Incidence Rates Of Herpes Zoster Research Articles

Incidence Rates of Infections in Rheumatoid Arthritis Patients Treated with Janus Kinase or Interleukin-6 Inhibitors: Results of a Retrospective, Multicenter Cohort Study.

Objective: This study aimed to compare the incidence rates (IRs) of infections, including herpes zoster (HZ), in rheumatoid arthritis (RA) patients treated with Janus kinase inhibitors (JAKis) or interleukin-6 inhibitors (IL-6is). Methods: We retrospectively analyzed 444 RA patients treated using IL-6is (n = 283) or JAKis (n = 161). After adjusting for clinical characteristic imbalances by propensity score matching (PSM), we compared the IRs of infections including HZ between the JAKi and IL-6i groups. Results: Observational period: 1423.93 patient years (PY); median observational period: 2.51 years. After PSM, incidence rate ratios comparing JAKi with IL-6i were 3.45 (95% confidence interval [CI]: 1.48-9.04) for serious infections other than HZ indicating that the JAKi-treated group was more likely to develop serious infection than the IL-6i-treated group. Multivariate Cox regression analyses revealed that the use of prednisolone > 5.0 mg/day, coexisting interstitial lung disease (ILD), and diabetes mellitus (DM) were independent risk factors for serious infections. The crude IR for HZ was significantly higher in the JAKi group, but the difference between groups was not significant (IRR: 2.83, 95% CI: 0.87-10.96) in PSM analysis. Unadjusted and PSM analyses performed in our study showed increased IRs of serious infections in patients with RA treated with JAKis compared with those treated with IL-6is. Conclusions: The presence of ILD or DM and the use of prednisolone were found to be independent risk factors for serious infection in RA patients treated using JAKis. Whereas the IRs for HZ after PSM were not significantly different between the JAKi and IL-6i groups.

Systematic Literature Review on the Incidence of Herpes Zoster in Populations at Increased Risk of Disease in the EU/EEA, Switzerland, and the UK.

Older adults and patients with underlying conditions such as immunocompromised (IC) populations (e.g., due to medical conditions or immunosuppressive medication) are at increased risk for herpes zoster (HZ). The first HZ recombinant vaccine for IC patients was approved in 2020. Limited evidence exists to inform decision-makers on HZ incidence in high-risk patients in Europe. This systematic literature review (SLR) assessed HZ incidence across 14 high-risk populations in the European Union/European Economic Area, Switzerland, and the United Kingdom. An SLR (Embase, Medline, 2002-2022, observational studies) was performed to identify HZ incidence (i.e., primary outcomes: rate or cumulative; secondary: relative incidence) in type 1 and 2 diabetes mellitus (DM); chronic obstructive pulmonary disease and asthma; depression; rheumatic disorders (RD); multiple sclerosis (MS); inflammatory bowel diseases (IBD); psoriasis; lupus; human immunodeficiency virus (HIV); solid organ transplantation (SOT); solid organ malignancy (SOM); hematologic malignancy (HM); and stem cell transplantation (SCT). Of 776 unique records screened, 59 studies were included (24 reported incidence rate per 1000 person-years; two, cumulative incidence per 1000 persons; and 33, relative incidence). The highest incidence rates were reported for SOT (12.1-78.8) and SCT (37.2-56.1); HM (2.9-32.0); RD (0.41-21.5); lupus (11.0-16.5); IC mixed population (11.3-15.5); HIV/AIDS (11.8-13.0); chronic respiratory diseases (4.7-11.4); SOM (8.8-11.0); IBD (7.0-10.8); DM (4.3-9.4); depression (7.2-7.6); MS (5.7-6.3); and psoriasis (5.3-6.1). In many high-risk populations, HZ incidence was higher for older age groups, women, and some treatments. The HZ incidence rate in Europe increased with age and varied across high-risk populations, with high rates for solid organ and stem cell transplants, cancer, and rheumatoid arthritis. Most studies were retrospective with methodological differences affecting generalizability and comparability. Future studies should stratify data by IC population, age, sex, severity, medication, and study timeframe.

Incidence of Herpes Zoster and Postherpetic Neuralgia and Herpes Zoster Vaccination Uptake in a US Administrative Claims Database.

