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The effects of plasma exchange in patients with ANCA-associated vasculitis: an updated systematic review and meta-analysis
Walsh M, Collister D, Zeng L, Merkel PA, Pusey CD, Guyatt G, Au Peh C, Szpirt W, Ito-Hara T, Jayne DRW
BMJ (Clinical research ed.). 2022;376:e064604
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Editor's Choice
Abstract
OBJECTIVE To assess the effects of plasma exchange on important outcomes in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV). DESIGN Systematic review and meta-analysis of randomised controlled trials. ELIGIBILITY CRITERIA Randomised controlled trials investigating effects of plasma exchange in patients with AAV or pauci-immune rapidly progressive glomerulonephritis and at least 12 months' follow-up. INFORMATION SOURCES Prior systematic reviews, updated by searching Medline, Embase, and CENTRAL to July 2020. RISK OF BIAS Reviewers independently identified studies, extracted data, and assessed the risk of bias using the Cochrane Risk of Bias tool. SYNTHESIS OF RESULTS Meta-analyses were conducted using random effects models to calculate risk ratios and 95% confidence intervals. Quality of evidence was summarised in accordance with GRADE methods. Outcomes were assessed after at least12 months of follow-up and included all-cause mortality, end stage kidney disease (ESKD), serious infections, disease relapse, serious adverse events, and quality of life. RESULTS Nine trials including 1060 participants met eligibility criteria. There were no important effects of plasma exchange on all-cause mortality (relative risk 0.90 (95% CI 0.64 to 1.27), moderate certainty). Data from seven trials including 999 participants that reported ESKD demonstrated that plasma exchange reduced the risk of ESKD at 12 months (relative risk 0.62 (0.39 to 0.98), moderate certainty) with no evidence of subgroup effects. Data from four trials including 908 participants showed that plasma exchange increased the risk of serious infections at 12 months (relative risk 1.27 (1.08 to 1.49), moderate certainty). The effects of plasma exchange on other outcomes were uncertain or considered unimportant to patients. LIMITATIONS OF EVIDENCE There is a relative sparsity of events, and treatment effect estimates are therefore imprecise. Subgroup effects at the participant level could not be evaluated. INTERPRETATION For the treatment of AAV, plasma exchange has no important effect on mortality, reduces the 12 month risk of ESKD, but increases the risk of serious infections. FUNDING No funding was received. REGISTRATION This is an update of a previously unregistered systematic review and meta-analysis published in 2014.
PICO Summary
Population
Patients with anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (9 studies, n= 1,060).
Intervention
Plasma exchange.
Comparison
No plasma exchange.
Outcome
There were no important effects of plasma exchange on all-cause mortality (relative risk 0.90, moderate certainty). Data from seven trials (n= 999) reporting end stage kidney disease (ESKD) demonstrated that plasma exchange reduced the risk of ESKD at 12 months (relative risk 0.62, moderate certainty) with no evidence of subgroup effects. Data from four trials (n= 908) showed that plasma exchange increased the risk of serious infections at 12 months (relative risk 1.27, moderate certainty). The effects of plasma exchange on other outcomes were uncertain or considered unimportant to patients.
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Recent Advancements in the Management of Anti-neutrophil Cytoplasmic Antibody-Associated Vasculitis: A Systematic Review
Arzoun H, Srinivasan M, Thangaraj SR, Thomas SS, Yarema A, Lee B, Mohammed L
Cureus. 2022;14(2):e21814
Abstract
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a rare multisystem autoimmune condition that causes inflammation of small and medium-sized blood vessels and is more commonly seen in the geriatric population. ANCA-associated vasculitis (AAV) is typically characterized as necrotizing vasculitis and includes granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). The mortality rate remains high, with especially cardiovascular disease, infections, and malignancies being the leading causes of death. Existing treatment options depend heavily on the use of glucocorticoids (GCs), often in combination with cyclophosphamide (CYC); however, as the multitude of adverse effects associated with these agents has increased, numerous studies are being conducted to reduce not only these harmful effects but also improve remission rates. Rituximab, avacopan, corticosteroids, including intravenous pulse methylprednisolone, plasma exchange, and immunological targeting are among the emerging treatments. The purpose of this review is to emphasize the pathogenesis and traditional treatment modalities and give insights into the recent advances in managing this disorder in an attempt to spare the adverse effects of conventional therapies while achieving better remission rates with combination therapies as well. The authors explored multiple databases, employing appropriate keywords, satisfying the quality appraisal, after which a total of 14 reports were included in this review. Upon overall analysis, it can be concluded that rituximab and CYC, when used in combination, provided a safer alternative to GCs while exhibiting equal, if not superior, effectiveness and results, thus, paving the way for additional in-depth research in a larger population of interest.
