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Expert Opinion on Drug Safety Jul 2022The autoimmune-induced thyroid eye disease (TED) is a frequent extrathyroidal manifestation of Graves' disease and less frequently of Hashimoto's thyroiditis....
INTRODUCTION
The autoimmune-induced thyroid eye disease (TED) is a frequent extrathyroidal manifestation of Graves' disease and less frequently of Hashimoto's thyroiditis. Pathognomonic clinical signs, i.e. exophthalmos, double vision, and inflammation of the orbital tissue cause physical, ophthalmic, and socio-psychological limitations.
AREAS COVERED
PubMed and MeSH database were searched for specific guidelines, randomized controlled trials, prospective clinical studies, systematic reviews, and meta-analyses pertaining to the safety profile of currently administered immunosuppressive agents for the treatment of TED. Occurred adverse events (AE), severe AE (SAE), side effects (SE), and severe SE (SSE) were classified according to the standardized medical dictionary for regulatory activities (MedDRA).
EXPERT OPINION
This novel systematic analysis offers an overview of potential AE, SAE, and SE for currently recommended immunosuppressive drugs for the treatment of TED. Nonspecific, anti-inflammatory drugs and more specific, targeted biologicals are treatment options for active and severe TED. Critical evaluation of the pertinent literature confirms an evidence-based, beneficial efficacy/risk ratio of the current first-line and second-line treatment recommendations endorsed by the European Society of Endocrinology. However, further large, well-conceived trials are mandatory to enhance our knowledge and experience with novel specific small molecules and/or monoclonal antibodies targeting the key autoantigens in TED.
Topics: Antibodies, Monoclonal; Graves Disease; Graves Ophthalmopathy; Humans; Immunosuppressive Agents; Prospective Studies
PubMed: 35447047
DOI: 10.1080/14740338.2022.2069239 -
Epilepsia Sep 2022Autoimmune encephalitis (AE) is a neurological disorder caused by autoimmune attack on cerebral proteins. Experts currently recommend staged immunotherapeutic... (Meta-Analysis)
Meta-Analysis Review
Autoimmune encephalitis (AE) is a neurological disorder caused by autoimmune attack on cerebral proteins. Experts currently recommend staged immunotherapeutic management, with first-line immunotherapy followed by second-line immunotherapy if response to first-line therapy is inadequate. Meta-analysis of the evidence base may provide higher quality evidence to support this recommendation. We undertook a systematic review of observational cohort studies reporting AE patients treated with either second-line immunotherapy or first-line immunotherapy alone, and outcomes reported using the modified Rankin Scale (mRS; search date: April 22, 2020). We performed several one-stage multilevel individual patient data (IPD) meta-analyses to examine the association between second-line immunotherapy and final mRS scores (PROSPERO ID CRD42020181805). IPD were obtained for 356 patients from 25 studies. Most studies were rated as moderate to high risk of bias. Seventy-one patients (71/356, 19%) were treated with second-line immunotherapy. We did not find a statistically significant association between treatment with second-line immunotherapy and final mRS score for the cohort overall (odds ratio [OR] = 1.74, 95% confidence interval [CI] = .98-3.08, p = .057), or subgroups with anti-N-methyl-D-aspartate receptor encephalitis (OR = 1.03, 95% CI = .45-2.38, p = .944) or severe AE (maximum mRS score > 2; OR = 1.673, 95% CI = .93-3.00, p = .085). Treatment with second-line immunotherapy was associated with higher final mRS scores in subgroups with anti-leucine-rich glioma-inactivated 1 AE (OR = 6.70, 95% CI = 1.28-35.1, p = .024) and long-term (at least 12 months) follow-up (OR = 3.94, 95% CI = 1.67-9.27, p = .002). We did not observe an association between treatment with second-line immunotherapy and lower final mRS scores in patients with AE. This result should be interpreted with caution, given the risk of bias, limited adjustment for disease severity, and insensitivity of the mRS in estimating psychiatric and cognitive disability.
