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1.
RMD Open ; 10(1)2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38388170

RESUMO

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.


Assuntos
Antirreumáticos , Artrite Reumatoide , Vacina contra Herpes Zoster , Herpes Zoster , Idoso , Humanos , Vacina contra Herpes Zoster/efeitos adversos , Estudos Prospectivos , Estudos Longitudinais , Herpes Zoster/epidemiologia , Herpes Zoster/etiologia , Herpes Zoster/prevenção & controle , Antirreumáticos/efeitos adversos , Herpesvirus Humano 3 , Vacinas Sintéticas/efeitos adversos
2.
J Crohns Colitis ; 18(3): 488-491, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37702408

RESUMO

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 [n = 30] was ≥2 and that of Group 2 [n = 37] was ≤ 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.


Assuntos
Colite Ulcerativa , Herpes Zoster , Neoplasias , Piperidinas , Pirimidinas , Tromboembolia , Humanos , Idoso , Colite Ulcerativa/tratamento farmacológico , Estudos Retrospectivos , Tromboembolia/epidemiologia , Tromboembolia/etiologia , Tromboembolia/prevenção & controle , Herpes Zoster/epidemiologia , Herpes Zoster/etiologia , Herpes Zoster/prevenção & controle
3.
BMC Infect Dis ; 23(1): 854, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38057696

RESUMO

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.


Assuntos
COVID-19 , Vacina contra Varicela , Herpes Zoster , Feminino , Humanos , Lactente , COVID-19/complicações , COVID-19/virologia , Herpes Zoster/diagnóstico , Herpes Zoster/tratamento farmacológico , Herpes Zoster/etiologia , Herpes Zoster/virologia , Herpesvirus Humano 3 , Pandemias , RNA Viral , SARS-CoV-2 , Vacinas Virais/efeitos adversos , Vacina contra Varicela/efeitos adversos
5.
N Engl J Med ; 388(26): 2444-2455, 2023 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-37379135

RESUMO

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.).


Assuntos
Anti-Inflamatórios não Esteroides , Colite Ulcerativa , Adulto , Humanos , Colite Ulcerativa/tratamento farmacológico , Método Duplo-Cego , Herpes Zoster/induzido quimicamente , Herpes Zoster/etiologia , Quimioterapia de Indução/efeitos adversos , Quimioterapia de Indução/métodos , Quimioterapia de Manutenção/efeitos adversos , Quimioterapia de Manutenção/métodos , Infecções Oportunistas/induzido quimicamente , Infecções Oportunistas/etiologia , Indução de Remissão , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/imunologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Administração Intravenosa , Absorção Subcutânea
6.
N Engl J Med ; 388(21): 1966-1980, 2023 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-37224198

RESUMO

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.).


Assuntos
Doença de Crohn , Inibidores de Janus Quinases , Humanos , Doença de Crohn/complicações , Doença de Crohn/tratamento farmacológico , Herpes Zoster/induzido quimicamente , Herpes Zoster/etiologia , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Inibidores de Janus Quinases/administração & dosagem , Inibidores de Janus Quinases/efeitos adversos , Inibidores de Janus Quinases/uso terapêutico , Neutropenia/induzido quimicamente , Neutropenia/etiologia , Quimioterapia de Indução/efeitos adversos , Quimioterapia de Indução/métodos , Quimioterapia de Manutenção/efeitos adversos , Quimioterapia de Manutenção/métodos
7.
Chemotherapy ; 68(4): 222-227, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37231819

RESUMO

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.


Assuntos
Herpes Zoster , Herpesvirus Humano 3 , Adulto , Humanos , Criança , Adolescente , Herpesvirus Humano 3/fisiologia , Estudos Retrospectivos , Herpes Zoster/etiologia , Herpes Zoster/complicações , Hospedeiro Imunocomprometido
8.
Dermatitis ; 34(3): 241-249, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37074679

RESUMO

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.


