Efficacy Of Intravenous Immunoglobulin Research Articles

Prevention of recurrent miscarriage in women with antiphospholipid syndrome: A systematic review and network meta-analysis.

To compare and rank currently available pharmacological interventions for the prevention of recurrent miscarriage (RM) in women with antiphospholipid syndrome (APS). A search was performed using PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, CNKI, ClinicalTrials.gov, and the UK National Research Register on December 15, 2019. Studies comparing any types of active interventions with placebo/inactive control or another active intervention for the prevention of RM in patients with APS were considered for inclusion. The primary outcomes were efficacy (measured by live birth rate) and acceptability (measured by all-cause discontinuation); secondary outcomes were birthweight, preterm birth, preeclampsia, and intrauterine growth retardation. The protocol of this study was registered with Open Science Framework (DOI: 10.17605/OSF.IO/B9T4E). In total, 54 randomized controlled trials (RCTs) comprising 4,957 participants were included. Low-molecular-weight heparin (LMWH) alone, aspirin plus LMWH or unfractionated heparin (UFH), aspirin plus LMWH plus intravenous immunoglobulin (IVIG), aspirin plus LMWH plus IVIG plus prednisone were found to be effective pharmacological interventions for increasing live birth rate (ORs ranging between 2.88 to 11.24). In terms of acceptability, no significant difference was found between treatments. In terms of adverse perinatal outcomes, aspirin alone was associated with a higher risk of preterm birth than aspirin plus LMWH (OR 3.92, 95% CI 1.16 to 16.44) and with lower birthweight than LMWH (SMD -808.76, 95% CI -1596.54 to -5.07). Our findings support the use of low-dose aspirin plus heparin as the first-line treatment for prevention of RM in women with APS, and support the efficacy of hydroxychloroquine, IVIG, and prednisone when added to current treatment regimens. More large-scale, high-quality RCTs are needed to confirm these findings, and new pharmacological options should be further evaluated.

Longer-term effects of intravenous immunoglobulin treatment in chronic inflammatory demyelinating polyneuropathy: Who benefits?

Intravenous immunoglobulins (IVIg) represent an established cornerstone for the immunotherapy of chronic inflammatory demyelinating polyneuropathy (CIDP). Efficacy of IVIg for CIDP was proven in a large phase III trial. Yet, data on longer-term efficacy and effects in distinct subgroups are scarce. Our trial investigates the long-term efficacy of IVIg treatment in CIDP patients.In this observational real-world study, we retrospectively analyzed 49 CIDP patients receiving continuous IVIg treatment with a mean initial dosage of 87 g (1 g/kg body weight) every 4 weeks over a mean time of 45 months between 2010 and 2018. INCAT-Scores before the start of treatment and at the end of the observation period were compared.Over the observation period, IVIg treatment led to a median improvement of one INCAT score point. Subgroup analyses revealed a more pronounced improvement of INCAT scores in female CIDP patients, individuals with relapsing disease courses, patients with more pronounced motor impairment (higher initial INCAT scores) and in the cohort without need for concomitant other immunotherapies.These data argue for sustained beneficial effects of longer-term immunotherapy with IVIg in CIDP, particularly in females and relapsing disease forms with higher disease activity.

Randomized trial of intravenous immunoglobulin maintenance treatment regimens in chronic inflammatory demyelinating polyradiculoneuropathy.

High peak serum immunoglobulin G (IgG) levels may not be needed for maintenance intravenous immunoglobulin (IVIg) treatment in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and such high levels may cause side effects. More frequent lower dosing may lead to more stable IgG levels and higher trough levels, which might improve efficacy. The aim of this trial is to investigate whether high frequent low dosage IVIg treatment is more effective than low frequent high dosage IVIg treatment. In this randomized placebo-controlled crossover trial, we included patients with CIDP proven to be IVIg-dependent and receiving an individually established stable dose and interval of IVIg maintenance treatment. In the control arm, patients received their individual IVIg dose and interval followed by a placebo infusion at half the interval. In the intervention arm, patients received half their individual dose at half the interval. After a wash-out phase patients crossed over. The primary outcome measure was handgrip strength (assessed using a Martin Vigorimeter). Secondary outcome indicators were health-related quality of life (36-item Short-Form Health Survey), disability (Inflammatory Rasch-built Overall Disability Scale), fatigue (Rasch-built Fatigue Severity Scale) and side effects. Twenty-five patients were included and were treated at baseline with individually adjusted dosages of IVIg ranging from 20 to 80g and intervals ranging from 14 to 35days. Three participants did not complete the trial; the main analysis was therefore based on the 22 patients completing both treatment periods. There was no significant difference in handgrip strength change from baseline between the two treatment regimens (coefficient -2.71, 95% CI -5.4, 0.01). Furthermore, there were no significant differences in any of the secondary outcomes or side effects. More frequent lower dosing does not further improve the efficacy of IVIg in stable IVIg-dependent CIDP and does not result in fewer side effects.

