RESUMEN
BACKGROUND: Varicella-zoster virus (VZV) reactivation is the most common infectious complication in the late posthematopoietic stem cell transplantation (HSCT) period and is reported as 16%-41%. Acyclovir prophylaxis is recommended for at least 1 year after HSCT to prevent VZV infections. However, studies on the most appropriate prophylaxis are ongoing in pediatric patients. METHODS: Patients who underwent allogeneic HSCT between January 1, 1996 and January 1, 2020 were retrospectively analyzed to outline the characteristics of VZV reactivation after allogeneic HSCT in pediatric patients using 6 months acyclovir prophylaxis. RESULTS: There were 260 patients and 273 HSCTs. Median age was 10.43 (0.47-18.38), and 56% was male. Median follow-up was 2325 days (18-7579 days). VZV reactivation occurred in 21.2% (n = 58) at a median of 354 (55-3433) days post-HSCT. The peak incidence was 6-12 months post-HSCT (43.1%). Older age at HSCT, female gender, history of varicella infection, lack of varicella vaccination, low lymphocyte, CD4 count, and CD4/CD8 ratio at 9 and 12 months post-HSCT was found as a significant risk for herpes zoster (HZ) in univariate analysis, whereas history of varicella infection and low CD4/CD8 ratio at 12 months post-HSCT was an independent risk factor in multivariate analysis. CONCLUSIONS: Tailoring acyclovir prophylaxis according to pre-HCT varicella history, posttransplant CD4 T lymphocyte counts and functions, and ongoing immunosuppression may help to reduce HZ-related morbidity and mortality.
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Aciclovir , Antivirales , Trasplante de Células Madre Hematopoyéticas , Herpesvirus Humano 3 , Activación Viral , Humanos , Aciclovir/uso terapéutico , Masculino , Femenino , Niño , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Estudios Retrospectivos , Preescolar , Adolescente , Antivirales/uso terapéutico , Lactante , Activación Viral/efectos de los fármacos , Herpesvirus Humano 3/inmunología , Herpes Zóster/prevención & control , Herpes Zóster/etiología , Infección por el Virus de la Varicela-Zóster/prevención & control , Trasplante Homólogo , Factores de RiesgoRESUMEN
OBJECTIVES: This study aimed to determine the immunogenicity and the influence on disease activity of an adjuvanted recombinant varicella-zoster virus (VZV) subunit vaccine (RZV) in patients with rheumatoid arthritis (RA) treated with disease-modifying antirheumatic drugs (DMARDs). METHODS: This prospective longitudinal study enrolled 53 patients with RA (aged ≥50 years) treated with DMARDs (conventional synthetic (cs)DMARDs 20, biological (b)DMARDs 23 and targeted synthetic (ts)DMARDs 10) and 10 control individuals. The participants received two intramuscular RZV 2 months apart. VZV-specific CD4+ T cell responses (cell-mediated immunity; CMI) and IgG antibody responses (humoral immunity; HI) were assessed at 0 and 3 months after the first RZV administration using flow cytometry and enzyme immunoassay, respectively. Disease activity (Disease Activity Score 28-C reactive protein and Clinical Disease Activity Index), flares and adverse events were monitored for 6 months after the first vaccination. RESULTS: VZV-specific CMI and HI significantly increased in the three DMARDs-treated patients with RA after RZV administration compared with the corresponding prevaccination values (p<0.001-0.014), and the magnitudes and fold-increases of those responses were not significantly different among the three DMARDs-treated patients with RA. Furthermore, the vaccine response rates of CMI and HI were not significantly different between csDMARDs-treated patients and b-DMARDs or ts-DMARDs-treated patients. Meanwhile, no significant increases in disease activity indices or adverse events were observed in these patients during the 6-month follow-up period after the first vaccination. RZV-induced RA flares occurred in two patients (3.8%) but were mild and controllable. CONCLUSION: RZV is robustly immunogenic and has a clinically acceptable safety profile in elderly patients with RA receiving DMARDs.
