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1.
Efficacy and safety of intravenous immunoglobulin for treating refractory livedoid vasculopathy: a systematic review
Gao Y, Jin H
Therapeutic advances in chronic disease. 2022;13:20406223221097331
Abstract
INTRODUCTION Intravenous immunoglobulin (IVIG) was reported to be the third most used monotherapy in livedoid vasculopathy (LV). There is currently a lack of randomized controlled clinical trials and no standardized therapeutic regimen for IVIG therapy in LV. METHODS We performed a systematic review of the efficacy and safety of IVIG in treating patients with LV using PubMed, Cochrane, and Embase databases. RESULTS Eighty LV patients from 17 articles were included, receiving IVIG therapy at a dose of 1-2.1 g/kg body weight every 4 weeks. The effective rate of IVIG therapy in LV patients was 95% (76/80) in published studies, showing a good clinical response for resolution of pain, skin ulcerations, and neurological symptoms, and reducing the dependence on glucocorticoids and immunosuppressive agents. IVIG therapy was well tolerated, and no severe adverse events were observed. CONCLUSION Overall, to a certain degree, IVIG is probably a safe and effective treatment alternative for refractory LV patients, which still need to be confirmed by large-scale randomized controlled clinical trials.
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2.
A systematic review and meta-analysis of randomized controlled trials evaluating pharmacologic therapies for acute and recurrent pericarditis
Melendo-Viu M, Marchán-Lopez Á, Guarch CJ, Roubín SR, Abu-Assi E, Meneses RT, Ynsaurriaga FA, Hernandez AV, Bueno H
Trends in cardiovascular medicine. 2022
Abstract
Acute idiopathic pericarditis (AIP) is a benign inflammatory condition associated with high recurrence rates. Non-steroidal anti-inflammatory drug (NSAIDs) and colchicine are the recommended therapies. Our objective was to systematically assess effects of pharmacological therapies on recurrences or treatment failure in patients with first and subsequent AIP episodes. PubMed, BioMedCentral, Cochrane, Clinicaltrials.gov, Google Scholar and EMBASE (Ovid) were searched up to April 2020 for randomized controlled trials (RCT) evaluating NSAIDs, indomethacin, colchicine, steroids, intravenous immunoglobulins, immunomodulators, or interleukin receptor antagonists in adult patients with acute episode of idiopathic pericarditis. Mantel-Haenzel random effects models were used for meta-analyses, and effects were reported as odds ratios (ORs) and their 95% confidence intervals (CI). Six RCTs of colchicine plus NSAIDs (n=914 patients) and one RCT of anakinra (n=21) were found. No RCTs testing NSAIDs or corticosteroids were identified. Colchicine plus NSAIDs and anakinra significantly reduced recurrence (OR 0.37; 95%CI 0.27-0.51; and OR 0.02; 95%CI, 0.00-0.32, respectively). Colchicine plus NSAIDs also reduced treatment failure (OR 0.29; 95%CI 0.21-0.41). No differences in adverse events between colchicine and placebo were found (OR 1.16; 95%CI 0.72 to 1.86). In conclusion, Colchicine plus NSAIDS and anakinra are efficacious for preventing AIP recurrences. Colchicine reduces treatment failure as well. Although its use is supported by clinical experience, no solid evidence is currently available for the role of NSAIDs or steroids in the treatment of AIP.
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3.