Clinical and Molecular Phenotyping in Scleromyxedema Pretreatment and Posttreatment With Intravenous Immunoglobulin.

Scleromyxedema (SMX) is a rare systemic sclerosis mimic that often responds to intravenous immunoglobulin (IVIG) therapy, yet the resulting clinical and biochemical changes have not been well characterized. To better understand the pathogenesis of the disease and the efficacy of IVIG, we sought to explore whether IVIG would introduce a measurable biologic effect corresponding with clinical improvement. Fifteen patients with SMX were recruited for the study. Clinical information and peripheral blood mononuclear cells for flow cytometry were obtained immediately before and again 1-2 weeks after patients received IVIG therapy. Ten patients also underwent skin biopsies for gene expression analysis both before and after IVIG therapy. Clinical data included measures of skin involvement (modification of the modified Rodnan skin thickness score [MMRSS] and percentage of body surface area) and several patient-reported outcome measures assessing patients' skin. Posttreatment, the average MMRSS score decreased from mean ± SD 13.6 ± 2.6 to 10.3 ± 1.9; P = 0.003. There were also significant improvements in skin flexibility (mean ± SD 5.4 ± 0.8 to 3.2 ± 0.7; P = 0.003) and softening (mean ± SD 4.9 ± 0.9 to 2.6 ± 0.6; P = 0.022). Baseline levels of Tc17 cells (CD8+CCR6+CXCR3+CCR4-) correlated with the extent of skin involvement as measured by MMRSS pretreatment (r = 0.69, P = 0.012) and decreased after IVIG therapy (mean ± SD 3.4% ± 3.2% to 1.3% ± 1.7%; P = 0.008). Posttreatment analysis of RNA in skin tissue revealed a decrease in gene expression of transforming growth factor β (TGFβ) cytokines as well as several interferon-inducible proteins. This open-label study further supports the evidence that patients with SMX respond both objectively and subjectively to IVIG therapy. Biologic studies suggest a role for T lymphocytes in the pathogenesis of the disease and reveal the potential significance of TGFβ and interferon pathways.

Effectiveness of intravenous immunoglobulin for children with severe COVID-19: a rapid review.

BackgroundIntravenous immunoglobulin (IVIG) is usually used as supportive therapy, but the treatment of COVID-19 by IVIG is controversial. This rapid review aims to explore the clinical effectiveness and safety of IVIG in the treatment of children with severe COVID-19.MethodsWe systematically searched the literature on the use of IVIG in patients with COVID-19, severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS), including both adults and children. We assessed the risk of bias and quality of evidence and reported the main findings descriptively.ResultsA total of 1,519 articles were identified by initial literature search, and finally six studies met our inclusion criteria, included one randomized controlled trial (RCT), four case series and one case report involving 198 patients. One case series showed the survival of COVID-19 patients with acute respiratory distress syndrome (ARDS) was not improved by IVIG. One case report showed high-dose IVIG could improve the outcome of COVID-19 adults. Three observational studies showed inconsistent results of the effect of IVIG on SARS patients. One RCT showed that IVIG did not reduce mortality or the incidence of nosocomial infection in adults with severe SARS. The quality of evidence was between low and very low.ConclusionsThe existing evidence is insufficient to support the efficacy or safety of IVIG in the treatment of COVID-19.

Beneficial effects of intravenous immunoglobulin as an add-on therapy to azathioprine for NMO-IgG-seropositive neuromyelitis optica spectrum disorders

