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Advances in Therapy Jun 2021A network meta-analysis (NMA) was performed to assess the efficacy and safety of avatrombopag, relative to eltrombopag, romiplostim, and fostamatinib, for patients with... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
A network meta-analysis (NMA) was performed to assess the efficacy and safety of avatrombopag, relative to eltrombopag, romiplostim, and fostamatinib, for patients with chronic immune thrombocytopenia (ITP) not responding adequately to corticosteroids.
METHODS
A systematic search of publication and clinical trial databases was conducted to identify relevant randomized controlled trials (RCTs) and observational studies. Data from eligible studies were extracted and analyzed in a Bayesian framework using relative effect sizes vs placebo. Outcomes included durable platelet response; need for rescue therapy; reduction in use of concomitant ITP medication; incidence of any or World Health Organization (WHO) grade 2-4 bleeding events, and any adverse events. Results were reported as odds ratios or incidence rate ratios (IRR) with 95% credible intervals (CrIs).
RESULTS
The NMA included seven phase 3 RCTs. Compared with placebo, avatrombopag was associated with statistically significant improvements in durable platelet response, reduction in use of concomitant ITP medication, and incidence of any bleeding events. Statistically significant differences vs placebo were also observed for durable platelet response and need for rescue therapy (eltrombopag, romiplostim, and fostamatinib); reduction in use of concomitant ITP medication (eltrombopag and romiplostim); incidence of any bleeding events (fostamatinib); and incidence of WHO grade 2-4 bleeding events (romiplostim and fostamatinib). No statistically significant differences were observed for any adverse events. Avatrombopag was associated with a statistically significant lower incidence of any bleeding events vs eltrombopag (IRR 0.38 [95% CrI 0.19, 0.75]) and romiplostim (IRR 0.38 [95% Crl 0.17, 0.86]); no other between-treatment differences were observed.
CONCLUSION
In this NMA, avatrombopag significantly increased the chance of achieving durable platelet response and reducing the use of concomitant ITP medication vs placebo, and significantly reduced the incidence of any bleeding events compared with placebo, eltrombopag, and romiplostim. The study aims to help guide clinicians managing patients with chronic ITP and insufficient response to previous treatment.
Topics: Benzoates; Humans; Network Meta-Analysis; Purpura, Thrombocytopenic, Idiopathic; Randomized Controlled Trials as Topic; Recombinant Fusion Proteins; Thiazoles; Thiophenes
PubMed: 33934279
DOI: 10.1007/s12325-021-01752-4 -
Acta Haematologica 2023The aim of the study was to conduct a network meta-analysis to assess the efficacy and incidence of treatment-related adverse events (TRAEs) of eltrombopag, romiplostim,... (Meta-Analysis)
Meta-Analysis
Efficacy and Incidence of Treatment-Related Adverse Events of Thrombopoietin Receptor Agonists in Adults with Immune Thrombocytopenia: A Systematic Review and Network Meta-Analysis of Randomized Controlled Study.
INTRODUCTION
The aim of the study was to conduct a network meta-analysis to assess the efficacy and incidence of treatment-related adverse events (TRAEs) of eltrombopag, romiplostim, avatrombopag, recombinant human thrombopoietin (rhTPO), and hetrombopag for adult immune thrombocytopenia (ITP).
METHODS
Randomized controlled trials (RCTs) of the five therapies from inception to June 1, 2022, were included. The efficacy outcome was the rate of platelet response, defined as the achievement of platelet counts above 50 × 109/L. Pairwise odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. The surface under the cumulative ranking (SUCRA) was used to rank the included therapies for each outcome.
RESULTS
In total, 1,360 participants were analyzed in 14 eligible RCTs. All of the therapies showed a significantly better platelet response than the placebo, and avatrombopag (OR, 7.42; 95% CI: 1.74-31.69) and rhTPO (OR, 3.86; 95% CI: 1.62-9.18) were better than eltrombopag. Regarding TRAEs, no significant differences were found between patients receiving eltrombopag, romiplostim, and avatrombopag. Avatrombopag carried the highest platelet response rate with SUCRA value of 87.5, and carried the least TRAEs risk with SUCRA value of 37.0.
CONCLUSIONS
These findings indicated that avatrombopag appeared to be the optimal choice as the second-line therapy for adult ITP.
