RESUMEN
PURPOSE OF REVIEW: Sodium glucose cotransporter 2 (SGLT2) inhibitors are a class of medications initially developed for the treatment of diabetes, although their cardiac and renal protective benefits are far reaching. There has been marked interest in the rheumatology community to adopt these medications into our clinical practice, particularly for chronic kidney disease with persistent proteinuria. RECENT FINDINGS: SGLT2 inhibitors have been approved for patients with type 2 diabetes mellitus, heart failure with reduced or preserved ejection fraction, atherosclerotic cardiovascular disease in the setting of type 2 diabetes mellitus, as well as chronic kidney disease with proteinuria. Large studies on SGLT2 inhibitors have largely excluded patients with proteinuric chronic kidney disease due to autoimmune glomerulonephritis due to concerns for confounding from immunosuppression. The Dapagliflozin and Prevention of Adverse Outcomes in CKD Trial (DAPA-CKD) showed that SGLT2 inhibition decreased progression of renal disease in patients with IgA nephropathy. Expanding this to other autoimmune glomerulonephropathies, several small studies have shown improvements in proteinuria in patients with lupus nephritis treated with SGLT2 inhibitors. A study evaluating safety of SGLT2 inhibitors in patients with lupus identified no specific concerns even with concomitant use of immunosuppression. SUMMARY: Small studies have shown that SGLT2 inhibitors can been utilized safely and efficaciously in patients with lupus nephritis. Additional research is needed to identify where these medications fit into the rheumatology treatment armamentarium.
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Diabetes Mellitus Tipo 2 , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Insuficiencia Renal Crónica/tratamiento farmacológico , ReumatólogosRESUMEN
BACKGROUND: Mycophenolate mofetil is an immunosuppressant commonly used to treat systemic lupus erythematosus (SLE) and lupus nephritis. It is a known teratogen associated with significant toxicities, including an increased risk of infections and malignancies. Mycophenolate mofetil withdrawal is desirable once disease quiescence is reached, but the timing of when to do so and whether it provides a benefit has not been well-studied. We aimed to determine the effects of mycophenolate mofetil withdrawal on the risk of clinically significant disease reactivation in patients with quiescent SLE on long-term mycophenolate mofetil therapy. METHODS: This multicenter, open-label, randomised trial was conducted in 19 centres in the USA. Eligible patients were aged between 18 and 70 years old, met the American College of Rheumatology (ACR) 1997 SLE criteria, and had a clinical SLEDAI score of less than 4 at screening. Mycophenolate mofetil therapy was required to be stable or decreasing for 2 years or more if initiated for renal indications, or for 1 year or more for non-renal indications. Participants were randomly allocated in a 1:1 ratio to a withdrawal group, who tapered off mycophenolate mofetil over 12 weeks, or a maintenance group who maintained their baseline dose (1-3g per day) for 60 weeks. Adaptive random allocation ensured groups were balanced for study site, renal versus non-renal disease, and baseline mycophenolate mofetil dose (≥2 g per day vs <2 g per day). Clinically significant disease reactivation by week 60 following random allocation, requiring increased doses or new immunosuppressive therapy was the primary endpoint, in the modified intention-to-treat population (all randomly allocated participants who began study-provided mycophenolate mofetil). Non-inferiority was evaluated using an estimation-based approach. The trial was registered at ClinicalTrials.gov (NCT01946880) and is completed. FINDINGS: Between Nov 6, 2013, and April 27, 2018, 123 participants were screened, of whom 102 were randomly allocated to the maintenance group (n=50) or the withdrawal group (n=52). Of the 100 participants included in the modified intention-to-treat analysis (49 maintenance, 51 withdrawal), 84 (84%) were women, 16 (16%) were men, 40 (40%) were White, 41 (41%) were Black, and 76 (76%) had a history of lupus nephritis. The average age was 42 (SD 12·7). By week 60, nine (18%) of 51 participants in the withdrawal group had clinically significant disease reactivation, compared to five (10%) of 49 participants in the maintenance group. The risk of clinically significant disease reactivation was 11% (95% CI 5-24) in the maintenance group and 18% (10-32) in the withdrawal group. The estimated increase in the risk of clinically significant disease reactivation with mycophenolate mofetil withdrawal was 7% (one-sided upper 85% confidence limit 15%). Similar rates of adverse events were observed in the maintenance group (45 [90%] of 50 participants) and the withdrawal group (46 [88%] of 52 participants). Infections were more frequent in the mycophenolate mofetil maintenance group (32 [64%]) compared with the withdrawal group (24 [46%]). INTERPRETATIONS: Mycophenolate mofetil withdrawal is not significantly inferior to mycophenolate mofetil maintenance. Estimates for the rates of disease reactivation and increases in risk with withdrawal can assist clinicians in making informed decisions on withdrawing mycophenolate mofetil in patients with stable SLE. FUNDING: The National Institute of Allergy and Infectious Diseases and the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
