Randomized Trial of Different initial IVIG Regimens in Kawasaki Disease
Pediatrics international : official journal of the Japan Pediatric Society. 2021
BACKGROUND We aimed to assess the efficacy of different initial intravenous immunoglobulin (IVIG) regimens in Kawasaki disease (KD) patients to find more cost-effective therapy options. METHODS A multicentre, open-label, blind-endpoint randomized controlled trial was conducted from January 2014 to December 2015. KD Patients within 10 days of illness were randomly assigned to receive different IVIG regimens (Group A, 2 g/kg once; Group B, 1 g/kg for 2 consecutive days; Group C, 1 g/kg once) and aspirin 30mg/kg/d. Primary outcomes included hours to defervescence and development of coronary artery lesions (CAL) during the study period. Major secondary outcomes included total fever days, total dose of IVIG, changes of laboratory data, length of stay, and hospitalization expenses. (ClinicalTrials.gov: NCT02439996). RESULTS A total of 404 patients underwent randomization. No difference was found in the outcomes of defervescence among three groups at 6, 12, 24, and 36 hours after completion of initial IVIG infusion. There were no differences in the incidence of CAL during the study period (at week 2, month 1, month 3, and month 6 of illness), changes of laboratory data, total fever days and length of stay. Group C patients had the lowest total dose of IVIG (mean: 1.2 vs 2.2 vs 2.1 g/kg; P<0.001) and hospitalization expenses (mean: 8443.8 vs 10798.4 vs 11011.4 RMB; P<0.001) than other two groups. CONCLUSIONS A single dose of 1g/kg IVIG is a low-cost treatment with the same efficacy as 2 g/kg IVIG and can be an option for the initial therapy of KD patients.
The Efficacy of High-Dose Dexamethasone vs. Other Treatments for Newly Diagnosed Immune Thrombocytopenia: A Meta-Analysis
Frontiers in medicine. 2021;8:656792
Objective: To compare the therapeutic efficacies of high dose dexamethasone, prednisone and rituximab in combination with dexamethasone for newly diagnosed ITP (Immune Thrombocytopenia, ITP) patients. Methods and results: Relevant publications for this study were obtained by searching PubMed, Embase, Cochrane, and CNKI (National Knowledge Infrastructure, CNKI) databases following the PRISMA guidelines. A total of, 15 publications were retrieved that contained sufficient data from 1,362 patients for high quality analysis of this study endpoints. Data analysis was carried out using Stata 11.0 software. The primary outcomes were OR (Overall Response, OR) at 1 month after intervention and SR at 6 and 12 months. The secondary outcomes were AEs and relapse. There were no differences in the OR, while the SR was higher at 6 months (p = 0.001) as well as 12 months (p < 0.001) in the rituximab + dexamethasone group. In addition, the incidences of AEs (p = 0.008) were also higher in the rituximab + dexamethasone group. Dexamethasone was superior to prednisone based on OR (p = 0.006). We found no differences in SR at 6 months between dexamethasone and prednisone but SR at 12 months was higher in the dexamethasone group (p = 0.014). The relapse rate was higher in the high dose dexamethasone group compared to the rituximab + dexamethasone group (p = 0.042). Conclusion: This demonstrated that new treatment options such as Rituximab + dexamethasone, could be a good alternative to traditional therapy in improving long-term response and reducing the rate of relapse. However, further studies are required on the increased risk of AEs associated with Rituximab + dexamethasone.
Patient Preferences for Subcutaneous versus Intravenous Administration of Treatment for Chronic Immune System Disorders: A Systematic Review
Patient preference and adherence. 2021;15:811-834
BACKGROUND For many chronic immune system disorders, the available treatments provide several options for route of administration. The objective of this systematic literature review is to inform discussions about therapy choices for individual patients by summarizing the available evidence regarding the preferences of patients with chronic immune system disorders for intravenous (IV) or subcutaneous (SC) administration. METHODS Searches of the MEDLINE, Embase and Cochrane Library databases were conducted using terms designed to capture studies reporting patient preferences between IV and SC therapy published in English. Relevant studies were limited to those in which mode of administration, including treatment frequency and setting, was the main difference between comparators. RESULTS In total, 49 studies were included in the review. Among 18 studies that compared IV and SC immunoglobulin therapy, 16 found patients to prefer the SC administration route. The results of the 31 studies comparing IV infusion and SC injection of non-immunoglobulin therapies were mixed, with patients favoring SC administration in 20, IV infusion in seven, and having no overall preference in four. Patient experience had a strong effect on preferences, with treatment-experienced patients preferring their current administration route in most studies. Patients preferring SC administration tended also to prefer treatment at home, mainly due to the convenience and comfort of home treatment and the avoidance of having to attend hospital. By contrast, patients preferring IV infusion tended to cite the lower treatment frequency and a dislike of self-injecting, and preferred hospital treatment, mainly due to the presence of healthcare professionals and resulting feelings of safety. CONCLUSION In general patients with chronic immune system disorders tend to be more likely to choose SC administration than IV infusion, but preferences may vary according among individuals. These findings may assist discussions around appropriate treatment choices for each patient.
