Intravenous Immunoglobulin Protocol Research Articles

Intravenous Immunoglobulin is Associated with Lower Rates of Reinfection in Solid Organ Recipients with Infection and Secondary Antibody Deficiency: A Multicenter Randomized Clinical Trial

<h3>Purpose</h3> In a multicenter randomized clinical trial we evaluated the safety and efficacy of an intravenous immunoglobulin (IVIG) protocol to decrease the rate of reinfection in solid organ recipients with severe infections and secondary antibody deficiency. <h3>Methods</h3> Distribution: Heart 20, Lung 15, Kidney 5, Liver transplantation 4 were randomized. Patients with post transplant severe infections and secondary antibody deficiency (defined as IgG < 600 mg/dL) were included. IVIG protocol: Two doses of 15 grams (interval between doses 7-15 days) followed by another 3 doses of 20 grams (interval between doses 15-30 days) of a 5% IVIG product. 39 patients that completed the protocol were analysed [IVIG in combination with conventional antimicrobial therapy (n=21) versus conventional antimicrobial therapy alone (n=18)]. Specific antibodies were tested at inclusion in the clinical trial (V1) and 30-45 days after last IVIG dose (last-visit, V7) in a subgroup of patients to assess the kinetics of humoral immunity reconstitution. <h3>Results</h3> The primary outcome measure (rate of reinfection) was significantly lower in patients randomized to receive IVIG as compared with patients receiving only conventional antimicrobial therapy (28.6 vs 66.7%, chi-square test, p=0.017). Mean number of reinfections tended to be lower in IVIG group (0.47, interval 1-3, versus 0.89, interval 1-4, Mann-Whitney test, p=0.056). IVIG recipients tended to have lower IgG levels in V1 but disclosed significantly higher IgG concentrations at distinct visits during follow-up. Significantly higher levels of specific IgG anti-cytomegalovirus, IgG anti-clostridium difficile toxins A and B and IgG1 anti-tetanus toxoid antibodies was demonstrated at V7 in patients who received IVIG as compared with patient that were treated with antimicrobial therapy alone. A significant decrease of serum IL6 and BAFF levels (V1 versus V7) was demostrated in IVIG treated patients. IVIG infusions were well tolerated. <h3>Conclusion</h3> In a multicenter randomized clinical trial we have demonstrated that IVIG is associated with a lower rate of reinfection in solid organ transplantation with severe infection and secondary IgG hypogammaglobulinemia.

Modified method of intravenous immunoglobulin administration for patients with intractable multifocal motor neuropathy: A case report

AbstractBackgroundWe report a case of a 64‐year‐old Japanese man who was diagnosed with definite multifocal motor neuropathy and successfully treated with administration of intravenous immunoglobulin (IVIg) spread over two separate weeks.Case presentationAfter IVIg administration (30 g/day, five consecutive days), motor function was improved, but it was not possible to maintain the muscle strength just a few months after treatment. Although plasma exchange and cyclosporine were combined, the patient developed muscle weakness just 2 weeks after initial IVIg treatment. His grip strength decreased to 0 kg, proximal upper‐limb muscle strength reduced to 2/5 according to manual muscle testing, and muscle weakness developed in the proximal lower limb muscle. We modified IVIg administration protocol from five consecutive days to two separate weeks: 3 days in the first week and 2 days in the third week without changing the total dose per month. After initiation of divided IVIg protocol, muscle weakness dramatically improved, and muscle power could be kept normal. Corrected optical density value of immunoglobulin M antibodies against GM1 elevated in the all clinical course did not correlate with muscle strength improvement. Serum immunoglobulin G levels became stable in ≥2000 mg/dL, and were associated with muscle strength improvement.ConclusionAdministration of IVIg over two separate weeks might be a treatment option in intractable patients with multifocal motor neuropathy.

AB0937 Intravenous Immunoglobulin (IVIG) is Effective and Safe in Severe or Refractory Rheumatic Diseases

BackgroundIntravenous immunoglobulin (IVIG) is effective in a wide range of clinical conditions, other than primary immunodeficiency, including rheumatic diseases. In fact, in the era of newer immunosuppressive drugs, there has...