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Antirreumáticos , Artritis Reumatoide , Vacuna contra el Herpes Zóster , Herpes Zóster , Anciano , Humanos , Vacuna contra el Herpes Zóster/efectos adversos , Estudios Prospectivos , Estudios Longitudinales , Herpes Zóster/epidemiología , Herpes Zóster/etiología , Herpes Zóster/prevención & control , Antirreumáticos/efectos adversos , Herpesvirus Humano 3 , Vacunas Sintéticas/efectos adversosRESUMEN
Herpes zoster (HZ) refers to the rash appearing on dermatomes due to varicella zoster virus (VZV) reactivation. The incidence of HZ is significantly higher in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients than in non-HSCT recipients. Although acyclovir prophylaxis is routinely administered to every allo-HSCT recipient for 1 year after transplantation, some individuals eventually develop late-onset HZ after completing prophylaxis. Little information is known about the clinical features of HZ after prophylactic antiviral treatment discontinuation, and an effective predictive model of late-onset HZ needs to be established. A total of 3366 patients who had received allo-HSCT from 2012 to 2017 were included in our study, among whom 201 developed HZ after 1 year (late-onset HZ). We designed a nested case-control study to identify potential predictors of late-onset HZ. Finally, we established a predictive model using binary logistic regression analysis. Age (p < .001), use of immunosuppressants at +1 year (p < .001), CD4-CD8 ratio at +1 year (p < .001), certain mental disorders (depression, anxiety, insomnia and adjustment disorder) (p < .001), engraftment time of neutrophils (p < .001), and CD8+ cell count at +30 days (p < .001) were independent predictors of late-onset HZ. A risk grading system was established based on regression coefficients. Discrimination and calibration analysis indicated that the model had good performance. We also identified several predictive factors of the incidence of HZ-related complications. This is the first scoring system for predicting the incidence of late-onset HZ after allo-HSCT. This model can be applied to identify individuals at high risk of late-onset HZ in the early period after receiving allo-HSCT.
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Trasplante de Células Madre Hematopoyéticas , Herpes Zóster , Humanos , Herpesvirus Humano 3 , Antivirales/uso terapéutico , Estudios de Casos y Controles , Trasplante Homólogo/efectos adversos , Herpes Zóster/epidemiología , Herpes Zóster/etiología , Herpes Zóster/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Estudios RetrospectivosRESUMEN
BACKGROUND AND AIMS: Older patients with ulcerative colitis treated with tofacitinib are at risk for major cardiovascular events, thromboembolism, herpes zoster, and malignancies and, accordingly, its use is limited by the regulatory authorities. The aim of the present study was to evaluate the occurrence of adverse events and potential preventive measures. METHODS: We retrospectively evaluated patients treated with tofacitinib, divided into two groups according to comorbidities and age. Patient- and disease-related variables were recorded [primary non-response, loss of response, and persistence], together with deviations from the recommended induction regimen, ie, dose reduction, and concomitant treatments with anti-thrombotic therapy. RESULTS: The age-adjusted Charlson comorbidity index of Group 1 [nâ =â 30] wasâ ≥2 and that of Group 2 [nâ =â 37] was ≤â 1. No differences were observed for primary or secondary treatment failures. Both groups achieved comparable steroid-free remission rates at 12 months [53% and 46%, respectively]. Herpes zoster occurred in two patients per group, and no more cases occurred after strict recombinant zoster vaccination. No major cardiovascular event or thromboembolism was registered. Half of patients in Group 1 were treated with a reduced induction dose of 5 mg twice daily and 47% were on concomitant anti-thrombotic therapy. Malignancies were registered in two patients from Group 1 and one patient from Group 2. CONCLUSIONS: Modulation of induction dose and anti-thrombotic therapy may have contributed to prevent cardiological events and thromboembolism. The introduction of zoster vaccine virtually eliminated zoster risk after the first cases. Potential malignancies deserve a careful work-up of older patients before treatment start.