Intravenous immunoglobulin for presumed viral myocarditis in children and adults
Robinson J, Hartling L, Vandermeer B, Sebastianski M, Klassen TP
The Cochrane database of systematic reviews. 2020;8:Cd004370
Abstract
BACKGROUND This is an update of a previous review. Case reports and case series have described dramatic responses to intravenous immunoglobulin (IVIG) in people with presumed viral myocarditis, and its administration has become commonplace. OBJECTIVES The primary objective of this review was to compare event-free (death, requirement for a cardiac transplant, or placement of a left ventricular assist device) or overall (death) survival of adults and children with presumed viral myocarditis treated with IVIG versus those who did not receive IVIG. A secondary objective was to determine if a group of patients with presumed viral myocarditis could be identified (on the basis of age, duration of symptoms, acuity of onset of symptoms, cardiac function at presentation, virological results, or the presence or absence of histological evidence of acute myocarditis on cardiac biopsy in patients in whom a biopsy was performed) who would be the most likely to benefit from IVIG. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, DARE, CINAHL, Web of Science Core Collection, and LILACS in July 2019, and two trial registries in November 2019. We contacted authors of trials and checked reference lists of relevant papers. We applied no language restrictions. SELECTION CRITERIA We included studies if (1) participants had a clinical diagnosis of acute myocarditis with a left ventricular ejection fraction (LVEF) ≤ 0.45, left ventricular end-diastolic diameter (LVEDD) > 2 standard deviations (SDs) above the norm, or a left ventricular shortening fraction (LVSF) > 2 SDs below the mean, with duration of cardiac symptoms < 6 months; (2) participants had no evidence of non-infectious or bacterial cardiac disease; and (3) participants were randomly assigned to receive at least 1 g/kg of IVIG versus no IVIG or placebo. We excluded studies if (1) participants had received immunosuppression before outcome assessment; or (2) onset of myocarditis was reported to have occurred < 6 months postpartum. DATA COLLECTION AND ANALYSIS Two review authors independently screened the search results and extracted data. We assessed risk of bias with the Cochrane 'Risk of bias' tool. We conducted meta-analysis for two outcomes (overall survival and improvement in LVEF) with two adult trials. Other meta-analyses were not possible because only three relevant trials were included, and researchers analysed markedly different populations and used different outcome measures. MAIN RESULTS In this update we added two trials to the two previously included trials. A quasi-randomised trial was previously included due to a paucity of evidence from randomised trials; however, with the addition of two new randomised trials, it was removed from this update. For two adult trials, the overall risk of bias was unclear with very low-certainty evidence for all outcomes. The first trial studied 62 adults with recent-onset dilated cardiomyopathy randomly assigned to receive IVIG or an equivalent volume of 0.1% albumin in a blinded fashion. The effect on event-free survival between groups was uncertain (risk ratio (RR) of any event 1.76, 95% confidence interval (CI) 0.48 to 6.40). The second trial studied 41 adults with acute myocarditis randomised to either high-dose IVIG (1 to 2 g/kg over two days) or no treatment. The IVIG group reported greater survival time after 60 days (no raw data, P < 0.01), but the evidence is uncertain. We pooled the reported number of deaths in both trials, with no evidence of a difference between groups (RR 0.91, 95% CI 0.23 to 3.62, I(2) = 31%, very low-certainty evidence). The evidence on the effect of IVIG treatment on LVEF (pooled mean difference (MD) -0.01, 95% CI -0.06 to 0.05) after 12 months and an unknown time frame is uncertain. The results for functional capacity, assessed by peak oxygen consumption at 12 months, were uncertain (MD -0.80, 95% CI -4.57 to 2.97). The results for infusion-related side effects were also uncertain due to a very large CI (RR 20.29, 95% CI 1.25 to 329.93). Lastly, there was uncertain evidence addressing failure to attain complete recovery (RR 0.46, 95% CI 0.19 to 1.14). Evidence for improvement in LVEDD, left ventricular shortening fraction, and hospitalisation status in adults was not reported. In the single included paediatric trial, the overall risk of bias was low with very low-certainty evidence for all outcomes. The trial included 86 children in Egypt presenting with acute myocarditis. Children were randomly assigned to 1 g/kg IVIG daily for two consecutive days or placebo followed by echocardiography one and six months post randomisation for recording of LVEDD and LVSF. The evidence for overall survival after six months was uncertain (risk of death RR 0.48, 95% CI 0.20 to 1.15). The evidence was also uncertain for improvement in LVEDD and LVSF after six months (LVEDD MD -4.00, 95% CI -9.52 to 1.52; LVSF no raw data). Evidence for improvement in LVEF, functional capacity, side effects, complete recovery, and hospitalisation status in children was not reported. AUTHORS' CONCLUSIONS Evidence from two trials of very low certainty and with unclear risk of bias provides contradictory evidence on the use of IVIG in the treatment of adults with presumed viral myocarditis. One trial reported that use of IVIG results in longer survival time after 60 days, whilst the other trial found that IVIG does not provide an appreciable benefit. The evidence of a difference in event-free or overall survival, LVEDD, or LVSF is of very low certainty in a single paediatric trial with a low risk of bias. Until higher-quality studies with low risk of bias and larger sample sizes have demonstrated benefit in a particular group of patients, the evidence for treatment with IVIG for presumed viral myocarditis is uncertain. Further studies of the pathophysiology of myocarditis would lead to improved diagnostic criteria, which would facilitate future research.