Monoclonal antibody and anti-cytokine biologics for Kawasaki disease: A systematic review and meta-analysis
Seminars in arthritis and rheumatism. 2021;51(5):1045-1056
BACKGROUND Kawasaki disease (KD) is a form of self-limiting vasculitis that causes coronary artery abnormalities in children. Although clinical trials of monoclonal antibodies and anti-cytokine biologics that block cytokine cascades have been conducted, the studies have revealed contradictory results. To examine the effectiveness of treatment with monoclonal antibodies and anti-cytokine biologics for KD patients, we conducted this systematic review and meta-analysis. METHODS Relevant randomized controlled trials (RCTs) and observational studies (e.g., cohort studies, case-control studies, case-series, and case-reports) were included to summarize available evidence, both qualitatively and quantitatively. The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and ICUSHI were used for systematic research. Meta-analysis of the included studies was conducted using fixed-effect or random-effects models, depending on the degree of between-study heterogeneity. We assessed coronary artery and treatment outcomes of the interventions. The certainty of evidence and risk of bias were assessed using the GRADE and Cochrane risk of bias tool. The protocol of this review is registered with PROSPERO (CRD42016033079). RESULTS Results: Of all searched studies, 183 studies were qualitatively analyzed. We finally included four randomized controlled trials with 456 patients in quantitative syntheses. Monoclonal antibodies and anti-cytokine biologics did not reduce the frequency of CAA (risk ratio [RR], 0.93; 95% confidence interval [95%CI], 0.65 to 1.32, low certainty of evidence), compared with the conventional treatment with IVIG. However, the frequency of treatment resistance (RR, 0.60; 95%CI, 0.38 to 0.95, moderate certainty of evidence) was reduced by the antibodies. We found no statistical differences in either "any adverse event" (RR, 0.92; 95%CI, 0.80 to 1.06, low certainty of evidence) or "adverse events attributable to the administration of the medication" (RR, 1.10; 95%CI, 0.72 to 1.69, low certainty of evidence) between the two groups. CONCLUSION Conclusions: Although monoclonal antibodies and anti-cytokine biologics were not effective in reducing the frequency of CAA in KD patients, the frequency of treatment resistance might be reduced by those agents compared with conventional IVIG therapy alone.
Intravenous immunoglobulin treatment for steroid-resistant optic neuritis: a multicenter, double-blind, randomized, controlled phase III study
Japanese journal of ophthalmology. 2021
PURPOSE To evaluate the efficacy and safety of intravenous "freeze-dried sulfonated human normal immunoglobulin (GGS)" in patients with steroid-resistant optic neuritis (ON). STUDY DESIGN Multicenter, prospective, double-blind, parallel-group, randomized controlled trial. METHODS Patients with steroid-resistant acute ON were randomly assigned to receive either intravenous GGS (GGS group) or intravenous methylprednisolone (steroid pulse [SP] group). Visual acuity (logarithm of the minimum angle of resolution [logMAR]), mean deviation (MD) value of the Humphrey Field Analyzer, and critical flicker fusion frequency were measured as efficacy endpoints; adverse events (AEs) were assessed as the safety endpoint. RESULTS Thirty-two patients (16 patients/group) received the study drugs. The primary endpoint, change in logMAR at week 2 compared to baseline, showed no statistically significant intergroup difference. However, compared with the SP group, change in the GGS group was increasingly indicative of visual improvement, with least squares mean difference of > 0.3 logMAR. On post-hoc analyses, the percentage of patients in the GGS and SP groups with improvement by ≥ 0.3 logMAR at week 2 were 75.0% and 31.3%, respectively. Changes in MD values at week 2 compared to baseline were 9.258 ± 8.296 (mean ± standard deviation) dB and 3.175 ± 6.167 dB in the GGS and SP groups, respectively. These results showed statistically significant intergroup differences (visual acuity improvement, P = 0.032; change in MD values, P = 0.030). No clinically significant AEs were observed. CONCLUSION Our results suggest that intravenous immunoglobulin could be a safe and efficacious therapeutic option for prompt treatment of steroid-resistant acute ON. TRIAL REGISTRATION JapicCTI-132080.
