-
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 -
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 -
Frontiers in Neurology 2021IgA vasculitis/Henoch-Schoenlein purpura (IgAV/HSP) is a systemic small vessel vasculitis of unknown pathogenesis predominantly affecting children. While skin, GI...
Focal Seizures and Posterior Reversible Encephalopathy Syndrome as Presenting Signs of IgA Vasculitis/Henoch-Schoenlein Purpura-An Educative Case and Systematic Review of the Literature.
IgA vasculitis/Henoch-Schoenlein purpura (IgAV/HSP) is a systemic small vessel vasculitis of unknown pathogenesis predominantly affecting children. While skin, GI tract, joints, and kidneys are frequently affected and considered, central nervous system (CNS) involvement of this disease is underestimated. We provide a case report and systematically review the literature on IgAV, collecting data on the spectrum of neurological manifestations. We report on a 7-year-old girl with IgAV who presented with diplopia and afebrile focal seizures, which preceded the onset of purpura. Cranial magnetic resonance imaging was consistent with posterior reversible encephalopathy syndrome (PRES), showing typical focal bilateral parietal swelling and cortical and subcortical high signal intensities on T2-fluid attenuated inversion recovery (FLAIR) images predominantly without diffusion restriction. Cerebrospinal fluid analysis and blood tests excluded systemic inflammation or vasculitis. Interestingly, hypertension was not a hallmark of the developing disease in the initial phase of PRES manifestation. Renal disease and other secondary causes for PRES were also excluded. Supportive- and steroid treatment resulted in restitution . Reviewing the literature, we identified 28 other cases of IgAV with CNS involvement. Severe CNS involvement includes seizures, cerebral edema, or hemorrhage, as well as PRES. Thirteen patients fulfilled all diagnostic criteria of PRES. The mean age was 11.2 years (median 8.0, range 5-42 years), with no reported bias toward gender or ethnic background. Treatment regimens varied from watchful waiting to oral and intravenously steroids up to plasmapheresis. Three cases showed permanent CNS impairment. Collectively, our data demonstrate that (I) severe CNS involvement such as PRES is an underappreciated feature of IgAV, (II) CNS symptoms may precede other features of IgAV, (III) PRES can occur in IgAV, and differentiation from CNS vasculitis is challenging, (IV) pathogenesis of PRES in the context of IgAV remains elusive, which hampers treatment decisions. We, therefore, conclude that clinical awareness and the collection of structured data are necessary to elucidate the pathophysiological connection of IgAV and PRES.
PubMed: 34867743
DOI: 10.3389/fneur.2021.759386 -
Journal of Emergency Nursing Jul 2022Immunoglobulin A vasculitis is historically more commonly found in children after certain viral infections such as Epstein-Barr, varicella virus, and parvovirus B19....
INTRODUCTION
Immunoglobulin A vasculitis is historically more commonly found in children after certain viral infections such as Epstein-Barr, varicella virus, and parvovirus B19. COVID-19 has not been formally established in literature as a trigger for immunoglobulin A vasculitis. However, a main pathogenetic mechanism of COVID-19 is vascular damage, which makes it likely that vasculitis associated with COVID-19 (ie, COVID-19-mediated immunoglobulin A vasculitis) could be biologically plausible, with serious implications, especially for adults. The purpose of this review is to assist emergency nurses in gaining knowledge on the pathophysiology, symptoms, and treatment of COVID-19-mediated immunoglobulin A vasculitis.
METHODS
A systematic search for case reports of COVID-19-associated immunoglobulin A vasculitis was conducted in the PubMed and Scopus electronic databases. The search terms used were COVID-19, coronavirus 2019, SARS COVID-19, and IgA vasculitis, case reports. The following were the inclusion criteria: publication dates between December 1, 2019, and December 1, 2021; full-text article, clinical case studies, and letters to the editor available electronically in English. The following were exclusion criteria: a summary of reports and newspaper publications.
RESULTS
Only 13 clinical cases met the inclusion criteria. The median age of patients described in the case reports were 38.1 years. Of them, 3 children were less than 5 years old. Twelve patients were male. In 7 of 13 cases of immunoglobulin A vasculitis, renal involvement was found.
DISCUSSION
The analysis of published clinical cases showed that COVID-19-associated immunoglobulin A vasculitis affected mostly adults and was characterized by a more severe course because of renal involvement. COVID-19 may be a possible trigger for immunoglobulin A-related disorders. More research is needed to better understand the relationship between immunoglobulin A vasculitis and COVID-19.