The objective of this study was to estimate the annual incidence rates of herpes zoster (HZ) and postherpetic neuralgia (PHN) among individuals aged ≥19 years and the proportion who received HZ vaccination among those aged ≥50 years. This observational cohort study was conducted with administrative claims data from HealthVerity and included insured individuals across the US. Crude and US age- and sex-standardized incidence rates of HZ and PHN were calculated from 1 January 2019 to 31 May 2022 by calendar year in persons aged ≥19 years. Outcomes were defined as ≥1 ICD-10 diagnosis code for HZ or PHN. Analyses were stratified by age, sex, and immunocompromised status. Among those aged ≥50 years, the proportion who received 1 or 2 doses of recombinant zoster vaccine (Shingrix) or 1 dose of Zostavax was calculated. Standardized annual incidence rates from 2019 to 2021 were 542 to 685 per 100 000 person-years for HZ and 35 to 38 per 100 000 person-years for PHN. Rates were highest among females, older adults, and individuals who were immunocompromised. From 1 January 2019 to 31 May 2022, 4.3% and 9.0% of persons aged ≥50 years received 1 and 2 doses of Shingrix, respectively, and 0.2% received 1 dose of Zostavax. In this US claims database analysis, HZ and PHN were more frequent among older adults, females, and individuals who were immunocompromised. Between 1 January 2019 and 31 May 2022, 9% of persons aged ≥50 years received 2 doses of the Shingrix vaccine. Greater efforts are needed to increase vaccine uptake against HZ, especially for those at highest risk.

Risk of herpes zoster in adults with SARS-CoV-2 infection in Spain: A population-based, retrospective cohort study

ObjectivesWe aimed to compare the risk of herpes zoster (HZ) in adults with and without laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. MethodsThis retrospective dynamic cohort study analyzed data from a public healthcare database in Spain between November 2020 and October 2021. The main outcome was incident cases of HZ in individuals ≥18-year-old. Relative risk (RR) of HZ in SARS-CoV-2-confirmed versus SARS-CoV-2-free individuals was estimated by a multivariable negative binomial regression adjusted by age, sex, and comorbidities. ResultsData from 4,085,590 adults were analyzed. The overall HZ incidence rate in adults was 5.76 (95% confidence interval [CI], 5.66-5.85) cases per 1000 person-years. Individuals ≥18-year-old with SARS-CoV-2-confirmed infection had a 19% higher risk of developing HZ versus SARS-CoV-2-free ≥18-year-olds (adjusted RR = 1.19; 95% CI, 1.09-1.29); this percentage was 16% (adjusted RR = 1.16; 95% CI, 1.05-1.29) in ≥50-year-olds. Severe (hospitalized) cases of SARS-CoV-2 infection had a 64% (if ≥18 years old) or 44% (if ≥50 years old) higher risk of HZ versus nonhospitalized cases. ConclusionThese results support an association between SARS-CoV-2 infection and HZ, with a greater HZ risk in severe cases of SARS-CoV-2 infection.

Relationship between lymphocyte count and risk of infection in Japanese rheumatoid arthritis patients treated with tofacitinib.

We characterised changes in absolute lymphocyte counts (ALCs) and lymphocyte subset counts (LSCs), and their relationship to incidence of serious infection events (SIEs) and herpes zoster (HZ) events in Japanese patients with moderate to severe rheumatoid arthritis enrolled in the tofacitinib clinical programme. Data included 765 patients receiving tofacitinib in Phase 2, Phase 3, and long-term extension studies. ALCs/LSCs and incidence rates (patients with events/100 patient-years) of SIEs and HZ were analysed over 75 months. Median ALCs were generally stable over 75 months of treatment. Transient numerical increases from baseline in median LSCs were observed at Month 3; LSCs were generally lower than baseline for Months 36-75. SIE/HZ incidence rates were higher in patients with ALC <0.5 × 103 cells/mm3 versus those with ALC ≥0.5 × 103 cells/mm3 during tofacitinib treatment. Baseline LSCs were similar in patients with/without SIEs or HZ events. SIE/HZ risk was highest in patients with ALC <0.5 × 103 cells/mm3, supporting this threshold as clinically relevant for defining increased SIE/HZ risk in Japanese patients with rheumatoid arthritis receiving tofacitinib. However, SIEs and HZ events did not necessarily occur simultaneously with confirmed lymphopenia, preventing conclusions on possible causal relationships being drawn.

Incidencia de herpes zóster en pacientes con enfermedad inflamatoria intestinal: estudio observacional y retrospectivo en dos hospitales españoles de tercer nivel

