity mechanism. The protocolized study drug hypersensitivity performed showed only the Prick Test positivity with infliximab at 30/60 minutes. Patch test with infliximab was negative and any adverse event was reported. Actually the patient is treated with etanercept and this drug is well tolerated. This result suggested a type I hypersensitivity mediated reaction. Urticaria could be induced as immunologic reaction of the host against the murine part of infliximab, just as it hapens with other antichimeric antibodies. [source] Infliximab safety profile and long-term applicability in inflammatory bowel disease: 9-year experience in clinical practiceALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2010Y. ZABANA Aliment Pharmacol Ther,31, 553,560 Summary Background, Most available data on infliximab therapy come from large, short-term, pivotal RCTs and concerns about long-term safety profile still remain. Aim, To evaluate the long-term safety profile of infliximab in inflammatory bowel disease (IBD) in a clinical practice setting. Methods, Since 1999, all IBD patients treated with infliximab were registered and clinical outcomes prospectively recorded up to March 2008, loss of follow-up or patient's death. Infliximab regimens and preventive measures were in accordance with the prevalent guidelines or with the manufacturer's recommendations. Results, One hundred fifty-two patients were included (121 Crohn's disease, 24 ulcerative colitis, 7 indeterminate colitis), with a median of 5 infliximab infusions (IQR 3,8) and 87% of patients received at least three infusions. Seventy-nine per cent of them received concomitant immunomodulators and 70% were pre-medicated with hydrocortisone from the first infusion. After a median follow-up of 142 weeks, 13% presented infusion reactions, 13% viral or bacterial infections and two patients developed neoplasia. The mortality rate was 2.6% (four patients). Conclusions, Infliximab therapy is safe when the recommended preventive measures are implemented, with a rate of serious adverse events less than 10%. No new safety signals were found. [source] Clinical trial: benefits and risks of immunomodulators and maintenance infliximab for IBD-subgroup analyses across four randomized trialsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2009G. R. LICHTENSTEIN Summary Background, Benefits and risks of concomitant immunomodulators and maintenance infliximab in inflammatory bowel disease (IBD) patients have not been adequately evaluated. Aim, To assess the effect of concomitant immunomodulator and infliximab maintenance therapy using data from four prospective, randomized Phase 3 trials in IBD patients. Methods, Overall, 1383 patients from ACCENT I and ACCENT II [luminal and fistulizing Crohn's disease trials] and ACT 1 and ACT 2 [ulcerative colitis trials] were analysed. Patients were treated with placebo or infliximab 5 or 10 mg/kg at weeks 0, 2 and 6 followed by every-8-week maintenance therapy. Clinical response, clinical remission, fistula response, complete fistula response, infection and infusion reaction rates; serum infliximab concentrations and immunogenicity were summarized by baseline concomitant immunomodulator subgroup (use or non-use). Results, Overall, almost 40% of evaluated IBD patients received concomitant immunomodulators. Efficacy, infection, and serious infection rates were generally similar in patients who received maintenance therapy with or without concomitant immunomodulators. There were no consistent differences in serum infliximab concentrations with or without immunomodulators in patients who received scheduled maintenance therapy. Concomitant immunomodulators reduced infusion reactions and immunogenicity. Conclusion, Concomitant immunomodulators did not improve efficacy or pharmacokinetics in IBD patients who received maintenance infliximab. [source] Review article: infliximab therapy for inflammatory bowel disease , seven years onALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2006P. 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] Rituximab-associated acute thrombocytopenia: An under-diagnosed phenomenon,AMERICAN JOURNAL OF HEMATOLOGY, Issue 4 2009Ron Ram Acute infusion reactions are the most common documented adverse reactions reported with rituximab, with overt cytokine release syndrome, and hematological adverse events being much rarer. The clinical course of a patient with mantle cell lymphoma, who developed acute thrombocytopenia and leukopenia following rituximab administration, is described and the literature reviewed. Serum complement and the levels of three cytokines,TNF-,, IL-6, and IL-1, were measured 2 days after the infusion of rituximab by using ELISA assay. Drug-dependent antibodies against platelets were evaluated by two procedures as follows: an immunofluorescence test applying flow cytometry and Monoclonal Antibody Immobilization of Platelet Antigen (MAIPA). Serum levels of TNF-a were significantly increased compared with normal, whereas those of IL-6 and IL-1 were not increased significantly. Flow cytometry assay and the MAIPA assay failed to detect rituximab-dependent antibodies against platelets. Complement levels were decreased compared with normal. Literature search yielded 10 publications reporting on another 15 patients. The most common type of lymphoma was mantle cell lymphoma, six patients had bone marrow involvement, and 10 patients had splenomegaly. In 10 patients, acute cytopenia was preceded by cytokine release syndrome or infusion-related symptoms. Usually, thrombocytopenia was not associated with bleeding manifestations. Thrombocytopenia was the most commonly acute cytopenia reported. The postulated pathogenesis is associated with cytokine release syndrome and complement activation. Patients with potential risk factors like splenomegaly and bone marrow involvement, who develop clinical manifestations compatible with cytokine release syndrome, should be closely monitored for rituximab-associated cytopenia. Am. J. Hematol., 2009. © 2009 Wiley-Liss, Inc. [source] B cell depletion with rituximab in patients with diffuse cutaneous systemic sclerosisARTHRITIS & RHEUMATISM, Issue 2 2009Robert Lafyatis Objective To determine the safety of rituximab, to provide preliminary data regarding the potential efficacy of rituximab, and to investigate the effects of rituximab on autoimmunity and fibrosis in patients with diffuse cutaneous systemic sclerosis (dcSSc). Methods Fifteen patients with dcSSc, all of whom experienced their first non,Raynaud's disease,associated disease manifestation within 18 months of trial entry, were recruited to receive 2 intravenous doses of rituximab (1,000 mg), administered 2 weeks apart. Safety, clinical, and exploratory outcomes were evaluated at baseline and at 6 months. The primary outcome was the change in the modified Rodnan skin thickness score (MRSS) at 6 months compared with baseline. Results Adverse events included frequent infusion reactions and rare infections (urinary tract infection and dental abscess occurred in 1 patient each). The mean change in the MRSS between baseline and 6 months was not significant. Results of pulmonary function tests and other measures of major organ involvement were stable. The modest B cell infiltrates that were present in most skin biopsy specimens at baseline were completely depleted at 6 months in most patients. Autoantibody titers showed only modest and variable changes after treatment. Conclusion In this pilot study, treatment with rituximab appeared to be safe and well tolerated among patients with dcSSc. Rituximab treatment resulted in both depletion of circulating B cells and depletion of dermal B cells but had little effect on the levels of SSc-associated autoantibodies. Rituximab treatment did not appear to result in a significant beneficial effect on skin disease. The potential efficacy of rituximab in other organs such as the lung could not be clearly evaluated in this small open-label trial. [source] | ||||||||||