Topics: Adult; COVID-19; Child; Child, Preschool; Female; Humans; IgA Vasculitis; Immunoglobulin A; Male; Vasculitis
PubMed: 35691763
DOI: 10.1016/j.jen.2022.05.002 -
Journal of Clinical Medicine Aug 2023Health-related quality of life (HRQoL) impacts of thrombotic thrombocytopenic purpura (TTP) have been captured in clinical studies using patient-reported outcome (PRO)... (Review)
Review
Health-related quality of life (HRQoL) impacts of thrombotic thrombocytopenic purpura (TTP) have been captured in clinical studies using patient-reported outcome (PRO) measures (PROMs) that are validated for other diseases. However, the validity evidence to support the use of existing PROMs in patients with TTP is unknown. In a systematic review of the literature, including studies of adults and children with TTP, we assessed the validity evidence for use of PROMs in clinical research and clinical practice, characterized HRQoL, described the integration of PROMs in clinical practice and evaluated PRO scores for patients with TTP compared with reference populations. From an initial 4518 studies, we identified 14 studies using 16 PROMs to assess general HRQoL domains in patients in remission. No identified studies assessed the validity of PROMs for the context of use of TTP and no studies described PROM integration into TTP clinical practice or evaluated PROMs that were specific for patients with TTP. Moreover, PRO scores were worse in patients with TTP compared with reference populations and other chronic conditions. We conclude that, in patients with TTP, PROMs pick up on important patient experiences not captured by clinical outcomes at present. There is, therefore, a need for studies that assess the validity of existing PROMs in patients with TTP to determine if TTP-specific PROMs specific to patients with TTP should be developed.
PubMed: 37568558
DOI: 10.3390/jcm12155155 -
BMC Pediatrics Nov 2019We have recognized 15 children with jSLE and the antecedent of IgA vasculitis (HSP). This association is not broadly present in the literature.
BACKGROUND
We have recognized 15 children with jSLE and the antecedent of IgA vasculitis (HSP). This association is not broadly present in the literature.
AIM
To know the age and gender distribution of children with IgA vasculitis (HSP), compare it to our IgA vasculitis (HSP) + jSLE cases, and identify prognostic factors to develop jSLE within our case series, IgA vasculitis (HSP) vs. IgA vasculitis (HSP) + jSLE.
METHODS
A systematic review was carried out to know the age and gender distribution of children with IgA vasculitis (HSP). The information obtained plus data from 110 children with IgA vasculitis (HSP) from the Instituto Nacional de Pediatría were used to compare groups and identify prognostic factors. We performed a case-control study in patients < 18 years, consisting of 15 cases retrospectively identified with IgA vasculitis (HSP) + jSLE, and 110 IgA vasculitis (HSP) control subjects.
RESULTS
The information of 12,819 IgA vasculitis (HSP) subjects from the systematic review and 110 IgA vasculitis (HSP) controls was obtained and compared to our 15 IgA vasculitis (HSP) + jSLE cases. The mean age of IgA vasculitis (HSP) was 7.1-years vs. 10.4-years of IgA vasculitis (HSP) + jSLE at the HSP diagnosis. Female to male ratio of IgA vasculitis (HSP) was 1:1.33 vs. 1:0.25 of IgA vasculitis (HSP) + jSLE. Patients with IgA vasculitis (HSP) + jSLE had lower levels of Hemoglobin (Hb) compared to patients with IgA vasculitis (HSP) 109 g/L vs. 141 g/L. For the development of jSLE, we found older age and lower levels of Hb as prognostic factors with OR [95% CI]: 1.37 [1.06, 1.89] and 5.39 [2.69, 15.25], respectively.
CONCLUSION
IgA vasculitis (HSP) + jSLE patients are older and have lower levels of Hb than patients with IgA vasculitis (HSP). It is necessary to confirm these findings through a prospective study.
Topics: Adolescent; Age Distribution; Case-Control Studies; Child; Child, Preschool; Female; Hemoglobins; Humans; IgA Vasculitis; Lupus Erythematosus, Systemic; Male; Prognosis; Retrospective Studies; Sex Distribution
PubMed: 31771531
DOI: 10.1186/s12887-019-1829-4 -
International Journal of Environmental... Jul 2021Vulvar lichen sclerosus (VLS) is a chronic inflammatory condition affecting the anogenital region, which may present in a prepubertal or adolescent patient. The most...
Vulvar lichen sclerosus (VLS) is a chronic inflammatory condition affecting the anogenital region, which may present in a prepubertal or adolescent patient. The most popular theories are its autoimmune and genetic conditioning, although theories concerning hormonal and infectious etiology have also been raised. The most common presenting symptoms of VLS is vulva pruritus, discomfort, dysuria and constipation. In physical examination, a classic "Figure 8" pattern is described, involving the labia minora, clitoral hood, and perianal region. The lesions initially are white, flat-topped papules, thin plaques, or commonly atrophic patches. Purpura is a hallmark feature of VLS. The treatment includes topical anti-inflammatory agents and long-term follow-up, as there is a high risk of recurrence and an increased risk of vulvar cancer in adult women with a history of lichen sclerosus. This article reviews vulvar lichen sclerosus in children and provides evidence-based medicine principles for treatment in the pediatric population. A systematic search of the literature shows recurrence of VLS in children. Maintenance regimens deserve further consideration.