BackgroundHerpes zoster (HZ) is a prevalent disease caused by the reactivation of the varicella-zoster virus (VZV) and associated with chronic morbidity, particularly with post-herpetic neuralgia (PHN). Inflammatory bowel disease (IBD) has been associated with an increased risk of HZ, mainly when immunosuppressive treatment (IMT) is used. However, studies assessing the risk of HZ in IBD are scarce. AimsTo evaluate the incidence rate and risk factors of HZ in IBD. MethodsRetrospective study in IBD patients with a positive VVZ serology from two referral hospitals from the area of Barcelona. Diagnosis of HZ and its clinical features were recorded. ResultsA total of 398 IBD patients with a positive IgG-VVZ serology were identified. Fifty-eight percent of the patients received IMT (46.5% immunosuppressants monotherapy, 20.6% biologics monotherapy and, 32.7% combination therapy). After a median follow-up of 71 months (IQR 41.5-138.0), 17 (4.3%) patients developed HZ (cumulative incidence of 5.2 per 1000 person-year), 12 of them (70.6%) while receiving IMT. Median age at HZ episode was 38 years (IQR 27.5-52.5). Two (11%) developed PHN. Biological therapy was the only risk factor for developing HZ (OR 3.8 IC 95% 1.3-11.5; p=0.018). ConclusionsHZ is quite prevalent in IBD, occurring at early ages and particularly among patients using IMT. NPH appears to occur in a notable proportion of cases.

P986 Effectiveness of the adjuvanted recombinant zoster vaccine (RZV) in preventing herpes zoster (HZ) among patients ≥50 years of age with Inflammatory Bowel Disease in the United States: A retrospective real-world database analysis from 2018 to 2021

Abstract Background Patients with inflammatory bowel disease (IBD) are at higher risk of developing HZ compared to general population.1 The US Food and Drug Administration (FDA) approved RZV for adults ≥50 years of age (YOA) in Oct 2017 and for adults ≥18 YOA who are or will be at increased risk of HZ due to immunodeficiency or immunosuppression, as patients with IBD, in Jul 2021. This study addresses an information gap for RZV vaccine effectiveness (VE) in preventing HZ among IBD patients ≥50 YOA. Methods We conducted a retrospective matched cohort study using the Optum Clinformatics Data Mart healthcare administrative claims database from Jan 2018 to Dec 2021. Patients ≥50 YOA with IBD who received 2 RZV doses with dose interval ≥28 days (RZV [2-dose] cohort) were 1:3 matched to their unvaccinated counterparts (non-RZV cohort) by age, medication category, and other confounders (propensity score). The index date for RZV cohort was the date of the second dose and for non-RZV cohort was the same index date as their vaccinated match. Follow-up started from index date +30 days until earliest date of HZ occurrence, end of enrolment, death, receipt of HZ vaccine, or study end. The first HZ episode during follow-up was identified using an algorithm that included ICD-10 diagnosis code, inpatient or outpatient claims and/or HZ antiviral medication used within 7 days pre/post-HZ diagnosis. Incidence rates (IRs) of HZ were calculated overall, stratified by condition (ulcerative colitis [UC], Crohn’s disease [CD]) and age. Cox hazards models were used to estimate overall and stratified hazard ratios (HRs). VE (%) was calculated as (1−HR) × 100. A similar approach was used to evaluate VE for patients who received 1 RZV dose. Results We identified 6501 RZV vaccinated and 19962 matched unvaccinated IBD patients who were included in the 2-dose analysis (Table). The IR of HZ was 2.92/1000 person-years (PY) in the RZV cohort and 10.96/1000 PY in the non-RZV cohort, resulting in a VE of 73.4% (95% confidence intervals [CIs]: 60.8-82.0) for IBD patients (Figure). VE against HZ was 63.5% (95%CIs: 43.0-76.6) and 85.7% (95%CIs: 69.5-93.3) in UC and CD 2-dose cohorts. IRs and VE stratified by condition and age are presented in Figure. Adjusted VE for IBD patients who received 1 RZV dose was 63.4% (95%CIs: 24.9-82.2). Conclusion Our analysis provides real-world evidence that RZV vaccination is effective in preventing HZ in IBD patients ≥50 YOA and reduce the burden in this population with increased risk of HZ. These findings are consistent with the available literature on RZV effectiveness in patients with IBD, suggesting that this population could greatly benefit from RZV vaccination. 1. Yun H et al, Arthritis Rheumatol 2016;68:2328-37 Funding GSK

P1157 Burden of herpes zoster in patients with inflammatory bowel disease treated with immunosuppressive agents