BackgroundThe efficacy of intravenous immunoglobulin (IVIG) in neuromyelitis optica spectrum disorders (NMOSD) has rarely been investigated, despite it being a conceivable therapeutic strategy based on its mode of action. We aimed to evaluate the efficacy of IVIG as an add-on therapy to azathioprine in the prevention of NMOSD relapse. MethodsWe retrospectively reviewed the medical records of NMO-IgG-positive NMOSD patients treated with IVIG infusions (0.4 g/kg/day) every one to three months as a part of combination therapy with azathioprine for more than six months. Treatment efficacy and safety were assessed based on the changes in the pre-IVIG and post-IVIG treatment annualized relapse rates (ARR), and on the proportion of relapse-free and progression-free patients and adverse events. ResultsThis study was performed on 20 patients (19 women; median age 52 years). After add-on therapy with IVIG, 19 patients (95%) showed a significant reduction in the median ARR from 1.1 [interquartile range, 0.6‒1.4] to 0.3 [interquartile range, 0‒0.6] (p < 0.001). Seven patients (35%) were relapse-free during 43.5 months (median) of treatment. The median Expanded Disability Status Scale (EDSS) score remained stable at 4.0. In addition, 80% of the patients showed no disability progression, and 25% of the patients experienced an improvement in EDSS. The median NMO-IgG titer decreased from 1:480 (n = 19) to 1:120 (n = 13) after treatment (p = 0.006) and was found to be negative in three patients. Six patients (30%) stopped IVIG due to relapses after 27.5 months (median; interquartile range, 15.3‒43.3) of IVIG initiation. There were no severe side effects that led to discontinuation of IVIG. ConclusionIVIG as add-on therapy may be associated with beneficial effects in preventing relapse and disability progression in NMO-IgG-positive NMOSD patients who have breakthrough disease activity despite immunosuppressive treatment with azathioprine. Further randomized controlled trials are necessary to validate the efficacy of IVIG in NMOSD.

Could Intravenous Immunoglobulin Collected from Recovered Coronavirus Patients Protect against COVID-19 and Strengthen the Immune System of New Patients?

The emergence of the novel coronavirus in Wuhan, China, which causes severe respiratory tract infections in humans (COVID-19), has become a global health concern. Most coronaviruses infect animals but can evolve into strains that cross the species barrier and infect humans. At the present, there is no single specific vaccine or efficient antiviral therapy against COVID-19. Recently, we showed that intravenous immunoglobulin (IVIg) treatment reduces inflammation of intestinal epithelial cells and eliminates overgrowth of the opportunistic human fungal pathogen Candida albicans in the murine gut. Immunotherapy with IVIg could be employed to neutralize COVID-19. However, the efficacy of IVIg would be better if the immune IgG antibodies were collected from patients who have recovered from COVID-19 in the same city, or the surrounding area, in order to increase the chance of neutralizing the virus. These immune IgG antibodies will be specific against COVID-19 by boosting the immune response in newly infected patients. Different procedures may be used to remove or inactivate any possible pathogens from the plasma of recovered coronavirus patient derived immune IgG, including solvent/detergent, 60 °C heat-treatment, and nanofiltration. Overall, immunotherapy with immune IgG antibodies combined with antiviral drugs may be an alternative treatment against COVID-19 until stronger options such as vaccines are available.

Treatment of parvovirus B19 viremia to facilitate kidney transplantation in a patient with collapsing glomerulopathy

Collapsing glomerulopathy (CG) is a severe form of glomerulopathy which results in nephrotic syndrome and often ensues in rapid progression to end-stage kidney disease (ESKD). Although most commonly a result of HIV infection, other conditions such as parvovirus B19 (PB19) infection have been associated with CG. We present a case of an 18-year-old male with CG associated with PB19 infection who was heterozygous for APOL1 G1 and G2 genetic variants. In an attempt to treat, he was started on intravenous immunoglobulin (IVIg), however rapidly progressed to ESKD. During workup for a living donor kidney transplant he was found to have persistent low-grade PB19 viremia. Despite having no major immunodeficiency and given subsequent courses of IVIg, viremia continued to persist. In a final attempt to eradicate the PB19 we began treatment with cidofovir, an antiviral agent with in vitro efficacy against PB19. Subsequent to initiation of cidofovir, PB19 viremia slowly cleared after which he received a living unrelated kidney transplant. The patient had an early cellular rejection treated with rabbit antithymocyte globulin after which he recovered kidney function without signs of recurrent CG. Our case report suggests efficacy of IVIg and cidofovir for persistent PB19 infection in ESKD to allow subsequent transplantation, while minimizing the risk of recurrent CG.

Intravenous immunoglobulins for epilepsy.

