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Frontiers in Immunology 2023To present the pooled quantitative evidence of baseline characteristics and clinical outcomes of tocilizumab (TCZ) in patients with refractory Takayasu arteritis (TAK). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To present the pooled quantitative evidence of baseline characteristics and clinical outcomes of tocilizumab (TCZ) in patients with refractory Takayasu arteritis (TAK).
METHODS
A comprehensive systematic review and meta-analysis was performed on all available studies retrieved from the MEDLINE, Embase, and Cochrane databases, using TCZ in patients with refractory TAK. We applied the commands and in Stata Software to pool overall estimates of continuous data and binomial data, respectively. A random-effects model was recruited for analysis.
RESULTS
Nineteen studies with 466 patients were included in this meta-analysis. The mean age at implementation of TCZ was 34.32 years. Female sex and Numano Type V were the most prominent baseline characteristics. During the 12-month follow-up when receiving TCZ treatment, pooled CRP was 1.17 mg/L (95% confidence interval [CI] -0.18-2.52), pooled ESR was 3.54 mm/h (95% CI 0.51-6.58), and pooled glucocorticoid dose was 6.26 mg/d (95% CI 4.24-8.27). Approximately 76% (95% CI 58-87%) of patients achieved a decrease in glucocorticoid dosage. Meanwhile, patients with TAK had a remission rate of 79% (95% CI 69-86%), a relapse rate of 17% (95% CI 5-45%), an imaging progress rate of 16% (95% CI 9-27%), and a retention rate of 68% (95% CI 50-82%). Adverse events occurred in 16% (95% CI 5-39%) of patients, and infection was the most common adverse event, with a rate of 12% (95% CI 5-28%).
CONCLUSION
TCZ treatment can provide favorable outcomes in terms of inflammatory markers, steroid-sparing effects, clinical response, drug retention and minimizing adverse effects for patients with refractory TAK.
Topics: Humans; Female; Adult; Glucocorticoids; Takayasu Arteritis; Treatment Outcome; Antibodies, Monoclonal, Humanized
PubMed: 36845158
DOI: 10.3389/fimmu.2023.1084558 -
Heart Rhythm Aug 2020Failure of drugs and catheter ablation procedures for the treatment of ventricular arrhythmias is still extremely relevant. Recently, stereotactic body radiotherapy has...
Failure of drugs and catheter ablation procedures for the treatment of ventricular arrhythmias is still extremely relevant. Recently, stereotactic body radiotherapy has been introduced to treat therapy refractory patients. In this systematic review (International Prospective Register of Systematic Reviews, CRD42019133212), we aimed to summarize electrophysiological and histopathological effects of radioablation in animals, patients, and extracted and perfused hearts. A systematic search was performed in OVID MEDLINE, OVID Embase, the Cochrane Central Register of Controlled Trials, Web of Science, Google Scholar, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) from inception to September 2019. Identified records were independently screened for eligibility by 2 reviewers. Risk of bias and methodological quality were assessed using the SYRCLE, ROBINS-I, or Murad tool and tailored to the different study designs. We included 13 preclinical and 10 clinical publications. Large heterogeneity in study designs prompted a narrative synthesis approach. Baseline, (pre-)procedural details, outcome, target tissue analyses, and safety data were extracted and summarized. In animal studies evaluating electrophysiological parameters, radioablation induced a reduction in voltage/potential amplitude or bidirectional block in target areas in 93.2% of animals. Atrioventricular block (first to third degree) was induced in 78.3% of animals, and in studies evaluating ventricular arrhythmia inducibility, 75% reduction was achieved. In patients, predominantly ventricular tachycardias were targeted with >85% reduction in arrhythmia episodes during follow-up with an encouraging short-term safety profile. Preclinical and clinical evidence on the efficacy and safety of radioablation is limited in both quantity and quality. The results of radioablation for therapy refractory patients with ventricular tachycardia are promising, but further research is needed.
Topics: Catheter Ablation; Heart Conduction System; Humans; Tachycardia, Ventricular
PubMed: 32205299
DOI: 10.1016/j.hrthm.2020.03.013 -
Frontiers in Neurology 2021Approximately 10-20% of patients WITH myasthenia gravis (MG) are refractory to conventional immunotherapies. The purpose of this study was to conduct a systematic...