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Lupus Eritematoso Sistémico , Nefritis Lúpica , Masculino , Humanos , Femenino , Adulto , Adolescente , Adulto Joven , Persona de Mediana Edad , Anciano , Ácido Micofenólico/efectos adversos , Nefritis Lúpica/tratamiento farmacológico , Resultado del Tratamiento , Inmunosupresores/efectos adversos , Lupus Eritematoso Sistémico/tratamiento farmacológicoRESUMEN
BACKGROUND: Environmental factors can influence epigenetic regulation, including DNA methylation, potentially contributing to systemic lupus erythematosus (SLE) development and progression. We compared methylation of the B cell costimulatory CD70 gene, in persons with lupus and controls, and characterized associations with age. RESULTS: In 297 adults with SLE and 92 controls from the Michigan Lupus Epidemiology and Surveillance (MILES) Cohort, average CD70 methylation of CD4+ T cell DNA across 10 CpG sites based on pyrosequencing of the promoter region was higher for persons with SLE compared to controls, accounting for covariates [ß = 2.3, p = 0.011]. Using Infinium MethylationEPIC array data at 18 CD70-annoted loci (CD4+ and CD8+ T cell DNA), sites within the promoter region tended to be hypomethylated in SLE, while those within the gene region were hypermethylated. In SLE but not controls, age was significantly associated with pyrosequencing-based CD70 methylation: for every year increase in age, methylation increased by 0.14 percentage points in SLE, accounting for covariates. Also within SLE, CD70 methylation approached a significantly higher level in Black persons compared to White persons (ß = 1.8, p = 0.051). CONCLUSIONS: We describe altered CD70 methylation patterns in T lymphocyte subsets in adults with SLE relative to controls, and report associations particular to SLE between methylation of this immune-relevant gene and both age and race, possibly a consequence of "weathering" or accelerated aging which may have implications for SLE pathogenesis and potential intervention strategies.
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Epigénesis Genética , Lupus Eritematoso Sistémico , Adulto , Humanos , Linfocitos T CD4-Positivos/metabolismo , Michigan/epidemiología , Lupus Eritematoso Sistémico/epidemiología , Lupus Eritematoso Sistémico/genética , Metilación de ADN , ADN , Ligando CD27/genética , Ligando CD27/metabolismoRESUMEN
OBJECTIVES: Medication access and adherence play key roles in determining patient outcomes. We investigated whether cost-related non-adherence (CRNA) to prescription medications was associated with worse patient-reported outcomes in a population-based systemic lupus erythematosus (SLE) cohort. METHODS: Sociodemographic and prescription data were collected by structured interviews in 2014-2015 from patients meeting SLE criteria in the established Michigan Lupus Epidemiology & Surveillance (MILES) Cohort. We examined the associations between CRNA and potential confounders such as sociodemographics and health insurance coverage, and outcome measures of SLE activity and damage using multivariable linear regression. RESULTS: 462 SLE participants completed the study visit: 430 (93.1%) female, 208 (45%) Black, and mean age 53.3 years. 100 (21.6%) participants with SLE reported CRNA in the preceding 12 months. After adjusting for covariates, CRNA was associated with both higher levels of current SLE disease activity [SLAQ: ß coeff 2.7 (95% CI 1.3, 4.1), p < 0.001] and damage [LDIQ ß coeff 1.4 (95% CI 0.5, 2.4), p = 0.003]. Race, health insurance status, and fulfilling Fibromyalgia (FM) Survey Criteria were independently associated with both higher (worse) SLAQ and LDIQ scores; female sex was further associated with higher SLAQ scores. CONCLUSION: Patients with SLE who reported CRNA in the previous 12 months had significantly worse self-reported current disease activity and damage scores compared to those not reporting CRNA. Raising awareness and addressing barriers or concerns related to financial implications and accessibility issues in care plans may help to improve these outcomes.