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4.
Role of intravenous immunoglobulin therapy in the survival rate of pediatric patients with acute myocarditis: A systematic review and meta-analysis
Yen CY, Hung MC, Wong YC, Chang CY, Lai CC, Wu KG
Scientific reports. 2019;9(1):10459
Abstract
The treatment of pediatric myocarditis is controversial, and the benefits of intravenous immunoglobulin (IVIG) are inconclusive due to limited data. We searched studies from PubMed, MEDLINE, Embase, and Cochrane Library databases since establishment until October 1st, 2018. Thirteen studies met the inclusion criteria. We included a total of 812 patients with IVIG treatment and 592 patients without IVIG treatment. The meta-analysis showed that the survival rate in the IVIG group was higher than that in the non-IVIG group (odds ratio = 2.133, 95% confidence interval (CI): 1.32-3.43, p = 0.002). There was moderate statistical heterogeneity among the included studies (I(2) = 35%, p = 0.102). However, after adjustment using Duval and Tweedie's trim and fill method, the point estimate of the overall effect size was 1.40 (95% CI 0.83, 2.35), which became insignificant. Moreover, the meta-regression revealed that age (coefficient = -0.191, 95% CI (-0.398, 0.015), p = 0.069) and gender (coefficient = 0.347, 95% CI (-7.586, 8.279), p = 0.93) were not significantly related to the survival rate. This meta-analysis showed that IVIG treatment was not associated with better survival. The use of IVIG therapy in acute myocarditis in children cannot be routinely recommended based on current evidence. Further prospective and randomized controlled studies are needed to elucidate the effects of IVIG treatment.
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5.
Intravenous Immunoglobulin Therapy for Acute Myocarditis in Children and Adults
Huang X, Sun Y, Su G, Li Y, Shuai X
International heart journal. 2019
Abstract
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.
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6.
The therapeutic efficacy of intravenous immunoglobulin in anti-neutrophilic cytoplasmic antibody-associated vasculitis: a meta-analysis
Shimizu T, Morita T, Kumanogoh A
Rheumatology (Oxford, England). 2019
Abstract
OBJECTIVES The therapeutic effects of IVIG in patients with ANCA-associated vasculitis (AAV) have not been established so far. This study aims to estimate the effects of IVIG on AAV by conducting a systematic review and meta-analysis. METHODS A comprehensive systematic review was conducted in accordance with the guidelines of PRISMA (Preferred Reporting Items for Systematic Reviews And Meta-analyses). PubMed and Google Scholar were used to search for original studies on AAV and collect clinical data before and after IVIG treatment. A meta-analysis of each clinical parameter was performed, and standardized mean difference (SMD) and 95% CI were calculated using the random effects model. RESULTS A total of 220 studies were identified, and nine met the selection criteria for the meta-analysis. IVIG was administered to active AAV patients as an immunomodulatory therapy in the nine studies selected. Significant reductions in BVAS (SMD -1.7; 95% CI [-2.66, -0.73]; P = 0.0006), ANCA (SMD -0.72; 95% CI [-1.13, -0.31]; P = 0.0006) and CRP (SMD -0.92; 95% CI [-1.49, -0.35]; P = 0.002) were noted within 6 months after administration of IVIG. Subgroup analysis in the unmodified immunotherapy population showed reductions in BVAS (SMD -1.39; 95% CI [-2.31, -0.48]; P = 0.003) and CRP (SMD -0.56; 95% CI [-0.93, -0.19]; P = 0.002) within half a month after IVIG treatment. CONCLUSION IVIG was associated with rapid improvements in disease activity and the related biomarkers in patients with active AAV.