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Colitis Ulcerosa , Herpes Zóster , Neoplasias , Piperidinas , Pirimidinas , Tromboembolia , Humanos , Anciano , Colitis Ulcerosa/tratamiento farmacológico , Estudios Retrospectivos , Tromboembolia/epidemiología , Tromboembolia/etiología , Tromboembolia/prevención & control , Herpes Zóster/epidemiología , Herpes Zóster/etiología , Herpes Zóster/prevención & controlRESUMEN
After primary infection, Varicella Zoster (VZV) persists in sensory dorsal root ganglia and may be reactivated in periods of diminished T-cell immunity. Varicella Zoster reactivation post allogenic stem cell transplantation (HSCT) can be challenging to diagnose as it does not always present with characteristic skin lesions. We describe a pediatric patient who presented with isolated severe abdominal pain with no other symptoms. Cutaneous lesions appeared only 10 days later resulting in delayed diagnosis and treatment. He was successfully treated with intravenous acyclovir and recovered after a prolonged hospital stay with post-herpetic neuralgia. Abdominal pain in children post HSCT has a broad differential and VZV reactivation should be considered even in absence of cutaneous lesions. Early diagnosis and treatment are essential to reduce VZV-related morbidity and mortality. In this article we present a case report and review clinical presentation and outcome of similar cases in the literature.
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Varicela , Trasplante de Células Madre Hematopoyéticas , Herpes Zóster , Humanos , Niño , Herpes Zóster/diagnóstico , Herpes Zóster/tratamiento farmacológico , Herpes Zóster/etiología , Herpesvirus Humano 3/fisiología , Activación Viral , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Dolor Abdominal/complicaciones , Trasplante de Células Madre/efectos adversosRESUMEN
BACKGROUND: Herpes zoster (HZ) is the clinical syndrome associated with reactivation of latent varicella-zoster virus (VZV). Several factors have been implicated to promote VZV reactivation; these include immunosuppression, older age, mechanical trauma, physiologic stress, lymphopenia, and more recently, infection with severe acute respiratory syndrome coronavirus-2 (SARS- CoV-2). Recent reports suggest an increase in the number of HZ cases in the general population during the global COVID-19 pandemic. However, it is unknown what proportion of HZ during the pandemic is due to reactivation of wild-type or vaccine-strain VZV. CASE: Here we report the first known case of HZ concomitant with SARS-CoV2 infection in a 20-month-old female who was treated with a single dose of dexamethasone, due to reactivation of the vaccine-type strain of VZV after presenting with a worsening vesicular rash. CONCLUSION: In this case, we were able to show vaccine-strain VZV reactivation in the context of a mild acute symptomatic COVID-19 infection in a toddler. Being able to recognize HZ quickly and effectively in a pediatric patient can help stave off the significant morbidity and mortality associated with disease process.
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COVID-19 , Vacuna contra la Varicela , Herpes Zóster , Femenino , Humanos , Lactante , COVID-19/complicaciones , COVID-19/virología , Herpes Zóster/diagnóstico , Herpes Zóster/tratamiento farmacológico , Herpes Zóster/etiología , Herpes Zóster/virología , Herpesvirus Humano 3 , Pandemias , ARN Viral , SARS-CoV-2 , Vacunas Virales/efectos adversos , Vacuna contra la Varicela/efectos adversosRESUMEN
BACKGROUND: Mirikizumab, a p19-directed antibody against interleukin-23, showed efficacy in the treatment of ulcerative colitis in a phase 2 trial. METHODS: We conducted two phase 3, randomized, double-blind, placebo-controlled trials of mirikizumab in adults with moderately to severely active ulcerative colitis. In the induction trial, patients were randomly assigned in a 3:1 ratio to receive mirikizumab (300 mg) or placebo, administered intravenously, every 4 weeks for 12 weeks. In the maintenance trial, patients with a response to mirikizumab induction therapy were randomly assigned in a 2:1 ratio to receive mirikizumab (200 mg) or placebo, administered subcutaneously, every 4 weeks for 40 weeks. The primary end points were clinical remission at week 12 in the induction trial and at week 40 (at 52 weeks overall) in the maintenance trial. Major secondary end points included clinical response, endoscopic remission, and improvement in bowel-movement urgency. Patients who did not have a response in the induction trial were allowed to receive open-label mirikizumab during the first 12 weeks of the maintenance trial as extended induction. Safety was also assessed. RESULTS: A total of 1281 patients underwent randomization in the induction trial, and 544 patients with a response to mirikizumab underwent randomization again in the maintenance trial. Significantly higher percentages of patients in the mirikizumab group than in the placebo group had clinical remission at week 12 of the induction trial (24.2% vs. 13.3%, P<0.001) and at week 40 of the maintenance trial (49.9% vs. 25.1%, P<0.001). The criteria for all the major secondary end points were met in both trials. Adverse events of nasopharyngitis and arthralgia were reported more frequently with mirikizumab than with placebo. Among the 1217 patients treated with mirikizumab during the controlled and uncontrolled periods (including the open-label extension and maintenance periods) in the two trials, 15 had an opportunistic infection (including 6 with herpes zoster infection) and 8 had cancer (including 3 with colorectal cancer). Among the patients who received placebo in the induction trial, 1 had herpes zoster infection and none had cancer. CONCLUSIONS: Mirikizumab was more effective than placebo in inducing and maintaining clinical remission in patients with moderately to severely active ulcerative colitis. Opportunistic infection or cancer occurred in a small number of patients treated with mirikizumab. (Funded by Eli Lilly; LUCENT-1 and LUCENT-2 ClinicalTrials.gov numbers, NCT03518086 and NCT03524092, respectively.).
