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1.
Lupus Sci Med ; 8(1)2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33875571

RESUMEN

OBJECTIVE: To report the results of a survey exploring the experience of patients with SLE facing hydroxychloroquine (HCQ) shortage that occurred during the early phases of the COVID-19 pandemic. METHODS: A survey was designed by Lupus Europe's patient advisory network and distributed through its social media, newsflash and members' network. People with lupus were asked about their last HCQ purchases and their level of anxiety (on a 0-10 scale) with regard to not being able to have access to HCQ, once in April 2020 (first wave) and after 11 August (second wave). The results were compared. RESULTS: 2075 patients responded during the first wave; 1001 (48.2%) could get HCQ from the first place they asked, 230 (11.1%) could get the drug by going to more than one pharmacy, 498 (24.0%) obtained HCQ later from their usual pharmacy and 126 (6.1%) from other sources. 188 (9.1%) could not get any; 32 (1.5%) did not respond to this question. All countries showed significant improvement in HCQ availability during the second wave. 562 (27.4%) patients reported an extremely high level of anxiety in wave 1 and 162 (10.3%) patients in wave 2; 589 (28.7%) and 268 (17.1%) patients reported a high level of anxiety in wave 1 and wave 2, respectively. CONCLUSIONS: The HCQ shortage had a significant impact on patients with SLE and has been responsible for psychological consequences including anxiety. Indeed, despite an objective improvement in drug availability, the event is leaving significant traces in patients' mind and behaviours.


Asunto(s)
Ansiedad , Servicios Comunitarios de Farmacia/estadística & datos numéricos , Accesibilidad a los Servicios de Salud , Hidroxicloroquina , Lupus Eritematoso Sistémico , Antirreumáticos/provisión & distribución , Antirreumáticos/uso terapéutico , Ansiedad/diagnóstico , Ansiedad/etiología , /epidemiología , Defensa Civil/métodos , Defensa Civil/normas , Europa (Continente)/epidemiología , Accesibilidad a los Servicios de Salud/normas , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Humanos , Hidroxicloroquina/provisión & distribución , Hidroxicloroquina/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/epidemiología , Lupus Eritematoso Sistémico/psicología , Distrés Psicológico , Autoinforme/estadística & datos numéricos , Encuestas y Cuestionarios
2.
Int J Mol Sci ; 22(5)2021 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-33800867

RESUMEN

During tissue injury events, the innate immune system responds immediately to alarms sent from the injured cells, and the adaptive immune system subsequently joins in the inflammatory reaction. The control mechanism of each immune reaction relies on the orchestration of different types of T cells and the activators, antigen-presenting cells, co-stimulatory molecules, and cytokines. Mitochondria are an intracellular signaling organelle and energy plant, which supply the energy requirement of the immune system and maintain the system activation with the production of reactive oxygen species (ROS). Extracellular mitochondria can elicit regenerative effects or serve as an activator of the immune cells to eliminate the damaged cells. Recent clarification of the cytosolic escape of mitochondrial DNA triggering innate immunity underscores the pivotal role of mitochondria in inflammation-related diseases. Human mesenchymal stem cells could transfer mitochondria through nanotubular structures to defective mitochondrial DNA cells. In recent years, mitochondrial therapy has shown promise in treating heart ischemic events, Parkinson's disease, and fulminating hepatitis. Taken together, these results emphasize the emerging role of mitochondria in immune-cell-mediated tissue regeneration and ageing.


Asunto(s)
Envejecimiento/inmunología , Células Presentadoras de Antígenos/inmunología , Subgrupos de Linfocitos B/inmunología , Mitocondrias/fisiología , Regeneración/inmunología , Subgrupos de Linfocitos T/inmunología , Inmunidad Adaptativa , Animales , Citocinas/fisiología , ADN/metabolismo , ADN Mitocondrial/metabolismo , Reposicionamiento de Medicamentos , Péptido 1 Similar al Glucagón/agonistas , Homeostasis , Humanos , Inmunidad Innata , Inflamación , Péptidos y Proteínas de Señalización Intercelular/fisiología , Lupus Eritematoso Sistémico/tratamiento farmacológico , Metformina/farmacología , Metformina/uso terapéutico , Mitocondrias/efectos de los fármacos , Proteínas Mitocondriales/fisiología , Especies Reactivas de Oxígeno/metabolismo , Inmunología del Trasplante , Heridas y Traumatismos/inmunología , Heridas y Traumatismos/fisiopatología
3.
Clin Exp Rheumatol ; 39(2): 231-241, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33843578

RESUMEN

In 2020 many contributions have been produced on SLE. Our critical digest of the recent literature will be focused on genetic factors that contribute to the development of the disease, novel potential therapeutic targets (including IL-23, IL-17, interferons and JAKs), diagnostic and prognostic biomarkers, classification criteria, clinical manifestations and comorbidities. We will then present new treatment options (with a special focus on belimumab, anifrolumab, tacrolimus, voclosporin and EULAR/ERA-EDTA recommendations for the management of LN) and treat-to-target strategy. Lastly, we will concentrate on some of the aspects that influence patients' disease perception and quality of life.