Assuntos
Produtos Biológicos , Dermatite Atópica , Herpes Zoster , Humanos , Estudos de Coortes , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/epidemiologia , Dermatite Atópica/complicações , Estudos Retrospectivos , Incidência , Herpes Zoster/epidemiologia , Herpes Zoster/etiologia , Fatores de Risco
9.
Am J Case Rep ; 24: e938667, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36650730

RESUMO

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.


Assuntos
COVID-19 , Diabetes Mellitus Tipo 2 , Herpes Zoster , Masculino , Humanos , Idoso , Idoso de 80 Anos ou mais , Vacinas contra COVID-19/efeitos adversos , Herpesvirus Humano 3 , Vacina BNT162 , COVID-19/prevenção & controle , COVID-19/etiologia , Herpes Zoster/etiologia , Vacinação/efeitos adversos , Dor/etiologia , Vesícula/etiologia
11.
Mod Rheumatol ; 33(6): 1078-1086, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36308397

RESUMO

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.


Assuntos
Antirreumáticos , Artrite Reumatoide , Herpes Zoster , Infecções Oportunistas , Pneumonia por Pneumocystis , Tuberculose , Humanos , Idoso , Incidência , Estudos Retrospectivos , Pneumonia por Pneumocystis/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Infecções Oportunistas/epidemiologia , Tuberculose/complicações , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia , Herpes Zoster/etiologia , Antirreumáticos/uso terapêutico
12.
Am J Epidemiol ; 192(2): 276-282, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36227263

RESUMO

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.


Assuntos
Vacina contra Herpes Zoster , Herpes Zoster , Humanos , Vacina contra Herpes Zoster/efeitos adversos , Herpes Zoster/epidemiologia , Herpes Zoster/prevenção & controle , Herpes Zoster/etiologia , Herpesvirus Humano 3 , Vacinação/efeitos adversos , Mineração de Dados/métodos
14.
Pediatr Blood Cancer ; 69(12): e29979, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36151963

RESUMO

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.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Herpes Zoster , Adulto , Criança , Humanos , Aciclovir/farmacologia , Aciclovir/uso terapêutico , Herpesvirus Humano 3/fisiologia , Estudos Retrospectivos , Herpes Zoster/etiologia , Herpes Zoster/prevenção & controle , Herpes Zoster/tratamento farmacológico , Transplante Homólogo/efeitos adversos , Ativação Viral , Antivirais/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos
15.
N Engl J Med ; 387(4): 321-331, 2022 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-35939578

RESUMO

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.).


Assuntos
Anticorpos Monoclonais Humanizados , Lectinas Tipo C , Lúpus Eritematoso Cutâneo , Glicoproteínas de Membrana , Receptores Imunológicos , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Herpes Zoster/etiologia , Humanos , Lectinas Tipo C/antagonistas & inibidores , Lectinas Tipo C/imunologia , Lúpus Eritematoso Cutâneo/tratamento farmacológico , Glicoproteínas de Membrana/antagonistas & inibidores , Glicoproteínas de Membrana/imunologia , Receptores Imunológicos/antagonistas & inibidores , Receptores Imunológicos/imunologia , Índice de Gravidade de Doença , Resultado do Tratamento
16.
Eur J Haematol ; 109(3): 298-304, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35687019

RESUMO

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.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Herpes Zoster , Linfoma , Mieloma Múltiplo , Aciclovir/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Herpes Zoster/diagnóstico , Herpes Zoster/etiologia , Herpes Zoster/prevenção & controle , Herpesvirus Humano 3 , Humanos , Linfoma/complicações , Linfoma/diagnóstico , Linfoma/terapia , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/terapia , Estudos Retrospectivos , Transplante de Células-Tronco/efeitos adversos , Transplante Autólogo/efeitos adversos
18.
J Eur Acad Dermatol Venereol ; 36(8): 1342-1348, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35470920