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Antiinflamatorios no Esteroideos , Colitis Ulcerosa , Adulto , Humanos , Colitis Ulcerosa/tratamiento farmacológico , Método Doble Ciego , Herpes Zóster/inducido químicamente , Herpes Zóster/etiología , Quimioterapia de Inducción/efectos adversos , Quimioterapia de Inducción/métodos , Quimioterapia de Mantención/efectos adversos , Quimioterapia de Mantención/métodos , Infecciones Oportunistas/inducido químicamente , Infecciones Oportunistas/etiología , Inducción de Remisión , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/efectos adversos , Antiinflamatorios no Esteroideos/inmunología , Antiinflamatorios no Esteroideos/uso terapéutico , Administración Intravenosa , Absorción SubcutáneaRESUMEN
INTRODUCTION: Herpes zoster (HZ) is caused by endogenous reactivation of latent varicella-zoster virus (VZV) that persists in sensory ganglia after primary infection. The incidence and severity of HZ increase during immunosuppression. Especially, immunocompromised patients are at high risk of developing a cutaneous rash and suffering from delayed healing of lesions. Bromovinyl deoxyuridine (brivudine), one of the most potent oral inhibitors of VZV replication, is widely used in the therapy of HZ in adult patients, particularly in Europe. In this study, we investigated the efficacy of brivudine in immunocompromised children to provide an outpatient treatment option. METHODS: In this retrospective study, we included 64 immunocompromised pediatric patients with a median age of 14 years. Forty-seven patients received immunosuppressive therapy as part of hematopoietic stem cell transplantation and 17 patients as part of chemotherapy. Primary diagnosis was made clinically by examining the nature and the localization of the skin lesions. Laboratory confirmation was conducted based on the detection of VZV DNA in vesicle fluid and blood samples. Brivudine was administered orally at a single dose of 2 mg/kg per day. We monitored the patients' response for the full time of treatment and observed the time of full crusting of lesions, loss of crusts, and any adverse effects that occurred. RESULTS: Patients received medication for 7-21 days (median: 14 days). All children responded promptly to antiviral treatment and recovered completely from their HZ infections without complications. Crusting of lesions was reached after 3-14 days (median: 6 days). Full healing of skin lesions was ascertained within 7-21 days (median: 12 days). Overall, brivudine therapy was well tolerated. No clinical side effects during or after the treatment were observed. High compliance was achieved due to the once-daily dosing regimen. All patients were treated in an outpatient manner. CONCLUSION: Oral brivudine was a very effective and well-tolerated therapy in immunocompromised children with HZ infection. The oral administration offers the potential for outpatient treatment of HZ in these patients.