Asunto(s)
Lupus Eritematoso Sistémico , Calidad de Vida , Humanos , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/tratamiento farmacológico
4.
Rev Med Suisse ; 17(733): 684-689, 2021 Apr 07.
Artículo en Francés | MEDLINE | ID: mdl-33830700

RESUMEN

Systemic lupus erythematosus is a complex autoimmune disease that remains challenging to treat. Recent advances in the understanding of the pathogenesis of SLE pave the way for the evaluation of biologic medicine. The most promising therapeutic targets in SLE are those that interfere with B cells count or normal function, interferon inhibitors, JAK inhibitors and biologicals that alter the cytokines imbalance that characterizes SLE. Recent phase 3 clinical trials have evaluated the role of belimumab in lupus nephritis and the usefulness of anifrolumab in the treatment of moderate to severe SLE. Many more trials are currently underway and may improve the level of care of patients with SLE in the near future.


Asunto(s)
Productos Biológicos , Inhibidores de las Cinasas Janus , Lupus Eritematoso Sistémico , Linfocitos B , Citocinas , Humanos , Lupus Eritematoso Sistémico/tratamiento farmacológico
5.
Z Rheumatol ; 80(4): 332-338, 2021 May.
Artículo en Alemán | MEDLINE | ID: mdl-33721043

RESUMEN

Treatment of systemic lupus erythematosus (SLE) without permanent glucocorticoid therapy is inconceivable for most patients and their physicians. Although we have significantly improved the prognosis of SLE, management remains constrained by a lack of effective, targeted therapies and the lack of evidence-based approaches to the use of existing compounds. For example, for glucocorticoids (GC), which are used continuously in a majority of patients, there are no evidence-based recommendations for initiation, tapering, and cessation in the treatment of SLE. Even today, GC are without alternatives in acute situations, especially organ- or life-threatening ones. However, due to the known long-term adverse effects, the role of GC is viewed increasingly critically. Long-term data from cohorts show that the use of GC actually contributes to morbidity and mortality in SLE. Strategies to reduce the use of GC in SLE are therefore urgently needed and are proposed in this paper.


Asunto(s)
Glucocorticoides , Lupus Eritematoso Sistémico , Humanos , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Pronóstico
6.
Medicine (Baltimore) ; 100(11): e24423, 2021 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-33725933

RESUMEN

ABSTRACT: The association between Glutathione S-transferase Pi 1(GSTP1) genetic polymorphism (rs1695, 313A>G) and cyclophosphamide-induced toxicities has been widely investigated in previous studies, however, the results were inconsistent. This study was performed to further elucidate the association.A comprehensive search was conducted in PubMed, Embase, Web of Science, China National Knowledge Infrastructure, and Wan Fang database up to January 5, 2020. Risk ratios (RRs) and 95% confidence intervals (95% CIs) were used to estimate the association between GSTP1 rs1695 polymorphism and cyclophosphamide-induced hemotoxicity, gastrointestinal toxicity, infection, and neurotoxicity.A total of 13 studies were eventually included. Compared with the GSTP1 rs1695 AA genotype carriers, patients with AG and GG genotypes had an increased risk of cyclophosphamide-induced gastrointestinal toxicity (RR, 1.61; 95% CI, 1.18-2.19; P = .003) and infection (RR, 1.57; 95% CI, 1.00-2.48; P = .05) in the overall population. In the subgroup analyses, there were significant associations between GSTP1 rs1695 polymorphism and the risk of cyclophosphamide-induced myelosuppression (RR, 2.10; 95% CI, 1.60-2.76; P < .00001), gastrointestinal toxicity (RR, 1.77; 95%CI, 1.25-2.53; P = .001), and infection (RR, 2.01; 95% CI, 1.14-3.54; P = .02) in systemic lupus erythematosus (SLE) or lupus nephritis syndrome patients, but not in cancer patients.Our results confirmed an essential role for the GSTP1 rs1695 polymorphism in the prediction of cyclophosphamide-induced myelosuppression, gastrointestinal toxicity, and infection in SLE or lupus nephritis syndrome patients. More studies are necessary to validate our findings in the future.


Asunto(s)
Ciclofosfamida/efectos adversos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/genética , Predisposición Genética a la Enfermedad/genética , Gutatión-S-Transferasa pi/genética , Polimorfismo Genético , Enfermedades Gastrointestinales/inducido químicamente , Enfermedades Gastrointestinales/genética , Genotipo , Humanos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Nefritis Lúpica/tratamiento farmacológico , Estudios Observacionales como Asunto , Factores de Riesgo
8.
CNS Drugs ; 35(3): 317-330, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33743151

