Intravenous immunoglobulin (Endobulin) clinical tolerance: prospective therapeutic follow-up of 142 adults and children

PURPOSE: Prospective report of Endobulin clinical tolerance experience for 19 months over a large number of patients. METHOD: Collect diagnosis, age, gender, weight, dose regimen, infusion duration, and clinical tolerance of Endobulin. Treatment with this product was the only inclusion criteria in this follow-up. RESULTS: A hundred and forty-two patients, 85 children and 57 adults, mean age 23 (1-85 years) received 70 substitutive treatments for primary immunodeficiency, 36 substitutive treatments for secondary immunodeficiency and 36 immunomodulatory treatments. A thousand six hundred and sixty Endobulin infusions that led to 14, 061.5 g, from 52 different batches. Tolerance was judged as good for 135 patients even though side effects occurred in 2 of them. Thus, 133 out of 142 patients, that is 93.7% did not present any side effect and their tolerance to Endobulin infusions was defined as good. Tolerance was bad for 7 patients because of side effects occurrence. For a mean number of 11.7 infusions per patient (1-31), the 9 side effects observed led to a rate of 0.54% of collected infusions and 6.3% of patients included. CONCLUSION: This therapeutic follow-up of 142 patients confirms Endobulin clinical tolerance judged as good in 93.7% of patients (133/142) with a very low rate of side effects of 0.54% of infusions (9 side effects for 1660 infusions) for a mean number of 11.7 infusions per patient for an average of 10.9 months follow-up.     

Intravenous immunoglobulin therapy: New aspects and outlook

Summary Experiences gathered while exploring the usefulness of intravenous immunoglobulin for children with idiopathic (immune) thrombocytopenic purpura (ITP) are reviewed in view of further investigations characterizing the effects of IgG i.v. in other immune diseases without detectable antibody deficiency. The most pertinent factors to be considered are i) the heterogeneity of an immune disease investigated; ii) the criteria used to evaluate the effects of the IgG therapy; iii) the IgG preparations used and i.v. dose-fractionation. Controlled, prospective clinical trials will be required to further explore the practical usefulness of IgG i.v.     

Intravenous immunoglobulin for secondary immunodeficiency

Summary Viral and bacterial infections are a serious cause of morbidity and mortality in patients immunocompromised as a result of malignancy, burns, trauma, viral infections or chemotherapy. The development of safe and effective antibody preparations suitable for intravenous use have transformed the lives of patients suffering from forms of primary immunodeficiency characterised by antibody deficiency. However, the role of intravenous immunoglobulin (IV IgG) preparations in the treatment of secondary immunodeficiencies is less clear and although many anecdotal reports exist for the use of IV IgG in various secondary immunodeficiencies (Table 1), there have been few controlled trials of a sufficient size that have demonstrated clear-cut efficacy in many of the suggested new indications.     

Intravenous immunoglobulin treatment in hematological diseases

Abstract: In the last decade large amounts of intravenous immunoglobulin (IVIg) have been used worldwide. Doubts exist as to whether this increased use is paralleled by a comparable growth of reliable data on the therapeutic effectiveness of IVIg. We performed a literature search using MEDLINE from January 1981 to January 1997 and analysed articles on the use of IVIg in hematological disorders and searched for published guidelines. For most hematological disorders, evidence to use IVIg as first line therapy is not very strong. For many disorders no controlled trials have been performed. In published guidelines, IVIg is only recommended, with a few exceptions, when other treatments have failed or are contraindicated. Therefore the increase of consumption of IVIg can not be explained by an increase in established indications in hematology.     

Intravenous immunoglobulin treatment for pregnancy-associated dermatomyositis

Pregnancy-associated dermatomyositis (DM) is a rare disorder, until recently treated only with corticosteroids due to the toxicity of other immunosuppressive agents for the fetus. We present a pregnant woman with DM treated successfully with intravenous immunoglobulin (IVIG) and medium dose corticosteroids. A 42-year-old woman presented with a rash, muscle weakness and increased muscle enzymes on the 15th week of her first pregnancy. After the diagnosis of DM she was treated with the combination of medium dose corticosteroids and IVIG. The patients’ symptoms resolved rapidly. No complications were noted for either her or the fetus. Both she and her son remain disease-free after 6 years follow-up. In conclusion, IVIG treatment is a safe and effective alternative for pregnancy-associated DM.     