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Comparison of multiple treatments in the management of transplant-related thrombotic microangiopathy: a network meta-analysis
Yang J, Xu X, Han S, Qi J, Li X, Pan T, Zhang R, Han Y
Annals of hematology. 2022
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Editor's Choice
Abstract
Hematopoietic stem cell transplantation-associated thrombotic microangiopathy (TA-TMA) is a fatal post-transplant complication. It has a high mortality rate and worse prognosis, but treatment strategies remain controversial. We screened 6 out of 3453 studies on the treatment of TA-TMA. These investigations compared 5 treatment strategies with a network meta-analysis approach. The final outcome was the proportion of patients who responded to these therapies. There were significant differences in response rates for each treatment. Achieving analysis through direct and indirect evidence in the rank probabilities shows that rTM (recombinant human soluble thrombomodulin) is most likely to be rank 1 (64.98%), Eculizumab intervention rank 2 (48.66%), ISM (immunosuppression manipulation) rank 3 (32.24%), TPE (therapeutic plasma exchange) intervention rank 4 (69.56%), and supportive care intervention rank 5 (70.20%). Eculizumab and ISM have significantly higher efficacy than supportive care (odds ratio (OR): 18.04, 18.21 respectively); and TPE having lower efficacy than all other TA-TMA therapies exception to supportive care. In our study, rTM and Eculizumab may be the best choice when treating TA-TMA.
PICO Summary
Population
Patients receiving treatment for transplantation-associated thrombotic microangiopathy (TA-TMA), (6 studies, n= 71).
Intervention
Therapeutic plasma exchange (TPE).
Comparison
Recombinant human soluble thrombomodulin (rTM). Eculizumab. Immunosuppression manipulation (ISM). Supportive care.
Outcome
There were significant differences in response rates for each treatment. Achieving analysis through direct and indirect evidence in the rank probabilities showed that rTM was most likely to be rank 1 (64.98%), Eculizumab intervention rank 2 (48.66%), ISM rank 3 (32.24%), intervention rank 4 (69.56%), and supportive care intervention rank 5 (70.20%). Eculizumab and ISM had significantly higher efficacy than supportive care (odds ratio (OR): 18.04, 18.21 respectively); and TPE had lower efficacy than all other TA-TMA therapies exception to supportive care.
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Granulomatosis With Polyangiitis Presenting With Diffuse Alveolar Hemorrhage: A Systematic Review
Da Silva RC, Adhikari P
Cureus. 2022;14(10):e29909
Abstract
Granulomatosis with polyangiitis (GPA) is a systemic disease that has variable clinical expression. GPA is the most common antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Diffuse alveolar hemorrhage (DAH) is one of the least common pulmonary manifestations in patients with GPA. DAH is clinically marked by hemoptysis, anemia, and diffuse alveolar infiltrates on imaging as well as hypoxemic respiratory failure. The diagnosis and treatment are challenging. Recommendations for ANCA-associated vasculitis, in general, are already established; however, there is a knowledge gap that addresses the association of GPA and DAH. The aim of this systematic review is to focus on the main clinical aspects and treatment of patients with GPA who present with DAH. Thorough research of available literature was performed, including studies published in the last 10 years, following the Preferred Items for Systematic Review and Meta-Analysis (PRISMA) 2020 recommendations. The following databases were included: PubMed, Medline, Embase, ClinicalTrials.com, Google Scholar, and Prospero. The search terms included: [granulomatosis] AND [polyangiitis] AND [diffuse alveolar hemorrhage] OR [diffuse pulmonary hemorrhage] NOT [microscopic polyangiitis] NOT [eosinophilic granulomatosis]. NOS was used to assess the internal validity of the study in four domains, including selection, ascertainment, causality, and reporting. Our initial search identified 8989 studies. After excluding duplicated data and using our predetermined inclusion and exclusion criteria, we were able to retrieve 18 studies. Twelve out of 18 (67%) studies were case reports. Five were retrospective cohorts and one controlled trial. The average age of patients with GPA with DAH was 49.55 ± 17.54 years (18 - 76). Male individuals had a slight predominance (59%) in comparison to female individuals (41%). The hemoglobin level at the time of presentation was 8.86 mg/dL ± 1.43. The majority of patients (61.5%) reported hemoptysis. Renal involvement was present in 66.7%. Patients who required mechanical ventilation represented 61.5%. Plasmapheresis was used in 71.4%. Mortality was 20%, and gender was not associated with mortality (p = 0.822). Hemoptysis was not associated with the need for mechanical ventilation (p = 0.928). Renal impairment was not a predictor of mechanical ventilation (p = 0.207). In summary, patients with GPA and DAH were severely ill, frequently had renal impairment upon admission, and frequently required mechanical ventilation. Steroids, rituximab, and cyclophosphamide are the first-line treatment, and plasmapheresis is still in use. Eventually, extracorporeal membrane oxygenation (ECMO) can be the salvage therapy. Randomized controlled clinical trials (RCTs) are needed to address the best therapeutic options for this population.