RESUMEN

BACKGROUND: Disease-modifying therapies (DMTs) for multiple sclerosis (MS) target immunity and have the potential to increase the risk of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and alter its clinical course. We assessed these risks in patients with MS (PwMS). OBJECTIVE: The objective of this study was to describe the overall risk of coronavirus disease 2019 (COVID-19) infection, severe disease course, and potential population-level predictors of COVID-19 infection in PwMS, and to provide a context using a cohort of patients with systemic lupus erythematosus (SLE). In addition, the association of different MS DMTs with the incidence and clinical course of COVID-19 was evaluated. Safety data from the Biogen Global Safety Database are also presented on reported cases of COVID-19 in patients treated with Biogen MS therapies. METHODS: The IBM® Explorys electronic health record database of > 72,000,000 patients from US healthcare networks identified patients with MS or SLE, with and without polymerase chain reaction-confirmed COVID-19. COVID-19 cumulative incidence, hospitalization, and deaths among DMT classes were compared using logistic regression (adjusted for age, sex, body mass index, comorbidities, and race/ethnicity). As a secondary data source to assess safety data, COVID-19 reports for Biogen MS therapies were extracted and described from Biogen's Global Safety Database. RESULTS: 30,478 PwMS with an open DMT prescription were identified within Explorys; 344 were COVID-19 positive. The most significant risk factors for acquiring COVID-19 were comorbidity score ≥ 1, body mass index ≥ 30, and Black/African ancestry. Similar risk factors were also identified for patients with SLE. Patients with MS were less likely to develop COVID-19 when treated with interferons (0.61%) and glatiramer acetate (0.51%), vs all other MS DMTs (both p < 0.001); anti-CD20 therapy was associated with the highest risk (3.45%; p < 0.0001). In the Biogen Global Safety Database, we identified 1217 patients who were COVID-19 positive treated with intramuscular interferon beta-1a, peginterferon beta-1a, natalizumab, dimethyl fumarate, diroximel fumarate, or fampridine. CONCLUSIONS: Comorbidities, obesity, and Black/African ancestry, but not age, were associated with a higher risk of SARS-CoV-2 infection in PwMS. Interferons and glatiramer acetate were associated with a reduced COVID-19 risk, whereas anti-CD20 therapies were associated with an increased risk, within the treated MS cohort. COVID-19 safety reports for patients receiving Biogen MS therapies were consistent with the Explorys database and MS literature, illustrating the replicability and power of this approach.


Asunto(s)
/epidemiología , Hospitalización/estadística & datos numéricos , Inmunosupresores/uso terapéutico , Esclerosis Múltiple/tratamiento farmacológico , Adolescente , Adulto , Afroamericanos/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Alemtuzumab/uso terapéutico , Azatioprina/uso terapéutico , Cladribina/uso terapéutico , Comorbilidad , Crotonatos/uso terapéutico , Ciclofosfamida/uso terapéutico , Ciclosporina/uso terapéutico , Bases de Datos Factuales , Dimetilfumarato/uso terapéutico , Grupo de Ascendencia Continental Europea/estadística & datos numéricos , Femenino , Clorhidrato de Fingolimod/uso terapéutico , Humanos , Factores Inmunológicos/uso terapéutico , Incidencia , Interferón beta/uso terapéutico , Modelos Logísticos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/epidemiología , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Mitoxantrona/uso terapéutico , Esclerosis Múltiple/epidemiología , Ácido Micofenólico/uso terapéutico , Natalizumab/uso terapéutico , Obesidad/epidemiología , Factores de Riesgo , Rituximab/uso terapéutico , Toluidinas/uso terapéutico , Estados Unidos/epidemiología , Adulto Joven
9.
Medicine (Baltimore) ; 100(10): e24919, 2021 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-33725851

RESUMEN

INTRODUCTION: Hydroxychloroquine (HCQ) has received much attention in the treatment of coronavirus disease 2019 recently. However, it can cause irreversible vision loss. Few cases have been reported in pediatric patient with HCQ-related adverse reactions. Appropriate administration and early disease recognition are important for reducing the adverse drug reactions of HCQ. PATIENT CONCERNS: We report a case of a 14-year-old Chinese girl who sought treatment for rapidly decreasing vision in the left eye over 3 days. The simulation results of the population pharmacokinetic model of HCQ revealed that the plasma concentration of HCQ abnormally increased before the visual acuity of the eye decreased. DIAGNOSIS: She was diagnosed as HCQ related drug adverse reaction. INTERVENTIONS: The daily dose of HCQ for this patient was adjusted from 100 mg/d to 50 mg/d. OUTCOMES: Follow-up for 6 months showed no more vision loss recurrence. However, the existing decreased visual acuity of the eye did not recover either. CONCLUSION: Although decreased visual acuity is an infrequent symptom, ophthalmologists should be aware of the possibility of HCQ concentration enrichment and consider minimizing HCQ use when a child with renal hypofunction seeks treatment for shortsightedness.