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Herpes Zóster , Herpesvirus Humano 3 , Adulto , Humanos , Niño , Adolescente , Herpesvirus Humano 3/fisiología , Estudios Retrospectivos , Herpes Zóster/etiología , Herpes Zóster/complicaciones , Huésped InmunocomprometidoRESUMEN
BACKGROUND: Upadacitinib, an oral selective Janus kinase (JAK) inhibitor, is under investigation for the treatment of Crohn's disease. METHODS: In two phase 3 induction trials (U-EXCEL and U-EXCEED), we randomly assigned patients with moderate-to-severe Crohn's disease to receive 45 mg of upadacitinib or placebo (2:1 ratio) once daily for 12 weeks. Patients who had a clinical response to upadacitinib induction therapy were randomly assigned in the U-ENDURE maintenance trial to receive 15 mg of upadacitinib, 30 mg of upadacitinib, or placebo (1:1:1 ratio) once daily for 52 weeks. The primary end points for induction (week 12) and maintenance (week 52) were clinical remission (defined as a Crohn's Disease Activity Index score of <150 [range, 0 to 600, with higher scores indicating more severe disease activity]) and endoscopic response (defined as a decrease in the Simple Endoscopic Score for Crohn's Disease [SES-CD; range, 0 to 56, with higher scores indicating more severe disease] of >50% from baseline of the induction trial [or for patients with an SES-CD of 4 at baseline, a decrease of ≥2 points from baseline]). RESULTS: A total of 526 patients underwent randomization in U-EXCEL, 495 in U-EXCEED, and 502 in U-ENDURE. A significantly higher percentage of patients who received 45-mg upadacitinib than those who received placebo had clinical remission (in U-EXCEL, 49.5% vs. 29.1%; in U-EXCEED, 38.9% vs. 21.1%) and an endoscopic response (in U-EXCEL, 45.5% vs. 13.1%; in U-EXCEED, 34.6% vs. 3.5%) (P<0.001 for all comparisons). At week 52 in U-ENDURE, a higher percentage of patients had clinical remission with 15-mg upadacitinib (37.3%) or 30-mg upadacitinib (47.6%) than with placebo (15.1%), and a higher percentage had an endoscopic response with 15-mg upadacitinib (27.6%) or 30-mg upadacitinib (40.1%) than with placebo (7.3%) (P<0.001 for all comparisons). Herpes zoster infections occurred more frequently in the 45-mg and 30-mg upadacitinib groups than in the respective placebo groups, and hepatic disorders and neutropenia were more frequent in the 30-mg upadacitinib group than in the other maintenance groups. Gastrointestinal perforations developed in 4 patients who received 45-mg upadacitinib and in 1 patient each who received 30-mg or 15-mg upadacitinib. CONCLUSIONS: Upadacitinib induction and maintenance treatment was superior to placebo in patients with moderate-to-severe Crohn's disease. (Funded by AbbVie; U-EXCEL, U-EXCEED, and U-ENDURE ClinicalTrials.gov numbers, NCT03345849, NCT03345836, and NCT03345823.).
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Enfermedad de Crohn , Inhibidores de las Cinasas Janus , Humanos , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/tratamiento farmacológico , Herpes Zóster/inducido químicamente , Herpes Zóster/etiología , Compuestos Heterocíclicos con 3 Anillos/administración & dosificación , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Inhibidores de las Cinasas Janus/administración & dosificación , Inhibidores de las Cinasas Janus/efectos adversos , Inhibidores de las Cinasas Janus/uso terapéutico , Neutropenia/inducido químicamente , Neutropenia/etiología , Quimioterapia de Inducción/efectos adversos , Quimioterapia de Inducción/métodos , Quimioterapia de Mantención/efectos adversos , Quimioterapia de Mantención/métodosRESUMEN
Background: In the wake of the emerging development of biologics in atopic dermatitis (AD), herpes zoster (HZ) infection has been reported as a treatment-related adverse event. Objectives: This study aims at investigating the association between AD and HZ, and the risk factors within. Methods: 28,677 participants with AD from the Taiwan National Health Insurance Research Database 2000-2015 were enrolled. Risk of HZ infection was compared in the study cohort (with AD) and the control cohort (without AD). Further analyses were conducted in gender-, age-, and treatment strategy-stratified subgroups. Results: Significantly higher adjusted hazard ratios (aHRs) of HZ infection were revealed in AD patients (aHR = 2.303, P < 0.001), and remained this trend in gender- and age-stratified models. All AD groups, irrespective of the treatment type, had higher aHRs (AD without systemic treatment: aHR = 2.356, P < 0.001; AD with systemic treatment: aHR = 2.182, P < 0.001) compared with those without AD. However, no differences in HZ risk were shown between each treatment type. Conclusions: Risk of HZ infection in AD is higher irrespective of treatment type. Considering that AD per se increases susceptibility to HZ infection, the administration of biologics requires careful considerations.