Abstract Background Patients with inflammatory bowel disease (IBD) are at increased risk of infections such as herpes zoster (HZ) due to immunosuppressive (IS) therapy. We conducted a targeted literature review to identify the burden of HZ in patients with IBD treated with IS agents. Methods We conducted a PubMed search to collate publications reporting on HZ in patients with IBD receiving IS treatment (from 01/01/2013 to 01/11/2023; excluding preclinical studies, narrative reviews and case reports). Findings were supplemented with a second PubMed search specific to paediatric patients with IBD (aged ≤18 years). Additional publications were included based on authors’ expertise as well as relevant abstracts presented at ECCO and DDW in 2022 and 2023. Results Overall, 178 publications were identified and 77 were included, along with ten recent congress abstracts. The most common IS treatments were Janus kinase inhibitors (JAKi), including tofacitinib and upadacitinib, followed by tumour necrosis factor inhibitors (TNFi). Additional treatments included anti-interleukin (IL)-23 agents (risankizumab, ustekinumab, mirikizumab) and sphingosine-1-phosphate (S1P) receptor modulators (etrasimod, ozanimod). HZ incidence rates are typically higher in patients with IBD compared with non-IBD populations (7.02–18.34 vs 3.22–11.29 per 1000 patient years, respectively). In paediatric patients, incidence rates are as high as 8.49/1000 patient years, with a standardised incidence ratio of 3.38 compared with the general population. Two studies reported a significant association between IBD and risk of hospitalisation for HZ in children and adolescents. Patients with IBD aged &amp;lt;50 years may have higher incidence of HZ compared with those aged &amp;gt;60 years without IBD. Risk factors for HZ in IBD patients include older age, lower weight, geographic region, prior TNFi failure and use, dose, and combination of IS medications. Increased incidence of HZ is associated with IS medication, particularly JAKis. Limited data exists on novel anti IL-23 agents and S1P receptor modulators, with some studies reporting a similar risk of HZ in treated patients compared with placebo, and others reporting an increased risk. HZ-related discontinuation is rare. Vaccination can reduce the risk of HZ in treated IBD populations, and studies have identified areas to improve vaccination adherence. Conclusion Patients with IBD of all ages, but specifically those aged &amp;lt;50 years, are at higher risk of HZ compared with non-IBD cohorts, and IS medications contribute to this risk. Vaccination against HZ prior to initiating IS treatment could benefit patients with IBD.

The Risk of Herpes Zoster Events in Patients with Spondyloarthritis and the Effect of BNT162b2 mRNA COVID-19 Vaccine.

The data on the risk of herpes zoster (HZ) in spondyloarthropathy (SpA) patients are sparse, especially regarding its association with the novel mRNA COVID-19 vaccines and immunosuppressants. We aimed to evaluate whether SpA diagnosis and/or immunosuppressant use affect HZ risk and the influence of mRNA COVID-19 vaccination. We assessed the association between SpA (psoriatic arthritis (PsA) and ankylosing spondylitis (AS)) diagnoses and HZ in a large population database with patients matched by age and sex to controls. We also assessed the association between the COVID-19 vaccine and new-onset HZ using two nested case-control studies, identifying all new HZ cases diagnosed from 1 January-31 December 2021 within the SpA and general population cohorts, matched randomly by sex, age and HZ index date to controls without HZ. Exposure to mRNA COVID-19 vaccination was ascertained in the 6 weeks prior to the index date both in cases and controls. In our results, the incidence rate of HZ was higher in PsA patients vs. the general population, at 1.03 vs. 0.64 per 100 person-years, respectively (adjusted HR = 1.55; 95%CI, 1.19-2.02). Within the SpA group, Jak-I treatment was associated with a higher risk of developing new-onset HZ (adjusted OR = 3.79; 1.15-12.5). Multivariable conditional logistic regression models we used showed no association between COVID-19 vaccination and new-onset HZ among the SpA patients (OR = 1.46; 0.68-3.14).

Incidence of New-Onset Inflammatory Bowel Disease, Oral and Gastrointestinal Candidiasis, Herpes Zoster, Pulmonary Tuberculosis, and Major Cardiovascular Events in Patients with Moderate-to-Severe Psoriasis Exposed to Biologics.

The multicenter, retrospective cohort study was aimed at examining adverse events in biologic-treated patients with moderate-to-severe psoriasis by using a real-world database. Thus, we analyzed exposure-adjusted incidence rates for new-onset inflammatory bowel disease (IBD), oral and gastrointestinal candidiasis, pulmonary tuberculosis, herpes zoster, and major cardiovascular events (MACEs) in biologic-treated patients with moderate-to-severe psoriasis. Overall, 2085 patients were found to have been exposed to tumor necrosis factor (TNF)-α, interleukin (IL)-12/23, IL-17, and IL-23 inhibitors (n = 463, 540, 635, and 447, respectively). No patient developed new-onset IBD. The incidence rates of oral and gastrointestinal candidiasis were comparable between patients treated with IL-23 and IL-17 inhibitors (5.6 and 5.3 per 1000 PY, respectively). None treated with IL-17 or IL-23 inhibitors reported pulmonary tuberculosis. The incidence rate of herpes zoster was the highest in patients treated with TNF-α inhibitors (17.0 per 1000 PY), followed by IL-17, IL-23, and IL-12/23 inhibitors (13.3, 7.8, and 2.7 per 1000 PY, respectively). MACEs were not reported in patients treated with IL-17 inhibitors but were reported in those treated with TNF-α, IL-23, and IL-12/23 inhibitors (incidence: 5.6, 3.8, and 1.8 per 1000 PY, respectively). The study indicated favorable safety profiles of biologics in Korean patients with moderate-to-severe psoriasis.