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7.
Corticosteroids and Intravenous Immunoglobulin in Pediatric Myocarditis: A Meta-Analysis
Li Y, Yu Y, Chen S, Liao Y, Du J
Frontiers in pediatrics. 2019;7:342
Abstract
Background: The efficacy of corticosteroids and intravenous immunoglobulin (IVIG) in pediatric myocarditis remains controversial. Objectives: The authors performed a meta-analysis to assess the therapeutic efficacy of corticosteroids and IVIG in children with myocarditis. Methods: We retrieved the trials on corticosteroids and IVIG therapy, respectively, in pediatric myocarditis from nine databases up to December 2018. Statistical analysis was performed using Review Manager 5.3. Results: Our analysis included 8 studies and 334 pediatric patients. The data demonstrated that children receiving corticosteroids showed no significant improvement on left ventricular ejection fraction (LVEF) from 1 to 8 month-follow-up (MD = 5.17%, 95% CI = -0.26% to 10.60%, P = 0.06), and no significant improvement in death or heart transplantation incidence at the end of follow-up (OR = 1.33, 95% CI = 0.27-6.70, P = 0.73). However, children receiving IVIG revealed a statistically remarkable increase in LVEF at a follow-up over the course of 6 months to 1 year (MD = 18.91%, 95% CI = 11.74-26.08%, P < 0.00001), and a decrease in death or heart transplantation at the end of follow-up (OR = 0.31, 95% CI = 0.12-0.75, P = 0.01). Further comparisons showed that the mortality and heart transplantation rate of children with myocarditis treated with IVIG were significantly lower than those with corticosteroid therapy (t' = 11.336, P < 0.001). Conclusions: IVIG might be beneficial to improve LVEF and survival for myocarditis in children. However, the present evidence does not support corticosteroids as superior to conventional therapy in children with myocarditis. Further randomized controlled trials with a larger sample size are required.
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8.
Intravenous human immunoglobulins for refractory recurrent pericarditis: a systematic review of all published cases
Imazio M, Lazaros G, Picardi E, Vasileiou P, Carraro M, Tousoulis D, Belli R, Gaita F
Journal of Cardiovascular Medicine. 2016;17((4)):263-9.
Abstract
AIMS: Refractory recurrent pericarditis is a major clinical challenge after colchicine failure, especially in corticosteroid-dependent patients. Human intravenous immunoglobulins (IVIGs) have been proposed as possible therapeutic options for these cases. The goal of this systematic review is to assess the efficacy and safety of IVIGs in this context. METHODS Studies reporting the use of IVIG for the treatment of recurrent pericarditis and published up to October 2014 were searched in several databases. All references found, upon initial assessment at title and abstract level for suitability, were consequently retrieved as full reports for further appraisal. RESULTS Among the 18 citations retrieved, 17 reports (4 case series and 13 single case reports, with an overall population of 30 patients) were included. The mean disease duration was 14 months and the mean number of recurrences before IVIG was 3. Approximately 47% of patients had idiopathic recurrent pericarditis, 10% had an infective cause, and the remainder a systemic inflammatory disease. Nineteen out of the 30 patients (63.3%) were on corticosteroids at IVIG commencement. IVIGs were generally administered at a dose of 400-500 mg/kg/day for 5 consecutive days with repeated cycles according to the clinical response. Complications were uncommon (headache in ~3%) and not life-threatening. After a mean follow-up of approximately 33th months, recurrences occurred in 26.6% of cases after the first IVIG cycle, and 22 of the 30 patients (73.3%) were recurrence-free. Five patients (16.6%) were on corticosteroids at the end of the follow-up. CONCLUSIONS IVIGs are rapidly acting, well tolerated, and efficacious steroid-sparing agents in refractory pericarditis.