Epilepsy is a common neurological condition, with an estimated incidence of 50 per 100,000 persons. People with epilepsy may present with various types of immunological abnormalities, such as low serum immunoglobulin A (IgA) levels, lack of the immunoglobulin G (IgG) subclass and identification of certain types of antibodies. Intravenous immunoglobulin (IVIg) treatment may represent a valuable approach and its efficacy has important implications for epilepsy management. This is an update of a Cochrane review first published in 2011 and last updated in 2017. To examine the effects of IVIg on the frequency and duration of seizures, quality of life and adverse effects when used as monotherapy or as add-on treatment for people with epilepsy. For the latest update, we searched the Cochrane Register of Studies (CRS Web) (20 December 2018), MEDLINE (Ovid, 1946 to 20 December 2018), Web of Science (1898 to 20 December 2018), ISRCTN registry (20 December 2018), WHO International Clinical Trials Registry Platform (ICTRP, 20 December 2018), the US National Institutes of Health ClinicalTrials.gov (20 December 2018), and reference lists of articles. Randomised or quasi-randomised controlled trials of IVIg as monotherapy or add-on treatment in people with epilepsy. Two review authors independently assessed the trials for inclusion and extracted data. We contacted study authors for additional information. Outcomes included percentage of people rendered seizure-free, 50% or greater reduction in seizure frequency, adverse effects, treatment withdrawal and quality of life. We included one study (61 participants). The included study was a randomised, double-blind, placebo-controlled, multicentre trial which compared the treatment efficacy of IVIg as an add-on with a placebo add-on in patients with drug-resistant epilepsy. Seizure freedom was not reported in the study. There was no significant difference between IVIg and placebo in 50% or greater reduction in seizure frequency (RR 1.89, 95% CI 0.85 to 4.21; one study, 58 participants; low-certainty evidence). The study reported a statistically significant effect for global assessment in favour of IVIg (RR 3.29, 95% CI 1.13 to 9.57; one study, 60 participants; low-certainty evidence). No adverse effects were demonstrated. We found no randomised controlled trials that investigated the effects of IVIg monotherapy for epilepsy. Overall, the included study was rated at low to unclear risk of bias. Using GRADE methodology, the certainty of the evidence was rated as low. We cannot draw any reliable conclusions regarding the efficacy of IVIg as a treatment for epilepsy. Further randomised controlled trials are needed.

The Use of Intravenous Immunoglobulin (IVIG) during Severe Neurotoxicity Among the Recipients of Chimeric Antigen Receptor T-Cell (CAR-T) Therapy

INTRODUCTION: Severe neurotoxicity occurs in ~30% of Diffuse Large B Cell Lymphoma (DLBCL) patients treated with CAR-T cell therapy. The current treatment for severe neurotoxicity is glucocorticoids +/- tocilizumab (an IL-6 antagonist) depending on concurrent cytokine release syndrome. Even with these treatments, neurotoxicity can have a complicated course. It is therefore essential to find the optimal treatment to reverse neurotoxicity timely. METHOD:This is a retrospective cohort study of neurologic and oncologic outcomes among patients with grade ≥ 3 neurotoxicity treated with glucocorticoids and IVIG compared to glucocorticoids only. Severe neurotoxicity was defined as grade 3 and graded by CRES/CARTOX score. Time to resolution of severe neurotoxicity (TTR) was defined as improvement of severe neurotoxicity to grade ≤ 2. RESULTS: We identified a total of 20 patients who received CAR-T therapy and developed severe neurotoxicity. Ten patients received glucocorticoids and IVIG (group A) and ten patients received glucocorticoids alone (group B). The median age was 62 (range: 52-74) for group A vs 64 years (range: 48-75) for group B. Both groups had similar ECOG performance status (p=0.17), IPI scores (p=0.34), and onset of severe neurotoxicity (median=6 days in both groups). Median TTR was 3 days (range, 1-7) for group A and 4.5 days (range, 2-22) for group B. There was no significant difference in TTR of severe neurotoxicity among both groups (Log-rank p=0.18, Figure). The median time to administration of IVIG after initiation of glucocorticoids was 2 days (range, 0.5-8). The median TTR following initiation of IVIG was 0.5 day (0.5-4). The objective response rate at 30 days was 80% in both groups. None of the patients who received IVIG developed thromboembolism, renal failure, autoimmune hemolytic anemia or acute lung injury. CONCLUSIONS: Although the use of IVIG during severe neurotoxicity after CAR-T therapy appeared to be safe, this pilot retrospective analysis demonstrated no significant difference in resolution of severe neurotoxicity with addition of IVIG to glucocorticoids. Further controlled studies limiting selection bias inherent in this retrospective analysis will help to determine the efficacy of IVIG in severe neurotoxicity in the context of CAR-T cell therapy. Disclosures Mokhtari: KITE PHARMA: Other: Clinical Advisor; NOVARTIS: Other: Clinical Advisor. Bachmeier:Kite/Gilead: Speakers Bureau. Jain:Kite/Gilead: Consultancy. Forsyth:Department of Defense: Research Funding; Pfizer: Research Funding; State of Florida Bankhead Coley: Research Funding; Moffitt Center of Excellence Celgene Project: Research Funding; Florida Academic Cancer Center Alliance: Research Funding; NIH/NCI 1R21 Grant: Research Funding; NIT DT Study Section Grant Review: Membership on an entity's Board of Directors or advisory committees; AbbVie Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees; Ziopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Tocagen: Consultancy, Membership on an entity's Board of Directors or advisory committees; BTG: Consultancy, Membership on an entity's Board of Directors or advisory committees; Inovio: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novocure: Consultancy, Membership on an entity's Board of Directors or advisory committees. Locke:Novartis: Other: Scientific Advisor; Cellular BioMedicine Group Inc.: Consultancy; Kite: Other: Scientific Advisor. Lazaryan:Kadmon: Consultancy.