Burden of Herpes Zoster in Individuals with Immunocompromised Conditions and Autoimmune Diseases in the Republic of Korea: A Nationwide Population-Based Database Study.

To estimate herpes zoster (HZ) incidence rate (IR) and economic burden in individuals with immunocompromised conditions and autoimmune diseases (IC/AID) in the Republic of Korea (ROK). The nationwide Health Insurance Review and Assessment Service database was used to identify HZ cases from 2016 to 2020 in ROK. HZ and non-HZ IC/AID cases were matched 1:3 using age, sex, institution, Charlson comorbidity index, IC/AID, and index date. Annual HZ IRs/1000 persons and 1-year HZ-associated all-cause direct medical costs for IC/AID cases were calculated. Among 65,976 individuals with IC/AID (mean age 57.14years [standard deviation 14.1]; 64.94% female), annual HZ IR (95% confidence interval) fluctuated from 2016 to 2020, averaging 23.41/1000 persons (22.21-24.62) and was higher in women (26.85 [25.40-28.31]) than men (18.96 [18.03-19.89]). IRs were highest in individuals aged ≥ 50years, and in those with transplants (including solid organ and hematopoietic stem cell transplants; 37.12 [35.45-38.79]) and hemato-oncology conditions (35.5 [31.6-39.3]). Mean 12-month all-cause direct medical costs were higher in individuals with IC/AID and HZ (4,759,671 Korean Republic won [KRW]; approximately 4046 United States dollar [USD; according to the 2020 conversion rate from UNCTAD; 1 KRW = 0.00085 USD]) than those without HZ (3,786,658 KRW; 3219 USD). Individuals with IC/AID have a substantial disease and economic burden from HZ in ROK, highlighting the need for appropriate HZ prevention measures in the IC/AID population.

Burden of Herpes Zoster Among Patients with Psoriasis in the United States.

Patients with psoriasis (PsO) are at increased risk of herpes zoster (HZ), but recentdata on the incidence of HZ among patients with PsO and the impact of HZ on healthcare resource use (HRU) and costs for patients with PsO have not been described. This retrospective, longitudinal, cohort study estimated HZ incidence in cohorts of adults with vs without PsO (PsO + vs PsO-) and HRU and costs among those with PsO, with vs without HZ (PsO + /HZ + vs PsO + /HZ-) using Optum's de-identified Clinformatics Data Mart Database during 2015-2020. Patients with psoriatic arthritis were excluded from all four cohorts. Comparisons between cohorts used generalized linear models to adjust outcomes based on various baseline characteristics. The incidence rate of HZ was significantly higher in the PsO + (n = 144,115) vs PsO- (n = 23,837,237) cohorts at 11.35 vs 7.67 per 1000 patient-years; adjusted incidence rate ratio (aIRR): 1.21, 95% confidence interval (CI): 1.16-1.25. HRU (outpatient, emergency department, and inpatient) was significantly higher in the PsO + /HZ + (n = 1859) vs PsO + /HZ- (n = 78,664) cohorts during 1 month and 3 months after HZ diagnosis (e.g., outpatient visits during month: 2.83 vs 1.30 per patient; aIRR: 1.96; 95% CI 1.86-2.06). Mean all-cause costs were also significantly higher in the PsO + /HZ + vs PsO + /HZ- cohort during both month ($5020 vs $2715 per patient; adjusted cost difference: $1390; 95% CI $842-$1964) and 3months ($12,305 vs $8256; adjusted cost difference: $1422; 95% CI $280-$2889) after HZ diagnosis. These findings show the increased incidence of HZ among patients with PsO and the clinical and economic burdens of HZ in this population. Considering the high prevalence of PsO, insights into the impact of HZ in these patients provide valuable evidence to inform clinical decision-making.

