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International Immunopharmacology Mar 2024Programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) immune checkpoint inhibitors (ICIs) are used for a variety of cancers and are associated with a...
INTRODUCTION
Programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) immune checkpoint inhibitors (ICIs) are used for a variety of cancers and are associated with a risk of developing immune-related adverse events, most commonly dermatitis, colitis, hepatitis, and pneumonitis. Immune-mediated hematologic toxicities have been reported, but are less well-described in the literature. Immune thrombocytopenia (ITP) is a rare autoimmune, hematologic adverse event that has been reported with PD-1/PD-L1 inhibitors.
METHODS
We performed a retrospective observational analysis of the United States Food and Drug Administration Adverse Event Reporting System (FAERS) data. We searched for cases of ITP reported with exposure to PD-1/PD-L1 inhibitors from initial FDA approval for each agent to September 30, 2022. Disproportionality signal analysis was done by calculating the reporting odds ratio (ROR). Oxaliplatin was used as a positive control for sensitivity analysis as it is an anticancer therapy that has been associated with drug-induced ITP. A systematic review of the PubMed database was also conducted to identify published cases of PD-1/PD-L1 inhibitor-induced ITP.
RESULTS
There were 329 reports of ITP with ICIs in the FAERS database that were reviewed for a disproportionality signal, including atezolizumab (n = 27), durvalumab (n = 17), nivolumab (n = 160), and pembrolizumab (n = 125). The ROR was significant for atezolizumab (ROR 5.39, 95 % CI 3.69-7.87), avelumab (ROR 10.32, 95 % CI 4.91-21.69), durvalumab (ROR 7.91, 95 % CI 4.91-12.75), nivolumab (ROR 9.76, 95 % CI 8.34-11.43), and pembrolizumab (ROR 12.6, 95 % CI 10.55-15.06). In our systematic review, we summated 57 cases of ICI-induced ITP. Nivolumab and pembrolizumab had the most reported cases of ITP in the literature. Most cases reported (53 %) included ITP-directed therapies beyond corticosteroids for the management of ICI-induced ITP.
CONCLUSION
There is a significant reporting signal of ITP with several ICI agents. Clinicians should be aware of and monitor for signs of this potentially serious adverse event.
Topics: United States; Humans; Nivolumab; Immune Checkpoint Inhibitors; Programmed Cell Death 1 Receptor; Purpura, Thrombocytopenic, Idiopathic; Pharmacovigilance; Retrospective Studies; Drug-Related Side Effects and Adverse Reactions; Thrombocytopenia
PubMed: 38359661
DOI: 10.1016/j.intimp.2024.111606 -
British Journal of Haematology Feb 2024Immune thrombotic thrombocytopenic purpura (iTTP) is a rare and life-threatening haematological condition. Initial treatment involves plasma exchange (PLEX),...
Immune thrombotic thrombocytopenic purpura (iTTP) is a rare and life-threatening haematological condition. Initial treatment involves plasma exchange (PLEX), corticosteroids, caplacizumab and rituximab. In relapsed and refractory cases despite initial treatments, further immune-modulating therapy includes the proteasome inhibitor, bortezomib. Evidence for bortezomib in this setting is limited to case reports and case series. We report our experience and perform a systematic review of the literature. We identified 21 publications with 28 unique patients in addition to our cohort of eight patients treated with bortezomib. The median age of patients was 44 years (IQR: 27-53) and 69% female. They were usually in an initial, refractory presentation of iTTP where they had received PLEX, corticosteroids, rituximab and another line of therapy. After bortezomib administration, 72% of patients had a complete response, with 85% maintaining a durable response without relapse at the last follow-up.
Topics: Humans; Female; Adult; Middle Aged; Male; Bortezomib; Rituximab; Purpura, Thrombotic Thrombocytopenic; Retrospective Studies; Purpura, Thrombocytopenic, Idiopathic; Adrenal Cortex Hormones; Plasma Exchange; ADAMTS13 Protein
PubMed: 37571963
DOI: 10.1111/bjh.19035 -
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 -
Frontiers in Pharmacology 2024Treatment of glomerulonephritis presents several challenges, including limited therapeutic options, high costs, and potential adverse reactions. As a recognized Chinese... (Review)
Review
Treatment of glomerulonephritis presents several challenges, including limited therapeutic options, high costs, and potential adverse reactions. As a recognized Chinese patent medicine, poly-glycosides (TWP) have shown promising benefits in managing autoimmune diseases. To evaluate clinical effectiveness and safety of TWP in treating glomerulonephritis, we systematically searched PubMed, Cochrane Library, Web of Science, and Embase databases for controlled studies published up to 12 July 2023. We employed weighted mean difference and relative risk to analyze continuous and dichotomous outcomes. This meta-analysis included 16 studies that included primary membranous nephropathy (PMN), type 2 diabetic kidney disease (DKD), and Henoch-Schönlein purpura nephritis (HSPN). Analysis revealed that additional TWP administration improved patients' outcomes and total remission rates, reduced 24-h urine protein (24hUP) and decreased relapse events. The pooled results demonstrated the non-inferiority of TWP to glucocorticoids in achieving total remission, reducing 24hUP, and converting the phospholipase A2 receptor (PLA2R) status to negative. For DKD patients, TWP effectively reduced 24hUP levels, although it did not significantly improve the estimated glomerular filtration rate (eGFR). Compared to valsartan, TWP showed comparable improvements in 24hUP and eGFR levels. In severe cases of HSPN in children, significant clinical remission and a reduction in 24hUP levels were observed with the addition of TWP treatment. TWP did not significantly increase the incidence of adverse reactions. Therefore, TWP could offer therapeutic benefits to patients with PMN, DKD, and severe HSPN, with a minimal increase in the risk of side effects.