Topics: Humans; Adult; Purpura, Thrombocytopenic, Idiopathic; Receptors, Thrombopoietin; Incidence; Network Meta-Analysis; Thrombocytopenia; Hydrazines; Benzoates; Recombinant Fusion Proteins; Receptors, Fc; Thrombopoietin; Randomized Controlled Trials as Topic
PubMed: 36572014
DOI: 10.1159/000528642 -
Obstetrics and Gynecology Jan 2020To evaluate disease presentation, diagnosis, treatment, and clinical outcomes in pregnancy-associated atypical hemolytic uremic syndrome (aHUS).
OBJECTIVE
To evaluate disease presentation, diagnosis, treatment, and clinical outcomes in pregnancy-associated atypical hemolytic uremic syndrome (aHUS).
DATA SOURCES
We searched PubMed, MEDLINE, Cochrane Library, ClinicalTrials.gov, Web of Science, EMBASE and Google Scholar, from inception until March 2018.
METHODS OF STUDY SELECTION
We included English-language articles describing aHUS in pregnancy or postpartum. The diagnosis of aHUS was characterized by hemolysis, thrombocytopenia, and renal failure and was distinguished from typical diarrhea-associated hemolytic uremic syndrome. Patients were excluded if individual data could not be obtained, the diagnosis was unclear, or an alternative etiology was more likely, such as thrombotic thrombocytopenic purpura or Shiga toxin-producing Escherichia coli. Reports were appraised by two reviewers, with disagreements adjudicated by a third reviewer.
TABULATION, INTEGRATION, AND RESULTS
The search identified 796 articles. After review of titles, abstracts, and full text, we identified 48 reports describing 60 unique cases of pregnancy-associated aHUS, with 66 pregnancies. Twelve cases involved pregnancy in women with known aHUS, and 54 cases involved first-episode pregnancy-associated aHUS. Women with known aHUS, particularly those with baseline creatinine at or above 1.5 mg/dL, had a high rate of adverse pregnancy outcomes. For first-episode pregnancy-associated aHUS, diagnosis most often occurred postpartum (94%), after a cesarean delivery (70%), in nulliparous women (58%). Preceding obstetric complications were common and included fetal death, preeclampsia, and hemorrhage. Diagnosis was usually made clinically, based on the triad of microangiopathic hemolysis, thrombocytopenia, and renal failure. Additional testing included renal biopsy, complement genetic testing, and ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) testing. Treatment modalities included corticosteroids, plasma exchange, dialysis, and eculizumab. More women with first-episode pregnancy-associated aHUS achieved disease remission when treated with eculizumab, compared with those not treated with eculizumab (88% vs 57%, P=.02).
CONCLUSION
Pregnancy-associated aHUS usually presents in the postpartum period, often after a pregnancy complication, and eculizumab is effective for achieving disease remission.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, CRD42019129266.
Topics: Antibodies, Monoclonal, Humanized; Atypical Hemolytic Uremic Syndrome; Complement Inactivating Agents; Female; Humans; Plasma Exchange; Postpartum Period; Pregnancy; Pregnancy Complications, Hematologic; Renal Dialysis
PubMed: 31809447
DOI: 10.1097/AOG.0000000000003554 -
PloS One 2023Thrombocytopenia is defined as a decreased number of platelets in the circulating blood as a result of hypo-proliferation in marrow or peripheral destruction of... (Meta-Analysis)
Meta-Analysis
The diagnostic accuracy of mean platelet volume in differentiating immune thrombocytopenic purpura from hypo-productive thrombocytopenia: A systematic review and meta-analysis.
BACKGROUND
Thrombocytopenia is defined as a decreased number of platelets in the circulating blood as a result of hypo-proliferation in marrow or peripheral destruction of platelets. Several diagnostic methods have been proposed to discriminate the underline cause of thrombocytopenia. Recent studies showed that mean platelet volume (MPV) could be used for differential diagnosis of immune thrombocytopenic purpura (ITP). Thus, we aimed to investigate the diagnostic accuracy of MPV for differential diagnosis of ITP from hypo-productive thrombocytopenia.
METHODS
This study was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines (PRISMA). The study protocol was registered on PROSPERO with the reference number CRD42023447789. Relevant published studies that were published up to April 10, 2023, in peer-reviewed journals were searched on electronic different databases. The methodological quality of the included studies was appraised using the quality assessment of diagnostic accuracy studies 2 (QADAS-2) tool. The pooled weight mean difference (WMD) of MPV between the ITP group and hypo-productive group was analyzed using a random-effects model meta-analysis. Relevant data were extracted using a Microsoft Excel spreadsheet and analyzed using STATA 11.0 and Meta-disc 1.4 software. Publication bias was evaluated using Deek's funnel plot asymmetry test.