Aneurysms in primary antiphospholipid syndrome: a case-based review
Clinical rheumatology. 2021
To perform a review on patients with primary antiphospholipid syndrome (APS) who developed an aneurysm. A review of articles published in PubMed/MEDLINE, LILACS, and SciELO dating from 1966 to October 2020 was conducted using the following search words: "Antiphospholipid syndrome" and "aneurysm." No language limitation was applied. This review includes 10 articles on APS patients and aneurysms entailing 14, including our additional case. Age varied from 20 to 76 years old, and female sex was predominant and presented in 54%. The arterial vessels compromised were aorta (n = 6), coronary (n = 2), hepatic (n = 2), renal (n = 2), middle cerebral artery (n = 2), and then splenic, superior mesenteric, pancreatic, retinal, jejunal, carotid, and pulmonary. Frequencies of antiphospholipid antibodies were described as follows: lupus anticoagulant (n = 6), anti-beta2-glycoprotein I (n = 4), IgG and IgM anticardiolipin (n = 3), IgG anticardiolipin (n = 3), and antiphosphatidylserine (n = 2). The presence of APS manifestations was distributed as deep venous thrombosis (n = 4), recurrent abortions (n = 4), pulmonary embolism (n = 3), stroke, or transitory ischemic accident (n = 3), and then limb ischemia and thrombocytopenia. The therapies used in these patients were warfarin, antiplatelet agent, vascular surgery, heparin, hydroxychloroquine, coil embolism, and intravenous immunoglobulin. Regarding outcomes, 5 patients were alive, and 3 were dead. This article reviewed all published cases on APS and aneurysm and showed that women who presented with abortions and deep venous thromboses with a lupus anticoagulant are those patients more commonly affected by aneurysms in APS.
Acetylcholinesterase Inhibitors in Myasthenic Crisis: A Systematic Review of Observational Studies
Neurocritical care. 2021;:1-17
Current myasthenia gravis guidelines recommend intravenous immunoglobulin or plasmapheresis and discontinuation of pyridostigmine during myasthenic crisis. However, intravenous immunoglobulin or plasmapheresis is expensive and frequently not available in developing countries. This study aims to summarize the evidence of giving an acetylcholinesterase inhibitor in myasthenic crisis. Medline, Embase, and Cochrane databases and references were searched for observational studies that determined the use of acetylcholinesterase inhibitor in myasthenic crisis. The eligibility criteria were as follows: population, patients with myasthenic crisis, intervention (acetylcholinesterase inhibitor administration), and outcome (clinical improvement and complications). In total, 106 studies were identified, 92 through database searching (after removing duplicates) and 14 through other sources. Only eight were analyzed in the present systematic review. In five, acetylcholinesterase inhibitor was given at the start of the crisis, whereas in the other three, acetylcholinesterase inhibitor was discontinued initially and then restarted prior to extubation. Two observational analytic studies and three case reports showed improvement in different outcome measures. In the other three, improvement of outcome measures was also observed. Overall, a small proportion of patients developed cardiac arrhythmia and pneumonia after administration of acetylcholinesterase inhibitor alone, although this was not statistically different compared with those subjected to plasmapheresis. In summary, continuous intravenous infusion of pyridostigmine or neostigmine can be a substitute for intravenous immunoglobulin or plasmapheresis if these are not available during crisis; however, caution should be observed because of the aforementioned possible complications.
Kawasaki Disease: A Systematic Review and Meta-Analysis of Benefits and Harms of Common Treatments
ACR open rheumatology. 2021
OBJECTIVE Kawasaki disease (KD) is a self-limited vasculitis affecting medium-sized vessels with a predilection for the coronary arteries. Although treatment reduces the likelihood of developing of coronary artery aneurysms, 5% of patients still develop aneurysms despite treatment, making KD the leading cause of acquired heart disease in children in the United States. Consequently, there is a great deal of interest in optimizing treatment regimens, particularly for higher-risk patients, to decrease morbidity. The aim of this systematic review is to support the development of the American College of Rheumatology/Vasculitis Foundation for the diagnosis and management of KD, focusing on the more complex scenarios in which rheumatologists may become involved, such as high-risk and refractory disease. METHODS Eighty-nine articles were considered for full review in this systematic literature review to address 16 Population, Intervention, Comparison, and Outcome questions related to KD. Data were abstracted in hierarchical fashion. Randomized control trials (RCTs) were considered first; if none were identified or if they contained insufficient information, comparative observational studies were then viewed, followed by single-arm observational studies/single arms from comparative studies. Only observational studies with more than 10 subjects with vasculitis were included. RESULTS Eight RCTs and 28 observational studies that addressed the questions were identified. Two questions were addressed by RCTs, seven questions had at least some comparative observational studies, three questions were only addressed by single-arm data, and four questions had no relevant studies. CONCLUSION This systematic review evaluates the benefits and harms of treatments for KD beyond first-line therapy.