Intravenous immunoglobulin therapy of antiphospholipid syndrome

OBJECTIVE: To review the role of intravenous immunoglobulin (IVIg) in antiphospholipid syndrome (APS). METHODS: A literature search was carried out for the immunopathogenesis of APS, laboratory evidence for the beneficial effect of IVIg in APS, and the clinical use of IVIg in APS. RESULTS: There is both laboratory and clinical evidence for the beneficial role of IVIg in APS. IVIg succeeded in in vitro inhibition of anticardiolipin antibodies and lupus anticoagulant, and in the amelioration of experimental APS. Although there are few case reports about IVIg therapy in the haematological manifestations of APS, most of the reports focus on the use of IVIg in the obstetric complications of APS. Hence, in several patient series the use of IVIg either solely or in combination with aspirin/heparin resulted in successful pregnancy outcome in the vast majority of APS patients with recurrent abortions. In addition, IVIg was also beneficial in antiphospholipid antibody-positive patients undergoing in vitro fertilization. CONCLUSION: APS, an autoimmune disease whose main features are vascular thrombosis and pregnancy morbidity, is a good candidate for immunotherapy with IVIg that contains anti-idiotypes directed towards patients' pathogenic antiphospholipid antibodies. Future research should determine when to use anticoagulation, IVIg or both in the treatment of APS.     

Intravenous immunoglobulin treatment of lupus nephritis

OBJECTIVE: To evaluate the clinical response of treatment-resistant membranous and membranoproliferative lupus nephritis to intravenous immunoglobulin (IVIg). METHODS: Seven lupus nephritis patients who failed to respond to at least prednisone and cyclophosphamide were studied. A kidney biopsy showing either membranous or membranoproliferative glomerulonephritis was available in six patients. They were treated with six courses (patients 1 and 2) or 1 or 2 courses (patients 3 through 7) of high-dose IVIg. For patients 3 through 7, the plasma levels of albumin, total cholesterol, urea, creatinine, dsDNA antibody titers, and daily proteinuria were measured just before the IVIg therapy, immediately on completion, and 6 months later. RESULTS: All seven patients had a beneficial response to IVIg. In patient 1, decrease in proteinuria was evident 2 weeks after IVIg was started, nephrotic syndrome gradually disappeared, and she had no proteinuria in 3 years' follow-up. Decline in proteinuria was evident in patient 2 after the 4th IVIg course, but proteinuria reached the pretreatment level 4 months after the therapy ended. In patients 3 through 7, the mean daily proteinuria before IVIg (5.3 +/- 2.1 g) decreased after 1 or 2 IVIg courses (3.3 +/- 1.4 g), and further decreased when measured 6 months later (2.1 +/- 1.3 g). Similarly, the plasma cholesterol level decreased while the plasma albumin level increased after IVIg. CONCLUSIONS: IVIg might be effective in treatment-resistant membranous or membranoproliferative lupus nephritis. Future studies should concentrate on determining the preferred treatment protocol of IVIg for the various classes of lupus nephritis.     

Intravenous immunoglobulin therapy for diabetic amyotrophy

A 49-year-old woman with diabetes mellitus developed progressive weakness and atrophy of both thighs rendering her wheelchair-bound within two months. The neurological findings and electrophysiological test results were compatible with diabetic amyotrophy (DA). Immediately after intravenous immunoglobulin (IVIg) therapy (20 g x 3 days), she became able to walk with a cane. After the next course of the therapy, she could walk without assistance. This dramatic effect of IVIg therapy together with the recent observation of vasculitic neuropathy in DA indicates an inflammatory process in this condition, and gives support to this treatment for DA.     

Intravenous immunoglobulin therapy for juvenile dermatomyositis: efficacy and safety

OBJECTIVE: To assess the efficacy of intravenous immunoglobulin (IVIG) for the treatment of juvenile dermatomyositis (JDM) in patients who were unresponsive to corticosteroids (steroid resistant or steroid dependent) or showed unacceptable toxicity. METHODS: A retrospective chart review of the course of all patients with JDM treated with IVIG who attended the Dermatomyositis Clinic at The Hospital for Sick Children, Toronto, Canada, from August 1986 to December 1996. RESULTS: Eighteen patients with JDM were treated with IVIG. Ten patients were taking additional 2nd line treatments, methotrexate, azathioprine, cyclosporine, and cyclophosphamide. The main indication for starting IVIG was the failure of steroid therapy to induce remission of JDM. Twelve patients showed clinical improvement with IVIG. In these patients, the corticosteroid dose was reduced by > 50% for > 3 months without clinical or biochemical flare. Nine of these 12 patients had IVIG alone as a 2nd line agent, whereas 3 patients were treated with additional agents. Six patients remained steroid dependent; they subsequently required multiple agents to induce remission of JDM. CONCLUSION: Most steroid dependent or steroid resistant patients in our clinic were able to markedly reduce their dose of corticosteroid with the addition of IVIG. Given the retrospective nature of our data and the fact that multiple agents were sometimes used together, it will be important to confirm these findings in a controlled trial.     