RESULTS
A total of 14 articles were included in this systematic review and meta-analysis. The comparison of MPV between groups revealed that the pooled mean value of MPV increased significantly in ITP patients compared to patients with hypo-productive thrombocytopenia (WMD = 2.03; 95% CI, 1.38-2.69). The pooled sensitivity and specificity of MPV in differentiating ITP from hypo-productive thrombocytopenia were 76.0% (95% CI: 71.0%, 80.0%) and 79.0% (95% CI: 75.0%, 83.0%), respectively. The summary positive likelihood ratio (PLR) and negative likelihood ratio (NLR)using the random effects model were 3.89 (95% CI: 2.49, 6.10) and 0.29 (95% CI: 0.18, 0.46), respectively.
CONCLUSION
MPV can be used to discriminate ITP from hypo-productive thrombocytopenia. It can possess large advantages as it is noninvasive, simple, quick, inexpensive, easy to perform, reliable, and routinely generated by automated cell counters.
Topics: Humans; Purpura, Thrombocytopenic, Idiopathic; Mean Platelet Volume; Platelet Count; Thrombocytopenia; Blood Platelets
PubMed: 38033118
DOI: 10.1371/journal.pone.0295011 -
Journal of Autoimmunity Oct 2022Coronavirus disease 2019 (COVID-19) and vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been associated with autoimmune phenomena.... (Review)
Review
Coronavirus disease 2019 (COVID-19) and vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been associated with autoimmune phenomena. However, the interplay between COVID-19 or vaccination against SARS-CoV-2 and Berger glomerulonephritis or Henoch-Schönlein vasculitis, two diseases mediated by immunoglobulin A, has never been comprehensively investigated. Therefore, we carried out a systematic review of the literature on this topic. Following databases were used: Google Scholar, Excerpta Medica and the United States National Library of Medicine. Eighty-seven patients with immunoglobulin A-mediated diseases associated with SARS-CoV-2 infection or vaccination against coronavirus were sorted out (53% males, 47% females; 34 17-51 years of age, median and interquartile range): 47 cases of Berger glomerulonephritis and 40 of Henoch-Schönlein vasculitis. Approximately 50% (N = 24) of Berger glomerulonephritis and 10% (N = 4) of Henoch-Schönlein vasculitis patients presented with a pre-existing history of immunoglobulin A-mediated disease. Almost all cases of Berger glomerulonephritis were vaccine-associated (N = 44; 94%), while most cases of Henoch-Schönlein vasculitis were infection-associated (N = 23; 57%). Among vaccine-associated immunoglobulin A diseases, about 90% were associated to mRNA-based vaccines. Our analysis supports the hypothesis that COVID-19 and vaccination against SARS-CoV-2 may trigger or exacerbate an immunoglobulin A-mediated diseases.
Topics: Humans; Male; Female; Immunoglobulin A; COVID-19; SARS-CoV-2; IgA Vasculitis; Glomerulonephritis; Vaccination
PubMed: 36108473
DOI: 10.1016/j.jaut.2022.102899 -
PloS One 2012Rituximab has been widely used off-label as a second line treatment for children with immune thrombocytopenia (ITP). However, its role in the management of pediatric ITP... (Review)
Review
BACKGROUND
Rituximab has been widely used off-label as a second line treatment for children with immune thrombocytopenia (ITP). However, its role in the management of pediatric ITP requires clarification. To understand and interpret the available evidence, we conducted a systematic review to assess the efficacy and safety of rituximab for children with ITP.
METHODOLOGY/PRINCIPAL FINDINGS
We searched MEDLINE, EMBASE, Cochrane Library, CBM, CNKI, abstract databases of American Society of Hematology, American Society of Clinical Oncology and Pediatric Academic Society. Clinical studies published in full text or abstract only in any language that met predefined inclusion criteria were eligible. Efficacy analysis was restricted to studies enrolling 5 or more patients. Safety was evaluated from all studies that reported data of toxicity. 14 studies (323 patients) were included for efficacy assessment in children with primary ITP. The pooled complete response (platelet count ≥ 100 × 10(9)/L) and response (platelet count ≥ 30 × 10(9)/L) rate after rituximab treatment were 39% (95% CI, 30% to 49%) and 68% (95%CI, 58% to 77%), respectively, with median response duration of 12.8 month. 4 studies (29 patients) were included for efficacy assessment in children with secondary ITP. 11 (64.7%) of 17 patients associated with Evans syndrome achieved response. All 6 patients with systemic lupus erythematosus associated ITP and all 6 patients with autoimmune lymphoproliferative syndrome associated ITP achieved response. 91 patients experienced 108 adverse events associated with rituximab, among that, 91 (84.3%) were mild to moderate, and no death was reported.