Efficacy and safety associated with the infusion speed of intravenous immunoglobulin for the treatment of Kawasaki disease: a randomized controlled trial
Pediatric rheumatology online journal. 2021;19(1):107
BACKGROUND High-dose intravenous immunoglobulin (IVIG) is the mainstay of treatment for Kawasaki disease (KD). Usually, 2 g/kg of IVIG is administered over 10-24 h, depending on the institution or physician, but the association between infusion speed and effectiveness has not been reported. In this study, we evaluated the differences in efficacy and safety between two different IVIG administration speeds. METHODS This was a multicenter, unblinded, randomized controlled study. Patients newly diagnosed with KD were randomized into two groups: one who received IVIG over 12 h (12H group, double speed), and one that received IVIG over 24 h (24H group, reference speed). The endpoints included the duration of fever, incidence of coronary artery abnormalities (CAAs) and of adverse events. Laboratory data were evaluated before and after IVIG administration. RESULTS A total of 39 patients were enrolled. There was no difference between groups in fever duration after the initiation of IVIG (21 h vs. 21.5 h, p = 0.325), and no patient experienced CAAs. Two adverse events were observed in the 12H group (elevation of aspartate aminotransferase and vomiting), however no severe adverse events requiring treatments or extension of hospital stay were observed in either group. After initial IVIG administration, the change ratio of inflammatory markers, such as white blood cell counts, neutrophils, C-reactive protein, and albumin, did not show significant differences between the two groups. On the other hand, a greater increase of serum immunoglobulin G from its baseline level was observed in the 24H group compared to the 12H group (3037 ± 648 mg/dl vs. 2414 ± 248 mg/dl, p < 0.01). CONCLUSION The efficacy and safety of IVIG administered over 12 h (double speed) were similar to those administered over 24 h (reference speed). TRIAL REGISTRATION University Hospital Medical Information Network ( UMIN000014665 ). Registered 27 July 2014 - Prospectively registered, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000017058.
Observation on the clinical effect of high-dose Intravenous Immunoglobulin combined with low-dose prednisone acetate in the treatment of patients with Kawasaki Disease
Pakistan journal of medical sciences. 2021;37(4):1122-1127
OBJECTIVE To evaluate the clinical effect of high-dose intravenous immunoglobulin (HDIVIG) single dose and pulse therapy combined with small-dose prednisone acetate in the treatment of patients with Kawasaki disease (KD). METHODS Eighty patients with KD from Baoding Children's Hospital, China, were randomly divided into two groups: the experimental group and the control group, each with 40 cases. Patients in the experimental group were treated with HDIVIG single dose, pulse therapy combined with low-dose prednisone acetate, while patients in the control group were treated with conventional-dose immunoglobulin. Patients in both groups were treated with aspirin orally, and given symptomatic treatment including anti-inflammatory, nutritional support, correction of water and electrolyte disturbance and acid-base balance. Peripheral venous blood samples were drawn from all patients at the time of admission, Day-1, Day-7 and Day-14 after treatment, and in the basic state of getting up in the morning, and then the levels of tumor necrosis factor (TNF-a), C-reactive protein (CRP), interleukin-6 (IL-6) and other inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). The time of body temperature falling to normal, lymph node swelling recovery, hands and feet swelling, mucosal hyperemia regression after treatment in the two groups was recorded, and the treatment effect of the two groups was comprehensively evaluated. RESULTS After treatment, the levels of inflammatory factors such as TNF-a, CRP, IL-6 in the experimental group were significantly lower than those in the control group, with a statistically significant difference (P<0.05). In addition, the time of body temperature falling to normal, lymph node swelling recovery, hands and feet swelling, and mucosal hyperemia regression in the experimental group was significantly shorter than that in the control group (p=0.00). The effective rate of the experimental group was 95% and that of the control group was 80%, with a statistically significant difference (p=0.04). CONCLUSION HDIVIG single dose, pulse therapy combined with small-dose prednisone acetate has a favourable therapeutic effect in the treatment of patients with KD, by which the inflammatory factors can be significantly improved, clinical symptoms and weight can be quickly ameliorated, and therapeutic effect can be enhanced.