Asunto(s)
Hidroxicloroquina/efectos adversos , Baja Visión/inducido químicamente , Adolescente , Femenino , Humanos , Hidroxicloroquina/farmacocinética , Hidroxicloroquina/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Agudeza Visual
10.
Medicine (Baltimore) ; 100(10): e25063, 2021 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-33725895

RESUMEN

RATIONALE: Systemic lupus erythematosus (SLE) is a complex autoimmune inflammatory disease that frequently affects various organs. Neuropsychiatric manifestations in SLE patients, known as neuropsychiatric SLE, are clinically common. However, the principal manifestation of cranial neuropathy in patients with SLE and comorbidities is relatively rare. PATIENT CONCERNS: In this report, we describe a 51-year-old Chinese woman who was admitted with a chief complaint of chronic-onset facial paresthesia, dysphagia, and choking cough when drinking water, accompanied by slurred speech, salivation, and limb weakness. The blood autoantibody test results showed that many SLE-associated antibodies were positive. Meanwhile, anti-nuclear matrix protein 2 (NXP2) antibody was strongly positive in the idiopathic inflammatory myopathy (IIM) spectrum test from the serum. Muscle biopsy indicated inflammatory infiltration of the muscle fiber stroma. DIAGNOSES: Taking into account the clinical manifestations and laboratory tests of the present case, the diagnosis of SLE and probable IIM was established. INTERVENTIONS: Corticosteroids and additional gamma globulin were administered and the clinical symptoms were relieved during the treatment process. OUTCOMES: Unfortunately, the patient experienced sudden cardiac and respiratory arrest. Multiple system dysfunctions exacerbated disease progression, but in the present case, we speculated that myocardial damage resulting from SLE could explain why she suddenly died. LESSONS: To our knowledge, multiple neurological manifestations in patients with SLE and anti-NXP2-positive myositis are rare. Note that SLE is still a life-threatening disease that causes multiple system dysfunctions, which requires increasing attention.


Asunto(s)
Enfermedades de los Nervios Craneales/inmunología , Trastornos de Deglución/inmunología , Lupus Eritematoso Sistémico/diagnóstico , Parestesia/inmunología , Polimiositis/diagnóstico , Adenosina Trifosfatasas/inmunología , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Biopsia , Enfermedades de los Nervios Craneales/diagnóstico , Enfermedades de los Nervios Craneales/tratamiento farmacológico , Proteínas de Unión al ADN/inmunología , Trastornos de Deglución/diagnóstico , Trastornos de Deglución/tratamiento farmacológico , Quimioterapia Combinada/métodos , Resultado Fatal , Femenino , Humanos , Factores Inmunológicos/administración & dosificación , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/inmunología , Persona de Mediana Edad , Músculo Esquelético/inmunología , Músculo Esquelético/patología , Parestesia/diagnóstico , Parestesia/tratamiento farmacológico , Polimiositis/complicaciones , Polimiositis/tratamiento farmacológico , Polimiositis/inmunología , Quimioterapia por Pulso
11.
Medicine (Baltimore) ; 100(12): e23597, 2021 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-33761626

RESUMEN

BACKGROUND: The efficacy and safety of integrated Chinese and western medicine in the treatment of Systemic Lupus Erythematosus (SLE) have not been systematically evaluated. METHODS: This systematic review and meta-analysis will be performed and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We will search PubMed, Embase, Cochrane Library, Chinese Biomedical Database WangFang, VIP, and China National Knowledge Infrastructure (CNKI) for potentially eligible studies from their inception to Dec. 2020, and we will select all the eligible randomized controlled trials (RCTs) of the integrated Chinese and western medicine for Systemic Lupus Erythematosus. All the studies will be screened according to the inclusion and exclusion criteria and meta-analysis will be conducted using Review Manager V.5.3. and Stata V.12.0. The primary endpoint was the clinical efficacy rate, the secondary outcomes were SLEDAI score, adverse reaction rate, and laboratory test parameters (white blood cells, complement C3). RESULTS: The results of this study will systematically evaluate the effectiveness and safety of the integrated Chinese and western medicine in the treatment of primary dysmenorrhea. CONCLUSION: The efficacy and safety of integrated Chinese and western medicine will be systematically evaluated in this paper, thus providing evidence for the clinical application of this therapy. ETHICS AND DISSEMINATION: This study is a systematic review, which is based on the published studies, so examination and agreement by the ethics committee are not required in this study. We intend to publish the study results in a journal or conference presentations. OPEN SCIENCE FRAMEWORK OSFREGISTRATION NUMBER: https://osf.io/mabxh.


Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Glucocorticoides/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Quimioterapia Combinada/métodos , Humanos , Lupus Eritematoso Sistémico/diagnóstico , Metaanálisis como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Índice de Severidad de la Enfermedad , Revisiones Sistemáticas como Asunto , Resultado del Tratamiento
12.
Zhonghua Er Ke Za Zhi ; 59(2): 107-112, 2021 Feb 02.
Artículo en Chino | MEDLINE | ID: mdl-33548956