Evaluating the impact of pre‐transplant desensitization utilizing a plasmapheresis and low‐dose intravenous immunoglobulin protocol on BK viremia in renal transplant recipients

A correlation exists between polyomavirus BK (BKV) viremia in renal transplant recipients (RTR) and the degree of immunosuppression. However, the impact of pre-transplant desensitization on the incidence of BKV viremia is unknown. This retrospective study evaluated living-donor RTR between January 2004 and December 2008 receiving routine BKV viral load monitoring. Patients were divided into those who underwent pre-transplant desensitization (n = 20) and those who did not (n = 71). The primary endpoint was the incidence of BKV viremia at 1 year post transplant. All demographic data were similar, except for more female patients (65% vs. 36.6%; P = 0.0392) in the desensitized group. More desensitized patients had a previous transplant (75% vs. 12.7%; P < 0.0001) and were more likely to be induced with basiliximab (75% vs. 35.2%; P = 0.0021). Following transplantation, antibody-mediated rejection (AMR) rates were highest in the desensitized group (55% vs. 1.4%; P < 0.0001). The incidence of BKV viremia at 1 year post transplant was significantly higher in desensitized patients (45% vs. 19.7%; P = 0.0385). Desensitization was also associated with a higher prevalence of BKV viremia at any time post transplant (50% vs. 22.5%; P = 0.0245), polyomavirus-associated nephropathy (20% vs. 2.8%; P = 0.0198) and BKV-related allograft loss (10% vs. 0%; P = 0.0464). Also of note, in a subgroup analysis of only our desensitized patients, it did not appear that development of AMR significantly impacted the incidence of BKV viremia in these individuals. This analysis reveals that pre-transplant desensitization significantly increases the risk for BKV viremia and nephropathy.

Restoration of humoral immunity after intravenous immunoglobulin replacement therapy in heart recipients with post‐transplant antibody deficiency and severe infections

IgG hypogammaglobulinemia is a risk factor for infection in heart recipients. We assessed reconstitution of humoral immunity after non-specific intravenous immunoglobulin (IVIg) replacement therapy administered to treat secondary IgG hypogammaglobulinemia in heart recipients with severe infections. The study population comprised 55 heart recipients who were administered IVIg (IVIg group) and 55 heart recipients with no severe infectious complications (control group). An event was defined as a severe infection requiring intravenous drug therapy during the first year after transplantation. The IVIg protocol comprised non-specific 5% pasteurized IVIg at a dose of 300-400 mg/kg/months. IgG titers were lower in the IVIg group than in controls at seven d (577 vs. 778 mg/dL, p < 0.001) and at one month (553 vs. 684, p = 0.003). After IVIg therapy, IgG concentrations were similar in both groups at three months (681 vs. 737, p = 0.25) and at six months (736 vs. 769, p = 0.46). At three months, the IVIg group had higher levels of antitetanus toxoid and anti-HBs (ELISA, 2.07 ± 2.11 vs. 0.60 ± 1.24 mg/dL [p = 0.003] and 42 ± 40 vs. 11 ± 31 IU/mL [p = 0.005], respectively) than controls. The mean number of infectious complications was significantly lower after IVIG therapy in the IVIG group. IVIg was associated with restoration of humoral immunity in heart recipients with post-transplant IgG hypogammaglobulinemia and severe infections.