CONCLUSIONS/SIGNIFICANCE
Randomized controlled studies on effect of rituximab for children with ITP are urgently needed, although a series of uncontrolled studies found that rituximab resulted in a good platelet count response both in children with primary and children secondary ITP. Most adverse events associated with rituximab were mild to moderate, and no death was reported.
Topics: Antibodies, Monoclonal, Murine-Derived; Child; Drug Administration Schedule; Humans; Platelet Count; Purpura, Thrombocytopenic, Idiopathic; Rituximab; Treatment Outcome
PubMed: 22666325
DOI: 10.1371/journal.pone.0036698 -
Autoimmunity Reviews Apr 2023Recent population-based cohort studies suggest that the incidence of systemic lupus erythematosus (SLE) is increased in patients with immune thrombocytopenic purpura... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Recent population-based cohort studies suggest that the incidence of systemic lupus erythematosus (SLE) is increased in patients with immune thrombocytopenic purpura (ITP). We performed a systematic review and meta-analysis to evaluate the development of SLE in patients with ITP.
METHODS
Literature search was performed in PubMed, Web of Science and Cochrane Library for studies published prior to October 2022. Studies were included that reported development of SLE in ITP patients. Forest plot was used to detect overall SLE frequency in ITP and compare risk ratios for SLE development in different ITP subgroups. Study heterogeneity was assessed by using I statistics.
RESULTS
26 eligible studies comprising 14867 ITP patients were included in analysis. 311 ITP patients developed SLE during the follow-up period (range: 1.1-14 years) (2.09%, 95%CI: 1.87-2.33). Relative risk (RR) for developing SLE was significantly higher in female ITP patients (RR: 4.23, 95%CI: 2.52-7.12, p < 0.0001). Anti-nuclear antibody (ANA) was reported in 23 studies, there were 766/4377 ANA positive patients with ITP (17.5%). The risk of SLE development in ANA positive ITP patients was significant (RR: 26.29, 95%CI: 14.45-47.81, p < 0.0001).
CONCLUSIONS
Our study suggests ITP patients are at high risk of developing SLE in future. Pooled data revealed that females and patients with a positive ANA titer are at a significantly high risk of developing SLE.
Topics: Female; Humans; Antibodies, Antinuclear; Incidence; Lupus Erythematosus, Systemic; Purpura, Thrombocytopenic, Idiopathic
PubMed: 36781038
DOI: 10.1016/j.autrev.2023.103297 -
Annals of Hematology Apr 2023There are currently three thrombopoietin receptor agonists (TPO-RAs) approved in Europe for treating patients with immune thrombocytopenia (ITP): romiplostim (Nplate®),...
There are currently three thrombopoietin receptor agonists (TPO-RAs) approved in Europe for treating patients with immune thrombocytopenia (ITP): romiplostim (Nplate®), eltrombopag (Revolade®), and avatrombopag (Doptelet®). However, comparative clinical data between these TPO-RAs are limited. Therefore, the purpose of this study was to perform a literature review and seek expert opinion on the relevance and strength of the evidence concerning the use of TPO-RAs in adults with ITP. A systematic search was conducted in PubMed and Embase within the last 10 years and until June 20, 2022. A total of 478 unique articles were retrieved and reviewed for relevance. The expert consensus panel comprised ITP senior hematologists from eight countries across Central Europe. The modified Delphi method, consisting of two survey rounds, a teleconference and email correspondence, was used to reach consensus. Forty articles met the relevancy criteria and are included as supporting evidence, including five meta-analyses analyzing all three European-licensed TPO-RAs and comprising a total of 31 unique randomized controlled trials (RCTs). Consensus was reached on seven statements for the second-line use of TPO-RAs in the management of adult ITP patients. In addition, the expert panel discussed TPO-RA treatment in chronic ITP patients with mild/moderate COVID-19 and ITP patients in the first-line setting but failed to reach consensus. This work will facilitate informed decision-making for healthcare providers treating adult ITP patients with TPO-RAs. However, further studies are needed on the use of TPO-RAs in the first-line setting and specific patient populations.