RESUMEN

Objective: To analyze the disease spectrum among children who were using hydroxychloroquine (HCQ), and evaluate the drug's safety and compliance. Methods: From January 2008 to December 2019, children from Children's Hospital of Fudan University who used HCQ were selected as subjects, the disease spectrum of HCQ was analyzed, and the drug safety and compliance were evaluated for the patients who were followed up for more than 6 months. Demographic information, diagnosis, initial dose, time of continuous use, cumulative dosage and related adverse reactions report, project and the results of eye test were collected. Results: A total of 528 cases used HCQ during the 12 years, with 156 male cases and 372 female cases, and age at initial medication was (10.5±3.2) years. Among them, 514 cases (97.3%) had rheumatic disease, 5 had pulmonary interstitial lesions and 9 had other system diseases. The top three of the rheumatic diseases were systemic lupus erythematosus (SLE) in 316 cases (316/514,61.5%), juvenile idiopathic arthritis in 69 cases (69/514,13.4%), and juvenile dermatomyositis in 56 cases (56/514,10.9%). During the same period, 397 cases were diagnosed with SLE, and the utilization rate was 79.6% (316/397), which was the highest compared with other diseases and increased year by year. Pulmonary interstitial lesions included 4 cases with SFTPC gene defect related interstitial lung disease. Of the 528 ceses who were treated with HCQ, 397 cases were included for evaluating HCQ's safety and compliance, the initial dose was (4.2±1.0) mg/kg, duration was 29.6 (14.9, 48.8) months, the longest usage time was 127 months, the largest cumulative dosage was 566.8 g. The continuous usage duration (Z=-3.191, P=0.001) of SLE was significantly higher than those of other diseases, as well as cumulative dosage (Z=-5.355, P=0.001). All cases received comprehensive eye exams before medication, 354 cases (354/397, 89.2%) were followed up in the ophthalmological department, and 65.5% (232/354) of them could be reviewed regularly at least 1 time per year. One case suffered from severe skin adverse reactions when the drug was used for 32.7 months, and no other serious adverse reactions were reported. HCQ related retinopathy was not seen during the follow-up period. There were 5 cases stopped HCQ on their own. Conclusions: HCQ was widely used in rheumatic disease in children, especially in those with SLE. It was safe for long-time usage in children, and the medication compliance and the ophthalmic follow-up was good.


Asunto(s)
Antirreumáticos , Lupus Eritematoso Sistémico , Enfermedades Reumáticas , Adolescente , Antirreumáticos/efectos adversos , Niño , Enfermedad Crónica , Femenino , Humanos , Hidroxicloroquina/efectos adversos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Masculino , Enfermedades Reumáticas/tratamiento farmacológico
14.
Cochrane Database Syst Rev ; 2: CD010668, 2021 02 25.
Artículo en Inglés | MEDLINE | ID: mdl-33631841

RESUMEN

BACKGROUND: Belimumab, the first biologic approved for the treatment of systemic lupus erythematosus (SLE), has been shown to reduce autoantibody levels in people with SLE and help control disease activity. OBJECTIVES: To assess the benefits and harms of belimumab (alone or in combination) in systematic lupus erythematosus. SEARCH METHODS: An Information Specialist carried out the searches of CENTRAL, MEDLINE, Embase, CINAHL, Web of Science, the World Health Organization (WHO) International Clinical Trials Registry Platform, and clinicaltrials.gov from inception to 25 September 2019. There were no language or date restrictions. SELECTION CRITERIA: We included randomized controlled trials (RCTs) or controlled clinical trials (CCTs) of belimumab (alone or in combination) compared to placebo/control treatment (immunosuppressive drugs, such as azathioprine, cyclosporine, mycophenolate mofetil or another biologic), in adults with SLE. DATA COLLECTION AND ANALYSIS: We used standard methodologic procedures expected by Cochrane. MAIN RESULTS: Six RCTs (2917 participants) qualified for quantitative analyses. All included studies were multicenter, international or US-based. The age range of the included participants was 22 to 80 years; most were women; and study duration ranged from 84 days to 76 weeks. The risk of bias was generally low except for attrition bias, which was high in 67% of studies. Compared to placebo, more participants on belimumab 10 mg/kg (Food and Drug Administration (FDA)-approved dose) showed at least a 4-point improvement (reduction) in Safety of Estrogen in Lupus National Assessment (SELENA) - Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, a validated SLE disease activity index: (risk ratio (RR) 1.33, 95% confidence interval (CI) 1.22 to 1.45; 829/1589 in belimumab group and 424/1077 in placebo; I2= 0%; 4 RCTs; high-certainty evidence). Change in health-related quality of life (HRQOL), assessed by Short Form-36 Physical Component Summary score improvement (range 0 to 100), showed there was probably little or no difference between groups (mean difference 1.6 points, 95% CI 0.30 to 2.90; 401 in belimumab group and 400 in placebo; I2= 0%; 2 RCTs; moderate-certainty evidence). The belimumab 10 mg/kg group showed greater improvement in glucocorticoid dose, with a higher proportion of participants reducing their dose by at least 50% compared to placebo (RR 1.59, 95% CI 1.17 to 2.15; 81/269 in belimumab group and 52/268 in placebo; I2= 0%; 2 RCTs; high-certainty evidence). The proportion of participants experiencing harm may not differ meaningfully between the belimumab 10 mg/kg and placebo groups: one or more serious adverse event (RR 0.87, 95% CI: 0.68 to 1.11; 238/1700 in belimumab group and 199/1190 in placebo; I2= 48%; 5 RCTs; low-certainty evidence; ); one or more serious infection (RR 1.01, 95% CI: 0.66 to 1.54; 44/1230 in belimumab group and 40/955 in placebo; I2= 0%; 4 RCTs; moderate-certainty evidence); and withdrawals due to adverse events (RR 0.82, 95% CI: 0.63 to 1.07; 113/1700 in belimumab group and 94/1190 in placebo; I2= 0%; 5 RCTs; moderate-certainty evidence). Mortality was rare, and may not differ between belimumab 10 mg/kg and placebo (Peto odds ratio 1.15, 95% CI 0.41 to 3.25; 9/1714 in belimumab group and 6/1203 in placebo; I2= 4%; 6 RCTs; low-certainty evidence). AUTHORS' CONCLUSIONS: The six studies that provided evidence for benefits and harms of belimumab were well-designed, high-quality RCTs. At the FDA-approved dose of 10 mg/kg, based on moderate to high-certainty data, belimumab was probably associated with a clinically meaningful efficacy benefit compared to placebo in participants with SLE at 52 weeks. Evidence related to harms is inconclusive and mostly of moderate to low-certainty evidence. More data are needed for the longer-term efficacy of belimumab.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Inmunosupresores/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/efectos adversos , Sesgo , Femenino , Glucocorticoides/uso terapéutico , Humanos , Inmunosupresores/efectos adversos , Lupus Eritematoso Sistémico/mortalidad , Masculino , Persona de Mediana Edad , Placebos/uso terapéutico , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Adulto Joven
15.
JAMA Netw Open ; 4(2): e2036321, 2021 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-33533931