Topics: Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Encephalitis; Hashimoto Disease; Humans; Immunologic Factors; Immunotherapy; Retrospective Studies
PubMed: 35700069
DOI: 10.1111/epi.17327 -
The Journal of Dermatology Aug 2019The association between alopecia areata (AA) and autoimmune thyroid diseases (AITD) has been suggested; however, the chronological relationship between AA and AITD... (Meta-Analysis)
Meta-Analysis
The association between alopecia areata (AA) and autoimmune thyroid diseases (AITD) has been suggested; however, the chronological relationship between AA and AITD remains elusive. A systematic review and meta-analysis were conducted to assess the association between AA and AITD focusing on the prevalence of thyroid antibodies, thyroid diseases and serological thyroid dysfunctions, respectively. Data collection was performed in October 2018 by searching for articles in two electronic databases: Medline and Embase. Case-control, cohort and cross-sectional studies were included. Meta-analysis of studies eligible for quantitative synthesis was performed to estimate pooled odds ratios of thyroid antibodies; thyroid peroxidase antibody (TPO-Ab) and thyroglobulin antibody (TG-Ab), diagnosed thyroid diseases and serological thyroid dysfunctions. Four hundred and eighty nine research papers were identified and 17 studies with 262 581 patients and 1 302 655 control subjects were included for quantitative synthesis. AA was significantly associated with both TPO-Ab and TG-Ab. In comparison, there was no significant association between AA and diagnosed hypothyroidism or hyperthyroidism and serological hypothyroidism or hyperthyroidism. In conclusion, AA is significantly associated with the existence of thyroid antibodies rather than with clinical or laboratory thyroid abnormality. Lack of long-term follow-up data is a limitation of the existing published work. Our findings do not support routine screening of thyroid diseases for asymptomatic AA patients but highlight the potential future risk of AITD particularly in severe and refractory AA.
Topics: Alopecia Areata; Autoantibodies; Humans; Prevalence; Thyroid Gland; Thyroiditis, Autoimmune; Time Factors
PubMed: 31197884
DOI: 10.1111/1346-8138.14940 -
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 -
International Journal of Molecular... Apr 2024Brassica vegetables are widely consumed all over the world, especially in North America, Asia, and Europe. They are a rich source of sulfur compounds, such as... (Review)
Review
Brassica vegetables are widely consumed all over the world, especially in North America, Asia, and Europe. They are a rich source of sulfur compounds, such as glucosinolates (GLSs) and isothiocyanates (ITCs), which provide health benefits but are also suspected of having a goitrogenic effect. Adhering to PRISMA guidelines, we conducted a systematic review to assess the impact of dietary interventions on thyroid function, in terms of the potential risk for people with thyroid dysfunctions. We analyzed the results of 123 articles of in vitro, animal, and human studies, describing the impact of brassica plants and extracts on thyroid mass and histology, blood levels of TSH, T3, T4, iodine uptake, and the effect on thyroid cancer cells. We also presented the mechanisms of the goitrogenic potential of GLSs and ITCs, the limitations of the studies included, as well as further research directions. The vast majority of the results cast doubt on previous assumptions claiming that brassica plants have antithyroid effects in humans. Instead, they indicate that including brassica vegetables in the daily diet, particularly when accompanied by adequate iodine intake, poses no adverse effects on thyroid function.
Topics: Animals; Humans; Vegetables; Brassica; Isothiocyanates; Glucosinolates; Goiter; Iodine
PubMed: 38612798
DOI: 10.3390/ijms25073988 -
Heliyon Feb 2023Standardised sex-adjusted prevalence ratios (SSPRs) have not been published for any autoimmune diseases (ADs) in patients with Postural Orthostatic Tachycardia Syndrome... (Review)
Review
Sex adjusted standardized prevalence ratios for celiac disease and other autoimmune diseases in patients with postural orthostatic tachycardia syndrome (POTS): A systematic review and meta-analysis.