Approximately 10-20% of patients WITH myasthenia gravis (MG) are refractory to conventional immunotherapies. The purpose of this study was to conduct a systematic review and meta-analysis to explore the optimal therapies for refractory MG. Correlative studies were performed through a search in PubMed, Cochrane Library, and Embase databases. The primary outcome was defined by changes in the quantitative myasthenia gravis score (QMG). Secondary outcomes were defined by the Myasthenia Gravis Activities of Daily Living Scale (MG-ADL), Myasthenia Gravis Foundation of America (MGFA) post intervention status, adverse events, and disease exacerbation after treatment. A total of 16 studies were included with 403 patients with refractory MG on therapies with rituximab, eculizumab, tacrolimus, and cladribine. Therapeutic efficacy of rituximab and eculizumab was identified with an estimated reduction in QMG score (4.158 vs. 6.928) and MG-ADL (4.400 vs. 4.344), respectively. No significant changes were revealed in efficacy or exacerbation density between the two independent therapeutic cohorts. The estimated adverse event density of eculizumab was more significant than that in the rituximab group (1.195 vs. 0.134 per patient-year), while the estimated serious event density was similar. The efficacy and safety of rituximab and eculizumab have been approved in patients with refractory MG. Rituximab had a superior safety profile than eculizumab with a lower incidence of adverse events. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021236818, identifier CRD42021236818.
PubMed: 34925206
DOI: 10.3389/fneur.2021.725700 -
RMD Open Dec 2023Refractory autoimmune diseases remain a significant challenge in clinical practice and new therapeutic options are needed. This systematic review evaluates the existing...
OBJECTIVE
Refractory autoimmune diseases remain a significant challenge in clinical practice and new therapeutic options are needed. This systematic review evaluates the existing reported data on the CD38-targeting antibody daratumumab as a new therapeutic approach in autoantibody-mediated autoimmune diseases.
METHODS
A protocolised systematic literature review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed. Two databases (Medline and Embase) were searched for suitable studies. Usage of daratumumab in non-oncological or non-transplantation associated diseases with autoimmune pathophysiology was analysed including patient characteristics, therapeutic regimen, adverse events and patient outcome.
RESULTS
38 publications reporting the clinical course of 83 patients met the inclusion criteria. Daratumumab usage was reported in therapy-refractory cases (median of 5 different previous therapies) in 24 different autoimmune diseases. The median number of applications of daratumumab was 4, mainly via intravenous applications (87%). Concomitant treatment included glucocorticoids in 64% of patients, intravenous immunoglobulins (33%) and rituximab (17%). Remission or improvement of disease was reported in 81% of patients. Autoantibody depletion or reduction was stated in 52% of patients. Death occurred in three patients (3%). Adverse events were reported in 45% of patients including application-associated reaction (20%), infection (19%) and hypogammaglobulinaemia (33%).
CONCLUSION
Targeting CD38 via daratumumab is a new promising therapeutic option in therapy refractory autoimmune diseases. Efficacy as well as optimal therapeutic regimen and management or prevention of adverse events require further investigation. Therefore, systematic clinical trials of this therapeutic approach are needed.
Topics: Humans; Antibodies, Monoclonal; Rituximab; Autoimmune Diseases; Autoantibodies
PubMed: 38101819
DOI: 10.1136/rmdopen-2023-003604 -
Journal of Gastroenterology and... Apr 2023Patients with ulcerative proctitis have favorable long-term outcomes but are typically excluded from ulcerative colitis clinical trials. Refractory proctitis presents a... (Review)
Review
Patients with ulcerative proctitis have favorable long-term outcomes but are typically excluded from ulcerative colitis clinical trials. Refractory proctitis presents a management conundrum for gastroenterologists, and there remains a lack of clarity as to the best therapeutic strategy. This study aimed to undertake a systematic review of studies assessing the clinical efficacy and safety of therapies for refractory proctitis. PubMed, Embase, Cochrane Library, and MEDLINE databases were searched without restriction from inception to October 27, 2022. Both interventional and noninterventional studies examining efficacy of therapeutic modalities for the induction and/or maintenance of remission in refractory proctitis were included. Included studies were grouped by therapeutic modalities as follows: (i) immunomodulators, (ii) monoclonal antibodies, (iii) topical calcineurin inhibitors, (iv) other topical therapies, and (v) appendicectomy. The search strategy identified 3301 studies, of which 13 met eligibility criteria for inclusion. Clinical remission rates for systemic therapies ranged from 20-26% for azathioprine to 50-69% for tumor necrosis factor-α inhibitor therapies. The use of systemic therapies for proctitis raised safety concerns, with 22-37% of patients discontinuing therapies due to adverse effects across four retrospective cohort studies. Prospective clinical trials of topically applied tacrolimus demonstrated clinical remission rates of 42-46%, with a favorable safety profile. Substantial heterogeneity in study design precluded meta-analysis. Refractory ulcerative proctitis remains a neglected entity, with a dearth of prospective clinical trials to guide therapeutic decision-making. Current evidence supports a role for topically administered tacrolimus.