Clinico-Epidemiological Profile of Immunocompetent Patients Diagnosed with Herpes Zoster: A Single-Center Retrospective Cohort Study from Sinop

Aim: Herpes zoster (HZ) mainly occurs in immunocompetent individuals, even though immunosuppression&#x0D; is a well-known risk factor. The aim of this study was to evaluate the demographic and clinical features&#x0D; of immunocompetent HZ patients and HZ-related complications with a special focus on possible&#x0D; contributing factors.&#x0D; Material and Methods: This single-center, retrospective cohort study included 98 patients with no&#x0D; known immunosuppressive condition out of 103 patients diagnosed with HZ between September 2019&#x0D; and August 2020. The patients were evaluated in terms of age, sex, medical history, clinical features,&#x0D; triggering factors, seasonality, complications, and neutrophil-to-lymphocyte ratio (NLR) as a marker of&#x0D; systemic inflammation.&#x0D; Results: Ninetyeight immunocompetent patients (male:female ratio=1.1:1) were diagnosed with HZ,&#x0D; with a median age of 59 years (age range: 5-88). Thoracic dermatome was the leading dermatome&#x0D; (n=45). Trigeminal nerve was involved in 11 patients, eight of them presenting with ophthalmic HZ. HZ&#x0D; attacks were mainly detected in summer, while ophthalmic HZ cases were exclusively diagnosed during&#x0D; fall and winter. Two patients developed ophthalmic HZ following trauma. Eleven patients experienced&#x0D; postherpetic neuralgia (PHN) during follow-up with a male predominance (p=0.009). A higher mean NLR&#x0D; value was detected in PHN patients, although it was not statistically significant (p=0.136).&#x0D; Conclusion: The findings of our study are compatible with the current literature regarding the main&#x0D; presentation pattern of HZ as unilateral thoracic dermatome involvement and the complications such as&#x0D; PHN and ophthalmic HZ occurring in a subgroup of patients. The high HZ incidence rate in our series is&#x0D; likely due to the high median age of the population in our region. The summer peak of HZ cases further&#x0D; supports the seasonal variability due to the ultraviolet effect, whereas mechanical trauma is another&#x0D; possible triggering factor. The predictive value of NLR for PHN should be evaluated in further studies.

Comparative risk of infections between JAK inhibitors versus TNF inhibitors among patients with rheumatoid arthritis: a cohort study

BackgroundTo compare infectious risk between JAK inhibitors (JAKis) versus TNF inhibitors (TNFis) among rheumatoid arthritis (RA) patients in Korea.MethodsUsing 2009–2019 Korea National Health Insurance Service database, we conducted a cohort study on RA patients initiating a JAKi or TNFi. The primary outcomes were herpes zoster (HZ), serious bacterial (SBI), and opportunistic infections (OI). Propensity-score fine-stratification (PSS) and weighting were applied to adjust for > 70 baseline covariates. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models comparing JAKi versus TNFi users.ResultsWe included 2963 JAKi initiators PSS-weighted on 5169 TNFi initiators. During a follow-up of 1.16 years, the most frequent type of infections was HZ with incidence rate (IR) per 100 person-years of 11.54 and 4.88 in JAKi and TNFi users, respectively. The IR of SBI was 1.39 and 1.32, respectively. The OI was rare with a majority being tuberculosis and showed an IR of 0.11 and 0.49 in JAKi and TNFi users, respectively. The PSS-weighted HR (95% CI) for individual types of infections was 2.37 (2.00–2.80) for HZ, 1.04 (0.71–1.52) for SBI, and 0.25 (0.09–0.73) for OI.ConclusionsThis population-based cohort study on RA patients treated with JAKi or TNFi in Korea showed an exceptionally high IR of HZ in both treatment groups compared to that from Western countries, with an approximately doubled risk associated with JAKi versus TNFi use. The risk of SBI was comparable, but the risk of OI, particularly tuberculosis, was less among JAKi than TNFi initiators.

Multiregional Population-Based Cohort Study for Evaluation of the Association Between Herpes Zoster and mRNA Vaccinations for Severe Acute Respiratory Syndrome Coronavirus-2: The VENUS Study.

This study was performed to assess the increased risk of herpes zoster (HZ) associated with mRNA vaccines for coronavirus disease 2019. This population-based cohort study was conducted in 4 municipalities in Japan. Individuals covered under public health insurance systems without a history of HZ were followed from October 1, 2020 to November 30, 2021. Incidence rates of HZ within 28 days of BNT162b2 or mRNA-1273 vaccination were compared. Adjusted incidence rate ratios (IRR) and 95% confidence intervals (CI) were estimated using a Poisson regression model, including vaccination status as a time-dependent covariate. Subgroup analyses by sex, age, and municipality were also conducted. A total of 339 548 individuals (median age, 74 years) were identified. During follow up, 296 242 individuals (87.2%) completed the primary series, among whom 289 213 and 7019 individuals received homologous BNT162b2 and mRNA-1273 vaccines, respectively. The adjusted IRRs of the first and second BNT162b2 vaccinations were 1.05 (95% CI, 0.84-1.32) and 1.09 (95% CI, 0.90-1.32), respectively. No cases of HZ were observed after mRNA-1273 vaccination. In subgroup analysis, the adjusted IRR of the second BNT162b2 vaccination was 2.94 (95% CI, 1.41-6.13) in individuals aged <50 years old. No increased risk of HZ was found after BNT162b2 vaccination in the overall study population. However, an increased risk was observed in the younger subgroup.