PubMed: 38841368
DOI: 10.3389/fphar.2024.1339153 -
American Journal of Hematology Dec 2023
Topics: Humans; Purpura, Thrombotic Thrombocytopenic; Thrombotic Microangiopathies
PubMed: 37753669
DOI: 10.1002/ajh.27104 -
BMC Oral Health Dec 2023Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can cause a range of symptoms, including oral mucosal lesions (OMLs). The prevalence of OMLs in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can cause a range of symptoms, including oral mucosal lesions (OMLs). The prevalence of OMLs in SLE patients and their associated factors have been studied in various regions, but the results are inconsistent. This study aims to evaluate the prevalence of OMLs in patients with SLE.
METHODS
Observational studies of OML prevalence in SLE patients published before 2022 were retrieved from PubMed, Embase, Web of Science, Google Scholar, and the Cochrane Library without language restriction. The quality of the studies was assessed using the Newcastle-Ottawa Scale (NOS) and Agency for Healthcare Research and Quality (AHRQ).
RESULTS
Our meta-analysis included 113 studies with a total of 53,307 SLE patients. We found that the prevalence of OMLs in SLE patients was 31% (95% CI: 28%, 35%), with oral ulcers being present in 30% of SLE patients (95% CI: 26%, 33%). Subgroup analysis showed that the prevalence of OMLs varied significantly by region, disease activity, and sample size (p ≤ 0.01). However, gender and year of publication had little effect on the prevalence of OMLs (p = 0.78 and 0.30, respectively). Oral ulcers were significantly associated with age of onset (p = 0.02), geographic location (p < 0.01), and race (p < 0.01). We also found that the prevalence of oral erythema was 9%, oral candidiasis was 9%, petechiae was 8%, cheilitis was 6%, and white plaque was 3%.
CONCLUSIONS
Our analysis showed that the prevalence of OMLs varied significantly by region and disease activity, and child-onset patients of Indian, Malay, and Caucasian descent were more likely to have oral ulcers. The high prevalence of OML in SLE patients emphasizes the importance of regular oral examination and management in the comprehensive care of individuals with SLE.
Topics: Humans; Oral Ulcer; Prevalence; Candidiasis, Oral; Lupus Erythematosus, Systemic; Observational Studies as Topic
PubMed: 38129844
DOI: 10.1186/s12903-023-03783-5 -
PeerJ 2024Immune disorders and autoantibodies has been noted in both primary immune thrombocytopenia (ITP) and systemic lupus erythematosus (SLE). Whether the two disorders are... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Immune disorders and autoantibodies has been noted in both primary immune thrombocytopenia (ITP) and systemic lupus erythematosus (SLE). Whether the two disorders are correlated is unclear. The lack of evidence on the incidence of and risk factors for SLE in primary ITP patients poses a challenge for prediction in clinical practice. Therefore, we conducted this study.
METHODS
The protocol was registered with PROSPERO (CRD42023403665). Web of Science, Cochrane, PubMed, and EMBASE were searched for articles published from inception to 30 September 2023 on patients who were first diagnosed with primary ITP and subsequently developed into SLE. Furthermore, the risk factors were analyzed. Study quality was estimated using the Newcastle-Ottawa Scale. The statistical process was implemented using the R language.
RESULTS
This systematic review included eight articles. The incidence of SLE during the follow-up after ITP diagnosis was 2.7% (95% CI [1.3-4.4%]), with an incidence of 4.6% (95% CI [1.6-8.6%]) in females and 0 (95% CI [0.00-0.4%]) in males. Older age (OR = 6.31; 95% CI [1.11-34.91]), positive antinuclear antibody (ANA) (OR = 6.64; 95% CI [1.40-31.50]), hypocomplementemia (OR = 8.33; 95% CI [1.62-42.91]), chronic ITP (OR = 24.67; 95% CI [3.14-100.00]), organ bleeding (OR = 13.67; 95% CI [2.44-76.69]), and female (OR = 20.50; 95% CI [4.94-84.90]) were risk factors for subsequent SLE in ITP patients.