RESUMEN

Importance: Rituximab is among the most frequently used immunotherapies in pediatrics. Few studies have reported long-term adverse events associated with its use for children. Objective: To describe the use of rituximab and to assess whether its use is associated with short- or long-term adverse events, infections, or time to immune reconstitution in a diverse group of young people. Design, Setting, and Participants: This retrospective cohort study included 468 patients aged younger than 21 years who received rituximab for diverse indications between October 1, 2010, and December 31, 2017, at Texas Children's Hospital, a large pediatric referral hospital. Patterns of adverse events, infections, and immune recovery are described. Data analyses were conducted from December 2019 to June 2020. Exposure: One or more doses of rituximab. Main Outcomes and Measures: Adverse drug events (eg, anaphylaxis), incidence of mild and severe infections, and time to recovery of B lymphocyte subset counts and immunoglobulin levels. Survival models and logistic regression analyses and were used to identify associated risk factors of infectious and noninfectious adverse drug events. Results: We identified 468 patients receiving at least 1 dose of rituximab. The total follow-up time was 11 713 person-months. Of the 468 patients, 293 (62.6%) were female, the median (interquartile range) age at receipt of dose was 14.3 (9.9-16.8) years, and 209 (44.7%) were self-reported White Hispanic. Adverse events associated with rituximab infusion occurred in 72 patients (15.4%), and anaphylaxis occurred in 17 patients (3.6%). Long-term adverse events, such as prolonged neutropenia and leukoencephalopathy, were absent. Infections occurred in 224 patients (47.9%); 84 patients (17.9%) had severe infections, and 3 patients (0.6%) had lethal infections. Concurrent use of intravenous chemotherapy, treatment of systemic lupus erythematosus, neutropenia, and use of intravenous immunoglobulin were associated with increased risk of infection. Among 135 patients (28.8%) followed up to B cell count recovery, CD19+ or CD20+ cell numbers normalized in a median of 9.0 months (interquartile range, 5.9-14.4 months) following rituximab use; 48 of 95 patients (51%) evaluated beyond a year had low-for-age B cell counts. Recovery of CD27+ memory B cell number occurred in a median of 15.7 months (interquartile range, 6.0-22.7 months). Among patients with normal baseline values, low immunoglobulin G (IgG) levels developed in 67 of 289 patients (23.2%) and low IgM levels in 118 of 255 patients (40.8%); of these patients evaluated beyond 12 months from rituximab, 16 of 117 (13.7%) had persistently low IgG and 37 (33.9%) of 109 had persistently low IgM. Conclusions and Relevance: Rituximab is well tolerated among young people and is associated with few serious adverse events, but infections are common, corresponding to a prolonged period of B cell count recovery often lasting for longer than a year. Further examination of strategies to prevent infections following rituximab should be pursued.


Asunto(s)
Anafilaxia/epidemiología , Factores Inmunológicos/efectos adversos , Infecciones/epidemiología , Reacción en el Punto de Inyección/epidemiología , Neutropenia/epidemiología , Rituximab/efectos adversos , Adolescente , Agammaglobulinemia/inducido químicamente , Agammaglobulinemia/epidemiología , Anafilaxia/inducido químicamente , Enfermedades Autoinmunes del Sistema Nervioso/tratamiento farmacológico , Linfocitos B , Niño , Preescolar , Estudios de Cohortes , Encefalitis/tratamiento farmacológico , Femenino , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Lactante , Infecciones/inducido químicamente , Leucoencefalopatía Multifocal Progresiva/epidemiología , Efectos Adversos a Largo Plazo/inducido químicamente , Efectos Adversos a Largo Plazo/epidemiología , Lupus Eritematoso Sistémico/tratamiento farmacológico , Recuento de Linfocitos , Linfoma/tratamiento farmacológico , Masculino , Esclerosis Múltiple/tratamiento farmacológico , Síndrome Nefrótico/tratamiento farmacológico , Neutropenia/inducido químicamente , Oportunidad Relativa , Modelos de Riesgos Proporcionales , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Factores de Tiempo , Adulto Joven
16.
Rheumatol Int ; 41(4): 799-809, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33543338