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Lupus Eritematoso Sistémico , Humanos , Femenino , Persona de Mediana Edad , Masculino , Michigan/epidemiología , ARN Complementario/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/epidemiología , Prescripciones , Medición de Resultados Informados por el PacienteRESUMEN
PURPOSE OF REVIEW: This review seeks to summarize the literature relevant to the treatment of glucocorticoid-induced osteoporosis in premenopausal women; an issue commonly encountered by rheumatologists and yet lacking good clinical practice guidelines. RECENT FINDINGS: Although most of the relevant literature on osteoporosis includes postmenopausal women only, data from both randomized controlled trials and case reports suggest bisphosphonates can be an effective and well tolerated treatment for premenopausal patients. Data for other medications to treat premenopausal osteoporosis is less robust. SUMMARY: The use of bisphosphonates in young women may be safer than initially thought and should likely be used for the treatment of glucocorticoid-induced osteoporosis in rheumatology clinics. Further research is needed to continue to understand long-term risk.
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Glucocorticoides , Osteoporosis , Humanos , Femenino , Glucocorticoides/efectos adversos , Reumatólogos , Densidad Ósea , Osteoporosis/inducido químicamente , Osteoporosis/tratamiento farmacológico , Difosfonatos/efectos adversosRESUMEN
OBJECTIVE: Proteinase 3 (PR3) is the major antigen for antineutrophil cytoplasmic antibodies (ANCAs) in the systemic autoimmune vasculitis, granulomatosis with polyangiitis (GPA). PR3-targeting ANCAs (PR3-ANCAs) recognize different epitopes on PR3. This study was undertaken to study the effect of mutations on PR3 antigenicity. METHODS: The recombinant PR3 variants, iPR3 (clinically used to detect PR3-ANCAs) and iHm5 (containing 3 point mutations in epitopes 1 and 5 generated for epitope mapping studies) immunoassays and serum samples from patients enrolled in ANCA-associated vasculitis (AAV) trials were used to screen for differential PR3-ANCA binding. A patient-derived monoclonal ANCA 518 (moANCA518) that selectively binds to iHm5 within the mutation-free epitope 3 and is distant from the point mutations of iHm5 was used as a gauge for remote epitope activation. Selective binding was determined using inhibition experiments. RESULTS: Rather than reduced binding of PR3-ANCAs to iHm5, we found substantially increased binding of the majority of PR3-ANCAs to iHm5 compared to iPR3. This differential binding of PR3-ANCA to iHm5 is similar to the selective moANCA518 binding to iHm5. Binding of iPR3 to monoclonal antibody MCPR3-2 also induced recognition by moANCA518. CONCLUSION: The preferential binding of PR3-ANCAs from patients, such as the selective binding of moANCA518 to iHm5, is conferred by increased antigenicity of epitope 3 on iHm5. This can also be induced on iPR3 when captured by monoclonal antibody MCPR2. This previously unrecognized characteristic of PR3-ANCA interactions with its target antigen has implications for studying antibody-mediated autoimmune diseases, understanding variable performance characteristics of immunoassays, and design of potential novel treatment approaches.
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Anticuerpos Anticitoplasma de Neutrófilos , Granulomatosis con Poliangitis , Humanos , Mieloblastina/genética , Epítopos , Granulomatosis con Poliangitis/genética , Anticuerpos MonoclonalesRESUMEN
OBJECTIVES: Lupus T cells demonstrate aberrant DNA methylation patterns dominated by hypomethylation of interferon-regulated genes. The objective of this study was to identify additional lupus-associated DNA methylation changes and determine the genetic contribution to epigenetic changes characteristic of lupus. METHODS: Genome-wide DNA methylation was assessed in naïve CD4+ T cells from 74 patients with lupus and 74 age-matched, sex-matched and race-matched healthy controls. We applied a trend deviation analysis approach, comparing methylation data in our cohort with over 16 500 samples. Methylation quantitative trait loci (meQTL) analysis was performed by integrating methylation profiles with genome-wide genotyping data. RESULTS: In addition to the previously reported epigenetic signature in interferon-regulated genes, we observed hypomethylation in the promoter region of the miR-17-92 cluster in patients with lupus. Members of this microRNA cluster play an important role in regulating T cell proliferation and differentiation. Expression of two microRNAs in this cluster, miR-19b1 and miR-18a, showed a significant positive correlation with lupus disease activity. Among miR-18a target genes, TNFAIP3, which encodes a negative regulator of nuclear factor kappa B, was downregulated in lupus CD4+ T cells. MeQTL identified in lupus patients showed overlap with genetic risk loci for lupus, including CFB and IRF7. The lupus risk allele in IRF7 (rs1131665) was associated with significant IRF7 hypomethylation. However, <1% of differentially methylated CpG sites in patients with lupus were associated with an meQTL, suggesting minimal genetic contribution to lupus-associated epigenotypes. CONCLUSION: The lupus defining epigenetic signature, characterised by robust hypomethylation of interferon-regulated genes, does not appear to be determined by genetic factors. Hypomethylation of the miR-17-92 cluster that plays an important role in T cell activation is a novel epigenetic locus for lupus.