CONCLUSION
Patients with primary ITP are at higher risk of SLE. Specific follow-up and prevention strategies should be tailored especially for older females with positive ANA, hypocomplementemia, or chronic ITP. In subsequent studies, we need to further investigate the risk factors and try to construct corresponding risk prediction models to develop specific prediction strategies for SLE.
Topics: Humans; Lupus Erythematosus, Systemic; Incidence; Risk Factors; Purpura, Thrombocytopenic, Idiopathic; Female; Male
PubMed: 38666084
DOI: 10.7717/peerj.17152 -
Cytokine May 2024Relation between the emergence of ITP and the presence of TNFα 308G/A polymorphism in the involved individuals has been studied by previous researchers in different... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Relation between the emergence of ITP and the presence of TNFα 308G/A polymorphism in the involved individuals has been studied by previous researchers in different ethnicity, but a definite result was not gained. So, this meta-analysis was performed to find an absolute answer to the question whether TNF-α-308G/A polymorphism is a susceptibility factor for ITP or not?
METHODS
Electronic databases including PubMed, Google scholar, and Science Direct were searched and case control studies compatible to the defined inclusion criteria were selected; their references were also evaluated manually. Pooled OR with 95 % confidence intervals (CIs) as a strength of association between TNF-α-308G/A polymorphism and risk of ITP were calculated using a random-effect model. Funnel plot and Egger's linear regression test were conducted to examine the risk of publication bias.
RESULTS
Totally, 16 eligible articles were found involving 1470 ITP cases and 2324 healthy controls. The Meta-results revealed that TNFα 308G/A polymorphism is associated with increased risk of ITP under the genetic models of recessive (OR: 1.54, 95 % CI: 1.03-2.29), dominant (OR: 2.29, 95 % CI: 1.44-3.64), and the heterozygote (OR: 2.46, 95 % CI:1.49-4.6). Subgroup analysis suggested a remarkable role for this SNP as a risk factor in the Caucasian ethnicity and the chronic subtype.
CONCLUSION
TNFα 308G/A polymorphism can be an ITP susceptibility factor in the Caucasian population and the chronic subtype. Although more studies in large scale are needed for clinical decision but this finding can be used in the clinical trials to prevent the ITP consequences in the involved individuals.
Topics: Humans; Tumor Necrosis Factor-alpha; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide; Purpura, Thrombocytopenic, Idiopathic; Heterozygote
PubMed: 38368694
DOI: 10.1016/j.cyto.2024.156538 -
Biomedical Reports Mar 2024Thrombopoietin receptor agonists (TPO-RAs) have a role in second-line immune thrombocytopenic purpura (ITP) treatment, binding to and activating thrombopoietin receptors...
Thrombopoietin receptor agonists use and risk of thrombotic events in patients with immune thrombocytopenic purpura: A systematic review and meta‑analysis of randomized controlled trials.
Thrombopoietin receptor agonists (TPO-RAs) have a role in second-line immune thrombocytopenic purpura (ITP) treatment, binding to and activating thrombopoietin receptors on megakaryocyte membranes in the bone marrow. This promotes megakaryocyte maturation and increases platelet production. Despite a 2-6% incidence of thrombotic events during TPO-RA treatment, it remains uncertain whether TPO-RAs elevate thrombosis rates. A comprehensive search of electronic databases was conducted using the relevant search criteria. To assess the risk of bias, the included studies were assessed using the revised Cochrane Risk of Bias Assessment Tool 2.0, and a meta-analysis was performed using RevMan 5.4.1. A total of 1,698 patients with ITP were included from randomized controlled trials (RCTs). There were 26 thromboembolic events in the TPO-RAs group and 4 in the control group. However, there was no significant difference in the incidence of thrombotic events between the two groups [odds ratio (OR)=1.76, 95% confidence interval (CI): 0.78-4.00, P=0.18], even if the duration of treatment was >12 weeks (OR=2.46, 95% CI: 0.81-7.43, P=0.11). Subgroup analysis showed that none of the four drugs significantly increased the incidence of thrombotic events (romiplostim: OR=0.92, 95% CI: 0.14-6.13, P=0.93; eltrombopag: OR=2.32, 95% CI: 0.64-8.47, P=0.20; avatrombopag: OR=4.15, 95% CI: 0.20-85.23, P=0.36; and hetrombopag: OR=0.76, 95% CI: 0.03-18.76, P=0.87). There was also no significant difference in the results of the double-blinded placebo-controlled RCTs (OR=1.21, 95% CI: 0.41-3.58, P=0.73). Compared to patients with ITP who did not receive TPO-RA treatment, those receiving TPO-RA treatment did not exhibit a significantly increased risk of thrombotic events.
PubMed: 38357229
DOI: 10.3892/br.2024.1732 -
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