Abstract

BACKGROUND Kawasaki disease (KD) is often complicated by coronary artery lesion (CAL), including dilatation or aneurysms. Intravenous immunoglobulin (IVIG) is used with aspirin to prevent CAL in KD. OBJECTIVE Given that the primary treatment for other vasculitis is the use of corticosteroids, this study has been performed to evaluate the effect of intravenous methylprednisolone pulse (IVMP) therapy in preventing CAL in KD. METHOD A randomized, single-blind clinical trial was conducted on 40 KD patients aged six months to five years. Patients were randomized into two groups according to the main treatment plan in addition to aspirin: case group (IVMP for three consecutive days and then oral prednisolone for three days) and control group (intravenous immunoglobulin 2 g/kg). Echocardiography was performed for all children at least three times, during the acute phase, two weeks, and two months later. RESULTS Data analysis at the end of the study was done on 40 patients (20 patients in each group). There were no significant differences in age and sex distribution, mean fever, and acute phase duration, as well as baseline echocardiography in the two groups. The frequency of CAL was 20% in the case group and 45% in the control group, after two weeks (p<0.05), but there was no significant difference between two groups in types of coronary artery lesion after two weeks and the frequency and severity of CAL after two months. CONCLUSION IVMP as initial line therapy effectively control systemic and vascular inflammation and decrease coronary artery damage in KD.

Abstract

BACKGROUND The Etanercept as Adjunctive Treatment for Acute Kawasaki Disease, a phase-3 clinical trial, showed that etanercept reduced the prevalence of IVIg resistance in acute Kawasaki disease. In patients who presented with coronary artery involvement, it reduced the maximal size and short-term progression of coronary artery dilation. Following up with this patient group, we evaluated the potential long-term benefit of etanercept for coronary disease. METHODS Patients were followed for at least 1 year after the trial. The size of dilated arteries (z-score ≥ 2.5) was measured at each follow-up visit. The z-score and size change from baseline were evaluated at each visit and compared between patients who received etanercept versus placebo at the initial trial. RESULTS Forty patients who received etanercept (22) or placebo (18) in the Etanercept as Adjunctive Treatment for Acute Kawasaki Disease trial were included. All patients showed a persistent decrease in coronary artery size measurement: 23.3 versus 5.9% at the 6-month visit, 24 versus 13.1% at the 1-year visit, and 20.8 versus 19.3% at the ≥ 2-year visit for etanercept or placebo, respectively, with similar results for decrease in coronary artery z-scores. In a multivariate analysis, correcting for patients' growth, a greater size reduction for patients on the etanercept arm versus placebo was proved significant for the 6-month (p = 0.005) and the 1-year visits (p = 0.019) with a similar end outcome at the ≥ 2-year visit. DISCUSSION Primary adjunctive therapy with etanercept for children with acute Kawasaki disease does not change the end outcome of coronary artery disease but may promote earlier resolution of artery dilation.

Abstract

BACKGROUND Although intravenous immunoglobulin (IVIG) is effective therapy for Kawasaki disease, 10-20% of patients have recrudescent fever as a sign of persistent inflammation and require additional treatment. We aimed to compare infliximab with a second infusion of IVIG for treatment of resistant Kawasaki disease. METHODS In this multicentre comparative effectiveness trial, patients (aged 4 weeks to 17 years) with IVIG resistant Kawasaki disease and fever at least 36 h after completion of their first IVIG infusion were recruited from 30 hospitals across the USA. Patients were randomly assigned (1:1) to second IVIG (2 g/kg over 8-12 h) or intravenous infliximab (10 mg/kg over 2 h without premedication), by using a randomly permuted block randomisation design with block size of two or four. Patients with fever 24 h to 7 days following completion of first study treatment crossed over to receive the other study treatment. The primary outcome measure was resolution of fever at 24 h after initiation of study treatment with no recurrence of fever attributed to Kawasaki disease within 7 days post-discharge. Secondary outcome measures included duration of fever from enrolment, duration of hospitalisation after randomisation, and changes in markers of inflammation and coronary artery Z score. Efficacy was analysed in participants who received treatment and had available outcome values. Safety was analysed in all randomised patients who did not withdraw consent. This clinical trial is registered with ClinicalTrials.gov, NCT03065244. FINDINGS Between March 1, 2017, and Aug 31, 2020, 105 patients were randomly assigned to treatment and 103 were included in the intention-to-treat population (54 in the infliximab group, 49 in the second IVIG group). Two patients randomised to infliximab did not receive allocated treatment. The primary outcome was met by 40 (77%) of 52 patients in the infliximab group and 25 (51%) of 49 patients in the second IVIG infusion group (odds ratio 0·31, 95% CI 0·13-0·73, p=0·0076). 31 patients with fever beyond 24 h received crossover treatment: nine (17%) in the infliximab group received second IVIG and 22 (45%) in second IVIG group received infliximab (p=0·0024). Three patients randomly assigned to infliximab and two to second IVIG with fever beyond 24h did not receive crossover treatment. Mean fever days from enrolment was 1·5 (SD 1·4) for the infliximab group and 2·5 (2·5) for the second IVIG group (p=0·014). Mean hospital stay was 3·2 days (2·1) for the infliximab group and 4·5 days (2·5) for the second IVIG group (p<0·001). There was no difference between treatment groups for markers of inflammation or coronary artery outcome. 24 (44%) of 54 patients in the infliximab group and 33 (67%) of 49 in the second IVIG group had at least one adverse event. A drop in haemoglobin concentration of at least 2g/dL was seen in 19 (33%) of 58 patients who received IVIG as either their first or second study treatment (three of whom required transfusion) and in three (7%) of 43 who received only infliximab (none required transfusion; p=0·0028). Haemolytic anaemia was the only serious adverse events deemed definitely or probably related to study treatment, and was reported in nine (15%) of 58 patients who received IVIG as either their first or second study treatment and none who received infliximab only. INTERPRETATION Infliximab is a safe, well tolerated, and effective treatment for patients with IVIG resistant Kawasaki disease, and results in shorter duration of fever, reduced need for additional therapy, less severe anaemia, and shorter hospitalisation compared with second IVIG infusion. FUNDING Patient Centered Outcomes Research Institute.