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Lupus Eritematoso Sistémico , MicroARNs , Linfocitos T , Linfocitos T CD4-Positivos/metabolismo , Metilación de ADN/genética , Epigénesis Genética/genética , Epigenómica , Humanos , Interferones/genética , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/metabolismo , MicroARNs/genética , MicroARNs/metabolismoRESUMEN
PURPOSE OF REVIEW: This review summarizes the recent literature exploring hydroxychloroquine levels and their relationship with disease activity and risk of toxicity. RECENT FINDINGS: There is no clear correlation between weight-based dosing of hydroxychloroquine and the resulting blood levels of the medication. Recent studies have shown that increased hydroxychloroquine levels are associated with lower lupus disease activity and likely also increased risk of medication toxicity. SUMMARY: Mounting evidence supports use of hydroxychloroquine levels in clinical practice to document adherence and ensure safety.
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Hidroxicloroquina , Lupus Eritematoso Sistémico , Humanos , Hidroxicloroquina/efectos adversos , Lupus Eritematoso Sistémico/inducido químicamente , Lupus Eritematoso Sistémico/tratamiento farmacológicoRESUMEN
OBJECTIVE: To estimate the annual incidence rate of SLE in the USA. METHODS: A meta-analysis used sex/race/ethnicity-specific data spanning 2002-2009 from the Centers for Disease Control and Prevention network of four population-based state registries to estimate the incidence rates. SLE was defined as fulfilling the 1997 revised American College of Rheumatology classification criteria. Given heterogeneity across sites, a random effects model was employed. Applying sex/race/ethnicity-stratified rates, including data from the Indian Health Service registry, to the 2018 US Census population generated estimates of newly diagnosed SLE cases. RESULTS: The pooled incidence rate per 100 000 person-years was 5.1 (95% CI 4.6 to 5.6), higher in females than in males (8.7 vs 1.2), and highest among black females (15.9), followed by Asian/Pacific Islander (7.6), Hispanic (6.8) and white (5.7) females. Male incidence was highest in black males (2.4), followed by Hispanic (0.9), white (0.8) and Asian/Pacific Islander (0.4) males. The American Indian/Alaska Native population had the second highest race-specific SLE estimates for females (10.4 per 100 000) and highest for males (3.8 per 100 000). In 2018, an estimated 14 263 persons (95% CI 11 563 to 17 735) were newly diagnosed with SLE in the USA. CONCLUSIONS: A network of population-based SLE registries provided estimates of SLE incidence rates and numbers diagnosed in the USA.
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Lupus Eritematoso Sistémico , Centers for Disease Control and Prevention, U.S. , Etnicidad , Femenino , Humanos , Incidencia , Lupus Eritematoso Sistémico/epidemiología , Masculino , Sistema de Registros , Estados Unidos/epidemiologíaRESUMEN
PURPOSE OF REVIEW: Although mycophenolate mofetil (MMF) has been used successfully to treat a myriad of autoimmune diseases, its complex pharmacokinetics make it difficult to determine the true drug exposure for an individual patient. This review summarizes the body of literature focused on the gold standard measurement of the area under the curve (AUC) of mycophenolic acid (MPA), the active metabolite of MMF. RECENT FINDINGS: Fixed dosing of MMF leads to highly variable drug exposure. Retrospective series have reported improved clinical outcomes when a minimum AUC value from 0 to 12âh (AUC0-12h) ≥30âmg h/l is achieved. MPA levels are affected by various drug interactions, hypoalbuminemia, and renal insufficiency and the measurement of free rather than total MPA levels is prudent in some situations. A limited number of studies employing prospective dose adjustment of MMF based on AUC0-12h measurements have yielded mixed results. SUMMARY: Given the wide range of MPA AUC encountered in autoimmune diseases, dose adjustments of MMF based on AUC rather than fixed dosing of MMF should be considered in both clinical practice and clinical trials. Limited sampling strategies have been proposed to improve clinical feasibility of measurements, but a standard is yet to be defined.