Long-Term Therapy with Intravenous Immunoglobulin is Beneficial in Patients with Autoimmune Diseases

The objective of our study is to evaluate the clinical response, steroid-sparing and adverse affects of long-term intravenous immunoglobulin (IVIG) treatment for autoimmune diseases. Patients were recruited from the Rheumatology clinic. All patients fulfilled the ACR criteria for the appropriate autoimmune disease. Beneficial effects of IVIG therapy in systemic lupus erythematosus (SLE) patients were evaluated utilizing the SLEDAI score. Clinical remission in patients with other autoimmune diseases was evaluated by a rheumatologist. Data were retrieved retrospectively from an IVIG database (Excel program). Seventeen patients-SLE (n = 11) and other autoimmune diseases (n = 6)-received a high dose IVIG protocol monthly for 6months, followed by therapy every 2-3months. The patients received a mean of 7.9courses/patient. The mean follow-up for long-term therapy was 30months. The response to IVIG treatment was remission in 12 patients. Change in the SLEDAI score following IVIG therapy was significant (p < 0.05). In responders, IVIG harbored a significant steroid-sparing effect (p < 0.05). Mild and transient adverse effects persisted with long-term therapy in 50% of patients. Severe adverse effects (pulmonary embolism and seizures) occurred early in two patients with SLE and secondary anti-phospholipid syndrome. Long-term IVIG therapy is beneficial and carries a good safety profile for SLE and other autoimmune diseases.

Use of intravenous immunoglobulin therapy during pregnancy in patients with pemphigus vulgaris

Pemphigus vulgaris (PV) is a potentially fatal autoimmune disease characterized by the presence of in vivo deposition of antibodies against cell surface antigens desmoglein 1 and desmoglein 2 in the epidermis. To report the treatment outcomes in pregnant PV patients treated with intravenous immunoglobulin (IVIg) therapy. Eight patients with active disease during pregnancy were treated. Patients were treated with a dose of 2 g/kg/cycle. Seven patients were treated for 2 months on post-partum basis. Main outcome measures were as follows: (i) pregnancy outcome; (ii) presence of neonatal pemphigus; (iii) post-partum flare; (iv) effect of IVIg on present and future pregnancies; (v) immediate and long-term side-effects in the mother and child. Patients ages ranged from 20 to 43 years (mean 29.6). All patients had severe and widespread disease involving the skin and multiple mucous membranes. Patients one to seven responded to IVIg therapy and did not have a post-partum flare. Patient eight could not tolerate IVIg because of intense headaches and significant post-partum flare. None of the neonates had pemphigus. Three patients who completed the IVIg protocol had normal second pregnancies. One patient who did not complete the protocol had a miscarriage during the second pregnancy. Since last observation, none of the patients have had a recurrence of the disease or another pregnancy. The data suggests that IVIg can be useful and safe in treating pregnant patients with PV. No long-term adverse effects of IVIg in the mother or in the child were observed based on a long-term follow-up.

Intravenous Immunoglobulin Therapy in Autoimmune Mucocutaneous Blistering Diseases

Intravenous immunoglobulin (IVIg) is a biologic agent that is being increasingly used in the treatment of autoimmune and chronic inflammatory disorders. It is approved by the US FDA for the treatment of primary immunodeficiencies, immune thrombocytopenic purpura, Kawasaki disease, bone marrow transplantation in patients aged over 20 years, chronic B-cell lymphocytic leukemia, and pediatric AIDS. IVIg has been used off-label for several diseases, clinical symptoms and syndromes. Our aim was to determine if there is evidence to support the efficacy of IVIg therapy in autoimmune mucocutaneous blistering diseases (AMBDs). We searched the PubMed database for studies on pemphigus and pemphigoid using the following criteria: (i) English language; (ii) minimum of five patients; (iii) diagnosis based on histology and immunopathology; and (iv) statistical analysis of data for comparison of efficacy provided. We evaluated the data and present information on the number of participants in each study, pre-IVIg therapy, indications for the use of IVIg, IVIg protocol (dose and interval) used, concomitant therapies, clinical outcome, follow-up period, and serologic studies. The quality of the evidence presented in this review is at Level A according to the UK National Health Service criteria. Twenty-three studies that were published between May 1999 and April 2010 were identified. One randomized controlled trial was found and all other studies were case series. Data on 260 patients treated with IVIg were analyzed: 191 patients with pemphigus and 69 patients with pemphigoid. Overall, 245 patients showed improvement with IVIg therapy. IVIg demonstrated a corticosteroid-sparing effect. In the studies presented, the incidence of serious adverse effects was not significant. The best available evidence in the literature indicates that IVIg is efficacious and has a good safety profile in the treatment of AMBDs.