Combined intravenous immunoglobulin and methylprednisolone as induction treatment in chronic inflammatory demyelinating polyneuropathy (OPTIC protocol): a prospective pilot study.

Background and purposeWe hypothesized that combining intravenous immunoglobulin (IVIg) and intravenous methylprednisolone (IVMP) leads to more frequent remission compared with IVIg alone while maintaining the fast efficacy of IVIg. In this uncontrolled pilot study, we evaluated remission, rate of improvement and safety in patients with chronic inflammatory demyelinating polyradiculoneuropathy receiving induction treatment with combined IVIg and IVMP.MethodsConsecutive treatment‐naive patients with chronic inflammatory demyelinating polyradiculoneuropathy were treated with IVIg infusions, consisting of a 2 g/kg loading dose and 1 g/kg maintenance treatment every 3 weeks, combined with 3‐weekly 1‐g IVMP infusions, for a total of 18 weeks. The cumulative steroid dose was 7 g. Primary outcome was remission at 1 year in patients who completed the treatment schedule. Remission was defined as improvement at 18 weeks without the need for further immune treatment between end of the treatment schedule and 1‐year follow‐up. Improvement was defined as a minimal clinically important difference on the Inflammatory Rasch‐Built Overall Disability Scale and/or an increase of ≥8 kPa in grip strength between baseline and week 18.ResultsA total of 20 patients were included; 17 completed the treatment schedule. A total of 13 (76%) of these patients improved at 18 weeks after start of treatment and 10 (59%) patients were in remission at 1 year. Serious adverse events were found in four patients.ConclusionsShort‐term combined induction treatment with IVIg and IVMP induced remission in almost 60% of patients who completed the treatment schedule. Combined induction therapy was generally well tolerated. A randomized controlled trial is currently running to confirm efficacy and safety of IVMP as add‐on treatment to IVIg.

Intravenous immunoglobulin for adjunctive treatment of severe infections in ICUs.

This review focuses on the emerging literature regarding the use of intravenous immunoglobulins (IVIg) in critically ill patients with severe infections. The aim is to provide an accessible summary of the most recent evidence of IVIg use in sepsis and septic shock and to help clinicians to understand why there is still equipoise regarding the potential benefit of this adjunctive therapy in this setting. Observational studies with propensity score matching analyses and investigating the effect of IVIg in severe infections including necrotizing soft tissue infection have been recently published. These studies suffer important flaws precluding robust conclusion to be drawn. Some recent randomized controlled trials raised interesting findings supportive of personalized medicine but are likely to be underpowered or confounded. Insufficient evidence is available to support IVIg use in sepsis and septic shock, apart from the specific case of streptococcal toxic shock syndrome. Current literature suggests that IVIg efficacy in sepsis or septic shock could depend on the IVIg preparation (IgM-enriched or minimal IgM), time of administration (<24 h), dose, and the inflammatory/immunomodulation profile of the patients. Investigator-initiated research, incorporating these parameters, is warranted to determine whether IVIg benefits critically ill patients with severe infection.

Intravenous Immunoglobulin Therapy in Refractory Autoimmune Dysautonomias: A Retrospective Analysis of 38 Patients.