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Productos Biológicos , Dermatitis Atópica , Herpes Zóster , Humanos , Estudios de Cohortes , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/epidemiología , Dermatitis Atópica/complicaciones , Estudios Retrospectivos , Incidencia , Herpes Zóster/epidemiología , Herpes Zóster/etiología , Factores de RiesgoRESUMEN
BACKGROUND Herpes zoster is a condition in which there is reactivation of varicella zoster virus (VZV), which is usually seen in the elderly and those with immunocompromised states. Recently, however, there have been many reports of herpes zoster after administration of COVID-19 vaccines, although initial trials showed that these vaccines have good safety and immunogenicity profiles. At the time of writing, about 5 billion people worldwide had received their full course of COVID-19 vaccination. This case report describes an elderly man who developed herpes zoster after receiving a booster dose of the Pfizer-BioNTech (BNT162b2) vaccine, with no adverse effects after the first and second dose. CASE REPORT An 82-year-old man with underlying type 2 diabetes mellitus, hypertension, dyslipidemia, and cerebrovascular disease presented with left-sided chest and upper back pain. The pain was intermittent, burning in nature, and disturbed his sleep. A week prior to his presentation, he received a COVID-19 vaccine (BNT162b2) booster dose. Examination revealed multiple vesicles along his anterior and posterior T3 dermatome. He was diagnosed with herpes zoster and treated with a course of oral acyclovir. Upon review 7 days later, he had recovered well, with resolution of his vesicles and pain. CONCLUSIONS COVID-19 vaccination remains an important measure to prevent transmission of infection and to reduce the mortality and morbidity caused by it. However, healthcare practitioners should be aware of the possible association between COVID-19 vaccination and herpes zoster. Appropriate explanation and safety advice on the possible adverse events following COVID-19 vaccination, including herpes zoster infection, should be given to patients. This will facilitate early recognition and treatment of this condition.
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COVID-19 , Diabetes Mellitus Tipo 2 , Herpes Zóster , Masculino , Humanos , Anciano , Anciano de 80 o más Años , Vacunas contra la COVID-19/efectos adversos , Herpesvirus Humano 3 , Vacuna BNT162 , COVID-19/prevención & control , COVID-19/etiología , Herpes Zóster/etiología , Vacunación/efectos adversos , Dolor/etiología , Vesícula/etiologíaRESUMEN
Tree-based scan statistics have been successfully used to study the safety of several vaccines without prespecifying health outcomes of concern. In this study, the binomial tree-based scan statistic was applied sequentially to detect adverse events in days 1-28 compared with days 29-56 after recombinant herpes zoster (RZV) vaccination, with 5 looks at the data and formal adjustment for the repeated analyses over time. IBM MarketScan data on commercially insured persons ≥50 years of age receiving RZV during January 1, 2018, to May 5, 2020, were used. With 999,876 doses of RZV included, statistically significant signals were detected only for unspecified adverse effects/complications following immunization, with attributable risks as low as 2 excess cases per 100,000 vaccinations. Ninety percent of cases in the signals occurred in the week after vaccination and, based on previous studies, likely represent nonserious events like fever, fatigue, and headache. Strengths of our study include its untargeted nature, self-controlled design, and formal adjustment for repeated testing. Although the method requires prespecification of the risk window of interest and may miss some true signals detectable using the tree-temporal variant of the method, it allows for early detection of potential safety problems through early initiation of ongoing monitoring.
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Vacuna contra el Herpes Zóster , Herpes Zóster , Humanos , Vacuna contra el Herpes Zóster/efectos adversos , Herpes Zóster/epidemiología , Herpes Zóster/prevención & control , Herpes Zóster/etiología , Herpesvirus Humano 3 , Vacunación/efectos adversos , Minería de Datos/métodosRESUMEN
OBJECTIVES: We compared the incidences of four opportunistic infections (OIs) in patients with rheumatoid arthritis (RA) treated with molecular-targeted drugs from big claims data. MATERIALS AND METHODS: We identified 205,906 patients with RA who were prescribed molecular-targeted drugs in 2010-17 from the National Database of Japan and calculated the incidence of four OIs (Pneumocystis pneumonia, tuberculosis, nontuberculous mycobacterial infection, and herpes zoster). RESULTS: The total number of Pneumocystis pneumonia, tuberculosis, nontuberculous mycobacterial infection, and herpes zoster patients with biological disease-modifying antirheumatic drugs or tofacitinib treatment history in RA was 765, 1158, 834, and 18,336, respectively. The incidence rates of each OI for all biological disease-modifying antirheumatic drugs were 0.14, 0.14, 0.09, and 2.40 per 100 person-years, respectively, while for tofacitinib they were 0.22, 0.22, 0.07, and 7.00 per 100 person-years. No big difference was observed among biological disease-modifying antirheumatic drugs. All OIs showed higher incidence in those >65 years, but Pneumocystis pneumonia, nontuberculous mycobacterial infection, and herpes zoster showed no difference between those 65-74 years old and those >75 years old. The median of occurrence was the third, seventh, ninth, and thirteenth month after treatment, respectively. CONCLUSIONS: We counted real incidence rates of OIs for the whole nation from big claims data.