RESUMEN

Systemic lupus erythematosus (SLE) is an autoimmune and multisystemic chronic inflammatory disease that can affect various organs, including skin, joints, kidneys, lungs and the nervous system. Infectious agents have long been implicated in the pathogenesis of SLE. The new viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shown that, in genetically predisposed patients could trigger the presentation or exacerbation of the autoimmune disease. We herein report a case of a 45-year-old man who presented respiratory symptoms, bilateral pleural effusion, ascites, splenomegaly, severe thrombocytopenia and renal failure with proteinuria and hematuria. SARS-CoV-2 PCR confirmed the COVID-19 diagnosis. We diagnosed the patient with SLE based on the clinical manifestations and positive immunological markers (2019 European League Against Rheumatism/American College of Rheumatology, score of 18). Glucocorticoid pulses were administered to the patient, which improved renal function. However, thrombocytopenia was also refractory to IV immunoglobulin and rituximab, so the patient underwent splenectomy. Through a systematic search of the medical literature, we retrieved two cases with newly onset SLE and five cases with previous SLE diagnosis that showed activity of the disease due to SARS-CoV-2 infection. We herein present a systemic review of these cases and discuss the clinical manifestations that could help to the diagnosis of this clinical condition.


Asunto(s)
/complicaciones , Lupus Eritematoso Sistémico/etiología , Autoinmunidad , Glucocorticoides/uso terapéutico , Humanos , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Masculino , Persona de Mediana Edad
17.
Medicine (Baltimore) ; 100(5): e24553, 2021 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-33592909

RESUMEN

ABSTRACT: Studies on predicting factors for adverse pregnancy outcomes (APOs) in Thai patients with systemic lupus erythematosus (SLE) are limited. This retrospective observation study determined APOs and their predictors in Thai patients with SLE.Medical records of pregnant SLE patients in a lupus cohort, seen from January 1993 to June 2017, were reviewed.Ninety pregnancies (1 twin pregnancy) from 77 patients were identified. The mean age at conception was 26.94 ±â€Š4.80 years. At conception, 33 patients (36.67%) had active disease, 23 (25.56%) hypertension, 20 (22.22%) renal involvement, and 6 of 43 (13.95%) positive anti-cardiolipin antibodies or lupus anti-coagulants, and 37 (41.11%) received hydroxychloroquine. Nineteen patients (21.11%) had pregnancy loss. Of 71 successful pregnancies, 28 (31.11%) infants were full-term, 42 (46.67%) pre-term and 1 (11.11%) post-term; 19 (26.39%) were small for gestational age (SGA), and 38 (52.58%) had low birth weight (LBW). Maternal complications occurred in 21 (23.33%) pregnancies [10 (11.11%) premature rupture of membrane (PROM), 8 (8.89%) pregnancy induced hypertension (PIH), 4 (4.44%) oligohydramnios, 2 (2.22%) post-partum hemorrhage, and 1 (1.11%) eclampsia]. Patients aged ≥ 25 years at pregnancy and those ever having renal involvement had predicted pregnancy loss with adjusted odds ratio (AOR) [95% CI] of 4.15 [1.10-15.72], P = .036 and 9.21 [1.03-82.51], P = .047, respectively. Renal involvement predicted prematurity (6.02 [1.77-20.52, P = .004), SGA (4.46 [1.44-13.78], P = .009), and LBW in infants (10.01 [3.07-32.62], P < .001). Prednisolone (>10 mg/day) and immunosuppressive drugs used at conception protected against prematurity (0.11 [0.02-0.85], P = .034). Flares and hematologic involvement predicted PROM (8.45 [1.58-45.30], P = .013) and PIH (9.24 [1.70-50.24], P = .010), respectively. Cutaneous vasculitis (33.87 [1.05-1,094.65], P = .047), and renal (31.89 [6.66-152.69], P < .001), mucocutaneous (9.17 [1.83-45.90], P = .007) and hematologic involvement (128.00 [4.60-3,564.46], P = .004) during pregnancy predicted flare; while prednisolone (>10 mg/day) and immunosuppressive drug use at conception reduced that risk (0.08 [0.01-0.68, P = .021).APOs remain a problem in Thai pregnant SLE patients. Renal involvement and SLE flares were associated with the risk of APOs.