Topics: Humans; Colitis, Ulcerative; Tacrolimus; Prospective Studies; Retrospective Studies; Proctitis; Remission Induction
PubMed: 36644922
DOI: 10.1111/jgh.16111 -
Annals of Palliative Medicine Sep 2021A systematic review and meta-analysis were performed to explore the adoption value of electronic bronchoscopy (EBS) in the diagnosis and treatment of refractory... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A systematic review and meta-analysis were performed to explore the adoption value of electronic bronchoscopy (EBS) in the diagnosis and treatment of refractory pneumonia and to provide a theoretical basis for the clinical bronchoscopy treatment of patients.
METHODS
Randomized controlled trials of treatment-resistant pneumonia searched on PubMed, Embase, and other websites before December 31, 2020 were collected. Literature was selected by inclusion and exclusion criteria. Bias risk was assessed using Cochrane intervention system Review manual 5.0.2 and Review Manager 5.3.
RESULTS
A total of 6 articles meeting the requirements were included, comprising 796 participants. The results of meta-analysis showed that the clinical efficacy [odds ratio (OR) =3.8; 95% confidence interval (CI): 1.11-12.99; Z=2.13; P =0.03] and white blood cell counts [mean difference (MD) =0.55; 95% CI: -0.57 to 1.67; Z=0.96; P=0.34] of patients both increased. The mortality rate (OR =0.7; 95% CI: 0.3-1.63; Z=0.82; P=0.41), the incidence of infection (OR =0.84; 95% CI: 0.5-1.39; Z=0.69; P=0.49), ICU hospitalization days (OR =0.59; 95% CI: 0.36-0.98; Z=2.04; P=0.04), days of antibiotic use (OR =0.39; 95% CI: 0.18-0.84; Z=2.41; P=0.02), body temperature (MD =-0.2; 95% CI: -0.24 to 0.16; Z=9.5; P<0.0001), and the PaO2:FIO2 ratio (MD =-9.96; 95% CI: -13.31 to -6.61; Z=5.83; P<0.0001) of patients in the experimental group were lower than those of the control group. Differences in white blood cell count, mortality rate, and incidence of infection of patients in the experimental group were not statistically significant compared with those in the control group.
DISCUSSION
EBS adopted in the diagnosis and treatment of refractory pneumonia can reduce the occurrence of postoperative adverse reactions, reduce the infection rate, and effectively improve the clinical symptoms. It is therefore suitable for the treatment of this disease.
Topics: Bronchoscopy; Electronics; Humans; Length of Stay; Pneumonia; Treatment Outcome
PubMed: 34628915
DOI: 10.21037/apm-21-2133 -
Frontiers in Neurology 2023Long-term sequelae of the new onset refractory status epilepticus (NORSE) include the development of epilepsy, cognitive deficits, and behavioral disturbances. The... (Review)
Review
BACKGROUND
Long-term sequelae of the new onset refractory status epilepticus (NORSE) include the development of epilepsy, cognitive deficits, and behavioral disturbances. The prevalence of these complications has been previously highlighted in case reports and case series: however, their full scope has not been comprehensively assessed.
METHODS
We conducted a systematic review of the literature (PROSPERO ID CRD42022361142) regarding neurological and functional outcomes of NORSE at 30 days or longer following discharge from the hospital. A systematic review protocol was developed using guidance from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).
RESULTS
Of the 1,602 records for unique publications, 33 reports on adults and 52 reports on children met our inclusion criteria. They contained the description of 280 adults and 587 children of whom only 75.7 and 85% of patients, respectively had data on long-term follow-up. The mean age of adult and pediatric patients was 34.3 and 7.9 years, respectively; and the longest duration of follow up were 11 and 20 years, respectively. Seizure outcomes received major attention and were highlighted for 93.4 and 96.6% of the adult and pediatric NORSE patients, respectively. Seizures remained medically refractory in 41.1% of adults and 57.7% of children, while seizure freedom was achieved in only 26 and 23.3% of these patients, respectively. The long-term cognitive outcome data was provided for just 10.4% of the adult patients. In contrast, cognitive health data were supplied for 68.9% of the described children of whom 31.9% were moderately or severely disabled. Long-term functional outcomes assessed with various standardized scales were reported in 62.2 and 25.5% of the adults and children, respectively with majority of patients not being able to return to a pre-morbid level of functioning. New onset psychiatric disorders were reported in 3.3% of adults and 11.2% of children recovering from NORSE.
CONCLUSION
These findings concur with previous observations that the majority of adult and pediatric patients continue to experience recurrent seizures and suffer from refractory epilepsy. Moderate to severe cognitive disability, loss of functional independence, and psychiatric disorders represent a hallmark of chronic NORSE signifying the major public health importance of this disorder.
PubMed: 36761344
DOI: 10.3389/fneur.2023.1095061 -
Minerva Pediatrics Apr 2024The relationship between cytokines and refractory mycoplasma pneumoniae pneumonia (RMPP) in children was conflicting. The aim of the current study was to perform a...