Abstract

BACKGROUND Therapeutic plasma exchange (TPE) and immunoadsorption (IA) are first or second line treatment options in patients with neurological autoimmune diseases, including multiple sclerosis, neuromyelitis optica spectrum disorders (NMSOD), chronic inflammatory demyelinating polyneuropathy, acute inflammatory demyelinating polyradiculoneuropathy (Guillain-Barré syndrome), and autoimmune encephalitis. METHODS In this prospective randomized controlled monocentric study, we assessed safety and efficacy of therapy with IA or TPE in patients with neurological autoimmune diseases. Treatment response was assessed using various neurological scores as well by measuring immunoglobulin and cytokine concentrations. Clinical outcome was evaluated by application of specific scores for the underlying diseases. RESULTS A total of 32 patients were analyzed. Among these, 19 patients were treated with TPE and 13 patients with IA. IA and TPE therapy showed a comparable significant treatment response. In patients with MS and NMOSD, mean EDSS before and after treatment showed a significant reduction after treatment with IA. We observed a significant reduction of the pro-inflammatory cytokines IL-12, lL-17, IL-6, INF-γ, and tumor necrosis factor alpha during IA treatment, whereas this reduction was not seen in patients treated with TPE. CONCLUSIONS In summary, both IA and TPE were effective and safe procedures for treating neurological autoimmune diseases. However, there was a trend towards longer therapy response in patients treated with IA compared to TPE, possibly related to a reduction in plasma levels of pro-inflammatory cytokines seen only in the IA-treated group.

Abstract

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.

Abstract

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.

Abstract

OBJECTIVES Oral lichen planus (OLP) is a chronic immune-mediated disease that affects the oral cavity. Topical steroids are considered the treatment of choice for painful lesions of OLP. The aim of this split-mouth study was to compare the efficacy of platelet-rich fibrin (PRF) and triamcinolone acetonide (TA) injective therapies in patients with symptomatic OLP. MATERIALS AND METHODS Participants with symptomatic OLP were recruited in the Academic Hospital of Magna Graecia University of Catanzaro, Italy. Once a week for a month, patients randomly received a 0.5-mL TA injection in one buccal mucosa and 1-mL PRF injection in the opposite side. The measured outcomes were reduction of the lesions area and symptomatology modifications using visual analogue scale (VAS) score RESULTS Four weeks after the last injections, an average reduction of 59.8% in the lesion extension and an average reduction of 47.6% in the VAS score for PRF-treated sites were observed; the same variation for TA-treated sites was respectively of 59.2% and 40%. There were no statistically significant differences between the two groups. CONCLUSIONS PRF was effective in reducing OLP lesions extension and symptomatology, and it seems to be as effective as TA. Additional data should be collected with a larger sample size, at a longer follow-up and on the PRF lowest effective dose. CLINICAL RELEVANCE Current treatment options for OLP are limited. The study proved benefits of PRF injections in management of painful lesions of OLP comparable with TA.

Abstract

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.

Abstract

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.

Abstract

BACKGROUND Standard first-step therapy for Kawasaki disease consists of Intravenous immunoglobulin and high dose Aspirin (80-100 mg/kg/day). The standard dose of Intravenous immunoglobulin (2gr/kg) is strongly effective in reducing the risk of coronary arteries abnormalities. So, the proper dose and efficacy of Aspirin to decrease the risk of coronary arteries abnormalities is a controversial issue. In this study, it is tried to assess the result of eliminating high-dose Aspirin in the treatment of the acute phase of Kawasaki and observe the incidence rate of coronary arteries abnormalities when only Intravenous immunoglobulin was administered. METHODS This study is a prospective randomized, open-label, blinded end-points clinical trial performed in Afzalipour hospital in Kerman University of Medical Sciences from September 2017 to September 2018 in 62 patients with typical and atypical Kawasaki disease. The study group received Intravenous immunoglobulin (2 g/kg) and the control group get the same dose of Intravenous immunoglobulin plus Aspirin with the dose of 80-100 mg/Kg/day until they were afebrile for 48 hours. Afterward, both groups received a daily single dose (3-5 mg/kg) of Aspirin for six weeks. Echocardiography was done after two weeks, six weeks, and six months. Internal diameter of the left and right main coronary arteries was measured and then the corresponding Z-score was calculated. RESULTS In the study group, coronary arteries abnormalities decreased from 38.7% in the 2nd week to 16.1% in the 6th month. In the control group, it declined from 54.8% to 22.6%. There was no statistically significant difference between the groups in term of frequency of abnormal coronary arteries at the study period (P=0.151). CONCLUSIONS We concluded that high dose Aspirin does not have a significant role in preventing coronary arteries abnormalities in Kawasaki disease and giving standard 2 gr/kg/day Intravenous immunoglobulin without high-dose Aspirin in acute-phases therapy does not increase the risk of coronary arteries abnormality.