Asunto(s)
Lupus Eritematoso Sistémico/epidemiología , Complicaciones del Embarazo/epidemiología , Resultado del Embarazo/epidemiología , Adulto , Factores de Edad , Peso al Nacer , Femenino , Edad Gestacional , Humanos , Inmunosupresores/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/fisiopatología , Embarazo , Complicaciones del Embarazo/tratamiento farmacológico , Complicaciones del Embarazo/fisiopatología , Insuficiencia Renal/epidemiología , Estudios Retrospectivos , Tailandia/epidemiología , Adulto Joven
18.
Clin Rheumatol ; 40(4): 1649-1657, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33452660

RESUMEN

In the early stage of the COVID-19 pandemic, Belgian health authorities endorsed the interim guidelines for the treatment of COVID-19 pneumonia: hydroxychloroquine (HCQ) recommended for treatment of hospitalized patients with moderate to severe disease. As a growing number of patients were admitted, inevitably, our internal medicine team questioned the efficacy and safety of HCQ, especially with regard to cardiac side effects. In parallel with our concerns, data regarding the safety and efficacy of HCQ were published, with discordant results and debate in the medical community. Media coverage of the possible risks and benefits of HCQ use in COVID-19 also caused confusion amongst the public. In this Perspectives in Rheumatology article, we review the use and safety of HCQ in autoimmune disease and its putative efficacy and toxicity in COVID-19. Finally, we share our concern about the future of this widely used and inexpensive drug after the COVID-19 pandemic has passed.


Asunto(s)
Enfermedades Autoinmunes/tratamiento farmacológico , Cardiotoxicidad/etiología , Hidroxicloroquina/efectos adversos , Antivirales/uso terapéutico , Humanos , Hidroxicloroquina/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento
19.
Lupus ; 30(5): 836-839, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33509065

RESUMEN

We report a case of COVID-19 in a pediatric patient with systemic lupus erythematosus (SLE), who presented with respiratory distress marked by increased work of breathing and low oxygen saturation. Lab tests confirmed COVID-19, and showed lymphocytopenia and elevated markers of inflammation and coagulopathy. Chest X-ray showed bilateral mid-lung opacities, and the patient required intubation early in his disease course. Imaging and clinical findings were consistent with acute respiratory distress syndrome (ARDS) with inflammation. The patient was treated with different combinations of antivirals (hydroxychloroquine and remdesivir), cytokine inhibitors (anakinra and tocilizumab), glucocorticoids (hydrocortisone and methylprednisolone), and an anticoagulant (enoxaparin). Inflammatory markers decreased before clinical improvement in lung aeration. This case highlights the potential for pediatric patients with SLE to present with COVID-19 similar to the clinical presentation described in adults.


Asunto(s)
/complicaciones , Lupus Eritematoso Sistémico/complicaciones , /etiología , Antivirales/uso terapéutico , /inmunología , Preescolar , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Síndrome de Liberación de Citoquinas/etiología , Síndrome de Liberación de Citoquinas/inmunología , Citocinas/antagonistas & inhibidores , Progresión de la Enfermedad , Enoxaparina/uso terapéutico , Glucocorticoides/uso terapéutico , Humanos , Inmunosupresores/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/inmunología , Masculino , /inmunología
20.
Medicine (Baltimore) ; 100(2): e24031, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33466148

RESUMEN

RATIONALE: Osteonecrosis (ON) is a devastating illness that leads to bone ischemia and potential joint destruction. Systemic lupus erythematosus (SLE) is a chronic, autoimmune disease, with multi-system involvement which is closely associated with occurrence of ON. Multifocal ON, with an estimated morbidity of 3% in SLE patients, is extremely rare in juvenile subjects. PATIENT CONCERNS: A 13.3-year-old female SLE patient was admitted to hospital 20 months following the SLE diagnosis because of a sudden aggravation of sore knees. She suffered from double knee joint pain and her left knee joint showed typical signs of inflammation including redness, swelling, heat, and pain. DIAGNOSES: The SLE patient was diagnosed with multifocal ON of her knee joint based on magnetic resonance imaging findings of bone destruction and osteoproliferation at the bilateral distal femur and proximal tibia. INTERVENTIONS: The patient received high-dose methylprednisolone and intravenous cyclophosphamide pulse therapies for controlling active lupus and nephritis. Oral calcitriol and dipyridamole were administered to alleviate knee pain and inhibit thrombi formation, thereby suppressing ON progress. OUTCOMES: Three weeks following the treatment, the swelling in patient's left knee subsided. Her self-reporting pain score decreased from 9 to 4 and walking time increased from 45minutes to 90minutes per day. Nearly 5 weeks later, the pain in bilateral knee joints disappeared and the patient could walk without difficulties. LESSONS: This patient is the youngest SLE patient who developed multifocal ON based on the reported literature. It suggests that ON can occur in young SLE patients. A combination of internal and external risk factors can promote the development of ON. The balanced approach to the application of corticosteroids and immunosuppressors in the treatment of SLE and prevention of ON is a challenging problem that deserves further exploration.


Asunto(s)
Lupus Eritematoso Sistémico/complicaciones , Osteonecrosis/complicaciones , Adolescente , Conservadores de la Densidad Ósea/uso terapéutico , Calcitriol/uso terapéutico , Ciclofosfamida/uso terapéutico , Dipiridamol/uso terapéutico , Femenino , Humanos , Inmunosupresores/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/patología , Metilprednisolona/uso terapéutico , Osteonecrosis/tratamiento farmacológico , Osteonecrosis/patología , Inhibidores de Agregación Plaquetaria/uso terapéutico
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