Standardised sex-adjusted prevalence ratios (SSPRs) have not been published for any autoimmune diseases (ADs) in patients with Postural Orthostatic Tachycardia Syndrome (POTS), who are predominantly young females. We performed a systematic review according to PRISMA guidelines of POTS cohorts reporting the prevalence of at least one AD. Only four studies were found: two providing data on celiac disease; and two with data on 'any AD', Hashimoto's thyroiditis, rheumatoid arthritis, systemic lupus erythematosus (SLE), Sjögren's syndrome and celiac disease and (one study) antiphospholipid syndrome. All studies were assessed as being at high risk of bias for estimating AD prevalence in POTS patients, with under-reporting of ADs likely due to the lack of rigorous prospective screening for ADs. A literature search found a 'gold standard' general population (GP) comparator only for celiac disease in the United States, leading to a pooled SSPR in POTS patients of 2.75 with 95% confidence interval (1.06-4.40). The lack of recent high-quality studies on GP prevalence for the other ADs was noteworthy. Exploratory pooled SSPRs were calculated for 'any AD' and for the other five ADs using GP comparator data from a comprehensive review. All pooled SSPRs were greater than one and statistically significant, implying a higher prevalence of these ADs, and any AD, in POTS patients. The magnitude of the exploratory SSPRs was very large for SLE, Sjögren's syndrome and antiphospholipid syndrome, perhaps reflecting the use of non-gold standard GP comparators, which may underestimate AD prevalence. Further research in a large POTS cohort with an appropriately age- and sex-matched GP control group is recommended, to confirm the SSPR for celiac disease and to determine whether SLE, Sjogren's syndrome and antiphospholipid syndrome are indeed many times more prevalent in POTS patients than in the GP. The findings are consistent with POTS itself being an AD.
PubMed: 36816268
DOI: 10.1016/j.heliyon.2023.e12982 -
Cancer Immunology, Immunotherapy : CII Aug 2022There is growing evidence suggesting that the occurrence of immune-related adverse events (irAEs) may be a predictor of immune checkpoint inhibitor efficacy. Whether... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is growing evidence suggesting that the occurrence of immune-related adverse events (irAEs) may be a predictor of immune checkpoint inhibitor efficacy. Whether this association extends to all irAEs or just those within particular organs/systems is yet to be resolved. As immune-related thyroid dysfunction (thyroid irAE) is one of the most commonly reported irAEs, this study aims to summarize the available data and determine if thyroid irAE is a surrogate marker for improved cancer outcomes during ICI therapy.
METHODS
PubMed, EMBASE and Cochrane Library were searched up to July 1st 2021 for studies assessing the relationship between thyroid irAE development during ICI therapy and cancer outcomes. Outcome measures of interest include overall survival (OS) and progression free survival (PFS). Sub-group analyses based on cancer type and adjustment for immortal time bias (ITB) were also performed.
RESULTS
Forty-seven studies were included in the systematic review. Twenty-one studies were included in the OS meta-analysis whilst 15 were included in the PFS meta-analysis. Development of thyroid irAE during ICI therapy was associated with improved OS and PFS (OS: HR 0.52, CI 0.43-0.62, p < 0.001; PFS: HR 0.58, CI 0.50-0.67, p < 0.001). Sub-group analyses involving non-small cell lung cancer populations and studies where ITB was accounted for, observed similar results (HR 0.37, CI 0.24-0.57, p < 0.001) and (HR 0.51, CI 0.39-0.69, p < 0.001), respectively.
CONCLUSION
Despite the heterogeneity and biases identified, the evidence does suggest that the development of thyroid irAE is associated with anti-tumor effects of ICIs and therefore, can be used as a surrogate marker for clinical response.
Topics: Biomarkers; Carcinoma, Non-Small-Cell Lung; Humans; Immune Checkpoint Inhibitors; Lung Neoplasms; Thyroid Diseases
PubMed: 35022907
DOI: 10.1007/s00262-021-03128-7 -
Journal of Clinical Neuroscience :... Nov 2022Treatment options for neuromyelitis optica spectrum disorder (NMOSD) are corticosteroids, immunosuppressive drugs, emerging monoclonal antibodies, rituximab, eculizumab,... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Treatment options for neuromyelitis optica spectrum disorder (NMOSD) are corticosteroids, immunosuppressive drugs, emerging monoclonal antibodies, rituximab, eculizumab, satralizumab, and inebilizumab. Due to disabling and deadly nature of NMOSD, there is a great motivation among physicians for finding new treatment options. Recently, several studies have been conducted on the therapeutic effects of autologous hematopoietic stem cell transplantation (AHSCT) on NMOSD patients.
METHODS
Several databases including PubMed, Scopus, Web of Science, and Google scholar were searched for studies on AHSCT in NMOSD patients.