RESUMO

BACKGROUND: Reactivation of the varicella-zoster virus (VZV), which causes herpes zoster (HZ, synonym: shingles) in humans, can be a rare adverse reaction to vaccines. Recently, reports of cases after COVID-19 vaccination have arisen. OBJECTIVES: The aim of this study was to assess whether the frequency of HZ is found to increase after COVID-19 vaccination in a large cohort, based on real-world data. As a hypothesis, the incidence of HZ was assumed to be significantly higher in subjects who received a COVID-19 vaccine (Cohort I) vs. unvaccinated individuals (Cohort II). METHODS: The initial cohorts of 1 095 086 vaccinated and 16 966 018 unvaccinated patients were retrieved from the TriNetX database and were matched on age and gender in order to mitigate confounder bias. RESULTS: After matching, each cohort accounted for 1 095 086 patients. For the vaccinated group (Cohort I), 2204 subjects developed HZ within 60 days of COVID-19 vaccination, while among Cohort II, 1223 patients were diagnosed with HZ within 60 days after having visited the clinic for any other reason (i.e. not vaccination). The risk of developing shingles was calculated as 0.20% and 0.11% for cohort I and cohort II, respectively. The difference was statistically highly significant (P < 0.0001; log-rank test). The risk ratio and odds ratio were 1.802 (95% confidence interval [CI] = 1.680; 1.932) and 1.804 (95% CI = 1.682; 1.934). CONCLUSIONS: Consistent with the hypothesis, a higher incidence of HZ was statistically detectable post-COVID-19 vaccine. Accordingly, the eruption of HZ may be a rare adverse drug reaction to COVID-19 vaccines. Even though the molecular basis of VZV reactivation remains murky, temporary compromising of VZV-specific T-cell-mediated immunity may play a mechanistic role in post-vaccination pathogenesis of HZ. Note that VZV reactivation is a well-established phenomenon both with infections and with other vaccines (i.e. this adverse event is not COVID-19-specific).


Assuntos
Vacinas contra COVID-19 , COVID-19 , Herpes Zoster , Herpesvirus Humano 3 , Ativação Viral , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Herpes Zoster/epidemiologia , Herpes Zoster/etiologia , Herpesvirus Humano 3/fisiologia , Humanos , Vacinação/efeitos adversos
19.
Int J Infect Dis ; 119: 184-186, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35398296

RESUMO

We present, to our knowledge, the second case report of a 46-year old female who developed varicella-zoster virus (VZV) meningitis after BNT162b2 mRNA COVID-19 vaccination. The patient is immunocompetent and has no known predisposing risk factors for developing VZV meningitis. The patient received acyclovir therapy and subsequently had a complete recovery. We describe possible mechanisms of VZV meningitis after mRNA COVID-19 vaccination.


Assuntos
COVID-19 , Herpes Zoster , Meningite , Adulto , Vacina BNT162 , COVID-19/diagnóstico , Vacinas contra COVID-19/efeitos adversos , Feminino , Herpes Zoster/diagnóstico , Herpes Zoster/tratamento farmacológico , Herpes Zoster/etiologia , Herpesvirus Humano 3/genética , Humanos , Meningite/complicações , Pessoa de Meia-Idade , RNA Mensageiro , Vacinação/efeitos adversos
20.
Int J Infect Dis ; 119: 214-216, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35367355

RESUMO

Most of the adverse effects reported in patients who have received COVID-19 vaccines have been mild. However, possible serious adverse effects are being monitored cautiously. There have also been a number of case reports of reactivation of varicella zoster infection within 28 days after immunization with mRNA COVID-19 vaccines. A few cases have also been reported after viral vector and inactivated COVID-19 vaccination. The incidence of meningitis following varicella zoster virus infection is rare. In the current study, we report two cases of male patients who received two different types of COVID-19 vaccine (inactivated and viral vector) and developed varicella zoster meningitis within 10 days after vaccination.


Assuntos
COVID-19 , Varicela , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Herpes Zoster , Meningite , Vacinas contra COVID-19/efeitos adversos , Varicela/prevenção & controle , Vacina contra Varicela/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Herpes Zoster/diagnóstico , Herpes Zoster/epidemiologia , Herpes Zoster/etiologia , Herpesvirus Humano 3 , Humanos , Masculino , Meningite/etiologia , Vacinação/efeitos adversos
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