JAK inhibitors and infections risk: focus on herpes zoster.
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ABSTRACT:
SUBMITTER: Sunzini F
PROVIDER: S-EPMC7328488 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
Publications
JAK inhibitors and infections risk: focus on herpes zoster.
Sunzini Flavia F McInnes Iain I Siebert Stefan S
Therapeutic advances in musculoskeletal disease 20200629
Currently, there is a growing interest in Janus kinase (JAK) intracellular signalling since targeted inhibitors against these pathways are proving effective in the treatment of a range of immune-mediated diseases, such as rheumatoid arthritis (RA), psoriasis, psoriatic arthritis (PsA), inflammatory bowel disease and atopic dermatitis. In particular, post marketing experience and the increasing development of new pharmacological inhibitors of broad and increasingly selective JAK pathways provide ...[more]
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Project description:Increased risk of herpes zoster (HZ) has been observed in patients with immune-mediated diseases, including rheumatoid arthritis (RA), psoriasis (PsO), and inflammatory bowel disease; this risk can be further increased by the use of immunosuppressive therapy. One advancing modality of therapy for these diseases is Janus kinase (JAK) inhibition. Tofacitinib is an oral JAK inhibitor for the treatment of RA and psoriatic arthritis, which is currently under investigation for the treatment of ulcerative colitis (UC) and was previously investigated for psoriasis. JAK inhibitors have been associated with HZ events in patients across a number of indications. The pathogenesis underlying this risk of HZ is currently unknown. An increased risk of HZ has been noted in patients receiving immunosuppressive therapies for UC, including tofacitinib. In clinical trials, there was a dose-dependent risk of HZ (higher dose linked with increased risk). However, the majority of HZ cases are nonserious and noncomplicated, mild to moderate in severity, and manageable without permanent discontinuation of treatment. This review will discuss HZ risk in patients receiving JAK inhibitors, focusing on tofacitinib with respect to the potential mechanisms and epidemiology of HZ. Current guidelines for the prevention of HZ will be highlighted, and proposed management reviewed.
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Project description:BackgroundThe incidence of recurrent herpes zoster (HZ) and the relationship between initial and recurrent HZ are not clear.MethodsThe Miyazaki Dermatologist Society has surveyed ~5000 patients with HZ annually since 1997. A questionnaire regarding HZ and its recurrence was completed by the dermatologists.ResultsA total of 34 877 patients with HZ were registered at 43 clinics between June 2009 and November 2015. Among 16 784 patients seen at 10 of the 43 clinics, 1076 patients (6.41%) experienced recurrence. Herpes zoster was more frequent in female than in male patients (5.27 vs 4.25 in 1000 person-years, P < .001), as was HZ recurrence (7.63% vs 4.73%, P < .001). Two and three recurrences were observed in 49 and 3 patients, respectively. Recurrence in the same dermatome was observed in 16.3% of patients, and more frequently this occurred in the left side (P = .027). The number of HZ-experienced persons increased with age, and one third of the population had experienced HZ by the age of 80.ConclusionsRecurrent HZ was observed in 6.41% of patients, with a higher incidence in women. Moreover, HZ experience reduced the HZ incidence to 31.7% of the incidence in the HZ-naive population.
| S-EPMC5414100 | biostudies-literature
Project description:There is literature that indicates the association of asthma with an increased risk of common and serious microbial infections. We recently reported an increased risk of vaccine-preventable diseases, e.g., herpes zoster (HZ) among children with asthma, defined by predetermined asthma criteria. Little is known about whether this association is persistent if the asthma status is defined by different asthma criteria, e.g., the Asthma Predictive Index, given the heterogeneity of asthma.To assess the consistency of the association between asthma and the risk of HZ in children.This is a population-based case-control study based on all pediatric patients with HZ between 1996 and 2001 in Olmsted County, Minnesota, and 1:1 age- and sex-matched controls without a history of HZ who were enrolled in our previous study. The original Asthma Predictive Index criteria was operationalized by two or more wheezing episodes in a year for the first 3 years of life plus one of the major (physician-diagnosed asthma for a parent or physician-diagnosed eczema for a patient) or two of the minor criteria (physician-diagnosed allergic rhinitis for a patient, wheezing apart from cold, or eosinophilia [?4%]). Data were fit to traditional logistic regression models to calculate odds ratios and 95% confident intervals.Of the original cohort (n = 554), 95 (17%) did not meet the enrollment criteria for this study, which left 459. Of the 221 patients, 53% were female, with a mean (standard deviation) age of 9.7 ± 4.2 years. The risk of HZ was increased in children with asthma defined by the API controlling for a varicella vaccine history and atopic status (adjusted odds ratio 2.56 [95% confidence interval, 1.08-6.56]).The association between asthma and increased risk of HZ in children and adolescents is consistent, independent of asthma definitions. Asthma might be an important clinical condition to be considered in HZ vaccine studies.