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Granulomatosis With Polyangiitis and Microscopic Polyangiitis: A Systematic Review and Meta-Analysis of Benefits and Harms of Common Treatments
Springer JM, Kalot MA, Husainat NM, Byram KW, Dua AB, James KE, Chang Lin Y, Turgunbaev M, Villa-Forte A, Abril A, et al
ACR open rheumatology. 2021
Abstract
OBJECTIVE The aim of this systemic review is to compare different treatments for patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) to inform evidence-based recommendations for the American College of Rheumatology (ACR)/Vasculitis Foundation (VF) Vasculitis Management Guidelines. METHODS A systemic review was conducted by searching articles in English using OVID Medline, PubMed, Embase, and the Cochrane Library. Articles were screened for suitability in addressing PICO questions, with studies presenting the highest level of evidence given preference. RESULTS A total of 729 full-text articles addressing GPA and MPA PICO questions were reviewed. For remission induction, rituximab was shown to be noninferior to cyclophosphamide (CYC) (odds ratio [OR]: 1.55, moderate certainty of evidence). The addition of plasma exchange to induction therapy in severe disease did not improve the composite end point of death or end stage renal disease (hazard ratio [HR]: 0.86 [95% confidence interval CI: 0.65, 1.13], moderate certainty of evidence). In nonsevere disease, methotrexate was noninferior to CYC for induction of remission (remission at 6 months of 90% vs. 94%). For maintenance of remission, methotrexate and azathioprine showed no difference in the risk of relapse over a mean follow-up of 29 months (HR: 0.92, [95% CI: 0.52, 1.65]low certainty of evidence). As maintenance therapy, rituximab was superior to a tapering azathioprine strategy in major relapse-free survival at 28 months (HR: 6.61, [95% CI: 1.56, 27.96], moderate certainty of evidence). In two randomized trials, longer-term azathioprine maintenance therapy (>24 months) is associated with fewer relapses without an increase in adverse events. CONCLUSION This comprehensive systematic review synthesizes and evaluates the benefits and toxicities of different treatment options for GPA and MPA.
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Effects of therapeutic plasma exchange on anticoagulants in patients receiving therapeutic anticoagulation: a systematic review
Hodulik KL, Root AG, Ledbetter LS, Onwuemene OA
Transfusion. 2019
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Abstract
Therapeutic plasma exchange (TPE) removes coagulation proteins, but its impact on therapeutic anticoagulation is unknown. We performed a systematic review of the literature to determine the coagulation effects of TPE in patients receiving systemic anticoagulation. We searched MEDLINE, CINAHL, EMBASE, and Web of Science until June 2018 for studies combining controlled vocabulary and keywords related to therapeutic plasma exchange, plasmapheresis, anticoagulants, and therapy. The primary outcome was the effect of TPE on anti-Xa activity, activated partial thromboplastin time (aPTT), or international normalized ratio (INR). The secondary outcome was reports of post-TPE bleeding or thrombosis. A total of 1830 references were screened and eight studies identified. Our selected studies (five case reports and three case series) involved 23 patients and evaluated the effects of seven anticoagulants. Six studies of unfractionated heparin, low-molecular-weight heparins, and direct oral anticoagulants demonstrated an anti-Xa level decline. Two studies of unfractionated heparin and low-molecular-weight heparins showed an aPTT increase. One study of warfarin showed a post-TPE INR increase. Reports of post-TPE bleeding occurred in two patients and thrombosis in one. In patients receiving therapeutic anticoagulation, TPE is associated with anti-Xa activity decline and aPTT and INR increase. These coagulation changes do not appear to significantly increase bleeding or thrombotic risk. Our data suggest the need for prospective studies to investigate the true clinical impact of TPE on therapeutic anticoagulation.