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Inmunosupresores/farmacocinética , Ácido Micofenólico/farmacocinética , Área Bajo la Curva , Enfermedades Autoinmunes/tratamiento farmacológico , Humanos , Inmunosupresores/farmacología , Inmunosupresores/uso terapéutico , Ácido Micofenólico/farmacología , Ácido Micofenólico/uso terapéuticoRESUMEN
OBJECTIVE: Epidemiologic data on systemic lupus erythematosus (SLE) are limited, particularly for racial/ethnic subpopulations in the US. This meta-analysis leveraged data from the Centers for Disease Control and Prevention (CDC) National Lupus Registry network of population-based SLE registries to estimate the overall prevalence of SLE in the US. METHODS: The CDC National Lupus Registry network includes 4 registries from unique states and a fifth registry from the Indian Health Service. All registries defined cases of SLE according to the American College of Rheumatology (ACR) 1997 revised classification criteria for SLE. Case findings spanned either 2002-2004 or 2007-2009. Given the heterogeneity across sites, a random-effects model was used to calculate the pooled prevalence of SLE. An estimate of the number of SLE cases in the US was generated by applying sex/race-stratified estimates to the 2018 US Census population. RESULTS: In total, 5,417 cases were identified as fulfilling the ACR SLE classification criteria. The pooled prevalence of SLE from the 4 state-specific registries was 72.8 per 100,000 person-years (95% confidence interval [95% CI] 65.3-81.0). The prevalence estimate was 9 times higher among females than among males (128.7 versus 14.6 per 100,000), and highest among Black females (230.9 per 100,000), followed by Hispanic females (120.7 per 100,000), White females (84.7 per 100,000), and Asian/Pacific Islander females (84.4 per 100,000). Among males, the prevalence of SLE was highest in Black males (26.7 per 100,000), followed by Hispanic males (18.0 per 100,000), Asian/Pacific Islander males (11.2 per 100,000), and White males (8.9 per 100,000). The American Indian/Alaska Native population had the highest race-specific SLE estimates, both among females (270.6 per 100,000) and among males (53.8 per 100,000). In 2018, an estimated 204,295 individuals (95% CI 160,902-261,725) in the US fulfilled the ACR classification criteria for SLE. CONCLUSION: A coordinated network of population-based SLE registries provides more accurate estimates of the prevalence of SLE and the numbers of individuals affected with SLE in the US in 2018.
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Lupus Eritematoso Sistémico/epidemiología , Negro o Afroamericano , Asiático , Centers for Disease Control and Prevention, U.S. , Hispánicos o Latinos , Humanos , Lupus Eritematoso Sistémico/etnología , Nativos de Hawái y Otras Islas del Pacífico , Prevalencia , Sistema de Registros , Distribución por Sexo , Estados Unidos/epidemiología , Población Blanca , Indio Americano o Nativo de AlaskaRESUMEN
OBJECTIVE: Medication access and adherence are important determinants of health outcomes. We investigated factors associated with access and cost-related nonadherence to prescriptions in a population-based cohort of systemic lupus erythematosus (SLE) patients and controls. METHODS: Detailed sociodemographic and prescription data were collected by structured interview in 2014-2015 from participants in the Michigan Lupus Epidemiology and Surveillance (MILES) cohort. We compared access between cases and frequency-matched controls and examined associated factors in separate multivariable logistic regression models. RESULTS: A total of 654 participants (462 SLE patients, 192 controls) completed the baseline visit; 584 (89%) were female, 285 (44%) were Black, and the mean age was 53 years. SLE patients and controls reported similar frequencies of being unable to access prescribed medications (12.1% versus 9.4%, respectively; P was not significant). SLE patients were twice as likely as controls to report cost-related prescription nonadherence in the preceding 12 months to save money (21.7% versus 10.4%; P = 0.001) but were also more likely to ask their doctor for lower cost alternatives (23.8% versus 15.6%; P = 0.02). Disparities were found in association with income, race, and health insurance status, but the main findings persisted after adjusting for these and other variables in multivariable models. CONCLUSION: SLE patients were more likely than controls from the general population to report cost-related prescription nonadherence, including skipping doses, taking less medicine, and delaying filling prescriptions; yet, <1 in 4 patients asked providers for lower cost medications. Consideration of medication costs in patient decision-making could provide a meaningful avenue for improving access and adherence to medications.