Intravenous immunoglobulin (IVIG) has recognized efficacy in autoimmune peripheral nerve disorders, but there has been limited study of the use of IVIG in autoimmune dysautonomias. To determine the efficacy and safety of IVIG in patients with disabling, refractory autoimmune dysautonomias, including patients with postural tachycardia syndrome and gastrointestinal dysmotility. Patients with one or more autonomic disorder(s) and persistent serological evidence for autoimmunity who were unable to work or attend school despite usual treatments for dysautonomia were treated with IVIG for at least 3 months at a dose of at least 1 gm/kg monthly. Outcome measures included the composite autonomic symptom scale 31 survey and a functional ability score. There were 38 patients, 84% female and mean age of 28.4 years. Of patients, 83.5% improved on IVIG as defined by at least 20% improvement in the composite autonomic symptom scale 31 and/or functional ability score. The mean pretreatment functional ability score was 21% (mostly bedridden), which improved to a mean of 74% (nearing able to return to work/school) for responsive patients after at least 1 year of IVIG. The mean time to the first sign of response was 5.3 weeks. There were no serious adverse events. The Mayo autoimmune dysautonomia panel antibodies and traditional Sjögren antibodies were present in only 13% and 8% of patients, respectively, but antiphospholipid antibodies and novel Sjögren antibodies were present in 76% and 42% of patients, respectively. There is increasing evidence that IVIG is safe and effective in a subset of patients with autonomic disorders and evidence for autoimmunity. A 4-month IVIG trial should be considered in severely affected patients who are refractory to lifestyle and pharmacological therapies. Antiphospholipid antibodies and novel Sjögren antibodies are often present in these patients and correlate with a high response rate to IVIG.

High level antibodies to TORCH in the IVIG preparation from Taiwanese.

Congenital TORCH (toxoplasmosis, other viruses [varicella-zoster virus, VZV, etc.], rubella, cytomegalovirus [CMV], Herpes simplex virus [HSV]) infections are major causes of prenatal, perinatal, and postnatal morbidity and mortality. Although treatment or prevention strategies are available for these pathogens, all drugs may not be safe during the pregnancy. The aim of this study is to measure the antibodies (Abs) concentration in the intravenous immunoglobulin (IVIG) preparation to evaluate the therapeutic potential for TORCH infection. We tested the only one commercial IVIG preparation from Taiwanese for the presence of Abs against Toxoplasma gondii, VZV, Epstein-Barr virus (EBV), measles, mumps, rubella, CMV, HSV type 1 (HSV-1), and HSV type 2 (HSV-2) by using enzyme-linked immunosorbent assay or chemiluminescent microparticle immunoassay. In our study, the median level (range) of anti-CMV immunoglobulin G (IgG) is > 250 (All > 250) (arbitrary unit, AU)/mL, anti-EBV > 200 (All > 200) (relative unit, RU)/mL, anti-HSV > 200 (152.75 to >200) RU/mL, anti-VZV > 5000 (All > 5000) IU/L, anti-measles > 5000 (All > 5000) IU/L, anti-mumps > 200 (156.5 to > 200) RU/mL, anti-rubella 209.8 IU/mL (192.7 to 238.5), and anti-Toxoplasma is 14.05 (12.3 to 16) IU/mL. There was not any immunoglobulin M (IgM) against HSV, VZV, mumps, measles, rubella, CMV, EBV, and Toxoplasma in the "Taiwan Blood Services Foundation" IVIG preparations. There was high activity against T. gondii, VZV, EBV, measles, mumps, rubella, CMV, HSV-1, and HSV-2 in all IVIG batches. Further investigation is warranted to confirm the efficacy of IVIG from Taiwanese for congenital TORCH infections.

Intravenous immunoglobulins for Alzheimer’s disease and mild cognitive impairment due to Alzheimer’s disease: A systematic review with meta-analysis

ABSTRACTIntroduction: Alzheimer’s disease (AD) is the most common phenotype of dementia. Mild cognitive impairment (MCI) due to AD is believed as a prodromal stage of AD. Intravenous immunoglobulin (IVIG) is a classical immunotherapy and potentially reduces AD-type pathology by anti-Aβ, anti-tau, anti-inflammatory effects, and non-antibody-mediated effects.Areas covered: The authors aimed to determine the efficacy and safety of IVIG for AD and MCI due to AD patients. The electronic databases including PubMed, EMBASE, CINAHL, Cochrane Library, and China National Knowledge Infrastructure were searched until March 2019. The results were pooled via a random-effects model. There were five eligible studies with 772 randomized patients with AD and MCI due to AD, which compared IVIG with placebo.Expert opinion: No significant differences were found in the scores of mini–mental state examination and Alzheimer’s disease assessment scale-cognitive subscale and number of patients with adverse events. IVIG is well tolerated in the patients with AD and MCI due to AD, even in long-term therapy for 18 months. Insufficient evidences support IVIG in the treatment of patients with AD and MCI due to AD to improve cognition or disease modification. Well-designed randomized controlled trials with large sample sizes are required in the future.