Topics: Humans; Adult; Purpura, Thrombocytopenic, Idiopathic; Receptors, Thrombopoietin; Consensus; COVID-19; Thrombocytopenia; Thrombopoietin; Receptors, Fc; Benzoates; Hydrazines; Recombinant Fusion Proteins
PubMed: 36826482
DOI: 10.1007/s00277-023-05114-8 -
European Journal of Pediatrics Apr 2017The occurrence of blistering eruptions in childhood Henoch-Schönlein syndrome has been so far addressed exclusively in individual case reports. To describe... (Review)
Review
UNLABELLED
The occurrence of blistering eruptions in childhood Henoch-Schönlein syndrome has been so far addressed exclusively in individual case reports. To describe epidemiology, clinical presentation, and therapeutic options in Henoch-Schönlein patients ≤18 years of age with blistering eruptions, we completed a systematic literature search. For the final analysis, we retained 39 reports. Ten children with blisters were found in 7 (1.5%) case series containing a total of 666 unselected pediatric Henoch-Schönlein cases. We also found 41 individually documented cases of Henoch-Schönlein syndrome with blistering eruptions. Blistering eruptions and purpura were distributed very similarly, blisters developed concomitantly with palpable purpura or with a latency of ≤14 days, and 80% of the cases remitted within 4 weeks with a similar course in children managed expectantly and in those managed with steroids.
CONCLUSION
Blistering eruptions are rare in Henoch-Schönlein syndrome. They can be a source of diagnostic dilemma but do not have any prognostic value since they almost always spontaneously subside within 4 weeks. What is known: • Textbooks and reviews marginally refer to the occurrence of blistering eruptions in children with Henoch-Schönlein syndrome. What is new • Blistering eruptions occur in <2% of cases. • Blisters and purpura are distributed similarly, blisters develop concomitantly with purpura or with a latency of ≤14 days. • Almost all cases remit within 4 weeks with a similar course in children managed expectantly and in those managed with systemic steroids.
Topics: Blister; Child; Female; Humans; IgA Vasculitis; Male; Skin Diseases, Vascular; Steroids
PubMed: 28161822
DOI: 10.1007/s00431-017-2858-3 -
Scientific Reports Jun 2022Autoimmune diseases caused by pathogenic IgG4 subclass autoantibodies (IgG4-AID) include diseases like MuSK myasthenia gravis, pemphigus vulgaris or thrombotic... (Meta-Analysis)
Meta-Analysis
Autoimmune diseases caused by pathogenic IgG4 subclass autoantibodies (IgG4-AID) include diseases like MuSK myasthenia gravis, pemphigus vulgaris or thrombotic thrombocytopenic purpura. Their etiology is still unknown. Polymorphisms in the human leukocyte antigen (HLA) gene locus, particularly in HLA-DRB1, are known genetic susceptibility factors for autoimmune diseases. We hypothesized a similar role for HLA polymorphisms in IgG4-AID and conducted a systematic review and meta-analysis with case-control studies on IgG4-AID based on MOOSE/ HuGENet guidelines. Genotype (G) and allele (A) frequencies of HLA-DQB1*05 (G: OR 3.8; 95% CI 2.44-5.9; p < 0.00001; A: OR 2.54; 95% CI 1.82-3.55; p < 0.00001) and HLA-DRB1*14 (G: OR 4.31; 95% CI 2.82-6.59; p < 0.00001; A: OR 4.78; 95% CI 3.52-6.49; p < 0.00001) and the HLA-DRB1*14-DQB1*05 haplotype (OR 6.3; 95% CI 3.28-12.09; p < 0.00001/OR 4.98; 95% CI 3.8-6.53; p < 0.00001) were increased while HLA-DRB1*13 (G: OR 0.48; 95% CI 0.34-0.68; p < 0.0001; A: OR 0.46; 95% CI 0.34-0.62; p < 0.00001) was decreased in IgG4-AID patients. In conclusion, the HLA-DQB1*05, HLA-DRB1*14 alleles and the HLA-DQB1*05-DRB1*14 haplotype could be genetic risk factors that predispose for the production of pathogenic IgG4 autoantibodies and the HLA-DRB1*13 allele may protect from IgG4 autoimmunity.
Topics: Autoantibodies; Autoimmunity; Gene Frequency; HLA-DRB1 Chains; Humans; Immunoglobulin G; Pemphigus
PubMed: 35654912
DOI: 10.1038/s41598-022-13042-2