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Costos de los Medicamentos , Accesibilidad a los Servicios de Salud/economía , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/economía , Cumplimiento de la Medicación , Adulto , Anciano , Estudios de Casos y Controles , Ahorro de Costo , Sustitución de Medicamentos/economía , Femenino , Gastos en Salud , Humanos , Entrevistas como Asunto , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/epidemiología , Masculino , Michigan/epidemiología , Persona de Mediana Edad , Vigilancia de la Población , Sistema de RegistrosRESUMEN
Epigenetic dysregulation is implicated in the pathogenesis of lupus. We performed a longitudinal analysis to assess changes in DNA methylation in lupus neutrophils over 4 years of follow-up and across disease activity levels using 229 patient samples. We demonstrate that DNA methylation profiles in lupus are partly determined by ancestry-associated genetic variations and are highly stable over time. DNA methylation levels in 2 CpG sites correlated significantly with changes in lupus disease activity. Progressive demethylation in SNX18 was observed with increasing disease activity in African American patients. Importantly, demethylation of a CpG site located within GALNT18 was associated with the development of active lupus nephritis. Differentially methylated genes between African American and European American lupus patients include type I IFN-response genes such as IRF7 and IFI44, and genes related to the NF-κB pathway. TREML4, which plays a vital role in TLR signaling, was hypomethylated in African American patients and demonstrated a strong cis-methylation quantitative trait loci (cis-meQTL) effect among 8855 cis-meQTL associations identified in our study.
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Biomarcadores/análisis , Negro o Afroamericano/genética , Metilación de ADN , Epigénesis Genética , Nefritis Lúpica/patología , Sitios de Carácter Cuantitativo , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Estudio de Asociación del Genoma Completo , Humanos , Factor 7 Regulador del Interferón/genética , Estudios Longitudinales , Nefritis Lúpica/genética , Persona de Mediana Edad , Pronóstico , Receptores Inmunológicos/genética , Transducción de Señal , Nexinas de Clasificación/genética , Población Blanca/genética , Adulto JovenRESUMEN
Administration of cyclophosphamide (CYC), an alkylating agent used to treat malignancies and severe rheumatic diseases, creates a risk of ovarian insufficiency that is related to the intensity and duration of therapy and the age of the patient. To preserve reproductive capacity in the appropriate clinical setting, oocyte, embryo, and/or ovarian tissue cryopreservation are recommended. Medical protection with depot gonadotropin-releasing hormone agonists (GNRHa) has emerged as a potential means to preserve both fertility and ovarian function through the suppression of ovarian activity during treatment with alkylators. We review the trials of GNRHa for ovarian protection in both cancer and rheumatic disease patients. Trials in cancer patients receiving CYC alone, or in combination with other gonadotoxic agents that have employed several different GNRHa have yielded mixed results. Trials in lupus patients receiving lower doses of CYC alone utilizing depot leuprolide acetate have tended to show favorable results.