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Antirreumáticos , Artritis Reumatoide , Herpes Zóster , Infecciones Oportunistas , Neumonía por Pneumocystis , Tuberculosis , Humanos , Anciano , Incidencia , Estudios Retrospectivos , Neumonía por Pneumocystis/tratamiento farmacológico , Artritis Reumatoide/tratamiento farmacológico , Infecciones Oportunistas/epidemiología , Tuberculosis/complicaciones , Tuberculosis/tratamiento farmacológico , Tuberculosis/epidemiología , Herpes Zóster/etiología , Antirreumáticos/uso terapéuticoRESUMEN
BACKGROUND: Varicella-zoster virus (VZV) reactivation is a serious complication of hematopoietic stem cell transplantation (HSCT). Although low-dose acyclovir can prevent VZV reactivation after HSCT in adults, the efficacy of a dose of acyclovir lower than the recommended dose, such as 60-80 mg/kg/day in children, is unclear. In this study, we aimed to evaluate the incidence of VZV reactivation after HSCT during and after low-dose acyclovir administration for preventing VZV reactivation in children. METHODS: This single-center retrospective study included children aged ≤15 years who received oral acyclovir (at 15 mg/kg/day) to prevent VZV reactivation after HSCT. We examined the cumulative incidence of VZV reactivation after HSCT, during and after prophylactic acyclovir administration. RESULTS: Fifty-three eligible patients were included in this study, of whom 37 underwent allogeneic HSCT. The median duration of prophylactic acyclovir therapy was 264 days (range: 69-1140 days). VZV reactivation occurred in 13 patients (24.5%, 95% confidence interval [CI]: 14.9-37.6). The cumulative incidence of VZV reactivation 1 and 2 years after HSCT was 6.26% (95% CI: 1.60-15.5) and 20.9% (95% CI: 10.3-34.0), respectively. While only one patient developed VZV reactivation during the administration of prophylactic acyclovir, the cumulative incidence of VZV reactivation increased to 24.2% (95% CI: 12.5-38.0) 1 year after the cessation of acyclovir. CONCLUSION: Low-dose acyclovir (15 mg/kg/day) could be effective for preventing VZV reactivation after HSCT in children because VZV reactivation seldom occurs during the administration of 15 mg/kg/day acyclovir.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Herpes Zóster , Adulto , Niño , Humanos , Aciclovir/farmacología , Aciclovir/uso terapéutico , Herpesvirus Humano 3/fisiología , Estudios Retrospectivos , Herpes Zóster/etiología , Herpes Zóster/prevención & control , Herpes Zóster/tratamiento farmacológico , Trasplante Homólogo/efectos adversos , Activación Viral , Antivirales/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/efectos adversosRESUMEN
BACKGROUND: Blood dendritic cell antigen 2 (BDCA2) is a receptor that is exclusively expressed on plasmacytoid dendritic cells, which are implicated in the pathogenesis of lupus erythematosus. Whether treatment with litifilimab, a humanized monoclonal antibody against BDCA2, would be efficacious in reducing disease activity in patients with cutaneous lupus erythematosus has not been extensively studied. METHODS: In this phase 2 trial, we randomly assigned adults with histologically confirmed cutaneous lupus erythematosus with or without systemic manifestations in a 1:1:1:1 ratio to receive subcutaneous litifilimab (at a dose of 50, 150, or 450 mg) or placebo at weeks 0, 2, 4, 8, and 12. We used a dose-response model to assess whether there was a response across the four groups on the basis of the primary end point, which was the percent change from baseline to 16 weeks in the Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity score (CLASI-A; scores range from 0 to 70, with higher scores indicating more widespread or severe skin involvement). Safety was also assessed. RESULTS: A total of 132 participants were enrolled; 26 were assigned to the 50-mg litifilimab group, 25 to the 150-mg litifilimab group, 48 to the 450-mg litifilimab group, and 33 to the placebo group. Mean CLASI-A scores