Increased risk of herpes zoster with tofacitinib treatment in Korean patients with rheumatoid arthritis: a single-center prospective study

We aimed to determine the risk of herpes zoster (HZ) in Korean rheumatoid arthritis (RA) patients on tofacitinib compared with tumor necrosis factor inhibitor (TNFi) treatment. From the prospective cohorts of RA patients who started tofacitinib or TNFi in an academic referral hospital in Korea, patients who started tofacitinib between March 2017 and May 2021 and those who started TNFi between July 2011 and May 2021 were included. Baseline characteristics of tofacitinib and TNFi users were balanced through inverse probability of treatment weighting (IPTW) using the propensity score including age, disease activity of RA and medication use. The incidence rate of HZ in each group and incidence rate ratio (IRR) were calculated. A total of 912 patients were included: 200 tofacitinib and 712 TNFi users. There were 20 cases of HZ among tofacitinib users and 36 among TNFi users during observation period of 331.4 person-years (PYs) and 1950.7 PYs, respectively. In IPTW analysis with a balanced sample, IRR of HZ was 8.33 (95% confidence interval 3.05–22.76). Tofacitinib use increased the risk of HZ compared with TNFi in Korean patients with RA, but the rate of serious HZ or permanent discontinuation of tofacitinib due to HZ event was low.

Herpes Simplex Virus (HSV), Varicella-Zoster Virus (VZV), and Cryptococcal Infections Associated With Sphingosine-1-Phosphate Receptor (S1PR) Modulators: A Review (P12-10.005)

<h3>Objective:</h3> To summarize the existing data on the incidence of herpes simplex virus (HSV), varicella-zoster virus (VZV), and Cryptococcus sp. infections with sphingosine-1-phosphate receptor (S1PR) modulators. <h3>Background:</h3> S1PR modulators are a novel class of disease-modifying therapies for multiple sclerosis (MS) that produce immunosuppression and potential lymphopenia. Herpesvirus and cryptococcal diseases were the most common opportunistic infections in clinical trials. Several post-hoc analyses have subsequently been published with revised incidence rates (IRs) for these conditions. <h3>Design/Methods:</h3> A literature review and descriptive analysis of phase-3 trials (n=6), post-marketing studies (n=8), and case reports (n=17) were conducted using PubMed and Google Scholar. Further data was accessed through Novartis AG, Bristol-Myers Squibb, and Janssen Pharmaceuticals. <h3>Results:</h3> <h3>FINGOLIMOD:</h3> Herpesvirus infection rates were similar between placebo (2.8%) and 0.5 mg (2.1%) but increased with 1.25 mg (5.5%) in the TRANSFORMS study. VZV rates were higher with fingolimod 0.5 mg (3.0%; 11 per 1000 patient-years [PY]) than with placebo (1.0%; 6 per 1000 PY), but comparable post-marketing. Cryptococcal infections (n=74) had an IR of 9 per 100,000 PY, and 13 cases were individually reported. <h3>SIPONIMOD:</h3> VZV reactivation occurred more frequently with siponimod (2%) than with placebo (1%); EXPAND extension analyses calculated an IR of 0.9 for HSV and 1.8 for VZV infections. One case of cryptococcal meningitis (from 7236 PY of exposure) was documented. <h3>OZANIMOD:</h3> An integrated safety analysis reported oral herpes at 1.5%, VZV at 1.4%, and HSV at 0.5% from all clinical trials versus 0.7%, 0.6%, and 0.1% from the phase-3 trials. The IR of herpes zoster was 5.3/1000 PY. <h3>PONESIMOD:</h3> The incidence of herpetic infections was equal between both groups (4.8%) in the OPTIMUM trial. Cryptococcal infections have not yet been reported with ozanimod or ponesimod. <h3>Conclusions:</h3> Overall, the incidence of these opportunistic infections associated with S1PR modulators in MS was low, with favorable outcomes and limited fatalities. <b>Disclosure:</b> Dr. Sharma has nothing to disclose. Mr. JHA has nothing to disclose. Dr. Khanal has nothing to disclose. Dr. Sriwastava has nothing to disclose.

Liver Cirrhosis Increases the Risk of Herpes Zoster: A Nationwide Population-Based Cohort Study.