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Alquilantes/efectos adversos , Ciclofosfamida/efectos adversos , Hormona Liberadora de Gonadotropina/administración & dosificación , Inmunosupresores/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Insuficiencia Ovárica Primaria/prevención & control , Alquilantes/administración & dosificación , Alquilantes/uso terapéutico , Ciclofosfamida/administración & dosificación , Ciclofosfamida/uso terapéutico , Femenino , Fármacos para la Fertilidad Femenina , Humanos , Leuprolida , Lupus Eritematoso Sistémico/complicaciones , Insuficiencia Ovárica Primaria/etiologíaRESUMEN
OBJECTIVE: To examine associations between dietary intake of omega-3 (n-3; generally antiinflammatory) and omega-6 (n-6; generally proinflammatory) fatty acids and patient-reported outcomes in systemic lupus erythematosus (SLE). METHODS: This study was based on the population-based Michigan Lupus Epidemiology and Surveillance cohort. Estimates of n-3 and n-6 intake were derived from Diet History Questionnaire II items (past year with portion size version). Patient-reported outcomes included self-reported lupus activity (Systemic Lupus Activity Questionnaire [SLAQ]). Multivariable regression, adjusted for age, sex, race, and body mass index, was used to assess associations between absolute intake of n-3 and n-6, as well as the n-6:n-3 ratio, and patient-reported outcomes. RESULTS: Among 456 SLE cases, 425 (93.2%) were female, 207 (45.4%) were African American, and the mean ± SD age was 52.9 ± 12.3 years. Controlling for potential confounders, the average SLAQ score was significantly higher by 0.3 points (95% confidence interval [95% CI] 0.1, 0.6; P = 0.013) with each unit increase of the n-6:n-3 ratio. Both lupus activity and Patient-Reported Outcomes Measurement Information System (PROMIS) sleep disturbance scores were lower with each 1-gram/1,000 kcal increase of n-3 fatty acids (SLAQ regression coefficient ß = -0.8 [95% CI -1.6, 0.0]; P = 0.055; PROMIS sleep ß = -1.1 [95% CI -2.0, -0.2]; P = 0.017). Higher n-3 intakes were nonsignificantly associated with lower levels of depressive symptoms and comorbid fibromyalgia, and with higher quality of life, whereas results for the n6:n3 ratio trended in the opposite direction. CONCLUSION: This population-based study suggests that higher dietary intake of n-3 fatty acids and lower n-6:n-3 ratios are favorably associated with patient-reported outcomes in SLE, particularly self-reported lupus activity and sleep quality.
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Dieta , Ácidos Grasos Omega-3 , Ácidos Grasos Omega-6 , Lupus Eritematoso Sistémico , Adulto , Anciano , Estudios de Cohortes , Encuestas sobre Dietas , Femenino , Humanos , Masculino , Michigan , Persona de Mediana Edad , Medición de Resultados Informados por el Paciente , Calidad de VidaRESUMEN
Rheumatic diseases are a leading cause of chronic, noncancer pain. Systemic lupus erythematosus (SLE) is a chronic autoimmune rheumatic disease characterized by periodic flares that can result in irreversible target organ damage, including end-stage renal disease. Both intermittent and chronic musculoskeletal pain, as well as fibromyalgia (considered a centralized pain disorder due to dysregulation of pain processing in the central nervous system), are common in SLE. Opioids are generally not indicated for long-term management of musculoskeletal pain or centralized pain (fibromyalgia) because of lack of efficacy, safety issues ranging from adverse medical effects to overdose, and risk for addiction (1,2). In this study of 462 patients with SLE from the population-based Michigan Lupus Epidemiology and Surveillance (MILES) Cohort and 192 frequency-matched persons without SLE, nearly one third (31%) of SLE patients were using prescription opioids during the study period (2014-2015), compared with 8% of persons without SLE (p<0.001). Among the SLE patients using opioids, 97 (68%) were using them for >1 year, and 31 (22%) were concomitantly on two or more opioid medications. Among SLE patients, those using the emergency department (ED) were approximately twice as likely to use prescription opioids (odds ratio [OR] = 2.1; 95% confidence interval [CI] = 1.3-3.6; p = 0.004). In SLE, the combined contributions of underlying disease and adverse effects of immunosuppressive and glucocorticoid therapies already put patients at higher risk for some known adverse effects attributed to long-term opioid use. Addressing the widespread and long-term use of opioid therapy in SLE will require strategies aimed at preventing opioid initiation, tapering and discontinuation of opioids among patients who are not achieving treatment goals of reduced pain and increased function, and consideration of nonopioid pain management strategies.
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Analgésicos Opioides/uso terapéutico , Prescripciones de Medicamentos/estadística & datos numéricos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Vigilancia de la Población , Adulto , Anciano , Estudios de Cohortes , Servicio de Urgencia en Hospital , Femenino , Humanos , Lupus Eritematoso Sistémico/epidemiología , Masculino , Michigan/epidemiología , Persona de Mediana Edad , Manejo del Dolor/métodos , RiesgoRESUMEN
A man in his 70s with known systemic lupus erythematosus (SLE) was admitted with confusion, worsening proteinuria and cutaneous vasculitis despite adherence to his home immunosuppressive regimen. Admission laboratories were consistent with active lupus. Despite treatment with pulse-dose glucocorticoids and intravenous immunoglobulin, he developed worsening mental status and meningeal signs. Investigations revealed cerebrospinal fluid (CSF) neutrophilic and plasmacytic pleocytosis and negative cultures. Empiric treatment for SLE flare with potential neuropsychiatric involvement was continued while workup for altered mental status was ongoing. Ultimately, West Nile encephalitis was diagnosed by CSF serologies, and steroids were tapered. Altered mental status in a patient with SLE has a broad differential, and primary neuropsychiatric SLE should be considered only after exclusion of secondary causes. Although evidence of end-organ SLE activity usually lends support to a neuropsychiatric SLE diagnosis, in this case, serological and clinical evidence of SLE activity may have been triggered by acute viral infection.