| S-EPMC4548895 | biostudies-other
Project description:Herpes zoster (HZ) affects approximately 1 in 3 persons in their lifetime, and the risk of HZ increases with increasing age. The most common, debilitating complication of HZ is the chronic neuropathic pain of postherpetic neuralgia (PHN). Two herpes zoster vaccines, a live-attenuated varicella-zoster virus (VZV) vaccine (zoster vaccine live [ZVL]; ZOSTAVAX [Merck]) and an adjuvanted VZV glycoprotein E (gE) subunit vaccine (recombinant zoster vaccine [RZV]; SHINGRIX [GlaxoSmithKline]) are licensed for the prevention of HZ and PHN in healthy older adults. The safety and efficacy of both vaccines has been demonstrated in clinical trials in immunocompetent adults and in selected immunocompromised persons and persons with immune-mediated diseases. Numerous real-world effectiveness studies have confirmed the safety and effectiveness of both ZVL and RZV. Recombinant zoster vaccine (RZV) is more effective for prevention of HZ than ZVL. Recombinant zoster vaccine is nonreplicating and is thus safe in immunocompromised persons. Additional zoster vaccines are in different stages of development. Wider distribution of safe and effective zoster vaccines will improve the health and well being of the rapidly growing population of older adults around the world.
| S-EPMC8482024 | biostudies-literature
Project description:ObjectiveTo determine the degree to which chronic conditions might contribute to the unexplained burden of herpes zoster.MethodsWe conducted a case-control study using MarketScan data from January 1, 2007, through December 31, 2007, to investigate chronic conditions as risk factors for herpes zoster among persons 20 to 64 years old. Cases were enrollees with a herpes zoster diagnosis (International Classification of Diseases, Ninth Revision, Clinical Modification codes 053.xx), and controls were those without a herpes zoster diagnosis, matched by age groups and insurance plan. We selected 10 chronic conditions based on their prevalence in the general population. We calculated the attributable fraction and created a comorbidity composite score by summing the significant coefficient of regression of chronic conditions. We used logistic regression to evaluate the associations between herpes zoster and chronic conditions.ResultsWe identified a total of 59,173 cases and 616,177 controls for the analysis. Risk of herpes zoster was significant for 8 of the 10 study conditions (odds ratios, 1.06-1.52). Herpes zoster risk also increased as a function of comorbidity composite score. The attributable fractions for these 8 significant conditions ranged from 0.24% to 2.89%.ConclusionThe risk of herpes zoster may be increased in people with chronic conditions. However, this risk may not contribute substantially to the burden of herpes zoster in the population. The causes for most cases of herpes zoster remain unknown.
| S-EPMC3538398 | biostudies-literature
Project description:BackgroundThe burden of herpes zoster (HZ) is significant worldwide, with millions affected and the incidence rising. Current literature has identified some risk factors for this disease; however, there is yet to be a comprehensive study that pools all evidence to provide estimates of risk. Therefore, the purpose of this study is to identify various risk factors, excluding immunosuppressive medication, that may predispose an individual to developing HZ.MethodsThe literature search was conducted in MEDLINE, EMBASE, and Cochrane Central, yielding case control, cohort, and cross-sectional studies that were pooled from January 1966 to September 2017. Search terms included the following: zoster OR herpe* OR postherpe* OR shingle* AND risk OR immunosupp* OR stress OR trauma OR gender OR ethnicity OR race OR age OR diabetes OR asthma OR chronic obstructive pulmonary disease OR diabetes. Risk ratios (RRs) for key risk factors were calculated via natural logarithms and pooled using random-effects modeling.ResultsFrom a total of 4417 identified studies, 88 were included in analysis (N = 3, 768 691 HZ cases). Immunosuppression through human immunodeficiency virus/acquired immune deficiency syndrome (RR = 3.22; 95% confidence interval [CI], 2.40-4.33) or malignancy (RR = 2.17; 95% CI, 1.86-2.53) significantly increased the risk of HZ compared with controls. Family history was also associated with a greater risk (RR = 2.48; 95% CI, 1.70-3.60), followed by physical trauma (RR = 2.01; 95% CI, 1.39-2.91) and older age (RR = 1.65; 95% CI, 1.37-1.97). A slightly smaller risk was seen those with psychological stress, females, and comorbidities such as diabetes, rheumatoid arthritis, cardiovascular diseases, renal disease, systemic lupus erythematosus, and inflammatory bowel disease compared with controls (RR range, 2.08-1.23). We found that black race had lower rates of HZ development (RR = 0.69; 95% CI, 0.56-0.85).ConclusionsThis study demonstrated a number of risk factors for development of HZ infection. However, many of these characteristics are known well in advance by the patient and clinician and may be used to guide discussions with patients for prevention by vaccination.