for the groups at baseline were 15.2, 18.4, 16.5, and 16.5, respectively. The difference from placebo in the change from baseline in CLASI-A score at week 16 was -24.3 percentage points (95% confidence interval [CI] -43.7 to -4.9) in the 50-mg litifilimab group, -33.4 percentage points (95% CI, -52.7 to -14.1) in the 150-mg group, and -28.0 percentage points (95% CI, -44.6 to -11.4) in the 450-mg group. The least squares mean changes were used in the primary analysis of a best-fitting dose-response model across the three drug-dose levels and placebo, which showed a significant effect. Most of the secondary end points did not support the results of the primary analysis. Litifilimab was associated with three cases each of hypersensitivity and oral herpes infection and one case of herpes zoster infection. One case of herpes zoster meningitis occurred 4 months after the participant received the last dose of litifilimab. CONCLUSIONS: In a phase 2 trial involving participants with cutaneous lupus erythematosus, treatment with litifilimab was superior to placebo with regard to a measure of skin disease activity over a period of 16 weeks. Larger and longer trials are needed to determine the effect and safety of litifilimab for the treatment of cutaneous lupus erythematosus. (Funded by Biogen; LILAC ClinicalTrials.gov number, NCT02847598.).
Asunto(s)
Anticuerpos Monoclonales Humanizados , Lectinas Tipo C , Lupus Eritematoso Cutáneo , Glicoproteínas de Membrana , Receptores Inmunológicos , Adulto , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Células Dendríticas/efectos de los fármacos , Células Dendríticas/inmunología , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Herpes Zóster/etiología , Humanos , Lectinas Tipo C/antagonistas & inhibidores , Lectinas Tipo C/inmunología , Lupus Eritematoso Cutáneo/tratamiento farmacológico , Glicoproteínas de Membrana/antagonistas & inhibidores , Glicoproteínas de Membrana/inmunología , Receptores Inmunológicos/antagonistas & inhibidores , Receptores Inmunológicos/inmunología , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
BACKGROUND: Herpes zoster (HZ) is a frequent complication after autologous stem cell transplantation (ASCT). The option of zoster prophylaxis with an antiviral drug is described in the literature, but there is no consensus on the drug and the dosage. PATIENTS AND METHODS: We analyzed the records of 310 patients treated with ASCT who were controlled regularly regarding HZ inter alia for at least 24 months following ASCT. Since 01/2015 patients received prophylactic low-dose acyclovir (400 mg per day) during the first 12 months following discharge after ASCT (n = 107). RESULTS: Twenty percent of patients without this kind of prophylaxis and 2.8% of patients with prophylaxis developed HZ (p < .001). No patient with this prophylaxis developed HZ in the first year after ASCT, 2.8% of patients in the second year after ASCT. A prognostic factor was the kind of diagnosis: 30% of lymphoma patients and 14% of myeloma patients developed HZ in the first 24 months after ASCT without prophylaxis, but only 6.3% and 0% of patients with prophylaxis, respectively. Neither an increase of HZ cases following prophylaxis nor acyclovir refractory HZ cases were observed. CONCLUSIONS: Zoster prophylaxis with low-dose acyclovir over 12 months after ASCT is effective and well tolerated.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Herpes Zóster , Linfoma , Mieloma Múltiple , Aciclovir/efectos adversos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Herpes Zóster/diagnóstico , Herpes Zóster/etiología , Herpes Zóster/prevención & control , Herpesvirus Humano 3 , Humanos , Linfoma/complicaciones , Linfoma/diagnóstico , Linfoma/terapia , Mieloma Múltiple/complicaciones , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/terapia , Estudios Retrospectivos , Trasplante de Células Madre/efectos adversos , Trasplante Autólogo/efectos adversosRESUMEN
Not available.