Limited data are available regarding the association between liver cirrhosis (LC) and the risk of herpes zoster (HZ). This study aimed to determine the risk of HZ in patients with LC. HZ was defined as the presence of the International Classification of Diseases-10th revision code for HZ and concomitant prescription of antiviral medication. The incidence rates and standardized incidence ratios (SIRs) of HZ in patients with LC were analyzed using data from the Health Insurance Review and Assessment Service in Korea claims database from 2009 to 2019. A total of 504,986 Korean patients with LC were included. The mean age was 52.4 years, and 60.8% were men. Chronic hepatitis B was the most common cause of LC. The incidence rates for HZ and HZ-related hospitalization were 21.6 of 1,000 and 1.81 of 1,000 person-years, respectively. The SIRs for HZ and HZ-related hospitalization were 1.09 (95% confidence interval [CI]: 1.08-1.09) and 1.48 (95% CI: 1.44-1.52), respectively, which were significantly higher than those in the general population. Patients with LC aged 20-29, 30-39, and 40-49 years had SIRs for HZ of 1.41 (95% CI: 1.33-1.48), 1.16 (1.13-1.19), and 1.17 (1.13-1.19), respectively. In multivariable analysis, woman (adjusted hazard ratio [AHR]: 1.48), steroid (AHR: 1.20), immunosuppressant use (AHR: 1.26), and combined comorbidities were associated with an increased risk of HZ among patients with LC. Patients with LC, particularly those who are not currently recommended for HZ vaccination, were at an increased risk of HZ and HZ-related hospitalization compared with the general Korean population.

Incidence of Herpes Zoster in Patients With Rheumatoid Arthritis in the United States: A Retrospective Cohort Study.

To estimate the incidence of herpes zoster (HZ) in patients with rheumatoid arthritis (RA) compared with the general population in the USA. This retrospective, longitudinal cohort study used data from an administrative claims database containing both commercial and Medicare Advantage Part D data, with a data period from October 2015 to February 2020. Patients were aged ≥ 18 years and divided into 2 cohorts: patients with RA and patients without RA. Diagnosis and procedure codes were used to identify HZ cases and calculate incidence rates (IRs) of HZ in the 2 cohorts. Data were stratified by age group (ie, 18-49, 18-29, 30-39, 40-49, 50-64, and ≥ 65 yrs) and RA therapy type. IR ratios (IRRs), adjusted by cohort baseline characteristics, were estimated using generalized linear models to compare the incidence of HZ between cohorts. The overall IR of HZ was higher in the RA cohort (21.5 per 1000 person-years [PY]; N = 67,650) than in the non-RA cohort (7.6 per 1000 PY; N = 11,401,743). The highest IRs in both cohorts were observed in the age group of ≥ 65 yrs (23.4 and 11.4 per 1000 PY in the RA cohort and non-RA cohort, respectively). The overall adjusted IRR of HZ was 1.93 (95% CI 1.87-1.99, P < 0.001) for the RA cohort compared with the non-RA cohort. In the RA cohort, the highest IRs by medication class were observed in patients using corticosteroids and those using Janus kinase inhibitors. These results highlight the increased incidence of HZ in patients with RA.

Risk of Herpes Zoster in Patients with Pulmonary Tuberculosis-A Population-Based Cohort Study.

Pulmonary tuberculosis (TB), a global health problem, is typically caused by the bacterium Mycobacterium tuberculosis. Herpes zoster (HZ) is caused by the reactivation of the varicella-zoster virus (VZV). The reactivation of VZV can be caused by stress. We investigated whether pulmonary TB increases the risk of HZ development. This study used data that sampled a population of 2 million people in 2000 from the National Health Insurance Research Database. This cohort study observed Taiwanese patients aged 20-100 years with pulmonary TB from 2000 to 2017 (tracked to 2018). Pulmonary TB was defined as having two or more outpatient diagnoses or at least one admission record. To address potential bias caused by confounding factors, the control cohort and pulmonary TB cohort were matched 1:1 by age, gender, index year, and comorbidities. Patients with HZ before the index date were excluded. A total of 30,805 patients were in the pulmonary TB and control cohorts. The incidence rate of HZ in pulmonary TB and control cohorts were 12.00 and 9.66 per 1000 person-years, respectively. The risk of HZ in the pulmonary TB cohort (adjusted hazard ratios = 1.23; 95% confidence interval = 1.16-1.30) was significantly higher than that of in control cohort. Among patients without comorbidities, the patients with TB were 1.28-fold more likely to have HZ than those without TB. Patients with TB should be well treated to avoid the potential risk of HZ occurrence. Although we identified the association between pulmonary TB and HZ, further studies are needed to confirm the result.