Evaluation of fetuses in a study of intravenous immunoglobulin as preventive therapy for congenital heart block: Results of a multicenter, prospective, open‐label clinical trial

The recurrence rate of anti-SSA/Ro-associated congenital heart block (CHB) is 17%. Sustained reversal of third-degree block has never been achieved. Based on potential reduction of maternal autoantibody titers as well as fetal inflammatory responses, intravenous immunoglobulin (IVIG) was evaluated as preventive therapy for CHB. A multicenter, prospective, open-label study based on Simon's 2-stage optimal design was initiated. Enrollment criteria included the presence of anti-SSA/Ro antibodies in the mother, birth of a previous child with CHB/neonatal lupus rash, current treatment with < or = 20 mg/day of prednisone, and <12 weeks pregnant. IVIG (400 mg/kg) was given every 3 weeks from week 12 to week 24 of gestation. The primary outcome was the development of second-degree or third-degree CHB. Twenty mothers completed the IVIG protocol before the predetermined stopping rule of 3 cases of advanced CHB in the study was reached. CHB was detected at 19, 20, and 25 weeks; none of the cases occurred following the finding of an abnormal PR interval on fetal Doppler monitoring. One of these mothers had 2 previous children with CHB. One child without CHB developed a transient rash consistent with neonatal lupus. Sixteen children had no manifestations of neonatal lupus at birth. No significant changes in maternal titers of antibody to SSA/Ro, SSB/La, or Ro 52 kd were detected over the course of therapy or at delivery. There were no safety issues. This study establishes the safety of IVIG and the feasibility of recruiting pregnant women who have previously had a child with CHB. However, IVIG at low doses consistent with replacement does not prevent the recurrence of CHB or reduce maternal antibody titers.

Recent Developments in the Management of Neonatal Hyperbilirubinemia

After completing this article, readers should be able to: 1. Describe the morbidity associated with exchange transfusion used to treat neonatal hyperbilirubinemia. 2. Explain how phototherapy affects bilirubin. 3. Describe potential toxicities of phototherapy. 4. Explain the role of carboxyhemoglobin in hemolysis. 5. Delineate the guidelines for administering intravenous immunoglobulin to healthy ABO-incompatible Coombs-positive neonates. 6. Describe the action of protoporphyrins on bilirubin. Recent clinical trends toward early discharge coupled with a new, more relaxed, “kinder, gentler approach” to the treatment of newborn hyperbilirubinemia have thrust concerns about bilirubin-related toxicity once again to the forefront of neonatologists’ consciousness. In recent years we even have witnessed a resurgence of kernicterus, which had been rendered almost nonexistent in the 1970s and 1980s. Although exchange transfusion is the oldest and most effective method of treating hyperbilirubinemia, mortality associated with this therapy has been reported to be between 0.3% and 1.2% in healthy infants and as high as 10% to 25% in sicker preterm infants. Furthermore, potential morbidity related to exchange transfusion remains significant and includes anemia, apnea, bradycardia, hypothermia, sepsis, necrotizing enterocolitis, thromboembolic phenomena, graft versus host disease, transient metabolic abnormalities, and thrombocytopenia. Accordingly, it behooves us to re-evaluate other therapeutic modalities for hyperbilirubinemia that may be equally efficacious but less invasive. Ever since the 1950s, when Sister Ward of Rochford General Hospital in Essex noted that a jaundiced baby’s skin had “faded” in natural sunlight, physicians have been searching for artificial light sources that might be used safely to treat neonatal hyperbilirubinemia. Phototherapy, which has become the standard of care, has had such a dramatic impact that a recent editorial raised the concern that exchange transfusions are becoming extinct and lamented the fact that future generations of house officers may not receive adequate training in this procedure. Under the effects of phototherapy light with maximal irradiance in the …