Topics: Adolescent; Adult; Anti-Inflammatory Agents; Child; Female; Humans; Lichen Sclerosus et Atrophicus; Vulvar Diseases; Vulvar Lichen Sclerosus
PubMed: 34281089
DOI: 10.3390/ijerph18137153 -
Frontiers in Immunology 2024The objective of this study is to evaluate the risk of secondary autoimmune diseases in multiple sclerosis (MS) patients treated with alemtuzumab (ALZ) through a... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND PURPOSE
The objective of this study is to evaluate the risk of secondary autoimmune diseases in multiple sclerosis (MS) patients treated with alemtuzumab (ALZ) through a meta-analysis.
METHODS
PubMed, Web of Science, OVID, EMBASE, and Cochrane central register of controlled trials were searched. Information and data were screened and extracted by 2 researchers. The obtained data were analyzed using the R software meta package. Quality assessment was conducted using the Newcastle-Ottawa Scale (NOS). The causes of heterogeneity were analyzed using subgroup analysis and sensitivity analysis. Publication bias was evaluated using funnel plots and Egger's test.
RESULTS
The search retrieved a total of 3530 papers from the databases. After screening, a total of 37 studies were included in the meta-analysis. The analysis results indicate that the pooled incidence rate of overall secondary autoimmune events (SAEs) in the included studies was 0.2824 [0.2348, 0.3300] (I²=94%, p<0.01). The overall incidence of autoimmune thyroid events (ATE) was 0.2257 [0.1810, 0.2703] (I²=94%, p<0.01). Among them, the rate of serious autoimmune thyroid events (SATE) was 0.0541 [0.0396, 0.0687] (I²=0%, p=0.44). The incidence rates of different thyroid events were as follows: Graves' disease (GD), 0.2266 [0.1632, 0.2900] (I²=83%, p<0.01); Hashimoto thyroiditis (HT), 0.0844 [0.0000, 0.2262] (I²=81%, p=0.02); Hashimoto thyroiditis with hypothyroidism (HTwH), 0.0499 [0.0058, 0.0940] (I²=37%, p=0.21); fluctuating thyroid dysfunction (FTD), 0.0219 [0.0015, 0.0424] (I²=0%, p=0.40); transient thyroiditis (TT), 0.0178 [0.0062, 0.0295] (I²=0%, p=0.94). The overall incidence of hematological events was 0.0431 [0.0274, 0.0621] (I²=70%, p<0.01). The incidence rates from high to low were as follows: lymphopenia, 0.0367 [0.0000, 0.0776] (I²=81%, p=0.02); Idiopathic thrombocytopenic purpura (ITP), 0.0258 [0.0199, 0.0323] (I²=25%, p=0.15); Hemolytic anemia (HA), 0.0177 [0.0081, 0.0391] (I²=29%, p=0.23); pancytopenia, 0.0136 [0.0000, 0.0314] (I²=0%, p=0.67); Neutropenia, 0.0081 [0.0000, 0.0183] (I²=0%, p=0.42). After excluding thyroid and hematological diseases, the combined incidence of other related SAEs was 0.0061 [0.0014, 0.0109] (I²=50%, p=0.02). The incidence of each disease ranked from highest to lowest as: skin psoriasis (SP), 0.0430 [0.0000, 0.0929] (I²=0%, p=0.57); alopecia areata (AA), 0.0159 [0.0024, 0.0372] (I²=19%, p=0.29); vitiligo, 0.0134 [0.0044, 0.0223] (I²=0%, p=0.81); inflammatory atrichia (IA), 0.0103 [0.0000, 0.0232] (I²=0%, p=0.43); chronic urticaria (CU), 0.0107 [0.0000, 0.0233] (I²=0%, p=0.60); and nephropathy, 0.0051 [0.0000, 0.0263] (I²=62%, p=0.02).
CONCLUSION
The occurrence of secondary autoimmune diseases in patients with MS treated with ALZ is noteworthy, particularly in the form of thyroid events and hematological events. Clinicians should monitor the overall condition of patients promptly for early management and avoid delayed diagnosis and treatment.
SYSTEMATIC REVIEW REGISTRATION
inplasy.com/inplasy-2024-4-0048/, identifier INPLASY202440048.
Topics: Humans; Alemtuzumab; Multiple Sclerosis; Autoimmune Diseases; Incidence; Hashimoto Disease
PubMed: 38690271
DOI: 10.3389/fimmu.2024.1343971