| S-EPMC6984676 | biostudies-literature
Project description:The varicella-zoster virus (VZV) infects over 95% of the population and establishes latency afterwards. Reactivation of VZV causes herpes zoster (HZ), commonly known as shingles, which presents as a painful rash in mostly the elderly and people with a weakened immune system. However, HZ might occur in otherwise healthy individuals too. In this study, we have analyzed the immune signature of HZ to better understand HZ’s pathophysiology. We provide a general overview of the antiviral state and the activation of innate and adaptive immune responses during HZ. An extensive exome-wide association study of HZ, incorporating UK Biobank data across white, black and Asian cohorts highlights the MHC locus as a risk factor for HZ development. Therefore, we conducted one of the largest human leukocyte antigen (HLA) association studies on HZ to date (n=138,701 participants) using Fisher’s exact test and identified five protective and four risk HLA alleles associated with the development of HZ. Additionally, differential gene expression and gene ontology analyses revealed upregulation of several genes and host immune pathways during herpes zoster, especially related to type I interferon response but also involved with adaptive immune responses. Intriguingly, no differences in gene expression were noted during convalescence between HZ patients and controls. Our research reveals that HZ susceptibility is largely governed by a complex pattern of variations in the major histocompatibility complex, resulting in modified antigen recognition in HZ patients. Further, we identified key genes and pathways involved in the host immune response to symptomatic VZV reactivation and provided new molecular insights into the development of HZ and its associated risk factors.
2023-09-08 | GSE242252 | GEO
Project description:OBJECTIVE:Histopathologic studies have implicated herpes zoster (HZ) as a causative organism of giant cell arteritis (GCA). The purpose of this study was to assess the epidemiologic association of HZ events with incident GCA. METHODS:We performed a retrospective cohort study in 2 large independent US administrative data sets: Medicare 5% and Truven Health Analytics MarketScan. Eligible subjects had 12 months of continuous coverage, were >50 years old, and had no history of GCA or polymyalgia rheumatica. HZ events (complicated and uncomplicated) and GCA were identified by the presence of International Classification of Diseases, Ninth Revision, Clinical Modification codes from physician visit or hospital discharge records. Antiviral therapies and vaccinations were identified from prescription claims and drug codes. Risk of incident GCA was calculated using multivariable Cox proportional hazards regression. RESULTS:Among 16,686,345 subjects, a total of 5,942 GCA cases occurred, with 3.1% (MarketScan) and 6.0% (Medicare) having preceding HZ events. Unadjusted GCA incidence rates were highest in the groups with complicated and uncomplicated HZ. After multivariable adjustment, complicated HZ was associated with an increased risk of GCA (hazard ratio [HR] 1.99 [95% confidence interval (95% CI) 1.32-3.02] in the Medicare cohort and 2.16 [95% CI 1.46-3.18] in the MarketScan cohort), as was uncomplicated HZ (HR 1.42 [95% CI 1.02-1.99] and HR 1.45 [95% CI 1.05-2.01] in the respective cohorts). Vaccination and antiviral treatment were not consistently associated with GCA risk, although antiviral treatment was marginally associated with a decreased risk of GCA in the Medicare cohort (HR 0.67 [95% CI 0.46-0.99]). CONCLUSION:HZ is associated with an increased risk of GCA. The infrequency of HZ in GCA patients suggests that it is only one potential trigger for GCA. Antivirals and vaccination did not consistently mitigate this risk.
| S-EPMC5711552 | biostudies-literature
Project description:Options for managing herpes zoster (HZ)-related pain and complications have limited effectiveness, making HZ prevention through vaccination an important strategy. Limited data are available on HZ vaccine effectiveness against confirmed HZ and manifestations of HZ among vaccinated persons. We conducted a matched case-control study to assess HZ vaccine effectiveness for prevention of HZ and other HZ-related outcomes and a cohort study of persons with HZ to compare HZ-related outcomes by vaccination status. Cases were identified through active surveillance among persons age ≥ 60 years with HZ onset and health-care encounters during 2010-2011 in Southeastern Minnesota. Controls were age- and sex-matched to cases. Data were collected by medical record review and from participants via interviews and daily pain diaries. 266 HZ case-patients and 362 matched controls were enrolled in the vaccine effectiveness studies and 303 case-patients in the cohort study of HZ characteristics by vaccination status. Vaccination was associated with 54% (95% CI:32%-69%) reduction in HZ incidence, 58% (95% CI:31%-75%) reduction in HZ prodromal symptoms, and 70% (95% CI:33%-87%) reduction in medically-attended prodrome. HZ vaccine was statistically significant effective at preventing postherpetic neuralgia (PHN) measured at 30 d after rash onset, 61% (95% CI: 22%-80%). Among persons who developed HZ, no differences were found by vaccination status in severity or duration of HZ pain after rash onset. In this population-based study, HZ vaccination was associated with >50% reduction in HZ, HZ prodrome, and medically-attended prodrome.
| S-EPMC4514415 | biostudies-literature