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9.
Intravenous immunoglobulin for presumed viral myocarditis in children and adults. Update of Cochrane Database Syst Rev. 2005;(1):CD004370; PMID: 15674945
Robinson J, Hartling L, Vandermeer B, Klassen TP
Cochrane Database of Systematic Reviews.. 2015;2015:CD004370.
Abstract
BACKGROUND This is an update of a previous review. Case reports and case series have described dramatic responses to intravenous immunoglobulin (IVIG) in people with presumed viral myocarditis, and its administration has become commonplace. OBJECTIVES The primary objective of this review was to compare transplant-free survival of adults and children with presumed viral myocarditis treated with IVIG versus those who did not receive IVIG. A secondary objective was to determine if a group of patients with presumed viral myocarditis could be identified (on the basis of age, duration of symptoms, acuity of onset of symptoms, cardiac function at presentation, virological results or the presence or absence of histological evidence of acute myocarditis on cardiac biopsy in patients in whom a biopsy was performed) who would be the most likely to benefit from IVIG. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 12 of 12), the Database of Abstracts of Reviews of Effects (DARE) (2013, Issue 4 of 4), MEDLINE (Ovid, 1946 to January Week 3 2014), EMBASE (Ovid, 1980 to Week 4 2014), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) EBSCO, Web of Science (Thomson Reuters, 1970 to 24 January 2014), the Latin American and Caribbean Health Science Information Database (LILACS) (1982 to 30 January 2014), trials registries and conference proceedings. We contacted authors of trials and checked reference lists of relevant papers. We applied no language restrictions. SELECTION CRITERIA We included studies if (1) participants had a clinical diagnosis of acute myocarditis with a left ventricular ejection fraction (LVEF) < 0.45, left ventricular end-diastolic diameter (LVEDD) > 2 standard deviations (SDs) above the norm or a shortening fraction (SF) > 2 SDs below the mean with duration of cardiac symptoms < 6 months; (2) participants had no evidence of non-infectious or bacterial cardiac disease; and (3) participants were randomly assigned to receive at least 1 g/kg of IVIG versus no IVIG or placebo. We excluded studies if (1) participants had received immunosuppression before outcome assessment; or (2) onset of myocarditis was reported to occur < 6 months post partum. DATA COLLECTION AND ANALYSIS Two review authors screened searches and extracted data independently. We assessed quality using the 'Risk of bias' tool. Meta-analysis was not possible because only two relevant studies were found, and researchers analysed markedly different populations. MAIN RESULTS In this update, review authors added one study to the study from the original review. The first relevant study involved 62 adults with recent-onset dilated cardiomyopathy randomly assigned to receive IVIG or an equivalent volume of 0.1% albumin in a blinded fashion. The overall risk of bias was unclear. The incidence of death or the requirement for cardiac transplant or placement of a left ventricular assist device was low in both groups (odds ratio (OR) for event-free survival 0.52, 95% confidence interval (CI) 0.12 to 2.30). Follow-up at six months and at 12 months showed equivalent improvement in LVEF (mean difference (MD) 0.00, 95% CI -0.07 to 0.07 at six months; MD 0.01, 95% CI -0.06 to 0.08 at 12 months). Functional capacity as assessed by peak oxygen consumption was equivalent in the two groups at 12 months (MD -0.80, 95% CI -4.57 to 2.97). Infusion-related side effects were more common in the treated group, but all were reported to be mild (OR 30.16, 95% CI 1.69 to 539.42).The second study added at this update included 83 children in India with suspected viral encephalitis and myocarditis. The overall risk of bias was high. The odds ratio for event-free survival was 7.39 (95% CI 0.91 to 59.86). Follow-up occurred only until hospital discharge, and LVEF was 49.5% in the treated group versus 35.9% in the placebo group (risk difference 13.6%, 95% CI 5.1 to 22.1%; P value = 0.001). AUTHORS' CONCLUSIONS Evidence from one trial does not support the use of IVIG for the treatment of adults with presume
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10.