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Confusión/virología , Inmunosupresores/uso terapéutico , Lupus Eritematoso Sistémico/virología , Vasculitis por Lupus del Sistema Nervioso Central/diagnóstico , Proteinuria/virología , Fiebre del Nilo Occidental/diagnóstico , Virus del Nilo Occidental/aislamiento & purificación , Anciano , Diagnóstico Diferencial , Electroencefalografía , Resultado Fatal , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/fisiopatología , Masculino , Punción Espinal , Fiebre del Nilo Occidental/fisiopatología , Fiebre del Nilo Occidental/terapiaRESUMEN
PURPOSE OF REVIEW: Medical therapies for the treatment of immune thrombocytopenia (ITP) complicating SLE are increasingly being investigated as alternatives to splenectomy and IVIG. The purpose of this review is to highlight the therapies that are utilized in the treatment of primary ITP and ITP secondary to lupus. RECENT FINDINGS: Corticosteroids are still the standard initial treatment of ITP, with the addition of IVIG when a rapid response is needed. There are few studies dedicated to assessing the efficacy of disease-modifying antirheumatic (DMARD), biologic, and nonimmunosuppressive agents as treatment for lupus thrombocytopenia/lupus ITP. Rituximab and thrombopoeitin mimetics have been the most extensively studied therapies for primary ITP in recent years. Results of trials show adequate initial responses; however, the duration of therapy and sustainability of responses are variable. Splenectomy is less often utilized. SUMMARY: Although corticosteroids, intravenous immunoglobulin and splenectomy have proven to be effective measures to treat immune thrombocytopenia, newer studies have demonstrated positive outcomes of immunosuppressives and thrombopoeitin mimetics. In most cases, the reported duration of therapy was not prolonged. More studies are needed to fully assess the effect of medical therapy in lupus ITP and to determine how long to continue maintenance therapy.
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Corticoesteroides/uso terapéutico , Antirreumáticos/uso terapéutico , Inmunoglobulinas Intravenosas/uso terapéutico , Inmunosupresores/uso terapéutico , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Humanos , Púrpura Trombocitopénica Idiopática/cirugía , Rituximab/uso terapéutico , Esplenectomía , Resultado del TratamientoRESUMEN
OBJECTIVE: To investigate the long-term safety and efficacy of intravenous (IV) belimumab plus standard of care (SOC) therapy for systemic lupus erythematosus (SLE) in patients with active, autoantibody-positive SLE. METHODS: The study was designed as a multicenter, open-label, continuation study of IV belimumab given every 4 weeks in conjunction with SOC therapy in patients with SLE who completed a phase II, double-blind study. Adverse events (AEs) and laboratory data were monitored from the first belimumab dose (in either study) until 24 weeks after the final dose. Efficacy assessments included SLE Responder Index (SRI) and flare index scores (each assessed at 16-week intervals) and glucocorticoid use (assessed at 4-week intervals). RESULTS: Of the 476 patients in the parent study, 298 (62.6%) entered the continuation study, of whom 96 (32.2%) remained in the study. Patients received belimumab for up to 13 years (median duration of exposure 3,334.0 days [range 260-4,332 days], total belimumab exposure 2,294 patient-years, median number of infusions 115.5 [range 7-155]). The percentage of patients with AEs each year remained stable or decreased. Normal serum IgG levels were maintained in the majority of patients over the study, and the rate of infections remained stable. The percentage of patients who achieved an SRI response increased from 32.8% (year 1) to 75.6% of those remaining on treatment at year 12. The glucocorticoid dose was decreased in patients who had been receiving >7.5 mg/day at baseline. CONCLUSION: This study is the longest to date to assess belimumab treatment in patients with SLE in clinical trials. Belimumab was well tolerated with no new safety concerns, and efficacy was maintained in patients who continued the study. For patients who initially exhibited a satisfactory response to belimumab, the treatment continues to be well tolerated and provides long-term disease control.