RESULTS
After screening titles and abstracts, and reviewing full texts, nine studies with 39 severe cases of NMOSD met the criteria of our study. The pooled standardized mean difference (SMD) for EDSS score before and after treatment was -0.81 (95 %CI:-1.07, -0.15; Q = 1.99, P = 0.58, I = 0 %). Also, the PFS and RFS were 69 % and 53 % respectively (PFS: 69 %, 95 %CI 42 %, 96 %; Q = 8.63, P = 0.01, I = 73.07 %; RFS: 53 %, 95 %CI 27 %, 79 %; Q = 12.33, P = 0.01, I = 71.87 %). Also, there were three cases with secondary autoimmune diseases including myasthenia gravis, hyperthyroidism, and thyroiditis.
CONCLUSION
According to the present study, AHSCT could be an alternative therapy for NMOSD in severe cases instead of conventional immunotherapies. However, physicians should pay attention to its serious complications. The diversity of results from the published trials on the efficacy and safety of AHSCT calls for further investigations on determining the ideal AHSCT conditioning and the characteristics of patients.
Topics: Antibodies, Monoclonal; Aquaporin 4; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Neuromyelitis Optica; Rituximab
PubMed: 36075186
DOI: 10.1016/j.jocn.2022.08.020 -
Neurological Sciences : Official... Aug 2022Autoimmune encephalitis (AE) is caused by the antibodies that target receptors and intracellular or surface proteins. To achieve the appropriate therapeutic results,... (Review)
Review
INTRODUCTION
Autoimmune encephalitis (AE) is caused by the antibodies that target receptors and intracellular or surface proteins. To achieve the appropriate therapeutic results, early and proper diagnosis is still the most important issue. In this review, we provide an overview of FDG-PET imaging findings in AE patients and possible relation to different subtypes and clinical features.
METHODS
PubMed, Web of Science, and Scopus were searched in August 2021 using a predefined search strategy.
RESULTS
After two-step reviewing, 22 studies with a total of 332 participants were entered into our qualitative synthesis. In anti-NMDAR encephalitis, decreased activity in the occipital lobe was present, in addition, to an increase in frontal, parietal, and specifically medial temporal activity. Anti-VGKC patients showed altered metabolism in cortical and subcortical regions such as striata and cerebellum. Abnormal metabolism in patients with anti-LGI1 has been reported in diverse areas of the brain including medial temporal, hippocampus, cerebellum, and basal ganglia all of which had hypermetabolism. Hypometabolism in parietal, frontal, occipital lobes, temporal, frontal, and hippocampus was observed in AE patients with anti-GAD antibodies.
CONCLUSION
Our results indicate huge diversity in metabolic patterns among different AE subtypes and it is hard to draw a firm conclusion. Moreover, the timing of imaging, seizures, and acute treatments can alter the PET patterns strongly. Further prospective investigations with specific inclusion and exclusion criteria should be carried out to identify the metabolic defect in different AE subtypes.
Topics: Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Autoantibodies; Brain; Encephalitis; Fluorodeoxyglucose F18; Hashimoto Disease; Humans; Magnetic Resonance Imaging; Positron-Emission Tomography
PubMed: 35486333
DOI: 10.1007/s10072-022-06094-9 -
Frontiers in Medicine 2020Membranous nephropathy (MN) is a common cause of proteinuria and nephrotic syndrome all over the world. It can be subdivided into primary and secondary forms. Primary...
Membranous nephropathy (MN) is a common cause of proteinuria and nephrotic syndrome all over the world. It can be subdivided into primary and secondary forms. Primary form is an autoimmune disease clinically characterized by nephrotic syndrome and slow progression. It accounts for ~70% cases of MN. In the remaining cases MN may be secondary to well-defined causes, including infections, drugs, cancer, or autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), urticarial vasculitis, sarcoidosis, thyroiditis, Sjogren syndrome, systemic sclerosis, or ankylosing spondylitis. The clinical presentation is similar in primary and secondary MN. However, the outcome may be different, being often related to that of the original disease in secondary MN. Also, the treatment may be different, being targeted to the etiologic cause in secondary MN. Thus, the differential diagnosis between primary and secondary MN is critical and should be based not only on history and clinical features of the patient but also on immunofluorescence and electron microscopy analysis of renal biopsy as well as on the research of circulating antibodies. The identification of the pathologic events underlying a secondary MN is of paramount importance, since the eradication of the etiologic factors may be followed by remission or definitive cure of MN. In this review we report the main diseases and drugs responsible of secondary MN, the outcome and the pathogenesis of renal disease in different settings and the possible treatments.
PubMed: 33344486
DOI: 10.3389/fmed.2020.611317