Anti-inflammatory treatment for carditis in acute rheumatic fever
Cilliers A, Manyemba J, Adler AJ, Saloojee H
Cochrane Database of Systematic Reviews. 2012;6:CD003176
Abstract
BACKGROUND Rheumatic heart disease remains an important cause of acquired heart disease in developing countries. Although the prevention of rheumatic fever and the management of recurrences is well established, the optimal management of active rheumatic carditis is still unclear. This is an update of a review published in 2003 and previously updated in 2009. OBJECTIVES To assess the effects of anti-inflammatory agents such as aspirin, corticosteroids, immunoglobulin and pentoxifylline for preventing or reducing further heart valve damage in patients with acute rheumatic fever. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials on The Cochrane Library (Issue 3, 2011), MEDLINE (1966 to Aug 2011), EMBASE (1998 to Sept 2011), LILACS (1982 to Sept 2011), Index Medicus (1950 to April 2001) and references lists of identified studies. No language restrictions were applied. SELECTION CRITERIA Randomised controlled trials comparing anti-inflammatory agents (e.g. aspirin, steroids, immunoglobulins, pentoxifylline) with placebo or controls, or comparing any of the anti-inflammatory agents with one another, in adults and children with acute rheumatic fever diagnosed according to the Jones, or modified Jones criteria. The presence of cardiac disease one year after treatment was the major outcome criteria selected. DATA COLLECTION AND ANALYSIS Two reviewers independently extracted data. Risk of bias was assessed using methodology outlined in the Cochrane handbook. MAIN RESULTS No new studies were included in this update. Eight randomised controlled trials involving 996 people were included. Several steroidal agents corticotrophin, cortisone, hydrocortisone, dexamethasone and prednisone, and intravenous immunoglobulin were compared to aspirin, placebo or no treatment in the various studies. Six of the trials were conducted between 1950 and 1965, one study was done in 1990, and the final study was published in 2001. Overall there was no significant difference in the risk of cardiac disease at one year between the corticosteroid-treated and aspirin-treated groups (six studies, 907 participants, relative risk 0.87, 95% confidence interval 0.66 to 1.15). Similarly, use of prednisone (two studies, 212 participants, relative risk 1.13, 95% confidence interval 0.52 to 2.45) compared to aspirin did not reduce the risk of developing heart disease after one year. Adverse events were not reported in five studies. The three studies reporting on adverse events all reported substantial adverse events. However, all results should be interpreted with caution due to the age of the studies and to substantial risk of bias. AUTHORS' CONCLUSIONS There is little evidence of benefit from using corticosteroids or intravenous immunoglobulins to reduce the risk of heart valve lesions in patients with acute rheumatic fever. The antiquity of most of the trials restricted adequate statistical analysis of the data and acceptable assessment of clinical outcomes by current standards. Additionally there was substantial risk of bias, so results should be viewed with caution. New randomised controlled trials in patients with acute rheumatic fever to assess the effects of corticosteroids such as oral prednisone and intravenous methylprednisolone, and other new anti-inflammatory agents are warranted. Advances in echocardiography will allow for more objective and precise assessments of cardiac outcomes.