Classification of pregnancy complicating Guillain-Barré syndrome

Objective: To explore the classification, clinical features, the short-term efficacy of intravenous immunoglobulin (IVIg) for Guillain-Barré syndrome(GBS) and look for predictors of acute motor axonal neuropathy (AMAN) during pregnancy. Methods: The clinical data of 45 hospitalized pregnant patients with GBS recruited from October 2008 to October 2017 at the Tianjin Medical University general hospital, Handan City First Hospital and Nankai University Affiliated Tianjin Fourth Central Hospital, were collected and analyzed retrospectively, and patients were divided into the acute inflammatory demyelinating polyneuropathies (AIDP) group and the AMAN group. The clinical features and efficacy of IVIg were compared between the two groups. Logistic regression analysis was used to analyze the predictors of AMAN. Results: There were 25 cases in the AIDP group and 20 cases in the AMAN group. AIDP usually started with distal limb weakness (P=0.001), and AMAN often started with limb weakness (P=0.001) and mostly accompanied by dyspnea (P=0.042). AIDP was often associated with paresthesia (P=0.001) and autonomic dysfunction (P=0.007). The response days of active treatment in the AIDP group and the AMAN group were (1.6±0.5)d and (2.3±0.8)d (P=0.022), the improvement days were (3.6±0.8)d and (5.9±1.0)d (P=0.000), the basic cure days were (7.7±1.3)d and (9.0±0.8)d (P=0.002), the cure days were (12.3±1.1)d and (12.8±0.9)d (P=0.148). Multivariate Logistic regression analysis revealed that preceding diarrhea (OR=13.750; 95% CI 1.386-136.387), limb weakness(OR=12.000;95% CI 2.359-61.048) and limb weakness with dyspnea (OR=10.000; 95% CI 1.048-95.457) were significantly associated with the AMAN-type GBS. Conclusions: AIDP and AMAN are the main types of pregnancy complicating GBS. Most patients present with a single and benign course of disease. IVIg is generally safe and effective. Preceding diarrhea, limb weakness and limb weakness with dyspnea are the predictors of AMAN-type pregnancy complicating GBS.

Clinical factors influencing the response to intravenous immunoglobulin treatment in cases of treatment-resistant pyoderma gangrenosum

Background: Pyoderma gangrenosum (PG) is a neutrophilic disorder which classically presents as chronic, painful ulcers on the lower extremities. There is evidence supporting a potential role for intravenous immunoglobulin (IVIG) as adjuvant therapy for treatment-resistant cases; however, it is unclear which patients will most benefit from this modality of treatment – an especially important consideration given the cost per infusion ($5000–$10,000). Thus, we sought to identify the clinical characteristics of patients with refractory PG lesions who demonstrated complete healing when IVIG was incorporated into the therapeutic plan.Methods: We performed a literature search of PubMed/MEDLINE and Embase using the keywords ‘pyoderma gangrenosum’ and ‘IVIG’. We also added four institutional cases. Descriptive statistics were used to analyze the data. Significance was set at p < .05.Results: We discovered a total of 45 cases. Twenty-three patients with treatment-resistant PG had complete healing, 22 had partial or unhealed PG ulcers. Patients with one ulcer were 4.1 (95% CI: 1.1–18.5) times more likely to achieve complete healing than patients with more than one ulcer, when IVIG was added (p = .041).Conclusion: There is increased efficacy of IVIG as a treatment for patients with a solitary treatment-resistant PG lesion compared to patients with multiple refractory lesions.

Efficacy and Safety of Octagam® in Patients With Chronic Inflammatory Demyelinating Polyneuropathy.

IntroductionChronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a debilitating autoimmune neuropathy that is treated with intravenous immunoglobulin (IVIG). The aim of this retrospective study was to investigate the efficacy and safety of the sucrose-free IVIG Octagam® (Octapharma AG, Lachen, Switzerland) in patients with CIDP.MethodsData from 47 patients who received at least one dose of Octagam were collected from the records of 11 centres in France. Efficacy was assessed using Overall Neuropathy Limitation Scale (ONLS). Safety was evaluated using adverse event rates.ResultsData from 24 patients who were IVIG naïve (n = 11) or had stopped IVIG ≥ 12 weeks before initiation of Octagam therapy (washout group; n = 13) were included in the efficacy analysis. At 4 months post-initiation of Octagam treatment, 41.7% of patients had improved their functional status (decrease of ≥ 1 ONLS score) with a significant change in the ONLS score from baseline (– 0.42; p = 0.04; signed test). Functional status was reduced in only two patients: one patient in the IVIG-naïve group and one patient in the IVIG-washout group. All 47 patients were included in the safety analysis, which showed that Octagam was well tolerated, with a frequency of 0.04 adverse events per Octagam course. The most common adverse drug reaction was headache.ConclusionsThese real-life results are consistent with the efficacy and safety of IVIG reported in randomised controlled studies. A long-term prospective study of Octagam in patients with CIDP is warranted.FundingOctapharma, France SAS.

Intravenous Immunoglobulin Therapy for Acute Myocarditis in Children and Adults.

The efficacy of intravenous immunoglobulin (IVIG) in the treatment of acute myocarditis remains controversial. The aim of this study was to conduct a meta-analysis to assess the efficacy of IVIG in children and adults with acute myocarditis.We searched PubMed, Scopus, Embase, Medline, the Cochrane Library, Google Scholar, and the ClinicalTrials.gov website. Eligible studies were clinical trials of patients with acute myocarditis who received IVIG therapy. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the outcomes.Thirteen studies with 1534 cases were incorporated into our meta-analysis. Pooled results showed that IVIG therapy significantly reduced in-hospital mortality (OR: 0.44, 95% CI 0.17 to 0.71, P < 0.001) and improved the left ventricular ejection fraction (LVEF) (OR: 1.73, 95% CI 1.34 to 2.13, P < 0.001) in acute myocarditis patients. Furthermore, patients with acute fulminant myocarditis (AFM) exhibited a significantly higher survival rate (OR: 2.80, 95% CI 1.16 to 6.77, P = 0.022) in the IVIG group.IVIG therapy can not only result in lower in-hospital mortality and superior recovery of left ventricular function in patients with acute myocarditis, but also increase the survival rate of AFM patients. The present study provides some supportive evidence for IVIG therapy in acute myocarditis patients.

Efficacy and safety of IVIG in CIDP: Combined data of the PRIMA and PATH studies.

Intravenous immunoglobulin (IVIG) is a potential therapy for chronic inflammatory demyelinating polyneuropathy (CIDP). To investigate the efficacy and safety of the IVIG IgPro10 (Privigen) for treatment of CIDP, results from Privigen Impact on Mobility and Autonomy (PRIMA), a prospective, open‐label, single‐arm study of IVIG in immunoglobulin (Ig)‐naïve or IVIG pre‐treated subjects (NCT01184846, n = 28) and Polyneuropathy And Treatment with Hizentra (PATH), a double‐blind, randomized study including an open‐label, single‐arm IVIG phase in IVIG pre‐treated subjects (NCT01545076, IVIG restabilization phase n = 207) were analyzed separately and together (n = 235). Efficacy assessments included change in adjusted inflammatory neuropathy cause and treatment (INCAT) score, grip strength and Medical Research Council (MRC) sum score. Adverse drug reactions (ADRs) and ADRs/infusion were recorded. Adjusted INCAT response rate was 60.7% in all PRIMA subjects at Week 25 (76.9% in IVIG pre‐treated subjects) and 72.9% in PATH. In the pooled cohort (n = 235), INCAT response rate was 71.5%; median time to INCAT improvement was 4.3 weeks. No clear demographic differences were noticed between early (responding before Week 7, n = 148) and late responders (n = 21). In the pooled cohort, median change from baseline to last observation was −1.0 (interquartile range −2.0; 0.0) point for INCAT score; +8.0 (0.0; 20.0) kPa for maximum grip strength; +3.0 (1.0; 7.0) points for MRC sum score. In the pooled cohort, 271 ADRs were reported in 105 subjects (44.7%), a rate of 0.144 ADRs per infusion. This analysis confirms the efficacy and safety of IgPro10, a recently FDA‐approved IVIG for CIDP, in a population of mainly pre‐treated subjects with CIDP [Correction added on 14 March 2019 after first online publication: the INCAT response rate has been corrected.].