Intravenous immunoglobulin and autoimmune thrombocytopenic purpura: 22 years on

Autoimmune thrombocytopenic purpura is now commonly treated with high doses of intravenous immunoglobulins. Twenty-two years after this treatment was first shown to be effective, several questions remain. We review here current knowledge concerning the frequency and type of side-effects and the probable mechanism of action of intravenous immunoglobulins. We suggest that the currently recommended dose of intravenous immunoglobulins (2 g/kg body weight) could be halved, that the total dose of intravenous immunoglobulins should be administered as a single infusion, that non-responders could be given another equal dose on day 3, and that intravenous immunoglobulins plus prednisolone should be considered as the gold standard for treatment of the most severe forms of the disease. Finally, as intravenous immunoglobulins have only a transient effect, they cannot be considered as a curative treatment for patients with chronic autoimmune thrombocytopenic purpura.     

Intravenous immunoglobulins as therapeutic agents

Intravenous immunoglobulins are stable monomeric pooled human IgG preparations for therapeutic use. Three intravenous immunoglobulins licensed in the United States are generally therapeutically equivalent. Intravenous immunoglobulin is the preferred agent for replacement therapy for most patients with primary or secondary antibody immunodeficiency because of the rapidity and ease of giving large quantities of IgG, even by self-administration. Disadvantages of intravenous immunoglobulins include frequent (approximately 10%) but usually not serious side effects, the need for venous access (often difficult in infants and young children), and high cost. Intravenous immunoglobulins are also beneficial in the prevention of certain viral infections, such as cytomegalovirus pneumonia and varicella; they may also have a synergistic effect with antibiotics in certain bacterial diseases. Intravenous immunoglobulin has also been used successfully in the management of idiopathic thrombocytopenia purpura, Kawasaki disease, and certain autoimmune diseases. Intravenous immunoglobulin may also be of use in certain high-risk and premature newborns.     

Intravenous immunoglobulin for resistant Clostridium difficile infection

Clostridium difficile (CD)-associated diarrhoea and colitis may relapse in up to 20% of treated patients. We present a patient who failed to respond over a 6-month period to treatment either singly or in combination with metronidazole, vancomycin, rifampicin, cholestyramine and probiotics. Her diarrhoea rapidly resolved after a 3-day course of intravenous immunoglobulin. This treatment may compensate for a failed immune response to CD toxin and should be considered for relapsing CD-associated diarrhoea where there is no response to conventional treatment strategies.     

静脉用免疫球蛋白在系统性红斑狼疮治疗中的应用

静脉用免疫球蛋白(IVIg)主要通过Fc受体介导免疫调节作用治疗系统性红斑狼疮(SLE),其他机制包括抑制补体介导的损伤,调控细胞因子的产生;调控独特型抗体网络,中和病理性自身抗体;调节B细胞和T细胞功能,下调抗体的产生等。IVIg已成功治疗SLE相关的顽固性血小板减少症、中枢神经系统狼疮、狼疮性肾炎及对传统免疫治疗无效或同时合并感染的SLE。     

Intravenous immunoglobulin therapy in thrombocytopenic infectious mononucleosis

Severe haemorrhagic thrombocytopenia in infectious mononucleosis with positive Epstein-Barr virus (EBV) serology remains a threatening clinical problem. Although rare, fatalities have been reported. We present clinical, haematological and serological details of two patients with diffuse bleeding associated with this disease who failed conventional steroid treatment and who both responded promptly and effectively to infusions of intravenous immunoglobulin (i.v. Ig). A platelet immunofluorescence test was used to detect platelet antibodies in acute and recovery phase patient sera against autologous recovery platelets and against normal allogeneic group O platelets. In one patient, indirect immunofluorescence using recovery platelets detected an IgG platelet autoantibody with acute phase autologous serum. No platelet antibody was detected in the second patient. The data presented demonstrate that response to i.v. Ig is independent of serological detection of platelet autoantibodies. Therapy with i.v. Ig should be considered in any case of haemorrhagic thrombocytopenia associated with EBV infection shown to be refractory to steroid treatment.