INTRODUCTION
The relationship between cytokines and refractory mycoplasma pneumoniae pneumonia (RMPP) in children was conflicting. The aim of the current study was to perform a systematic review to determine the relationship between cytokines and RMPP in children.
EVIDENCE ACQUISITION
We searched PubMed, and the search was done on 21 November 2022. This search was limited to human studies, with language restriction of English. Studies were included if they reported the relationship between cytokines and RMPP.
EVIDENCE SYNTHESIS
A total of 22 relevant full articles were included in the review. TNF-α levels in the bronchoalveolar lavage fluid (BALF) and IL-18 levels in the blood samples were likely to be associated with RMPP. IL-2 and IL-4 lost significance regardless in the BALF or blood samples. Additionally, there was no significant difference in IFN-γ levels between RMPP patients and non-refractory mycoplasma pneumoniae pneumonia (NRMPP) patients in the BALF. Patients receiving different treatments had different levels of cytokines.
CONCLUSIONS
This analysis offers evidence linking abnormalities of cytokines with RMPP in children, which may be essential for identifying individuals with RMPP. Large prospective studies are needed for further clarification of roles of cytokines in RMPP.
Topics: Child; Humans; Mycoplasma pneumoniae; Cytokines; Pneumonia, Mycoplasma; Bronchoalveolar Lavage Fluid; Tumor Necrosis Factor-alpha
PubMed: 37155205
DOI: 10.23736/S2724-5276.23.07158-6 -
Cureus Nov 2022Interleukin 1 (IL-1) has been indicated as a mediator of recurrent pericarditis. Rilonacept, a soluble IL-1 receptor chimeric fusion protein neutralizing interleukin 1... (Review)
Review
Interleukin 1 (IL-1) has been indicated as a mediator of recurrent pericarditis. Rilonacept, a soluble IL-1 receptor chimeric fusion protein neutralizing interleukin 1 alpha (IL-1α) and interleukin 1 beta (IL-1β), has demonstrated promising results in a phase II study in recurrent or refractory pericarditis. Anakinra is a recombinant inhibitor of the IL-1 receptor with a demonstrated reduction in the incidence of recurrent pericarditis. Definite pharmacological management of pericarditis is key to preventing recurrences, mostly treatment options for recurrent pericarditis refractory to conventional drugs. Here we critically discuss the existing therapy options for recurrent pericarditis, with a focus on new pharmacological approaches: rilonacept and anakinra. A systematic search was conducted across online databases such as PubMed, Cochrane, Google Scholar, ScienceDirect, CINAHL, Scopus, and Embase to obtain clinical trials that assess the effectiveness of anti-interleukin 1 therapy such as anakinra and rilonacept in the management of recurrent pericarditis. Our study concluded that anti-interleukin 1 therapy significantly improved both the quality of life and the clinical outcomes of the study population. These outcomes were most prominent with the use of rilonacept and anakinra in the trial treatment. Rilonacept and anakinra are valuable options in case of recurrent pericarditis refractory to conventional drugs.
PubMed: 36505131
DOI: 10.7759/cureus.31226 -
SAGE Open Medicine 2023C5 inhibitors such as eculizumab and ravulizumab are the first-line treatment in the management of paroxysmal nocturnal hemoglobinuria (PNH). However, some patients... (Review)
Review
OBJECTIVES
C5 inhibitors such as eculizumab and ravulizumab are the first-line treatment in the management of paroxysmal nocturnal hemoglobinuria (PNH). However, some patients develop novel symptoms as part of their treatment with eculizumab, and the disease is termed as eculizumab refractory PNH. The aim of this study was to conduct a systematic review on the available treatment modalities for the management of eculizumab refractory PNH.
METHODS
Two authors independently searched two databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 70 studies were obtained: 4 out 70 studies were found to meet the inclusion criteria.
RESULTS
Four studies were found to meet the inclusion criteria of our study. Two studies were published in 2021 and two studies were published in 2020. All four studies were multicenter clinical trials. Two studies were phase III clinical trials, one study was a phase II clinical trial, and one study was a phase I clinical trial. Two studies were about pegcetacoplan, one was about danicopan, and one was about iptacopan.
CONCLUSION
Based upon the findings of our systematic review, we recommend an individualized treatment plan based on the mechanism of eculizumab refractoriness and the mechanism of PNH breakthrough. This recommendation is subject to the available resources and clinical expertise available at different hospitals. More studies using study designs such as randomized controlled trials comparing multiple drugs should be performed to accurately assess the different medications and aid in designing guidelines of the management of eculizumab refractory PNH.
LEVEL OF EVIDENCE
Level I.
PubMed: 37388903
DOI: 10.1177/20503121231181267